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Diastereoselective α‑Amination of N-tert-Butanesulfinyl Imidates Using N‑Aryl‑N‑diphenylphosphinyldiazenes Zheng-Fei Li,†,§ Yun Yao,‡ Yan-Jun Xu,† and Chong-Dao Lu*,†,‡ †

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Key Laboratory of Plant Resources and Chemistry of Arid Zones, Xinjiang Technical Institute of Physics & Chemistry, Chinese Academy of Sciences, Urumqi 830011, China ‡ School of Chemical Science and Technology, Yunnan University, Kunming 650091, China § University of Chinese Academy of Sciences, Beijing 100049, China S Supporting Information *

ABSTRACT: Diastereoselective α-amination of N-tert-butanesulfinyl imidates has been developed using N-aryl (or N-tert-butyl) Ndiphenylphosphinyldiazenes as nitrogen sources. The chiral 1azaenolates derived from imidates undergo nucleophilic addition with diazenes to give α-hydrazino imidates in good yields.

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Scheme 1. α-Amination of N-tert-Butanesulfinyl Imidates with N-Aryl (or N-tert-Butyl)-NDiphenylphosphinyldiazenes

INTRODUCTION Enantioselective construction of C−N bonds is an important pathway to access chiral amines that are building blocks in a variety of natural products and bioactive agents. A range of synthetic methods have been developed for asymmetric C−N bond formation, which includes nucleophilic substitution, reductive amination, transition-metal-mediated cross-coupling, nucleophilic addition to CN bonds, and electrophilic amination.1 Amination of an enolate or its equivalents with suitable NN or NO bonds allows straightforward installation of an amino group at the α-position of carbonyl compounds. Asymmetric catalysis of this reaction has been extensively explored, especially with aldehydes2 or activated carbonyl compounds3,4 as substrates. In addition, asymmetric α-amination reaction can proceed well with substrates that are not easily enolizable by using a stoichiometric amount of strong base; stereochemistry can be controlled in these cases by using a chiral auxiliary. The pioneering work of Evans and others has demonstrated the effectiveness of diastereoselective electrophilic α-amination of chiral carboximides using dialkyl azodicarboxylates.5 Several chiral variants of acid derivatives have subsequently been reported.6 N-tert-Butanesulfinyl imidates (or amidines) are chiral equivalents of esters (or amides) that can function well in diastereoselective α-functionalization (Scheme 1a).7−15 Recently, we reported that nitrosoarenes (ArNO) are suitable amination reagents to intercept the metal trans 1-azaenolates8b,16 derived from N-tert-butanesulfinyl (N-tBS) imidates (Scheme 1b).15 As a continuation of this work, we are interested in common amination reagents based on NN that might show electrophilic reactivity and diastereocontrol toward aza-enolate intermediates. Here, we report that N-aryl (or Ntert-butyl) N-diphenylphosphinyldiazenes can serve as effective © XXXX American Chemical Society

electrophilic amination reagents to realize diastereoselective αamination of N-tert-butanesulfinyl imidates (Scheme 1c). Initially, we examined α-amination of enolized N-tertbutanesulfinyl imidate 1a with N-phenyl-N-benzoyldiazene (2),2d a commonly used electrophilic amine source. Addition of LiHMDS to a solution of 1a and 2 at −78 °C gave the desired α-amination product 6a but with lack of diasterReceived: March 29, 2019

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DOI: 10.1021/acs.joc.9b00877 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry

reagent, even though the compound has been known for at least half a century.19 Diazenes 2 and 3 did not show good diastereocontrol under optimized conditions using LiHMDS and CH2Cl2 (entries 10−11). In our prior studies,15 nitrosobenzene (5a) was successfully used as the electrophilic amination reagent to react with sodium or potassium aza-enolates that had been generated by deprotonating N-tert-butanesulfinyl imidate 1a using NaHMDS or KHMDS in THF. We obtained α-hydroxyamino imidate 9a in yields of 81 or 67% with excellent diastereoselectivity (>20:1 dr) (Table 1, entries 12−13). In contrast, enolization of 1a with LiHMDS gave the desired product 9a but with relatively low diastereocontrol (entry 14, 3:1 dr). These results led us to re-investigate the reactivity and stereocontrol of diazenes 2, 3, and 4a in the α-amination of 1a under the reaction conditions that we previously established for nitrosobenzene. With NaHMDS as base and THF as the solvent, amination product 6a was obtained with moderate diastereoselectivity (7:1 dr, entry 15), while 7a and 8a were generated with excellent diastereoselectivity (>20:1 dr, entries 16−17). Excellent diastereoselectivity was also observed for diazenes 2, 3, and 4a in the presence of KHMDS in THF (entries 18−20). Using N-phenyl-N-diphenylphosphinyldiazene as an amination reagent, we examined the α-amination reaction of a range of linear aliphatic-substituted imidates 1b−f (Table 2, entries 2−6). Good yields and excellent diastereoselectivities were obtained in most cases. For imidates bearing α-branched alkyl groups such as iso-propyl and cyclohexyl groups, low conversion (20:1 dr). Next, α-phenyl N-tBS imidate 1h was subjected to the optimized amination conditions (4a, LiHMDS, CH2Cl2), but excellent diastereoselectivity could not be obtained (Table 3, entry 1). To improve this result, we rescreened (a) the bases that provided excellent diastereocontrol with α-methyl N-tBS imidate 1a (Table 1, entries 7−9, 17, and 20; Table 3, entries 3−5); (b) solvents such as dichloromethane, ether, toluene, and THF (Table 3, entries 5−7); and (c) the amount of base (Table 3, entry 8). We found that 0.2 equiv of potassium tertbutoxide in ether gave desired product 8t in acceptable yield (64%) with excellent diastereoselectivity of >20:1 dr (Table 3, entry 8). Similarly, we previously found that a catalytic amount of base was effective at promoting hydroxyamination of α-aryl N-tBS imidates using nitrosoarenes as amination reagents.22

eoselectivity (1:1 dr) and simultaneous production of substantial byproducts (Table 1, entry 1).17 Under the same Table 1. Optimization of the Diastereoselectivity of αAminationa

entry

base

solvent

1 2 3 4 5 6

LiN(SiMe3)2 LiN(SiMe3)2 LiN(SiMe3)2 LiN(SiMe3)2 LiN(SiMe3)2 LiN(SiMe3)2

THF THF THF toluene Et2O CH2Cl2

7 8 9 10 11 12 13 14 15 16 17 18 19 20

NaN(SiMe3)2 KN(SiMe3)2 tBuOK LiN(SiMe3)2 LiN(SiMe3)2 NaN(SiMe3)2 KN(SiMe3)2 LiN(SiMe3)2 NaN(SiMe3)2 NaN(SiMe3)2 NaN(SiMe3)2 KN(SiMe3)2 KN(SiMe3)2 KN(SiMe3)2

CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 THF THF THF THF THF THF THF THF THF

product (cov)b 6a (>95%) 7a (>95%) 8a (95%) 8a (>95%) 8a (>95%) 8a (86%) (>95%)e 8a (78%) 8a (37%) 8a (66%) 6a(50%) 7a (>95%) 9a (>95%) 9a (>95%) 9a (>95%) 6a (>95%) 7a (>95%) 8a (>95%) 6a (>95%) 7a (>95%) 8a (>95%)

d

drb (yield)c ∼1:1 4:1 13:1 15:1 6:1 >20:1 >20:1 >20:1 >20:1 >20:1 ∼1:1 1:1.5 >20:1 >20:1 3:1 7:1 >20:1 >20:1 >20:1 >20:1 >20:1

(84%) (94%)e

(81%) (67%)

(94%) (94%) (82%) (84%) (90%)

a

Reaction conditions for entries 1−11 and 15−20: imidate (0.20 mmol), base (1.2 equiv), and diazene (1.3 equiv) in the anhydrous solvent at −78 °C. Reaction conditions for entries 12−14: imidate (0.30 mmol), base (1.2 equiv), and nitrosobenzene (1.3 equiv) in anhydrous THF at −78 °C. bConversion and diastereoselective ratios were determined by 1H NMR spectroscopy of the crude reaction mixture. cIsolated yield after silica gel chromatography. dFormation of a substantial amount of byproducts (products/byproducts = 1:1). e Gram-scale synthesis of 8a.

conditions [LiHMDS/tetrahydrofuran (THF)], N-phenyl-Ntosyldiazene (3) was better able to trap enolized N-tBS imidate to give α-amination product 7a with moderate diastereoselectivity (4:1 dr, entry 2). To our delight, diastererocontrol was further improved to 13:1 dr by using N-phenyl-N-diphenylphosphinyldiazene (4a) as the amination agent (entry 3). Solvent screening (entries 4−6) indicated that dichloromethane was the best choice, giving excellent dr and good isolated yield (84%, entry 6). The reaction was easily scaled up to gram scale while retaining diastereoselectivity, and even higher yield (94%) was obtained. With 4a as the amination agent and dichloromethane as the solvent, excellent diastereoselectivities were generally achieved using the bases NaHMDS (entry 7), KHMDS (entry 8), and tBuOK (entry 9), although these conditions led to lower conversion of N-tBS imidate.18 This appears to be the first report of N-phenyl-Ndiphenylphosphinyldiazene as an electrophilic amination B

DOI: 10.1021/acs.joc.9b00877 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry Table 2. Substrate Scope of α-Amination of α-Alkyl N-tert-Butanesulfinyl Imidatesa

entry

imidate (R)

diazene/nitrosoarene (R′)

product

yield (%)b

drc

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

1a (Me) 1b (nPr) 1c (Bn) 1d (allyl) 1e (PhCCCH2) 1f [PMBO(CH2)2] 1a (Me) 1a (Me) 1a (Me) 1a (Me) 1a (Me) 1a (Me) 1a (Me) 1a (Me) 1a (Me) 1b (nPr) 1c (Bn) 1d (allyl) 1g (BnCH2)

4a/5a (Ph) 4a/5a (Ph) 4a/5a (Ph) 4a (Ph) 4a (Ph) 4a (Ph) 4b (4-MeC6H4) 4c/5b (3-MeC6H4) 4d/5c (2-MeC6H4) 4e/5d (4-MeOC6H4) 4f (4-FC6H4) 4g/5e (4-ClC6H4) 4h/5f (4-BrC6H4) 4i (2-naphthyl) 4j (tBu) 4j (tBu) 4j (tBu) 4j (tBu) 4j (tBu)

8a/9a 8b/9b 8c/9c 8d 8e 8f 8g 8h/9d 8i/9e 8j/9f 8k 8l/9g 8m/9h 8n 8o 8p 8q 8r 8s

84/81 93/81d 97/80 93 97 77e 97 97e/80 37e/80 90/76d 88 86/60 82/62 90 96 92 52 91 79

>20:1/>20:1 25:1/>20:1 >20:1/>20:1 >20:1 >20:1 25:1 >20:1 12:1/>20:1 6:1/>20:1 >20:1/5:1 >20:1 28:1/>20:1 15:1/>20:1 >20:1 >20:1 >20:1 >20:1 >20:1 >20:1

a Reaction conditions: imidate (0.20 mmol), LiHMDS (1.2 equiv), and diazene (1.3 equiv) in anhydrous dichloromethane at −78 °C; or imidate (0.30 mmol), NaHMDS (1.2 equiv), and nitrosobenzene (1.3 equiv) in anhydrous THF at −78 °C. bIsolated yield after silica gel chromatography. c Ratio of diastereomers was determined by 1H NMR spectroscopy of the crude reaction mixture. dRefers to the N−O cleavage product after treatment with Zn/AcOH. eIsolated product was a mixture of diastereomers.

The α-amination of 1h was also carried out under various reaction conditions with N-benzoyldiazene 2 (entries 9−13) and N-tosyldiazene 3 (entries 14−18). Good yield and excellent diastereocontrol were only achieved for N-tosyldiazene 3 when the reaction was carried out in ether with tBuOK as a base (entry 17). Then, we tested a range of α-aryl N-tBS imidates 1i−1n for α-amination with N-phenyl-N-diphenylphosphinyldiazene (4a) in the presence of a catalytic amount of tBuOK, giving the corresponding α-hydrazino imidates 8u−8z in moderate to high yields (58−88%) with good diastereoselectivities (Table 4). These results are comparable to those we obtained previously when we used nitrosobenzene as the amination reagent in the presence of catalytic amount (0.2 equiv) of NaHMDS (entries 1−6, 8t−8y vs 9i−9n).15 For the electronrich α-heteroaromatic substituted N-tBS imidate 1o, 1.2 equiv of base was required for high conversion, affording amination product 8aa in 54% yield (entry 8). To demonstrate the synthetic usefulness of this approach, we subjected the α-hydrazino N-tBS imidates to further reactions (Scheme 2). Conversion of imidate 8g to the corresponding N-tBS carboxamide 10 via acidic hydrolysis (4 M H2SO4) was easily realized in high yield (90%).10b Highyielding reduction of 8j with Red-Al provided N-tBS amine 11. Lithium−liquid ammonia reduction cleaved the N−N bond of 11 in quantitative yield to afford vicinal chiral amine 12, which bears different protecting groups on the two nitrogen atoms. Sodium−liquid ammonia was also effective for this cleavage transformation, albeit in lower yield (78%). Surprisingly, using cerium(IV) ammonium nitrate to remove the para-methoxyphenyl group from 11 resulted in the formation of diamine 12

in 68% yield, leaving the para-methoxyphenyl group intact. We were unable to directly cleave the N−N bond of the αaminated imidates using Raney Ni/H223 and SmI2/MeOH2d prior to reduction of the imidate group. In contrast, in our previous report,15 the N−O bond of α-hydroxyamino imidates can be easily cleavaged under mild conditions (Zn/AcOH). X-ray diffraction analysis of crystals of the aminated αmethyl N-tBS imidate 8g and α-2-methylphenyl counterpart 8u allowed us to assign their absolute configuration as (RS, 2S).24 This stereochemical outcome is consistent with that of electrophilic α-hydroxyamination of N-tBS imidate with nitrosoarene.15 The bulkiness of the diphenylphosphinyl group may explain why 1-diphenylphosphinyl diazenes aminate N-tBS imidates have greater diastereocontrol than analogues containing 1-benzoyl or tosyl groups under a range of reaction conditions (Tables 1 and 3).

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CONCLUSIONS Here, N-aryl (or N-tert-butyl) N-diphenylphosphinyldiazenes are introduced as an electrophilic amination reagent based on the NN bond, which can realize highly diastereoselective αamination of N-tert-butanesulfinyl imidates. This amination protocol enables construction of a range of chiral α-hydrazino imidates that are useful precursors for enantioenriched αamino acid derivatives and 1,2-diamines.

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EXPERIMENTAL SECTION

General Experimental Details. All reactions were performed under an argon atmosphere in flame-dried glassware with magnetic stirring using standard Schlenk techniques. All solvents were dried and distilled before use. Purification of the reaction products was carried C

DOI: 10.1021/acs.joc.9b00877 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry Table 3. Optimization of Amination of α-Aryl Imidatea

Entry

base

solvent

product (cov)b

drb (yield)c

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

LiN(SiMe3)2 LiN(SiMe3)2 NaN(SiMe3)2 KN(SiMe3)2 tBuOK tBuOK tBuOK tBuOK LiN(SiMe3)2 NaN(SiMe3)2 KN(SiMe3)2 tBuOK tBuOK LiN(SiMe3)2 NaN(SiMe3)2 KN(SiMe3)2 tBuOK tBuOK

CH2Cl2 THF THF THF CH2Cl2 THF Et2O Et2O THF THF THF Et2O Et2O THF THF THF Et2O Et2O

8t (>95%) 8t (>95%) 8t (72%) 8t (81%) 8t (>95%) 8t (94%) 8t (>95%) 8t (91%) 6b (>95%) 6b (>95%) 6b (>95%) 6b (>95%) 6b (34%) 7b (>95%) 7b (>95%) 7b (>95%) 7b (>95%) 7b (45%)

6:1−15:1 1:4 >20:1 3.3:1 15:1 2.4:1 >20:1 (68%) >20:1 (64%) ∼7:1 (95%) ∼6:1e ∼5:1e ∼6:1e naf ∼1:1 4:1 15:1 >20:1 (85%) >20:1

Scheme 2. Manipulations of α-Aminated N-tertButanesulfinyl Imidates

out by flash column chromatography using 200−300 mesh silica gel. Visualization on thin-layer chromatography was achieved by the use of UV light (254 nm) and treatment with aqueous ceric ammonium molybdate staining followed by heating. High-resolution mass spectra (HRMS) were measured using electron spray ionization with a timeof-flight mass analyzer (ESI-TOF). Proton and carbon magnetic resonance spectra (1H NMR and 13C{1H} NMR) were recorded on a 400 MHz (1H NMR at 400 MHz and 13C{1H} NMR at 100 MHz) spectrometer with solvent resonance as the internal standard (1H NMR, CDCl3 at 7.26 ppm, C6D6 at 7.16 ppm; 13C{1H} NMR, CDCl3 at 77.16 ppm, C6D6 at 128.06 ppm). 1H NMR data are reported as follows: chemical shifts, multiplicity (s = singlet, d = doublet, t = triplet, q = quadruplet, m = multiplet), coupling constant(s) in Hz, and integration. Materials. Dichloromethane was distilled from CaH2. Toluene and ether were distilled from sodium/benzophenone. All N-tertbutylsulfinyl imidates were prepared according to the reported procedure.8,12,13 N-Phenyl-N-diphenylphosphinyldiazene 4a was prepared according to the reported procedure.19a,25 N-aryl-Ndiphenylphosphinyldiazenes were synthesized by the following procedure. General Procedure for Synthesis of N-Diphenylphosphinyldiazenes. Hydrazine hydrochloride (1.0 equiv) and Et3N (2.0 equiv) were dissolved in DCM at −20 °C before 4-(dimethylamino)pyridine (5.0 equiv) was added. After the reaction mixture was stirred for 30 min at −20 °C, the solution of diphenylphosphinyl chloride (0.8 equiv) in 3.0 mL DCM was added. The reaction mixture was stirred for 4 h before being quenched with saturated aqueous sodium chloride. The mixture was diluted with ethyl acetate and washed sequentially with 1 M HCl solution, aq NaHCO3, and brine. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give crude hydrazide. The crude hydrazide prepared above (∼1.0 equiv) was dissolved in dichloromethane before addition of pyridine (1.1 equiv) at −78 °C. After the reaction mixture was stirred for 10 min at −78 °C, Nbromosuccinimide (NBS) (1.0 equiv) was added. After 30 min, the reaction solution was warmed to rt for 2 h. The solvent was removed under reduced pressure. The reaction mixture was diluted with ethyl acetate and washed sequentially with 1 M HCl solution, aq NaHCO3, and brine. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel to afford diazene. Diphenyl(p-tolyldiazenyl)phosphine Oxide (4b). Reaction of ptolylphenylhydrazine hydrochloride (1.59 g, 10.0 mmol), diphenylphosphinyl chloride (1.53 mL, 8.0 mmol), Et3N (2.78 mL, 20.0 mmol), and 4-(dimethylamino)pyridine (6.10 g, 50.0 mmol) in dichloromethane (30 mL) afforded crude P,P-diphenyl-N′-(p-tolyl)phosphinic hydrazide (1.07 g, ∼3.3 mmol) that was oxidized by NBS (0.59 g, 3.3 mmol) in the presence of pyridine (0.30 mL, 3.7 mmol) in dichloromethane (50 mL) according to the general procedure to give the title compound (0.87 g, 34%) as a deep red solid, mp 135.3− 136.4 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); 1H NMR (400 MHz, CDCl3): δ 8.0−7.94 (m, 4H), 7.89 (d, J = 8.4 Hz, 2H), 7.59−7.55 (m, 2H), 7.53−7.48 (m, 4H), 7.31 (d, J = 8.4 Hz, 2H),

a

Reaction conditions: imidate (0.20 mmol), base (1.2 equiv), and diazene (1.3 equiv) in the anhydrous solvent at −78 °C, unless otherwise noted. bConversion and diastereomeric ratios were determined by 1H NMR spectroscopy of the crude reaction mixture. c Isolated yield after silica gel chromatography. d0.2 equiv of base was used. eDiastereomeric ratio could not be accurately determined because of the presence of byproducts. fNot analyzed.

Table 4. Substrate Scope of α-Amination of α-Aryl N-tertButanesulfinyl Imidatesa

entry 1 2 3 4 5 6 7 8

imidate (Ar) 1h (Ph) 1i (2-MeC6H4) 1j (3-MeC6H4) 1k (4-MeC6H4) 1l (4-MeOC6H4) 1m (4-FC6H4) 1n (4-ClC6H4) 1o (2-thienyl)

product d

8t /9i 8ue/9j 8ve/9k 8we/9l 8xe/9m 8yd/9n 8zd 8aaf

yield (%)b

drc

64/85 88/79 63/45g 71/87 73/88 73/81 58 54

>20:1/>20:1 30:1/>20:1 27:1/>20:1 22:1/>20:1 22:1/>20:1 33:1/>20:1 33:1 27:1

a

Reaction conditions: imidate (0.20 mmol), tBuOK, and diazene 4a (1.3 equiv) in anhydrous CH2Cl2 at −78 °C; or imidate (0.30 mmol), NaHMDS (0.2 equiv), and nitrosobenzene (1.3 equiv) in anhydrous THF at −78 °C. bIsolated yield after silica gel chromatography. cRatio of diastereomers was determined by 1H NMR spectroscopy of the crude reaction mixture. d0.2 equiv tBuOK was used. e0.4 equiv tBuOK was used. f1.2 equiv tBuOK was used. gRefers to the N−O cleavage product after treatment with Zn/AcOH. D

DOI: 10.1021/acs.joc.9b00877 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry 2.43 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 153.1 (d, JC−P = 44 Hz), 145.2, 132.6 (d, JC−P = 2.7 Hz), 132.5 (d, JC−P = 8.5 Hz), 129.9, 129.8 (d, JC−P = 116 Hz), 128.8 (d, JC−P = 12 Hz), 123.4 (d, JC−P = 1.8 Hz), 21.9; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C19H18N2OP, 321.1151; found, 321.1147. Diphenyl(m-tolyldiazenyl)phosphine Oxide (4c). Reaction of mtolylphenylhydrazine hydrochloride (1.59 g, 10.0 mmol), diphenylphosphinyl chloride (1.53 mL, 8.0 mmol), Et3N (2.78 mL, 20.0 mmol), and 4-(dimethylamino)pyridine (6.10 g, 50.0 mmol) in dichloromethane (30 mL) afforded crude P,P-diphenyl-N′-(m-tolyl)phosphinic hydrazide (1.24 g, ∼3.8 mmol) that was oxidized with NBS (0.68 g, 3.8 mmol) in the presence of pyridine (0.34 mL, 4.20 mmol) in dichloromethane (50 mL) according to the general procedure to give the title compound (0.98 g, 38%) as a deep red solid, mp 98.2−99.5 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); 1H NMR (400 MHz, CDCl3): δ 8.0−7.95 (m, 4H), 7.80 (d, J = 7.2 Hz, 1H), 7.75 (s, 1H), 7.58−7.49 (m, 6H), 7.41−7.35 (m, 2H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 154.8 (d, JC−P = 43 Hz), 139.3, 134.7, 132.7 (d, JC−P = 2.6 Hz), 132.6 (d, JC−P = 8.5 Hz), 129.6 (d, JC−P = 116 Hz), 129.1, 128.8 (d, JC−P = 12 Hz), 123.1 (d, JC−P = 1.9 Hz), 121.3 (d, JC−P = 2.0 Hz), 21.4; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C19H18N2OP, 321.1151; found, 321.1149. Diphenyl(o-tolyldiazenyl)phosphine Oxide (4d). Reaction of otolylhydrazine hydrochloride (1.59 g, 10.0 mmol), diphenylphosphinyl chloride (1.53 mL, 8.0 mmol), Et3N (2.78 mL, 20.0 mmol), and 4-(dimethylamino)pyridine (6.10 g, 50.0 mmol) in dichloromethane (30 mL) afforded crude P,P-diphenyl-N′-(o-tolyl)phosphinic hydrazide (1.19 g, ∼3.7 mmol) that was oxidized with NBS (0.66 g, 3.7 mmol) in the presence of pyridine (0.32 mL, 4.0 mmol) in dichloromethane (50 mL) according to the general procedure to give the title compound (0.95 g, 37%) as a deep red solid, mp 75.0−77.0 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); 1H NMR (400 MHz, CDCl3): δ 7.95−7.88 (m, 5H), 7.60−7.56 (m, 3H), 7.52−7.43 (m, 7H), 7.35−7.33 (m, 2H), 7.22 (t, J = 7.2 Hz, 1H), 2.64 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 152.7 (d, JC−P = 42 Hz), 141.4 (d, JC−P = 1.4 Hz), 134.2, 132.6 (d, JC−P = 5.1 Hz), 132.5 (d, JC−P = 8.9 Hz), 131.9 (d, JC−P = 1.2 Hz), 129.6 (d, JC−P = 114 Hz), 128.7 (d, JC−P = 12 Hz), 126.3, 113.3 (d, JC−P = 2.2 Hz), 17.5; HRMS (ESITOF) m/z: [M + H]+ calcd for C19H18N2OP, 321.1151; found, 321.1152. ((4-Methoxyphenyl)diazenyl)diphenylphosphine Oxide (4e). Reaction of 4-methoxyphenylhydrazine hydrochloride (1.75 g, 10.0 mmol), diphenylphosphinyl chloride (1.53 mL, 8.0 mmol), Et3N (2.78 mL, 20.0 mmol), and 4-(dimethylamino)pyridine (6.10 g, 50.0 mmol) in dichloromethane (30.0 mL) afforded crude N′-(4methoxyphenyl)-P,P-diphenylphosphinic hydrazide (1.45 g, ∼4.3 mmol) that was oxidized with NBS (0.76 g, 4.3 mmol) in the presence of pyridine (0.38 mL, 4,7 mmol) in dichloromethane (50 mL) according to the general procedure to give the title compound (1.0 g, 37%) as a deep red solid, mp 101.5−103.0 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); 1H NMR (400 MHz, CDCl3): δ 8.01−7.94 (m, 6H), 7.58−7.54 (m, 2H), 7.52−7.47 (m, 4H), 7.0− 6.97 (m, 2H), 3.89 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 164.6, 149.8 (d, JC−P = 44 Hz), 132.6 (d, JC−P = 8.7 Hz), 132.5 (d, JC−P = 2.9 Hz), 130.2 (d, JC−P = 116 Hz), 128.7 (d, JC−P = 12 Hz), 125.9 (d, JC−P = 1.7 Hz), 114.4, 55.9; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C19H18N2O2P, 337.1100; found, 337.1102. ((4-Fluorophenyl)diazenyl)diphenylphosphine Oxide (4f). Reaction of 4-fluorophenylhydrazine hydrochloride (1.63 g, 10.0 mmol), diphenylphosphinyl chloride (1.53 mL, 8.0 mmol), Et3N (2.78 mL, 20.0 mmol), and 4-(dimethylamino)pyridine (6.10 g, 50.0 mmol) in dichloromethane (30 mL) afforded crude N′-(4-fluorophenyl)-P,Pdiphenylphosphinic hydrazide (2.16 g, ∼6.6 mmol) that was oxidized with NBS (1.17 g, 6.6 mmol) in the presence of pyridine (0.58 mL, 7.3 mmol) in dichloromethane (100 mL) according to the general procedure to give the title compound (2.03 g, 78%) as a deep red solid, mp 125.5−127.5 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); 1H NMR (400 MHz, CDCl3): δ 8.04−7.94 (m, 6H), 7.61−7.56 (m, 2H), 7.54−7.49 (m, 4H), 13C{1H} NMR (100 MHz, CDCl3): δ 166.2 (d, JC−F = 255 Hz), 151.3 (dd, JC−P = 44 Hz, JC−F = 2.8 Hz),

132.8 (d, JC−P = 2.7 Hz), 132.5 (d, JC−P = 8.6 Hz), 129.5 (d, JC−P = 116 Hz), 128.8 (d, JC−P = 12 Hz), 125.7 (dd, JC−F = 9.6 Hz, JC−P = 1.8 Hz), 116.4 (d, JC−F = 23 Hz); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H15FN2OP, 325.0901; found, 325.0900. ((4-Chlorophenyl)diazenyl)diphenylphosphine Oxide (4g). Reaction of 4-chlorophenylhydrazine hydrochloride (1.79 g, 10.0 mmol), diphenylphosphinyl chloride (1.53 mL, 8.0 mmol), Et3N (2.78 mL, 20.0 mmol), and 4-(dimethylamino)pyridine (6.10 g, 50.0 mmol) in dichloromethane (30 mL) afforded crude N′-(4-chlorophenyl)-P,Pdiphenylphosphinic hydrazide (1.36 g, ∼4.0 mmol) that was oxidized with NBS (0.71 g, 4.0 mmol) in the presence of pyridine (0.35 mL, 4.4 mmol) in dichloromethane (50 mL) according to the general procedure to give the title compound (1.12 g, 41%) as a deep red solid, mp 148.5−150.5 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); 1H NMR (400 MHz, CDCl3): δ 8.0−7.90 (m, 6H), 7.61−7.56 (m, 2H), 7.54−7.47 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 152.8 (d, JC−P = 42 Hz), 140.3, 132.9 (d, JC−P = 2.8 Hz), 132.6 (d, JC−P = 8.9 Hz), 129.7, 129.2 (d, JC−P = 116 Hz), 128.9 (d, JC−P = 12 Hz), 124.5 (d, JC−P = 1.7 Hz); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H15ClN2OP, 341.0605; found, 341.0603. ((4-Bromophenyl)diazenyl)diphenylphosphine Oxide (4h). Reaction of 4-bromophenylhydrazine hydrochloride (2.24 g, 10.0 mmol), diphenylphosphinyl chloride (1.53 mL, 8.0 mmol), Et3N (2.78 mL, 20.0 mmol), and 4-(dimethylamino)pyridine (6.10 g, 50.0 mmol) in dichloromethane (30 mL) afforded crude N′-(4bromophenyl)-P,P-diphenylphosphinic hydrazide (1.98 g, ∼5.1 mmol) that was oxidized with NBS (0.91 g, 5.1 mmol) in the presence of pyridine (0.45 mL, 5.6 mmol) in dichloromethane (50.0 mL) according to the general procedure to give the title compound (1.39 g, 45%) as a deep red solid, mp 158.5−159.5 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); 1H NMR (400 MHz, CDCl3): δ 8.01−7.94 (m, 4H), 7.86−7.83 (m, 2H), 7.68−7.65 (m, 2H), 7.61− 7.57 (m, 2H), 7.54−7.50 (m, 4H); 13C{1H} NMR (100 MHz, CDCl3): δ 153.2 (d, JC−P = 43 Hz), 132.9 (d, JC−P = 2.7 Hz), 132.7, 132.6 (d, JC−P = 8.9 Hz), 129.4 (d, JC−P = 106 Hz), 128.9 (d, JC−P = 12 Hz), 124.7 (d, JC−P = 1.7 Hz), 123.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H15BrN2OP, 385.0100; found, 385.0103. (Naphthalen-2-yldiazenyl)diphenylphosphine Oxide (4i). Reaction of 2-naphthylhydrazine hydrochloride (1.95 g, 10.0 mmol), diphenylphosphinyl chloride (1.53 mL, 8.0 mmol), Et3N (2.78 mL, 20.0 mmol), and 4-(dimethylamino)pyridine (6.10 g, 50.0 mmol) in dichloromethane (30.0 mL) afforded crude N′-(naphthalen-2-yl)-P,Pdiphenylphosphinic hydrazide (2.59 g, ∼7.2 mmol) that was oxidized with NBS (1.28 g, 7.2 mmol) in the presence of pyridine (0.64 mL, 7.9 mmol) in dichloromethane (50 mL) according to the general procedure to give the title compound (1.38 g, 48%) as a deep red solid, mp 158.0−159.5 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); 1H NMR (400 MHz, CDCl3): δ 8.73 (s, 1H), 8.05−8.0 (m, 5H), 7.91−7.85 (m, 3H), 7.63−7.50 (m, 8H), 13C{1H} NMR (100 MHz, CDCl3): δ 152.3 (d, JC−P = 44 Hz), 136.2, 133.2, 132.8 (d, JC−P = 1.9 Hz), 132.7 (d, JC−P = 2.6 Hz), 132.6 (d, JC−P = 8.7 Hz), 130.3, 129.8 (d, JC−P = 116 Hz), 129.3, 129.2, 128.8 (d, JC−P = 12 Hz), 128.1, 127.3, 114.5 (d, JC−P = 1.7 Hz); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C22H18N2OP, 357.1151; found, 357.1152. (tert-Butyldiazenyl)diphenylphosphine Oxide (4j). Reaction of tert-butylhydrazine hydrochloride (1.25 g, 10.0 mmol), diphenylphosphinyl chloride (1.53 mL, 8.0 mmol), Et3N (2.78 mL, 20.0 mmol), and 4-(dimethylamino)pyridine (6.10 g, 50.0 mmol) in dichloromethane (30 mL) afforded crude N′-(tert-butyl)-P,P-diphenylphosphinic hydrazide (1.71 g, ∼5.9 mmol) that was oxidized with NBS (1.05 g, 5.9 mmol) in the presence of pyridine (0.52 mL, 6.5 mmol) in dichloromethane (50 mL) according to the general procedure to give the title compound (1.03 g, 45%) as a yellow solid, mp 120.0− 122.0 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); 1H NMR (400 MHz, CDCl3): δ 7.92−7.87 (m, 4H), 7.58−7.54 (m, 2H), 7.51−7.46 (m, 4H), 1.30 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3): δ 132.6 (d, JC−P = 2.7 Hz), 132.4 (d, JC−P = 7.6 Hz), 129.7 (d, JC−P = 114 Hz), 128.7 (d, JC−P = 12 Hz), 75.4 (d, JC−P = 38 Hz), 26.3 (d, JC−P = 2.0 Hz); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H20N2OP, 287.1308; found, 287.1312. E

DOI: 10.1021/acs.joc.9b00877 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry

MeOH); 1H NMR (400 MHz, C6D6): δ 8.16−8.07 (m, 4H), 7.80 (s, 1H), 7.34−7.32 (m, 4H), 7.13−7.06 (m, 4H), 7.04−6.96 (m, 7H), 6.92 (t, J = 7.6 Hz, 1H), 5.80 (dd, J = 11.2 Hz, 3.6 Hz, 1 H), 3.55 (s, 1H), 3.34 (t, J = 12 Hz, 1H), 3.24 (s, 3H), 0.83 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 171.4, 151.2 (d, JC−P = 1.7 Hz), 137.5, 133.3 (d, JC−P = 130 Hz), 133.1 (d, JC−P = 8.9 Hz), 132.9 (d, JC−P = 9.3 Hz), 132.9 (d, JC−P = 128 Hz), 131.6 (d, JC−P = 2.3 Hz), 131.5 (d, JC−P = 2.5 Hz), 129.8, 128.7, 128.6, 128.2, 127.9, 126.8, 124.6, 123.7, 71.7, 56.1, 53.5, 39.4, 21.9; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H37N3O3PS, 574.2288; found, 574.2294. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)pent-4-enimidate (8d). According to the general procedure A, reaction using imidate 1d (43.5 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv) afforded 8d (97.4 mg, 93%) as a colorless oil; Rf = 0.30 (petroleum ether/ethyl acetate = 1:1); [α]20 D −4.5 (c 0.16, MeOH); 1H NMR (400 MHz, CDCl3): δ 7.87−7.83 (m, 2H), 7.72− 7.67 (m, 2H), 7.49−7.45 (m, 1H), 7.41−7.35 (m, 3H), 7.24−7.18 (m, 3H), 7.10 (d, J = 7.6 Hz, 2H), 7.0 (t, J = 7.2 Hz, 1H), 6.49 (d, JP−H = 24 Hz, 1H), 5.82−5.71 (m, 1H), 5.23 (dd, J = 8.8 Hz, 6.8 Hz, 1H), 5.10−5.01 (m, 2H), 3.61 (s, 3H), 2.73−2.65 (m, 2H), 1.02 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3): δ 171.0, 150.6 (d, JC−P = 3.7 Hz), 133.4, 132.6 (d, J = 9.5 Hz), 132.4 (d, J = 9.2 Hz), 131.9 (d, J = 2.6 Hz), 131.8 (d, JC−P = 114 Hz), 131.7 (d, JC−P = 2.6 Hz), 130.8 (d, JC−P = 133 Hz), 128.7, 128.4 (d, J = 12 Hz), 128.1 (d, J = 13 Hz), 124.0, 121.8, 118.4, 66.3, 56.9, 54.0, 36.5, 22.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C28H35N3O3PS, 524.2131; found, 524.2136. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)-5-phenylpent-4-ynimidate (8e). According to the general procedure A, reaction using imidate 1e (58.3 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv) afforded 8e (115.5 mg, 97%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:2); [α]20 D −28.3 (c 0.41, MeOH); 1H NMR (400 MHz, CDCl3): δ 7.87−7.82 (m, 2H), 7.78− 7.74 (m, 2H), 7.47 (t, J = 7.2 Hz, 1H), 7.38 (t, J = 7.2 Hz, 3H), 7.31− 7.29 (m, 2H), 7.25−7.22 (m, 6H), 7.15 (d, J = 7.6 Hz, 2H), 7.01 (t, J = 7.2 Hz, 1H), 6.52 (d, JP−H = 24 Hz, 1H), 5.50 (dd, J = 9.2, 5.2 Hz, 1H), 3.67 (s, 3H), 3.16−3.09 (m, 1H), 2.96−2.91 (m, 1H), 1.05 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 170.6, 150.9 (d, JC−P = 4.0 Hz), 133.2 (d, JC−P = 13 Hz), 133.1 (d, JC−P = 128 Hz), 133.0 (d, JC−P = 8.7 Hz), 132.5 (d, JC−P = 130 Hz), 132.1, 131.7, 131.5 (d, JC−P = 1.4 Hz), 128.9, 128.6, 128.5, 128.4, 128.0, 124.5, 124.3, 122.8, 88.3, 83.6, 66.5, 56.7, 54.0, 23.7, 22.1; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C34H37N3O3PS, 598.2288; found, 598.2291. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)-4-((4-methoxybenzyl)oxy)butanimidate (8f). According to the general procedure A, reaction using imidate 1f (66.9 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv) afforded 8f (99.8 mg, 77%) as a colorless oil.; Rf = 0.4 (petroleum ether/ethyl acetate = 1:2); [α]20 D +4.1 (c 0.39, MeOH); 1H NMR (400 MHz, C6D6): δ 8.16−8.12 (m, 2H), 8.07−8.04 (m, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.10 (t, J = 8.0 Hz, 2H), 7.04−7.03 (m, 3H), 6.98−6.98 (m, 3H), 6.89 (t, J = 7.2 Hz, 1H), 6.82−6.80 (m, 2H), 5.55 (t, J = 7.6 Hz, 1H), 4.36 (s, 2H), 3.46−3.43 (m, 2H), 3.33 (s, 3H), 3.23 (s, 3H), 2.25 (t, J = 7.2 Hz, 2H), 1.87−1.80 (m, 2H), 0.98 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 172.6, 159.6, 133.4 (d, JC−P = 129 Hz), 133.0 (d, JC−P = 8.4 Hz), 132.8 (d, JC−P = 127 Hz), 131.6, 131.6 (d, JC−P = 1.2 Hz), 131.4 (d, JC−P = 2.5 Hz), 129.5, 128.7, 128.6, 128.5, 128.0, 124.3, 123.2, 114.0, 72.7, 69.9, 56.6, 54.8, 53.7, 29.4, 27.0, 22.1; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C36H45N3O5PS, 662.2812; found, 662.2817. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1(p-tolyl)hydrazinyl)propanimidate (8g). According to the general procedure A, reaction using imidate 1a (38.3 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and diphenyl(p-tolyldiazenyl)phosphine oxide 4b (83.3 mg, 0.26

General Procedure A for the Preparation of Products 8a− 8s. To a solution of 1 (0.20 mmol, 1.0 equiv) and 4 (0.26 mmol, 1.3 equiv) in 4.0 mL of dichloromethane was added LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv) at −78 °C. The resulting mixture was maintained at −78 °C for 2 h and quenched with saturated solution of NH4Cl. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash column chromatography on silica gel. General Procedure B for the Preparation of Products 8t− 8aa. To a solution of 1 (0.20 mmol, 1.0 equiv) and 4a (0.26 mmol, 1.3 equiv) in 4.0 mL of Et2O was added t-BuOK (1.0 M in THF, 0.040 or 0.080 mmol, 0.20 or 0.40 equiv) at −78 °C. The resulting mixture was maintained at −78 °C for 2 h and quenched with saturated solution of NH4Cl. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash column chromatography on silica gel. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)propanimidate (8a). According to the general procedure A, reaction using imidate 1a (38.3 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv) afforded 8a (83.6 mg, 84%) as a yellow solid, mp 70.5−72.4 °C; Rf = 0.30 (petroleum ether/ethyl acetate = 1:1); [α]20 D +21.1 (c 0.32, MeOH); 1H NMR (400 MHz, CDCl3): δ 7.88−7.83 (m, 2 H), 7.80−7.75 (m, 2H), 7.51−7.47 (m, 1H), 7.43−7.39 (m, 3H), 7.31−7.28 (m, 2H), 7.23−7.15 (m, 4H), 6.95−6.91 (m, 1H), 6.0 (d, JP−H = 27 Hz, 1H), 5.36 (q, J = 6.8 Hz, 1H), 3.57 (s, 3H), 1.46 (d, J = 7.2 Hz, 3H), 1.08 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3): δ 173.6, 150.6 (d, JC−P = 3.0 Hz), 132.6 (d, JC−P = 9.4 Hz), 132.3 (d, JC−P = 9.1 Hz), 132.0 (d, JC−P = 2.4 Hz), 131.9 (d, JC−P = 2.5 Hz), 131.5 (d, JC−P = 122 Hz), 130.3 (d, JC−P = 122 Hz), 128.8, 128.4 (d, JC−P = 12 Hz), 128.1 (d, JC−P = 12 Hz), 122.8, 119.3, 60.2, 57.0, 54.1, 22.1, 17.1; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C26H32N3NaO3PS, 520.1794; found, 520.1800. Procedure for Gram-Scale Preparation of 8a. To a solution of 1a (1.05 g, 5.5 mmol) and 4a (2.19 g, 7.15 mmol) in 30 mL of dichloromethane was added LiHMDS (1.0 M in THF, 6.6 mL, 6.6 mmol) at −78 °C. The resulting mixture was maintained at −78 °C for 1 h and quenched with saturated solution of NH4Cl. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash column chromatography (petroleum ether/ethyl acetate = 1:1), providing 2.56 g (94%) of 8a as a yellow solid. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)pentanimidate (8b). According to the general procedure A, reaction using imidate 1b (43.9 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv) afforded 8b (97.8 mg, 93%) as a colorless oil; Rf = 0.30 (petroleum ether/ethyl acetate = 1:2); [α]20 D +7.0 (c 0.16, MeOH);1H NMR (400 MHz, C6D6): δ 8.16−8.12 (m, 2H), 8.05− 8.01 (m, 2H), 7.32 (d, J = 7.6 Hz, 2H), 7.10 (t, J = 7.6 Hz, 2H), 7.04−7.03 (m, 3H), 6.98−6.97 (m, 3H), 6.90 (t, J = 7.2 Hz, 1H), 5.46 (t, J = 7.6 Hz, 1H), 3.32 (s, 3H), 2.05−2.0 (m, 2H), 1.47−1.34 (m, 2H), 0.99 (s, 9H), 0.89 (t, J = 7.6 Hz, 3H); 13C{1H} NMR (100 MHz, C6D6): δ 172.6, 151.8 (d, JC−P = 2.2 Hz), 133.6 (d, JC−P = 128 Hz), 133.1 (d, JC−P = 8.7 Hz), 132.9 (d, JC−P = 131 Hz), 131.6 (d, JC−P = 2.3 Hz), 131.3 (d, JC−P = 2.5 Hz), 128.8, 128.5, 128.2, 127.9, 124.5, 123.5, 68.9, 56.6, 53.9, 34.5, 22.1, 19.9, 14.2; HRMS (ESITOF) m/z: [M + H]+ calcd for C28H37N3O3PS, 526.2288; found, 526.2289. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)-3-phenylpropanimidate (8c). According to the general procedure A, reaction using imidate 1c (53.5 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv) afforded 8c (111.3 mg, 97%) as a colorless oil; Rf = 0.40 (petroleum ether/ethyl acetate = 1:1); [α]20 D +15.0 (c 0.19, F

DOI: 10.1021/acs.joc.9b00877 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry

Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D +16.9 (c 0.39, MeOH); 1H NMR (400 MHz, C6D6): δ 8.08−8.05 (m, 2H), 7.97− 7.93 (m, 2H), 7.31 (d, JP−H = 24 Hz, 1H), 7.14−7.12 (m, 2H), 7.06− 7.05 (m, 3H), 6.99−6.97 (m, 3H), 6.77−6.73 (m, 2H), 5.34 (q, J = 6.4 Hz, 1H), 3.34 (s, 3H), 1.37 (d, J = 6.0 Hz, 3H), 0.99 (s, 9H); 13 C{1H} NMR (100 MHz, C6D6): δ 172.9, 160.0 (d, JC−F = 241 Hz), 147.5, 133.2 (d, JC−P = 128 Hz) 133.0 (d, JC−P = 9.2 Hz), 132.9 (d, JC−P = 8.6 Hz), 132.8 (d, JC−P = 131 Hz), 131.7 (d, JC−P = 1.9 Hz), 131.4, 128.5 (d, JC−P = 11 Hz), 128.3 (d, JC−P = 15 Hz), 124.4 (d, JC−F = 7.6 Hz), 115.3 (d, JC−F = 22 Hz), 63.6, 56.7, 54.1, 22.0, 17.6; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C26H32FN3O3PS, 516.1881; found, 516.1881. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(1-(4-chlorophenyl)-2(diphenylphosphoryl)hydrazinyl)propanimidate (8l). According to the general procedure A, reaction using imidate 1a (38.3 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and ((4-chlorophenyl)diazenyl)diphenylphosphine oxide 4g (88.3 mg, 0.26 mmol, 1.3 equiv) afforded 8l (91.7 mg, 86%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D +13.2 (c 0.34, MeOH); 1H NMR (400 MHz, C6D6): δ 8.09−8.04 (m, 2H), 8.0−7.95 (m, 2H), 7.15−7.13 (m, 2H), 7.09−7.08 (m, 1H), 7.06−7.02 (m, 4H), 7.0−6.94 (m, 3H), 5.44 (q, J = 6.8 Hz, 1H), 3.17 (s, 3H), 1.49 (d, J = 6.8 Hz, 3H), 0.97 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 172.7, 150.0 (d, JC−P = 3.9 Hz), 133.0 (d, JC−P = 128 Hz), 133.0 (d, JC−P = 12 Hz), 132.8 (d, JC−P = 8.8 Hz), 132.5 (d, JC−P = 128 Hz), 131.8 (d, JC−P = 2.6 Hz), 131.6 (d, JC−P = 2.6 Hz), 128.8, 128.5, (d, JC−P = 12 Hz), 128.2, 122.4, 110.4, 62.5, 56.8, 53.8, 22.0, 17.5; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C26H32ClN3O3PS; found, 532.1586. Methyl (S)-2-(1-(4-Bromophenyl)-2-(diphenylphosphoryl)hydrazinyl)-N-((R)-tert-butylsulfinyl)propanimidate (8m). According to the general procedure A, reaction using imidate 1a (38.3 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and ((4-bromophenyl)diazenyl)diphenylphosphine oxide 4h (100.3 mg, 0.26 mmol, 1.3 equiv) afforded 8m (94.7 mg, 82%) as a colorless solid, mp 168.0−170.0 °C; Rf = 0.4 (petroleum 1 ether/ethyl acetate = 1:1); [α]20 D +10.4 (c 0.16, MeOH); H NMR (400 MHz, C6D6): δ 8.07−8.03 (m, 2H), 8.0−7.95 (m, 2H), 7.24− 7.20 (m, 2H), 7.14−7.11 (m, 2H), 7.05−7.03 (m, 3H), 7.0−6.95 (m, 3H), 5.45 (q, J = 7.2 Hz, 1H), 3.14 (s, 3H), 1.51 (d, J = 6.8 Hz, 3H), 0.97 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 172.7, 150.4 (d, JC−P = 3.8 Hz), 132.9 (d, JC−P = 128 Hz), 132.9 (d, JC−P = 9.2 Hz), 132.8 (d, JC−P = 8.9 Hz), 132.4 (d, JC−P = 128 Hz), 131.8 (d, JC−P = 2.6 Hz), 131.8, 131.7 (d, JC−P = 2.6 Hz), 128.5 (d, JC−P = 12 Hz), 128.3 (d, JC−P = 12 Hz), 122.5, 115.9, 62.0, 56.8, 53.8, 22.0, 17.5; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C26H32BrN3O3PS, 576.1080; found, 576.1085. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1(naphthalen-2-yl)hydrazinyl)propanimidate (8n). According to the general procedure A, reaction using imidate 1a (38.3 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and (naphthalen-2-yldiazenyl)diphenylphosphine oxide 4i (92.3 mg, 0.26 mmol, 1.3 equiv) afforded 8n (98.7 mg, 90%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D +1.6 (c 0.37, MeOH); 1H NMR (400 MHz, C6D6): δ 8.17−8.12 (m, 2H), 8.06− 8.02 (m, 2H), 7.75−7.56 (m, 5H), 7.26−7.18 (m, 2H), 7.04−7.03 (m, 3H), 6.97−6.89 (m, 3H), 5.68 (q, J = 6.8 Hz, 1H), 3.20 (s, 3H), 1.58 (d, J = 6.8 Hz, 3H), 0.99 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 173.2, 148.9 (d, JC−P = 3.7 Hz), 134.4, 133.3 (d, JC−P = 128 Hz), 133.1 (d, JC−P = 11 Hz), 132.9 (d, JC−P = 8.8 Hz), 132.6 (d, JC−P = 131 Hz), 131.7 (d, JC−P = 2.4 Hz), 131.5 (d, JC−P = 2.4 Hz), 130.9, 128.9, 128.6, 128.5 (d, JC−P = 12 Hz), 128.1, 127.9, 126.4, 124.8, 121.4, 117.9, 62.3, 56.8, 53.4, 22.1, 17.7; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H35N3O3PS, 548.2131; found, 548.2133. Methyl (S)-2-(1-(tert-Butyl)-2-(diphenylphosphoryl)hydrazinyl)N-((R)-tert-butylsulfinyl)propanimidate (8o). According to the general procedure A, reaction using imidate 1a (38.3 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and (tert-butyldiazenyl)diphenylphosphine oxide 4j (74.4 mg, 0.26 mmol, 1.3 equiv) afforded 8o (91.7 mg, 96%) as a colorless oil;

mmol, 1.3 equiv) afforded 8g (99.3 mg, 97%) as a yellow solid, mp 163.7−165.0 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); 1 [α]20 D +17.0 (c 0.35, MeOH); H NMR (400 MHz, C6D6): δ 8.17− 8.11 (m, 2H), 8.06−8.01 (m, 2H), 7.27 (d, J = 8.4 Hz, 2H), 7.05− 7.03 (m, 3H), 7.0−6.97 (m, 3H), 6.94 (d, J = 8.4 Hz, 2H), 6.24 (s, 1H), 5.48 (q, J = 6.8 Hz, 1H), 3.33 (s, 3H), 2.07 (s, 3H), 1.47 (d, J = 6.8 Hz, 3H), 1.01 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 173.4, 149.2 (d, JC−P = 3.8 Hz), 134.7 (d, JC−P = 109 Hz), 133.3, 133.2 (d, JC−P = 9.1 Hz), 132.9 (d, JC−P = 131 Hz), 132.9 (d, JC−P = 8.8 Hz), 131.6 (d, JC−P = 2.5 Hz), 131.4 (d, JC−P = 2.5 Hz), 129.5, 128.5, 122.2, 110.4, 77.8, 56.7, 54.0, 22.1, 20.8, 17.7; HRMS (ESI-TOF) m/ z: [M + H]+ calcd for C27H35N3O3PS, 512.2131; found, 512.2135. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1(m-tolyl)hydrazinyl)propanimidate (8h). According to the general procedure A, reaction using imidate 1a (38.3 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and diphenyl(m-tolyldiazenyl)phosphine oxide 4c (83.3 mg, 0.26 mmol, 1.3 equiv) afforded 8h (99.3 mg, 97%) as a yellow solid, mp 68.7−70.0 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D +14.4 (c 0.42, MeOH); 1H NMR (400 MHz, C6D6): δ 8.15−8.10 (m, 2H), 8.07−8.01 (m, 2H), 7.28 (d, J = 8.0 Hz, 1H), 7.09 (t, J = 8.0 Hz, 1H), 7.05−7.03 (m, 3H), 7.0−6.96 (m, 3H), 6.72 (d, J = 7.2 Hz, 1H), 5.54 (q, J = 6.8 Hz, 1H), 3.26 (s, 3H), 2.14 (s, 3H), 1.52 (d, J = 7.2 Hz, 2H), 1.01 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 173.4, 151.5 (d, JC−P = 4.2 Hz), 138.4, 133.4 (d, JC−P = 127 Hz), 133.1 (d, JC−P = 9.0 Hz), 132.9 (d, JC−P = 8.7 Hz), 132.8 (d, JC−P = 131 Hz), 131.7 (d, JC−P = 2.4 Hz), 131.4 (d, JC−P = 2.5 Hz), 128.8, 128.5, 128.2, 124.4, 122.2, 118.2, 62.8, 56.7, 53.9, 22.1, 21.6, 17.6; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C27H34N3NaO3PS, 534.1951; found, 534.1953. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1(o-tolyl)hydrazinyl)propanimidate (8i). According to the general procedure A, reaction using imidate 1a (38.3 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and diphenyl(o-tolyldiazenyl)phosphine oxide 4d (83.3 mg, 0.26 mmol, 1.3 equiv) afforded 8i (37.9 mg, 37%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D +41.7 (c 0.29, MeOH); 1H NMR (400 MHz, C6D6): δ 8.17−8.12 (m, 2H), 7.86− 7.81 (m, 2H), 7.77 (d, J = 8.0 Hz, 1H), 7.46−7.36 (m, 1H), 7.06− 7.04 (m, 3H), 6.97−6.93 (m, 2H), 6.89−6.84 (m, 3H), 5.21 (q, J = 6.4 Hz, 1H), 3.58 (s, 3H), 1.71 (s, 3H), 1.36 (d, J = 6.8 Hz, 2H), 0.91 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 172.3, 150.8 (d, JC−P = 3.3 Hz), 135.9, 133.9 (d, JC−P = 125 Hz), 133.4 (d, JC−P = 9.0 Hz), 133.1 (d, JC−P = 134 Hz), 132.8 (d, JC−P = 8.0 Hz), 131.6, 131.1, 130.6, 128.6, 128.5 (d, JC−P = 12 Hz), 127.0, 125.9, 123.7, 63.3, 56.8, 54.3, 22.0, 17.1, 16.5; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C27H35N3O3PS, 512.2131; found, 512.2135. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1(4-methoxyphenyl)hydrazinyl)propanimidate (8j). According to the general procedure A, reaction using imidate 1a (38.3 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and ((4-methoxyphenyl)diazenyl)diphenylphosphine oxide 4e (87.4 mg, 0.26 mmol, 1.3 equiv) afforded 8j (95.0 mg, 90%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D +11.9 (c 0.14, MeOH); 1H NMR (400 MHz, C6D6): δ 8.17−8.11 (m, 2H), 8.03−7.98 (m, 2H), 7.50 (d, JP−H = 24 Hz, 1H), 7.23−7.20 (m, 2H), 7.07−7.04 (m, 3H), 7.0−6.96 (m, 3H), 6.71−6.67 (m, 2H), 5.34 (q, J = 6.8 Hz, 1H), 3.51 (s, 3H), 3.28 (s, 3H), 1.33 (d, J = 6.8 Hz, 3H), 1.03 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 173.4, 157.4, 144.9 (d, JC−P = 5.3 Hz), 133.7 (d, JC−P = 127 Hz), 133.3 (d, JC−P = 9.3 Hz), 133.1 (d, JC−P = 132 Hz), 133.0 (d, JC−P = 8.5 Hz), 131.5 (d, JC−P = 2.4 Hz), 131.2 (d, JC−P = 1.5 Hz), 128.4, 128.2, 125.2, 114.1, 64.5, 56.7, 54.9, 54.3, 22.1, 17.8; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C27H35N3O4PS, 528.2080; found, 528.2083. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1(4-fluorophenyl)hydrazinyl)propanimidate (8k). According to the general procedure A, reaction using imidate 1a (38.3 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and ((4-fluorophenyl)diazenyl)diphenylphosphine oxide 4f (84.3 mg, 0.26 mmol, 1.3 equiv) afforded 8k (90.7 mg, 88%) as a colorless oil.; G

DOI: 10.1021/acs.joc.9b00877 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry Rf = 0.4 (petroleum ether/ethyl acetate = 1:2); [α]20 D −6.9 (c 0.76, MeOH); 1H NMR (400 MHz, C6D6): δ 8.11−8.06 (m, 2H), 8.03− 7.98 (m, 2H), 7.13−7.11 (m, 6H), 5.64 (d, JP−H = 26.0 Hz, 1H), 5.17 (q, J = 7.2 Hz, 1H), 3.07 (s, 3H), 1.62 (d, J = 7.2 Hz, 3H), 1.12 (s, 9H), 1.07 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 178.6, 133.5 (d, JC−P = 131 Hz), 133.2 (d, JC−P = 8.5 Hz), 133.1 (d, JC−P = 8.8 Hz), 132.5 (d, JC−P = 120 Hz), 131.7 (d, JC−P = 2.0 Hz), 131.5 (d, JC−P = 2.7 Hz), 128.4, 128.1, 60.7 (d, JC−P = 4.0 Hz), 56.2, 54.1, 53.0, 27.5, 22.1, 19.4; HRMS (ESI-TOF) m/z: [M + H] + calcd for C24H37N3O3PS, 478.2288; found, 478.2291. Methyl (S)-2-(1-(tert-Butyl)-2-(diphenylphosphoryl)hydrazinyl)N-((R)-tert-butylsulfinyl)pentanimidate (8p). According to the general procedure A, reaction using imidate 1b (43.9 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and (tert-butyldiazenyl)diphenylphosphine oxide 4j (74.4 mg, 0.26 mmol, 1.3 equiv) afforded 8p (93.7 mg, 92%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:2); [α]20 D +8.4 (c 0.90, MeOH); 1H NMR (400 MHz, C6D6): δ 8.14−8.04 (m, 4H), 7.14− 7.09 (m, 6H), 5.82 (s, 1H), 5.12 (dd, J = 8.4, 5.2 Hz, 1H), 3.10 (s, 3H), 2.47 (s, 1H), 1.77 (s, 2H), 1.59−1.53 (m, 1H), 1.19 (s, 9H), 1.08 (s, 9H), 1.04 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, C6D6): δ 178.2, 134.8, 133.5, 133.0 (d, JC−P = 8.4 Hz), 132.9 (d, JC−P = 8.8 Hz), 131.6 (d, JC−P = 1.8 Hz), 131.4 (d, JC−P = 2.5 Hz), 128.5 (d, JC−P = 12 Hz), 128.2, 60.6 (d, JC−P = 4.1 Hz), 58.2, 56.5, 53.0, 35.3, 27.2, 22.2, 20.6, 14.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C26H41N3O3PS, 506.2601; found, 506.2598. Methyl (S)-2-(1-(tert-Butyl)-2-(diphenylphosphoryl)hydrazinyl)N-((R)-tert-butylsulfinyl)-3-phenylpropanimidate (8q). According to the general procedure A, reaction using imidate 1c (53.5 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and (tert-butyldiazenyl)diphenylphosphine oxide 4j (74.4 mg, 0.26 mmol, 1.3 equiv) afforded 8q (57.7 mg, 52%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:2); [α]20 D +26.8 (c 0.48, MeOH); 1H NMR (400 MHz, C6D6): δ 8.20 (s, 3H), 7.91 (s, 2H), 7.65 (d, J = 6.8 Hz, 2H), 7.14−7.12 (m, 4H), 7.08 (s, 4H), 5.91 (br, 1H), 5.65 (br, 1H), 4.04 (dd, J = 13, 6.0 Hz, 1H), 3.56 (s, 1H), 3.12 (s, 3H), 1.11 (s, 9H), 0.93 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 176.2, 138.7, 134.5, 134.3, 133.4 (d, JC−P = 8.6 Hz), 132.9 (d, JC−P = 8.7 Hz), 131.4, 130.6, 128.6, 128.5, 128.0, 126.7, 61.1, 59.5, 56.0, 53.1, 40.2, 27.5, 22.0; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H41N3O3PS, 554.2601; found, 554.2606. Methyl (S)-2-(1-(tert-Butyl)-2-(diphenylphosphoryl)hydrazinyl)N-((R)-tert-butylsulfinyl)pent-4-enimidate (8r). According to the general procedure A, reaction using imidate 1d (43.5 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and (tert-butyldiazenyl)diphenylphosphine oxide 4j (74.4 mg, 0.26 mmol, 1.3 equiv) afforded 8r (91.7 mg, 91%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D −4.8 (c 0.65, MeOH); 1H NMR (400 MHz, C6D6): δ 8.18−8.13 (m, 2H), 8.05 (s, 2H), 7.13−7.09 (m, 6H), 6.14 (s, 1H), 5.86 (s, 1H), 5.33−5.26 (m, 2H), 5.09 (d, J = 9.6 Hz, 1H), 3.32−3.26 (m, 1H), 3.09 (s, 3H), 3.01−2.94 (m, 1H), 1.14 (s, 9H), 1.07 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 176.3, 135.7, 134.4, 134.2, 133.2 (d, JC−P = 8.5 Hz), 133.0 (d, JC−P = 8.9 Hz), 131.7, 131.4 (d, JC−P = 2.3 Hz), 128.5, 128.2, 117.8, 60.8 (d, JC−P = 4.4 Hz), 58.7, 56.6, 53.0, 38.7, 27.6, 22.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C26H39N3O3PS, 504.2444; found, 504.2449. Methyl (S)-2-(1-(tert-Butyl)-2-(diphenylphosphoryl)hydrazinyl)N-((R)-tert-butylsulfinyl)-4-phenylbutanimidate (8s). According to the general procedure A, reaction using imidate 1g (56.5 mg, 0.20 mmol, 1.0 equiv), LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv), and (tert-butyldiazenyl)diphenylphosphine oxide 4j (74.4 mg, 0.26 mmol, 1.3 equiv) afforded 8s (89.7 mg, 79%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D +9.4 (c 0.16, MeOH); 1H NMR (400 MHz, C6D6): δ 8.17−8.12 (m, 2H), 8.05 (s, 2H), 7.62 (s, 2H), 7.22 (t, J = 7.2 Hz, 2H), 7.11−7.08 (m, 4H), 7.07−7.06 (m, 3H), 5.96 (s, 1H), 5.21 (dd, J = 9.2, 4.0 Hz, 1H), 3.55 (s, 1H), 3.21 (s, 1H), 3.04 (s, 3H), 2.9−2.83 (m, 1H), 2.04 (s, 1H), 1.14 (s, 9H), 1.05 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 178.2, 142.8, 134.1 (d, JC−P = 131 Hz), 134.0 (d, JC−P = 125 Hz), 133.0 (d,

JC−P = 9.1 Hz), 132.9 (d, JC−P = 8.0 Hz), 131.7 (d, JC−P = 1.1 Hz), 131.3 (d, JC−P = 2.5 Hz), 129.5, 128.7, 128.6, 128.3, 126.1, 60.7 (d, JC−P = 4.7 Hz), 58.4, 56.2, 53.1, 34.9, 34.4, 27.2, 22.1; HRMS (ESITOF) m/z: [M + Na]+ calcd for C31H42N3NaO3PS, 590.2577; found, 590.2573. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)-2-phenylacetimidate (8t). According to the general procedure B, reaction using imidate 1h (50.5 mg, 0.20 mmol, 1.0 equiv), diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv), and t-BuOK (1.0 M in THF, 40.0 μL, 0.040 mmol, 0.20 equiv) afforded 8t (71.7 mg, 64%) as a colorless solid, mp 81.7−83.7 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1 1:1); [α]20 D −93.8 (c 0.32, MeOH); H NMR (400 MHz, C6D6): δ 7.98−7.92 (m, 2H), 7.90−7.85 (m, 2H), 7.56−7.53 (m, 2H), 7.37− 7.34 (m, 2H), 7.12−6.94 (m, 12H), 6.81 (t, J = 7.2 Hz, 1H), 6.71 (s, 1H), 3.48 (s, 3H), 1.02 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 171.3, 152.4 (d, JC−P = 3.1 Hz), 136.0, 133.5 (d, JC−P = 9.2 Hz), 133.0 (d, JC−P = 131 Hz), 132.9 (d, JC−P = 123 Hz), 132.9 (d, JC−P = 9.0 Hz), 131.5 (d, JC−P = 2.8 Hz), 131.4 (d, JC−P = 2.8 Hz), 130.8, 128.8, 128.6, 128.4 (d, JC−P = 13 Hz), 128.2 (d, JC−P = 13 Hz), 128.2, 124.3, 122.8, 73.1 (d, JC−P = 3.3 Hz), 56.9, 54.7, 22.0; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H35N3O3PS, 560.2131; found, 560.2136. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)-2-(o-tolyl)acetimidate (8u). According to the general procedure B, reaction using imidate 1i (53.5 mg, 0.20 mmol, 1.0 equiv), diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv), and t-BuOK (1.0 M in THF, 80.0 μL, 0.080 mmol, 0.40 equiv) afforded 8u (101.0 mg, 88%) as a colorless solid, mp 182.3−183.7 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 1 1:1); [α]20 D −107.4 (c 0.24, MeOH); H NMR (400 MHz, C6D6): δ 8.07−8.02 (m, 2H), 7.85 (d, J = 7.2 Hz, 2H), 7.58 (d, J = 7.2 Hz, 1H), 7.51 (dd, J = 12, 8.0 Hz, 2H), 7.25−7.22 (m, 3H), 7.09−7.03 (m, 4H), 6.96−6.92 (m, 1H), 6.87−6.79 (m, 4H), 6.28 (d, JP−H = 22 Hz, 1H), 3.13 (s, 3H), 2.09 (s, 3H), 0.94 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 171.5, 152.4, 140.3, 133.6 (d, JC−P = 8.8 Hz), 133.1 (d, JC−P = 118 Hz), 133.0 (d, JC−P = 128 Hz), 132.7 (d, JC−P = 9.3 Hz), 131.9 (d, JC−P = 2.5 Hz), 131.4, 131.2, 131.1 (d, JC−P = 2.7 Hz), 129.1, 128.8, 128.6, 128.5, 128.1, 125.5, 123.0, 119.9, 66.5, 56.9, 53.7, 22.0, 19.1; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H37N3O3PS, 574.2288; found, 574.2289. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)-2-(m-tolyl)acetimidate (8v). According to the general procedure B, reaction using imidate 1j (53.5 mg, 0.20 mmol, 1.0 equiv), diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv), and t-BuOK (1.0 M in THF, 80.0 μL, 0.080 mmol, 0.40 equiv) afforded 8v (72.2 mg, 63%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D −77.6 (c 0.26, MeOH); 1H NMR (400 MHz, C6D6): δ 8.0−7.95 (m, 2H), 7.86− 7.81 (m, 2H), 7.65−7.63 (m, 2H), 7.29 (d, J = 7.6 Hz, 1H), 7.13− 7.08 (m, 2H), 7.06−6.92 (m, 8H), 6.86−6.80 (m, 2H), 6.77 (s, 1H), 3.43 (s, 3H), 1.97 (s, 3H), 1.02 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 171.5, 152.4 (d, JC−P = 2.6 Hz), 137.9, 135.8, 133.5 (d, JC−P = 9.2 Hz), 133.0 (d, JC−P = 130 Hz), 132.8 (d, JC−P = 9.0 Hz), 132.8 (d, JC−P = 129 Hz), 131.6, 131.5 (d, JC−P = 2.7 Hz), 131.3 (d, JC−P = 2.4 Hz), 129.4, 128.8, 128.6, 128.2, 128.1, 124.0, 122.2, 72.6 (d, JC−P = 3.3 Hz), 56.9, 54.5, 22.1, 21.4; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H37N3O3PS, 574.2288; found, 574.2286. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)-2-(p-tolyl)acetimidate (8w). According to the general procedure B, reaction using imidate 1k (53.5 mg, 0.20 mmol, 1.0 equiv), diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv), and t-BuOK (1.0 M in THF, 80.0 μL, 0.080 mmol, 0.40 equiv) afforded 8w (81.2 mg, 71%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D −83.8 (c 0.32, MeOH); 1H NMR (400 MHz, C6D6): δ 7.98−7.87 (m, 4H), 7.56 (d, J = 7.6 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.10−6.97 (m, 9H), 6.83− 6.79 (m, 3H), 6.70 (s, 1H), 3.51 (s, 3H), 1.98 (s, 3H), 1.03 (s, 9H); 13 C{1H} NMR (100 MHz, C6D6): δ 171.6, 152.5 (d, JC−P = 2.7 Hz), 138.1, 133.5 (d, JC−P = 9.1 Hz), 133.1 (d, JC−P = 131 Hz), 133.0 (d, JC−P = 128 Hz), 132.9, 132.9 (d, JC−P = 8.9 Hz), 131.4 (d, JC−P = 2.2 H

DOI: 10.1021/acs.joc.9b00877 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry

128 Hz), 133.0 (d, JC−P = 8.8 Hz), 131.4 (d, JC−P = 2.4 Hz), 131.3 (d, JC−P = 2.5 Hz), 130.1, 128.7, 128.6, 128.2, 127.6, 126.3, 124.9, 123.6, 68.5 (d, JC−P = 2.6 Hz), 57.2, 54.9, 22.1; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C29H33N3O3PS2, 566.1695; found, 566.1697. General Procedure for the Preparation of Products 6 and 7. To a solution of imidate (0.20 mmol, 1.0 equiv) and diazene (0.26 mmol, 1.3 equiv) in 4.0 mL of solvent was added base (0.24 mmol, 1.2 equiv) at −78 °C. The resulting mixture was maintained at −78 °C for 1 h and quenched with saturated solution of NH4Cl. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash column chromatography on silica gel. Methyl (S,E)-2-(2-Benzoyl-1-phenylhydrazinyl)-N-((R)-tertbutylsulfinyl)propanimidate (6a). According to the general procedure, reaction of 1a (38.3 mg, 0.20 mmol, 1.0 equiv) and 2 (54.7 mg, 0.26 mmol, 1.3 equiv) in 4.0 mL of THF using KHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv) as base afforded 6a (65.9 mg, 82%; Table 1, entry 18) as a white solid; mp 149−151 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 3:1); [α]20 D +37.7 (c 0.17, MeOH); 1 H NMR (400 MHz, C6D6): δ 10.39 (s, 1H), 8.15−8.13 (m, 2H), 7.21−7.17 (m, 2H), 7.09−7.0 (m, 5H), 6.79 (t, J = 7.2 Hz, 1H), 4.98 (q, J = 7.2 Hz, 1H), 3.18 (s, 3H), 1.66 (d, J = 8.8 Hz, 3H), 1.0 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 174.1, 166.6, 147.9, 133.2, 132.0, 129.7, 129.0, 119.8, 112.3, 60.0, 56.5, 54.1, 22.1, 17.0; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C21H27N3NaO3S, 424.1655; found, 424.1667. Methyl (S,E)-N-((R)-tert-Butylsulfinyl)-2-(1-phenyl-2tosylhydrazinyl)propanimidate (7a). According to the general procedure, reaction of 1a (38.3 mg, 0.20 mmol, 1.0 equiv) and 3 (67.7 mg, 0.26 mmol, 1.3 equiv) in 4.0 mL of THF using NaHMDS (2.0 M in THF, 0.12 mL, 0.24 mmol, 1.2 equiv) as base afforded 7a (84.9 mg, 94%; Table 1, entry 17) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 3:1); [α]20 D +32.2 (c 0.27, MeOH); 1 H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 7.05 (t, J = 8.4 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 6.81 (t, J = 7.2 Hz, 1H), 5.55 (s, 1H), 3.51 (s, 3H), 2.34 (s, 3H), 1.39 (d, J = 7.2 Hz, 3H), 1.11 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 172.7, 148.0, 143.8, 136.4, 129.4, 128.8, 128.2, 122.2, 117.0, 58.6, 57.2, 54.1, 22.2, 21.6, 16.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H30N3O4S2, 452.1672; found, 452.1679. Methyl (S,E)-2-(2-Benzoyl-1-phenylhydrazinyl)-N-((R)-tert-butylsulfinyl)-2-phenylacetimidate (6b). According to the general procedure, reaction of 1h (50.7 mg, 0.20 mmol, 1.0 equiv) and 2 (54.7 mg, 0.26 mmol, 1.3 equiv) in 4.0 mL of THF using LiHMDS (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv) as base afforded 6b (87.9 mg, 95%; Table 3, entry 9) as a mixture of diastereomers (∼10:1 dr); colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 3:1); 1H NMR (400 MHz, CDCl3): δ 8.78 (s, 1H), 7.57−7.56 (m, 2H), 7.49−7.47 (m, 2H), 7.45−7.39 (s, 1H), 7.34−7.29 (m, 4H), 7.28−7.24 (m, 3H), 6.94 (d, J = 8.0 Hz, 2H), 6.91−6.87 (m, 1H), 6.52 (s, 1H), 3.76 (s, 3H), 1.22 (s, 9H) [minor isomer: 7.13 (t, J = 7.6 Hz, 0.3H), 7.07−6.99 (m, 0.9H), 6.78 (s, 0.1H), 3.74 (s, 0.3H), 1.13 (s, 1H)]; 13C{1H} NMR (100 MHz, CDCl3): δ 171.3, 166.6, 147.4, 133.2, 133.0, 131.7, 131.1, 130.3, 129.4, 128.9, 128.6, 127.1, 120.6, 113.4, 67.3, 57.0, 55.0 (d, J = 5.5 Hz), 22.1 (minor isomer: 173.4, 170.9, 148.6, 132.3, 131.9, 130.8, 129.9, 128.7, 128.0, 127.3, 121.7, 114.7, 64.4, 57.3, 21.1); HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C26H29N3NaO3S, 486.1822; found, 486.1821. Methyl (S,E)-N-((R)-tert-Butylsulfinyl)-2-phenyl-2-(1-phenyl-2tosylhydrazinyl)acetimidate (7b). According to the general procedure, reaction of 1h (50.7 mg, 0.20 mmol, 1.0 equiv) and 3 (67.7 mg, 0.26 mmol, 1.3 equiv) in 4.0 mL of Et2O using t-BuOK (1.0 M in THF, 0.24 mL, 0.24 mmol, 1.2 equiv) as base afforded 7b (87.3 mg, 85%; Table 3, entry 9) as a brown oil; Rf = 0.4 (petroleum ether/ethyl 1 acetate = 3:1); [α]20 D −11.8 (c 0.33, MeOH); H NMR (400 MHz, CDCl3): δ 7.37 (d, J = 8.4 Hz, 2H), 7.27−7.25 (m, 2H), 7.21−7.12 (m, 8H), 6.96 (d, J = 8.0 Hz, 2H), 6.94−6.90 (m, 1H), 6.60 (s, 1H), 3.63 (s, 3H), 2.32 (s, 3H), 1.07 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3): δ 170.3, 149.0, 143.1, 136.0, 133.5, 130.6, 129.3, 129.0, 128.6, 128.4, 127.8, 122.8, 118.0, 68.1, 57.2, 54.4 (d, J = 5.6 Hz), 22.1,

Hz), 131.1 (d, JC−P = 2.3 Hz), 130.8, 129.1, 128.8, 128.6, 128.2, 124.3, 122.8, 72.8 (d, JC−P = 2.7 Hz), 56.9, 54.6, 22.1, 21.1; HRMS (ESITOF) m/z: [M + H]+ calcd for C32H37N3O3PS, 574.2288; found, 574.2293. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)-2-(4-methoxyphenyl)acetimidate (8x). According to the general procedure B, reaction using imidate 1l (56.5 mg, 0.20 mmol, 1.0 equiv), diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv), and t-BuOK (1.0 M in THF, 80.0 μL, 0.080 mmol, 0.40 equiv) afforded 8x (86.2 mg, 73%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D −77.8 (c 0.24, MeOH); 1H NMR (400 MHz, C6D6): δ 8.01−7.96 (m, 2H), 7.94−7.89 (m, 2H), 7.56 (d, J = 7.6 Hz, 2H), 7.31 (d, J = 8.8 Hz, 2H), 7.10−6.96 (m, 9H), 6.82 (t, J = 7.2 Hz, 1H), 6.66 (s, 1H), 6.59 (d, J = 8.8 Hz, 2H), 3.54 (s, 3H), 3.19 (s, 3H), 1.05 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 171.7, 160.2, 152.5 (d, JC−P = 3.0 Hz), 133.5 (d, JC−P = 9.1 Hz), 133.1 (d, JC−P = 131 Hz), 133.0 (d, JC−P = 128 Hz), 132.9 (d, JC−P = 8.9 Hz), 132.2, 131.4 (d, JC−P = 3.0 Hz), 131.4 (d, JC−P = 2.9 Hz), 128.8, 128.6, 128.2, 128.1, 124.3, 122.9, 113.9, 72.5 (d, JC−P = 3.0 Hz), 56.9, 54.7, 54.7, 22.1; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H37N3O4PS, 590.2237; found, 590.2239. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)-2-(4-fluorophenyl)acetimidate (8y). According to the general procedure B, reaction using imidate 1m (54.5 mg, 0.20 mmol, 1.0 equiv), diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv), and t-BuOK (1.0 M in THF, 40.0 μL, 0.040 mmol, 0.20 equiv) afforded 8y (84.2 mg, 73%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D −66.1 (c 0.23, MeOH); 1H NMR (400 MHz, C6D6): δ 7.95−7.85 (m, 4H), 7.47−7.44 (m, 2H), 7.24 (d, JP−H = 25 Hz, 1H), 7.19 (d, J = 3.2 Hz, 1H), 7.07−6.96 (m, 8H), 6.82 (t, J = 7.6 Hz, 1H), 6.62 (t, J = 8.8 Hz, 2H), 6.57 (s, 1H), 3.53 (s, 3H), 1.03 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 170.8, 163.1 (d, JC−F = 246 Hz), 152.2 (d, JC−P = 3.3 Hz), 133.4 (d, JC−P = 9.2 Hz), 133.0 (d, JC−P = 127 Hz), 132.9 (d, JC−P = 131 Hz), 132.8 (d, JC−P = 8.8 Hz), 132.6 (d, JC−P = 8.1 Hz), 131.8 (d, JC−P = 3.1 Hz), 131.5 (d, JC−P = 2.3 Hz), 128.8, 128.6, 128.2, 128.1, 124.6, 123.0, 115.2 (d, JC−F = 21 Hz), 72.4 (d, JC−P = 2.0 Hz), 57.1, 54.8, 22.0; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H34FN3O3PS, 578.2037; found, 578.2039. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(4-chlorophenyl)-2-(2-(diphenylphosphoryl)-1-phenylhydrazinyl)acetimidate (8z). According to the general procedure B, reaction using imidate 1n (57.5 mg, 0.20 mmol, 1.0 equiv), diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv), and t-BuOK (1.0 M in THF, 40.0 μL, 0.040 mmol, 0.20 equiv) afforded 8z (69.2 mg, 58%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D −78.2 (c 0.29, MeOH); 1H NMR (400 MHz, C6D6): δ 7.95−7.85 (m, 4H), 7.46 (d, J = 7.6 Hz, 2H), 7.23 (d, JP−H = 24 Hz, 1H), 7.14− 7.12 (m, 2H), 7.06−6.91 (m, 10H), 6.82 (t, J = 7.2 Hz, 1H), 6.56 (s, 1H), 3.51 (s, 3H), 1.02 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 170.5, 152.1 (d, JC−P = 3.2 Hz), 134.6 (d, JC−P = 4.5 Hz), 133.3 (d, JC−P = 9.1 Hz), 132.9 (d, JC−P = 127 Hz), 132.8 (d, JC−P = 131 Hz), 132.7 (d, JC−P = 8.9 Hz), 132.1, 131.5, 128.9, 128.5, 128.2, 128.1, 124.7, 122.9, 72.6 (d, JC−P = 2.7, Hz), 57.1, 54.8, 22.0; HRMS (ESITOF) m/z: [M + H]+ calcd for C31H34ClN3O3PS, 594.1742; found, 594.1746. Methyl (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1phenylhydrazinyl)-2-(thiophen-2-yl)acetimidate (8aa). According to the general procedure B, reaction using imidate 1o (51.9 mg, 0.20 mmol, 1.0 equiv), diphenyl(phenyldiazenyl)phosphine oxide 4a (79.6 mg, 0.26 mmol, 1.3 equiv), and t-BuOK (1.0 M in THF, 0.12 mL, 0.12 mmol, 1.20 equiv) afforded 8aa (61.2 mg, 54%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 1:1); [α]20 D −73.8 (c 0.28, MeOH); 1H NMR (400 MHz, C6D6): δ 8.04−7.95 (m, 4H), 7.42− 7.39 (m, 2H), 7.04−6.97 (m, 8H), 6.93 (s, 1H), 6.83 (t, J = 7.2 Hz, 1H), 6.78 (dd, J = 5.2, 1.2 Hz, 1H), 6.74 (dd, J = 3.6, 0.8 Hz, 1H), 6.45 (dd, J = 5.2, 3.6 Hz, 1H), 3.67 (s, 3H), 1.04 (s, 9H); 13C{1H} NMR (100 MHz, C6D6): δ 169.4, 151.9 (d, JC−P = 3.9 Hz), 137.3, 133.3 (d, JC−P = 9.2 Hz), 133.1 (d, JC−P = 131 Hz), 133.0 (d, JC−P = I

DOI: 10.1021/acs.joc.9b00877 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry 21.6 (d, J = 3.0 Hz); HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C26H31N3NaO4S2, 536.1648; found, 536.1645. General Procedure for the Preparation of Products 9o and 9p. To a stirred solution of N-tert-butanesulfinyl imidate (0.30 mmol, 1.0 equiv) in 2.0 mL THF was added NaHMDS (2.0 M in THF, 180 μL, 0.36 mmol, 1.2 equiv) at −78 °C. After the reaction mixture was stirred at −78 °C for 15 min, a solution of nitrosobenzene (41.7 mg, 0.39 mmol, 1.3 equiv) in 1.0 mL THF was added dropwise. After stirring for 30 min at −78 °C, the reaction was quenched with saturated aqueous ammonium chloride. The solution was warmed to room temperature and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under vacuum. The residue was rapidly purified by flash column chromatography on silica gel. The hydroxyamination product was not stable enough for storage at rt and was immediately treated with Zn dust (100 mg) and AcOH (1.1 mL) in 5 mL of DCM at 0 °C. After vigorous stirring at 30 °C until complete consumption of starting material, the reaction mixture was quenched with saturated aqueous solution of ammonium chloride and extracted with dichloromethane. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The crude residue was purified by flash column chromatography to afford N−O cleavage product. Methyl (S,E)-N-((R)-tert-Butylsulfinyl)-3-methyl-2(phenylamino)butanimidate (9o). According to the general procedure, reaction using imidate 1p (65.8 mg, 0.30 mmol, 1.0 equiv), NaHMDS (2.0 M in THF, 0.18 mL, 0.36 mmol, 1.2 equiv), and nitrosobenzene 5a (41.8 mg, 0.39 mmol, 1.3 equiv) was followed by cleavage of N−O bond. Column chromatography afforded 9o (66.1 mg, 71%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl 1 acetate = 3:1); [α]20 D −112.6 (c 0.34, MeOH); H NMR (400 MHz, CDCl3): δ 7.19−7.14 (m, 2H), 6.72−6.69 (m, 3H), 4.59 (d, J = 6.4 Hz, 1H), 4.30 (t, J = 7.6 Hz, 1H), 3.68 (s, 3H), 2.27−2.15 (m, 1H), 1.20 (s, 9H), 1.09 (d, J = 6.4 Hz, 3H), 1.03 (d, J = 6.8 Hz, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 173.2, 147.2, 129.4, 118.0, 113.3, 62.1, 57.0, 54.0, 33.7, 22.4, 20.1, 19.7; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C16H26N2NaO2S 333.1607; found, 333.1612. Methyl (S,E)-N-((R)-tert-Butylsulfinyl)-2-cyclohexyl-2(phenylamino)acetimidate (9p). According to the general procedure, reaction using imidate 1q (77.8 mg, 0.30 mmol, 1.0 equiv), NaHMDS (2.0 M in THF, 0.18 mL, 0.36 mmol, 1.2 equiv), and nitrosobenzene 5a (41.8 mg, 0.39 mmol, 1.3 equiv) was followed by cleavage of N−O bond. Column chromatography afforded 9p (64.1 mg, 61%) as a colorless oil; Rf = 0.4 (petroleum ether/ethyl acetate = 3:1); [α]20 D −107.0 (c 0.16, MeOH); 1H NMR (400 MHz, CDCl3): δ 7.16 (t, J = 7.2 Hz, 2H), 6.71−6.68 (m, 3H), 4.54 (d, J = 8.8 Hz, 1H), 4.41 (t, J = 8.8 Hz, 1H), 3.67 (s, 3H), 2.08 (d, J = 12.8 Hz, 1H), 1.93−1.85 (m, 1H), 1.76−1.60 (m, 4H), 1.31−1.17 (m, 14H), 1.09−0.98 (m, 1H); 13 C{1H} NMR (100 MHz, CDCl3): δ 172.8, 147.2, 129.3, 117.9, 113.3, 61.1, 56.9, 54.0, 42.9, 30.6, 29.9, 26.4, 26.1, 25.9, 22.4; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C19H30N2NaO2S, 373.1920; found, 373.1918. Procedure for Hydrolysis of 8g. To a stirred solution of 8g (51.2 mg, 0.10 mmol, 1.0 equiv) in 3.0 mL of MeOH was added 4.0 M aq H2SO4 (1.0 mL) at 0 °C. The reaction mixture was stirred vigorously at rt. After complete consumption of the starting material, the reaction mixture was treated with saturated aqueous NaHCO3 and extracted with ethyl acetate three times. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel. (S)-N-((R)-tert-Butylsulfinyl)-2-(2-(diphenylphosphoryl)-1-(ptolyl)hydrazinyl)propanamide (10). Colorless oil (44.8 mg, 90%), Rf = 0.4 (petroleum ether/ethyl acetate = 1:5); [α]20 D −2.0 (c 0.20, MeOH); 1H NMR (400 MHz, C6D6): δ 11.12 (s, 1H), 8.05−8.0 (m, 2H), 7.94−7.89 (m, 2H), 7.22−7.19 (m, 5H), 6.97−6.92 (m, 5H), 4.56−4.53 (m, 1H), 2.05 (s, 3H), 1.37−1.34 (m, 3H), 1.12 (s, 9H); 13 C{1H} NMR (100 MHz, C6D6): δ 175.5, 147.1 (d, JC−P = 2.6 Hz), 132.8 (d, JC−P = 10 Hz), 132.5 (d, JC−P = 1.9 Hz), 132.4 (d, JC−P = 9.6 Hz), 132.0 (d, JC−P = 125 Hz), 131.9 (d, JC−P = 1.8 Hz), 131.6 (d,

JC−P = 121 Hz), 131.6, 129.7, 129.0 (d, JC−P = 12 Hz), 128.5 (d, JC−P = 13 Hz), 119.1, 68.9, 56.1, 22.5, 20.6, 12.5; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C26H33N3O3PS, 498.1975; found, 498.1972. Procedure for Reduction of 8j. To a solution of compound 8j (105.5 mg, 0.20 mmol, 1.0 equiv) in THF (3.0 mL) was slowly added a solution of Red-Al (0.10 mL, 0.50 mmol, 2.5 equiv) at −78 °C. The mixture was stirred at −78 °C for 1 h and then was gradually warmed to −15 °C. The reaction was quenched with addition of a saturated sodium potassium tartrate solution, and the resulting mixture was diluted with water and ethyl acetate. The organic layer was collected and the aqueous layer was extracted with ethyl acetate. The combined organic portions were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash column chromatography on silica gel. (R)-N-((S)-2-(2-(Diphenylphosphoryl)-1-(4-methoxyphenyl)hydrazinyl)propyl)-2-methylpropane-2-sulfinamide (11). White solid (88.9 mg, 89%), mp 177.0−179.0 °C; Rf = 0.4 (petroleum 1 ether/ethyl acetate = 1:5); [α]20 D −30.0 (c 0.47, MeOH); H NMR (400 MHz, CDCl3): δ 7.92−7.88 (m, 2H), 7.70−7.66 (m, 2H), 7.55−7.51 (m, 1H), 7.47−7.43 (m, 2H), 7.34−7.30 (m, 1H), 7.22− 7.17 (m, 2H), 7.13 (d, J = 8.8 Hz, 2H), 6.76−6.72 (m, 2H), 5.17 (dd, J = 10, 2.4 Hz, 1H), 5.02 (d, JP−H = 28 Hz, 1H), 3.81−3.66 (m, 5H), 3.15−3.08 (m, 1H), 1.19 (s, 9H), 0.84 (d, J = 6.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 155.5, 145.3 (d, JC−P = 4.4 Hz), 132.5 (d, JC−P = 9.9 Hz), 132.4 (d, JC−P = 2.6 Hz), 132.2 (d, JC−P = 9.1 Hz), 131.8 (d, JC−P = 2.6 Hz), 131.0 (d, JC−P = 125 Hz), 129.9 (d, JC−P = 134 Hz), 128.8 (d, JC−P = 12 Hz), 128.1 (d, J = 13 Hz), 121.8, 113.9, 65.2, 55.9, 55.5, 50.0, 22.9, 10.6; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C26H35N3O3PS, 500.2131; found, 500.2134. Procedure for N−N Bond Cleavage of 11 Using Li/NH3. To a mixture of liquid ammonia (4.0 mL) and lithium (2.0 mmol) was added THF solution of 11 (100 mg 0.20 mmol) at −78 °C. The mixture was stirred at −78 °C for 1 h. After quenching with saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate three times. The combined organic layers were washed with brine and dried over anhydrous Na2SO4, filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel. (R)-N-((S)-2-((4-Methoxyphenyl)amino)propyl)-2-methylpropane-2-sulfinamide (12). Colorless oil (56.8 mg, ∼100%), Rf = 0.4 (petroleum ether/ethyl acetate = 1:4); [α]20 D −78.9 (c 0.25, MeOH); 1 H NMR (400 MHz, C6D6): δ 6.84−6.80 (m, 2H), 6.71−6.67 (m, 2H), 3.80−3.79 (m, 1H), 3.45−3.39 (m, 4H), 3.13−3.06 (m, 1H), 2.87−2.80 (m, 1H), 1.02 (s, 9H), 0.87 (d, J = 6.4 Hz, 3H); 13C{1H} NMR (100 MHz, C6D6): δ 153.1, 142.2, 116.0, 115.3, 55.5, 55.3, 51.2, 51.0, 22.7, 18.5; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C14H25N2O2S, 285.1631; found, 285.1633. Procedure for N−N Bond Cleavage of 11 Using CAN. A solution of 11 (100.0 mg 0.20 mmol) in CH3CN (2.5 mL) was cooled to 0 °C and a solution of ammonium cerium nitrate (CAN, 274.1 mg, 0.50 mmol, in 1.25 mL H2O) was directly added. The resulting solution was stirred under ambient temperature for 1 h and then treated with 2 N HCl to achieve an approximate PH = 1. The aqueous phase was extracted with ethyl acetate three times and the combined organic layers were washed with sol. NaHCO3 and brine sequentially, dried over anhydrous Na2SO4, filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel.

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.9b00877. 1

H and 13C NMR spectra of all new compounds and Xray crystal structures of compounds 8g (CCDC 1880621) and 8u (CCDC 1880622) (PDF) J

DOI: 10.1021/acs.joc.9b00877 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Chong-Dao Lu: 0000-0001-8968-0134 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (21572262 and 21871292).

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REFERENCES

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DOI: 10.1021/acs.joc.9b00877 J. Org. Chem. XXXX, XXX, XXX−XXX

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(24) See the Supporting Information for the single crystal structures of compounds 8g (CCDC 1880621) and 8u (CCDC 1880622). (25) (a) Bock, H.; Rudolph, G. Azo-Verbindungen, V: Substituenten-Effekte bei Azo-Phosphorsäure-Derivaten. Chem. Ber. 1965, 98, 2273−2283. (b) Bock, H.; Rudolph, G.; Baltin, E. Notiz zur Oxydation 1.2-disubstituierter Hydrazine mitN-Brom-succinimid. Chem. Ber. 1965, 98, 2054−2055.

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DOI: 10.1021/acs.joc.9b00877 J. Org. Chem. XXXX, XXX, XXX−XXX