95123-99-2Relevant academic research and scientific papers
Mechanistic dichotomy in CpRu(CH3CN)3PF6 catalyzed enyne cycloisomerizations
Trost, Barry M.,Toste, F. Dean
, p. 5025 - 5036 (2007/10/03)
Enynes are easily accessible building blocks as a result of the rich chemistry of alkynes and thus represent attractive substrates for ring formation, A ruthenium catalyst for cycloisomerization effects such reaction of 1,6- and 1,7-enynes typically at room temperature in acetone or DMF under neutral conditions. The reaction is effective for forming five- and six-membered rings of widely divergent structure. The alkyne may bear both election-donating and election-withdrawing substituents. The alkene may be di- or trisubstituted. Introduction of a quaternary center at the propargylic position of an ynoate, however, completely changes the nature of the reaction. In the case of a 1,6-enynoate, a seven-membered ring forms in excellent yield under equally mild conditions. Evidence is presented to indicate a complete change in mechanism. In the former case, the reaction involves the intermediacy of a ruthenacyclopentene. In the latter case, a C-H insertion to form a π-allylruthenium intermediate is proposed and supported by deuterium-labeling studies. A rationale is presented for the structural dependence of the mechanism.
Pd-catalyzed cycloisomerization to 1,2-dialkylidenecycloalkanes. 1
Trost, Barry M.,Tanoury, Gerald J.,Lautens, Mark,Chan, Chuen,MacPherson, David T.
, p. 4255 - 4267 (2007/10/02)
Enhancing synthetic efficiency requires the development of synthetic reactions that, to the extent possible, are simple additions wherein everything else is required only in catalytic amounts. The Alder ene reaction constitutes a classical reaction that meets this requirement that has much unrealized potential. A transition-metal-catalyzed version helps to increase that potential by permitting this reaction to proceed under mild conditions. A significant benefit of transition metal catalysis is the feasibility of diverting the reaction along pathways not feasible under thermal conditions. The synthesis of 1,3-dienes rather than 1,4-dienes is a very important diversion because of the utility of 1,3-dienes as reaction partners in the Diels-Alder reaction, another highly atom economical process. A catalyst derived from palladium acetate cycloisomerizes 1,6- and 1,7-enynes to dialkylidenecyclopentanes and -cyclohexanes. 1,3-Diene formation is favored over the Alder ene process by both steric and electronic effects. The reaction is highly chemoselective - tolerating a wide diversity of functionality including hydroxyl groups, ketones, esters, alkynyl and enol ethers, alkynyl and vinyl silanes, and enones. Many of the substrates are available by palladium-catalyzed alkylation reactions - highlighting the effectiveness of palladium catalyzed methodology in organic synthesis. The atom-economical nature of these reactions combined with the Diels-Alder reaction permit butadiene and dimethyl propargylmalonate to be molded into a polyhydro-as-indacene. The mechanism of this reaction may involve a tautomerization of an enyne-Pd(+2) complex to a pallada(+4)cyclopentene intermediate as a key step.
Annulation via alkylation - Alder ene cyclizations. Pd-catalyzed cycloisomerization of 1,6-enynes
Trost, Barry M.,Lautens,Chan,Jebaratnam,Mueller
, p. 636 - 644 (2007/10/02)
A Pd(0)-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°C instead of the > 250°C (in static systems) to > 500°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(0) catalyzes formation of the first bond and a simple electronic switch to Pd(2+) catalyzes formation of the second bond.
