Stereochemistry of the aldol reaction between [4-t-butyldimethylsilyloxy-5-(3-t-butyldimethylsilyloxyoct-1-enyl)cyclopent-2-enyl]ethanal and cyclopentanone enolates; a key step in the total synthesis of prostacyclin

Abstract

Reactions of lithium, boron, zirconium, and tin enolates derived from cyclopentanone with [4-t-butyldimethylsilyloxy-5-(3-t-butyldimethylsilyloxyoct-1-enyl)cyclopent-2-enyl]ethanal (6) gave mainly the 5R, 6R, and 5S, 6S(prostaglandin numbering), threo-adducts, regardless of the nature of the enolate; the highest yield of threo-products (83% of a total yield of 93%) was obtained with lithium enolate in pentane at –78 °C. In contrast, the ratio of 5R,6R to 5S,6S products was significantly affected by the nature of the enolate, ranging from ca. 1:1.3 with a boron enolate to ca. 1:3 with a tin enolate, and ca. 1:4 with a lithium enolate.