REGIOCHEMICAL CONTROL OF THE RING-OPENING OF 1,2-EPOXIDES BY MEANS OF CHELATING PROCESSES - SYNTHESIS AND REACTIONS OF THE CIS-OXIDES AND TRANS-OXIDES DERIVED FROM 4-(BENZYLOXY)CYCLOHEXENE

The synthesis and reactions of diastereomeric epoxides cis-1 and trans-2 with heteronucleophiles were carried out in order to probe the effect of remote polar functionality on the regioselectivity of nucleophilic addition to the epoxide ring. The reaction of cis-epoxide 1 with TiCl4in CH2C12 gave exclusively the chlorohydrin 7, whereas the regioisomeric chlorohydrin 6 was obtained as the main product from the reaction of 1 with HC1 in CHC13. The same reactions with epoxide 2 yielded chlorohydrins 8 and 9, the main product being 8 in both cases. Chlorohydroxylation of olefin 3 via Sharpless conditions (TiCl4and TBHP) gave 7, 8, and 9 in a 96:6:2 ratio. The regiochemical outcome of ring-opening addition reactions with epoxide 2 is necessarily independent of any bidentate chelation effects; however, in some of the comparable nucleophilic reactions of epoxide 1, chelation of the counterion by the oxirane oxygen and the remote benzyloxy group can substantially alter the regioselectivity of addition. Thus, the 10:11 regioisomeric ratio (85:15) obtained from the H+-catalyzed methanolysis of 1 was completely inverted (2:98) when the solvolysis was carried out with concentrated methanolic LiC104. The ring-opening of 1 with LiAlH4afforded 14 and 15 in a 2:98 ratio; however, reaction of 1 with premixed LiAlH4/12-crown-4 gave the opposite result, 14:15 = 82:18. In all of the addition reactions of 1 and 2 the ring-opened products were consistent with the well-known preference for diaxial nucleophilic ring-opening in cyclohexene oxides derivatives; our results are further interpreted as evidence for chelation control in some of the addition reactions of 1. © 1990, American Chemical Society. All rights reserved.