Stereoselective Synthesis of Conjugated Fluoro Enynes

Metalation–electrophilic fluorination of TMS-
and TIPS-protected
1,3-benzothiazol-2-yl (BT) propargyl sulfones gave corresponding BT
fluoropropargyl sulfones, Julia–Kocienski reagents for the
synthesis of fluoro enynes. Both reagents reacted with aldehydes under
mild DBU- or LHMDS-mediated conditions, giving high yields of conjugated
fluoro enynes with E-stereoselectivity. In comparison
to DBU-mediated reactions, stereoselectivity was higher in low-temperature
LHMDS-mediated reactions. Two ketones were shown to react as well,
using LHMDS as base. In situ removal of the TMS group gave terminal
conjugated 2-fluoro 1,3-enynes. Synthetic utility of the fluoro enynes
was demonstrated by conversion to internal alkynes and to stereoisomeric
fluoro dienes via Sonogashira and Heck couplings.