Homeomorphic Isomerism in a Peptidic Macrobicycle

摘要

Bicyclic molecules with sp~2-hybridized carbon bridgehead atoms exhibit an unusual form of isomerism, since such molecules can exist as in-in (1), out-out (2), or in-out isomers (3 and 4) (Scheme l). In principle, isomers (atropisomers) 1 and 2 caninterconvert when one of'the chains slips through the center of the ring it bridges, effectively turning the molecule inside out--a process referred to as homeomorphic isomerization. A similar homeomorphic isomerization is also possible for the in-out isomers 3 and 4, although these two structures are degenerate unless one of the chains is appropriately labeled, since the sense of each bridgehead is simply exchanged. Although a number of possible isomers of bicyclic systems with sp~3-hybridized carbon bridgehead atoms have been prepared, interconver-sion of such compounds by homeomorphic isomerization has rarely been reported. In-out homeomorphic isomerism was first observed for large bicyclic polyethers,'51 based on changes in the NMR spectra of thesecompounds at low temperature, and more recently in-in to out-out homeomorphic isomerism of bicyclo[6.5.1]tetradecane has been described, again based on NMR studies of the equilibrium mixture.