Functional Phosphine Derivatives Having Stationary and Flexible

Article pubs.acs.org/joc

Cite This: J. Org. Chem. 2019, 84, 8423−8439

Functional Phosphine Derivatives Having Stationary and Flexible Chiralities: Their Preparation and Chirality Controlling Yu Zhang, Shao-Zhen Nie, Jing-Jing Ye, Ji-Ping Wang, Meng-Meng Zhou, Chang-Qiu Zhao,* and Qiang Li* College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, Shandong 252059, China

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S Supporting Information *

ABSTRACT: Various functional secondary and tertiary phosphines, or their derivatives, containing stationary chiral phosphorus and flexible chiral axis were prepared, which could be further modified to afford diversely chelating ligands. The flexible axial chirality was fixed by stereogenic phosphorus via a cyclic linkage of chemical bonds or coordination with a metallic ion.

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created as a stereogenic center, the flexible chirality on biphenyl axis would be induced and fixed (Figure 1). The generation of P-stereogenic phosphines in high optical purity, especially as R and/or S stereoisomer, still remains a challenge to chemists. Perhaps due to the difficulty, to the best of our knowledge, the formation of axial chirality on biphenyl inducted by stereogenic phosphorus, which is closer to the active center of a catalyst,10b,17 has scarcely been reported. A chiral (−)-menthyl linking to phosphorus could assist to generate P-stereogenic center. It was unnecessary to remove the group because of the existence of C−P bond. As discussed below, the CDOP was converted to (−)-menthyl-containing SPO derivative via the Grignard reaction and hydrolysis. The subsequent desymmetry afforded P-stereogenic precursors, as R and/or S stereoisomers and in more than 80% total yield. The precursors were converted to various phosphine borane complexes and oxides that could afford tertiary phosphines via well-established procedures.18 The flexible axial chirality was successfully fixed via creation of a cyclic linkage to phosphorus.

INTRODUCTION Chiral tertiary phosphines (CTPs) are widely applied in asymmetric catalysis as ligands of metallic catalysts and as organocatalysts, which contain either chiral carbon skeleton or stereogenic phosphorus atom.1−3 The CTPs, even for that have sole chirality, are usually acquired from multistep conversions4 or via tedious kinetic resolutions.5 A chiral auxiliary is usually employed for the preparation of Pstereogenic CTPs, via alkylating, cross-coupling, addition, and substitution.6−10 The lengthy synthesis route probably results in chirality loss so that the reactions are usually performed under harsh conditions such as low temperature or strong alkali reagents.10b To reduce the difficulties to acquire CTPs, a temporarily formed asymmetric structure is supposed. The potential or flexible chiral moieties form asymmetric circumstance via inducing by a chiral factor. As seen in Figure 1, the flexible

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RESULTS AND DISCUSSION CDOP 1 was converted to SP-2/RP-2′, in the ratio around 50:50, via the reaction with (−)-menthyl Grignard reagent.19 The mixture was isolated as the corresponding borane complex SP-3/RP-3′. After alkali hydrolysis, RP-4/SP-4′ was afforded, also as a mixture. The structures of 2−4 were confirmed by Xray diffraction (Scheme 1 and Table 4, vide infra). The stereoselective conversion or separation of RP-4/SP-4′ was realized via several facile methods. First, desymmetric cyclization of RP-4/SP-4′ with hydrochloride afforded RP-3′, which was formed from dehydration of SP-4′; meanwhile, RP-4 kept unchanged. Second, stereoselective deprotection of RP-4/ SP-4′ with acetone at 0 °C afforded SP-5′. The deprotection occurred only for SP-4′, and the coordinated borane was

Figure 1. Proposed flexible model of chiral catalyst based on the induction of a chiral factor.

chiral axis of biphenyl is fixed. It is well known that CTPs containing biaryl axis show excellent catalysis activity, as represented by BINAP that was honored 2001 Nobel prize.11 The biphenyl derivatives exhibit excellent stereoselectivity during the chirality transferring from the center to axis,12 which is also realized via co-coordination with a chiral ligand13 or by a chiral moiety such as oxazoline.14 As an industrial material, 15 6-chloro-6H-dibenzo[c,e][1,2]oxaphosphinine (CDOP) 1, contains a flexible chiral axis on biphenyl and a phosphorus atom, and is widely used for the preparation of functionalized phosphines.16 When the phosphorus was © 2019 American Chemical Society

Received: February 14, 2019 Published: May 28, 2019 8423

DOI: 10.1021/acs.joc.9b00346 J. Org. Chem. 2019, 84, 8423−8439

Article

The Journal of Organic Chemistry Scheme 1. Stereoselective Conversion of 1 to Single Stereoisomers of 3 to 5

Scheme 2. Stereoselective Conversions of 3 to 7−10

The substitutions of SP-2 with various Grignard reagents afforded RP-7 in >99:1 drP and poor drA (Table 1). Aliphatic alkyl Grignard reagents formed RP-7 at room temperature. The

removed as a reducing agent (as seen in the SI for details). Third, RP-4 was obtained from direct recrystallization (Scheme 1). The mixture of RP-4/SP-4′ (50:50) was recrystallized to afford RP-4, and the remaining mother liquid contained SP-4′ in dominant ratio, which afforded RP-3′ or SP-5′ in higher yields and optical purities via the above desymmetric reactions. Cyclization of RP-4 afforded SP-3 that was converted to RP-5 via deprotection and hydrolysis.20 Thus, SP-3, RP-3′, RP-4, RP5, and SP-5′ were conveniently obtained, all in satisfied yields and >99% optical purities. The optically pure 3−5 were used as precursors of various Pstereogenic substances via selectively modified on oxygen or phosphorus. For example, S P -3 was deprotected and substituted with methyl magnesium bromide, and afforded Pinversed RP-6a that was isolated as borane complex RP-7a, in total 95% yield (route A of Scheme 2).21 On 1H NMR spectrum, RP-7a gave two doublet peaks at 1.20 and 1.42 ppm, in the ratio of 80:20, which was assigned as the stereoisomers derived from the axial chirality on biphenyl.

Table 1. Substitution of SP-3/2 with Grignard Reagents To Afford RP-6/7 (Route A of Scheme 2) entry

R

1 2 3 4 5 6 7 8 9 10 11

Me Et nBu nC5H11 iBu allyl PhCH2 p-tBuC6H4CH2 p-MeC6H4CH2 o-ClC6H4CH2 o-MeC6H4CH2

temp. rt rt rt rt 80 rt 80 80 80 80 80

°C °C °C °C °C °C

RP-7, yield % (drA)a 7a, 95 (80:20) 7b, 80 (56:44) 7c, 68 (61:39) 7d, 38 (59:41) 7e, 48 (58:42) 7f, 89 (59:41) 7g, 75 (52:48) 7h, 80 (48:52) 7i, 79 (48:52) 7j, 30 (63:37) 7k, 28 (60:40)

a

The yield and drA, assigned as the ratio of two axial stereoisomers, were estimated by 31P{1H} NMR spectrum. 8424


Article

The Journal of Organic Chemistry reactions with benzyl Grignard reagents were carried out at elevated temperature. Secondary alkyl or aromatic Grignard reagent cannot afford RP-7. Further O-alkylation of RP-7 afforded RP-8 (Scheme 2). The regioselective alkylation on O−H or P−H, for either RP-5 or SP-5′, was realized (routes B and C of Scheme 2). When equal molar amount of base was used, O-alkylated secondary phosphine oxide RP-9 or SP-9′ was obtained. Under phase-transfer condition, O,P-alkylation afforded P-stereospecific TP oxides RP-10 or SP-10′ (vide infra).18h Various primary alkyl and benzyl halides gave 9 and 10 in high yields. For secondary alkyl, such as isopropyl bromide, only RP-9c was obtained (Table 2).

Table 3. To Connect Two Chiral Phosphorus Moieties via Oxygen or Phosphorusa

a

Table 2. Alkylation of RP-5 or SP-5′ with Alkyl Halides in the Presence of Base (Routes B and C of Scheme 2) entry

5 or 5′

RX

9 or 10, yield % (drA)a

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

RP-5 SP-5′ RP-5 RP-5 RP-5 SP-5′ RP-5 SP-5′ RP-5 RP-5 RP-5 RP-5 RP-5 RP-5 RP-5 SP-5′ RP-5 SP-5′ RP-5 RP-5

CH3I CH3I EtBr iPrBr CH3I CH3I EtBr EtBr nBuBr isoBuBr allylBr PhCH2Cl p-MeC6H4CH2Cl p-tBuC6H4CH2Cl o-MeC6H4CH2Cl o-MeC6H4CH2Cl m-MeOC6H4CH2Cl m-MeOC6H4CH2Cl p-ClC6H4CH2Cl o-ClC6H4CH2Cl

RP-9a, 97 (56:44) SP-9a′, 94 (55:45) RP-9b, 97 (52:48) RP-9c, 90 (48:52) RP-10a, 99 (62:38) SP-10a′, 99 (65:35) RP-10b, 99 (53:47) SP-10b′, 99 (32:68) RP-10c, 99 (53:47) RP-10d, 70 (52:48) RP-10e, 99 (85:15) RP-10f, 96 (71:29) RP-10g, 99 (72:28) RP-10h, 99 (76:24) RP-10i, 99 (76:24) RP-10i′, 99 (28:72) RP-10j, 99 (72:28) SP-10j′, 99 (40:60) RP-10k, 99 (68:32) RP-10l, 99 (79:21)

Isolated yields.

between P/axial chiralities. RP,RA-4 gave the signals of single axial stereoisomer even in the solution of chloroform, which was ascribed to intramolecular hydrogen bonding between two hydroxyl groups. Due to interference to the hydrogen bonding, the flexibility of axial chirality became obvious in methanol. Although as the mixtures of stereoisomers, 7, 8, and 10 could be obtained as single crystals, whose X-ray diffractions showed the stationary chirality on axials (Table 4). Cyclic 2 and 3 were observed as single stereoisomers by NMR spectrum and X-ray diffraction. Thus, a cyclic linkage was hoped to fix the chirality on axis. As seen in Scheme 1, RP,RA-4 was P,axial-stereospecifically converted to cyclic SP,SA3. In Scheme 3a, cyclization of RP,RA-4 afforded RP,RA-15 also as a single stereoisomer, whose structure was confirmed by NMR spectrum and X-ray diffraction (Table 4). RP,RA-4 was converted to 16 with formaldehyde, then to 17 via chlorination. Both 16 and 17 were obtained as the axial mixtures.22 After cyclization, only a peak at 40.2 ppm was observed for RP-18, whose SA-configuration was confirmed by X-ray diffraction (Scheme 3 and Table 4). In methanol, RP-5 distinctly gave the signals of two axial stereoisomers on NMR spectrum. When lithium hydroxide was added, only a peak was observed at 40.7 ppm that was assigned as a single stereoisomer 19. Treatment of SP-5′ with lithium hydroxide gave the similar NMR variations (Scheme 3).23 The results indicated that a possible coordination of O and P to lithium fixed the axial chirality. Similar mixing with silver triflate also resulted in the clear 1H NMR spectrum of RP-5. The coordination of RP,RA-5/RP,SA-5 with palladium failed to give a cyclic complex. However, axial-stereospecific cyclization afforded RP,SA-2, which coordinated with palladium, forming cis-(RP,SA-2)2·PdCl2 in excellent yield (Table 4). Some acyclic complexes, such as trans-(SP,RA-20)2·PdCl2 and (SP,RA-20·PdCl)2(μ-Cl)2, were also observed to have the stationary axial chirality by X-ray diffraction (Table 4). In summary, various phosphine derivatives that contained stationary P-chirality and flexible axial chirality were prepared in high optical purities and yields. The selective modifications on O and P afforded entirely P-inversed or retained products. Most of the acyclic products were observed as the mixtures of axial stereoisomers. The axial chirality was fixed by stereogenic phosphorus via a cyclic linkage, and the axial stereoisomers were converted to a single one. Our study supplied a model that exploited flexible chiral moiety to form temporary chiral substance, which was hoped to supply beneficial inspiration in asymmetric catalysis.

a

The yield and drA were estimated by 31P{1H} NMR spectrum.

Compounds 2 to 5 showed P-configurational stability toward base during the above conversions, which was benefited from (−)-menthyl.21 The hydrolysis of SP-2 was proposed as water attacking opposite P−O bond, forming hydroxylphosphine intermediate that was converted to P-inversed RP-5 via isomerization. Similar attacking of the Grignard reagent afforded P-inversed RP-7. Alkylation of RP-5 gave P-retained RP-10. O-Methylation of RP-7a gave RP-8a that was converted to SP-10a′ via oxidization (route D of Scheme 2), which had the same NMR spectrum to that obtained from SP-5′ via route B. The results, as well as the X-ray diffraction of RP-7c, RP-8a, and RP-10b (Table 4, vide infra), unambiguously confirmed the above-proposed P-stereochemistry. Selective O-alkylation of SP-5′ with alkyl dihalides afforded bisphosphine oxides SP,SP-11 and SP,SP-12, which could be further modified on phosphorus to form chelating ligands. Similarly, O-alkylation of RP-7a formed bisphosphine−borane complex RP,RP-13. P-Alkylation of RP-9b gave RP,RP-14 (Table 3). Besides 4, the above-obtained acyclic 5−14 were observed as the mixtures of two stereoisomers deriving from the flexible axial chirality. In a solution, varied drA that depended on solvents and substituents indicated the variable interaction 8425


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The Journal of Organic Chemistry Table 4. X-ray Diffraction Results of Some Compoundsa,b

a

The detailed structural data are presented in the SI. bCompound 20 was obtained from deprotection of RP-8a.

Scheme 3. Stereospecific Formation of Cyclic P,axial-Stereogenic Phosphorus Derivatives

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with CDCl3. 13C NMR spectra were recorded at 101 MHz. Chemical shifts for 13C NMR spectra are reported (in parts per million) relative to CDCl3 (δ = 77.0 ppm). 31P NMR spectra were recorded at 162 MHz, and chemical shifts are reported (in parts per million) relative to external 85% phosphoric acid (δ = 0.0 ppm). TLC plates were

EXPERIMENTAL SECTION

General Chemistry. 1H NMR spectra were recorded on a 400 MHz spectrometer. Chemical shift for 1H NMR spectra (in parts per million) is related to internal tetramethylsilane (Me4Si, δ = 0.00 ppm) 8426


Article

The Journal of Organic Chemistry

11.8, 1H), 1.18−0.40 (m, 14H), 0.33 (t, J = 7.4, 2H), 0.21 (d, J = 6.8, 1H). Desymmetry of 4/4′ with Hydrochloride, To Form RP-3′. Hydrochloric acid (35%, 2.7 mL) was added to THF (10.8 mL) dropwise. After the solution was cooled to room temperature, 4/4′ (5.00 g, 13.50 mmol, 65:35 dr) was added and the solution was stirred at room temperature, with monitoring by NMR spectroscopy. The results are presented in Figure S1 (SI). After the reaction was completed, sodium carbonate (11.60 g) was added, and the mixture was extracted with dichloromethane (3 × 30 mL), washed with water (3 × 50 mL), and dried over magnesium sulfate. After removing the solvents, the residue was purified with column chromatography on silica gel (petroleum ether/dichloromethane = 4/1) to afford RP-3′ (1.33 g, 28%, > 99:1 dr ). After the eluent was changed to petroleum ether/ethyl acetate = 2/1, RP-4 was obtained (2.12 g, 42%, > 99:1 dr). RP-6-(−)-Menthyl-6H-dibenzo[c,e][1,2]oxaphosphinine-borane Complex (RP-3′). The optically pure RP-3′ was obtained as a white solid, mp 96.5−100.3 °C; 31P NMR (162 MHz, CDCl3) δ = 112.1 (broad m); 1H NMR (400 MHz, CDCl3) δ = 7.88 (t, J = 8.4, 2H), 7.79−7.70 (m, 1H), 7.64 (t, J = 7.7, 1H), 7.51−7.43 (m, 1H), 7.35 (t, J = 7.7, 1H), 7.26 (dd, J = 4.4, 3.2, 1H), 7.15 (d, J = 8.1, 1H), 2.70− 2.56 (m, 1H), 1.94 (dd, J = 25.9, 13.6, 1H), 1.70 (ddd, J = 36.4, 21.8, 5.8, 3H), 1.09−0.94 (m, 6H), 0.87 (dt, J = 19.0, 8.6, 5H), 0.72 (d, J = 6.3, 3H), 0.64 (d, J = 6.8, 3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 149.3 (d, J = 12.6), 133. 6 (s), 132.5 (dd, J = 14.4, 9.4), 130.3 (s), 128.0 (d, J = 12.2), 125.1 (s), 124. 6 (s), 124.2−123.5 (m), 123.3 (d, J = 10.0), 121.2 (d, J = 4.3), 43.1 (d, J = 2.8), 35.9 (s), 35.7 (s), 35.1 (d, J = 3.9), 34.0 (d, J = 1.5), 32.8 (d, J = 12.6), 29.0 (d, J = 2.9), 24.4 (d, J = 12.5), 22.4 (s), 21.5 (s), 16.6 (s); HRMS (ESI+) Calcd. for C22H28OP [M-BH3 + H+]: 339.1878, Found: 339.1879. RP-(2′-Hydroxy-1,1′-biphenyl-2-yl)(hydroxy)(menthyl)phosphine borane Complex (RP-4). The optically pure RP-4 was obtained as a white solid, mp 155.4−159.5 °C; 31P NMR (162 MHz, CDCl3) δ = 113.1 (broad m); 1H NMR (400 MHz, CDCl3) δ = 8.22 (dd, J = 13.8, 7.9, 1H), 7.65−7.47 (m, 2H), 7.45−7.27 (m, 2H), 7.19−6.95 (m, 3H), 2.42−2.23 (m, 0.9H), 2.22-2.03 (m, 0.1H), 1.59 (d, J = 8.2, 3H), 1.28 (dd, J = 29.0, 12.6, 1H), 0.95 (s, 3H), 0.85 (t, J = 7.0, 4H), 0.81−0.52 (m, 7H), 0.35 (t, J = 6.2, 3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 153.0 (s), 150.8 (s), 139.4 (s), 139.1 (s), 135.8 (s), 135.4 (s), 135.2 (s), 132.2 (d, J = 2.1), 131.8 (t, J = 16.4), 131.6−131.3 (m), 131.1 (s), 130.5 (d, J = 27.3), 130.1 (s), 129.4 (s), 128.2 (d, J = 12.9), 122.0 (s), 120.5 (s), 117.2 (s), 115.9 (s), 43.9 (s), 43.5(s), 38.7 (d, J = 13.1), 38.4 (d, J = 9.9), 35.6 (s), 35.2 (d, J = 5.4), 34.2 (s), 32.8 (t, J = 13.7), 28.3 (s), 28.0 (d, J = 2.3), 24.5 (t, J = 11.7), 22.4 (s), 21.3 (d, J = 7.5), 14.7 (d, J = 4.5); HRMS (ESI+) Calcd. for C22H30O2P [M-BH3 + H+]: 357.1983, Found: 357.1978. 31 P NMR (202 MHz, CD3OD) δ = 113.5 (broad m,61%), 112.1 (broad m, 39%); 1H NMR (500 MHz, CD3OD) δ = 8.10−8.00 (m, 1H), 7.48 (t, J = 7.5, 0.4H), 7.42−7.33 (m, 1H), 7.33−7.26 (m, 0.6H), 7.24 (dd, J = 7.6, 1.5, 0.6H), 7.23−7.17 (m, 1H), 7.13 (d, J = 7.5, 0.4H), 7.08 (td, J = 8.1, 1.6, 0.6H), 6.94 (dd, J = 7.5, 1.7, 0.4H), 6.90 (d, J = 7.3, 0.4H), 6.86 (d, J = 8.1, 0.4H), 6.77 (d, J = 8.1, 0.6H), 6.70 (td, J = 7.5, 0.8, 0.6H), 2.32−2.24 (m, 0.4H), 2.24−2.16 (m, 0.6H), 1.55−1.18 (m, 5H), 1.05−0.83 (m, 2H), 0.72 (t, J = 7.4, 4H), 0.68−0.61 (m, 2H), 0.60 (d, J = 6.3, 2H), 0.58 (d, J = 6.5, 3H), 0.31 (d, J = 6.8, 3H); 13C {1H} NMR (126 MHz, CD3OD) δ = 156.0 (s), 155.0 (d, J = 247.4), 163.5−142.7 (m), 149.1 (dd, J = 1495.3, 196.2), 149.1 (dd, J = 1495.3, 196.2), 142.5 (ddd, J = 791.0, 133.7, 56.1), 163.5−134.3 (m), 163.5−134.0 (m), 163.5−133.7 (m), 163.5−133.4 (m), 219.8−132.6 (m), 132.4 (s), 131.5 (s), 131.0 (s), 130.8 (s), 130.1 (s), 129.0 (s), 128.4 (d, J = 12.8), 127.5 (d, J = 13.3), 121.5 (s), 119.3 (s), 117.5 (s), 115.7 (s), 45.5 (s), 45.1 (s), 39.8 (s), 39.5 (s), 38.9 (s), 38.6 (s), 36.9 (d, J = 5.2), 36.3 (d, J = 5.9), 35.8 (d, J = 25.6), 34.0 (dd, J = 20.8, 14.2), 29.0 (d, J = 9.2), 25.8 (dd, J = 20.5, 12.3), 22.9 (d, J = 7.7), 21.8 (d, J = 17.7), 15.6 (d, J = 18.1). Desymmetry of 4/4′ with Acetone, To Form SP-5′. To the icewater-cooled acetone (13.5 mL), 4/4′ (5.00 g, 13.50 mmol, 65:35 dr) was added, and the clear solution was stirred at room temperature for 2 h. After removing the solvent, the residue was analyzed with NMR spectrum, and the results are presented in Figure S2 (SI). After

visualized by UV. All products were further characterized by HRMS (high-resolution mass spectroscopy). HR-MS was obtained using a QTOF instrument equipped with ESI source. Copies of their 1H, 31P, and 13C NMR spectra were provided. Melting points were determined on a Reichert Thermovar melting point apparatus and are uncorrected. Unless otherwise noted, the ratio of stereoisomers was estimated based on 1H NMR spectrum. Reagent and Solvents. All of the solvents used were dried and freshly distilled prior to use. Toluene, chloroform, and dichloromethane were distilled under calcium hydride. THF and ether were distilled under sodium and benzophenone. Unless otherwise stated, the commercially available reagents were used without further purification. Some of the Grignard reagents were prepared according to standard procedure in ca. 0.8 M solution in ether or THF. All reactions were carried out under N2 atmosphere in dry glassware using Schlenk line techniques. Air- and moisture-sensitive liquids and solutions were transferred via a syringe. Preparation of 6-(−)-Menthyl-6H-dibenzo[c,e][1,2]oxaphosphinine-borane Complex 3/3′. To a solution of CDOP (5.00 g, 21.31 mmol) in THF (5 mL), a solution of (−)-menthyl magnesium chloride (prepared according to standard procedure, 0.8 M solution in THF, 40 mL, 32 mmol) was added dropwise. The mixture was stirred at room temperature for 8 h, and the solution of borane-THF (1.0 M solution in THF, 21.3 mL, 21.31 mmol) was added dropwise. After stirring for 2 h, the reaction was quenched with diluted hydrochloric acid (7%) and the solvent was removed in vacuo. The mixture was extracted with dichloromethane (3 × 30 mL), washed with water (3 × 50 mL), and dried over magnesium sulfate. After removing the solvent, the residue was purified from recrystallization with dichloromethane−petroleum ether (60−90 °C) to afford 3/3′ (6.50 g, 87%, 50:50 dr). RP/SP-6-(−)-Menthyl-6H-dibenzo[c,e][1,2]oxaphosphinine-borane Complex (3/3′). The pure 3/3′ was obtained as a white solid, mp 123.4−124.8 °C; 31P NMR (162 MHz, CDCl3) δ = 112.1 (broad m, 50%), 109.7 (broad m, 50%); 1H NMR (400 MHz, CDCl3) δ = 7.91 (ddd, J = 17.4, 14.9, 8.2, 2H), 7.85−7.71 (m, 1H), 7.63 (dd, J = 14.5, 7.5, 1H), 7.47 (td, J = 7.2, 3.8, 1H), 7.42−7.31 (m, 1H), 7.30−7.21 (m, 1H), 7.16 (dd, J = 15.1, 8.1, 1H), 2.64 (dt, J = 13.3, 6.5,0.5H), 2.19−1.88 (m, 1.5H), 1.88−1.53 (m, 4H), 1.33 (ddd, J = 25.0, 12.4, 6.0, 1H), 1.16−0.94 (m, 4H), 0.94−0.78 (m, 6H), 0.72 (d, J = 6.2, 2H), 0.65 (d, J = 6.8, 1.6H), 0.06 (d, J = 6.8, 1.4H); 13C {1H} NMR (101 MHz, CDCl3) δ = 149.3 (dd, J = 12.2, 8.8), 134.2 (s), 133.6 (s), 132.6 (d, J = 17.1), 131.9 (d, J = 18.3), 130.6 (s), 130.3 (s), 128.1 (dd, J = 27.5, 12.3), 126.3 (s), 125.8 (s), 125.2 (d, J = 10.8), 124.6 (s), 124.1 (dd, J = 11.3, 5.7), 123.8 (s), 123.3 (d, J = 9.9), 121.2 (d, J = 4.3), 120.6 (d, J = 4.3), 43.6 (d, J = 4.1), 43.1 (d, J = 2.7), 38.2 (s), 38.0 (s), 35.9 (s), 35.7 (s), 35.4−34.9 (m), 34.1 (d, J = 19.0), 32.8 (dd, J = 11.7, 7.4), 29.0 (d, J = 3.5), 24.5 (dd, J = 12.3, 4.9), 22.4 (d, J = 12.3), 21.5 (s), 21.2 (s), 16.6 (s), 14.2 (s); HRMS (ESI+) Calcd. for C22H28OP [M-BH3 + H+]: 339.1878, Found: 339.1940. Hydrolysis of R P /S P -6-(−)-Menthyl-6H-dibenzo[c,e][1,2]oxaphosphinine-borane Complex 3/3′ To Form RP/SP-(2′-Hydroxy-1,1′-biphenyl-2-yl)(hydroxy)(menthyl)phosphine Borane Complex 4/4′. To a solution of 3/3′ (5.00 g, 14.19 mmol, 50:50 dr) in ethanol (10 mL), potassium hydroxide was added (1.87 g, 28.38 mmol) and the solution was stirred at room temperature for 4 h. Diluted hydrochloric acid (7%) was added to adjust pH to 5−6. After the solvent was removed in vacuo, the mixture was extracted with dichloromethane (3 × 30 mL), washed with water (3 × 50 mL), and dried over magnesium sulfate. After removing the solvent in vacuo, the residue was purified from recrystallization with ether− petroleum ether (60−90 °C) to afford 4/4′ (5.21 g, 99%, 65:35 dr). R P /S P -(2′-Hydroxy-1,1′-biphenyl-2-yl)(hydroxy)(menthyl)phosphine Borane Complex (4/4′). Pure 4/4′ was obtained as a white solid, mp 155.4−159.5 °C; 31P NMR (162 MHz, CDCl3) δ = 114.6 (broad m, 50%), 109.6 (broad m, 50%); 1H NMR (400 MHz, CDCl3) δ = 8.32−8.12 (m, 0.9H), 8.03 (d, J = 7.3, 0.1H), 7.69−7.44 (m, 2H), 7.42−7.30 (m, 1H), 7.30−7.16 (m, 2H), 7.05 (ddt, J = 18.7, 9.4, 4.9, 2H), 2.33−2.19 (m, 1H), 1.69−1.37 (m, 3H), 1.29 (d, J = 8427


Article

The Journal of Organic Chemistry recrystallization with ether, SP-5′ was afforded (1.25 g, 26%, > 99:1 drP and 77:23 drA). RP-4 (2.41 g, 48%, > 99:1 dr) was obtained from recrystallization with ether−petroleum ether (60−90 °C). SP-(−)-Menthyl (2-Hydroxy-1,1′-biphenyl-2-yl)phosphine Oxide (SP-5′). The pure SP-5′ was obtained as a white solid, mp 163.8− 166.8 °C; 31P NMR (162 MHz, CDCl3) δ = 24.47 (s, 77%), 24.04 (s, 23%); 1H NMR (400 MHz, CDCl3) δ = 9.47 (s, 1H), 8.20 (s, 0.12H), 8.11 (s, 0.38H), 8.06−7.84 (m, 1H), 7.57 (t, J = 7.4, 1H), 7.47 (t, J = 7.4, 1H), 7.36−7.13 (m, 2H), 7.09 (d, J = 7.8, 0.5H), 6.99 (d, J = 7.8, 1.5H), 6.93−6.78 (m, 1H), 2.10−1.88 (m, 1H), 1.65 (d, J = 7.3, 3H), 1.44−0.94 (m, 4H), 0.79 (ddd, J = 28.1, 20.0, 6.3, 8H), 0.29 (d, J = 6.7, 0.7H), 0.24 (d, J = 6.7, 2.3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 155.3 (s), 154.3 (s), 141.1 (dd, J = 46.1, 11.6), 133.1 (dd, J = 46.2, 6.0), 132.8−132.6 (m), 132.1 (s), 132.1−132.1 (m), 132.1−131.1 (m), 131.1−130.3 (m), 130.1 (d, J = 22.7), 129.9 (s), 128.0 (d, J = 15.3), 127.3 (t, J = 10.4), 126.0 (dd, J = 25.4, 2.8), 119.4 (s), 119.1 (s), 116.8 (s), 116.3 (s), 41.8 (dd, J = 16.1, 2.5), 39.4 (s), 38.7 (s), 34.4 (d, J = 17.1), 32.6 (d, J = 13.6), 31.7 (d, J = 3.4), 27.5 (d, J = 5.2), 24.0 (d, J = 12.4), 22.4 (s), 21.4 (s), 14.8 (s), 14.6 (s); HRMS (ESI+) Calcd. for C22H30O2P [M + H+]: 357.1983, Found: 357.1965. RP-(2′-Hydroxy-1,1′-biphenyl-2-yl)(hydroxy)(menthyl)phosphine borane Complex (RP-4). The compound obtained here had the same spectrum data as those obtained above. Recrystallization of 4/4′ To Form RP-4. The solution of 4/4′ (5.00 g, 13.50 mmol, 65:35 dr) in ether (8 mL) and petroleum ether (60− 90 °C) was cooled in a refrigerator at −40 °C for 1 day. After filtration and washing with petroleum ether, RP-4 (2.00 g, 40%, > 99:1 dr) was obtained. The solid and mother liquid were analyzed with NMR spectrum, and the results are presented in Figure S3 (SI). The compound had the same spectrum data as those obtained above. Stereospecific Cyclization of RP-4 To Form SP-3. To the ice-watercooled solution of RP-4 (540.0 mg, 1.458 mmol) and pyridine (150.6 μL, 1.75 mmol) in THF (9 mL) was added thionyl chloride (212 μL, 2.917 mmol). The mixture was warmed to room temperature and stirred for 8 h. After removing the solvent in vacuo, water (5 mL) was added and the mixture was extracted with dichloromethane (3 × 10 mL), washed with water (3 × 20 mL), and dried over magnesium sulfate. After removing the solvent, the residue was purified by recrystallization with dichloromethane−petroleum ether (60−90 °C) to afford SP-3(493.0 mg, 96%, > 99:1 dr). SP-6-(−)-Menthyl-6H-dibenzo[c,e][1,2]oxaphosphinine-borane Complex (SP-3). The optically pure SP-3 was obtained as a white solid, mp 126.5−127.6 °C; 31P NMR (162 MHz, CDCl3) δ = 109.6 (broad m); 1H NMR (400 MHz, CDCl3) δ = 7.97−7.87 (m, 2H), 7.82 (d, J = 7.8, 1H), 7.62 (t, J = 7.7, 1H), 7.47 (td, J = 7.4, 1.7, 1H), 7.38 (t, J = 7.4, 1H), 7.26 (t, J = 7.3, 1H), 7.18 (d, J = 8.1, 1H), 2.08 (dt, J = 13.9, 7.0, 1H), 2.03−1.92 (m, 1H), 1.84 (d, J = 10.2, 1H), 1.72−1.49 (m, 4H), 1.44−1.23 (m, 2H), 0.97−0.70 (m, 10H), 0.05 (d, J = 6.8, 3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 149.2 (d, J = 11.7), 134.2 (s), 132.5 (d, J = 2.3), 131.9 (d, J = 18.3), 130.6 (s), 128.3 (d, J = 12.4), 126.3 (s), 125.8 (s), 125.2 (s), 124.6 (s), 124.2 (t, J = 6.8), 120.7 (d, J = 4.3), 43.6 (d, J = 4.2), 38.1 (s), 37.9 (s), 35.2 (s), 34.2 (s), 32.9 (d, J = 10.8), 29.0 (d, J = 3.6), 24.5 (d, J = 12.1), 22.5 (s), 21.2 (s), 14.2 (s); HRMS (ESI+) Calcd. for C22H28OP [MBH3 + H+]: 339.1878, Found: 339.1871. Deprotection and Hydrolysis of SP-3 To Form RP-5. To the solution of SP-3 (500.0 mg, 1.42 mmol) in THF (2.5 mL) was added diethylamine (2.5 mL). The mixture was stirred at 50 °C for 8 h. After removing amine and solvent, potassium hydroxide (187.5 mg, 2.84 mmol) and ethanol (2 mL) were added and the mixture was stirred at room temperature for 2 h. After the reaction was completed, dilute hydrochloric acid (7%) was added to adjust pH to 5−6, and then the solvent was removed in vacuo. The mixture was extracted with dichloromethane (3 × 10 mL), washed with water (3 × 20 mL), and dried over magnesium sulfate. After removing the solvent in vacuo, the residue was purified by recrystallization with dichloromethane− petroleum ether (60−90 °C) to afford RP-5 (470.1 mg, 93%, > 99:1 drP and 38:62 drA).

(R P )-(−)-Menthyl (2′-Hydroxy-1,1′-biphenyl-2-yl)phosphine Oxide (RP-5). The pure RP-5 was obtained as a white solid, mp 155.7−159.5 °C; 31P NMR (162 MHz, CDCl3) δ = 48.20 (s, 38%), 37.79 (s, 62%); 1H NMR (400 MHz, CDCl3) δ = 8.03−7.87 (m, 0.6H), 7.85−7.66 (m, 1H), 7.65−7.51 (m, 1H), 7.45 (d, J = 7.3, 1H), 7.37−7.18 (m, 2H), 7.10 (t, J = 14.3, 2H), 7.02−6.82 (m, 1H), 6.56 (d, J = 17.8, 0.4H), 2.31 (d, J = 4.5, 0.4H), 2.00 (d, J = 7.0, 0.6H), 1.59 (s, 3H), 1.44 (d, J = 10.5, 1H), 1.09−0.50 (m, 12H), 0.40 (d, J = 5.8, 1.2H), 0.33 (d, J = 5.8, 1.8H); 13C {1H} NMR (101 MHz, CDCl3) δ = 154.2 (s), 154.0 (s), 141.6 (d, J = 7.4), 141.1 (d, J = 12.6), 132.4 (s), 132.0 (d, J = 32.3), 131.8 (s), 131.4−130.1 (m), 130.7−129.4 (m), 130.1 (s), 127.5 (d, J = 10.5), 126.3 (d, J = 3.7), 120.9 (s), 120.6 (s), 119.5 (s), 116.5 (s), 44.0 (s), 42.6 (s), 40.7 (s), 40.0 (s), 38.7 (s), 38.1 (s), 37.0 (s), 35.2 (s), 34.0 (s), 33.2 (d, J = 16.2), 32.7 (d, J = 16.7), 31.6 (s), 28.7 (d, J = 2.7), 24.2 (d, J = 13.5), 22.3 (s), 21.4 (s), 15.0 (s), 14.11 (s); HRMS (ESI+) Calcd. for C22H30O2P [M + H+]: 357.1983, Found: 357.1978. Conversion of Optically Pure Starting Material Based on Substitution of 2 with Grignard Reagents, Deprotection of SP-3 To Form SP-2. To the solution of SP-3 (500.0 mg, 1.42 mmol) in THF (2.5 mL) was added diethylamine (2.5 mL), and the mixture was stirred at 50 °C for 8 h. After removing the solvent and amine, the residue was purified by recrystallization with petroleum ether (60−90 °C) to afford SP-2 (432.3 mg, 90%, > 99:1 dr). SP-6-(−)-Menthyl-6H-dibenzo[c,e][1,2]oxaphosphinine (SP-2). The optically pure SP-2 was obtained as a white solid, mp 100.6− 103.4 °C; 31P NMR (162 MHz, CDCl3) δ = 102.39 (s); 1H NMR (400 MHz, CDCl3) δ = 7.82 (dd, J = 11.0, 4.5, 2H), 7.48 (dt, J = 14.8, 8.0, 2H), 7.33 (t, J = 7.4, 1H), 7.26 (td, J = 8.0, 1.4, 1H), 7.10 (t, J = 7.2, 1H), 7.04 (d, J = 8.1, 1H), 2.26 (ddd, J = 10.1, 6.7, 3.5, 1H), 1.75−1.54 (m, 4H), 1.53−1.43 (m, 1H), 1.02−0.93 (m, 1H), 0.91 (d, J = 6.8, 3H), 0.88−0.73 (m, 3H), 0.69 (d, J = 6.4, 3H), 0.37 (d, J = 6.8, 3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 152.6 (d, J = 10.1), 133.7−133.3 (m), 131.6 (s), 131.1 (s), 130.1 (s), 129.5 (s), 127.3 (d, J = 12.9), 124.8 (s), 124.4 (d, J = 5.2), 123.6 (d, J = 1.6), 122.8 (s), 120.4 (s), 45.0 (d, J = 15.7), 44.0 (s), 43.7 (s), 36.7 (d, J = 3.9), 34.7 (s), 33.1 (d, J = 5.4), 29.1 (d, J = 13.7), 24.8 (d, J = 8.3), 22.6 (s), 21.7 (s), 14.9 (s). Because it is sensitive to air, SP-2 could not give satisfied results of HRMS. Substitution of SP-2 with Grignard Reagents To Form RP-7, Typical Procedure. To the ice-water-cooled solution of SP-2 (80.0 mg, 0.24 mmol) in THF (1 mL), the solution of ethyl magnesium bromide (0.8 M solution in ether, 0.9 mL, 0.72 mmol) was added dropwise. The mixture was warmed to room temperature and stirred for 8 h, and the solution of borane-THF (1.0 M solution in THF, 0.48 mL, 0.48 mmol) was added dropwise. After stirring at room temperature for 2 h, dilute hydrochloric acid (7%, 2 mL) was added, and the solvent was removed in vacuo. The mixture was extracted with dichloromethane (3 × 5 mL), washed with water (3 × 10 mL), and dried over magnesium sulfate. After removing solvents, the residue was purified with preparative TLC (silica gel, dichloromethane/petroleum ether = 4/1 as eluent) to afford RP-7b (62.4 mg, 68%, > 99:1 drP and 56:44 drA). (R P )-(−)-Menthyl Methyl (2′-Hydroxy-1,1′-biphenyl-2-yl)phosphine Borane (RP-7a). The crude RP-7a was obtained from methyl magnesium bromide (3.0 M solution in diethyl ether), and the pure RP-7a was obtained as a white solid (72.5 mg, 82%, > 99:1 drP and 80:20 drA) from preparative TLC (silica gel, dichloromethane/ petroleum ether = 4/1 as eluent), mp 62.0−64.6 °C; 31P NMR (162 MHz, CDCl3) δ = 21.27 (broad m); 1H NMR (400 MHz, CDCl3) δ = 8.21−8.05 (m, 1H), 7.50 (dt, J = 15.0, 6.7, 2H), 7.40−7.20 (m, 2H), 7.18 (d, J = 7.4,0.3H), 7.06−6.89 (d, J = 7.4, 2.7H), 4.58 (s, 1H), 2.02−1.76 (m, 2H), 1.75−1.59 (m, 2H), 1.53 (s, 1H), 1.42 (d, J = 10.1, 0.6H), 1.25 (s, 3H), 1.19 (d, J = 10.1, 2.4H), 1.03−0.52 (m, 11H), 0.39 (t, J = 7.9, 3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 153.1 (d, J = 9.6), 139.7 (s), 139.1 (s), 137.1 (d, J = 17.0), 136.5 (d, J = 16.8), 132.2−131.6 (m), 131.4 (dd, J = 25.9, 7.6), 130.9 (s), 130.5 (s), 130.2 (s), 129.9 (s), 128.4 (dd, J = 12.3, 5.2), 127.4 (t, J = 7.1), 119.9 (d, J = 5.3), 115.9 (s), 44.4 (s), 44.1 (s), 38.0 (s), 37.7 (s), 37.0 (d, J = 6.5), 36.1 (s), 35.8 (s), 34.2 (d, J = 7.7), 33.2 (dd, J = 29.5, 8428


Article

The Journal of Organic Chemistry 12.6), 29.71 (s), 28.7−28.3 (m), 24.8 (t, J = 10.1), 22.5 (d, J = 9.8), 21.3 (d, J = 16.0), 15.6−14.8 (m), 12.0 (s), 11.7 (s); HRMS (ESI+) Calcd. for C23H32OP [M-BH3 + H+]: 355.2191, Found: 355.2188. (RP)-(−)-Menthyl Ethyl (2′-Hydroxy-1,1′-biphenyl-2-yl)phosphine Borane (RP-7b). The pure RP-7b was obtained as a white solid, mp 153.9−156.2 °C; 31P NMR (162 MHz, CDCl3) δ = 35.4 (broad m); 1 H NMR (400 MHz, CDCl3) δ = 8.16 (dd, J = 13.3, 7.7, 1H), 7.62− 7.46 (m, 2H), 7.41−7.22 (m, 2H), 7.15 (d, J = 7.5, 0.5H), 7.00 (dd, J = 12.1, 8.5, 2.5H), 4.36 (s, 1H), 2.01 (dt, J = 14.9, 7.2, 0.7H), 1.89 (dt, J = 20.7, 7.5, 1.3H), 1.75−1.37 (m, 5H), 1.27 (d, J = 10.8, 1H), 1.22−0.98 (m, 2H), 0.98−0.81 (m, 8H), 0.78 (d, J = 6.2, 3H), 0.66 (t, J = 34.6, 3H), 0.43 (d, J = 6.8, 1.7H), 0.38 (d, J = 6.8, 1.3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 153.8 (s), 153.4 (s), 139.8 (d, J = 7.6), 138.5 (dd, J = 18.9, 16.2), 131.9 (dd, J = 9.2, 6.0), 131.1 (s), 130.5−123.0 (m), 129.8 (s), 128.6−127.8 (m), 127.7 (s), 127.3 (d, J = 11.5), 119.9 (s), 119.4 (s), 116.0 (d, J = 3.6), 44.3 (s), 44.1 (d, J = 23.0), 37.3 (d, J = 6.9), 37.0 (s), 35.9 (s), 35.6 (s), 34.2 (s), 33.1 (dd, J = 25.1, 11.8), 29.0−28.5 (m), 24.9 (dd, J = 11.7, 3.6), 22.4 (d, J = 14.6), 21.4 (s), 21.3 (d, J = 20.5), 20.8 (s), 18.4 (s), 18.0 (s), 15.0 (d, J = 12.1), 9.0 (d, J = 2.7), 8.8 (s); HRMS (ESI+) Calcd. for C24H34OP [M-BH3 + H+]: 369.2347, Found: 369.2348. (RP)-(−)-Menthyl Butyl (2′-Hydroxy-1,1′-biphenyl-2-yl)phosphine Borane (RP-7c). The crude RP-7c was obtained from butyl magnesium bromide (0.8 M solution in ether), and the pure RP-7c was obtained as a white solid (56.1 mg, 57%, > 99:1 drP and 61:39 drA) from preparative TLC (silica gel, dichloromethane/petroleum ether = 4/1 as eluent), mp 142.9−144.4 °C; 31P NMR (162 MHz, CDCl3) δ = 31.78 (broad m); 1H NMR (400 MHz, CDCl3) δ = 8.22−8.10 (m, 1H), 7.53 (dq, J = 20.5, 7.0, 2H), 7.38−7.24 (m, 2H), 7.11 (d, J = 7.4, 0.5H), 6.99 (d, J = 7.4, 2.5H), 4.19 (s, 1H), 2.05 (dd, J = 16.4, 9.8, 1H), 1.87 (ddd, J = 26.1, 22.6, 12.1, 2H), 1.69 (d, J = 7.0, 1H), 1.65− 1.40 (m, 4H), 1.32 (ddd, J = 21.3, 14.8, 7.2, 3H), 1.20−1.08 (m, 2H), 1.08−0.92 (m, 2H), 0.89 (d, J = 6.6, 3H), 0.84 (d, J = 7.3, 3H), 0.80− 0.75 (m, 4H), 0.74−0.50 (m, 3H), 0.46 (d, J = 6.8, 1.8H), 0.39 (d, J = 6.8, 1.2H); 13C {1H} NMR (101 MHz, CDCl3) δ = 153.2 (s), 139.5 (s), 139.2 (s), 138.8 (d, J = 16.3), 138.3 (d, J = 16.2), 131.8 (dd, J = 5.9, 2.6), 131.1 (dd, J = 5.9, 2.2), 130.3 (d, J = 10.8), 129.9 (d, J = 4.1), 129.1 (s), 128.9−127.9 (m), 127.2 (d, J = 7.7), 120.0 (s), 119.8 (s), 116.0 (d, J = 11.5), 44.2 (s), 44.0 (d, J = 1.7), 37.6 (s), 37.3 (d, J = 19.8), 36.0 (s), 35.7 (s), 34.2 (s), 33.3 (d, J = 11.2), 33.0 (d, J = 12.1), 28.6 (dd, J = 11.6, 1.8), 27.8 (s), 27.47 (s), 26.7 (d, J = 1.9), 26.3 (s), 25.3−24.6 (m), 24.3 (dd, J = 15.0, 5.8), 22.4 (d, J = 14.8), 21.4 (s), 21.2 (s), 15.1 (d, J = 6.9), 13.7 (s); HRMS (ESI+) Calcd. for C26H38OP [M-BH3 + H+]: 397.2660, Found: 397.2651. (R P )-(−)-Menthyl Pentyl (2′-Hydroxy-1,1′-biphenyl-2-yl)phosphine Borane (RP-7d). The crude RP-7d was obtained from pentyl magnesium bromide (0.8 M solution in ether), and the pure RP-7d was obtained as a white solid (32.6 mg, 32%, > 99:1 drP and 59:41 drA) from preparative TLC (silica gel, dichloromethane/ petroleum ether = 4/1 as eluent), mp 160.2−163.8 °C; 31P NMR (162 MHz, CDCl3) δ = 31.96 (broad m); 1H NMR (400 MHz, CDCl3) δ = 8.14 (dd, J = 10.7, 6.4, 1H), 7.61−7.42 (m, 2H), 7.38− 7.21 (m, 2H), 7.08 (d, J = 7.5, 0.4H), 6.98 (t, J = 8.2, 2.6H), 4.14 (s, 1H), 2.10−1.98 (m, 1H), 1.98−1.72 (m, 2H), 1.72−1.34 (m, 6H), 1.23 (s, 3H), 1.11 (s, 3H), 1.05−0.72 (m, 13H), 0.68 (d, J = 6.1, 2H), 0.44 (d, J = 6.8, 1.8H), 0.37 (d, J = 6.8, 1.2H); 13C {1H} NMR (101 MHz, CDCl3) δ = 153.4 (d, J = 14.6), 139.5 (s), 139.3 (s), 138.5 (dd, J = 35.2, 16.3), 132.1−131.6 (m), 131.1 (s), 130.3 (d, J = 10.5), 129.9 (d, J = 4.1), 129.2 (s), 128.6 (dd, J = 30.1, 12.0), 127.3 (s), 119.9 (s), 119.6 (s), 116.0 (d, J = 5.8), 44.2 (s), 44.0 (d, J = 1.6), 37.7 (s), 37.4 (s), 37.2 (s), 36.0 (s), 35.7 (s), 34.2 (s), 33.7−33.1 (m), 33.0 (d, J = 12.1), 28.9−28.4 (m), 28.0 (s), 27.7 (s), 25.5−24.6 (m), 24.5 (s), 24.1 (s), 22.3 (dd, J = 16.8, 8.4), 21.4 (s), 21.2 (s), 15.1 (d, J = 7.6), 14.0 (s); HRMS (ESI+) Calcd. for C27H40OP [M-BH3 + H+]: 411.2817, Found: 411.2816. (R P)-(−)-Menthyl iso-Butyl (2′-Hydroxy-1,1′-biphenyl-2-yl)phosphine Borane (RP-7e). The preparation of RP-7e was carried out in toluene at 80 °C, and the crude product was obtained from isobutyl magnesium bromide (0.8 M solution in ether). The pure RP-7e was obtained as a white solid (39.4 mg, 40%, > 99:1 drP and 58:42

drA) from preparative TLC (silica gel, dichloromethane/petroleum ether = 4/1 as eluent), mp 131.9−132.8 °C; 31P NMR (162 MHz, CDCl3) δ = 31.10 (broad s, 42%), 29.42 (broad s, 58%); 1H NMR (400 MHz, CDCl3) δ = 8.32−8.20 (m, 1H), 7.62−7.45 (m, 2H), 7.45−7.10 (m, 3H), 6.99 (d, J = 5.5, 2H), 4.58 (s, 1H), 2.13−1.98 (m, 1H), 1.97−1.74 (m, 2H), 1.69 (d, J = 8.6, 1H), 1.65−1.47 (m, 3H), 1.44−1.33 (m, 1H), 1.27 (d, J = 14.0, 1H), 1.17 (s, 1H), 1.03 (dd, J = 14.9, 9.5, 1H), 0.98 (d, J = 6.5, 2H), 0.90 (dd, J = 6.3, 3.1, 4H), 0.86 (t, J = 5.9, 4H), 0.76 (d, J = 6.3, 3H), 0.66 (dd, J = 28.0, 8.9, 4H), 0.52 (d, J = 6.8, 1.7H), 0.43 (d, J = 6.8, 1.3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 153.1 (s), 152.6 (s), 139.5 (s), 139.1 (s), 138.3 (dd, J = 21.7, 16.7), 132.1 (d, J = 6.0), 131.8 (d, J = 5.9), 131.2 (t, J = 2.4), 130.5−130.1 (m), 129.8 (t, J = 10.4), 129.1 (s), 128.6 (dd, J = 12.2, 7.9), 127.2 (d, J = 8.6), 119.9 (d, J = 2.3), 44.4− 44.0 (m), 38.1 (s), 37.8 (s), 37.3 (s), 36.9 (t, J = 15.2), 36.5 (s), 36.2 (s), 34.2 (d, J = 2.9), 33.4−32.7 (m), 32.5 (s), 28.6 (d, J = 1.9), 28.3 (d, J = 2.2), 26.2 (d, J = 2.5), 25.5−24.8 (m), 24.6 (d, J = 9.0), 24.3 (d, J = 7.3), 23.7 (d, J = 4.2), 22.5 (s), 22.3 (s), 21.4 (s), 21.1 (s), 15.3 (d, J = 3.0); HRMS (ESI+) Calcd. for C26H38OP [M-BH3 + H+]: 397.2660, Found: 397.2656. (RP)-(−)-Menthyl Allyl (2′-Hydroxy-1,1′-biphenyl-2-yl)phosphine Borane (RP-7f). The crude RP-7f was obtained from allylmagnesium bromide (1 M solution in ether), and the pure RP-7f was obtained as a white solid (69.1 mg, 73%, > 99:1 drP and 59:41 drA) from preparative TLC (silica gel, dichloromethane/petroleum ether = 4/1 as eluent), mp 122.4−125.5 °C; 31P NMR (162 MHz, CDCl3) δ = 30.86 (broad m); 1H NMR (400 MHz, CDCl3) δ = 8.12 (td, J = 13.1, 7.9, 1H), 7.56 (t, J = 7.3, 1H), 7.49 (t, J = 7.3, 1H), 7.41−7.33 (m, 1H), 7.33−7.17 (m, 1.5H), 7.10−6.93 (m, 2.5H), 5.67−5.33 (m, 1H), 5.13−4.89 (m, 2H), 4.83 (d, J = 11.2, 1H), 2.92 (td, J = 14.9, 6.8, 0.4H), 2.75 (dt, J = 14.0, 7.1, 0.4H), 2.65-2.48 (m, 0.6H), 2.44− 2.27 (m, 0.6H), 1.93 (ddd, J = 31.2, 15.9, 6.1, 2H), 1.76−1.52 (m, 3H), 1.45 (dd, J = 24.3, 12.2, 1H), 1.26 (s, 2H), 1.17−0.95 (m, 2H), 0.86 (dd, J = 12.4, 6.6, 5H), 0.78 (d, J = 6.3, 2H), 0.72 (d, J = 6.3, 2H), 0.45 (d, J = 6.9, 1.3H), 0.42 (d, J = 6.9, 1.7H); 13C {1H} NMR (101 MHz, CDCl3) δ = 153.3 (d, J = 6.2), 139.6 (d, J = 6.0), 138.0 (dd, J = 16.2, 6.4), 132.1 (d, J = 6.1), 131.9 (d, J = 6.2), 131.2 (d, J = 2.5), 130.5−129.7 (m), 129.0 (s), 128.4 (t, J = 11.4), 128.1 (s), 127.3 (d, J = 7.6), 119.9 (d, J = 22.4), 119.4 (d, J = 11.2), 119.0 (d, J = 11.9), 116.2 (d, J = 4.8), 44.3 (s), 43.9 (s), 37.6 (s), 37.4 (s), 37.0 (d, J = 8.6), 36.1 (s), 35.9 (s), 34.1 (s), 33.8 (s), 33.5 (s), 33.1 (dd, J = 18.7, 11.9), 30.5 (s), 30.2 (s), 28.9−28.4 (m), 24.9 (dd, J = 11.7, 3.3), 22.4(d, J = 15.9), 21.4 (s), 21.2 (s), 15.1 (d, J = 11.7); HRMS (ESI+) Calcd. for C25H34OP [M-BH3 + H+]: 381.2347, Found: 381.2339. (R P )-(−)-Menthyl Benzyl (2′-Hydroxy-1,1′-biphenyl-2-yl)phosphine Borane (RP-7g). The preparation of RP-7g was carried out in toluene at 80 °C, and the crude product was obtained from benzyl magnesium chloride (0.8 M solution in ether). The pure RP-7g was obtained as a white solid (69.3 mg, 65%, > 99:1 drP and 52:48 drA) from preparative TLC (silica gel, dichloromethane/petroleum ether = 4/1 as eluent), mp 143.1−146.2 °C; 31P NMR (162 MHz, CDCl3) δ = 34.07 (broad s, 52%), 32.44 (broad s, 48%); 1H NMR (400 MHz, CDCl3) δ = 7.95 (dd, J = 12.8, 7.8, 0.5H), 7.70 (dd, J = 12.8, 7.8, 0.5H), 7.51 (dt, J = 21.7, 7.4, 1H), 7.46−7.31 (m, 2H), 7.28 (s, 1H), 7.23−6.96 (m, 5H), 6.91 (t, J = 10.7, 3H), 3.60 (t, J = 14.5, 0.5H), 3.43−3.31 (m, 1H), 2.95 (dd, J = 14.3, 8.1, 0.5H), 2.27−2.07 (m, 1H), 1.96 (dd, J = 23.6, 11.2, 1H), 1.69 (s, 2H), 1.56 (dd, J = 31.8, 11.8, 1H), 1.43−1.22 (m, 2H), 1.17−0.98 (m, 2H), 0.90 (dd, J = 9.7, 5.2, 4H), 0.86−0.67 (m, 5H), 0.60 (d, J = 6.9, 1.6H), 0.57 (d, J = 6.9, 1.4H), 0.52−0.11 (m, 1H); 13C {1H} NMR (101 MHz, CDCl3) δ = 153.1 (s), 152.9 (s), 140. 5 (s), 139.7 (s), 137.7 (d, J = 14.1), 137.4 (d, J = 15.1), 133.6 (d, J = 3.6), 133.1 (d, J = 5.3), 132.4 (d, J = 6.5), 132.1 (d, J = 6.4), 131.1 (s), 130.6 (s), 130.4−129.9 (m), 129.1 (s), 128.6 (s), 128.1 (dd, J = 11.5, 7.1), 127.7 (t, J = 2.7), 127.4 (s), 126.6 (dd, J = 12.1, 2.9), 120.0 (d, J = 6.5), 116.5 (s), 116.1 (s), 44.4 (s), 44.1 (s), 37.6 (s), 37.4−36.9 (m), 36.6 (s), 36.3 (d, J = 6.1), 36.0 (s), 34.2 (s), 33.2 (t, J = 11.8), 32.1 (s), 31.8 (s), 28.9 (s), 28.5 (s), 25.0 (d, J = 11.5), 22.5 (s), 22.2 (s), 21.4 (s), 21.2 (s), 15.4 (d, J = 8.8); HRMS (ESI+) Calcd. for C29H36OP [M-BH3 + H+]: 431.2504, Found: 431.2504. 8429


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MHz, CDCl3) δ = 153.0 (s), 152.7 (s), 140.0 (d, J = 12.2), 138.3− 137.8 (m), 135.0 (d, J = 6.9), 132.8−132.2 (m), 131.9 (d, J = 3.7), 131.6−131.1 (m), 130.8 (d, J = 5.2), 130.5−130.1 (m), 129.3 (d, J = 2.1), 128.9 (d, J = 3.2), 128.3 (dd, J = 12.1, 3.1), 127.9 (dd, J = 18.7, 2.3), 127.3 (dd, J = 16.5, 1.7), 126.1 (dd, J = 3.7, 1.8), 44.7 (s), 44.3 (s), 37.7 (s), 37.4 (s), 37.2 (s), 36.9 (s), 36.5 (s), 36.2 (s), 34.2 (s), 33.2 (dd, J = 25.7, 11.7), 32.0 (s), 31.7 (s), 28.8 (s), 28.4 (s), 28.4− 28.0 (m), 25.0 (dd, J = 11.6, 3.8), 22.5 (s), 22.3 (s), 21.4 (s), 21.1 (s), 15.3 (d, J = 16.5); HRMS (ESI+) Calcd. for C29H35ClOP [M-BH3 + H+]: 465.2114, Found: 465.2113. (RP)-(−)-Menthyl o-Methylbenzyl (2′-Hydroxy-1,1′-biphenyl-2yl)phosphine Borane (RP-7k). The preparation of RP-7k was carried out in toluene at 80 °C, and the crude product was obtained from 2methylbenzyl magnesium bromide (0.8 M solution in ether). The pure RP-7k was obtained as a white solid (26.4 mg, 24%, > 99:1 drP and 60:40 drA) from preparative TLC (silica gel, dichloromethane/ petroleum ether = 4/1 as eluent), mp 143.7−147.4 °C; 31P NMR (162 MHz, CDCl3) δ = 34.28 (broad s, 39%), 31.24 (broad s, 61%); 1 H NMR (400 MHz, CDCl3) δ = 8.17 (dd, J = 13.0, 8.1, 0.6H), 7.86 (dd, J = 13.0, 8.1, 0.4H), 7.52 (dt, J = 29.0, 7.4, 2H), 7.42−7.27 (m, 2H), 7.19 (d, J = 6.3, 1H), 7.11 (d, J = 7.8, 0.6H), 7.05 (t, J = 6.3, 1H), 7.02−6.92 (m, 2H), 6.77 (td, J = 16.5, 8.3, 2H), 6.36 (d, J = 7.8, 0.4H), 3.83 (s, 1H), 3.56−3.36 (m, 1H), 3.15 (t, J = 15.7, 0.5H), 3.00 (dd, J = 15.8, 7.9, 0.5H), 2.26 (d, J = 12.9, 2H), 2.09−1.82 (m, 3H), 1.70 (d, J = 8.6, 3H), 1.61 (d, J = 10.6, 1H), 1.41−1.22 (m, 2H), 1.20−0.99 (m, 2H), 0.91 (dd, J = 12.4, 10.0, 4H), 0.79 (d, J = 6.0, 1.8H), 0.74 (d, J = 6.0, 1.2H), 0.61 (d, J = 4.6, 5H); 13C {1H} NMR (101 MHz, CDCl3) δ = 153.5−153.4 (m), 153.3 (d, J = 20.2), 140.5 (s), 139.9 (s), 138.4 (d, J = 14.8), 138.1−137. 5 (m), 132.8 (d, J = 3.4), 132.4 (t, J = 5.9), 132.1 (d, J = 4.7), 131.3 (s), 131.1 (s), 130.4 (s), 130.2 (d, J = 5.0), 129.2 (dd, J = 20.4, 5.1), 128.8 (d, J = 11.5), 128.3 (t, J = 12.0), 127.8 (s), 127.3 (s), 126.9−126.4 (m), 125.2 (s), 125.00 (d, J = 2.2), 119.9 (s), 119.7 (s), 116.4 (d, J = 16.0), 44.8 (s), 44.2 (s), 38.1 (s), 37.8 (s), 37.5−37.3 (m), 37.1 (d, J = 21.1), 36.3 (s), 36.1 (s), 34.2 (s), 33.2 (dd, J = 25.4, 11.5), 32.1−31.9 (m), 31.7 (d, J = 27.5), 29.0 (s), 28.6 (d, J = 18.5), 28.2 (s), 25.0 (dd, J = 11.5, 5.1), 22.5 (s), 22.3 (s), 21.4 (s), 21.1 (s), 20.8(s), 20.5 (s), 15.4 (d, J = 15.9); HRMS (ESI+) Calcd. for C30H38OP [M-BH3 + H+]: 445.2660, Found: 445.2666. The Alkylation of RP-7 To Form RP-8, Typical Procedure. To the solution of RP-7a (80.0 mg, 0.217 mmol) and potassium hydroxide (14.3 mg, 0.217 mmol) in ethanol (1 mL) was added methyl iodide (52.3 μL, 0.434 mmol) and the mixture was stirred at room temperature for 10 h. After the reaction was completed, as monitored with TLC, a saturated solution of ammonium chloride (5 mL) was added. The mixture was extracted with dichloromethane (3 × 5 mL), washed with water (3 × 10 mL), and dried over magnesium sulfate. After removing the solvent, the residue was purified with preparative TLC (silica gel, dichloromethane/petroleum ether = 4/1 as eluent) to afford RP-8a (57.2 mg, 69%, > 99:1 drP and 70:30 drA). (R P )-(−)-Menthyl Methyl (2′-Methoxy-1,1′-biphenyl-2-yl)phosphine Borane (RP-8a). The pure RP-8a was obtained as a white solid, mp 117.5−121.8 °C; 31P NMR (162 MHz, CDCl3) δ = 20.5 (broad m); 1H NMR (400 MHz, CDCl3) δ = 8.07 (dd, J = 13.7, 7.9, 1H), 7.44 (ddd, J = 15.5, 13.4, 7.8, 3H), 7.17 (d, J = 7.4, 1H), 7.06−6.91 (m, 3H), 3.73 (s, 3H), 1.92−1.76 (m, 1H), 1.67 (d, J = 8.3, 2H), 1.31 (d, J = 10.3, 0.9H), 1.25 (s, 1H), 1.17 (d, J = 10.3, 2.1H), 1.10−0.43 (m, 14H), 0.39 (dd, J = 6.8, 4.5, 4H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.9 (s), 142.0 (s), 141.7 (s), 135.8 (dd, J = 36.7, 17.1), 132.3−131.91 (m), 131.7 (d, J = 6.3), 130.6 (s), 130.4−129.9 (m), 129.8 (s), 129.3 (s), 127.2 (dd, J = 12.6, 9.6), 119.7 (d, J = 13.6), 110.6 (d, J = 4.8), 55.5 (s), 55.1 (s), 44.0 (d, J = 10.7), 37.9 (s), 37.6 (s), 36.9 (s), 36.4 (s), 36.1 (s), 35.8 (s), 34.3 (d, J = 4.4), 33.5−33.2 (m), 28.4 (dd, J = 6.9, 2.4), 24.9 (dd, J = 11.5, 9.1), 22.4 (d, J = 15.5), 21.3 (d, J = 13.8), 15.3−14.8 (m), 12.2 (s), 11.8 (s); HRMS (ESI+) Calcd. for C24H34OP [M-BH3 + H+]: 369.2347, Found: 369.2345. (R P )-(−)-Menthyl Methyl (2′-Butoxy-1,1′-biphenyl-2-yl)phosphine Borane (RP-8b). The crude RP-8b was obtained from the reaction of RP-7a with n-butyl bromide, and the pure compound

(RP)-(−)-Menthyl p-tert-Butyl (2′-Hydroxy-1,1′-biphenyl-2-yl)phosphine Borane (RP-7h). The preparation of RP-7h was carried out in toluene at 80 °C, and the crude product was obtained from (4(tert-butyl)benzyl)magnesium bromide (0.8 M solution in ether). The pure RP-7h was obtained as a white solid (76.8 mg, 64%, > 99:1 drP and 48:52 drA) from preparative TLC (silica gel, dichloromethane/petroleum ether = 4/1 as eluent), mp 145.8−149.4 °C; 31P NMR (162 MHz, CDCl3) δ = 33.86 (broad s, 48%), 31.78 (broad s, 52%); 1H NMR (400 MHz, CDCl3) δ = 7.94 (dd, J = 12.6, 7.9, 0.6H), 7.79 (d, J = 8.3, 0.4H), 7.67 (dd, J = 12.6, 7.9, 0.6H), 7.54 (d, J = 8.3, 0.4H), 7.52−7.37 (m, 2H), 7.33 (dd, J = 15.6, 7.8, 1H), 7.26− 7.17 (m, 1H), 7.12 (d, J = 8.2, 1H), 7.06 (d, J = 8.2, 1H), 7.01 (t, J = 7.6, 1H), 6.96−6.75 (m, 3H), 4.54 (s, 1H), 3.55 (t, J = 14.5, 0.5H), 3.41−3.25 (m, 1H), 2.91 (dd, J = 14.3, 8.6, 0.5H), 2.26−2.06 (m, 1H), 1.97 (q, J = 10.6, 1H), 1.66 (d, J = 9.5, 2H), 1.56 (t, J = 15.4, 1H), 1.47−1.13 (m, 12H), 1.13−0.95 (m, 2H), 0.88 (dd, J = 20.4, 13.1, 4H), 0.78 (t, J = 8.0, 2H), 0.73 (d, J = 5.8, 2H), 0.59 (d, J = 6.8, 1.4H), 0.55 (d, J = 6.8, 1.6H), 0.47−0.12 (m, 1H); 13C {1H} NMR (101 MHz, CDCl3) δ = 153.2 (s), 149.6 (d, J = 3.2), 149.3 (s), 140.9 (s), 139.9 (s), 137.6 (d, J = 13.7), 136.9 (d, J = 14.8), 132.4 (d, J = 6.6), 132.1 (d, J = 6.5), 130.9 (s), 130.7−130.2 (m), 130.2−129.6 (m), 129.1 (s), 127.9 (d, J = 11.3), 127.5 (s), 44.4 (s), 44.1 (s), 37.7 (s), 37.3 (d, J = 18.5), 37.0 (s), 36.6 (s), 36.4 (s), 35.7 (s), 35.4 (s), 34.3 (d, J = 9.0), 33.2 (dd, J = 15.1, 11.5), 31.4 (t, J = 7.1), 31.1 (s), 28.9 (s), 28.5 (s), 25.0 (dd, J = 11.3, 5.0), 22.5 (s), 22.3 (s), 21.5 (s), 21.3 (s), 15.4 (d, J = 8.6); HRMS (ESI+) Calcd. for C33H44OP [MBH3 + H+]: 487.3130, Found: 487.3112. (RP)-(−)-Menthyl p-Methylbenzyl (2′-Hydroxy-1,1′-biphenyl-2yl)phosphine Borane (RP-7i). The preparation of RP-7i was carried out in toluene at 80 °C, and the crude product was obtained from (4methylbenzyl)magnesium chloride (0.8 M solution in ether). The pure RP-7i was obtained as a white solid (72.6 mg, 66%, > 99:1 drP and 48:52 drA) from preparative TLC (silica gel, dichloromethane/ petroleum ether = 4/1 as eluent), mp 57.9−60.1 °C; 31P NMR (162 MHz, CDCl3) δ = 34.23 (broad s, 49%), 32.33 (broad s, 51%); 1H NMR (400 MHz, CDCl3) δ = 7.93 (dd, J = 12.9, 7.9, 0.4H), 7.76 (dd, J = 12.9, 7.9, 0.6H), 7.47 (t, J = 7.0, 1H), 7.43−7.29 (m, 2H), 7.29− 7.16 (m, 2H), 7.01 (t, J = 7.9, 1H), 6.89 (dd, J = 14.7, 8.6, 3H), 6.78 (dd, J = 14.1, 7.3, 2H), 4.81 (s, 1H), 3.56 (t, J = 14.5, 0.5H), 3.41− 3.24 (m, 1H), 2.86 (dd, J = 14.2, 9.1, 0.5H), 2.23 (s, 3H), 2.16−1.86 (m, 1H), 1.66 (s, 3H), 1.59−1.45 (m, 1H), 1.33 (dd, J = 28.0, 20.4, 2H), 1.18−0.93 (m, 2H), 0.87 (t, J = 15.3, 4H), 0.77 (d, J = 6.4, 2H), 0.73 (d, J = 5.1, 2H), 0.59 (d, J = 6.7, 1.4H), 0.54 (d, J = 6.7, 1.6H); 13 C {1H} NMR (101 MHz, CDCl3) δ = 153.2 (s), 140.7 (s), 139.9 (s), 138.0−137.4 (m), 137.3 (s), 136.2 (d, J = 3.1), 136.0 (s), 132.3 (dd, J = 30.5, 6.4), 132.0−131.7 (m), 131.0 (d, J = 2.8), 130.8−130.1 (m), 130.1−129.3 (m), 128.5 (dd, J = 15.1, 12.5), 128.1 (dd, J = 23.7, 11.4), 127.5 (s), 119.9 (d, J = 9.8), 116.6 (s), 116.2 (s), 44.4 (s), 44.1 (s), 37.5 (s), 37.3−36.8 (m), 36.6 (s), 36.3 (s), 35.8 (s), 35.5 (s), 34.2 (s), 33.1 (t, J = 11.8), 31.5 (s), 31.3 (s), 28.9 (s), 28.5 (s), 25.0 (d, J = 11.4), 22.5 (s), 22.3 (s), 21.5 (s), 21.1 (d, J = 19.9), 15.4 (d, J = 7.8); HRMS (ESI+) Calcd. for C30H38OP [M-BH3 + H+]: 445.2660, Found: 445.2670. (RP)-(−)-Menthyl o-Chlorobenzyl (2′-Hydroxy-1,1′-biphenyl-2yl)phosphine Borane (RP-7j). The preparation of RP-7j was carried out in toluene at 80 °C, and the crude product was obtained from 2chlorobenzyl magnesium chloride (0.8 M solution in ether). The pure RP-7j was obtained as a white solid (29.8 mg, 26%, > 99:1 drP and 63:37 drA) from preparative TLC (silica gel, dichloromethane/ petroleum ether = 4/1 as eluent), mp 146.1−148.5 °C; 31P NMR (162 MHz, CDCl3) δ = 33.70 (broad s, 37%), 32.29 (broad s, 63%); 1 H NMR (400 MHz, CDCl3) δ = 8.10 (dd, J = 13.5, 7.8, 0.6H), 7.92 (dd, J = 13.5, 7.8, 0.4H), 7.56 (dd, J = 17.3, 8.3, 1H), 7.48 (t, J = 7.6, 1H), 7.44−7.32 (m, 2H), 7.29 (d, J = 6.3, 1H), 7.13−7.01 (m, 3H), 6.98 (d, J = 7.5, 0.4H), 6.96−6.86 (m, 2H), 6.78 (d, J = 7.5, 0.6H), 4.77 (s, 1H), 3.69 (t, J = 15.1, 0.4H), 3.55 (dd, J = 15.0, 6.7, 0.4H), 3.34 (t, J = 15.1, 0.6H), 3.22 (dd, J = 15.5, 7.9, 0.6H), 2.42−2.19 (m, 1H), 2.02 (q, J = 11.6, 1H), 1.65 (dd, J = 37.9, 7.8, 3H), 1.42−1.18 (m, 2H), 1.16−0.99 (m, 1H), 1.00−0.83 (m, 5H), 0.80 (t, J = 8.6, 3H), 0.73 (d, J = 5.5, 1H), 0.62 (t, J = 6.6, 5H); 13C {1H} NMR (101 8430


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(s), 39.6 (s), 38.9 (s), 37.5 (s), 37.2 (s), 34.1−33.5 (m), 33.2 (d, J = 16.0), 29.1−28.5 (m), 24.3 (dd, J = 25.4, 13.0), 22.2 (d, J = 5.0), 21.5 (d, J = 17.5), 15.0 (s), 14.4 (s); HRMS (ESI+) Calcd. for C23H32O2P [M + H+]: 371.2140, Found: 371.2161. (S P )-(−)-Menthyl (2′-Methoxy-1,1′-biphenyl-2-yl)phosphine Oxide (SP-9a′). The crude SP-9a′ was obtained from SP-5′ and methyl iodide, and the pure compound was obtained as a white solid (66.6 mg, 80%, > 99:1 drP and 55:45 drA ) from preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/3 as eluent), mp 125.4− 128.5 °C; 31P NMR (162 MHz, CDCl3) δ = 21.19 (s, 55%), 18.66 (s, 45%); 1H NMR (400 MHz, CDCl3) δ = 8.18 (s, 0.27H), 8.16−8.05 (m, 1H), 8.04 (s, 0.23H), 7.64−7.49 (m, 2H), 7.45−7.33 (m, 1H), 7.24 (dd, J = 15.2, 10.4, 1H), 7.15 (d, J = 8.3, 0.6H), 7.06 (dd, J = 8.8, 6.8, 1H), 7.00 (d, J = 9.0, 1H), 6.97 (s, 0.27H), 6.94 (d, J = 8.3, 0.4H), 6.84 (s, 0.23H), 3.73 (s, 3H), 2.20−2.04 (m, 1H), 1.74−1.55 (m, 3H), 1.33 (s, 1H), 1.17−0.95 (m, 3H), 0.88 (d, J = 6.5, 4H), 0.78 (dd, J = 12.2, 6.0, 4H), 0.26 (d, J = 6.8, 3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.7 (s), 155.8 (s), 140.4 (s), 140.0(d, J = 11.3), 133.6 (d, J = 6.0), 133.1 (d, J = 6.1), 131.7 (s), 131.2−130.3 (m), 130.3 (s), 130.0 (d, J = 9.8), 129.3 (s), 128.7 (s), 128.0 (d, J = 52.2), 127.6 (s), 127.5−126.7 (m), 120.9 (s), 120.5 (s), 110.9 (d, J = 11.7), 55.3 (d, J = 17.6), 41.6 (dd, J = 7.2, 3.6), 39.6 (s), 38.9 (d, J = 7.7), 38.2 (s), 34.3 (d, J = 4.4), 33.1 (d, J = 14.0), 32.6 (d, J = 13.7), 31.6 (dd, J = 16.4, 3.6), 27.4 (d, J = 5.4), 24.2 (dd, J = 23.2, 12.1), 22.4 (d, J = 5.7), 21.4 (d, J = 3.1), 14.7 (s); HRMS (ESI+) Calcd. for C23H32O2P [M + H+]: 371.2140, Found: 371.2148. (RP)-(−)-Menthyl (2′-Ethoxy-1,1′-biphenyl-2-yl)phosphine Oxide (RP-9b). The crude RP-9b was obtained from bromoethane, and the pure compound was obtained as a white solid (70.2 mg, 81%, > 99:1 drP and 52:48 drA) from preparative TLC (silica gel, petroleum ether/ ethyl acetate = 1/3 as eluent), mp 100.3−102.0 °C; 31P NMR (162 MHz, CDCl3) δ = 36.63 (s, 52%), 33.87 (s, 48%); 1H NMR (400 MHz, CDCl3) δ = 8.14−7.96 (m, 1H), 7.82 (s, 0.24H), 7.64 (s, 0.26H), 7.52 (dd, J = 18.0, 6.8, 2H), 7.36 (t, J = 7.7, 1H), 7.30−7.11 (m, 2H), 6.99 (dt, J = 17.7, 8.0, 2H), 6.63 (s, 0.24H), 6.44 (s, 0.26H), 4.09−3.87 (m, 2H), 2.17−1.96 (m, 1H), 1.58 (d, J = 7.7, 3H), 1.45 (s, 1H), 1.25 (t, J = 7.0, 3H), 1.09−0.90 (m, 2H), 0.84 (d, J = 6.3, 2H), 0.80 (d, J = 6.7, 3H), 0.73 (d, J = 4.5, 4H), 0.30 (t, J = 6.3, 3H); 13 C {1H} NMR (101 MHz, CDCl3) δ = 155.9 (s), 155.3 (s), 141.1 (s), 140.7 (d, J = 11.1), 132.1 (s), 131.8−131.6 (m), 131.6−131.1 (m), 130.7 (dd, J = 23.7, 14.0), 129.8 (s), 128.6 (s), 128.1−127.8 (m), 127.4 (dd, J = 29.0, 18.9), 120.7 (s), 120.3 (s), 112.0 (s), 111.8 (s), 63.9 (s), 63.5 (s), 42.5 (d, J = 3.4), 40.6 (s), 39.9 (d, J = 19.9), 39.1 (s), 37.7 (s), 37.0 (s), 34.0 (s), 33.7 (d, J = 16.7), 33.1 (d, J = 15.7), 28.7 (d, J = 28.3), 24.3 (dd, J = 24.8, 12.7), 22.2 (d, J = 10.3), 21.5 (d, J = 12.0), 15.0 (s), 14.6 (s); HRMS (ESI+) Calcd. for C24H34O2P [M + H+]: 385.2296, Found: 385.2318. (RP)-(−)-Menthyl (2′-Isopropoxy-1,1′-biphenyl-2-yl)phosphine Oxide (RP-9c). The crude RP-9c was obtained from 2-bromopropane, and the pure compound was obtained as a white solid (67.2 mg, 75%, > 99:1 drP and 48:52 drA) from preparative TLC (silica gel, petroleum ether/ethyl acetate = 2/1 as eluent), mp 113.1−115.3 °C; 31P NMR (162 MHz, CDCl3) δ = 36.23 (s, 48%), 34.01 (s, 52%); 1H NMR (400 MHz, CDCl3) δ = 8.03 (dd, J = 23.5, 10.6, 1H), 7.85 (s, 0.26H), 7.72 (s, 0.24H), 7.60−7.43 (m, 2H), 7.35 (t, J = 7.8, 1H), 7.27−7.11 (m, 2H), 6.99 (dq, J = 14.4, 7.1, 2H), 6.66 (s, 0.26H), 6.52 (s, 0.24H), 4.58 (dt, J = 11.7, 5.8, 0.5H), 4.39 (dt, J = 11.7, 5.8, 0.5H), 2.17−2.07 (m, 0.5H), 2.06−1.96 (m, 0.5H), 1.73 (d, J = 12.9, 1H), 1.59 (s, 3H), 1.47 (s, 1H), 1.26 (t, J = 5.8, 3H), 1.21 (d, J = 5.9, 2H), 1.08 (d, J = 6.0, 2H), 1.04−0.92 (m, 2H), 0.84 (d, J = 6.7, 2H), 0.80 (d, J = 6.8, 2H), 0.73 (d, J = 5.9, 4H), 0.29 (dd, J = 6.6, 3.1, 3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 154.9 (s), 154.5 (s), 141.3 (d, J = 10.8), 140.9 (d, J = 11.5), 132.1 (s), 132.0−131.0 (m), 130.9 (s), 130.8−130.2 (m), 129.7 (t, J = 7.7), 128.2 (s), 127.2 (dd, J = 15.1, 10.5), 120.8 (s), 120.1 (s), 114.6 (s), 113.3 (s), 71.3 (s), 70.2 (s), 42.7−42.2 (m), 40.6 (s), 40.0 (s), 39.4 (s), 38.8 (s), 37.9 (s), 37.2 (s), 34.0 (s), 33.3 (dd, J = 25.9, 16.1), 28.9 (s), 28.6 (s), 24.2 (dd, J = 12.8, 8.6), 22.2 (dd, J = 17.3, 11.1), 21.9 (s), 21.5 (d, J = 14.6), 15.1 (d, J = 14.3); HRMS (ESI+) Calcd. for C25H36O2P [M + H+]: 399.2453, Found: 399.2465.

was obtained as a colorless oil (66.2 mg, 72%, > 99:1 drP and 68:32 drA) from preparative TLC (silica gel, petroleum ether/ethyl acetate = 2/1 as eluent); 31P NMR (162 MHz, CDCl3) δ = 20.8 (broad m); 1H NMR (400 MHz, CDCl3) δ = 8.07 (dt, J = 13.7, 7.0, 1H), 7.50−7.33 (m, 3H), 7.22−7.14 (m, 1H), 7.06−6.89 (m, 3H), 4.02−3.82 (m, 2H), 1.95−1.75 (m, 2H), 1.73−1.46 (m, 6H), 1.40 (d, J = 10.0, 1H), 1.25 (dd, J = 14.6, 7.5, 3H), 1.18 (d, J = 10.3, 2H), 1.13−0.68 (m, 15H), 0.39 (t, J = 7.2, 3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.8 (s), 156.5 (s), 142.0 (d, J = 11.9), 135.9 (d, J = 17.5), 135.5 (d, J = 17.2), 132.4−131.9 (m), 131.8 (d, J = 6.3), 130.5 (d, J = 4.8), 130.2−129.6 (m), 129.1 (s), 127.0 (dd, J = 12.6, 6.1), 119.6 (s), 119.3 (s), 112.6 (s), 111.6 (s), 68.5 (s), 67.6 (s), 44.1 (d, J = 1.7), 37.9 (s), 37.6 (s), 36.9 (s), 36.2 (d, J = 2.2), 35.9 (s), 35.6 (s), 34.3 (d, J = 3.9), 33.2 (dd, J = 32.6, 12.6), 31.0 (d, J = 3.6), 28.3 (dd, J = 11.6, 2.5), 24.8 (d, J = 11.8), 22.4 (d, J = 9.4), 21.3 (d, J = 13.9), 19.0 (d, J = 9.0), 15.7 (s), 15.3 (s), 15.0 (d, J = 6.0), 13.6 (d, J = 3.5), 12.40 (s), 12.0 (s); HRMS (ESI+) Calcd. for C27H40OP [M-BH3 + H+]: 411.2817, Found: 411.2809. Deprotection and Oxidization of RP-8 to for SP-10′. Under air, the solution of RP-8a (80.0 mg, 0.209 mmol) in THF (0.4 mL) and diethylamine (0.4 mL) was stirred at 50 °C for 8 h. After removing the solvents, the residue was purified with preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/5 as eluent) to afford SP-10a′ (53.8 mg, 67%, > 99:1 drP and 65:35 drA). (S P )-(−)-Menthyl Methyl (2′-Methoxy-1,1′-biphenyl-2-yl)phosphine Oxide (SP-10a′). The pure compound SP-10a′ was obtained as a colorless oil; 31P NMR (162 MHz, CDCl3) δ = 43.06 (s, 65%), 42.77 (s, 35%); 1H NMR (400 MHz, CDCl3) δ = 8.26−8.05 (m, 1H), 7.49 (s, 2H), 7.40 (dd, J = 15.6, 8.2, 1H), 7.20 (s, 1H), 7.13 (d, J = 7.3, 1H), 7.08−6.86 (m, 2H), 3.79−3.53 (m, 3H), 2.59 (d, J = 20.6, 1H), 2.11 (dd, J = 22.7, 6.7, 1H), 1.68 (s, 3H), 1.51 (d, J = 12.6, 1H), 1.47−1.38 (m, 1H), 1.33 (d, J = 12.4, 2H), 1.25 (d, J = 12.3, 1H), 1.05 (ddd, J = 29.5, 17.7, 8.9, 1H), 0.95−0.80 (m, 5H), 0.76 (t, J = 7.0, 3H), 0.48 (d, J = 6.6, 3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.8 (d, J = 2.4), 139.6 (d, J = 9.3), 139.1 (d, J = 9.8), 135.0 (s), 134.7 (s), 134.1 (s), 133.9 (s), 133.0−132.6 (m), 131.9 (s), 131.3 (dd, J = 28.3, 10.0), 130.6−129.9 (m), 129.7 (s), 127.2 (dd, J = 13.3, 10.2), 119.7 (d, J = 5.0), 110.6 (d, J = 7.3), 55.4 (s), 55.1 (s), 42.9 (d, J = 3.4), 42.3 (d, J = 3.3), 41.8 (s), 41.1 (s), 40.7 (s), 40.1 (s), 35.7 (d, J = 2.5), 34.8 (d, J = 2.6), 34.1 (d, J = 11.9), 33.0 (dd, J = 13.7, 5.7), 28.6 (s), 24.5 (dd, J = 12.5, 4.3), 22.4 (d, J = 15.6), 21.9 (s), 21.6 (s), 21.3 (s), 18.7 (s), 18.1 (s), 15.4 (d, J = 7.9); HRMS (ESI+) Calcd. for C24H34O2P [M + H+]: 385.2296, Found: 385.2306. O-Alkylation of RP-5 in the Presence of Equal Molar of Base, Typical Procedure. To the solution of RP-5 (80.0 mg, 0.225 mmol) and potassium hydroxide (14.9 mg, 0.225 mmol) in ethanol (1 mL) was added methyl iodide (27.1 μL, 0.225 mmol), and the mixture was stirred at room temperature for 10 h. After the reaction was completed, as monitored with TLC, a saturated solution of ammonium chloride (10 mL) was added. The mixture was extracted with dichloromethane (3 × 10 mL), washed with water (3 × 20 mL), and dried over magnesium sulfate. After removing the solvents, the residue was purified with preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/5 as eluent) to afford RP-9a (69.1 mg, 83%, > 99:1 drP and 56:44 drA). (R P )-(−)-Menthyl (2′-Methoxy-1,1′-biphenyl-2-yl)phosphine Oxide (RP-9a). The crude RP-9a was obtained from methyl iodide, and the pure compound was obtained as a white solid, mp 109.5− 110.9 °C; 31P NMR (162 MHz, CDCl3) δ = 36.75 (s, 56%), 33.77 (s, 44%); 1H NMR (400 MHz, CDCl3) δ = 8.11−7.98 (m, 1H), 7.75 (s, 0.22H), 7.59 (s, 0.28H), 7.56 (d, J = 7.7, 1H), 7.52 (d, J = 6.2, 1H), 7.40 (t, J = 7.8, 1H), 7.23 (ddd, J = 36.1, 19.5, 6.5, 2H), 7.10−6.93 (m, 2H), 6.56 (s, 0.22H), 6.40 (s, 0.28H), 3.75 (s, 3H), 2.17−1.96 (m, 1H), 1.59 (s, 3H), 1.52−1.36 (m, 1H), 1.07−0.89 (m, 2H), 0.85 (d, J = 6.8, 2H), 0.81 (d, J = 6.7, 3H), 0.74 (d, J = 5.8, 4H), 0.32 (d, J = 6.8, 1.3H), 0.29 (d, J = 6.8, 1.7H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.4 (s), 155.7 (s), 140.8 (d, J = 10.9), 140.4 (d, J = 11.1), 132.1 (s), 131.8−130.6 (m), 130.5 (d, J = 9.9), 129.9 (d, J = 4.5), 128.1 (d, J = 4.1), 127.8−127.1 (m), 120.8 (s), 120.5 (s), 110.7 (d, J = 7.1), 55.4 (s), 54.9 (s), 42.4 (dd, J = 11.3, 3.3), 40.6 (s), 40.0 8431


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The Journal of Organic Chemistry O,P-Alkylation of 5 under Phase-Transfer Condition, Typical Procedure. To a solution of RP-5 (80.0 mg, 0.225 mmol), bromoethane (101 μL, 0.1.35 mmol), tetrabutyl ammonium bromide (7.3 mg, 0.0225 mmol, 10% mol), and ethanol (0.1 mL) in toluene (0.8 mL) was added a solution of potassium hydroxide in water (50%, 0.8 mL), and the mixture was stirred at room temperature for 8 h. After the reaction was completed, as monitored with TLC, a saturated solution of ammonium chloride (10 mL) was added. The mixture was extracted with dichloromethane (3 × 10 mL), washed with water (3 × 20 mL), and dried over magnesium sulfate. After removing the solvents, the residue was purified with preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/5 as eluent) to afford RP-10b (77.3 mg, 83%, > 99:1 drP and 53:47 drA). (R P )-(−)-Menthyl Methyl (2′-Methoxy-1,1′-biphenyl-2-yl)phosphine Oxide (RP-10a). The crude RP-10a was obtained from methyl iodide, and the pure compound was obtained as a white solid (74.3 mg, 86%, > 99:1 drP and 62:38 drA) from preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/5 as eluent), mp 143.3− 146.8 °C; 31P NMR (162 MHz, CDCl3) δ = 45.17 (s, 62%), 42.32 (s, 38%); 1H NMR (400 MHz, CDCl3) δ = 8.05 (dd, J = 11.9, 0.4H), 7.88 (dd, J = 11.9, 7.5,0.6H), 7.60−7.51 (m, 1H), 7.51−7.41 (m, 2H), 7.38 (t, J = 7.9, 1H), 7.24 (ddd, J = 17.9, 7.5, 5.2, 1H), 7.13−7.00 (m, 1H), 6.96 (dd, J = 20.7, 7.8, 1H), 3.75 (s, 1.1H), 3.70 (s, 1.9H), 2.55−2.42 (m, 0.6H), 2.41−2.28 (m, 0.4H), 1.88 (dd, J = 20.3, 9.0, 1H), 1.62 (t, J = 13.5, 2H), 1.48 (d, J = 12.2, 2H), 1.44 (s, 1H), 1.36 (d, J = 12.6, 1H), 1.27 (s, 1H), 1.11 (d, J = 17.2, 1H), 1.02−0.88 (m, 1H), 0.83 (d, J = 6.8, 3H), 0.79 (d, J = 6.1, 2H), 0.74 (d, J = 6.5, 2H), 0.67−0.52 (m, 1H), 0.44 (d, J = 6.7, 1.9H), 0.32 (d, J = 6.7, 1.1H); 13 C {1H} NMR (101 MHz, CDCl3) δ = 156.6 (d, J = 11.3), 140.8 (dd, J = 22.4, 8.5), 135.8 (s), 134.9 (s), 134.6 (s), 133.7 (s), 132.7 (s), 132.2 (d, J = 9.7), 131.9−131.0 (m), 130.3 (dd, J = 18.5, 2.4), 129.9− 129.0 (m), 127.0 (d, J = 10.6), 119.9 (s), 119.6 (s), 110.4 (s), 110.0 (s), 55.0 (d, J = 4.9), 44.0 (d, J = 3.0), 43.6 (d, J = 3.5), 40.7 (s), 40.5 (s), 40.0 (s), 39.8 (s), 36.0 (d, J = 12.4), 34.4 (d, J = 6.7), 33.3 (dd, J = 30.9, 14.3), 28.1 (dd, J = 9.6, 2.3), 24.8 (dd, J = 12.6, 2.5), 22.5 (d, J = 16.2), 21.7 (d, J = 14.1), 16.5 (s), 15.8 (s), 15.3 (s), 14.5 (s), 12.7 (s), 12.0 (s); HRMS (ESI+) Calcd. for C24H34O2P [M + H+]: 385.2296, Found: 385.2301. (S P )-(−)-Menthyl Methyl (2′-Methoxy-1,1′-biphenyl-2-yl)phosphine Oxide (SP-10a′). The crude SP-10a′ was obtained from SP-5′ and methyl iodide, and the pure compound was obtained as a colorless oil (72.6 mg, 84%, > 99:1 drP and 65:35 drA) from preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/5 as eluent).The compound had the same spectrum data as those obtained above. (RP)-(−)-Menthyl Ethyl (2′-Ethoxy-1,1′-biphenyl-2-yl)phosphine Oxide (RP-10b). The crude RP-10b was obtained from bromoethane, and the pure compound was obtained as a white solid from preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/5 as eluent), mp 109.2−114.5 °C; 31P NMR (162 MHz, CDCl3) δ = 46.07 (s, 53%), 45.90 (s, 47%); 1H NMR (400 MHz, CDCl3) δ = 8.18− 8.08 (m, 0.5H), 8.06−7.96 (m, 0.5H), 7.44 (dd, J = 7.4, 3.4, 2H), 7.36 (dd, J = 18.6, 8.3, 1H), 7.20 (d, J = 3.2, 1H), 7.04 (d, J = 7.6, 1H), 7.01−6.88 (m, 2H), 4.11−3.98 (m, 0.9H), 3.98−3.86 (m, 1.1H), 2.52−2.31 (m, 1H), 1.94 (ddd, J = 23.4, 11.6, 4.3, 1H), 1.82−1.39 (m, 5H), 1.26 (t, J = 7.0, 1H), 1.18 (t, J = 7.0, 2H), 1.04 (ddt, J = 22.4, 14.8, 7.4, 4H), 0.97−0.40 (m, 10H), 0.31 (d, J = 6.8, 1.6H), 0.23 (d, J = 6.8, 1.4H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.4 (s), 155.9 (s), 140.7 (dd, J = 15.9, 9.4), 134.4 (s), 133.9 (s), 133.6 (s), 133.4−133.0 (m), 132.5 (d, J = 7.2), 132.1 (d, J = 9.7), 131.7−131.3 (m), 129.9 (ddd, J = 25.0, 14.4, 3.2), 129.4 (s), 126.7 (dd, J = 10.0, 3.3), 119.4 (d, J = 5.5), 111.7 (s), 111.2 (s), 63.7 (s), 63.5−44.5 (m), 43.5 (dd, J = 16.0, 3.8), 40.5 (dd, J = 120.2, 65.7), 35.7 (dd, J = 14.0, 1.7), 34.4−32.5 (m), 28.2 (dd, J = 11.3, 2.2), 24.8 (dd, J = 12.3, 6.5), 23.1−21.3 (m), 19.3 (d, J = 67.2), 14.9 (dd, J = 59.0, 7.6), 5.9 (dd, J = 25.5, 5.1); HRMS (ESI+) Calcd. for C26H38O2P [M + H+]: 413.2609, Found: 413.2609. (SP)-(−)-Menthyl Ethyl (2′-Ethoxy-1,1′-biphenyl-2-yl)phosphine Oxide (SP-10b′). The crude SP-10b′ was obtained from SP-5′ and bromoethane, and the pure compound was obtained as a colorless oil

(76.1 mg, 82%, > 99:1 drP and 32:68 drA) from preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/5 as eluent); 31P NMR (162 MHz, CDCl3) δ = 50.26 (s, 32%), 50.11 (s, 68%); 1H NMR (400 MHz, CDCl3) δ = 8.17 (dd, J = 9.3, 6.2, 1H), 7.48 (s, 2H), 7.41−7.31 (m, 1H), 7.20 (d, J = 2.8, 1H), 7.10 (d, J = 7.5, 0.3H), 7.03 (d, J = 7.3, 0.7H), 6.95 (dd, J = 16.2, 7.7, 2H), 4.02−3.86 (m, 2H), 2.76−2.65 (m, 0.4H), 2.29−2.14 (m, 0.6H), 2.11−1.94 (m, 1H), 1.86−1.50 (m, 4H), 1.43 (d, J = 8.7, 2H), 1.29−1.15 (m, 4H), 1.06− 0.84 (m, 7H), 0.79 (t, J = 7.5, 4H), 0.71 (d, J = 6.3, 1H), 0.49 (d, J = 6.8, 2H), 0.45 (d, J = 6.8, 1H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.5 (s), 156.3 (s), 139.4 (dd, J = 23.5, 9.2), 134.3 (dd, J = 23.8, 5.6), 131.7 (dd, J = 21.0, 12.8), 131.1 (s), 130.8 (s), 130.2 (ddd, J = 22.8, 17.7, 10.0), 129.7 (d, J = 4.1), 126.9 (t, J = 10.5), 119.6 (d, J = 13.2), 112.4 (s), 111.5 (s), 64.1 (s), 63.4 (s), 42.8 (d, J = 3.3), 41.5 (d, J = 3.0), 41.2 (s), 40.4 (d, J = 14.1), 39.7 (s), 35.9 (d, J = 2.6), 34.3 (d, J = 2.6), 34.1 (s), 33.7 (s), 32.9 (d, J = 13.1), 32.5 (d, J = 13.3), 29.1−28.6 (m), 26.3 (s), 25.7 (s), 24.5 (t, J = 12.2), 23.9 (s), 23.3 (s), 22.4 (d, J = 11.2), 21.6 (d, J = 10.5), 15.4 (d, J = 3.1), 14.5 (d, J = 11.5), 7.1 (d, J = 5.7), 6.5 (d, J = 5.8); HRMS (ESI+) Calcd. for C26H38O2P [M + H+]: 413.2609, Found: 413.2626. (RP)-(−)-Menthyl Butyl (2′-Butoxy-1,1′-biphenyl-2-yl)phosphine Oxide (R P -10c). The crude R P -10c was obtained from 1bromobutane, and the pure compound was obtained as a colorless oil (89.6 mg, 85%, > 99:1 drP and 53:47 drA) from preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/5 as eluent); 31P NMR (162 MHz, CDCl3) δ = 44.74 (s, 53%), 44.41 (s, 47%); 1H NMR (400 MHz, CDCl3) δ = 8.19−8.08 (m, 0.5H), 8.05−7.93 (m, 0.5H), 7.38 (ddd, J = 25.8, 14.0, 5.1, 3H), 7.19 (d, J = 4.0, 1H), 7.03 (d, J = 6.5, 1H), 7.01−6.88 (m, 2H), 4.01 (dd, J = 12.7, 7.8, 0.5H), 3.95− 3.78 (m, 1.5H), 2.82 (s, 1H), 2.53−2.33 (m, 1H), 2.10−1.82 (m, 1H), 1.76−1.42 (m, 8H), 1.38−1.14 (m, 5H), 1.11−0.63 (m, 16H), 0.30 (d, J = 6.8, 1.6H), 0.21 (d, J = 6.8, 1.4H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.6 (s), 156.0 (s), 140.5 (dd, J = 19.5, 9.3), 134.9 (s), 134.4 (s), 134.1 (s), 133.6 (s), 133.2 (d, J = 6.7), 132.5− 131.9 (m), 131.5 (d, J = 9.3), 130.1−129.6 (m), 129.3 (s), 126.7 (t, J = 9.4), 119.4 (s), 111.8 (s), 111.5 (s), 67.8 (d, J = 12.6), 43.6 (dd, J = 14.1, 3.7), 41.8 (s), 41.2 (s), 40.3 (s), 39.7 (s), 36.0−35.6 (m), 34.2 (d, J = 4.8), 33.5 (dd, J = 32.2, 13.7), 31.0 (d, J = 19.8), 29.4 (s), 28.8 (s), 28.1 (dd, J = 11.6, 2.1), 26.6 (s), 25.9 (s), 25.1−24.3 (m), 24.1 (d, J = 15.2), 23.7 (dd, J = 10.3, 4.0), 22.5 (d, J = 4.1), 21.6 (d, J = 16.3), 18.9 (d, J = 4.4), 15.1 (d, J = 11.1), 13.9−13.5 (m); HRMS (ESI+) Calcd. for C30H46O2P [M + H+]: 469.3235, Found: 469.3220. (RP)-(−)-Menthyl iso-Butyl (2′-iso-Butoxy-1,1′-biphenyl-2-yl)phosphine Oxide (RP-10d). The crude RP-10d was obtained from isobutene, and the pure compound was obtained as a white solid (63.2 mg, 60%, > 99:1 drP and 52:48 drA) from preparative TLC (silica gel, petroleum ether/ethyl acetate = 3/1 as eluent), mp 125.6− 130.1 °C; 31P NMR (162 MHz, CDCl3) δ = 44.36 (s, 52%), 43.33 (s, 48%); 1H NMR (400 MHz, CDCl3) δ = 8.22−8.09 (m, 0.5H), 8.07− 7.89 (m, 0.5H), 7.44 (dt, J = 13.7, 7.3, 3H), 7.34 (dd, J = 16.3, 8.3, 1H), 7.24 (dd, J = 14.1, 9.2, 1H), 7.13−6.85 (m, 2H), 3.82 (dd, J = 8.7, 5.3, 0.5H), 3.76−3.66 (m, 0.5H), 3.55 (q, J = 8.4, 1H), 2.45 (s, 1H), 2.24 (d, J = 11.1, 1H), 2.12−1.71 (m, 3H), 1.71−1.37 (m, 5H), 1.24 (d, J = 11.3, 1H), 1.09 (d, J = 6.4, 1H), 1.04 (d, J = 6.4, 2H), 0.94 (t, J = 7.2, 3H), 0.90−0.45 (m, 15H), 0.31 (d, J = 6.7, 1.6H), 0.22 (d, J = 6.7, 1.4H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.4 (s), 156.2 (s), 140.9−140.4 (m), 135.4 (s), 134.9 (s), 134.6 (s), 134.0 (s), 133.1 (d, J = 6.9), 132.7 (d, J = 9.6), 132.2 (d, J = 5.1), 132.0− 131.5 (m), 130.1 (s), 130.1−129.5 (m), 129.3 (s), 126.7 (dd, J = 15.7, 10.0), 119.3 (d, J = 7.4), 111.8 (s), 111.3 (s), 74.6 (s), 74.4 (s), 43.7 (t, J = 3.4), 42.2 (s), 41.6 (s), 40.8 (s), 40.2 (s), 37.4 (s), 36.8 (s), 35.9 (d, J = 15.2), 34.7−33.9 (m), 33.9−33.1 (m), 28.0 (dd, J = 29.6, 11.4), 25.6 (dd, J = 12.9, 8.7), 24.9 (dd, J = 12.3, 8.1), 23.9 (ddd, J = 22.6, 14.8, 4.5), 22.5 (d, J = 6.2), 21.6 (d, J = 15.2), 19.2 (d, J = 4.8), 19.0 (s), 15.1 (d, J = 14.9); HRMS (ESI+) Calcd. for C30H46O2P [M + H+]: 469.3235, Found: 469.3220. (RP)-(−)-Menthyl Allyl (2′-Allyloxy-1,1′-biphenyl-2-yl)phosphine Oxide (RP-10e). The crude RP-10e was obtained from allyl chloride, and the pure compound was obtained as a white solid (79.5 mg, 81%, > 99:1 drP and 85:15 drA) from preparative TLC (silica gel, petroleum 8432


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ethyl acetate = 3/1 as eluent), mp 75.8−78.3 °C; 31P NMR (162 MHz, CDCl3) δ = 42.32 (s, 76%), 41.39 (s, 24%); 1H NMR (400 MHz, CDCl3) δ = 7.71 (dd, J = 21.6, 10.9, 1H), 7.49 (dd, J = 16.0, 8.4, 1H), 7.44−7.19 (m, 9H), 7.14 (dt, J = 15.9, 8.0, 2H), 7.07−6.96 (m, 3H), 5.01 (dt, J = 23.3, 7.1, 2H), 3.46−3.29 (m, 1.5H), 3.19 (d, J = 13.1, 0.5H), 2.35−2.00 (m, 2H), 1.75 (q, J = 11.6, 1H), 1.65−1.38 (m, 2H), 1.37−1.14 (m, 20H), 1.11−0.88 (m, 1H), 0.87−0.72 (m, 3H), 0.67 (dd, J = 22.2, 5.8, 3H), 0.43 (d, J = 5.9, 2H), 0.39 (d, J = 6.8, 2H), 0.19 (d, J = 6.7, 2.3H), 0.09 (d, J = 6.7, 0.7H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.1 (s), 155.6 (s), 150.4 (d, J = 17.0), 149.1 (t, J = 10.5), 142.2 (d, J = 7.2), 141.2 (d, J = 9.1), 134.2 (s), 134.0 (s), 133.6 (s), 133.4 (s), 133.1 (d, J = 9.5), 132.6 (s), 132.0 (d, J = 9.7), 131.51 (s), 131.0 (d, J = 8.5), 130.5−129.9 (m), 129.8 (d, J = 6.9), 129.5 (s), 129.2 (s), 126.8 (s), 126.5 (d, J = 10.5), 126.1 (s), 125.3−124.6 (m), 120.2 (s), 120.0 (s), 113.0 (s), 112.6 (s), 70.1 (s), 69.5 (s), 43.8 (d, J = 3.3), 41.6 (s), 41.3 (s), 41.0 (s), 40.7 (s), 36.5 (d, J = 21.3), 35.76 (s), 35.2 (s), 34.4 (dd, J = 22.9, 10.2), 33.4 (d, J = 13.6), 33.3−32.6 (m), 32.4 (s), 31.3 (d, J = 2.4), 28.0 (s), 27.7 (s), 25.1 (t, J = 14.7), 22.5 (s), 22.2 (s), 21.4 (s), 21.1 (s), 14.9 (d, J = 15.8); HRMS (ESI+) Calcd. for C44H58O2P [M + H+]: 649.4174, Found: 649.4197. (RP)-(−)-Menthyl o-Methylbenzyl (2′-o-Methylbenzyloxy-1,1′biphenyl-2-yl)phosphine Oxide (RP-10i). The crude RP-10i was obtained from 2-bromobenzyl bromide, and the pure compound was obtained as a white solid (101.6 mg, 80%, > 99:1 drP and 76:24 drA) from preparative TLC (silica gel, petroleum ether/ethyl acetate = 3/1 as eluent), mp 52.0−54.2 °C; 31P NMR (162 MHz, CDCl3) δ = 42.96 (s, 76%), 41.60 (s, 24%); 1H NMR (400 MHz, CDCl3) δ = 7.78− 7.68 (m, 1H), 7.50−7.36 (m, 2H), 7.35−7.23 (m, 3H), 7.07 (ddd, J = 21.5, 11.8, 6.6, 8H), 6.93 (d, J = 6.4, 2H), 5.10−4.88 (m, 2H), 3.26 (ddt, J = 44.9, 27.7, 14.7, 2H), 2.32 (s, 2H), 2.20 (d, J = 6.0, 4H), 1.90 (dd, J = 18.9, 9.0, 1H), 1.71−1.05 (m, 5H), 1.04−0.64 (m, 6H), 0.61 (d, J = 5.7, 2H), 0.48 (d, J = 6.8, 2H), 0.23 (d, J = 6.8, 2.3H), 0.07 (d, J = 6.8, 0.7H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.1 (s), 155.5 (s), 142.2 (d, J = 6.9), 141.0 (d, J = 8.3), 137.3 (d, J = 5.7), 136.2 (s), 135.2 (s), 134.9 (s), 134.6 (s), 134.3 (s), 133.5 (s), 133.12−132.7 (m), 132.5−131.6 (m), 131.4−130.8 (m), 130.4− 129.7 (m), 129.5 (s), 129.1 (s), 128.1 (s), 127.8 (s), 127.5 (s), 127.0 (s), 126.8−126.0 (m), 125.7 (dd, J = 10.4, 6.7), 120.0 (s), 112.5 (s), 111.6 (s), 68.8 (s), 68.0 (s), 43.7 (s), 43.3 (d, J = 3.2), 41.9 (s), 41.6 (s), 41.3 (s), 40.9 (s), 36.2 (d, J = 18.0), 34.4 (d, J = 9.2), 33.6 (d, J = 13.5), 33.3 (d, J = 13.7), 32.9 (s), 32.2 (s), 31.2 (s), 30.6 (s), 27.9 (d, J = 14.9), 24.9 (d, J = 12.4), 22.5 (d, J = 16.4), 21.5 (s), 21.1 (s), 20.6 (d, J = 12.5), 18.9 (d, J = 9.6), 15.1 (s), 14.8 (s); HRMS (ESI+) Calcd. for C38H46O2P [M + H+]: 565.3235, Found: 565.3242. (SP)-(−)-Menthyl o-Methylbenzyl (2′-o-Methylbenzyloxy-1,1′-biphenyl-2-yl)phosphine Oxide (SP-10i′). The crude SP-10i′ was obtained from SP-5′ and 2-bromobenzyl bromide, and the pure compound was obtained as a colorless oil (109.2 mg, 86%, > 99:1 drP and 28:72 drA) from preparative TLC (silica gel, petroleum ether/ ethyl acetate = 3/1 as eluent); 31P NMR (162 MHz, CDCl3) δ = 44.71 (s, 28%), 44.42 (s, 72%); 1H NMR (400 MHz, CDCl3) δ = 7.95−7.78 (m, 1H), 7.40 (ddd, J = 25.8, 15.9, 7.4, 3H), 7.27−7.16 (m, 1H), 7.16−6.79 (m, 9H), 6.67 (d, J = 7.4, 1H), 6.56 (t, J = 7.4, 1H), 4.95 (d, J = 14.7, 1.4H), 4.82 (d, J = 12.4, 0.6H), 3.54−2.96 (m, 2H), 2.51−2.36 (m, 1H), 2.19 (d, J = 3.3, 1.5H), 2.16 (d, J = 3.3,4.5H), 1.76−1.58 (m, 3H), 1.49 (d, J = 26.5, 2H), 1.23 (s, 1H), 1.11−0.80 (m, 5H), 0.77 (d, J = 6.7, 1H), 0.70 (d, J = 6.3, 2H), 0.62 (d, J = 6.7, 2H), 0.59 (d, J = 6.7, 1H), 0.48 (d, J = 5.1, 1H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.2 (s), 155.7 (s), 140.5 (d, J = 8.0), 139.7 (s), 137.7 (dd, J = 20.5, 6.2), 135.6 (s), 135.2 (s), 134.6 (d, J = 13.9), 134.1 (d, J = 6.4), 133.4−132.9 (m), 132.8 (s), 132.4−131.6 (m), 131.6−130.9 (m), 130.7 (s), 130.4 (d, J = 4.8), 130.0 (dd, J = 15.4, 10.8), 129.6 (d, J = 5.9), 127.6 (d, J = 11.3), 127.3−126.8 (m), 126.3 (s), 126.1 (d, J = 2.6), 125.8 (s), 125.7−124.9 (m), 120.3 (s), 120.1 (s), 112.9 (s), 112.2 (s), 68.3 (d, J = 13.8), 42.8 (d, J = 3.3), 42.2 (d, J = 3.1), 41.3 (s), 41.1 (s), 40.5 (d, J = 25.0), 36.8 (s), 36.1 (d, J = 14.8), 35.4 (s), 34.8 (s), 34.2 (s), 34.0 (d, J = 20.5), 32.9 (d, J = 13.3), 32.6 (d, J = 13.4), 28.9 (s), 28.5 (d, J = 2.2), 24.6 (dd, J = 12.4, 5.5), 22.4 (s), 22.2 (s), 21.5 (d, J = 7.7), 20.6 (d, J = 10.9), 18.8

ether/ethyl acetate = 1/1 as eluent), mp 132.8−134.8 °C; 31P NMR (162 MHz, CDCl3) δ = 38.69 (s, 85%), 33.78 (s, 15%); 1H NMR (400 MHz, CDCl3) δ = 7.89 (dd, J = 11.9, 7.2, 0.2H), 7.82 (dd, J = 11.9, 7.2, 0.8H), 7.68 (dd, J = 12.7, 7.6, 1H), 7.44 (dd, J = 10.5, 4.3, 1H), 7.41−7.33 (m, 2H), 7.07 (q, J = 7.8, 1H), 7.01−6.85 (m, 2H), 6.03−5.81 (m, 2H), 5.24−5.03 (m, 2H), 4.57−4.37 (m, 2H), 2.50 (dd, J = 12.6, 5.7, 1H), 2.02 (d, J = 6.5, 2H), 1.79 (d, J = 6.4, 1H), 1.58 (dd, J = 33.5, 10.1, 2H), 1.40−0.86 (m, 4H), 0.86−0.70 (m, 5H), 0.66 (t, J = 8.6, 4H), 0.49 (d, J = 6.8, 2.5H), 0.45 (d, J = 6.8, 0.5H), 0.40 (dd, J = 11.9, 5.7, 1H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.2 (s), 155.3 (s), 148.2 (s), 145.7 (s), 141.2 (d, J = 7.9), 134.1 (d, J = 7.5), 133.5 (s), 133.2 (s), 132.9−132.5 (m), 132.2 (d, J = 10.1), 131.6 (dd, J = 9.3, 5.1), 130.1 (s), 129.7 (d, J = 2.4), 129.6−129.2 (m), 126.8 (t, J = 14.3), 121.0 (s), 120.1 (d, J = 6.7), 119.5 (s), 116.6 (s), 116.3 (s), 112.0 (s), 110.9 (s), 69.0 (s), 68.0 (s), 44.2 (d, J = 2.3), 43.8 (s), 40.4 (s), 39.7 (s), 39.1 (s), 36.5 (s), 36.0 (s), 34.6 (d, J = 10.2), 33.2 (t, J = 14.3), 27.7 (t, J = 10.4), 24.8 (t, J = 11.3), 22.5 (d, J = 14.8), 21.5 (d, J = 8.4), 20.4 (t, J = 16.6), 15.3 (s); HRMS (ESI+) Calcd. for C28H38O2P [M + H+]: 437.2609, Found: 437.2616. (R P )-(−)-Menthyl Benzyl (2′-Benzyloxy-1,1′-biphenyl-2-yl)phosphine Oxide (RP-10f). The crude RP-10f was obtained from benzyl chloride, and the pure compound was obtained as a white solid (94.1 mg, 78%, > 99:1 drP and 71:29 drA) from preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/1 as eluent), mp 68.1− 71.3 °C; 31P NMR (162 MHz, CDCl3) δ = 42.04 (s, 71%), 41.14 (s, 29%); 1H NMR (400 MHz, CDCl3) δ = 7.70 (dd, J = 11.1, 8.0, 1H), 7.45 (dt, J = 15.0, 7.5, 1H), 7.40−7.28 (m, 5H), 7.28−7.14 (m, 7H), 7.11 (t, J = 6.8, 2H), 7.06−6.94 (m, 2H), 5.09−4.91 (m, 2H), 3.44− 3.29 (dd, 1.4H), 3.22 (dd, J = 25.1, 14.7, 0.6H), 2.37−1.99 (m, 1H), 1.79 (q, J = 11.3, 1H), 1.64−1.43 (m, 2H), 1.42−0.88 (m, 3H), 0.86− 0.51 (m, 5H), 0.50−0.35 (m, 4H), 0.22 (d, J = 6.8, 2.1H), 0.11 (d, J = 6.8, 0.9H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.1 (s), 155.5 (s), 142.1 (d, J = 7.2), 141.1 (d, J = 8.4), 136.9 (d, J = 2.1), 134.0 (s), 134.5 (s), 133.1 (dd, J = 8.2, 3.2), 131.9 (d, J = 9.8), 131.5−131.0 (m), 130.7 (t, J = 8.1), 130.3 (d, J = 5.6), 129.9 (dd, J = 16.3, 2.6), 129.6 (s), 129.23 (s), 128.4−127.9 (m), 127.5 (d, J = 6.8), 126.9 (s), 126.8−125.9 (m), 112.8 (s), 111.6 (s), 70.1 (s), 69.6 (s), 43.7 (d, J = 3.3), 41.6 (s), 41.3 (s), 40.9 (s), 40.8 (d, J = 22.0), 36.7−36.0 (m), 35.6 (s), 34.6 (s), 34.3 (s), 33.6 (d, J = 13.5), 33.4−32.8 (m), 28.1 (s), 27.8 (d, J = 1.8), 25.1 (t, J = 12.5), 22.6 (s), 22.3 (s), 21.5 (s), 21.2 (s), 15.1 (s), 14.9 (s); HRMS (ESI+) Calcd. for C36H42O2P [M + H+]: 537.2922, Found: 537.2924. (RP)-(−)-Menthyl p-Methylbenzyl (2′-p-Methylbenzyloxy-1,1′biphenyl-2-yl)phosphine Oxide (RP-10g). The crude RP-10g was obtained from 4-methyl benzyl chloride, and the pure compound was obtained as a white solid (106.7 mg, 84%, > 99:1 drP and 72:28drA) from preparative TLC (silica gel, petroleum ether/ethyl acetate = 2/1 as eluent), mp 154.3−155.4 °C; 31P NMR (162 MHz, CDCl3) δ = 41.98 (s, 72%), 41.10 (s, 28%); 1H NMR (400 MHz, CDCl3) δ = 7.78−7.66 (m, 1H), 7.46 (dd, J = 14.0, 6.6, 1H), 7.42−7.27 (m, 3H), 7.24 (dd, J = 8.9, 5.0, 2H), 7.11 (d, J = 6.9, 1H), 7.07−6.88 (m, 8H), 5.08−4.87 (m, 2H), 3.42−3.25 (m, 1.4H), 3.25−3.09 (m, 0.6H), 2.27 (d, J = 9.1, 6H), 1.75 (dd, J = 23.5, 11.3, 1H), 1.65−1.43 (m, 2H), 1.34−1.17 (m, 2H), 1.15−0.55 (m, 7H), 0.47 (t, J = 6.5, 4H), 0.23 (d, J = 6.8, 2.2H), 0.11 (d, J = 6.8, 0.8H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.0 (s), 155.6 (s), 142.0 (d, J = 7.2), 137.1 (d, J = 7.5), 136.0−135.5 (m), 134.0 (t, J = 9.9), 133.5 (s), 133.3−132.5 (m), 131.9 (d, J = 10.0), 131.5−130.9 (m), 130.5 (s), 130.0 (ddd, J = 37.1, 31.4, 11.8), 129.2 (s), 129.1−128.5 (m), 70.0 (s), 69.5 (s), 43.7 (d, J = 3.5), 41.5 (s), 41.2 (s), 40.8 (s), 40.6 (s), 36.4 (d, J = 18.5), 35.7 (s), 35.1 (s), 34.6 (s), 34.3 (s), 33.6 (d, J = 13.7), 33.3−32.8 (m), 32.4 (s), 28.1 (s), 27.8 (s), 25.1 (t, J = 12.5), 22.6 (s), 22.3 (s), 21.5 (s), 21.1 (dd, J = 7.7, 5.5), 15.1 (s), 14.8 (s); HRMS (ESI+) Calcd. for C38H46O2P [M + H+]: 565.3235, Found: 565.3246. (RP)-(−)-Menthyl p-tert-Butylbenzyl (2′-p-tert-Butylbenzyloxy1,1′-biphenyl-2-yl)phosphine Oxide (RP-10h). The crude RP-10h was obtained from 4-tert-buthylbenzyl bromide, and the pure compound was obtained as a white solid (119.6 mg, 82%, > 99:1 drP and 76:24 drA) from preparative TLC (silica gel, petroleum ether/ 8433


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The Journal of Organic Chemistry (s), 15.8 (d, J = 10.1); HRMS (ESI+) Calcd. for C38H46O2P [M + H+]: 565.3235, Found: 565.3243. (RP)-(−)-Menthyl m-Methoxybenzyl (2′-m-Methoxybenzyloxy1,1′-biphenyl-2-yl)phosphine Oxide (RP-10j). The crude RP-10j was obtained from 3-methoxybenzyl chloride, and the pure compound was obtained as a white solid (112.7 mg, 84%, > 99:1 drP and 72:28 drA) from preparative TLC (silica gel, petroleum ether/ ethyl acetate =2/1 as eluent), mp 57.5−60.3 °C; 31P NMR (162 MHz, CDCl3) δ = 42.42 (s, 72%), 41.62 (s, 28%); 1H NMR (400 MHz, CDCl3) δ = 7.80−7.67 (m, 1H), 7.51−7.41 (m, 1H), 7.41− 7.20 (m, 4H), 7.19−6.95 (m, 4H), 6.91 (d, J = 9.1, 1H), 6.74 (ddd, J = 38.0, 25.5, 15.2, 5H), 5.09−4.92 (m, 2H), 3.68 (s, 2H), 3.62 (d, J = 9.7, 4H), 3.36 (d, J = 12.6, 2H), 2.32 (dd, J = 11.8, 6.2, 1H), 2.08 (dd, J = 20.1, 9.1, 0.3H), 1.80 (dd, J = 23.9, 12.3, 0.7H), 1.61 (d, J = 9.1, 1H), 1.49 (d, J = 10.1, 2H), 1.29 (dd, J = 39.7, 8.5, 2H), 1.07−0.61 (m, 6H), 0.49 (t, J = 6.8, 4H), 0.22 (d, J = 6.8, 2.2H), 0.12 (d, J = 6.8, 0.8H); 13C {1H} NMR (101 MHz, CDCl3) δ = 159.6 (d, J = 6.4), 159.3 (d, J = 14.0), 155.9 (s), 155.4 (s), 142.2 (d, J = 7.2), 141.0 (d, J = 8.2), 138.5 (d, J = 6.7), 134.5 (d, J = 6.9), 134.3 (s), 134.0 (s), 133.4 (s), 133.2−132.5 (m), 131.9 (d, J = 9.8), 131.5−131.1 (m), 130.6 (s), 130.2 (s), 130.0 (d, J = 2.3), 129.7 (d, J = 4.3), 129.4− 128.8 (m), 126.6 (t, J = 9.5), 123.1 (d, J = 5.4), 122.7 (d, J = 5.9), 120.1 (d, J = 15.7), 118.8 (s), 118.4 (s), 115.6 (d, J = 5.0), 115.2 (d, J = 5.4), 113.6 (d, J = 5.0), 112.6 (dd, J = 9.1, 7.1), 111.6 (s), 111.4 (s), 111.0 (s), 69.7 (s), 69.2 (s), 55.3−54.9 (m), 43.6 (d, J = 3.4), 41.5 (s), 41.2 (s), 40.9 (s), 40.6 (s), 36.3 (d, J = 18.9), 35.6 (s), 34.7−34.6 (m), 34.4 (d, J = 24.1), 34.0−33.4 (m), 33.4−33.0 (m), 28.1 (s), 27.8 (d, J = 1.8), 25.0 (t, J = 11.6), 22.5 (s), 22.3 (s), 21.5 (s), 21.2 (s), 15.1 (s), 14.9 (s); HRMS (ESI+) Calcd. for C38H46O4P [M + H+]: 597.3134, Found: 597.3147. (SP)-(−)-Menthyl m-Methoxybenzyl (2′-m-Methoxybenzyloxy1,1′-biphenyl-2-yl)phosphine Oxide (SP-10j′). The crude SP-10j′ was obtained from SP-5′ and 3-methoxybenzyl chloride, and the pure compound was obtained as a colorless oil (111.4 mg, 83%, > 99:1 drP and 40:60 drA) from preparative TLC (silica gel, petroleum ether/ ethyl acetate = 2/1 as eluent); 31P NMR (162 MHz, CDCl3) δ = 44.89 (s, 40%), 43.68 (s, 60%); 1H NMR (400 MHz, CDCl3) δ = 7.92−7.78 (m, 1H), 7.51−7.32 (m, 3H), 7.28 (dd, J = 12.5, 6.4, 2H), 7.13 (t, J = 7.8, 1H), 7.06 (dd, J = 14.5, 6.3, 1H), 7.03−6.92 (m, 2H), 6.86 (dd, J = 22.3, 14.5, 1H), 6.72 (t, J = 8.6, 2H), 6.63 (s, 1H), 6.60− 6.41 (m, 2H), 5.06−4.85 (m, 2H), 3.68 (s, 1H), 3.60 (s, 3H), 3.47 (d, J = 12.3, 2H), 3.27−3.05 (m, 2H), 2.44−2.12 (m, 2H), 1.76−1.41 (m, 5H), 1.26 (t, J = 24.7, 1H), 0.89 (p, J = 12.2, 3H), 0.80 (d, J = 6.5, 2H), 0.72 (t, J = 8.2, 2H), 0.58 (d, J = 6.7, 1.8H), 0.53 (d, J = 6.7, 1.2H), 0.44 (d, J = 4.6, 1H); 13C {1H} NMR (101 MHz, CDCl3) δ = 159.7 (s), 159.2 (s), 159.0 (s), 156.0 (s), 155.6 (s), 140.4 (d, J = 8.2), 139.4 (s), 138.2 (d, J = 6.7), 134.4 (d, J = 6.9), 134.0 (d, J = 8.5), 133.5 (d, J = 6.9), 132.9 (s), 132.0 (dd, J = 16.7, 9.9), 131.3 (s), 130.9 (s), 130.6 (d, J = 16.9), 130.4−129.9 (m), 129.7 (d, J = 16.3), 129.3 (d, J = 5.3), 128.9 (s), 128.6 (d, J = 2.1), 126.8 (dd, J = 15.1, 10.1), 122.8 (d, J = 5.4), 122.4 (d, J = 6.0), 120.2 (d, J = 3.0), 118.8 (s), 118.3 (s), 115.3 (d, J = 5.1), 114.8 (d, J = 5.4), 113.7 (d, J = 6.4), 112.8 (d, J = 12.3), 112.6−112.2 (m), 111.6 (s), 111.0 (s), 69.5 (d, J = 14.9), 55.1 (d, J = 4.9), 54.9 (s), 53.4 (s), 42.8 (d, J = 3.3), 41.9 (d, J = 3.2), 41.1 (s), 40.9 (s), 40.5 (d, J = 9.0), 40.2 (s), 40.0 (s), 38.1 (s), 37.5 (s), 35.9 (s), 34.6 (s), 34.0 (d, J = 18.8), 32.7 (dd, J = 28.8, 13.4), 29.0 (s), 28.5 (s), 24.9−24.3 (m), 22.4 (s), 22.1 (s), 21.6 (d, J = 12.2), 15.6 (s); HRMS (ESI+) Calcd. for C38H46O4P [M + H+]: 597.3134, Found: 597.3148. (RP)-(−)-Menthyl p-Chlorobenzyl (2′-p-Chlorobenzyloxy-1,1′-biphenyl-2-yl)phosphine Oxide (RP-10k). The crude RP-10k was obtained from 4-chlorobenzyl chloride, and the pure compound was obtained as a white solid (110.1 mg, 81%, > 99:1 drP and 68:32 drA) from preparative TLC (silica gel, petroleum ether/ethyl acetate = 2/1 as eluent), mp 78.4−79.8 °C; 31P NMR (162 MHz, CDCl3) δ = 41.79 (s, 68%), 41.30 (s, 32%); 1H NMR (400 MHz, CDCl3) δ = 7.71− 7.63 (m, 1H), 7.54−7.43 (m, 1H), 7.42−7.29 (m, 3H), 7.28−7.15 (m, 5H), 7.15−7.08 (m, 2H), 7.08−6.93 (m, 4H), 5.07−4.86 (m, 2H), 3.52−3.12 (m, 2H), 2.38−2.16 (m, 1H), 2.04 (dd, J = 23.8, 12.8, 0.3H), 1.81 (dd, J = 23.8, 12.8, 0.7H), 1.62 (d, J = 10.9, 0.6H),

1.51 (d, J = 10.9, 1.4H), 1.33−0.99 (m, 2H), 0.96−0.57 (m, 6H), 0.58−0.32 (m, 4H), 0.23 (d, J = 6.8, 2H), 0.14 (d, J = 6.8, 1H); 13C {1H} NMR (101 MHz, CDCl3) δ = 155.9 (s), 155.3 (s), 141.9 (d, J = 7.4), 141.3 (d, J = 8.2), 135.4 (d, J = 13.2), 133.6 (d, J = 9.1), 133.3 (t, J = 4.3), 133.1−132.6 (m), 132.6−131.8 (m), 131.8−131.2 (m), 130.9 (d, J = 12.8), 130.4 (s), 130.2 (d, J = 2.4), 129.7 (d, J = 18.7), 129.4 (s), 128.6−128.1 (m), 127.8 (s), 126.7 (d, J = 10.5), 120.5 (s), 120.2 (s), 112.9 (s), 111.7 (s), 69.4 (s), 69.0 (s), 43.8 (t, J = 4.3), 41.6 (d, J = 7.4), 41.0 (d, J = 6.6), 36.4 (d, J = 6.0), 34.9 (s), 34.4 (d, J = 13.7), 33.6 (d, J = 13.7), 33.4−32.8 (m), 32.4 (s), 28.1 (s), 27.8 (d, J = 1.8), 25.0 (dd, J = 12.6, 6.1), 22.5 (s), 22.3 (s), 21.4 (s), 21.1(s),15.1(s),14.9(s); HRMS (ESI+) Calcd. for C36H40Cl2O2P [M + H+]: 605.2143, Found: 605.2158. (RP)-(−)-Menthyl o-Chlorobenzyl (2′-o-Chlorobenzyloxy-1,1′-biphenyl-2-yl)phosphine Oxide (RP-10l). The crude RP-10l was obtained from 2-methyl benzyl chloride, and the pure compound was obtained as a white solid (108.8 mg, 80%, > 99:1 drP and 79:21 drA) from preparative TLC (silica gel, petroleum ether/ethyl acetate =2/1 as eluent), mp 61.3−63.4 °C; 31P NMR (162 MHz, CDCl3) δ = 44.21 (s, 79%), 42.64 (s, 21%); 1H NMR (400 MHz, CDCl3) δ = 7.93 (d, J = 5.0, 1H), 7.85−7.71 (m, 1H), 7.61−7.53 (m, 1H), 7.51 (d, J = 7.4, 1H), 7.48−7.41 (m, 1H), 7.40−7.34 (m, 2H), 7.34−7.22 (m, 2H), 7.21−7.00 (m, 6H), 6.95 (d, J = 6.9, 1H), 5.06 (s, 2H), 3.84−3.27 (m, 2H), 2.24 (dd, J = 21.7, 15.0, 1H), 2.01 (d, J = 10.4, 1H), 1.79−1.54 (m, 1H), 1.47 (s, 2H), 1.28 (s, 1H), 1.14 (d, J = 37.5, 1H), 0.94−0.56 (m, 5H), 0.38 (d, J = 5.7, 4H), 0.22 (d, J = 6.7, 2.3H), 0.19 (d, J = 6.7, 0.7H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.0 (s), 155.3 (s), 141.8 (d, J = 7.4), 134.9 (s), 134.6 (s), 133.9 (d, J = 25.4), 133.7 (s), 133.5 (s), 133.3−133.0 (m), 132.8 (d, J = 3.6), 132.5−132.0 (m), 132.0−131.4 (m), 131.1−130.6 (m), 130.4 (s), 130.2 (d, J = 2.4), 129.8−128.7 (m), 128.5−128.2 (m), 127.7 (dd, J = 24.6, 5.1), 126.7 (dt, J = 8.7, 7.3), 120.4 (d, J = 17.1), 112.5 (s), 111.3 (s), 67.2 (s), 66.6 (s), 43.6 (d, J = 3.5), 43.3 (d, J = 3.3), 42.4 (s), 41.7 (s), 41.0 (s), 35.9 (s), 35.7 (s), 34.3 (s), 33.3 (dd, J = 23.1, 14.2), 31.7 (s), 31.1 (s), 29.1 (s), 28.5 (s), 28.1 (s), 27.9 (s), 25.0 (t, J = 11.5), 22.5 (s), 22.0 (s), 21.4 (s), 21.1 (s), 14.9 (d, J = 5.7); HRMS (ESI+) Calcd. for C36H40Cl2O2P [M + H+]: 605.2143, Found: 605.2164. O-Alkylation of 5′ with Alkyl Dihalide in the Presence of Equal Molar of Base, Typical Procedure. To the solution of SP-5′ (100.0 mg, 0.281 mmol), potassium hydroxide (18.6 mg, 0.281 mmol), and potassium iodide (9.3 mg, 0.0562 mmol, 20% mol) in ethanol (1 mL) was added 1,3-dibromopropane (14.3 μL, 0.140 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, as monitored with TLC, a saturated solution of ammonium chloride (10 mL) was added. The mixture was extracted with dichloromethane (3 × 10 mL), washed with water (3 × 20 mL), and dried over magnesium sulfate. After removing the solvents, the residue was purified with preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/3 as eluent) to afford SP,SP-11(141.6 mg, 66%, 31:26:21:22 drA, estimated by 31P NMR spectrum). SP,SP-1,3-Bis(2′-Menthylphosphinyl-1,1′-biphenyl-2-oxy)propane (SP,SP-11). The pure compound SP,SP-11 was obtained as a white solid, mp 108.5−110.2 °C; 31P NMR (162 MHz, CDCl3) δ = 21.56 (s, 31%), 20.95 (s, 26%), 18.58 (s, 21%), 18.56 (s, 22%); 1H NMR (400 MHz, CDCl3) δ = 8.23 (s, 0.5H), 8.06 (td, J = 18.8, 10.5, 2H), 7.97 (s, 0.5H), 7.52 (s, 3H), 7.37 (dd, J = 17.4, 7.3, 3H), 7.13 (d, J = 12.4, 2H), 7.09−6.95 (m, 4H), 6.91 (d, J = 9.7, 1H), 6.77 (d, J = 8.6, 2H), 4.02−3.68 (m, 3H), 3.57 (d, J = 8.4, 1H), 2.14 (d, J = 30.5, 3H), 1.84 (dd, J = 13.1, 6.7, 2H), 1.62 (s, 6H), 1.10 (dt, J = 25.4, 16.4, 9H), 0.86 (d, J = 6.3, 6H), 0.81 (d, J = 7.0, 3H), 0.78−0.70 (m, 5H), 0.60 (d, J = 4.4, 1H), 0.21 (dd, J = 14.5, 6.3, 5H); 13C {1H} NMR (101 MHz, CDCl3) δ = 155.8 (d, J = 17.4), 155.1 (s), 154.9 (s), 140.6 (d, J = 10.4), 140.2 (d, J = 6.5), 133.7 (d, J = 6.8), 132.9 (d, J = 7.6), 131.7 (s), 131.1 (d, J = 17.2), 130.6 (d, J = 15.7), 130.0−129.3 (m), 128.7 (s), 128.4 (s), 128.0 (s), 127.9−125.4 (m), 127.3−126.9 (m), 127.4−125.4 (m), 121.4 (s), 121.1 (s), 120.8 (d, J = 9.1), 112.8 (s), 112.1 (s), 64.6 (d, J = 30.5), 64.2 (s), 63.7−63.5 (m), 63.3 (d, J = 14.0), 41.69 (s), 41.4 (d, J = 28.2), 39.9 (s), 39.0 (d, J = 47.0), 37.9 (s), 34.3 (d, J = 17.0), 33.1 (s), 32.7 (d, J = 25.8), 31.6 (d, J = 14.6), 8434


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The Journal of Organic Chemistry 28.6 (s), 27.4 (d, J = 15.4), 24.1 (d, J = 16.5), 22.4 (d, J = 8.5), 21.4 (d, J = 7.5), 14.8 (d, J = 12.9); HRMS (ESI+) Calcd. for C47H63O4P2[M + H+]: 753.4202, Found: 753.4244; Elemental Analysis Calcd. for C47H62O4P2: C, 74.97, H, 8.30, Found: 74.68, H, 8.22. SP,SP-1,3-Bis(2′-Menthylphosphinyl-1,1′-biphenyl-2-oxymethyl)benzene (SP,SP-12). The crude SP,SP-12 was obtained from the reaction of SP-5′ with 1,3-dichloromethylbenzene, and the pure compound was obtained as a white solid (141.9 mg, 62%, 27:21:31:20 drA, estimated by 31P NMR spectrum) from preparative TLC (silica gel, petroleum ether/ethyl acetate =1/5 as eluent), mp 104.4−106.7 °C; 31P NMR (162 MHz, CDCl3) δ = 21.02 (s, 27%), 20.99 (s, 21%), 18.61 (s, 31%), 18.51 (s, 20%); 1H NMR (400 MHz, CDCl3) δ = 8.24 (d, J = 8.9, 0.4H), 8.09 (d, J = 11.6, 2.6H), 7.55 (d, J = 3.5, 4H), 7.37 (dd, J = 19.8, 12.4, 3H), 7.22 (d, J = 5.8, 2H), 7.14 (t, J = 7.7, 1H), 7.10−6.98 (m, 6H), 6.95 (s, 1H), 6.89 (s, 2H), 4.94 (ddd, J = 26.2, 21.6, 12.3, 4H), 2.08 (d, J = 6.3, 2H), 1.63 (s, 5H), 1.22−1.00 (m, 7H), 0.87 (t, J = 9.9, 10H), 0.74 (d, J = 19.4, 6H), 0.37 (d, J = 5.5, 1H), 0.26−0.16 (m, 7H); 13C {1H} NMR (101 MHz, CDCl3) δ = 155.8 (s), 155.0 (d, J = 11.3), 140.8−140.0 (m), 137.1−136.6 (m), 133.7 (s), 133.1 (d, J = 6.0), 132.0−131.7 (m), 131.6 (s), 130.9 (t, J = 22.6), 130.5−129.7 (m), 129.0 (d, J = 18.9), 128.6 (s), 127.4 (d, J = 10.2), 126.1 (d, J = 13.5), 125.4 (s), 124.6 (s), 121.2 (dd, J = 28.3, 11.7), 113.4 (s), 113.2 (s), 112.7 (s), 70.1 (d, J = 12.3), 69.4 (d, J = 16.7), 41.6 (d, J = 8.6), 39.8 (s), 39.1 (s), 38.9 (s), 38.2 (s), 34.3 (d, J = 5.1), 32.7 (d, J = 13.6), 31.7 (s), 31.3 (s), 27.4 (d, J = 5.4), 24.7− 23.9 (m), 22.4 (s), 21.9 (d, J = 17.8), 21.3 (s), 14.7 (s); HRMS (ESI+) Calcd. for C52H65O4P2[M + H+]: 815.4358, Found: 815.4402; Elemental Analysis Calcd. for C52H64O4P2: C, 76.63, H, 7.92, Found: 76.82, H, 7.98. O-Alkylation of 7a under Phase-Transfer Condition. To the solution of RP-7a (100.0 mg, 0.272 mmol), potassium hydroxide (17.9 mg, 0.272 mmol), and potassium iodide (9.1 mg, 0.0544 mmol, 20% mol) in ethanol (1 mL) was added 1,3-dibromopropane (13.8 μL, 0.136 mmol), and the mixture was stirred at room temperature for 48 h. After the reaction was completed, as monitored with TLC, a saturated solution of ammonium chloride (10 mL) was added. The mixture was extracted with dichloromethane (3 × 10 mL), washed with water (3 × 20 mL), and dried over magnesium sulfate. After removing the solvents, the residue was purified with preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/3 as eluent) to afford Rp,Rp-13 (143.6 mg, 68%). Rp,Rp-1,3-Bis(2′-menthylmethylphosphino-1,1′-biphenyl-2-oxy)propane Bis-borane Complex (Rp,Rp-13). The pure compound Rp,Rp-13 was obtained as a white solid, mp 163.5−164.9 °C; 31P NMR (162 MHz, CDCl3) δ = 20.51 (broad m); 1H NMR (400 MHz, CDCl3) δ = 8.06 (dd, J = 13.2, 7.5, 1H), 7.52−7.23 (m, 3H), 7.19 (t, J = 7.1,0.3H), 7.02 (q, J = 7.3, 2H), 6.92 (t, J = 7.1, 0.7H), 6.79 (dd, J = 16.9, 8.3, 1H), 3.98−3.79 (m, 1.1H), 3.79−3.62 (m, 0.9H), 1.84 (t, J = 18.1, 3H), 1.62 (dd, J = 41.2, 9.2, 4H), 1.40 (d, J = 10.2, 0.9H), 1.26 (s, 2H), 1.10 (d, J = 10.2, 2.1H), 1.04−0.61 (m, 11H), 0.37 (t, J = 8.1, 3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.5 (s), 156.1 (d, J = 15.3), 155.9 (s), 142.0 (s), 141.7 (d, J = 4.6), 136.0 (d, J = 17.5), 135.5 (d, J = 17.5), 132.2−131.8 (m), 131.6 (d, J = 6.3), 130.6 (s), 130.4 (s), 130.2−129.5 (m), 129.3 (s), 127.1 (t, J = 14.9), 120.0− 119.5 (m), 112.5 (d, J = 13.6), 111.8 (s), 111.5 (s), 64.9 (s), 63.8 (s), 63.6 (s), 44.1 (s), 37.9 (d, J = 30.4), 37.7−37.3 (m), 36.9 (s), 36.3 (s), 35.8 (s), 35.5 (s), 34.3 (s), 33.3 (d, J = 12.2), 33.0 (d, J = 13.0), 28.7−28.1 (m), 24.8 (d, J = 11.7), 22.5 (d, J = 5.8), 21.3 (d, J = 15.6), 15.9 (s), 15.6 (s), 15.0 (d, J = 6.2), 12.2 (s), 11.8 (d, J = 6.3); HRMS (ESI+) Calcd. for C49H67O2P2[M-BH3 + H+]: 749.4616, Found: 749.4645. P-Alkylation of 9b under Phase-Transfer Condition. To the solution of Sp-9b′ (100.0 mg, 0.26 mmol), tetrabutyl ammonium bromide (8.4 mg, 0.026 mmol, 10% mol), and potassium iodide (8.6 mg, 0.052 mmol, 20% mol) in toluene (1 mL) and ethanol (0.1 mL), 1,3-dichloromethyl-benzene (18.9 μL, 0.13 mmol) was added. The potassium hydroxide solution in water (50%, 1 mL) was added, and the mixture was stirred at room temperature for 48 h. After the reaction was completed, as monitored with TLC, a saturated solution

of ammonium chloride (10 mL) was added. The mixture was extracted with dichloromethane (3 × 10 mL), washed with water (3 × 20 mL), and dried over magnesium sulfate. After removing the solvents, the residue was purified with preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/1 as eluent) to afford Sp,Sp-14 (151.9 mg, 67%, 30:35:22:20 drA, estimated by 31P NMR spectrum). Rp,Rp-1,3-Bis(2′-ethoxy-1,1′-biphenyl-2menthylphosphinylmethyl)benzene (Rp,Rp-14). The pure compound Rp,Rp-14 was obtained as a white solid, mp 103.5−106.1 °C; 31 P NMR (162 MHz, CDCl3) δ = 42.87 (s, 30%), 42.84 (s, 35%), 41.32 (s, 22%), 40.91 (s, 20%); 1H NMR (400 MHz, CDCl3) δ = 7.86−7.58 (m, 2H), 7.45−7.33 (m, 4H), 7.33−7.16 (m, 7H), 7.13 (d, J = 5.6, 1H), 7.10−6.84 (m, 6H), 3.98 (dt, J = 18.2, 5.5, 4H), 3.42− 3.03 (m, 4H), 2.55−2.20 (m, 3H), 2.06 (d, J = 11.0, 1H), 1.78−1.44 (m, 6H), 1.32 (s, 2H), 1.27−1.11 (m, 7H), 0.94 (s, 5H), 0.82−0.67 (m, 12H), 0.60 (d, J = 6.8, 2H), 0.53 (d, J = 6.8, 1H), 0.28 (dd, J = 10.0, 6.6, 5H); 13C {1H} NMR (101 MHz, CDCl3) δ = 156.2 (s), 155.9 (s), 141.9 (d, J = 7.5), 140.9 (s), 134.4 (s), 133.1 (dd, J = 45.9, 33.5), 131.9−131.6 (m), 131.3 (dd, J = 17.4, 8.5), 130.1 (s), 129.8− 129.2 (m), 129.1 (s), 128.8−128.3 (m), 127.9 (d, J = 6.7), 126.5 (d, J = 10.7), 119.6 (s), 112.0 (s), 111.1 (d, J = 5.8), 77.4 (s), 77.1 (s), 76.8 (s), 63.8 (s), 63.6 (s), 43.8 (d, J = 3.9), 41.2 (d, J = 16.5), 40.6 (d, J = 16.7), 36.4 (t, J = 11.3), 35.8 (s), 34.5 (s), 34.2 (s), 33.4 (dd, J = 33.0, 14.0), 33.0 (s), 32.4 (s), 28.2 (s), 27.8 (s), 25.0 (t, J = 11.4), 22.5 (d, J = 8.0), 21.6 (s), 21.3 (s), 15.1 (d, J = 4.9), 14.7 (d, J = 4.8), 1.0 (s); HRMS (ESI+) Calcd. for C56H72NaO4P2[M + Na+]: 893.4804, Found: 893.4869; Elemental Analysis Calcd. for C56H72O4P2: C, 77.21, H, 8.33, Found: 77.43, H, 8.38. Stationary Axial Chirality via Cyclization. Cyclization with Thioyl Chloride. To the ice-water-cooled solution of Rp-4 (100.0 mg, 0.27 mmol) and pyridine (52.2 μL, 0.648 mmol) in THF (1.8 mL) was added thionyl chloride (23.5 μL, 0.324 mmol) dropwise. The mixture was stirred for 8 h while warmed to room. After removing the solvent, water (5 mL) was added and the mixture was extracted with dichloromethane (3 × 5 mL), washed with water (3 × 10 mL), and dried over magnesium sulfate. After removing the solvent, the residue was purified with recrystallization with dichloromethane−petroleum ether (60−90 °C) to afford Rp-15 (87.6 mg, 78%, > 99:1 dr). Rp-8-Menthyl-8H-dibenzo[e,g][1,3,2,4]dioxathiaphosphocine 6Oxide, 8-Borane Complex (Rp,RA-15). The optically pure Rp,RA-15 was obtained as a white solid, mp 121.6−123.8 °C; 31P NMR (162 MHz, CDCl3) δ = 131.72 (broad m); 1H NMR (400 MHz, CDCl3) δ = 8.11 (dd, J = 13.4, 7.3, 1H), 7.68 (d, J = 7.6, 1H), 7.58 (d, J = 5.1, 1H), 7.50 (dd, J = 9.6, 4.7, 1H), 7.48−7.41 (m, 2H), 7.34 (d, J = 6.6, 2H), 2.27−2.13 (m, 1H), 1.27 (s, 2H), 1.01 (d, J = 25.9, 3H), 0.93− 0.81 (m, 6H), 0.71 (dt, J = 22.3, 13.3, 7H), 0.24 (d, J = 6.7, 3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 144.3 (s), 140.2 (s), 135.8 (s), 135.5 (d, J = 12.9), 133.4 (s), 131.5 (d, J = 6.2), 130.2 (s), 130.0 (s), 128.4 (d, J = 13.5), 127.7 (s), 127.2 (s), 124.9 (s), 77.3 (s), 77.0 (s), 76.7 (s), 43.3 (s), 40.1 (s), 39.8 (s), 34.3−33.9 (m), 33.1 (d, J = 14.3), 28.2 (s), 24.3 (d, J = 13.5), 22.4 (s), 21.2 (s), 14.6 (s). Cyclization with Formaldehyde and Subsequent Chlorination. To the solution of Rp-4 (100.0 mg, 0.27 mmol) in THF (1.2 mL), formaldehyde (2 mL, 37% solution in water) was added at room temperature. The solution was stirred at room temperature for 12 h. After removing the solvents, the residue was purified with preparative TLC (silica gel, petroleum ethere/ethyl acetate = 1/2 as eluent) to afford Rp-16 (75.1 mg, 72%, > 99:1 drP and 80:20 drA). Rp-Menthyl Hydroxymethyl (2′-Hydroxy-1,1′-biphenyl-2-yl)phosphine Oxide (Rp-16). The pure Rp-16 was obtained as a white solid, mp 106.2−108.7 °C; 31P NMR (162 MHz, CDCl3) δ = 50.43 (s, 86%), 45.02 (s, 14%); 1H NMR (400 MHz, CDCl3) δ = 8.13 (dd, J = 11.3, 7.9, 0.2H), 7.72 (dd, J = 11.3, 7.8, 0.8H), 7.59−7.46 (m, 1H), 7.41 (t, J = 6.4, 1H), 7.34−7.25 (m, 2H), 7.08 (d, J = 8.1, 1H), 7.01 (d, J = 4.3, 1.6H), 6.91 (t, J = 7.4, 0.4H), 4.38 (dd, J = 33.1, 14.4, 1.6H), 3.89−3.72 (m, 0.4H), 2.42−2.25 (m, 0.8H), 2.25−2.12 (m, 0.2H), 1.74−1.41 (m, 4H), 1.19 (d, J = 9.9, 1H), 1.06 (s, 1H), 0.94 (d, J = 13.4, 1H), 0.82 (d, J = 6.7, 1H), 0.77 (t, J = 7.3, 3H), 0.71 (d, J = 6.3, 4H), 0.39 (d, J = 6.6, 2.4H), 0.31 (d, J = 6.8, 0.6H); 13C {1H} NMR (101 MHz, CDCl3) δ = 154.9 (s), 154.2 (s), 142.4 (d, J = 6.6), 8435


Article


1.9, 1H), 6.80 (d, J = 7.1, 1H), 6.59 (d, J = 8.2, 1H), 6.37 (t, J = 6.9, 1H), 1.82 (s, 1H), 1.49 (d, J = 11.0, 3H), 1.37 (s, 1H), 1.09 (dd, J = 14.5, 7.2, 1H), 0.89 (s, 2H), 0.70 (d, J = 6.8, 4H), 0.66 (d, J = 5.8, 4H), 0.12 (d, J = 4.9, 3H); 13C {1H} NMR (101 MHz, CD3OD) δ = 135.6 (s), 135.0 (s), 134.5 (s), 134.0 (s), 133.2 (s), 129.8 (d, J = 10.8), 124.4 (s), 116.9 (s), 46.1 (s), 43.8 (s), 41.9 (s), 37.8 (s), 37.1 (d, J = 20.1), 32.7 (s), 27.7 (d, J = 12.5), 25.1 (s), 24.3 (s), 18.1 (s). Lithium Sp-(2′-Hydroxy-1,1′-biphenyl-2-yl)menthylphosphinite (Sp-19′). 31P NMR (162 MHz, CD3OD) δ = 27.44 (t, J = 77. 5, 92%), 27.44 (t, J = 77. 5, 8%); 1H NMR (400 MHz, CD3OD) δ = 7.76 (dd, J = 11.1, 7.9, 1H), 7.50 (t, J = 7.4, 1H), 7.37 (t, J = 7.3, 1H), 7.25−7.13 (m, 1H), 6.92 (t, J = 7.1, 1H), 6.65 (d, J = 6.7, 1H), 6.56 (d, J = 8.2, 1H), 6.36 (t, J = 7.1, 1H), 2.02 (d, J = 5.1, 1H), 1.54 (d, J = 9.2, 2H), 1.47 (s, 1H), 1.20 (t, J = 11.9, 1H), 0.99 (d, J = 15.6, 2H), 0.79 (d, J = 6.7, 5H), 0.72 (d, J = 8.6, 1H), 0.64 (d, J = 6.1, 3H), 0.31 (d, J = 6.8, 3H); 13C {1H} NMR (101 MHz, CD3OD) δ = 168.2 (s), 149.2 (d, J = 13.0), 135.7 (d, J = 8.7), 134.9 (d, J = 10.7), 133.9 (s), 133.4 (s), 132.4−132.3 (m), 132.3−131.8 (m), 130.9 (s), 129.8 (d, J = 10.9), 124.6 (s), 116.8 (s), 45.8 (s), 42.6 (s), 41.9 (s), 38.2 (s), 36.2 (d, J = 14.0), 35.9 (s), 31.4 (d, J = 5.4), 27.8 (d, J = 12.2), 25.4 (s), 24.5 (s), 18.3 (s). Coordination of RP-5 to Silver Triflate. To the solution of RP-5 (30 mg, 0.084 mmol) in chloroform-d (0.5 mL), silver triflate (21.6 mg, 0.084 mmol) was added at room temperature. The solution was analyzed with NMR spectrum. 31P NMR (162 MHz, CDCl3) δ = 110.77 (broad s, 50%), 107.39 (broad s, 50%); 1H NMR (400 MHz, CDCl3) δ = 8.06 (d, J = 7.2, 1H), 7.90 (d, J = 7.8, 1H), 7.85 (d, J = 7.8, 1H), 7.60 (t, J = 7.6, 1H), 7.48 (t, J = 7.5, 1H), 7.36 (t, J = 7.7, 1H), 7.30−7.19 (t, 1H), 7.13 (d, J = 8.0, 1H), 6.05 (s, 1H), 2.69− 1.88 (m, 3H), 1.76 (d, J = 10.1, 1H), 1.62 (t, J = 12.7, 3H), 1.08 (d, J = 9.9, 2H), 0.88 (d, J = 6.4, 3H), 0.76 (d, J = 5.5, 4H), 0.31 (d, J = 6.7, 3H). Coordination of RP-5 to Bis(acetonitrile)palladium Dichloride. To the solution of bis(acetonitrile)palladium dichloride (10.9 mg, 0.042 mmol) in methanol (3 mL), the complex RP-5 (30 mg, 0.084 mmol) was added at room temperature. The mixture was stirred at room temperature for 12 h. After removing the solvent, the residue was dissolved in chloroform-d. The NMR spectrum was collected after 2 days. A yellow solid was obtained from evaporation of chloroform, to afford cis-(RP,SA-2)2·PdCl2 (34.2 mg, 96%, > 99:1 dr). cis-Bis(SP-6-methyl-6H-dibenzo[c,e][1,2]oxaphosphinine) Palladium Dichloride. 31P NMR (162 MHz, CDCl3) δ = 122.66 (s); 1H NMR (400 MHz, CDCl3) δ = 8.78 (dd, J = 15.1, 7.6, 1H), 7.97 (d, J = 7.9, 1H), 7.71 (dd, J = 18.5, 7.9, 2H), 7.59 (t, J = 7.4, 1H), 6.95 (t, J = 7.6, 1H), 6.81 (t, J = 7.6, 1H), 6.01 (d, J = 8.1, 1H), 3.76 (t, J = 11.3, 1H), 2.71−2.51 (m, 1H), 1.48 (d, J = 12.9, 2H), 1.35 (d, J = 11.6, 1H), 1.15 (d, J = 6.8, 6H), 0.51 (d, J = 6.6, 3H), 0.46 (d, J = 6.4, 3H), 0.42−0.21 (m, 2H); 13C {1H} NMR (101 MHz, CDCl3) δ = 150.5 (t, J = 5.8), 134.9 (t, J = 11.0), 133.8 (s), 132.7 (s), 130.0 (s), 128.8 (d, J = 6.8), 124.3 (s), 123.7 (s), 123.1 (s), 122.1 (s), 121.8 (s), 121.6 (s), 120.8 (s), 118.7 (s), 49.5 (t, J = 13.2), 45.7 (s), 37.6 (s), 34.2 (s), 33.1 (t, J = 6.0), 30.6 (t, J = 4.3), 25.0 (t, J = 5.8), 22.0 (s), 21.7 (s), 16.9 (s). Deprotection of RP-8a and Coordination to Pd(COD)Cl2 To Form trans-(SP,RA-20)2·PdCl2. To the solution of RP-8a (120 mg, 0.314 mmol) in toluene (3 mL) was added triethylenediamine (52.8 mg, 0.47 mmol), and the mixture was stirred at 70 °C for 5 h. After removing the solvent, the residue was purified under nitrogen atmosphere, with column chromatography on silica gel petroleum ether to afford RP-(−)-menthyl methyl (2′-methoxy-1,1′-biphenyl-2yl)phosphine 20 (100 mg, 87%). To the solution of the above-obtained 20 (50 mg, 0.136 mmol) in THF (1 mL) was added dropwise the solution of COD-palladium dichloride (19.4 mg, 0.068 mmol) in THF (3 mL) at room temperature. The mixture was stirred at room temperature for 12 h. After removing solvent, the residue was analyzed with NMR spectrum. 1H NMR spectrum was complicated and two major peaks at 12.9 (s, 45%), 11.9 (s, 55%) were observed on 31P NMR spectrum. The single crystal suited for the X-ray diffraction was obtained from the evaporation of the solution dichloromethane and

140.2 (d, J = 10.8), 133.4 (s), 132.6 (d, J = 9.7), 131.9 (d, J = 11.5), 131.5 (s), 130.7 (d, J = 12.2), 130.5−130.0 (m), 129.9 (s), 129.3 (s), 127.5 (d, J = 11.0), 121.7 (s), 121.2 (s), 119.2 (s), 117.1 (s), 60.7 (s), 60.0 (s), 57.3 (s), 56.6 (s), 43.5 (d, J = 2.6), 43.1 (s), 41.6 (s), 41.0 (s), 38.9 (s), 38.3 (s), 35.5 (s), 34.5 (s), 34.1 (d, J = 19.7), 33.3 (d, J = 14.3), 28.5 (t, J = 6.1), 24.8 (t, J = 16.2), 22.4 (s), 21.5 (d, J = 14.3), 15.3 (s), 15.0 (s); HRMS (ESI+) Calcd. for C23H32O3P[M + H+]: 387.2089, Found: 387.2076. To the ice-water-cooled solution of Rp-16 (50.0 mg, 0.129 mmol) and pyridine (13.4 μL, 0.155 mmol) in THF (0.8 mL) was added thionyl chloride (18.9 μL, 0.259 mmol). The mixture was stirred and warmed to room temperature for 8 h. After addition of water (5 mL), the mixture was extracted with dichloromethane (3 × 5 mL), washed with water (3 × 10 mL), and dried over magnesium sulfate. After removing the solvents, the residue was purified with preparative TLC (silica gel, petroleum ether/ethyl acetate = 2/1 as eluent) to afford Rp-17 (52.2 mg, 82%, > 99:1 drP and 88:12 drA). Rp-Menthyl Chloromethyl (2′-Hydroxy-1,1′-biphenyl-2-yl) Phosphine Oxide (Rp-17). Pure Rp-17 was obtained as a white solid, mp 204.3−206.1 °C; 31P NMR (162 MHz, CDCl3) δ = 49.02 (s, 88%), 45.25 (s, 12%); 1H NMR (400 MHz, CDCl3) δ = 8.86 (s, 1H), 7.93 (dd, J = 11.9, 8.2, 0.1H), 7.72 (dd, J = 11.7, 7.8, 0.9H), 7.62 (t, J = 7.6, 1H), 7.50 (t, J = 7.1, 1H), 7.34 (dd, J = 7.3, 4.1, 2H), 7.15 (d, J = 8.0, 1H), 7.03 (d, J = 3.5, 2H), 4.04 (d, J = 4.6, 1.8H), 3.57 (dd, J = 13.7, 5.4, 0.1H), 3.36 (dd, J = 13.3, 7.2, 0.1H), 2.47−2.33 (m, 0.9H), 2.24−2.14 (m, 0.1H), 1.55 (dd, J = 26.4, 13.2, 4H), 1.19 (t, J = 9.6, 1H), 0.94 (s, 1H), 0.84 (d, J = 6.9, 4H), 0.72 (d, J = 6.4, 5H), 0.60 (d, J = 6.7, 0.3H), 0.42 (d, J = 6.6, 2.7H); 13C {1H} NMR (101 MHz, CDCl3) δ = 154.3 (d, J = 10.8), 142.7 (d, J = 8.4), 133.0 (d, J = 10.2), 132.5 (dd, J = 15.1, 2.8), 131.1 (s), 130.6 (s), 130.1 (d, J = 12.3), 129.7 (d, J = 8.9), 129.4 (s), 128.4 (s), 127.5 (d, J = 11.0), 127.2 (d, J = 11.3), 122.4 (s), 121.3 (s), 120.7 (s), 119.3 (s), 43.8 (d, J = 3.0), 43.3 (s), 39.8 (s), 39.1 (s), 38.3 (s), 36.2 (s), 34.2 (s), 33.9 (s), 33.6− 32.9 (m), 28.7 (d, J = 2.2), 24.9 (d, J = 13.4), 22.4 (d, J = 16.4), 21.5 (d, J = 19.7), 16.1 (s), 14.9 (s); HRMS (ESI+) Calcd. for C23H31ClO2P[M + H+]: 405.1750, Found: 405.1747. To the solution of Rp-17 (50.0 mg, 0.123 mmol) in dimethyl sulfoxide (0.5 mL) was added potassium hydroxide (16.2 mg, 0.246 mmol) at room temperature. The solution was stirred at room temperature for 12 h. After the reaction was completed, a saturated solution of ammonium chloride (10 mL) was added. The mixture was extracted with dichloromethane (3 × 5 mL), washed with water (3 × 10 mL), and dried over magnesium sulfate. After removing the solvents, the residue was purified with preparative TLC (silica gel, petroleum ether/ethyl acetate = 1/2 as eluent) to afford Rp-18 (31.7 mg, 70%, > 99:1 dr). Rp,SA-7-Menthyl-6,7-dihydrodibenzo[d,f ][1,3]oxaphosphepine 7Oxide (Rp,SA-18). Pure Rp,SA-18 was obtained as a white solid, mp 118.5−120.4 °C; 31P NMR (162 MHz, CDCl3) δ = 40.15 (s); 1H NMR (400 MHz, CDCl3) δ = 8.15 (dd, J = 11.0, 8.0, 1H), 7.65 (t, J = 7.5, 1H), 7.55 (t, J = 7.5, 1H), 7.47−7.30 (m, 4H), 7.26 (d, J = 8.4, 1H), 5.20 (dd, J = 14.0, 3.5, 1H), 4.61 (t, J = 13.4, 1H), 2.00 (s, 1H), 1.89−1.75 (m, 1H), 1.53 (s, 3H), 1.23−1.09 (m, 1H), 0.93 (dd, J = 23.1, 9.6, 1H), 0.86−0.55 (m, 9H), −0.06 (d, J = 6.8, 3H); 13C {1H} NMR (101 MHz, CDCl3) δ = 153.2 (s), 136.8 (d, J = 9.9), 132.9 (s), 130.6 (s), 130.1−129.6 (m), 128.9 (d, J = 6.2), 127.6 (s), 127.2 (s), 126.3 (d, J = 10.0), 125.3 (d, J = 10.2), 123.9 (s), 120.4 (s), 74.0 (s), 73.3 (s), 40.2 (d, J = 4.0), 38.1 (s), 37.4 (s), 33.0 (d, J = 2.9), 31.2 (s), 30.8 (d, J = 13.3), 26.0 (d, J = 3.0), 21.5 (d, J = 12.4), 19.8 (s), 18.7 (s), 11.9 (s); HRMS (ESI+) Calcd. for C23H30O2P [M + H+]: 369.1983, Found: 369.1979. Cyclization with Lithium Hydroxide. To the solution of Rp-5 or Sp-5 (20 mg, 0.056 mmol) in methanol-d4 (0.5 mL), lithium hydroxide (2.4 mg, 0.056 mmol) was added at room temperature. The solution was analyzed with NMR spectrum, and the typical peaks are presented in Table S1 (SI). Lithium Rp-(2′-Hydroxy-1,1′-biphenyl-2-yl )menthylphosphinite (Rp-19). 31P NMR (162 MHz, CD3OD) δ = 40.72 (t, J = 77.8); 1H NMR (400 MHz, CD3OD) δ = 7.77 (dd, J = 11.6, 7.7, 1H), 7.48 (t, J = 7.5, 1H), 7.34 (t, J = 7.4, 1H), 7.22 (s, 1H), 6.95 (ddd, J = 8.4, 7.2, 8436


Article

The Journal of Organic Chemistry petroleum ether (60−90 °C), whose structure was confirmed as trans(SP,RA-20)2·PdCl2, as seen in Table S12. Deprotection of RP-8a and Coordination to Pd(COD)Cl2 To Form (SP,RA-20·PdCl)2(μ-Cl)2. Except (COD)PdCl2 (38.8 mg, 0.136 mmol) was used, the procedure was similarly performed to the above coordination. After removing the solvent, the residue was analyzed with NMR spectrum. 1H NMR spectrum was complicated and the major peaks at 32.1 (s, 22%), 31.9 (s, 41%). 12.9 (s, 17%), 11.9 (s, 20%) were observed on 31P NMR spectrum. The single crystal suited for the X-ray diffraction was obtained from the evaporation of the solution dichloromethane and petroleum ether (60−90 °C), whose structure was confirmed as (SP,RA-20·PdCl)2(μ-Cl)2, as seen in Table S13.

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Compounds. Asymmetric Oxidation of Phosphines under Appel Conditions. J. Am. Chem. Soc. 2007, 129, 9566−9567. (i) Chan, V. S.; Chiu, M.; Bergman, R. G.; Toste, F. D. Development of Ruthenium Catalysts for the Enantioselective Synthesis of P-Stereogenic Phosphines via Nucleophilic Phosphido Intermediates. J. Am. Chem. Soc. 2009, 131, 6021−6032. (j) Han, Z. S.; Goyal, N.; Herbage, M. A.; Sieber, J. D.; Qu, B.; Xu, Y.-B.; Li, Z.-B.; Reeves, J. T.; Desrosiers, J. N.; Ma, S.-G.; Grinberg, N.; Lee, H.; Mangunuru, H. P. R.; Zhang, Y.D.; Krishnamurthy, D.; Lu, B. Z.; Song, J. J.; Wang, G.-J.; Senanayake, C. H. Efficient Asymmetric Synthesis of P-Chiral Phosphine Oxides via Properly Designed and Activated Benzoxazaphosphinine-2-oxide Agents. J. Am. Chem. Soc. 2013, 135, 2474−2477. (3) (a) Tang, W.; Zhang, X. New Chiral Phosphorus Ligands for Enantioselective Hydrogenation. Chem. Rev. 2003, 103, 3029−3070. (b) Kollár, L.; Keglevich, G. P-Heterocycles as Ligands in Homogeneous Catalytic Reactions. Chem. Rev. 2010, 110, 4257− 4302. (c) Dutartre, M.; Bayardon, J.; Jugé, S. Applications and Stereoselective Syntheses of P-Chirogenic Phosphorus Compounds. Chem. Soc. Rev. 2016, 45, 5771−5794. (d) Zhang, J.; Yu, P.; Li, S.-Y.; Sun, H.; Xiang, S.-H.; Wang, J.; Houk, K. N.; Tan, B. Asymmetric Phosphoric Acid−Catalyzed Four-Component Ugi Reaction. Science 2018, 360, 1087−1092. (4) (a) Knowles, W. S. Asymmetric Hydrogenations. Angew. Chem., Int. Ed. 2002, 41, 1998−2007. (b) Bigler, R.; Huber, R.; Stöckli, M.; Mezzetti, A. Iron(II)/(NH)2P2 Macrocycles: Modular, Highly Enantioselective Transfer Hydrogenation Catalysts. ACS Catal. 2016, 6, 6455−6464. (5) (a) Chew, R. J.; Leung, P.-H. Our Odyssey with Functionalized Chiral Phosphines: From Optical Resolution to Asymmetric Synthesis to Catalysis. Chem. Rec. 2016, 16, 141−158. (b) Chan, V. S.; Chiu, M.; Bergman, R. G.; Toste, F. D. Development of Ruthenium Catalysts for the Enantioselective Synthesis of P-Stereogenic Phosphines via Nucleophilic Phosphido Intermediates. J. Am. Chem. Soc. 2009, 131, 6021−6032. (c) Beaud, R.; Phipps, R. J.; Gaunt, M. J. Enantioselective Cu-Catalyzed Arylation of Secondary Phosphine Oxides with Diaryliodonium Salts toward the Synthesis of P-Chiral Phosphines. J. Am. Chem. Soc. 2016, 138, 13183−13186. (d) Huang, Z.; Huang, X.; Li, B.; Mou, C.; Yang, S.; Song, B.-A.; Chi, Y.-R. Access to P-Stereogenic Phosphinates via N-Heterocyclic Carbene-Catalyzed Desymmetrization of Bisphenols. J. Am. Chem. Soc. 2016, 138, 7524− 7527. (6) (a) Berger, O.; Montchamp, J. L. A General Strategy for the Synthesis of P-Stereogenic Compounds. Angew. Chem., Int. Ed. 2013, 52, 11377−11380. (b) Kortmann, F. A.; Chang, M.-C.; Otten, E.; Couzijn, E. P. A.; Lutz, M.; Minnaard, A. Consecutive Dynamic Resolutions of Phosphine Oxides. Chem. Sci. 2014, 5, 1322−1327. (c) Bagi, P.; Varga, B.; Szilágyi, A.; Karaghiosoff, K.; Czugler, M.; Fogassy, E.; Keglevich, G. The resolution of acyclic P-stereogenic phosphine oxides via the formation of diastereomeric complexes: A case study on ethyl-(2-methylphenyl)-phenylphosphine oxide. Chirality 2018, 30, 509−522. (d) Liu, Y.; Ding, B.; Liu, D.; Zhang, Z.; Liu, Y.; Zhang, W. A new and convenient approach for the synthesis of Pstereogenic intermediates bearing a tert-butyl(methyl)phosphino group. Res. Chem. Intermed. 2017, 43, 4959−4966. (e) Han, Z.-S.; Wu, H.; Xu, Y.; Zhang, Y.; Qu, B.; Li, Z.; Caldwell, D. R.; Fandrick, K. R.; Zhang, L.; Roschangar, F.; Song, J.-J.; Senanayake, C. H. General and Stereoselective Method for the Synthesis of Sterically Congested and Structurally Diverse P-Stereogenic Secondary Phosphine Oxides. Org. Lett. 2017, 19, 1796−1799. (f) Włodarczyk, A.; Kozioł, A. E.; Stankevič, M. L-Menthol-Assisted Synthesis of P-Stereogenic Phosphinous Acid Amides and Phosphine-Boranes. Eur. J. Org. Chem. 2018, 13, 1589−1600. (7) (a) Imamoto, T.; Yashio, K.; Crépy, K. V. L.; Katagiri, K.; Takahashi, H.; Kouchi, M.; Gridnev, I. D. P-Chiral Tetraphosphine Dirhodium Complex as a Catalyst for Asymmetric Hydrogenation: Synthesis, Structure, Enantioselectivity, and Mechanism. Stereoselective Formation of a Dirhodium Tetrahydride Complex and Its Reaction with Methyl (Z)-α-Acetamidocinnamate. Organometallics 2006, 25, 908−914. (b) Kumaraswamy, G.; Venkata, R. G.;

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.9b00346. Desymmetry and recrystallization of RP-4/SP-4′; chirality-fixing with lithium hydroxide; crystallographic data for Table 4 (CIF) (CIF) (CIF) (CIF) (CIF) (CIF) (CIF) (CIF) (CIF) (CIF) (CIF) (CIF) 1 H, 31P, and 13C NMR spectra (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (C.Q.Z.). *E-mail: [email protected] (Q.L.). ORCID

Chang-Qiu Zhao: 0000-0002-9016-8151 Qiang Li: 0000-0002-8687-0773 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors acknowledge the financial support from the Natural Science Foundation of China (grant no. 20772055, 21802062) and the Natural Science Foundation of Shandong Province (grant no. ZR2016BM18, ZR2018PB008).

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REFERENCES

(1) (a) Kondepudi, D. K.; Asakura, K. Chiral Autocatalysis, Spontaneous Symmetry Breaking, and Stochastic Behavior. Acc. Chem. Res. 2001, 34, 946−954. (b) Lejczak, B.; Kafarski, P.; Zygmunt, J. Inhibition of Aminopeptidases by Aminophosphonatest. Biochemistry 1989, 28, 3549−3555. (2) (a) Dalko, P. I.; Moisan, L. Enantioselective Organocatalysis. Angew. Chem., Int. Ed. 2001, 40, 3726−3748. (b) Kolodiazhnyi, O. I. Asymmetric Synthesis in Organophosphorus Chemistry; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2017. (c) Korpiun, O.; Lewis, R. A.; Chickos, J.; Mislow, K. Synthesis and Absolute Configuration of Optically Active Phosphine Oxides and Phosphinates. J. Am. Chem. Soc. 1968, 90, 4842−4846. (d) Korpiun, O.; Mislow, K. A New Route to the Preparation and Configurational Correlation of Optically Active Phosphine Oxides. J. Am. Chem. Soc. 1967, 89, 4784−4786. (e) Juge, S.; Stephan, M.; Laffitte, J. A.; Genet, J. P. Efficient Asymmetric Synthesis of Optically Pure Tertiary Mono And Diphosphine Ligands. Tetrahedron Lett. 1990, 31, 6357−6360. (f) Bauduin, C.; Moulin, D.; Kaloun, E. B.; Darcel, C.; Juge, S. J. Org. Chem. 2003, 68, 4293−4301. (g) Moulin, D.; Bago, S.; Bauduin, C.; Darcel, C.; Juge, S. Asymmetric Synthesis of P-Stereogenic OHydroxyarylphosphine (Borane) and Phosphine-Phosphinite Ligands. Tetrahedron Asymmetry 2000, 11, 3939−3956. (h) Bergin, E.; O’Connor, C. T.; Robinson, S. B.; McGarrigle, E. M.; O’Mahony, C. P.; Gilheany, D. G. Synthesis of P-Stereogenic Phosphorus 8437


Article

The Journal of Organic Chemistry RamaKrishna, G. Stereocontrolled Copper Iodide Catalyzed Phosphorus−Carbon Bond Formation: An Efficient Synthesis of Scalemic Tertiary Phosphineboranes. Synlett 2006, 7, 1122−1124. (8) Ma, Y.-N.; Yang, S.-D. Asymmetric Synthesis of Chiral Atropisomeric Bis-Aryl Organophosphorus from Menthyl H-Phosphinate. Chem. Rec. 2016, 16, 977−986. (9) Cieslikiewicz, M.; Bouet, A.; Jugé, S.; Toffano, M.; Bayardon, J.; West, C.; Lewinski, K.; Gillaizeau, I. P.-C. Cross-Coupling Onto Enamides: Versatile Synthesis of α-Enamido Phosphane Derivatives. Eur. J. Org. Chem. 2012, 6, 1101−1106. (10) (a) Imamoto, T.; Saitoh, Y.; Koide, A.; Ogura, T.; Yoshida, K. Synthesis and Enantioselectivity of P-Chiral Phosphine Ligands with Alkynyl Groups. Angew. Chem., Int. Ed. 2007, 46, 8636−8639. (b) Imamoto, T.; Sugita, K.; Yoshida, K. An Air-Stable P-Chiral Phosphine Ligand for Highly Enantioselective Transition-MetalCatalyzed Reactions. J. Am. Chem. Soc. 2005, 127, 11934−11935. (11) (a) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R. Synthesis of 2,2′-Bis(dipheny1phosphino)-1,1′binaphthyl(BINAP), an Atropisomeric Chiral Bis(triaryl)phosphine, and Its Use in the Rhodium(I)-Catalyzed Asymmetric Hydrogenation of α-(Acy1amino)acrylic Acids. J. Am. Chem. Soc. 1980, 102, 7932− 7934. (b) Noyori, R.; Takaya, H. BINAP: An Efficient Chiral Element for Asymmetric Catalysis. Acc. Chem. Res. 1990, 23, 345−350. (12) (a) Ma, Y.-N.; Li, S.-X.; Yang, S.-D. New Approaches for BiarylBased Phosphine Ligand Synthesis via PO Directed C-H Functionalizations. Acc. Chem. Res. 2017, 50, 1480−1492. (b) Zhang, Z.; Dixneuf, P. H.; Soulé, J.-F. Late Stage Modifications of P-Containing Ligands Using Transition-Metal-Catalysed C−H Bond Functionalisation. Chem. Commun. 2018, 54, 7265−7280. (c) Jang, Y.-S.; Wozniak, Ł.; Pedroni, J.; Cramer, N. Access to P- and Axially Chiral Biaryl Phosphine Oxides by Enantioselective Cpx IrIIICatalyzed C-H Arylations. Angew. Chem. Int. Ed. 2018, 57, 12901− 12905. (13) (a) Mikami, K.; Korenage, T.; Terada, M.; Ohkuma, T.; Pham, T.; Noyori, R. Conformationally Flexible Biphenylphosphane Ligands for Ru-Catalyzed Enantioselective Hydrogenation. Angew. Chem., Int. Ed. 1999, 38, 495−497. (b) Aikawa, K.; Mikami, K. Atropos but Achiral Tris(phosphanyl)biphenyl Ligands for Ru-Catalyzed Asymmetric Hydrogenation. Angew. Chem., Int. Ed. 2003, 42, 5455−5458. (c) Liang, Y.; et al. Generation of Self-Supported Noyori-Type Catalysts Using Achiral Bridged-BIPHEP for Heterogeneous Asymmetric Hydrogenation of Ketones. Adv. Synth. Catal. 2006, 348, 1533−1538. (d) Reetz, M. T.; Neugebauer, T. New Diphosphite Ligands for Catalytic Asymmetric Hydrogenation: The Crucial Role of Conformationally Enantiomeric Diols. Angew. Chem., Int. Ed. 1999, 38, 179−181. (e) Blackmond, D. G.; Rosner, T.; Neugebauer, T.; Reetz, M. T. Kinetic Influences on Enantioselectivity for NonDiastereopure Catalyst Mixtures. Angew. Chem., Int. Ed. 1999, 38, 2196−2199. (f) Ooi, T.; Uematsu, Y.; Kameda, M.; Maruoka, K. Conformationally Flexible, Chiral Quaternary Ammonium Bromides for Asymmetric Phase-Transfer Catalysis. Angew. Chem., Int. Ed. 2002, 41, 1551−1554. (g) Ringwald, M.; Stürmer, R.; Brintzinger, H. H. Asymmetric Thermal Transformation, a New Way to Enantiopure Biphenyl-Bridged Titanocene and Zirconocene Complexes: Efficient Catalysts for Asymmetric Imine Hydrogenation. J. Am. Chem. Soc. 1999, 121, 1524−1527. (h) Luo, Z.-B.; Liu, Q.-Z.; Gong, L.-Z.; Cui, X.; Mi, A.-Q.; Jiang, Y.-Z. Novel Achiral Biphenol-Derived Diastereomeric Oxovanadium(IV) Complexes for Highly Enantioselective Oxidative Coupling of 2-Naphthols. Angew. Chem., Int. Ed. 2002, 41, 4532−4535. (14) (a) Liu, Y.-Y.; Yang, G.-Q.; Yao, D.-M.; Tian, F.-T.; Zhang, W.B. Convenient synthesis of tropos phosphine-oxazoline ligands. Sci. China Chem. 2011, 54, 87−94. (b) Mikami, K.; Aikawa, K.; Yusa, Y.; Jodry, J. J.; Yamanaka, M. Tropos or Atropos? That is the Question! Synlett 2002, 10, 1561−1578. (c) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I. Novel Chiral Bisoxazoline Ligands with a Biphenyl Backbone: Preparation, Complexation, and Application in Asymmetric Catalytic Reactions. J. Org. Chem. 2000, 65, 3326−3333. (d) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I. Novel Axial

Chiral Catalyst Derived from Biphenyl Ligand Bearing only Two ortho-Substituents. Tetrahedron Lett. 1997, 38, 2681−2684. (e) Xia, J.Z.; Nie, Y.; Yang, G.-Q.; Liu, Y.-G.; Zhang, W.-B. Iridium-Catalyzed Asymmetric Hydrogenation of 2H-Chromenes: A Highly Enantioselective Approach to Isoflavan Derivatives. Org. Lett. 2017, 19, 4884− 4887. (f) Shintani, R.; Yashio, K.; Nakamura, T.; Okamoto, K.; Shimada, T.; Hayashi, T. Rhodium-Catalyzed Asymmetric Synthesis of Indanones: Development of a New “Axially Chiral” Bisphosphine Ligand. J. Am. Chem. Soc. 2006, 128, 2772−2773. (15) (a) Salmeia, K. A.; Baumgartner, G.; Jovic, M.; Gössi, A.; Riedl, W.; Zich, T.; Gaan, S. Industrial Upscaling of DOPO-Based Phosphonamidates and Phosphonates Derivatives Using Cl2 Gas as a Chlorinating Agent. Org. Process Res. Dev. 2018, 22, 1570−1577. (b) Salmeia, K.; Gaan, S.; Malucelli, G. Recent Advances for Flame Retardancy of Textiles Based on Phosphorus Chemistry. Polymers 2016, 8, 319. (c) Velencoso, M. M.; Battig, A.; Markwart, J. C.; Schartel, B.; Wurm, F. R. Molecular Firefighting-How Modern Phosphorus Chemistry Can Help Solve the Flame Retardancy Task. Angew. Chem., Int. Ed. 2018, 57, 10450−10467. (16) (a) Keglevich, G.; Kerenyi, A.; Szelke, H.; Ludanyi, K.; Kortvelyesi, T. 2-Diphenylphosphino-2′-hydroxybiphenyl-Based PLigands and Their Platinum(II) Complexes. J. Organomet. Chem. 2006, 691, 5038−5044. (b) Kadyrov, R.; Heinicke, J.; Kindermann, M. K.; Heller, D.; Fischer, C.; Selke, R.; Fischer, A. K.; Jones, P. G. P/ O Ligand Systems: Facile Synthesis, Structure, and Catalytic Tests of 2′-Phosphanyl-l,l′-biphenyl-2-ols and 2′-Phosphanyl-l,1′-binaphthyl-2ols. Chem. Ber. 1997, 130, 1663−1670. (17) Landert, H.; Spindler, F.; Wyss, A.; Blaser, H. U.; Pugin, B.; Ribourduoille, Y.; Gschwend, B.; Ramalingam, B.; Pfaltz, A. Chiral Mixed Secondary Phosphine-Oxide−Phosphines: High-Performing and Easily Accessible Ligands for Asymmetric Hydrogenation. Angew. Chem., Int. Ed. 2010, 49, 6873−6876. (18) (a) Marsi, K. L. Phenylsilane Reduction of Phosphine Oxides with Complete Stereospecificity. J. Org. Chem. 1974, 39, 265−267. (b) Liu, D.; Zhang, X.-M. Practical P-Chiral Phosphane Ligand for Rh-Catalyzed Asymmetric Hydrogenation. Eur. J. Org. Chem. 2005, 2005, 646−649. (c) Rajendran, K. V.; Gilheany, D. G. Simple Unprecedented Conversion of Phosphine Oxides and Sulfides to Phosphine Boranes Using Sodium Borohydride. Chem. Commun. 2012, 48, 817−819. (d) Rajendran, K. V.; Nikitin, K. V.; Gilheany, D. G. Hammond Postulate Mirroring Enables Enantiomeric Enrichment of Phosphorus Compounds via Two Thermodynamically Interconnected Sequential Stereoselective Processes. J. Am. Chem. Soc. 2015, 137, 9375−9381. (e) Al Sulaimi, S. S.; Rajendran, K. V.; Gilheany, D. G. Lithium Borohydride for Achiral and Stereospecific Reductive Boronation at Phosphorus: Lack of Electronic Effects on Stereoselective Formation of Alkoxyphosphonium Salts. Eur. J. Org. Chem. 2015, 2015, 5959−5965. (f) Podyacheva, E.; Kuchuk, E.; Chusov, D. Reduction of phosphine oxides to phosphines. Tetrahedron Lett. 2019, 60, 575−582. (g) Hérault, D.; Nguyen, D. H.; Nuel, D.; Buono, G. Reduction of secondary and tertiary phosphine oxides to phosphines. Chem. Soc. Rev. 2015, 44, 2508−2528. (h) Nie, S.-Z.; Zhou, Z.-Y.; Wang, J.-P.; Yan, H.; Wen, J.-H.; Ye, J.-J.; Cui, Y.-Y.; Zhao, C.-Q. Nonepimerizing Alkylation of H−P Species to Stereospecifically Generate P-Stereogenic Phosphine Oxides: A Shortcut to Bidentate Tertiary Phosphine Ligands. J. Org. Chem. 2017, 82, 9425−9434. (19) Koller, S.; Gatzka, J.; Wong, K.-M.; Altmann, P. J.; Pöthig, A.; Hintermann, L. Stereochemistry of the Menthyl Grignard Reagent: Generation, Composition, Dynamics, and Reactions with Electrophiles. J. Org. Chem. 2018, No. 15009. (20) Stankevič, M.; Pietrusiewicz, K. M. Resolution and Stereochemistry of tert-Butylphenylphosphinous Acid-Borane. J. Org. Chem. 2007, 72, 816−822. (21) (a) Liu, L.-J.; Wang, W.-M.; Yao, L.; Meng, F.-J.; Sun, Y.-M.; Xu, H.; Xu, Z.-Y.; Li, Q.; Zhao, C.-Q.; Han, L.-B. Reinvestigation of the Substitutions Reaction of Stereogenic Phosphoryl Compounds: Stereochemistry, Mechanism, and Applications. J. Org. Chem. 2017, 82, 11990−12002. (b) Ye, J.-J.; Nie, S.-Z.; Wang, J.-P.; Wen, J.-H.; Zhang, Y.; Qiu, M.-R.; Zhao, C.-Q. Nucleophilic Substitution of P8438


Article

The Journal of Organic Chemistry Stereogenic Chlorophosphines: Mechanism, Stereochemistry, and Stereoselective Conversions of Diastereomeric Secondary Phosphine Oxides to Tertiary Phosphines. Org. Lett. 2017, 19, 5384−5387. (22) 17 gave two single peaks at 49.0 (88%) and 45.3 ppm (12%) on 31 P NMR spectrum. (23) On 31P NMR spectrum, RP-19 gave the peak at 40.7 ppm, similar to 5. The peak of H-P was not observed on its 1H NMR spectrum. Thus the lithium salt of penta-valent phosphorus was assigned.

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Functional Phosphine Derivatives Having Stationary and Flexible

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