Alkenylzinc reagents, asymmetric additions, aldehydes

Scheme 2.1.3.5 Asymmetric addition of alkenylzinc reagents to aldehydes [18].

Over the last five years, we have designed, synthesized, and applied new ligands for asymmetric 1,2- and 1,4-addition reactions. Suitable ligands were found for the addition of alkyl-, aryl-, and alkenylzinc reagents to a,(3-unsaturated aldehydes and ketones, a-branched and unbranched aliphatic aldehydes, and imines. Although some substrates such as ketones and other carbonyl compounds have remained a challenge, we believe that this system provides an excellent entry into various classes of chiral intermediates. Application of these synthesized complex molecules is the current pursuit in our laboratories. 

Addition of alkenylzinc 322 to the aldehyde 321 resulted in a diastere-omer mixture (1 1) of allylic alcohol, which was oxidized to afford ketone 303. Although Terashima s asymmetric aluminum reagent did not give the desired alcohol, the asymmetric borohydride reduction catalyzed by the Corey-Bakshi-Shibata reagent gave a 5 1 mixture of separable diastereomers, in favor of the (17J )-alcohol 323. Finally, protective group manipulation and oxidations led to a seco-acid, which was subjected to Yonemitsu-modified Ya-maguchi macrolactonization to yield the macrocycle (201) (Scheme 68). 

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