Asymmetric Michael addition of diphenylphosphine to β,γ-unsaturated α-keto esters catalyzed by a P-stereogenic pincer-Pd complex

Tetrahedron 71 (2015) 6832e6839

Contents lists available at ScienceDirect

Tetrahedron journal homepage: www.elsevier.com/locate/tet

Asymmetric Michael addition of diphenylphosphine to b,g-unsaturated a-keto esters catalyzed by a P-stereogenic pincer-Pd complex Yang Xu a, Zehua Yang a, Boqiang Ding b, Delong Liu a, *, Yangang Liu a, Masashi Sugiya c, Tsuneo Imamoto c, d, *, Wanbin Zhang a, b, * a

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China Organic R&D Department, Nippon Chemical Industrial Co., Ltd., Kameido, Koto-ku, Tokyo 136-8515, Japan d Department of Chemistry, Graduate School of Science, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan b c

a r t i c l e i n f o

a b s t r a c t

Article history: Received 14 April 2015 Received in revised form 7 July 2015 Accepted 10 July 2015 Available online 16 July 2015

An asymmetric Michael addition of diphenylphosphine to b,g-unsaturated a-keto esters was developed using a P-stereogenic pincer-Pd complex as a catalyst. The corresponding hydrophosphination products were obtained in good yields (up to 94%) and with moderate to good enantioselectivities (up to 93% ee) under the optimum reaction conditions. Ó 2015 Elsevier Ltd. All rights reserved.

Keywords: Asymmetric Michael addition Diphenylphosphine b,g-Unsaturated a-keto ester P-Stereogenic pincer-Pd complex

1. Introduction Organophosphorus compounds not only play an important role in modern synthetic organic chemistry as valuable building blocks, but can also be used in many pharmaceuticals such as biophosphate mimics, antibiotics, antiviral agents and antitumor agents.1 Among these, chiral phosphines are particularly important due to their significant catalytic behavior in asymmetric reactions, serving as P,O- or P,N-ligands for metal catalysts2 and because of their biological properties.3 Over the past several decades, the catalytic synthesis of organophosphorus compounds has attracted much attention, while the asymmetric catalytic synthesis of chiral phosphines has emerged only recently. The search for efficient methods to synthesize various chiral organophosphorus compounds is therefore worthy of further investigation. The catalytic asymmetric construction of PeC bonds is considered to be one of the most powerful methods for the preparation of chiral organophosphorus compounds.4 Amongst these

* Corresponding authors. E-mail addresses: [email protected] (D. Liu), imamoto@ faculty.chiba-u.jp (T. Imamoto), [email protected] (W. Zhang). http://dx.doi.org/10.1016/j.tet.2015.07.026 0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

methodologies, the asymmetric Michael addition of diarylphosphines to conjugated compounds is one of the most important synthetic methods for the construction of chiral PeC bonded phosphines. Chiral pincer-Pd complexes have also been proven to be efficient catalysts in this type of catalytic reaction.5 For example, Duan and co-workers have developed a PCP pincer-Pd catalyzed asymmetric addition of diarylphosphines to electrondeficient alkenes6 and N-tosylimines,7 providing the corresponding products with high to excellent enantiomeric excesses. Song et al. also reported the efficient additions of diarylphosphines to enones catalyzed by PCN8 or NCN9 pincer-Pd(II) complexes. Additionally, Leung and co-workers have disclosed that chiral phosphapalladacycle complexes can catalyze the enantioselective addition of diarylphosphines to a number of electrophiles, to afford chiral organophosphorus compounds in excellent yields and enantiomeric excesses.10 We recently developed novel P-stereogenic pincer-Pd complexes and applied them to asymmetric Michael addition reactions of diarylphosphines to nitroalkenes, whereby nitrodiarylphosphine oxides containing a nitro group were produced in high yields and with good enantioselectivities.11 In order to explore the application scope of our P-stereogenic pincer-Pd complexes and develop novel organophosphorus compounds, we

Y. Xu et al. / Tetrahedron 71 (2015) 6832e6839

herein report their application to the asymmetric Michael addition of diphenylphosphine to b,g-unsaturated a-keto esters. 2. Results and discussion 2.1. Improved preparation of Cat. A In our previous work, the PCP type pincer-Pd complex (Cat. A) was obtained in two steps from phosphineeborane 1 in 63% yield by using TfOH as a deprotection reagent.11 However, the whole reaction and workup had to be carried out under strictly anaerobic conditions, because the produced P-chiral phosphine ligand 2 was readily oxidized in contact with air. Thus, our improved procedure uses 1,4-diaza[2.2.2]bicyclooctane (DABCO) as a deprotection reagent, and the two steps can be carried out via a ‘one-pot’ procedure to furnish Cat. A (66% overall yield, Scheme 1).

Scheme 1. Improved preparation of Cat. A.

2.2. Pincer-Pd catalyzed asymmetric Michael addition We first chose methyl (E)-2-oxo-4-phenylbut-3-enoate (3a) as a model substrate and attempted the asymmetric Michael addition (hydrophosphination) with diphenylphosphine (Ph2PH, 4) using Cat. B12 as a catalyst at room temperature in dichloromethane (DCM) (Table 1, entry 1). The reaction was quenched with 30% H2O2 after 6 h and purified by silica gel column

6833

chromatography. The resulting product was obtained in moderate yield but only 11% ee. Nevertheless, the result indicated that the P-stereogenic PCP pincer-Pd complex can induce enantioselectivity in this reaction. The solvent dichloroethane (DCE) also showed a similar result (entry 2). When the reaction was carried out in toluene, a similar yield but an obvious improvement in enantioselectivity was observed (entry 3). Several ether solvents were screened and DME proved to be the best solvent, giving the desired product in 74% yield and with 38% ee (entries 4e7). When the reaction was carried out in acetonitrile, the product was obtained in high yield but very low ee (entry 8). The use of alcohol solvents resulted in inferior catalytic performance (entries 9e10). Subsequently, the effects of temperature and the R1 group of 3 on the reaction were investigated (Table 2). When the above reactions were carried out at room temperature and at 0
C, similar yields and enantioselectivities were obtained with different reaction activities (entries 1 and 2). Decreasing the reaction temperature to 20
C resulted in the exclusive formation of unwanted 1,2-addition product (entry 3). This result may be attributed to the formation of the kinetic product being favored over the formation of the thermodynamic product at the lower temperature. In order to suppress the formation of the 1,2-addition product, we attempted to increase the steric hindrance by the use of bulky R1 groups. As shown in Table 2, the corresponding 1,4-addition product was formed preferentially even at low temperatures (20
C and 40
C) when R1 was changed from a methyl group to a benzyl group (entries 4e7). To our delight, the desired product could be obtained with up to 66% ee when the reaction was carried out at a temperature of 40
C (entry 6). These results indicate that increasing the steric hindrance of the R1 group increases enantioselectivity and also suppresses the formation of the 1,2-addition product. The use of bulkier isopropyl and tert-butyl esters gave similar enantioselectivities but higher yields at 40
C (entries 8 and 9). Therefore, subsequent reactions were carried out in DME at 40
C using isopropyl ester 3c as a substrate.

Table 2 Optimization of the reaction conditions: temperature and hindrance of R1 groupa

Table 1 Optimization of the reaction conditions: solventa

Entry

Solvent

Time (h)

Yield (%)b

Ee (%)c

1 2 3 4 5 6 7 8 9 10

DCM DCE Toluene THF 1,4-Dioxane DME Et2O Acetonitrile EtOH t-BuOH

6 12 12 1 1 1 12 6 2 2

58 64 63 64 63 74 30 82 trace 71

11 9 33 30 32 38 34 10 nd 3

a The reactions of 3a (0.10 mmol) with 4 (0.11 mmol) were carried out in the presence of Cat. B (2 mol %) in a solvent (1 mL) at room temperature and quenched by 30% H2O2 (0.1 mL) after a certain reaction time. b Isolated yields. c The ee values were determined by HPLC analysis using chiral Daicel ChiralPak IC-3 column with n-hexane/i-PrOH as an eluent.

Entry

R1

Temp (
C)

5

Time (h)

Yield (%)b

ee (%)c

1 2 3 4 5 6 7 8 9

Me Me Me Bn Bn Bn Bn i-Pr t-Bu

rt 0 20 0 20 40 60 40 40

5a 5a 5a 5b 5b 5b 5b 5c 5d

1 3 3 3 3 3 4 3 4

74 65 traced 67 69 68 35 84 71

38 40 nd 47 51 66 67 66 46

a The reactions of 3 (0.10 mmol) with 4 (0.11 mmol) were carried out in the presence of Cat. B (2 mol %) at a certain temperature in DME (1 mL) and quenched by 30% H2O2 (0.1 mL) after 3 h. b Isolated yields. c The ee values were determined by HPLC analysis using Daicel ChiralPak IC-3 column with n-hexane/i-PrOH as eluent. d The unwanted 1,2-addition product was obtained in 67% yield.

The influence of different counter-anions and the amount of pincer-Pd complex on the asymmetric addition of diphenylphosphine to b,g-unsaturated a-keto isopropyl ester 3c were also

6834

Y. Xu et al. / Tetrahedron 71 (2015) 6832e6839

Table 3 Optimization of the reaction conditions: counter-anions of the Pd-complexes and catalyst loadinga

examined (Table 3). The complexes with I, OTf and Cl counter-ions were detrimental to reaction activity and no 1,4-addition product was obtained. These results show that this Pd-catalyzed Michael addition is largely affected by the counter-anion and that Cat. B with an acetate anion is the most efficient catalyst for the reaction. We then decreased the amount of Cat. B from 2 mol % to 1 mol % with the aim of improving catalytic efficiency. The reaction proceeded sluggishly to give the product in a very low yield. Increasing the amount of Cat. B from 2 mol % to 4 mol % gave a similar yield and ee. With the optimized reaction conditions in hand, we examined the reactions of various b,g-unsaturated a-keto esters with Ph2PH (Table 4). The influence of the electronic and steric effects of the substituents on the aromatic ring were first examined. The reactions of para-substituted substrates afforded the products in higher yields and enantioselectivities compared with those of the ortho-substituted substrates (entries 1e7). Among them, the para-fluorine substituted substrate gave the highest enantioselectivity (93% ee) (entry 3). Therefore, other substrates with a substituted group at the para-position were examined and all gave high yields and moderate enantioselectivities (entries 8e10). A 2,4-dichloro phenyl derivative was also subjected to the addition reaction. The reaction proceeded smoothly and gave the desired product in high yield but with lower ee (entry 11). When the phenyl ring was replaced with a naphthalene ring, high yields of product were also obtained, while the ee of the 1-naphthyl derivative was significantly lower than that of 2-naphthyl derivative (entries 12 and 13). b,g-Unsaturated a-keto esters bearing a furan or thiophene ring also gave their corresponding products in high yields (91 and 90%) but relatively low enantioselectivity for the furan species (entries 14 and 15). Product yield decreased remarkably for a substrate possessing a pyridyl group (entry 16). Substrates bearing R2 alkyl groups were also examined and the reactions provided the corresponding products in moderate yields and 33e69% enantioselectivities (entries 17e19). An X-ray crystallography study was performed to determine the absolute configuration of the addition products. Thus, recrystallization of 5k from a mixed solvent system of dichloromethane and n-hexane provided needle crystals, which were suitable for single crystal X-ray diffraction. The diffraction data

Table 4 Asymmetric Michael additions of diphenylphosphine to b,g-unsaturated a-keto estersa

Entry

R2

5

Yield (%)b

ee (%)c

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

Ph o-FC6H4 p-FC6H4 o-ClC6H4 p-ClC6H4 o-MeOC6H4 p-MeOC6H4 p-BrC6H4 p-NO2C6H4 p-CH3C6H4 2,4-Cl2C6H3 1-naphthyl 2-naphthyl 2-furyl 2-thienyl 3-pyridyl Me Et i-Pr

5c 5e 5f 5g 5h 5i 5j 5k 5l 5m 5n 5o 5p 5q 5r 5s 5t 5u 5v

84 61 80 83 87 77 88 94 87 80 83 82 85 91 94 62 70 63 57

66 44 93 41 71 21 59 66 62 64 49 29 83 50 75 69 33 35 69

a The reactions of 3 (0.10 mmol) with 4 (0.11 mmol) were carried out in the presence of Cat. B (2 mol %) at 40
C in DME (1 mL) and quenched by 30% H2O2 (0.1 mL) after 3 h. b Isolated yields. c The ee values were determined by HPLC analysis using Daicel ChiralPak IC-3 column with n-hexane/i-PrOH as an eluent.

Fig. 1. ORTEP diagram for complex 5k (thermal ellipsoids are at the 30% probability level).

showed that the absolute configuration of the major enantiomer of 5k was S (Fig. 1).13 Based on the absolute configuration of 5k and literature reports,6a we are able to propose a reaction pathway for this palladium catalyzed Michael addition reaction (Scheme 2). First, the diphenylphosphine 4 coordinates to Cat. B and then undergoes a transphosphination to afford the palladium phosphido complex A, releasing one molecule of AcOH. Subsequently, the phosphido anion of A adds to the C]C double bond of 3a from its down side via a favorable transition state B. Another transition state C is unfavorable due to the strong steric hindrance of the tert-butyl groups of Cat. B. Subsequent protonolysis with the released AcOH affords the Michael addition product 6a to regenerate Cat. B. In this reaction, Cat. B with an AcO counter-anion exhibited higher activity than catalysts bearing other counterions (Cl, I and TfO). This is presumably because of the generation of weak acid AcOH, a weak electrolyte, which influences the reaction equilibrium.

Y. Xu et al. / Tetrahedron 71 (2015) 6832e6839

6835

4.2. Improved preparation of Cat. A Compound 1 (1.42 g, 3.9 mmol) and DABCO (2.62 g, 23.4 mmol) were added to a two neck round bottom flask (100 mL). The reaction system was pump-charged with N2 three times, and kept under a N2 atmosphere. Dry degassed toluene (10 mL) was added by syringe and the mixture stirred continuously at room temperature until the solid was dissolved. The reaction solution was heated to 80
C and stirred for an additional 7 h. After the starting materials were completely consumed, the reaction solution was cooled to room temperature. A white solid appeared in the bottom of the flask. Dry degassed n-hexane (50 mL) was added to the reaction mixture and stirring was continued for a further 15 min. A large amount of white solid precipitated from the reaction system. The supernatant layer was sucked out using a syringe and transferred into another two neck round-bottom flask (100 mL) filled with a suspension of PdCl2(CH3CN)2 (1.01 g, 3.9 mmol) in dry degassed toluene (5 mL) under a N2 atmosphere. The yellow suspension immediately turned into a nut-brown color. The reaction mixture was heated to reflux and stirred for 8 h. After being cooled to room temperature, the reaction solution was evaporated in vacuo to give a dark brown solid, which was purified by the silica gel column chromatography (petroleum ethereethyl acetate¼10/1e3/1, v/v) to afford Cat. A as a yellow solid (1.23 g, 66% overall yield). Scheme 2. Proposed reaction pathway.

4.3. Pincer-Pd catalyzed asymmetric Michael addition 3. Conclusion We have developed an asymmetric Michael addition of b,gunsaturated a-keto esters with diphenylphosphine using the P-stereogenic PCP pincer-Pd complex Cat. B as a chiral catalyst. The corresponding hydrophosphination products were obtained in good yields (up to 94%) and with moderate to good enantioselectivities (up to 93% ee) under the optimum reaction conditions. 4. Experimental 4.1. General Unless otherwise stated, commercially available compounds were used without further purification. All the dry solvents were obtained by purification according to standard methods. The column chromatography was carried out with silica gel (200e300 mesh). 1H NMR spectra were recorded with a Varian MERCURYplus 400 MHz spectrometer. Chemical shifts were reported in parts per million (ppm) with the internal TMS signal at 0.0 ppm as a standard. The data are reported as follows: chemical shift (ppm), and multiplicity (s¼singlet, d¼doublet, t¼triplet, q¼quartet, m¼multiplet or unresolved, br s¼broad singlet), coupling constant(s) in Hertz (Hz), integration assignment. 13C NMR and 31P NMR spectra were recorded at 101 and 162 MHz, respectively. Infrared spectra were obtained with a Thermo Scientific Nicolet IS10 infrared spectrometer. The high resolution mass spectra (HRMS) were obtained with an electrospray spectrometer Waters Micromass Q-TOF Premier Mass Spectrometer. Optical rotations were measured with a Rudolph Research Analytical Autopol VI automatic polarimeter using a 50 mm path-length cell at 589 nm and at the indicated concentration with unit g/100 mL. The enantiomeric excesses were determined by chiral HPLC using a Shimadzu LC-10Avp system using n-hexane/i-PrOH mobile phase and UV detection.

4.3.1. General procedure 1. A solution of Cat. B (1.01 mg, 2 mol %) in dry DME (0.5 mL) was added to a 10 mL Schlenk tube under a N2 atmosphere. Diphenylphosphine (18.6 mg, 0.11 mmol) was added, whereupon the color of the solution turned to a bright yellow. After 15 min, the Schlenk tube was transferred to a 40
C cold bath and the mixture was stirred for 20 min. b,g-Unsaturated a-keto ester (oily liquid, 0.10 mmol) was added to the solution by syringe and the mixture was stirred for the allotted time. When the starting material was completely consumed (checked by TLC), the cold bath was removed and the reaction was quenched with 30% H2O2 (100 mL). After treatment with a saturated Na2S2O3 solution (200 mL), the solvent was evaporated in vacuo and the residue was purified by the silica gel column chromatography (DCM/ MeOH¼120/1e40/1, v/v) to afford pure products. 4.3.2. General procedure 2. This procedure was similar to that described above, except the following experimental operation: b,gUnsaturated a-keto ester (solid, 0.10 mmol) was dissolved in DME (0.5 mL) and the resulting solution was cooled to 40
C. This solution was then added to the mixture of Cat. B and diphenylphosphine in DME cooled at 40
C. 4.3.3. Methyl 4-(diphenylphosphoryl)-2-oxo-4-phenylbutanoate (5a). Procedure 2, white solid (25.5 mg, 65%). [a]20 D ¼53.7 (c 0.13, CHCl3); 1H NMR (400 MHz, CDCl3): d 7.95e7.90 (m, 2H), 7.57e7.51 (m, 3H), 7.43e7.40 (m, 2H), 7.38e7.34 (m, 1H), 7.28e7.22 (m, 4H), 7.17e7.14 (m, 3H), 4.23 (ddd, J¼11.2, 8.2, 3.2 Hz, 1H), 3.82 (ddd, J¼18.9, 10.4, 6.2 Hz, 1H), 3.76 (s, 3H), 3.31 (ddd, J¼18.9, 10.3, 3.3 Hz, 1H); 13C NMR (101 MHz, CDCl3): d 191.3, 191.1, 160.6, 135.0, 132.4, 131.8, 131.6, 131.5, 131.4, 131.3, 130.6, 130.5, 130.0, 129.9, 129.2, 129.1, 128.6, 128.4, 128.2, 127.6, 53.2, 41.7, 41.0, 40.1; 31P NMR (162 MHz, CDCl3): d 34.56 (s); IR (KBr) cm1: 3058, 2982, 2901, 1722, 1438, 1283, 1185, 1118, 1066, 839, 718, 695; HRMS (ESI): m/z calcd for C23H22O4P: 393.1259 [MþH]þ, found: 393.1256; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-PrOH¼60/40, 0.6 mL/

6836

Y. Xu et al. / Tetrahedron 71 (2015) 6832e6839

min, UIV 210 nm), tR1¼25.8 min (major), tR2¼36.0 min (minor), ee¼40%.

min, UIV 210 nm), tR1¼16.4 min (major), tR2¼19.7 min (minor), ee¼44%.

4.3.4. Benzyl 4-(diphenylphosphoryl)-2-oxo-4-phenylbutanoate (5b). Procedure 2, white solid (16.4 mg, 35%). [a]20 D ¼59.2 (c 0.20, CHCl3); 1H NMR (400 MHz, CDCl3): d 7.92e7.88 (m, 2H), 7.56e7.51 (m, 3H), 7.44e7.39 (m, 2H), 7.35e7.29 (m, 6H), 7.25e7.22 (m, 4H), 7.14e7.12 (m, 3H), 5.16 (s, 2H), 4.20 (ddd, J¼11.0, 8.2, 3.1 Hz, 1H), 3.80 (ddd, J¼18.8, 10.4, 6.1 Hz, 1H), 3.30 (ddd, J¼18.8, 10.2, 3.0 Hz, 1H); 13C NMR (101 MHz, CDCl3): d 191.4, 191.2, 160.0, 135.0, 134.9, 134.3, 132.4, 131.8, 131.6, 131.5, 131.3, 131.2, 130.5, 130.0, 129.9, 129.7, 129.2, 129.1, 129.0, 128.9, 128.8, 128.6, 128.4, 128.2, 127.6, 68.3, 41.7, 41.1, 40.1; 31P NMR (162 MHz, CDCl3): d 34.36 (s); IR (KBr) cm1: 3060, 2962, 2912, 1729, 1455, 1438, 1265, 1187, 1119, 1064, 803, 754, 696; HRMS (ESI): m/z calcd for C29H26O4P: 469.1569 [MþH]þ, found: 469.1588; HPLC (Daicel ChiralPak IC-3 column, nhexane/i-PrOH¼60/40, 0.6 mL/min, UIV 210 nm), tR1¼30.3 min (major), tR2¼36.6 min (minor), ee¼67%.

4.3.8. Isopropyl 4-(diphenylphosphoryl)-4-(4-fluorophenyl)-2oxobutanoate (5f). Procedure 1, white solid (35.1 mg, 80%). 1 [a]20 D ¼114 (c 0.12, CHCl3); H NMR (400 MHz, CDCl3): d 7.95e7.90 (m, 2H), 7.56 (t, J¼7.9 Hz, 3H), 7.47e7.36 (m, 3H), 7.29e7.26 (m, 4H), 6.86 (t, J¼8.6 Hz, 2H), 5.02 (heptet, J¼6.2 Hz, 1H), 4.22e4.17 (m, 1H), 3.81e3.72 (m, 1H), 3.26e3.19 (m, 1H), 1.25 (dd, J¼6.3, 2.2 Hz, 6H); 13 C NMR (101 MHz, CDCl3): d 192.0, 191.9, 163.5, 161.0, 159.8, 132.5, 131.9, 131.6, 131.5, 131.4, 131.2, 131.1, 130.9, 130.7, 129.3, 129.2, 128.5, 128.4, 115.7, 115.6, 71.3, 40.9, 40.2, 40.1, 21.7; 31P NMR (162 MHz, CDCl3): d 33.99 (s); IR (KBr) cm1: 3054, 2983, 2914, 1744, 1732, 1507, 1437, 1402, 1284, 1186, 1172, 1120, 1104, 1063, 846, 756, 748, 692; HRMS (ESI): m/z calcd for C25H25O4PF: 439.1474 [MþH]þ, found: 439.1467; HPLC (Daicel ChiralPak IC-3 column, n-hexane/iPrOH¼60/40, 0.6 mL/min, UIV 210 nm), tR1¼12.3 min (major), tR2¼12.9 min (minor), ee¼93%.

4.3.5. Isopropyl 4-(diphenylphosphoryl)-2-oxo-4-phenylbutanoate (5c). Procedure 1, white solid (35.3 mg, 84%). [a]20 D ¼79.2 (c 0.16, CHCl3); 1H NMR (400 MHz, CDCl3): d 7.95e7.90 (m, 3H), 7.58e7.52 (m, 2H), 7.45e7.34 (m, 3H), 7.27e7.25 (m, 4H), 7.18e7.14 (m, 3H), 5.01 (heptet, J¼6.2 Hz, 1H), 4.24e4.19 (m, 1H), 3.80 (ddd, J¼18.9, 10.5, 5.8 Hz, 1H), 3.27 (ddd, J¼18.9, 10.4, 3.1 Hz, 1H), 1.25 (dd, J¼6.3, 2.2 Hz, 6H); 13C NMR (101 MHz, CDCl3): d 192.1, 192.0, 159.8, 135.1, 135.0, 132.4, 131.8, 131.6, 131.5, 131.3, 131.2, 130.6, 130.1, 130.0, 129.2, 129.1, 128.6, 128.3, 128.2, 127.5, 71.2, 41.6, 40.9, 40.0, 21.7; 31P NMR (162 MHz, CDCl3): d 34.19 (s); IR (KBr) cm1: 3059, 2983, 2903, 1723, 1438, 1274, 1176, 1119, 1064, 832, 753, 723, 698; HRMS (ESI): m/z calcd for C25H26O4P: 421.1569 [MþH]þ, found: 421.1558; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-PrOH¼60/40, 0.6 mL/ min, UIV 210 nm), tR1¼19.3 min (major), tR2¼23.8 min (minor), ee¼66%.

4.3.9. Isopropyl 4-(2-chlorophenyl)-4-(diphenylphosphoryl)-2oxobutanoate (5g). Procedure 1, white solid (37.8 mg, 83%). 1 [a]20 D ¼51.8 (c 0.19, CHCl3); H NMR (400 MHz, CDCl3): d 7.79 (dt, J¼7.9, 1.7 Hz, 1H), 7.65e7.55 (m, 3H), 7.48 (ddd, J¼5.2, 4.5, 1.8 Hz, 1H), 7.45e7.37 (m, 2H), 7.36e7.34 (m, 1H), 7.29e7.17 (m, 4H), 7.13e7.04 (m, 2H), 5.02 (heptet, J¼6.0 Hz, 1H), 4.91 (ddd, J¼10.8, 7.5, 3.2 Hz, 1H), 3.77 (ddd, J¼18.2, 10.9, 6.1 Hz, 1H), 3.33 (ddd, J¼18.3, 9.2, 3.2 Hz, 1H), 1.25 (dd, J¼6.2, 2.2 Hz, 6H); 13C NMR (101 MHz, CDCl3): d 191.7, 191.6, 161.7, 159.8, 159.3, 132.6, 132.3, 132.0, 131.7, 131.5, 131.4, 131.2, 131.1, 130.9, 130.4, 130.1, 129.6, 129.3, 129.1, 128.7, 128.4, 128.3, 127.9, 127.7, 124.7, 121.0, 115.3, 115.1, 110.3, 71.3, 39.5, 32.7, 32.0, 21.7; 31P NMR (162 MHz, CDCl3): d 34.54 (s); IR (KBr) cm1: 3058, 2984, 2937, 1724, 1475, 1438, 1283, 1189, 1118, 1071, 828, 755, 714, 697; HRMS (ESI): m/z calcd for C25H25O4PCl: 455.1179 [MþH]þ, found: 455.1170; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-PrOH¼60/40, 0.6 mL/min, UIV 210 nm), tR1¼17.4 min (major), tR2¼21.8 min (minor), ee¼41%.

4.3.6. tert-Butyl 4-(diphenylphosphoryl)-2-oxo-4-phenylbutanoate (5d). Procedure 1, white solid (30.8 mg, 71%). [a]20 D ¼46.4 (c 0.10, CHCl3); 1H NMR (400 MHz, CDCl3): d 7.94e7.90 (m, 2H), 7.58e7.54 (m, 3H), 7.43e7.40 (m, 2H), 7.36e7.33 (m, 1H), 7.27e7.24 (m, 4H), 7.16e7.14 (m, 3H), 4.20 (t, J¼9.2 Hz, 1H), 3.76 (ddd, J¼15.0, 10.1, 5.1 Hz, 1H), 3.22 (dd, J¼17.6, 8.8 Hz, 1H), 1.43 (s, 9H); 13C NMR (101 MHz, CDCl3): d 192.9, 192.8, 159.7, 135.3, 135.2, 132.4, 131.8, 131.6, 131.5, 131.4, 131.3, 130.1, 130.0, 129.2, 129.1, 128.8, 128.6, 128.4, 128.2, 127.5, 84.6, 41.7, 41.1, 39.9, 27.9; 31P NMR (162 MHz, CDCl3): d 34.30 (s); IR (KBr) cm1: 3059, 2923, 2853, 1722, 1496, 1438, 1369, 1262, 1175, 1156, 1067, 1033, 826, 754, 722, 700; HRMS (ESI): m/z calcd. For C26H28O4P: 435.1725 [MþH]þ, found: 435.1722; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-PrOH¼60/40, 0.6 mL/ min, UIV 210 nm), tR1¼15.9 min (major), tR2¼18.3 min (minor), ee¼46%. 4.3.7. Isopropyl 4-(diphenylphosphoryl)-4-(2-fluorophenyl)-2oxobutanoate (5e). Procedure 1, white solid (26.7 mg, 61%). 1 [a]20 D ¼44.8 (c 0.43, CHCl3); H NMR (400 MHz, CDCl3): d 8.03e7.89 (m, 2H), 7.67e7.60 (m, 1H), 7.59e7.45 (m, 6H), 7.45e7.38 (m, 1H), 7.29e7.19 (m, 1H), 7.13e7.01 (m, 2H), 6.75 (dd, J¼10.3, 7.6 Hz, 1H), 5.00 (heptet, J¼6.2 Hz, 1H), 4.65 (ddd, J¼10.8, 7.6, 3.1 Hz, 1H), 3.83e3.71 (m, 1H), 3.33e3.21 (m, 1H), 1.23 (dd, J¼6.2, 2.1 Hz, 6H); 13 C NMR (101 MHz, CDCl3): d 191.7, 191.6, 161.7, 159.8, 132.6, 132.3, 132.0, 131.7, 131.5, 131.4, 131.2, 131.1, 131.0, 130.9, 130.5, 130.2, 129.6, 129.3, 129.2, 129.0, 128.7, 128.4, 128.3, 127.9, 127.7, 124.7, 121.0, 115.3, 115.1, 110.4, 71.3, 39.5, 32.7, 32.0, 21.7; 31P NMR (162 MHz, CDCl3): d 33.97 (s); IR (KBr) cm1: 3059, 2983, 2938, 1724, 1492, 1438, 1279, 1184, 1118, 1066, 825, 755, 721, 697; HRMS (ESI): m/z calcd for C25H25O4PF: 439.1474 [MþH]þ, found: 439.1448; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-PrOH¼60/40, 0.6 mL/

4.3.10. Isopropyl 4-(4-chlorophenyl)-4-(diphenylphosphoryl)-2oxobutanoate (5h). Procedure 2, white solid (39.6 mg, 87%). 1 [a]20 D ¼114 (c 0.19, CHCl3); H NMR (400 MHz, CDCl3): d 7.94e7.89 (m, 2H), 7.60e7.52 (m, 3H), 7.47e7.44 (m, 2H), 7.40e7.37 (m, 1H),7.24e7.22 (m, 2H), 7.29e7.27 (m, 2H), 7.13 (d, J¼8.5 Hz, 2H), 5.02 (heptet, J¼6.2 Hz, 1H), 4.18 (ddd, J¼10.6, 7.8, 2.8 Hz, 1H), 3.76 (ddd, J¼18.9, 10.7, 5.4 Hz, 1H), 3.23 (ddd, J¼19.0, 10.1, 2.9 Hz, 1H), 1.25 (dd, J¼6.3, 2.0 Hz, 6H); 13C NMR (101 MHz, CDCl3): d 191.9, 191.8, 159.8, 133.8, 133.6, 132.5, 132.0, 131.5, 131.4, 131.1, 130.4, 129.3, 129.2, 128.8, 128.6, 128.5, 71.4, 41.0, 40.3, 40.0, 21.7; 31P NMR (162 MHz, CDCl3): d 33.93 (s); IR (KBr) cm1: 3053, 2982, 2909, 1724, 1489, 1437, 1284, 1174, 1185, 1105, 1066, 846, 748, 724, 714, 692, 645; HRMS (ESI): m/z calcd for C25H25O4PCl: 455.1179 [MþH]þ, found: 455.1190; HPLC (Daicel ChiralPak IC-3 column, n-hexane/iPrOH¼60/40, 0.6 mL/min, UIV 210 nm), tR1¼14.5 min (major), tR2¼15.7 min (minor), ee¼71%. 4.3.11. Isopropyl 4-(diphenylphosphoryl)-4-(2-methoxyphenyl)-2oxobutanoate (5i). Procedure 1, white solid (34.7 mg, 77%). 1 [a]20 D ¼13.0 (c 0.19, CHCl3); H NMR (400 MHz, CDCl3): d 7.98 (ddd, J¼10.7, 7.6, 1.8 Hz, 2H), 7.62e7.51 (m, 4H), 7.45e7.38 (m, 2H), 7.30 (td, J¼7.4, 1.4 Hz, 1H), 7.19 (td, J¼7.6, 3.1 Hz, 2H), 7.13e7.06 (m, 1H), 6.91 (t, J¼7.5 Hz, 1H), 6.55 (d, J¼8.3 Hz, 1H), 5.01 (heptet, J¼6.2 Hz, 1H), 4.92 (ddd, J¼11.3, 8.1, 3.4 Hz, 1H), 3.75 (ddd, J¼17.8, 11.0, 6.6 Hz, 1H), 3.48 (s, 3H), 3.27 (ddd, J¼18.0, 9.3, 3.4 Hz, 1H), 1.23 (dd, J¼6.3, 2.6 Hz, 6H); 13C NMR (101 MHz, CDCl3): d 192.2, 192.1, 159.9, 156.8, 132.3, 131.8, 131.7, 131.6, 131.5, 131.2, 131.1, 131.0, 129.6, 129.2, 129.0, 128.7, 128.6, 128.5, 127.9, 127.7, 121.1, 110.4, 71.0, 55.4, 39.4, 32.7, 32.0, 21.7; 31P NMR (162 MHz, CDCl3): d 34.81 (s); IR (KBr) cm1:

Y. Xu et al. / Tetrahedron 71 (2015) 6832e6839

6837

3059, 2982, 2938, 2838, 1723, 1493, 1438, 1248, 1182, 1118, 754, 722, 697; HRMS (ESI): m/z calcd for C26H28O5P: 451.1650 [MþH]þ, found: 451.1648; HPLC (Daicel ChiralPak IC-3 column, n-hexane/iPrOH¼60/40, 0.6 mL/min, UIV 210 nm), tR1¼29.0 min (major), tR2¼38.7 min (minor), ee¼21%.

1439, 1288, 1186, 1174, 1120, 1104, 1067, 1026, 724, 717, 695; HRMS (ESI): m/z calcd for C26H28O4P: 435.1752 [MþH]þ, found: 435.1710; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-PrOH¼60/40, 0.6 mL/min, UIV 210 nm), tR1¼20.4 min (major), tR2¼21.9 min (minor), ee¼64%.

4.3.12. Isopropyl 4-(diphenylphosphoryl)-4-(4-methoxyphenyl)-2oxobutanoate (5j). Procedure 2, white solid (39.6 mg, 88%). 1 [a]20 H NMR (400 MHz, CDCl3): D ¼57.8 (c 0.16, CHCl3); d 7.94e7.89 (m, 2H), 7.56e7.53 (m, 3H), 7.46e7.43 (m, 2H), 7.36 (d, J¼6.4 Hz, 1H), 7.28e7.26 (m, 1H), 7.20e7.17 (m, 2H), 6.70 (d, J¼8.7 Hz, 3H), 5.01 (heptet, J¼6.2 Hz, 1H), 4.19e4.17 (m, 1H), 3.78e3.74 (m, 1H), 3.73 (s, 3H), 3.25e3.17 (m, 1H), 1.24 (dd, J¼6.3, 2.3 Hz, 6H); 13C NMR (101 MHz, CDCl3): d 192.3, 192.2, 159.9, 159.0, 132.3, 131.8, 131.6, 131.5, 131.4, 131.3, 131.1, 131.0, 130.8, 129.2, 129.1, 128.4, 128.3, 127.0, 126.8, 71.2, 55.4, 40.8, 40.2, 21.7; 31P NMR (162 MHz, CDCl3): d 34.30 (s); IR (KBr) cm1: 3055, 2981, 2933, 1722, 1512, 1437, 1277, 1249, 1180, 1105, 1029, 844, 720, 693; HRMS (ESI): m/z calcd for C26H28O5P: 451.1674 [MþH]þ, found: 451.1648; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-PrOH¼60/40, 0.6 mL/min, UIV 210 nm), tR1¼37.7 min (minor), tR2¼44.9 min (major), ee¼59%.

4.3.16. Isopropyl 4-(2,4-dichlorophenyl)-4-(diphenylphosphoryl)-2oxobutanoate (5n). Procedure 2, white solid (40.6 mg, 83%). 1 [a]20 H NMR (400 MHz, CDCl3): D ¼25.2 (c 0.25, CHCl3); d 8.07e7.97 (m, 2H), 7.75 (dd, J¼8.5, 2.0 Hz, 1H), 7.60 (dd, J¼8.1, 2.2 Hz, 3H), 7.50e7.35 (m, 4H), 7.31e7.22 (m, 2H), 7.15 (d, J¼2.1 Hz, 1H), 5.03 (heptet, J¼6.2 Hz, 1H), 4.88e4.77 (m, 1H), 3.79e3.61 (m, 1H), 3.31 (ddd, J¼18.4, 9.0, 3.1 Hz, 1H), 1.28e1.20 (m, 6H); 13C NMR (101 MHz, CDCl3): d 191.5, 191.3, 159.7, 134.0, 133.7, 132.7, 132.4, 132.2, 132.1, 131.6, 131.5, 131.2, 131.1, 131.0, 129.4, 129.3, 128.7, 128.4, 128.3, 71.4, 40.2, 36.6, 36.0, 21.7; 31P NMR (162 MHz, CDCl3): d 34.06 (s); IR (KBr) cm1: 3058, 2983, 2937, 1724, 1588, 1472, 1438, 1282, 1199, 1118, 1103, 1070, 838, 728, 699; HRMS (ESI): m/z calcd for C25H24O4PCl2: 489.0789 [MþH]þ, found: 489.0774; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-PrOH¼60/40, 0.6 mL/ min, UIV 210 nm), tR1¼13.4 min (major), tR2¼14.5 min (minor), ee¼49%.

4.3.13. Isopropyl 4-(4-bromophenyl)-4-(diphenylphosphoryl)-2oxobutanoate (5k). Procedure 2, white solid (46.9 mg, 94%). 1 [a]20 H NMR (400 MHz, CDCl3): D ¼101 (c 0.21, CHCl3); d 7.94e7.89 (m, 2H), 7.41e7.37 (m, 1H), 7.49e7.44 (m, 2H), 7.60e7.52 (m, 3H), 7.32e7.28 (m, 4H), 7.17 (dd, J¼8.5, 1.8 Hz, 2H), 5.02 (heptet, J¼6.2 Hz, 1H), 4.19e4.14 (m, 1H), 3.76 (ddd, J¼18.9, 10.7, 5.4 Hz, 1H), 3.23 (ddd, J¼18.9, 10.0, 2.9 Hz, 1H), 1.25 (dd, J¼6.3, 1.8 Hz, 6H); 13C NMR (101 MHz, CDCl3): d 192.0, 191.8, 159.8, 134.3, 132.6, 132.0, 131.8, 131.7, 131.6, 131.5, 131.4, 131.3, 131.2, 131.1, 130.4, 129.3, 129.2, 128.6, 128.5, 121.8, 71.4, 41.1, 40.4, 40.0, 21.7; 31P NMR (162 MHz, CDCl3): d 33.83 (s); IR (KBr) cm1: 3051, 2982, 2910, 1721, 1487, 1438, 1175, 1067, 844, 749, 724, 711, 696; HRMS (ESI): m/z calcd for C25H25O4PBr: 499.0674 [MþH]þ, found: 499.0653; HPLC (Daicel ChiralPak IC-3 column, n-hexane/ i-PrOH¼60/40, UIV 210 nm, 0.6 mL/min), tR1¼15.1 min (major), tR2¼16.3 min (minor), ee¼66%.

4.3.17. Isopropyl 4-(diphenylphosphoryl)-4-(naphthalen-1-yl)-2oxobutanoate (5o). Procedure 1, white solid (38.6 mg, 82%). 1 [a]20 D ¼8.7 (c 0.37, CHCl3); H NMR (400 MHz, CDCl3): d 8.06e7.93 (m, 4H), 7.66 (dd, J¼15.3, 7.8 Hz, 2H), 7.59e7.53 (m, 3H), 7.49e7.40 (m, 2H), 7.39e7.32 (m, 2H), 7.31e7.22 (m, 1H), 7.11e7.03 (m, 1H), 6.95 (td, J¼7.6, 2.9 Hz, 2H), 5.19 (td, J¼9.4, 3.4 Hz, 1H), 4.94 (heptet, J¼6.2 Hz, 1H), 3.88 (ddd, J¼18.6, 9.8, 6.8 Hz, 1H), 3.53 (ddd, J¼14.4, 10.3, 3.5 Hz, 1H), 1.15 (dd, J¼16.4, 5.3 Hz, 6H); 13C NMR (101 MHz, CDCl3): d 192.2, 192.1, 159.9, 133.8, 132.5, 132.0, 131.8, 131.7, 131.6, 131.0, 130.9, 130.6, 129.3, 129.2, 128.9, 128.3, 128.0, 127.9, 127.7, 126.5, 126.3, 125.6, 125.5, 122.8, 71.2, 41.2, 34.8, 34.1, 21.7, 21.6; 31P NMR (162 MHz, CDCl3): d 34.39 (s); IR (KBr) cm1: 3057, 2982, 2934, 1723, 1438, 1387, 1375, 1265, 1182, 1117, 1103, 1071, 778, 725, 697; HRMS (ESI): m/z calcd for C29H28O4P: 471.1725 [MþH]þ, found: 471.1702; HPLC (Daicel ChiralPak IC-3 column, n-hexane/iPrOH¼60/40, 0.6 mL/min, UIV 210 nm), tR1¼21.6 min (major), tR2¼26.3 min (minor), ee¼29%.

4.3.14. Isopropyl 4-(diphenylphosphoryl)-4-(4-nitrophenyl)-2oxobutanoate (5l). Procedure 1, white solid (39.6 mg, 87%). 1 [a]20 D ¼109 (c 0.18, CHCl3); H NMR (400 MHz, CDCl3): d 8.05 (d, J¼8.8 Hz, 1H), 7.95 (t, J¼10.9 Hz, 2H), 7.64e7.49 (m, 7H), 7.44e7.42 (m, 1H), 7.30 (t, J¼7.2 Hz, 3H), 5.06 (heptet, J¼6.4 Hz, 1H), 4.32 (s, 1H), 3.90e3.82 (m, 1H), 3.36e3.28 (m, 1H), 1.28 (dd, J¼6.2, 3.6 Hz,6H); 13C NMR (101 MHz, CDCl3): d 191.6, 191.5, 159.6, 147.3, 143.3, 132.9, 132.4, 131.5, 131.4, 131.1, 131.0, 130.9, 130.8, 129.5, 129.4, 128.8, 128.7, 123.7, 71.6, 41.7, 41.1, 40.0, 21.7; 31P NMR (162 MHz, CDCl3): d 33.29 (s); IR (KBr) cm1: 3053, 2985, 2920, 1747, 1728, 1515, 1456, 1346, 1261, 1176, 1108, 1070, 858, 827, 720, 703, 642; HRMS (ESI): m/z calcd for C25H25O6NP: 455.1419 [MþH]þ, found: 455.1410; HPLC (Daicel ChiralPak IC-3 column, n-hexane/iPrOH¼60/40, 0.6 mL/min, UIV 210 nm), tR1¼29.8 min (major), tR2¼62.2 min (minor), ee¼62%. 4.3.15. Isopropyl 4-(diphenylphosphoryl)-2-oxo-4-(p-tolyl) butanoate (5m). Procedure 1, white solid (34.8 mg, 80%). [a]20 D ¼70.8 (c 0.14, CHCl3); 1H NMR (400 MHz, CDCl3): d 7.93e7.89 (m, 2H), 7.54e7.43 (m, 6H), 7.34e7.24 (m, 2H), 7.15 (d, J¼7.8 Hz, 2H), 6.96 (d, J¼7.6 Hz, 2H), 4.99 (heptet, J¼6.2 Hz, 1H), 4.19 (t, J¼7.8 Hz, 1H), 3.79e3.72 (m, 1H), 3.24 (dd, J¼17.4, 9.0 Hz, 1H), 2.22 (s, 3H), 1.23 (d, J¼6.2 Hz, 6H); 13C NMR (101 MHz, CDCl3): d 192.1, 192.0, 159.9, 137.2, 132.3, 131.8, 131.5, 131.4, 131.3, 129.9, 129.8, 129.4, 129.2, 129.1, 128.4, 128.3, 71.2, 41.2, 40.6, 40.1, 21.7, 21.3; 31P NMR (162 MHz, CDCl3): d 34.18 (s); IR (KBr) cm1: 3054, 2983, 2909, 1721, 1515,

4.3.18. Isopropyl 4-(diphenylphosphoryl)-4-(naphthalen-2-yl)-2oxobutanoate (5p). Procedure 2, white solid (40.0 mg, 85%). 1 [a]20 D ¼92.2 (c 0.12, CHCl3); H NMR (400 MHz, CDCl3): d 7.98 (ddd, J¼10.8, 7.8, 1.5 Hz, 2H), 7.79e7.42 (m, 12H), 7.34e7.30 (m, 1H), 7.24e7.19 (m, 2H), 5.00 (heptet, J¼6.2 Hz, 1H), 4.43e4.37 (m, 1H), 3.94 (ddd, J¼18.7, 10.5, 5.6 Hz, 1H), 3.37 (ddd, J¼18.8, 10.2, 2.9 Hz, 1H), 1.27e1.22 (m, 6H); 13C NMR (101 MHz, CDCl3): d 191.9, 191.8, 159.7, 133.1, 132.7, 132.6, 132.5, 132.2, 131.7, 131.4, 131.2, 131.0, 130.6, 130.4, 129.1, 129.0, 128.9, 128.2, 128.1, 128.0, 127.9, 127.7, 127.6, 127.5, 126.0, 125.9, 71.0, 41.6, 40.9, 40.1, 21.5; 31P NMR (162 MHz, CDCl3): d 34.29 (s); IR (KBr) cm1: 3057, 2980, 2919, 1747, 1723, 1437, 1261, 1176, 1118, 1103, 1070, 1025, 903, 859, 835, 770, 726, 691, 646; HRMS (ESI): m/z calcd for C29H28O4P: 471.1725 [MþH]þ, found: 471.1720; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-PrOH¼60/40, 0.6 mL/min, UIV 210 nm), tR1¼20.0 min (major), tR2¼26.3 min (minor), ee¼83%. 4.3.19. Isopropyl 4-(diphenylphosphoryl)-4-(furan-2-yl)-2oxobutanoate (5q). Procedure 1, white solid (37.4 mg, 91%). 1 [a]20 D ¼12.5 (c 0.19, CHCl3); H NMR (400 MHz, CDCl3): d 7.88e7.78 (m, 2H), 7.59e7.43 (m, 6H), 7.42e7.32 (m, 2H), 7.16 (d, J¼1.2 Hz, 1H), 6.21e5.99 (m, 2H), 5.05 (heptet, J¼6.2 Hz, 1H), 4.57e4.44 (m, 1H), 3.65 (ddd, J¼18.7, 10.5, 6.5 Hz, 1H), 3.35 (ddd, J¼18.8, 9.4, 3.5 Hz, 1H), 1.26 (dd, J¼13.2, 4.2 Hz, 6H); 13C NMR (101 MHz, CDCl3): d 191.7, 191.6, 159.9, 148.3, 148.2, 142.2, 132.6, 132.3, 131.7, 131.6,

6838

Y. Xu et al. / Tetrahedron 71 (2015) 6832e6839

131.5, 130.5, 130.3, 129.5, 129.2, 129.0, 128.6, 128.5, 111.1, 109.4, 109.3, 71.3, 37.5, 36.4, 35.7, 21.8; 31P NMR (162 MHz, CDCl3): d 32.94 (s); IR (KBr) cm1: 3058, 2983, 2935, 1724, 1438, 1375, 1280, 1185, 1119, 1105, 1068, 725, 697; HRMS (ESI): m/z calcd for C23H24O5P: 411.1361 [MþH]þ, found 411.1358; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-PrOH¼60/40, 0.6 mL/min, UIV 210 nm), tR1¼32.2 min (minor), tR2¼34.3 min (major), ee¼50%. 4.3.20. Isopropyl 4-(diphenylphosphoryl)-2-oxo-4-(thiophen-2-yl) butanoate (5r). Procedure 1, yellow solid (40.1 mg, 94%). 1 [a]20 D ¼79.6 (c 0.16, CHCl3); H NMR (400 MHz, CDCl3): d 7.89 (ddd, J¼11.0, 8.1, 1.5 Hz, 2H), 7.58e7.48 (m, 5H), 7.44e7.38 (m, 1H), 7.31 (td, J¼7.5, 3.1 Hz, 2H), 7.06 (d, J¼5.1 Hz, 1H), 6.93 (t, J¼2.7 Hz, 1H), 6.81 (dd, J¼5.1, 3.6 Hz, 1H), 5.04 (heptet, J¼6.2 Hz, 1H), 4.64e4.52 (m, 1H), 3.73 (ddd, J¼18.6, 10.5, 5.8 Hz, 1H), 3.26 (ddd, J¼18.6, 9.5, 3.2 Hz, 1H), 1.25 (dd, J¼6.3, 2.0 Hz, 6H); 13C NMR (101 MHz, CDCl3): d 191.7, 191.6, 159.8, 132.6, 132.1, 131.6, 131.5, 131.4, 129.3, 129.2, 128.5, 128.4, 127.9, 127.8, 127.1, 125.5, 71.4, 40.9, 37.2, 36.5, 21.7; 31P NMR (162 MHz, CDCl3): d 33.35 (s); IR (KBr) cm1: 3058, 2983, 2933, 1723, 1438, 1278, 1185, 1118, 1105, 1064, 998, 850, 724, 699; HRMS (ESI): m/z calcd for C23H24O4PS: 427.1133 [MþH]þ, found 427.1122; HPLC (Daicel ChiralPak IC-3 column, n-hexane/iPrOH¼60/40, 0.6 mL/min, UIV 210 nm), tR1¼26.5 min (major), tR2¼32.8 min (minor), ee¼75%. 4.3.21. Isopropyl 4-(diphenylphosphoryl)-2-oxo-4-(pyridin-3-yl) butanoate (5s). Procedure 1, white solid (26.1 mg, 62%). [a]20 D ¼13.5 (c 0.10, CHCl3); 1H NMR (400 MHz, CDCl3): d 8.42 (s, 1H), 7.97e7.92 (m, 3H), 7.59e7.47 (m, 6H), 7.40 (t, J¼7.2 Hz, 1H), 7.33e7.29 (m, 3H), 5.03 (heptet, J¼6.2 Hz, 1H), 4.26e4.22 (m, 1H), 3.82e3.73 (m, 1H), 3.34e3.27 (m, 1H), 1.26 (d, J¼6.6 Hz, 6H); 13C NMR (101 MHz, CDCl3): d 191.7, 191.6, 159.8, 150.8, 148.5, 137.2, 132.7, 132.2, 131.5, 131.4, 131.1, 131.0, 129.4, 129.3, 128.8, 128.6, 123.7, 71.5, 39.7, 39.1, 38.4, 29.9, 21.7; 31P NMR (162 MHz, CDCl3): d 33.94 (s); IR (KBr) cm1: 3056, 2917, 2849, 1724, 1438, 1426, 1261, 1183, 1104, 1069, 1026, 724, 712, 699; HRMS (ESI): m/z calcd for C24H25O4PN: 422.1516 [MþH]þ, found 422.1519; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-PrOH¼60/40), tR1¼44.3 min (major), tR2¼53.0 min (minor), ee¼69%. 4.3.22. Isopropyl 4-(diphenylphosphoryl)-2-oxopentanoate (5t). Procedure 1, white solid (25.1 mg, 70%). [a]20 D ¼17.0 (c 0.19, CHCl3); 1H NMR (400 MHz, CDCl3): d 7.83e7.76 (m, 4H), 7.53e7.47 (m, 6H), 5.09 (heptet, J¼6.2 Hz, 1H), 3.12e2.29 (m, 3H), 1.30 (d, J¼6.2 Hz, 6H), 1.16 (dd, J¼16.1, 6.4 Hz, 3H); 13C NMR (101 MHz, CDCl3): d 193.0, 192.9, 160.3, 132.2, 132.1, 131.4, 131.2, 131.2, 129.1, 128.9, 128.8, 71.3, 39.6, 29.9, 28.1, 27.3, 21.7, 13.2; 31P NMR (162 MHz, CDCl3): d 37.56 (s); IR (KBr) cm1: 3058, 2981, 2934, 1724, 1455, 1438, 1376, 1279, 1259, 1184, 1119, 1073, 1050, 1029, 998, 754, 723, 711, 697; HRMS (ESI): m/z calcd for C20H24O4P: 359.1407 [MþH]þ, found 359.1409; HPLC (Daicel ChiralPak IC-3 column, nhexane/i-PrOH¼75/25), tR1¼45.5 min (major), tR2¼49.0 min (minor), ee¼33%. 4.3.23. Isopropyl 4-(diphenylphosphoryl)-2-oxohexanoate (5u). Procedure 1, white solid (23.4 mg, 63%). [a]20 D ¼64.2 (c 0.32, CHCl3); 1H NMR (400 MHz, CDCl3): d 7.85e7.75 (m, 4H), 7.52e7.42 (m, 6H), 5.07 (heptet, J¼6.2 Hz, 1H), 3.13e3.09 (m, 3H), 1.29 (d, J¼6.2 Hz, 6H), 1.24 (dd, J¼9.2, 5.8 Hz, 2H), 0.85 (t, J¼7.4 Hz, 3H); 13C NMR (101 MHz, CDCl3): d 193.1, 192.9, 164.3, 143.4, 143.3, 132.1, 131.9, 131.3, 129.1, 128.9, 128.5, 107.9, 71.2, 70.4, 39.6, 38.9, 37.6, 34.1, 33.4, 29.8, 21.9, 21.7, 21.5, 13.0, 12.9; 31P NMR (162 MHz, CDCl3): d 37.46 (s); IR (KBr) cm1: 3057, 2981, 2934, 1724, 1455, 1438, 1375, 1278, 1259, 1184, 1119, 1073, 1050, 1029, 998, 754, 723, 697; HRMS (ESI): m/z calcd for C21H26O4P: 373.1563 [MþH]þ, found 373.1567; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-

PrOH¼75/25), tR1¼42.8 min (minor), tR2¼45.4 min (major), ee¼35%. 4.3.24. Isopropyl 4-(diphenylphosphoryl)-5-methyl-2-oxohexanoate (5v). Procedure 1, white solid (22.0 mg, 57%). [a]20 D ¼39.9 (c 0.11, CHCl3); 1H NMR (400 MHz, CDCl3): d 8.11e7.61 (m, 4H), 7.61e7.31 (m, 6H), 5.82 (dd, J¼11.6, 8.5 Hz, 1H), 5.02 (heptet, 6.3 Hz, 1H), 3.61e3.55 (m, 1H), 3.26e3.10 (m, 0.5H), 2.59e2.50 (m, 0.5H), 2.24e2.21 (m, 1H), 1.27 (d, J¼6.2 Hz, 3H), 1.21 (d, J¼6.2 Hz, 3H), 1.09 (d, J¼6.8 Hz, 3H), 0.91 (d, J¼6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3): d 199.6, 164.3, 143.2, 132.4, 131.9, 131.8, 131.6, 131.4, 131.2, 130.9, 129.2, 128.9, 128.4, 128.2, 105.2, 70.6, 43.0, 42.3, 29.9, 29.0, 23.6, 23.4, 21.9, 19.3; 31P NMR (162 MHz, CDCl3): d 35.62 (s); IR (KBr) cm1: 3058, 2963, 2930, 1723, 1466, 1438, 1387, 1375, 1261, 1159, 1116, 1102, 1070, 1027, 998, 923, 748, 723, 698; HRMS (ESI): m/ z calcd for C22H28O4P: 387.1720 [MþH]þ, found 387.1719; HPLC (Daicel ChiralPak IC-3 column, n-hexane/i-PrOH¼75/25), tR1¼30.5 min (major), tR2¼34.1 min (minor), ee¼69%. Acknowledgements This work was partially supported by the National Natural Science Foundation of China (No. 21172143, 21232004, 21172145 and 21372152) and Shanghai Jiao Tong University (SJTU). We also thank the Instrumental Analysis Center of SJTU. Supplementary data Supplementary data associated with this article can be found in the online version, at http://dx.doi.org/10.1016/j.tet.2015.07.026. References and notes 1. For reviews, see: (a) Mikolajczyk, M.; Balczewski, P. Top. Curr. Chem. 2003, 223, 161e214; (b) Shimizu, G. K. H.; Vaidhyanathan, R.; Taylor, J. M. Chem. Soc. Rev. 2009, 38, 1430e1449; (c) Panigrahi, K.; Eggen, M.; Maeng, J.-H.; Shen, Q.; Berkowitz, D. B. Chem. Biol. 2009, 16, 928e936; (d) Demmer, C. S.; KrogsgaardLarsen, N.; Bunch, L. Chem. Rev. 2011, 111, 7981e8006; (e) Gagnon, K. J.; Perry, H. P.; Clearfield, A. Chem. Rev. 2012, 112, 1034e1054; (f) Roy, S.; Caruthers, M. Molecules 2013, 18, 14268e14284; (g) Corbridge, D. E. C., 6th ed;. Phosphorus: Chemistry, Biochemistry and Technology CRC: London, 2013; (h) Pinalli, R.; Dalcanale, E. Acc. Chem. Res. 2013, 46, 399e411; (i) Pradere, U.; Garnier-Amblard, E. C.; Coats, S. J. Chem. Rev. 2014, 114, 9154e9218. 2. (a) Herrmann, W. A. Angew. Chem., Int. Ed. 1991, 30, 818e819; (b) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029e3069; (c) Petz, A.; Kollar, L. Curr. Org. Chem. 2010, 14, 1185e1194; (d) Xie, J.-H.; Zhu, S.-F.; Zhou, Q.-L. Chem. Rev. 2011, 111, 1713e1760; (e) du Mont, W. W.; Gimeno, R. G.; Lungu, D.; Birzoi, R. M.; Daniliuc, C. G.; Goers, C.; Riecke, A.; Bartsch, R. Pure Appl. Chem. 2013, 85, 633e647; (f) Fernandez, E.; Guiry, P. J.; Connole, K. P. T.; Brown, J. M. J. Org. Chem. 2014, 79, 5391e5400; (g) Giri, R.; Thapa, S. Synlett 2015, 709e715. 3. (a) Ribeiro, A. R.; Castro, P. M. L.; Tiritan, M. E. Environ. Chem. Lett. 2012, 10, 239e253; (b) Wan, W. B.; Migawa, M. T.; Vasquez, G.; Murray, H. M.; Nichols, J. G.; Gaus, H.; Berdeja, A.; Lee, S.; Hart, C. E.; Lima, W. F.; Swayze, E. E.; Seth, P. P. Nucleic Acids Res. 2014, 42, 13456e13468; (c) Wiemer, A. J.; Wiemer, D. F. Top. Curr. Chem. 2015, 360, 115e160. 4. (a) Zhao, D.; Wang, R. Chem. Soc. Rev. 2012, 41, 2095e2108; (b) Wauters, I.; Debrouwer, W.; Stevens, C. V. Beilstein J. Org. Chem. 2014, 10, 1064e1096; (c) Allen, D. W. Organophosphorus Chem. 2014, 43, 1e51. 5. (a) Dani, P.; Karlen, T.; Gossage, R. A.; Gladiali, S.; Van Koten, G. Angew. Chem., Int. Ed. 2000, 39, 743e745; (b) Goettker-Schnetmann, I.; White, P.; Brookhart, M. J. Am. Chem. Soc. 2004, 126, 1804e1811; (c) Michael, F. E.; Cochran, B. M. J. Am. Chem. Soc. 2006, 128, 4246e4247; (d) Ito, J.-I.; Ujiie, S.; Nishiyama, H. Chem. Commun. 2008, 1923e1925; (e) Gnanaprakasam, B.; Balaraman, E.; Ben-David, Y.; Milstein, D. Angew. Chem., Int. Ed. 2011, 50, 12240e12244; (f) Wang, T.; Hao, X.-Q.; Zhang, X.-X.; Gong, J.-F.; Song, M.-P. Dalton Trans. 2011, 40, 8964e8976; (g) Hyodo, K.; Nakamura, S.; Shibata, N. Angew. Chem., Int. Ed. 2012, 51, 10337e10341; (h) Li, W.; Xie, J.-H.; Lin, H.; Zhou, Q.-L. Green Chem. 2012, 14, 2388e2390; (i) Ito, J.-I.; Fujii, K.; Nishiyama, H. Chem.dEur. J. 2013, 19, 601e605; (j) Peng, D.; Zhang, Y.; Du, X.; Zhang, L.; Leng, X.; Walter, M. D.; Huang, Z. J. Am. Chem. Soc. 2013, 135, 19154e19166; (k) Srimani, D.; DiskinPosner, Y.; Ben-David, Y.; Milstein, D. Angew. Chem., Int. Ed. 2013, 52, 14131e14134; (l) Wang, T.; Hao, X.-Q.; Huang, J.-J.; Niu, J.-L.; Gong, J.-F.; Song, M.-P. J. Org. Chem. 2013, 78, 8712e8721; (m) Wang, T.; Niu, J.-L.; Liu, S.-L.; Huang, J.-J.; Gong, J.-F.; Song, M.-P. Adv. Synth. Catal. 2013, 355, 927e937; (n) Haibach, M. C.; Lease, N.; Goldman, A. S. Angew. Chem., Int. Ed. 2014, 53, 10160e10163; (o) Kang, P.; Zhang, S.; Meyer, T. J.; Brookhart, M. Angew. Chem.,

Y. Xu et al. / Tetrahedron 71 (2015) 6832e6839

6.

7. 8.

9. 10.

Int. Ed. 2014, 53, 8709e8713; (p) Qu, S.; Dang, Y.; Song, C.; Wen, M.; Huang, K.W.; Wang, Z.-X. J. Am. Chem. Soc. 2014, 136, 4974e4991. (a) Feng, J.-J.; Chen, X.-F.; Shi, M.; Duan, W.-L. J. Am. Chem. Soc. 2010, 132, 5562e5563; (b) Du, D.; Duan, W.-L. Chem. Commun. 2011, 11101e11103; (c) Chen, Y.-R.; Duan, W.-L. Org. Lett. 2011, 13, 5824e5826; (d) Feng, J.-J.; Huang, M.; Lin, Z.-Q.; Duan, W.-L. Adv. Synth. Catal. 2012, 354, 3122e3126; (e) Du, D.; Lin, Z.-Q.; Lu, J.-Z.; Li, C.; Duan, W.-L. Asian J. Org. Chem. 2013, 2, 392e394; (f) Lu, J.; Ye, J.; Duan, W.-L. Org. Lett. 2013, 15, 5016e5019; (g) Huang, J.; Zhao, M.-X.; Duan, W.-L. Tetrahedron Lett. 2014, 55, 629e631; (h) Lu, J.; Ye, J.; Duan, W.-L. Chem. Commun. 2014, 698e700. Huang, M.; Li, C.; Huang, J.; Duan, W.-L.; Xu, S. Chem. Commun. 2012, 11148e11150. (a) Yang, M.-J.; Liu, Y.-J.; Gong, J.-F.; Song, M.-P. Organometallics 2011, 30, 3793e3803; (b) Hao, X.-Q.; Huang, J.-J.; Wang, T.; Lv, J.; Gong, J.-F.; Song, M.-P. J. Org. Chem. 2014, 79, 9512e9530. Hao, X.-Q.; Zhao, Y.-W.; Yang, J.-J.; Niu, J.-L.; Gong, J.-F.; Song, M.-P. Organometallics 2014, 33, 1801e1811. (a) Huang, Y.; Pullarkat, S. A.; Li, Y.; Leung, P.-H. Chem. Commun. 2010, 6950e6952; (b) Huang, Y.; Chew, R. J.; Li, Y.; Pullarkat, S. A.; Leung, P.-H. Org.

6839

Lett. 2011, 13, 5862e5865; (c) Xu, C.; Kennard, G. J. H.; Hennersdorf, F.; Li, Y.; Pullarkat, S. A.; Leung, P.-H. Organometallics 2012, 31, 3022e3026; (d) Huang, Y.; Pullarkat, S. A.; Teong, S.; Chew, R. J.; Li, Y.; Leung, P.-H. Organometallics 2012, 31, 4871e4875; (e) Huang, Y.; Pullarkat, S. A.; Li, Y.; Leung, P.-H. Inorg. Chem. 2012, 51, 2533e2540; (f) Huang, Y.; Chew, R. J.; Pullarkat, S. A.; Li, Y.; Leung, P.H. J. Org. Chem. 2012, 77, 6849e6854; (g) Chew, R. J.; Huang, Y.; Li, Y.; Pullarkat, S. A.; Leung, P.-H. Adv. Synth. Catal. 2013, 355, 1403e1408; (h) Chew, R. J.; Teo, K. Y.; Huang, Y.; Li, B. B.; Li, Y.; Pullarkat, S. A.; Leung, P.-H. Chem. Commun. 2014, 8768e8770; (i) Huang, Y.; Li, Y.; Leung, P.-H.; Hayashi, T. J. Am. Chem. Soc. 2014, 136, 4865e4868. 11. Ding, B.; Zhang, Z.; Xu, Y.; Liu, Y.; Sugiya, M.; Imamoto, T.; Zhang, W. Org. Lett. 2013, 15, 5476e5479. 12. Cat. B was prepared from Cat. A according to the procedure described in the literature.11 13. CCDC 1408771 contains the supplementary crystallo-graphic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.