THE CATALYTIC, ENANTIOSELECTIVE FAVORSKII REACTION: IN SITU FORMATION OF METAL ALKYNYLIDES AND THEIR ADDITIONS TO ALDEHYDES

摘要

In 1905, Alexei Y. Favorskii (originally spelled Favorsky) reported the action of potassium hydroxide on mixtures of phenylacetylene and aldehydes or ketones to furnish propargylic alcohol adducts (Scheme l).1'2 Favorskii's unsung, eponymous reaction has had significant impact on synthetic chemistry. Although the "classic" Favorskii reaction, which involves stoichiometric amounts of potassium hydroxide, often suffers from competitive formation of aldol condensation byproducts, as well as other degradation pathways (owing to the large amount of base employed), the propargylic alcohol adducts obtained as the primary products are versatile and useful building blocks. Propargylic alcohols have been widely employed as key intermediates in various syntheses of complex natural products and pharmaceutical targets.3-5 Moreover, it is historically interesting to note that the term "propargyl" dates to the mid-19th century. This portmanteau fuses propyne and argentum and alludes to the known metalation reaction of terminal alkynes with silver salts to produce silver alkynylides, as first noted by Berthelot in 1866.