Enantio- and Diastereoselective Additions to Aldehydes Using the
Bifunctional Reagent
2-(Chloromethyl)-3-(tributylstannyl)propene: Application to a
Synthesis of the C16-C27 Segment of Bryostatin 1
Gary E. Keck,*Tao Yu, andMark D. McLaws
Department of Chemistry, University of Utah, Salt Lake City, Utah 84112
keck@chemistry.utah.edu
Received September 22, 2004
Abstract:
Reactions of the bifunctional allylstannane 2-(chloromethyl)-3-(tributylstannyl)propene with aldehydes have been examined. These generally occur in high yields using Lewis acid promoters and
the products can be isolated and purified without incident. Good yields and high enantioselectivities
are also realized in catalytic asymmetric allylations (CAA reactions) using the previously described
BITIP catalyst system. Protection of the free hydroxyl can be accomplished without cyclization to
the derived tetrahydrofuran, although this transformation is also facile. The utility of the
incorporated allyl chloride functionality allows for the obvious use of such products in reactions
with nucleophiles. Use of these products in a less obvious connective strategy is demonstrated in
the synthesis of the C12-C27 segment of bryostatin 1 where a connective, or "lynchpin", double-allylation process was employed. The -hydroxy allyl chloride obtained from an initial chelation-controlled allylation of aldehyde 16 was converted to allylstannane 19 and applied in a second
allylation reaction, thus allowing for a highly convergent synthesis of the bryostatin C ring backbone
in a stereoselective fashion.
and
-hydroxy allyl chloride obtained from an initial chelation-controlled allylation of aldehyde 16 was converted to allylstannane 19 and applied in a second
allylation reaction, thus allowing for a highly convergent synthesis of the bryostatin C ring backbone
in a stereoselective fashion.
