Cyclopentanoids from phenol. VI. Chiral prostanoid intermediates

Abstract

(4S)-4-(t-Butyldimethylsilyloxy)-3-chlorocyclopent-2-enone (3a) is prepared from phenol in five steps including resolution of the initial ring-contraction product, (1RS,4RS)-3,5,5-trichloro- 1,4-dihydroxycyclopent-2-ene-1-carboxylic acid [(1) + (2)]. Conjugate addition-elimination reactions of functionalized alkylmagnesiocuprate reagents with the synthon (3a) lead to 3-substituted (4s)-4-hydroxycyclopent-2-enone derivatives, and thence by stereospecific transposition of the ring oxygen functions to 2-substituted (4R)-4-hydroxycyclopent-2-enones. The efficiency and versatility of the route are demonstrated by synthesis of the (4R)-2-(6-methoxycarbonylhexyl)- and (4R)-2-(7-hydroxy- heptyl)-4-hydroxycyclopent-2-enone derivatives, (5b) and (6b) respectively, which are important intermediates in prostaglandin and prostanoid synthesis.