SYNTHESIS OF OPTICALLY-ACTIVE CIS- AND TRANS-1,2-DISUBSTITUTED CYCLOPROPANE DERIVATIVES BY THE SIMMONS-SMITH REACTION OF ALLYL ALCOHOL DERIVATIVES DERIVED FROM (R)-2,3-O-ISOPROPYLIDENEGLYCERALDEHYDE

The Simmons-Smith reactions of Z- and E-allyl alcohol derivatives 6 derived from (R)-2,3-O-isopropylideneglyceraldehyde (5) were used for the synthesis of optically active cis- and trans-1,2 disubstituted cyclopropane derivatives. Reaction of 6 with diethyl zinc and diiodomethane gave cyclopropane derivatives 7 in 84% to quantitative yields with 35 to approximate to 100% des. Identical facial selectivities toward the double bonds, Ire-asi for Z-6 and 1re-2re for E-6, were observed in the cyclopropanations. The diastereoselectivity was dependent on the protecting group on the terminal allylic oxygen (R of 6, TBDPS > MOM > Bn) and on the stereochemistry of the double bond (Z > E). For TBDPS ethers Z- and E-6c, cis- and trans-7c were obtained as single diastereomers respectively. It was clearly demonstrated that the stereoselectivity of the cyclopropanation is controlled by the directing effect of the allylic oxygen (O-1) of the dioxolane ring which coordinates to the reagent. The terminal allylic oxygen (O-2) lowered the diastereoselectivity This reaction was applied to the synthesis of optically active cyclopropane analogs of gamma-aminobutyric acid (GABA) 18, 22, and ent-22.