Stereoselective Synthesis of Highly Substituted Annulated Dihydropyrans Based on γ-Lithiation and Homoaldol Reaction of an Enantiopure α-Silylated Vinyl Carbamate

Abstract

The N,N-diisopropylcarbamate of (-)-myrtenol is converted into the corresponding [1-(trimethylsilyl)vinyl] carbamate. Its γ-lithiation by means of sec-butyllithium/TMEDA, titanation, and addition to aldehydes leads with high stereoselectivity to enantiopure anti-homoaldol products. These add, under the influence of boron trifluoride-diethyl ether complex, a second equivalent of aldehyde and form, in an intermolecular silyl-Prins reaction, the title compounds, again with essentially complete stereoselectivity. After desilylation, the reaction takes the regular course with formation of an annulated five-membered ring.

chiral allyl carbamates - vinyl carbamates - diastereo­selective γ-lithiation - aldehyde addition - annulated dihydropyrans

References

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X-ray crystal structure analysis.

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X-ray crystal structure analysis for 12: formula C₂₀H₃₇NO₂Si, M = 351.60, colorless crystal 0.40 × 0.10 × 0.07 mm, a = 10.6208 (3), b = 7.4155 (2), c = 14.7983 (5) Å, β = 108.749 (2)˚, V = 1103.65 (6) Å^³, ρ_calc = 1.058 g cm^-³, µ = 1.010 mm^-¹, empirical absorption correction (0.688 ≤ T ≤ 0.933), Z = 2, monoclinic, space group P2₁ (No. 4), λ = 1.54178 Å, T = 223 K, ω and φ scans, 6133 reflections collected (±h, ±k, ±l), [(sinθ)/λ] = 0.60 Å^-¹, 2594 independent (R _int = 0.041) and 2497 observed reflections [I ≥ 2 σ(I)], 226 refined parameters, R = 0.044, wR ^² = 0.123, Flack parameter 0.01 (4), max. residual electron density 0.16 (-0.16) e Å^-³, hydrogen atoms calculated and refined as riding atoms.

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