Chiral Polyoxygenated Tertiary Alcohols through Kiyooka Aldol Reaction

Abstract

Here we present our work on a Kiyooka aldol protocol for the stereoselective synthesis of tertiary alcohols. In the obtained products, three oxygenated carbon atoms that could further be differentiated flank the chiral tertiary alcohol. This methodology can be applied to simple aromatic or aliphatic aldehydes and more complex substrates bearing a chiral center in the α and/or β-position. For complex substrates, an unexpected dependency between stereoselectivity and double bond geometry of the ketene acetal was observed. Furthermore, applications in or towards the synthesis of natural products are presented. 1 Introduction 2 Scope of the reaction 3 Synthetic applications 4 Conclusion

Development of the Synthesis of Desepoxy-Tedanolide C

“…The synthesis of 25 (Scheme 5) started with commercially available crotonaldehyde (26) that was first subjected to a Kiyooka aldol reaction 17 with ketene acetal 27 installing the secondary and tertiary alcohol in a stereoselective way. 16,18 Subsequent base-initiated silyl migration lead to aldehyde 28.…”

“…The synthesis of 25 (Scheme ) started with commercially available crotonaldehyde ( 26 ) that was first subjected to a Kiyooka aldol reaction with ketene acetal 27 installing the secondary and tertiary alcohol in a stereoselective way. , Subsequent base-initiated silyl migration lead to aldehyde 28 . Prior to the addition of ethylmagnesium bromide, aldehyde 28 had to be premixed with anhydrous cerium trichloride to suppress the otherwise occurring reduction to alcohol 29 (obtained in 20–30% without the use of CeCl 3 ) .…”

“…For the synthesis of northern fragment 11 (Scheme 2), literature known carboxylic acid 17 13 was first accessed from readily available 16 in a five step sequence. Subsequent esterification with allylic alcohol (18) provided 11 in 78% yield.…”