Palladium-catalyzed carbonylative cyclization via carbo- and acylpalladation of multiple bond systems
Abstract
Under high pressure of CO, typically 40 atm, Palladium-catalyzed cyclization of $\omega$-vinyl iodobenzenes in the presence of MeOH provides an efficient synthesis of 5- and 6-membered ring $\beta$-keto-esters (Type II Ac-Pd). Di- and tricarbosubstituted alkenes react similarly, but premature esterification and Type I Ac-Pd can be serious competitive reactions. Nonetheless the use of less nucleophilic trapping agents and lower polarity solvents allows clean cyclization. Moreover, free hydroxyls are detrimental to the cyclization process, while protected, they give good yield of Type II Ac-Pd products and allow high level of asymmetric induction. Cyclization of iodo-dienes and -trienes provides an efficient synthesis of polycyclic structures via cascading cyclic acylpalladation. The use of carbon monoxide as a one carbon unit in a cascading process allows the novel angular-fused-mode cascade. In the related carbonylative cyclization of alkynes, Ac-Pd is restricted to the formation of 5-membered rings; while the intermolecular process provides an efficient synthesis of butenolides from the carbonylation of aryl iodides in the presence of internal alkynes. Cyclic carbopalladation is indeed more favored and usually overshadows the competitive acylpalladation process. This has allowed the development of "zipper"-mode and "dumbbell"-mode cascade carbopalladation of alkynes where termination has been effectively achieved via various carbonylative trapping processes such as esterification, amidation, C-enolate trapping, and carbonylative cyclization of alkenes. 1,1-Disubstituted alkenes can also participate in tandem carbopalladation-carbonylative esterification processes. In this case, carbopalladation generates a stereogenic carbon. The use of TBDMS protected hydroxyls gives high level of 1,4-asymmetric induction (85-99%) and provides an efficient diastereoselective synthesis of the Colvin-Raphael lacton. The related non-carbonylative "zipper"-mode process was used toward the diastereoselective synthesis of epi-$\alpha$-Vetivone.
Degree
Ph.D.
Advisors
Negishi, Purdue University.
Subject Area
Organic chemistry
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