Unusual Strain-Releasing Nucleophilic Rearrangement of a Bicyclo[2.2.1]heptane System to a Cyclohexenyl Derivative

Abstract

We report an unusual strain-releasing reaction of 1-mesyloxy-8,7-dimethylbicyclo[2.2.1]heptane (3) by a base-promoted substitution at the chiral C3 followed by spontaneous concerted ring opening involving the most strained C2-C3-C4 bonds (with bond angle 94°) and the C2 bridgehead leading to anti-endo elimination of the C1-mesyloxy group by the conjugate base of adenine or thymine to give two diastereomeric C3'(S) and C3'(R) derivatives of 1-thyminyl and 9-adeninyl cyclohexene: 3 → T-4a + T-4b and 3 → A-5a + A-5b. These products have been unambiguously characterized by detailed 1D and 2D NMR (J-coupling constants and nOe analysis), mass, and UV spectroscopy. Evidence has been presented suggesting that the origin of these diastereomeric C3'(S) and C3'(R) derivatives of 1-thyminyl and 9-adeninyl cyclohexene from 3 is most probably a rearrangement mechanism of a trigonal bipyramidal intermediate formed in the S(N)2 displacement-ring-opening reaction.