Dess-Martin Periodinane Promoted Oxidative Coupling of Baylis-Hillman Adducts with Silyl Enol Ethers: A Novel Synthesis of cis-Fused Dihydropyrans

Abstract

Baylis-Hillman adducts undergo smooth oxidative Mukaiyama-Michael addition and a subsequent cyclization with silyl enol ethers in the presence of Dess-Martin periodinane (DMP) and pyridine under mild reaction conditions to afford a new class of dihydropyran derivatives in good yields with high diastereoselectivity. This is the first report on the preparation of cis-fused dihydropyrans from Baylis-Hillman adducts and silyl enol ethers.

Baylis-Hillman adducts - hypervalent iodine - enol ethers - oxidative Mukaiyama-Michael addition

References and Notes

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11

General Experimental Procedure
A mixture of Baylis-Hillman adduct (1 mmol), DMP (1.2 mmol), and pyridine (1.5 mmol) in anhyd CH₂Cl₂ (10 mL) was stirred at r.t. until complete oxidation took place. To this, trimethylsilyl enol ether (1.5 mmol) was added and stirred until complete addition (as indicated by TLC) took place. The reaction mixture was diluted with H₂O (50 mL) and extracted with Et₂O (3 × 15 mL). The combined ether layer was washed with sat. aq NaHCO₃ soln (1 × 15 mL), brine (1 × 10 mL), dried over Na₂SO₄, and evaporated. The crude product was purified by silica gel column chromatography using a gradient mixture of hexane-EtOAc (9:1) as eluent to afford pure substituted dihydropyran derivatives.
Spectral Data of Selected Compounds
Compound 3a (Table [1] ): colorless liquid. IR (KBr): ν_max = 2954, 2838, 1738, 1454, 1234, 1207, 1153, 1017, 781 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 0.0 (s, 9 H), 1.20-1.58 (m, 8 H), 1.61-1.76 (m, 1 H), 2.06 (dd, 1 H, J = 1.4, 16.4 Hz), 2.56 (dd, 1 H, J = 5.8, 16.8 Hz), 3.32 (s, 3 H), 7.14-7.18 (m, 5 H). ESI-MS: m/z = 361 [M + 1], 383 [M + Na]. HRMS:
m/z calcd for C₂₀H₂₈O₄NaSi: 383.1654; found: 383.1641.
Compound 3b (Table [1] ): ¹H NMR (600 MHz, CDCl₃): δ = 7.33 (m, 5 H, Ph), 3.92 (q, 2 H, J = 7.2 Hz, OCH₂), 2.72 (dd, 1 H, J = 16.7, 6.2 Hz, H6), 2.23 (dd, 1 H, J = 16.7, 2.0 Hz, H6′), 2.12 (dt, 1 H, J = 13.0, ca. 3.6 Hz, H1e), 1.85 (dddd, 1 H, J = 10.5, 6.2, 4.2, 2.0 Hz, H5a), 1.65 (m, 1 H, H3e), 1.62 (m, 1 H, H2e), 1.57 (m, 1 H, H4e), 1.55 (dt, 1 H, J = 3.8, ca. 12.8 Hz, H1a), 1.44 (tq, 1 H, J = ca. 3.5, ca. 12.6 Hz, H2a), 1.34 (dq, 1 H, J = 3.2, ca. 12.3 Hz, H4a), 1.28 (m, 1 H, H3a). 0.91 (t, J = 7.2 Hz, 1 H, CH₃), 0.15 (s, 9 H, 3 × CH₃).
Compound 3f (Table [1] ): colorless liquid. IR (KBr): ν_max = 3029, 2948, 2865, 1718, 1495, 1265, 1217, 1137, 1037, 854 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.0 (s, 9 H), 1.80 (ddd, 1 H, J = 1.8, 5.6, 13.4 Hz), 2.21 (ddd, 1 H, J = 3.5, 5.4, 13.4 Hz), 2.52 (ddd, 1 H, J = 3.5, 5.6, 16.9 Hz), 2.66 (ddd, 1 H, J = 5.4, 11.3, 16.8 Hz), 3.59 (s, 3 H), 7.07-7.13 (m, 5 H), 7.22 (td, 1 H, J = 1.1, 7.9 Hz), 7.3-7.43 (m, 6 H), 7.50 (dd, 2 H, J = 1.5, 7.7 Hz). HRMS: m/z calcd for C₂₈H₃₁O₅Si: 475.1940; found: 475.1954.
Compound 3h (Table [1] ): colorless liquid. IR (KBr): ν_max = 2928, 2857, 1715, 1504, 1433, 1151, 1039, 754 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.0 (s, 9 H), 0.78 (t, 3 H, J = 6.8 Hz), 1.10-1.27 (m, 6 H), 1.33-1.72 (m, 6 H), 1.86-2.02 (m, 1 H), 2.07 (dd, 1 H, J = 6.0, 12.0 Hz), 2.16 (dd, 1 H, J = 6.0, 12.0 Hz), 3.55 (s, 3 H).
Compound 4 (Scheme [2] ): colorless liquid. IR (KBr): ν_max = 2920, 2851, 1739, 1683, 1506, 1443, 1226, 1157, 1019, 755 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.20-2.39 (m, 2 H), 2.94-3.19 (m, 2 H), 3.61 (s, 3 H), 4.67 (dd, 1 H, J = 6.0, 7.5 Hz), 7.33-7.52 (m, 5 H), 7.87 (d, 2 H, J = 7.5 Hz), 7.99 (d, 2 H, J = 9.0 Hz). ESI-MS: m/z = 345 [M + 1], 367 [M + Na]. HRMS: m/z calcd for C₁₉H₁₇O₄NaCl: 367.0713; found: 367.0715.

12 Horiguchi Y. Sano T. Tsuda Y. Chem. Pharm. Bull.  1996,  44:  670