Diastereo- and Enantioselective Ruthenium-Catalyzed Hydrohydroxyalkylation of 2-Silyl-butadienes: Carbonyl syn-Crotylation from the Alcohol Oxidation Level

Abstract

Exposure of alcohols 2a–2j to 2-silyl-butadienes in the presence of ruthenium complexes modified by (R)-SEGPHOS or (R)-DM-SEGPHOS results in redox-triggered generation of allylruthenium–aldehyde pairs, which combine to form products of carbonyl crotylation 4a–4j in the absence of stoichiometric byproducts and with high levels of syn-diastereo- and enantioselectivity. In the presence of isopropanol under otherwise identical conditions, aldehydes 3a–3j are converted to an equivalent set of adducts 4a–4j. Whereas reactions conducted using conventional heating require 48 h, microwave irradiation enables full conversion in only 4 h. Finally, as illustrated in the conversion of adduct 4a to compounds 6a and 6b, diastereoselective hydroboration–Suzuki cross-coupling with aryl and vinyl halides followed by Fleming–Tamao oxidation enables generation of anti,syn-stereotriads found in numerous polyketide natural products.