Terminal substituent effects on the reactivity, thermodynamics, and stereoselectivity of the 8?-6? electrocyclization cascades of 1,3,5,7-tetraenes.

ABSTRACT: M06-2X/6-31+G(d,p) computations are reported for the 8?-6? electrocyclization cascades of 1,3,5,7-tetraenes. The rate-determining step for these cascades is typically the second (6?) ring closure. According to experiment and theory, un- and monosubstituted tetraenes readily undergo 8? electrocyclic ring closure to form 1,3,5-cyclooctatrienes; however, the 6? electrocyclizations of these cyclooctatriene intermediates are slow and reversible, and mixtures of monocyclic and bicyclic products are formed. Computations indicate that di- and trisubstituted tetraenes undergo facile but less exergonic 8? electrocyclization due to a steric clash that destabilizes the 1,3,5-cyclooctatriene intermediates. Relief of this steric clash ensures the subsequent 6? ring closures of these intermediates are both kinetically facile and thermodynamically favorable, and only the bicyclic products are observed for the cascade reactions of naturally occurring tri- and tetrasubstituted tetraenes (in agreement with computations). The 6? electrocyclization step of these cascade electrocyclizations is also potentially diastereoselective, and di- and trisubstituted tetraenes often undergo cascade reactions with high diastereoselectivities. The exo mode of ring closure is favored for these 6? electrocyclizations due to a steric interaction that destabilizes the endo transition state. Thus, theory explains both the recalcitrance of the unsubstituted 1,3,5,7-octatetraene and 1-substituted tetraenes toward formation of the bicyclo[4.2.0]octa-2,4-diene products, as well as the ease and the stereoselectivity with which terminal di- and trisubstituted tetraenes are known to react biosynthetically.

SUBMITTER: Patel A 

PROVIDER: S-EPMC4260667 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature