Studies on the factors controlling the stereoselectivity in electrophilic iodocyclization of alkylidenecyclopropyl ketones

An efficient electrophilic iodocyclization of alkylidenecyclopropyl ketones with N-iodosuccinimide (NIS) or I2 in aqueous CH3CN affording 3-oxabicyclo[3.1.0]hexan-2-ols is described. NIS is a better electrophilic iodocyclization reagent than I2. Four chiral centers were formed within one step. The stereochemistry was established by the X-ray diffraction studies of compounds 2e–2h, 2n, and 2c. It is quite interesting to observe that the substituent of the cyclopropane ring plays an important role in determining the relative stereochemistry at the 4-position: with R2 being an acyl or ester group a mixture of (1S∗,2R∗,4S∗,5R∗)-2 (major) and (1R∗,2R∗,4R∗,5R∗)-2 (minor) was formed with moderate selectivity while the reaction of the substrates with R2 being sulfonyl and p-methylphenylsulfonyl or R1 being phenyl afforded (1R∗,2R∗,4S∗,5S∗)-2 or (1S∗,2R∗,4S∗,5R∗)-2f as the only product. The reaction is general for a range of different substrates to afford the products in moderate to high yields.