Enantioselective Synthesis of the C1-C15 Fragment of Dolabelide C

Abstract

A synthesis of the C1-C15 fragment of dolabelide C is reported. The key step is a diastereoselective Mukaiyama aldol ­reaction to form the C6-C7 bond, followed by reduction and ­deoxygenation of the carbonyl group at C5. The trisubstituted vinyl iodide is introduced via the corresponding vinyl boronate by cross metathesis.

Key words

stereoselective synthesis - aldol reactions - metathesis - Michael additions - acetals

References and Notes

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21

This reaction has not been optimized.

23

Spectroscopic data for compound 23: ¹H NMR (400 MHz, CDCl₃): δ = 7.51 (dd, J = 7.9, 1.5 Hz, 2 H, Ph), 7.35-7.40 (m, 3 H, Ph), 7.27 (d, J = 8.6 Hz, 2 H, PMB), 6.86 (d, J = 8.6 Hz, 2 H, PMB), 5.94 (dd, J = 2.1, 1.3 Hz, 1 H, CH-15), 5.48 (s, 1 H, CHPh), 4.53 (d, J = 10.8 Hz, 1 H, CHHPh), 4.49 (d, J = 11.0 Hz, 1 H, CHHPh), 3.98-4.18 (m, 2 H, CH-7, CH-9), 3.78-3.82 (m, 1 H, CH-11), 3.79 (s, 3 H, OCH₃), 3.72 (dd, J = 9.6, 5.2 Hz, 1 H, CH-1), 3.63 (dd, J = 9.6, 3.0 Hz, 1 H, CH-1), 3.27 (dd, J = 8.7, 2.2 Hz, 1 H, CH-3), 2.35-2.48 (m, 2 H, CH₂-13), 1.87 (d, J = 1.2 Hz, 3 H, CH₃-14), 1.78-1.84 (m, 2 H, CH-2, CH-12), 1.30-1.75 (m, 10 H, CH-4, CH₂-5, CH₂-6, CH₂-8, CH₂-10, CH-12), 0.89-0.97 [m, 24 H, SiC(CH₃)₃, CH₃-2, CH₃-4], 0.09, 0.08, 0.06 [s, 12 H, Si(CH₃)₂]. ¹³C NMR (100 MHz, CDCl₃): δ = 147.6 (C-14), 158.9, 138.9, 131.6, 129.1, 128.5, 128.1, 126.0, 113.7 (Ar), 100.2 (CHPh), 83.6 (C-3), 75.9 (C-11), 74.9 (C-15), 74.5 (CH₂Ph), 73.0 (C-9), 67.9 (C-7), 65.0 (C-1), 55.3 (OCH₃), 43.3 (C-6), 38.6 (C-2), 37.5 (C-10), 36.3 (C-8), 35.6 (C-4), 35.1 (C-13), 33.9 (C-12), 29.6 (C-5), 26.0 [SiC(CH₃)₃], 24.0 (CH₃-14), 18.3, 18.1 (SiC), 14.7 (CH₃-2), 13.5 (CH₃-4), -4.1, -4.5, -5.3, -5.4 [Si(CH₃)₂]. HRMS (EI): m/z calcd for C₄₅H₇₅O₆I₁Si₂: 894.4147; found: 894.4155.