Cobalt-Catalyzed Oxidative C(sp3)–H Phosphonylation for α

May 22, 2018 - The first oxidative C(sp3)–H phosphonylation of tertiary aliphatic amines has been developed. The use of cobalt acetate as a catalyst...
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Cite This: J. Org. Chem. 2018, 83, 6754−6761

Cobalt-Catalyzed Oxidative C(sp3)−H Phosphonylation for α‑Aminophosphonates via C(sp3)−H/P(O)−H Coupling Binzhou Lin,† Shanshan Shi,† Rongcan Lin,† Yiqun Cui,† Meijuan Fang,‡ Guo Tang,*,† and Yufen Zhao† †

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Department of Chemistry, College of Chemistry and Chemical Engineering, and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005, China ‡ Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361000, China S Supporting Information *

ABSTRACT: The first oxidative C(sp3)−H phosphonylation of tertiary aliphatic amines has been developed. The use of cobalt acetate as a catalyst, N-hydroxyphthalimide as a cocatalyst, and air as an oxidant enabled the conversion of tertiary aromatic and aliphatic amines into α-aminophosphonates in moderate to excellent yields under mild conditions via a cross dehydrogenative coupling reaction. Scheme 1. Synthetic Routes to α-Aminophosphonates

C

arbon−phosphorus bonds are widely found in many biologically active compounds, among which α-aminophosphonates (N−C−P bond) and related α-aminophosphonic acids possess a broad capability of influencing physiologic and pathologic processes, with applications ranging from inhibitors of enzymes to medicine.1 Consequently, the increasing demand for α-aminophosphonates has generated considerable interest in the development of efficient and flexible synthetic methods. The classical methods for their preparations are the Pudovik reaction2 and the Kabachnik−Fields reaction3 found in 1952 involving the condensation of H-phosphonates with aldehydes or imines [Scheme 1a]. Since then, great efforts have been made to develop the Lewis acid catalytic4 and catalyst-free5 synthesis of α-aminophosphonates. Although these methods are effective, they need imines formed by prefunctionalized aldehydes and amines. In recent years, oxidative C(sp3)−H phosphonylation for the synthesis of α-aminophosphonates from amines by employing the atom efficient cross dehydrogenative coupling (CDC) method is of high relevance in organic synthesis and has been the focus of recent research [Scheme 1b]. Pioneered by Li,6 Koenigs,7 and König,8 the direct phosphonylation of sp3hybridized carbon−hydrogen bonds adjacent to tertiary arylamines, in particular N-aryltetrahydroisoquinolines, has seen an explosion of interest.9 However, although these methods are very elegant, the range of starting materials is limited to tertiary arylamines,6−10 and a general method for the synthesis of α-aminophosphonates from tertiary aromatic and aliphatic amines has not yet been described. This is likely because tertiary aromatic amines have a strong propensity toward dehydrogenation to form stable extended π-conjugated imine intermediates. Compared with tertiary arylamines, aliphatic amines form the unstable intermediates. On the other hand, P(O)H compounds can easily be oxidized to © 2018 American Chemical Society

P(O)OH.11 Since CDC involves an oxidant, there is a fine line between oxidation of tertiary amines to imines versus direct oxidation of P(O)H compounds to the acids. Received: March 20, 2018 Published: May 22, 2018 6754

DOI: 10.1021/acs.joc.8b00674 J. Org. Chem. 2018, 83, 6754−6761

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The Journal of Organic Chemistry Table 1. Reaction Conditions Optimizationa

entry

catalyst

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

FeCl2 CuBr CuBr2 Co(OAc)2 Co(OAc)2 Co(OAc)2 CoCl2 Co(NO3)2 Co(OEt)2 Co(OAc)2 Co(OAc)2 Co(OAc)2 Co(OAc)2 Co(OAc)2

cocatalyst

T (°C)

solvent

oxidant

yield (%)

NHPI NHPI NHPI NHPI NHPI NHPI NHPI NHPI NHPI HOSU HOBT

rt to 60 60 60 80 60 80 rt to 60 80 80 80 80 80 80 80 80

CH3CN CH3OH CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN

TBHP O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 air air air

0−15 10 0 38 0 80 25−50 80 78 77 31−43b 45 85 (62c, 60d) 72 80

CH3CN CH3CN CH3CN

a Reaction conditions: 1 (0.5 mmol), 2 (1.7 mmol), catalyst (0.05 mmol), cocatalyst (0.15 mmol), and solvent (2.5 mL) were heated at the refluxing temperature under air for 16 h. Isolated yield. All catalysts are hydrated salts and used without further purification. bTetrahydrofuran, dichloroethane, or 1,4-dioxane as a solvent. cCo(OAc)2 (5 mol %) and NHPI (30 mol %). dCo(OAc)2 (10 mol %) and NHPI (10 mol %).

isolated yield (entry 13). To elucidate the respective importance of cobalt acetate and NHPI further, we carried out two experiments (entries 14b and 14c). We found that a combination of 0.1 equiv of cobalt acetate with 0.3 equiv of NHPI provided the best results (entry 13). Screening other cocatalysts, such as N-hydroxysuccinimide (HOSU) and 1hydroxybenzotriazole (HOBT), revealed that NHPI was the best choice (entries 13−15). After a series of detailed investigations, we established an efficient route to substituted α-aminophosphonates via co-catalyzed CDC reactions. The optimal reaction conditions are 1 (0.5 mmol), 2 (1.7 mmol), Co(OAc)2 (10 mol %), NHPI (30 mol %), and CH3CN (2.5 mL) at 80 °C for 16 h under aerobic conditions (entry13 in Table 1) . We next explored the substrate scope of the C−H phosphonation reaction using a wide range of tertiary aromatic or aliphatic amines (Table 2). Good to excellent yields were observed in most cases, illustrating the efficiency of the developed CDC method. For the tertiary aliphatic amines, tri-nbutylamine, tri-n-propylamine, tri-n-hexylamine, and tri-n-octylamine, the steric hindrance has no influence on the formation of α-aminophosphonates. For example, tri-n-octylamine with three bulky octyl groups provided 6 in 70% yield. Triethylamine (7) gave a moderate yield. N,N-Dimethylaniline (8) and N,N-dimethyltetradecanamine (9) were quiet incompetent to do these transformations, and P(O)H was oxidized to P(O)OH completely. This behavior could be explained by the oxidation potentials of tertiary amines, which decrease with an increasing chain length (e.g., Me3N, +0.82 V; Et3N, +0.79 V; n-Bu3N, +0.62 V; measured vs SCE).16 In regard to the Hphosphonates, in addition to diethyl H-phosphonate (1), dimethyl, diisopropyl, dibutyl, and dibenzyl H-phosphonates all could be used as the substrates, generating the corresponding

As a continuation of our endeavor to develop step economical P−C formations,12 we reported a direct reductive phosphonylation of inert amide carbonyls promoted by Cp2ZrHCl for the preparation of α-aminophosphonates in 2013 [Scheme 1a].13 Herein, we describe the use of the inexpensive cobalt acetate in combination with N-hydroxyphthalimide (NHPI) and air as a highly active catalytic system for the oxidative α-phosphonylation of tertiary aliphatic and aromatic amines. This dehydrogenative coupling process provides access to a host of α-aminophosphonates from a wide variety of amine substrates. The use of air instead of pure oxygen and organic oxidants is advantageous in terms of safety. Initial investigations into the proposed cross dehydrogenative coupling focused on the reaction of diethyl H-phosphonate (1) with tri-n-butylamine (2) (Table 1). In the beginning, various copper and iron salts were tested, most of which behaved poorly (entries 1−3 in Table 1). We were delighted to find that the C−H phosphonylation in the presence of cobalt acetate (10 mol %) and molecular oxygen (1 atm, balloon) provided the desired α-aminophosphonate product in a moderate yield (38%; entry 4 in Table 1). Although NHPI alone has been revealed to be an efficient organocatalyst for free-radical processes and has found ample application in promoting the aerobic oxidation of a wide range of organic substrates,14 the reaction was inhibited in the absence of a cobalt salt (entry 5). A combination of cobalt acetate with NHPI furnished 3 in a good yield (80%; entry 6 vs 4).15 The yield of product 3 decreased when the reaction was operated in the temperature range from rt to 60 °C (entry 7). Subsequently, various cobalt salts were screened under similar conditions, and all cobalt salts showed a good efficacy (entries 8−10). The reaction performed best in acetonitrile (entries 10−12). Gratifyingly, air as an oxidant can further improve the reaction, giving 3 in 85% 6755

DOI: 10.1021/acs.joc.8b00674 J. Org. Chem. 2018, 83, 6754−6761

Note

The Journal of Organic Chemistry Table 2. Oxidative C(sp3)−H Phosphonylation for α-Aminophosphonates via C(sp3)−H/P(O)−H Coupling

α-aminophosphonates (10−13) in good yields. Not surprisingly, reacting diphenylphosphine oxide (Ph2P(O)H) with trin-butylamine in the presence of Co catalyst in one pot gave the desired product 14 in merely 20% yield. The tautomeric equilibria of diphenylphosphine oxide is well-known and the tricoordinated phosphite can be easily oxidized to Ph2P(O)OH.17 Oxidation of the diphenylphosphine oxide with air will inhibit the C−H activation step. Different N-aryltetrahydroisoquinolines were coupled with diethyl H-phosphonate. They can uniformly afford the desired products with almost quantitative yields (15−20). The reaction of diisopropyl H-phosphonate, dibutyl H-phosphonate, and dibenzyl H-phosphonate with 2-(4-bromophenyl)-1,2,3,4-tetrahydroisoquinoline gave slightly lower yields under the standard

conditions (22−24 vs 15−21). This is likely due to the high steric sensitivity of the addition reaction of the bulky O,Odialkyl phosphonyl anions with iminium cation intermediates. Although several methods have been developed for oxidative αC−H phosphonation of N-aryltetrahydroisoquinolines, diaryl phosphine oxides as reaction partners are rarely reported. Kobayashi and Zhu reported the aerobic phosphonylation reaction of N-aryl tetrahydroisoquinolines with Ph2P(O)H catalyzed by the noble iridium-based and gold-based photocatalyst under visible light irradiation, independently.18 The base cobalt catalytic system could proceed smoothly to furnish the C−P coupling products 25 and 26 in good yields. N-Benzyl and N-butyl-tetrahydroisoquinolines could be used as the substrates, generating the corresponding α-aminophosphonates 6756

DOI: 10.1021/acs.joc.8b00674 J. Org. Chem. 2018, 83, 6754−6761

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The Journal of Organic Chemistry 27 and 28 in 75 and 70% yields, respectively. N-Acyl tetrahydroisoquinolines were also examined. Unfortunately, only a trace amount of the desired product was detected (29). In order to demonstrate the practical application of this method, diethyl H-phosphonate (1, 5 mmol) and tri-nbutylamine (2, 17 mmol) were employed in a gram-scale reaction and delivered 3 in 75% yield (Scheme 2). The excess amount of amine was recovered in 75% yield.

In conclusion, we have developed a Co(OAc)2/NHPIcatalyzed α-aminophosphonylation of aliphatic and aromatic tertiary amines with P(O)H compounds, which is efficient for the synthesis of α-aminophosphonates. The protocol represents the first cross dehydrogenative coupling reaction between αC−H bonds of tertiary aliphatic amines and phosphinylidenes. Furthermore, the use of air instead of pure oxygen and organic oxidants is advantageous in terms of safety.

■

Scheme 2. Gram-Scale Preparation of 3

EXPERIMENTAL SECTION

General. All reagents were obtained from commercial suppliers and used without further purification. 1H NMR (500 MHz) and 13C NMR (125 MHz) spectra were measured on Bruker AVIII 500 M spectrometers with CDCl3 as a solvent and tetramethylsilane (TMS) as an internal standard. Chemical shifts were reported in units (ppm) by assigning TMS resonance in the 1H spectrum as 0.00 ppm and CDCl3 resonance in the 13C spectrum as 77.23 ppm. All coupling constants (J values) were reported in hertz (Hz). Chemical shifts of common trace 1H NMR impurities (ppm) are as follows: H2O, 1.56; CHCl3, 7.26. Column chromatography was performed on silica gel 300−400 mesh. The unknown products were further characterized by HRMS (FT-ICR-MS) and an electrospray ionization source in positive-ion mode. General Procedure for the Synthesis of 1,2,3,4-Tetrahydroisoquinoline Derivatives. 19 Copper(I) iodide (200 mg, 1.0 mmol) and anhydrous potassium phosphate (4.25 g, 20.0 mmol) were put into a Schlenk tube. (No product was obtained when hydrated potassium phosphate was used.) The tube was evacuated and refilled with nitrogen. 2-Propanol (10 mL), ethylene glycol (1.11 mL, 20.0 mmol), 1,2,3,4-tetrahydro-isoquinoline (2.0 mL, 15.0 mmol), and iodobenzene (1.12 mL, 10.0 mmol) were added successively using a syringe at room temperature. The reaction mixture was heated at 85−90 °C and kept for 24 h. The reaction mixture was allowed to cool to ambient temperature and then transferred to a round-bottom flask. Silica gel (3.0 g) was added, and the solvent was removed under reduced pressure to afford a free-flowing powder. This powder was then dryloaded onto a silica gel column and purified by flash chromatography using a petroleum ether/AcOEt mixture [from 50:1 to 20:1 (v/v)] as the eluent to give the desired product in 60% isolated yield. Diethyl (1-(Dibutylamino)butyl)phosphonate (3): CAS no. 875228-32-3;3a 137 mg, 85% yield, light yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 4.12−4.00 (m, 4H), 2.93−2.87 (m, 1H), 2.67−2.62 (m, 2H), 2.59−2.54 (m, 2H), 1.58−1.51 (m, 3H), 1.35− 1.20 (m, 15H), 0.89−0.85 (m, 9H); 13C NMR (125 MHz, CDCl3) δ (ppm) 61.5 (d, J = 7.4 Hz), 60.9 (d, J = 7.6 Hz), 58.4 (d, J = 134.2 Hz), 51.7 (d, J = 3.5 Hz), 31.8 (s), 30.0 (d, J = 7.2 Hz), 20.5 (d, J = 12.7 Hz), 20.4 (s), 16.7 (d, J = 5.7 Hz), 16.65 (d, J = 5.9 Hz), 14.2 (s), 14.0 (s); 31P NMR (202 MHz, CDCl3) δ (ppm) 29.8; HRMS calcd for C16H36NNaO3P+ [M + Na]+ 344.2325, found 344.2320. Diethyl (1-(Dipropylamino)propyl)phosphonate (4): 91 mg, 65% yield, light yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 4.09− 4.00 (m, 4H), 2.79−2.73 (m, 1H), 2.65−2.59 (m, 2H), 2.53−2.47 (m, 2H), 1.67−1.56 (m, 2H), 1.41−1.30 (m, 4H), 1.27−1.25 (m, 5H), 0.97 (t, J = 7.7 Hz, 3H), 0.81 (t, J = 7.4 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ (ppm) 61.5 (d, J = 7.4 Hz), 60.9 (d, J = 7.5 Hz), 60.6 (d, J = 133.8 Hz), 53.9 (d, J = 3.4 Hz), 22.6 (s), 21.0 (d, J = 7.6 Hz), 16.68 (d, J = 5.8 Hz), 16.60 (d, J = 5.6 Hz), 12.3 (d, J = 13.0 Hz), 11.7 (s); 31P NMR (202 MHz, CDCl3) δ (ppm) 29.6; HRMS calcd for C13H30NNaO3P+ [M + Na]+ 302.1856, found 302.1861. Diethyl (1-(Dihexylamino)hexyl)phosphonate (5): 142 mg, 70% yield, light yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 4.09− 4.01 (m, 4H), 2.88−2.82 (m, 1H), 2.65−2.59 (m, 2H), 2.56−2.50 (m, 2H), 1.58−1.49 (m, 2H), 1.32−1.23 (m, 28H), 0.85−0.81 (m, 9H); 13 C NMR (125 MHz, CDCl3) δ (ppm) 61.4 (d, J = 7.5 Hz), 60.9 (d, J = 7.6 Hz), 58.6 (d, J = 133.6 Hz), 51.9 (d, J = 3.3 Hz), 31.9 (s), 31.7 (s), 29.5 (s), 27.7 (d, J = 7.3 Hz), 26.967 (d, J = 12.3 Hz), 27.968 (s), 22.8 (s), 22.6 (s), 16.9 (d, J = 5.6 Hz), 16.60 (d, J = 5.8 Hz), 14.09 (s), 14.06 (s); 31P NMR (202 MHz, CDCl3) δ (ppm) 29.8; HRMS calcd for C22H48NNaO3P+ [M + Na]+ 428.3264, found 428.3264.

The reaction between 1 and 2 was inhibited obviously by adding 1.5 equiv of 2,2,6,6-tetra-methylpiperidinooxy (TEMPO) or butylated hydroxytoluene (BHT) (Scheme 3). Scheme 3. Control Experiments

Although the detailed mechanism remains ambiguous currently, a possible mechanism for this Co(II) complex-catalyzed αaminophosphonylation of aliphatic tertiary amines with P(O)H compounds is described in Scheme 4. Co(II)-NHPI complex A Scheme 4. Tentative Mechanistic Pathway

is formed when Co(OAc)2 and NHPI are added into acetonitrile. Co(II) complex activates the molecular oxygen to produce oxidized Co(III)-phthalimide-N-oxyl (PINO) radical B and HOO−. Subsequent coordination of Lewis basic tertiary amine to complex B produces complex C. Single electron abstraction from the nitrogen atom produces aminyl radical D, which is facilitated by the coordination of electrondeficient PINO. Concerted α-C−H bond cleavage, an intramolecular 1,4-hydrogen transfer, by the N-oxyl radical produces iminium cation intermediate E while regenerating Co(II)NHPI complex A. A further addition of anion F to iminium cation E gives the desired CDC product. 6757

DOI: 10.1021/acs.joc.8b00674 J. Org. Chem. 2018, 83, 6754−6761

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The Journal of Organic Chemistry

δ (ppm) 32.0; HRMS calcd for C24H37NOP+ [M + H]+ 386.2607, found 386.2610. Diethyl (2-Phenyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phosphonate (15): CAS no. 87992-94-7;6 155 mg, 90% yield, white solid, mp 62−64 °C; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.37 (t, J = 7.6 Hz, 1H), 7.25−7.22 (m, 2H), 7.19−7.13 (m, 3H), 6.97 (t, J = 8.3 Hz, 2H), 6.78 (t, J = 7.2 Hz, 1H), 5.18 (d, J = 20.0 Hz, 1H), 4.12−3.85 (m, 5H), 3.64−3.60 (m, 1H), 3.10−3.04 (m, 1H), 3.01−2.95 (m, 1H), 1.24 (t, J = 7.1 Hz, 3H), 1.13 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 149.6 (d, J = 5.7 Hz), 136.5 (d, J = 5.5 Hz), 130.7 (s), 129.2 (s), 128.8 (d, J = 2.5 Hz), 128.2 (d, J = 4.6 Hz), 127.5 (d, J = 3.4 Hz), 125.9 (d, J = 2.7 Hz), 118.5 (s), 114.9 (s), 63.4 (d, J = 7.2 Hz), 62.4 (d, J = 7.7 Hz), 58.9 (d, J = 159.2 Hz), 43.6 (s), 26.8 (s), 16.5 (d, J = 5.4 Hz), 16.4 (d, J = 5.7 Hz); 31P NMR (202 MHz, CDCl3) δ (ppm) 22.2; HRMS calcd for C19H25NO3P+ [M + H]+ 346.1567, found 346.1567. Diethyl (2-(4-Methoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-1yl)phosphonate (16): CAS no. 87992-95-8;6 187 mg, 100% yield, light yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.39 (t, J = 6.2 Hz, 2H), 7.20−7.11 (m, 3H), 6.92 (d, J = 9.1 Hz, 2H), 6.81 (d, J = 9.0 Hz, 2H), 5.02 (d, J = 21.5 Hz, 1H), 4.12−3.92 (m, 5H), 3.74 (s, 3H), 3.56−3.51 (m, 1H), 2.93 (s, 2H), 1.26 (t, J = 7.1 Hz, 3H), 1.16 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 153.2 (s), 144.2 (d, J = 8.2 Hz), 136.5 (d, J = 6.0 Hz), 130.6 (s), 129.0 (d, J = 2.1 Hz), 128.2 (d, J = 4.5 Hz), 127.3 (d, J = 3.4 Hz), 125.8 (d, J = 2.9 Hz), 118.6 (s), 114.6 (s), 63.4 (d, J = 7.2 Hz), 62.3 (d, J = 7.5 Hz), 58.5 (d, J = 158.5 Hz), 55.7 (s), 44.7 (s), 26.2 (s), 16.5 (d, J = 5.4 Hz), 16.4 (d, J = 5.7 Hz); 31P NMR (202 MHz, CDCl3) δ (ppm) 22.2; HRMS calcd for C20H27NO4P+ [M + H]+ 376.1672, found 376.1672. Diethyl (2-(4-(Trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)phosphonate (17): light yellow oil, 206 mg, 100% yield; 1 H NMR (500 MHz, CDCl3) δ (ppm) 7.47 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 6.8 Hz, 1H), 7.21−7.15 (m, 4H), 7.00 (d, J = 8.5 Hz, 2H), 5.23 (d, J = 18.2 Hz, 1H), 4.14−3.82 (m, 5H), 3.62−3.57 (m, 1H), 3.28− 3.22 (m, 1H), 3.02−2.96 (m, 1H), 1.22 (t, J = 7.1 Hz, 3H), 1.12 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 151.4 (s), 136.3 (d, JC−P = 5.1 Hz), 130.3 (s), 128.6 (d, JC−P = 2.6 Hz), 128.2 (d, JC−P = 4.7 Hz), 127.9 (d, JC−P = 3.5 Hz), 126.4 (d, JC−F = 3.6 Hz), 126.2 (d, JC−P = 2.6 Hz), 124.9 (d, JC−F = 270.2 Hz), 119.5 (d, JC−F = 32.7 Hz), 113.2 (s), 63.5 (d, JC−P = 7.3 Hz), 62.8 (d, JC−P = 7.6 Hz), 58.4 (d, JC−P = 159.7 Hz), 43.5 (s), 27.3 (s), 16.5 (d, JC−P = 5.4 Hz), 16.4 (d, JC−P = 5.5 Hz); 31P NMR (202 MHz, CDCl3) δ (ppm) 21.8; HRMS calcd for C20H23F3NNaO3P+ [M + Na]+ 436.1260, found 436.1263. Diethyl (2-(2-Bromophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)phosphonate (18): 212 mg, 100% yield, light yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.35 (t, J = 7.0 Hz, 1H), 7.22−7.14 (m, 3H), 7.11−7.07 (m, 2H), 6.89−6.87 (m, 2H), 5.14 (d, J = 18.7 Hz, 1H), 4.10−3.84 (m, 5H), 3.56−3.51 (m, 1H), 3.20−3.15 (m, 1H), 3.00−2.94 (m, 1H), 1.23 (t, J = 7.1 Hz, 3H), 1.16 (t, J = 7.0 Hz, 3H); 13 C NMR (125 MHz, CDCl3) δ (ppm) 155.4 (d, J = 4.2 Hz), 136.3 (d, J = 5.4 Hz), 133.9 (s), 130.3 (s), 128.7 (d, J = 2.8 Hz), 128.2 (d, J = 5.3 Hz), 127.7 (d, J = 3.4 Hz), 126.1 (d, J = 2.6 Hz), 123.3 (s), 121.0 (s), 117.2 (s), 112.9 (s), 63.4 (d, J = 7.3 Hz), 62.6 (d, J = 7.8 Hz), 58.8 (d, J = 159.6 Hz), 43.5 (s), 27.1 (s), 16.4 (d, J = 6.0 Hz), 16.4 (d, J = 6.0 Hz); 31P NMR (202 MHz, CDCl3) δ (ppm) 21.7; HRMS calcd for C19H23BrNaNO3P+ [M + Na]+ 446.0491, found 446.0488. Diethyl (2-(3-Bromophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)phosphonate (19): 211 mg, 100% yield, light yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.35 (t, J = 7.2 Hz, 1H), 7.23−7.15 (m, 3H), 7.11−7.07 (m, 2H), 6.90−6.87 (m, 2H), 5.13 (d, J = 18.5 Hz, 1H), 3.90−3.84 (m, 5H), 3.57−3.52 (m, 1H), 3.21−3.15 (m, 1H), 3.00−2.95 (m, 1H), 1.23 (t, J = 7.5 Hz, 3H), 1.15 (t, J = 7.2 Hz, 3H); 13 C NMR (125 MHz, CDCl3) δ (ppm) 150.5 (d, J = 4.4 Hz), 136.4 (d, J = 5.4 Hz), 130.5 (s), 130.4 (s), 128.7 (d, J = 2.7 Hz), 128.2 (d, J = 4.6 Hz), 127.8 (d, J = 3.5 Hz), 126.1 (d, J = 2.6 Hz), 123.4 (s), 121.0 (s), 117.2 (s), 112.9 (s), 63.3 (d, J = 7.3 Hz), 62.6 (d, J = 7.7 Hz), 58.8 (d, J = 159.2 Hz), 43.6 (s), 27.2 (s), 16.5 (d, J = 5.5 Hz), 16.4 (d, J = 6.0 Hz); 31P NMR (202 MHz, CDCl3) δ (ppm) 21.7; HRMS calcd for C19H23BrNaNO3P+ [M + Na]+ 446.0491, found 446.0486.

Diethyl (1-(Dioctylamino)octyl)phosphonate (6): 171 mg, 70% yield, light yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 4.08− 3.98 (m, 4H), 2.88−2.82 (m, 1H), 2.65−2.59 (m, 2H), 2.55−2.50 (m, 2H), 1.58−1.49 (m, 2H), 1.32−1.20 (m, 40H), 0.83−0.81 (m, 9H); 13 C NMR (125 MHz, CDCl3) δ (ppm) 61.4 (d, J = 7.4 Hz), 60.9 (d, J = 7.5 Hz), 58.6 (d, J = 133.4 Hz), 51.8 (d, J = 2.9 Hz), 31.92 (s), 31.90 (s), 29.5 (s), 29.7 (s), 29.49 (s), 29.47 (s), 29.4 (s), 29.3 (s), 27.75 (s), 27.70 (s), 27.32 (s), 27.29 (s), 27.23 (s), 22.7 (s), 16.66 (d, J = 5.7 Hz), 16.59 (d, J = 5.7 Hz), 14.1 (s); 31P NMR (202 MHz, CDCl3) δ (ppm) 29.8; HRMS calcd for C28H61NO3P+ [M + H]+ 490.4384, found 490.4383. Diethyl (1-(Diethylamino)ethyl)phosphonate (7): CAS no. 1909767-7;3a 44 mg, 37% yield, light yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 4.19−4.04 (m, 4H), 3.20−3.11 (m, 1H), 2.81−2.74 (m, 2H), 2.54−2.47 (m, 2H), 1.32−1.20 (m, 9H), 1.02 (t, J = 7.3 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ (ppm) 62.7 (d, J = 7.2 Hz), 61.1 (d, J = 7.3 Hz), 52.8 (d, J = 156.2 Hz), 44.8 (d, J = 7.3 Hz), 16.7 (d, J = 5.7 Hz), 16.6 (d, J = 5.6 Hz), 14.3 (s), 9.9 (d, J = 5.1 Hz), 31P NMR (202 MHz, CDCl3) δ (ppm) 28.2; HRMS calcd for C10H24NNaO3P+ [M + Na]+ 260.1386, found 260.1390. Dimethyl (1-(Dibutylamino)butyl)phosphonate (10): 110 mg, 75% yield, light yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 3.72−3.65 (m, 6H), 2.95−2.89 (m, 1H), 2.61−2.45 (m, 4H), 1.62− 1.52 (m, 3H), 1.34−1.19 (m, 9H), 0.89−0.82 (m, 9H); 13C NMR (125 MHz, CDCl3) δ (ppm) 58.2 (d, J = 135.8 Hz), 52.4 (d, J = 7.6 Hz), 51.7 (s), 51.6 (d, J = 3.6 Hz), 31.7 (s), 29.9 (d, J = 7.0 Hz), 20.5 (d, J = 12.6 Hz), 20.4 (s), 14.1 (s), 13.9 (s); 31P NMR (202 MHz, CDCl3) δ (ppm) 32.2; HRMS calcd for C14H33NO3P+ [M + H]+ 294.2193, found 294.2195. Diisopropyl (1-(Dibutylamino)butyl)phosphonate (11): 96 mg, 55% yield, light yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 4.69−4.63 (m, 2H), 2.83−2.77 (m, 1H), 2.69−2.63 (m, 2H), 2.59− 2.53 (m, 2H), 1.56−1.49 (m, 3H), 1.36−1.19 (m, 21H), 0.90−0.83 (m, 9H); 13C NMR (125 MHz, CDCl3) δ (ppm) 69.8 (d, J = 7.7 Hz), 69.4 (d, J = 8.1 Hz), 58.9 (d, J = 134.1 Hz), 51.6 (d, J = 2,7 Hz), 31.8 (s), 30.0 (d, J = 7.2 Hz), 24.5 (d, J = 2.9 Hz), 24.3 (d, J = 3.1 Hz), 24.2 (d, J = 5.3 Hz), 20.5 (s), 20.4 (s), 20.36 (s), 14.2 (s), 14.0 (s); 31P NMR (202 MHz, CDCl3) δ (ppm) 28.0; HRMS calcd for C18H41NO3P+ [M + H]+ 350.2819, found 350.2821. Dibenzyl (1-(Dibutylamino)butyl)phosphonate (12): 145 mg, 65% yield, light yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.34− 7.28 (m, 2H), 5.06−4.92 (m, 4H), 2.99−2.93 (m, 1H), 2.72−2.66 (m, 2H), 2.62−2.57 (m, 2H), 1.63−1.51 (m, 2H), 1.38−1.18 (m, 10H), 0.87−0.83 (m, 9H); 13C NMR (125 MHz, CDCl3) δ (ppm) 137.0 (s), 136.99 (s), 136.97 (s), 136.92 (s), 128.6 (s), 128.29 (s), 128.27 (s), 128.1 (s), 67.2 (d, J = 7.3 Hz), 66.5 (d, J = 7.7 Hz), 58.9 (d, J = 140.3 Hz), 51.7 (d, J = 3.2 Hz), 31.8 (s), 30.0 (d, J = 7.2 Hz), 20.44 (d, J = 12.8 Hz), 20.43 (s), 14.2 (s), 14.0 (s); 31P NMR (202 MHz, CDCl3) δ (ppm) 30.7; HRMS calcd for C26H41NO3P+ [M + H]+ 446.2819, found 446.2819. Dibutyl (1-(Dibutylamino)butyl)phosphonate (13): 126 mg, 67% yield, light yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 4.06− 3.95 (m, 4H), 2.96−2.90 (m, 1H), 2.69−2.63 (m, 2H), 2.61−2.55 (m, 2H), 1.65−1.55 (m, 6H), 1.43−1.20 (m, 14H), 0.94−0.87 (m, 15H); 13 C NMR (125 MHz, CDCl3) δ (ppm) 65.3 (d, J = 7.5 Hz), 64.7 (d, J = 7.6 Hz), 58.4 (d, J = 132.9 Hz), 51.7 (d, J = 3.0 Hz), 32.9 (s), 32.88 (s), 32.83 (s), 31.9 (s), 30.1 (d, J = 7.2 Hz), 20.6 (s), 20.47 (s), 20.45 (s), 19.0 (s), 14.2 (s), 14.0 (s), 13.7 (s); 31P NMR (202 MHz, CDCl3) δ (ppm) 30.0; HRMS calcd for C20H45NO3P+ [M + H]+ 378.3132, found 378.3132. (1-(Dibutylamino)butyl)diphenylphosphine Oxide (14): 39 mg, 20% yield, white paste; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.86− 7.80 (m,4H), 7.48−7.37 (m, 6H), 3.56−3.52 (m, 1H), 2.66−2.61 (m, 2H), 2.56−2.51 (m, 2H), 1.90−1.81 (m, 1H), 1.67−1.58 (m, 1H), 1.44−1.06 (m, 14H), 0.82−0.78 (m, 9H); 13C NMR (125 MHz, CDCl3) δ (ppm) 134.4 (d, J = 4.5 Hz), 133.7 (d, J = 5.1 Hz), 131.6 (d, J = 8.8 Hz), 131.4 (d, J = 2.5 Hz), 131.2 (d, J = 2.5 Hz), 131.1 (d, J = 8.2 Hz), 128.6 (d, J = 10.3 Hz), 128.1 (d, J = 11.3 Hz), 61.5 (d, J = 78.0 Hz), 52.5 (d, J = 5.0 Hz), 31.7 (s), 28.2 (d, J = 6.8 Hz), 21.7 (d, J = 10.9 Hz), 20.4 (s), 14.2 (s), 14.1 (s); 31P NMR (202 MHz, CDCl3) 6758

DOI: 10.1021/acs.joc.8b00674 J. Org. Chem. 2018, 83, 6754−6761

Note

The Journal of Organic Chemistry

J = 5.4 Hz); 31P NMR (202 MHz, CDCl3) δ (ppm) 20.5; HRMS calcd for C21H27BrNaNO3P+ [M + Na]+ 474.0804, found 474.0797. (2-(4-Bromophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)diphenylphosphine Oxide (25): CAS no. 1382465-08-8;18c 173 mg, 71% yield, white solid, mp 147.5−149.5 °C; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.76 (t, J = 8.8 Hz, 2H), 7.69 (t, J = 8.9 Hz, 2H), 7.55 (t, J = 7.2 Hz, 1H), 7.47−7.44 (m, 3H), 7.39−7.33 (m, 2H), 7.21−7.14 (m, 3H), 7.08 (d, J = 7.7 Hz, 1H), 6.94 (t, J = 7.5 Hz, 1H), 6.66−6.61 (m, 3H), 5.48 (d, J = 9.9 Hz, 1H), 4.05−4.00 (m, 1H), 3.52−3.48 (m, 1H), 2.83−2.69 (m, 2H); 13C NMR (125 MHz, CDCl3) δ (ppm) 149.0 (d, J = 7.1 Hz), 136.7 (d, J = 4.2 Hz), 132.4 (s), 132.3 (d, J = 8.4 Hz), 132.2 (d, J = 2.6 Hz), 132.0 (s), 131.7 (d, J = 8.8 Hz), 131.3 (s), 130.6 (s), 129.7 (s), 129.3 (d, J = 1.7 Hz), 128.6 (d, J = 11.2 Hz), 128.5 (d, J = 11.1 Hz), 127.8 (d, J = 3.2 Hz), 127.7 (d, J = 2.7 Hz), 125.7 (d, J = 2.7 Hz), 118.1 (s), 111.6 (s), 62.2 (d, J = 78.7 Hz), 45.2 (s), 25.9 (s); 31P NMR (202 MHz, CDCl3) δ (ppm) 30.6; HRMS calcd for C27H23BrNaNOP+ [M + Na]+ 510.0593, found 510.0591. Diphenyl(2-phenyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phosphine Oxide (26): CAS no. 1382465-02-2;18c 174 mg, 85% yield, white solid, mp 196.5−198.5 °C; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.80 (t, J = 8.6 Hz, 2H), 7.71 (t, J = 8.5 Hz, 2H), 7.71 (t, J = 5.4 Hz, 1H), 7.47− 7.42 (m, 3H), 7.36−7.32 (m, 2H), 7.16−7.07 (m, 4H), 6.94 (t, J = 7.5 Hz, 1H), 6.81−6.76 (m, 3H), 6.65 (d, J = 7.7 Hz, 1H), 5.57 (d, J = 10.6 Hz, 1H), 4.07−4.01 (m, 1H), 3.60−3.56 (m, 1H), 2.86−2.82 (m, 1H), 2.70−2.66 (m, 1H); 13C NMR (125 MHz, CDCl3) δ (ppm) 150.1 (d, J = 7.8 Hz), 137.0 (d, J = 4.0 Hz), 132.7 (s), 132.3 (d, J = 8.3 Hz), 132.0 (d, J = 2.7 Hz), 131.8 (d, J = 9.0 Hz), 131.76 (s), 131.1 (s), 130.0 (s), 129.3 (d, J = 1.7 Hz), 129.2 (s), 128.5 (d, J = 11.0 Hz), 128.4 (d, J = 11.1 Hz), 127.9 (d, J = 3.0 Hz), 127.5 (d, J = 2.7 Hz), 125.6 (d, J = 2.5 Hz), 119.6 (s), 116.9 (s), 62.1 (d, J = 79.7 Hz), 45.3 (s), 25.7 (s); 31P NMR (202 MHz, CDCl3) δ (ppm) 30.6; HRMS calcd for C27H24NaNOP+ [M + Na]+ 432.1488, found 432.1487. Diethyl (2-Benzyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phosphonate (27): 135 mg, 75% yield; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.42−7.27 (m, 6H), 7.23−7.14 (m, 3H), 4.21 (d, J = 21.5 Hz, 1H), 4.10−3.95 (m, 6H), 3.72−3.66 (m, 1H), 2.98−2.84 (m, 2H), 2.73 (d, J = 17.6 Hz, 1H), 1.30−1.23 (m, 6H); 13C NMR (125 MHz, CDCl3) δ (ppm) 138.7 (s), 136.0 (d, J = 5.8 Hz), 129.7 (s), 129.3 (d, J = 4.2 Hz), 129.0 (d, J = 2.7 Hz), 128.3 (s), 127.2 (s), 127.0 (d, J = 3.6 Hz), 125.6 (d, J = 3.2 Hz), 62.8 (d, J = 7.3 Hz), 62.3 (d, J = 7.4 Hz), 60.0 (d, J = 157.8 Hz), 59.5 (d, J = 12.4 Hz), 45.5 (d, J = 1.8 Hz), 25.1 (s), 16.5 (d, J = 2.8 Hz), 16.4 (d, J = 2.6 Hz); 31P NMR (202 MHz, CDCl3) δ (ppm) 23.3; HRMS calcd for C20H27NO3P+ [M + H]+ 360.1723, found 360.1720. Diethyl (2-Butyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phosphonate (28): 114 mg, 70% yield; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.31 (d, J = 7.2 Hz, 1H), 7.17−7.08 (m, 3H), 4.11 (d, J = 22.5 Hz, 1H), 4.09−3.97 (m, 4H), 3.66−3.61 (m, 1H), 2.89−2.80 (m, 2H), 2.69− 2.65 (m, 3H), 1.53−1.48 (m, 2H), 1.36−1.31 (m, 2H), 1.28−1.21 (m, 6H), 0.91 (t, J = 7.4 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 136.4 (d, J = 6.3 Hz), 130.0 (s), 129.3 (d, J = 3.9 Hz), 129.0 (d, J = 2.1 Hz), 127.0 (d, J = 3.5 Hz), 125.6 (d, J = 2.9 Hz), 63.2 (d, J = 7.5 Hz), 62.3 (d, J = 7.6 Hz), 60.5 (d, J = 159.7 Hz), 55.3 (d, J = 12.6 Hz), 45.8 (s), 30.1 (s), 24.9 (s), 20.5 (s), 16.5505 (s), 16.5501 (d, J = 10.4 Hz), 14.2(s); 31P NMR (202 MHz, CDCl3) δ (ppm) 23.3; HRMS calcd for C17H28NNaO3P+ [M + Na]+ 348.1699, found 348.1699.

Diethyl (2-(4-Bromophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)phosphonate (20): CAS no. 1315275-83-2;7 212 mg, 100% yield, white solid, mp 85−87 °C; quant; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.35 (d, J = 7.1 Hz, 1H), 7.33−7.29 (m, 2H), 7.22−7.14 (m, 3H), 6.85−6.82 (m, 2H), 5.10 (d, J = 19.1 Hz, 1H), 4.13−3.83 (m, 5H), 3.55−3.50 (m, 1H), 3.17−3.11 (m, 1H), 2.99−2.93 (m, 1H), 1.23 (t, J = 7.1 Hz, 3H), 1.13 (t, J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 148.3 (d, J = 4.9 Hz), 136.3 (d, J = 5.4 Hz), 131.8 (s), 130.4 (s), 128.7 (d, J = 2.6 Hz), 128.2 (d, J = 4.7 Hz), 127.7 (d, J = 4.0 Hz), 126.1 (d, J = 2.6 Hz), 116.2 (s), 110.3 (s), 63.4 (d, J = 7.3 Hz), 62.5 (d, J = 7.6 Hz), 58.8 (d, J = 159.0 Hz), 43.7 (s), 27.0 (s), 16.5 (d, J = 5.4 Hz), 16.4 (d, J = 5.6 Hz); 31P NMR (202 MHz, CDCl3) δ (ppm) 21.8; HRMS calcd for C19H23BrNaNO3P+ [M + Na]+ 446.0491, found 446.0490. Dimethyl (2-(4-Bromophenyl)-1,2,3,4-tetrahydroisoquinolin-1yl)phosphonate (21): CAS no. 1435940-00-3;9f 197 mg, 100% yield, white solid, mp 159.5−161.5 °C; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.33 (d, J = 9.0 Hz, 3H), 7.24−7.16 (m, 3H), 6.84 (d, J = 9.8 Hz, 2H), 5.12 (d, J = 19.1 Hz, 1H), 3.98−3.93 (m, 1H), 3.64 (t, J = 10.9 Hz, 6H), 3.56−3.51 (m, 1H), 3.16−3.12 (m, 1H), 3.00−2.94 (m, 1H); 13C NMR (125 MHz, CDCl3) δ (ppm) 148.2 (d, J = 5.0 Hz), 136.3 (d, J = 5.5 Hz), 132.0 (s), 130.2 (s), 128.8 (d, J = 2.6 Hz), 128.0 (d, J = 5.0 Hz), 127.8 (d, J = 3.4 Hz), 126.3 (d, J = 2.7 Hz), 116.2 (s), 110.6 (s), 58.7 (d, J = 159.8 Hz), 53.9 (d, J = 8.0 Hz), 53.1 (d, J = 8.0 Hz), 43.8 (s), 26.9 (s); 31P NMR (202 MHz, CDCl3) δ (ppm) 24.0; HRMS calcd for C17H19BrNaNO3P+ [M + Na]+ 418.0178, found 418.0175. Dibutyl (2-(4-Bromophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)phosphonate (22): 180 mg, 75% yield, white solid, mp 52−54 °C; 1 H NMR (500 MHz, CDCl3) δ (ppm) 7.35 (d, J = 7.3 Hz, 1H), 7.32− 7.29 (m, 2H), 7.21−7.14 (m, 3H), 6.85−6.82 (m, 2H), 5.11 (d, J = 18.0 Hz, 1H), 4.02−3.92 (m, 3H), 3.88−3.82 (m, 1H), 3.79−3.73 (m, 1H), 3.56−3.51 (m, 1H), 1.57−1.51 (m, 2H), 1.47−1.42 (m, 2H), 1.34−1.28 (m, 2H), 1.26−1.20 (m, 2H), 0.88 (t, J = 7.4 Hz, 3H), 0.82 (t, J = 7.3 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 148.4 (d, J = 4.8 Hz), 136.3 (d, J = 5.3 Hz), 131.9 (s), 130.6 (s), 128.8 (d, J = 2.6 Hz), 128.2 (d, J = 4.7 Hz), 127.7 (d, J = 3.4 Hz), 126.1 (d, J = 2.7 Hz), 116.2 (s), 110.4 (s), 67.0 (d, J = 7.7 Hz), 66.2 (d, J = 8.1 Hz), 58.8 (d, J = 158.8 Hz), 43.7 (s), 32.7 (d, J = 5.5 Hz), 32.6 (d, J = 5.5 Hz), 27.1 (s), 18.8 (d, J = 5.6 Hz), 13.7 (d, J = 4.8 Hz); 31P NMR (202 MHz, CDCl3) δ (ppm) 22.0; HRMS calcd for C23H31BrNaNO3P+ [M + Na]+ 502.1117, found 502.1119. Dibenzyl (2-(4-Bromophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)phosphonate (23): CAS no. 1322668-09-6;8 200 mg, 73% yield, white solid, mp 83−85 °C; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.35− 7.33 (m, 4H), 7.30−7.28 (m, 4H), 7.24−7.22 (m, 2H), 7.20−7.16 (m, 2H), 7.14−7.12 (m, 2H), 6.82 (d, J = 10.9 Hz, 2H), 5.22 (d, J = 18.8 Hz), 5.01−4.97 (m, 1H), 4.96−4.87 (m, 2H), 4.80−4.76 (m, 1H), 3.99−3.94 (m, 1H), 3.56−3.52 (m, 1H), 3.16−3.13 (m, 1H), 3.01− 2.96 (m, 1H); 13C NMR (125 MHz, CDCl3) δ (ppm) 148.2 (d, J = 4.6 Hz), 136.4 (d, J = 5.4 Hz), 136.27 (s), 136.22 (s), 131.18 (s), 131.9 (s), 130.2 (s), 128.9 (d, J = 2.6 Hz), 128.6 (s), 128.50 (s), 128.48 (s), 128.42 (s), 128.3 (d, J = 4.9 Hz), 128.2 (d, J = 1.4 Hz), 127.9 (d, J = 3.7 Hz), 126.5 (,d, J = 2.7 Hz), 116.4 (s), 110.6 (s), 68.8 (d, J = 7.4 Hz), 68.0 (d, J = 7.6 Hz), 59.0 (d, J = 157.6 Hz), 43.7 (s), 27.1 (s); 31P NMR (202 MHz, CDCl3) δ (ppm) 22.7; HRMS calcd for C29H27BrNaNO3P+ [M + Na]+ 570.0804, found 570.0798. Diisopropyl (2-(4-Bromophenyl)-1,2,3,4-tetrahydroisoquinolin-1yl)phosphonate (24): 153 mg, 68% yield, white solid, mp 80−82 °C; 1 H NMR (500 MHz, CDCl3) δ (ppm) 7.37 (d, J = 7.1 Hz, 1H), 7.31− 7.27 (m, 2H), 7.20−7.12 (m, 3H), 6.83−6.80 (m, 2H), 5.05 (d, J = 19.9 Hz, 1H), 4.63−4.55 (m, 2H), 4.00−3.95 (m, 1H), 3.57−3.52 (m, 1H), 3.13−3.07 (m, 1H), 2.97−2.91 (m, 1H), 1.28 (t, J = 6.0 Hz, 3H), 1.14 (d, J = 6.2 Hz, 2H), 0.94 (d, J = 6.3 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ (ppm) 148.5 (d, J = 5.5 Hz), 136.3 (d, J = 5.4 Hz), 131.7 (s), 130.7 (s), 128.7 (d, J = 2.6 Hz), 128.5 (d, J = 4.8 Hz), 127.6 (d, J = 3.4 Hz), 125.6 (d, J = 2.6 Hz), 116.4 (s), 110.1 (s), 72.3 (d, J = 7.9 Hz), 71.1 (d, J = 8.2 Hz), 58.9 (d, J = 161.4 Hz), 43.7 (s), 26.8 (s), 24.5 (d, J = 2.7 Hz), 24.2 (d, J = 3.3 Hz), 23.8 (d, J = 5.5 Hz), 23.4 (d,

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S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b00674. Compound list and 1H NMR, 31P NMR, and 13C NMR spectra (PDF)

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Corresponding Author

*E-mail: [email protected]. 6759

DOI: 10.1021/acs.joc.8b00674 J. Org. Chem. 2018, 83, 6754−6761

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The Journal of Organic Chemistry ORCID

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Guo Tang: 0000-0002-4349-398X Yufen Zhao: 0000-0002-8513-1354 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We acknowledge financial support from the NSFC (21772163, 21778042, and 21375113), NFFTBS (J1310024), and the Fundamental Research Funds for the Central Universities (20720160030).

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REFERENCES

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DOI: 10.1021/acs.joc.8b00674 J. Org. Chem. 2018, 83, 6754−6761

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DOI: 10.1021/acs.joc.8b00674 J. Org. Chem. 2018, 83, 6754−6761