シス-2-フルオロシクロプロパンカルボン酸の立体選択的な合成

抄録

cis-2-Fluorocyclopropanecarboxylic acid (cis-FCpCA) is a key intermediate for the synthesis of an antibacterial agent Sitafloxacin, therefore many synthetic efforts for the synthesis of dl-cis-FCpCA have been reported so far. We herein report an efficient stereoselective synthesis of dl-cis-FCpCA. The strategy for the synthesis of dl-cis-FCpCA derives from employment of stereoselective rhodium-catalyzed cyclopropanation reaction of (1-fluorovinylsulfonyl)benzene (1) with diazo esters 2. The cyclopropanation reaction of 1 with tert-butyl diazoacetate catalyzed by [Rh(O2CCPh3)2]2 proceeded stereoselectively to the desired tert-butyl trans-2-fluoro-2-phenylsulfonylcyclopropane carboxylate (trans-3, R = tert-Bu) in an 80% yield (trans:cis = 93:7). The synthesis of dl-cis-FCpCA was completed by reductive cleavage of a phenylsulfonyl group of trans-3 and subsequent hydrolysis of an ester group.