Homoallyl alcohols aldol equivalents

Studies on the stereochemical outcome of the reaction of 2-alkenyl organometallic reagents with aldehydes have increased recently, largely because stereoselectively produced homoallylic alcohols are synthetically equivalent, by cleavage at the carbon-carbon double bond, to the type of aldol adduct stereoisomers required for macrolide antibiotic total synthesis. A new stereoselective synthesis of (Z)-2-alkenyltins (46a) or the corresponding silanes (46b) from allyl or vinyl 9-BBN derivatives has appeared (Scheme 20). The... 

The Lewis-acid-catalyzed carbonyl-ene reaction represents an important alternative method for the addition of an allyl group to a carbonyl group (Equation 23). The resulting secondary homoallylic alcohols are amenable to a number of structural modifications and constitute useful synthetic building blocks. Because the olefin of the products can be a surrogate for a carbonyl functionality, these homoallylic alcohol are formally the synthetic equivalent of aldol addition products. Powerful asymmetric versions of the carbonyl-ene reaction [196, 197] provide an important alternative to the more traditional allylation methods, which primarily employ silanes, boranes, or stannanes (see Chapter 5). 

With this preliminary phase of synthetic work accomplished, the more intriguing elements of the anticipated epothilone A synthesis could now begin in earnest. As shown in Scheme 21, the initial merger of fragments 61, 63, and 64 into advanced intermediate 60 proceeded quite smoothly. Treatment of 63 with 2,3 equivalents of LDA in THF at —78°C with warming to —40°C over one hour (to effect both deprotonation of the free acid and formation of the enolate) was followed by the addition of 1.6 equivalents of aldehyde 64, leading to a facile aldol reaction which provided 62 and its C6—C7 syn diastereomer in a 3 2 ratio that favored the desired drawn product. This mixture was carried forward and the acid was esterified directly with the homoallylic thiazole alcohol 61 in the presence of DCC and 4-DM AP to afford, after chromatographic separation, pure 60 (in 52 % yield firom 63) and its alternative syn disposed C6—C7 isomer (in 31 % yield from 63). 

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