Iodocyclization of Allylic Alcohol Derivatives Containing Internal Nucleophiles. Control of Stereoselectivity by Substituents in the Acyclic Precursors

The effect of various substituents on the diastereoselectivity of a number of kinetically controlled iodocyclizations has been studied. The reaction of 3-hydroxy-4-alkenoic acids (1a-n) with iodine in a neutral two-phase medium gives stereoselective ring closure, usually to the m-3-hydroxy-4-iodoalkyl lactone. The stereoselectivity is unaffected by protection of alcohol moiety (lb,c), but replacement of the hydroxyl group with a methyl substituent (1e) lowers the stereoselectivity significantly. A 2-methyl substituent (1j-m) can have a dramatic effect on the diastereoselectivity of the reaction. Esters and ketones (l0a-c) undergo a related iodocyclization with similar stereoselectivity. In the absence of an internal nucleophile (13,16) iodohydrin formation results in reversed diastereoselectivity of iodine attack.