ANNULATION VIA ALKYLATION ALDER ENE CYCLIZATIONS - PD-CATALYZED CYCLOISOMERIZATION OF 1,6-ENYNES

A Pd(O)-catalyzed alkylation of an allyl substrate with a nucleophile containing a double or triple bond to permit subsequent thermal Alder ene reactions constitutes a novel annulation protocol. In the case of a triple bond, a Pd(2+) complex catalyzes an equivalent of an Alder ene reaction. This new cyclization is probed in terms of the effect of substitution on the olefin, the acetylene, and the tether connecting the two. The reaction produces both 1,4-dienes (Alder ene-type products) and 1,3-dienes. Mechanisms to account for the diversity of products are presented. The Pd(2+)-catalyzed reaction shows an ability to interact with remote nonreactive parts of substrates to affect conformation and thereby selectivity. Several advantages accrue to the Pd(2+)-catalyzed reaction. First, the reaction normally proceeds at temperatures between 25 and 65-degrees-C instead of the > 250-degrees-C (in static systems) to > 500-degrees-C (in flow systems) for the thermal reaction. Second, reactions that fail thermally succeed via the metal-catalyzed process. Third, complementary regioselectivity may be observed. Fourth, the ligating properties of the metal catalyst offer opportunities for exercising control not possible in a simple thermal process. A novel cyclopentannulation of allyl alcohols and related derivatives evolves in which Pd(O) catalyzes formation of the first bond and a simple electronic switch to Pd(2+) catalyzes formation of the second bond.