Trapping of Oxonium Ylides with Michael Acceptors: Highly Diastereoselective Three-Component Reactions of Diazo Compounds with Alcohols and Benzylidene Meldrum’s Acids/4-Oxo-enoates

Abstract

Trapping of oxonium ylides with a number of Michael acceptors via a 1,4-addition fashion has been investigated. Benzylidene Meldrum’s acids and 4-oxo-enoates have been found to be matched components as suitable Michael acceptors for the transformation. Thus, Rh₂(OAc)₄-catalyzed three-component reactions of diazo compounds, alcohols, and benzylidene Meldrum’s acids/4-oxo-enoates gave corresponding α-hydroxyesters in good yield with high to excellent diastereoselectivity. Synthetic utility of this efficient method was demonstrated by conversion of the addition product to a γ-butyrolactone through simple procedures.

Key words

oxonium ylide - multicomponent reaction - benzylidene Meldrum’s acid - 4-oxo-enoates - 1,4-addition

References and Notes

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General Procedure for Trapping Oxonium Ylides with Michael Acceptors
A suspension of Rh₂(OAc)₄ (8.8 mg, 1 mmol%), alcohols 3 (0.24 mmol, 1.2 equiv), Michael acceptors 1 (0.2 mmol, 1 equiv) in CH₂Cl₂ (3 mL) under argon atmosphere was stirred at r.t., and then diazo compound 2 (0.24 mmol, 1.2 equiv) in CH₂Cl₂ (4 mL) was added over 2 h via a syringe pump. After completion of the addition, the reaction was stirred for another 0.5 h. The crude product was subjected to ^¹H NMR spectroscopy analysis for the determination of diastereo-selectivity. The reaction mixture was purified by flash chromatography on silica gel (eluent: EtOAc-light PE = 1:20 to ca. 1:10) to give pure products.

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Analytical Data for (2 S *,3 R *)-Methyl 2-(Benzyloxy)-3-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)-3-(4-methoxy-phenyl)-2-phenylpropanoate (4gf)
^¹H NMR (400 MHz, CDCl₃): δ = 7.42-6.64 (m, 14 H), 5.08 (s, 1 H), 4.60-4.58 (d, 1 H), 4.09-4.06 (d, 1 H), 4.04 (s, 1 H), 3.78 (s, 3 H), 3.73 (s, 3 H), 1.66 (s, 3 H), 1.30 (s, 3 H). ^¹³C NMR (100 MHz, CDCl3): δ = 170.32, 165.78, 165.70, 158.51, 138.00, 137.74, 131.32, 129.80, 129.73, 129.07, 128.92, 128.66, 128.61, 128.56, 128.50, 128.14, 127.46, 126.60, 112.80, 104.40, 86.33, 68.97, 56.08, 55.01, 51.61, 48.64, 27.50, 27.42. ESI-HRMS: m/z calcd for C₃₀H₃₀NaO₈ [M + Na]⁺: 541.1838; found: 541.1800.

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Crystallographic Data for Compound 4gb Empirical formula: C₂₉H₂₇NO₉, CCl₄; formula weight: 685.04; bond precision: C-C = 0.0040 Å; λ = 0.71073 Å; unit cell dimensions: a = 14.3476 (4) Å, α = 90˚, b = 10.1897 (3) Å, β = 94.419 (1)˚, c = 20.8480 (5) Å, γ = 90˚; temp: 296 K; volume: 3038.87 (14) A^³, space group: P2 (1)/c; Z = 4; F(000) = 1280.0; h,k,l _max = 17, 12, 24; N _ref = 5339; T _min, T _max = 0.881, 1.000; correction method: MULTI-SCAN; data completeness = 0.997; θ _max = 25.010; R(reflections) = 0.0466 (3695); wR2 = 0.1310 (5339); S = 1.034; N _par = 398. CCDC 822168 contains the supplementary crystallographic data for this structure. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

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Analytical Data for (2R*,3S*)-2-Benzyloxy-3-(2-oxo-2-phenyl-ethyl)-2-phenyl-succinic Acid Dimethyl Ester (4ha)
^¹H NMR (400 MHz, CDCl₃): δ = 7.92-7.85 (m, 2 H), 7.58-7.50 (m, 3 H), 7.48-7.24 (m, 10 H), 4.57 (d, J = 11.9 Hz, 1 H), 4.33 (d, J = 11.9 Hz, 1 H), 4.26 (dd, J = 10.7, 2.7 Hz, 1 H), 3.93 (s, 3 H), 3.67 (s, 3 H), 3.55 (dd, J = 18.1, 10.7 Hz, 1 H), 3.15 (dd, J = 18.1, 2.7 Hz, 1 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 197.74, 172.32, 171.10, 138.30, 136.52, 135.41, 133.15, 128.75, 128.49, 128.45, 128.24, 128.08, 127.76, 127.30, 126.88, 85.84, 67.83, 52.45, 52.09, 50.69, 37.02. ESI-HRMS: m/z calcd for C₂₇H₂₆NaO₆ [M + Na]⁺: 469.1627; found: 469.1611.

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Crystallographic Data for Compound 4ha Empirical formula: C₂₇H₂₆O₆; formula weight: 446.48; temp: 293 (2) K; λ = 0.71073 Å; crystal system space group: monoclinic, P2 (1)/c; unit cell dimensions: a = 11.0595 (9) Å, α = 90˚, b = 12.4819 (10) Å, β = 106.3950 (10)˚, c = 17.3890 (14) Å, γ = 90˚; volume: 2302.8 (3) A^³, Z = 4; calcd density = 1.288 mg/m^³; absorption coefficient = 0.091 mm^-¹, F(000) 472; crystal size = 0.385 × 0.316 × 0.257 mm; θ range for data collection: 1.96-26.00˚; limiting indices, -13 ≤ h ≤ 13, -11 ≤ k ≤ 15, -17 ≤ l ≤ 21, reflections collected/unique: 12323/4530 [R(int) = 0.0223]; completeness to = 26.00, 100.0%; absorption correction: empirical; max. and min. transmission =: 1.00000 and 0.75342; refinement method, full-matrix least-squares on F^²; data/restraints/parameters, 4530/0/300; goodness-of-fit on F2, 1.020; final R indices [I > 2σ(I)], R1 = 0.0439, wR2 = 0.1097, R indices (all data), R1 = 0.0554, wR2 = 0.1171; largest diff. peak and hole, 0.180 and -0.151 e A^-³. CCDC 812578 contains the supplementary crystallographic data for this structure. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.