Newly Developed Methods for Functionalization of Quaternary Carbons: Decarboxylative Allylation, Benzylation, and Arylation of Nitriles and the Asymmetric Baeyer-Villiger Oxidation of 1,3-Diketones

Abstract

Decarboxylative carbon-carbon bond formations have emerged as a powerful synthetic tool within the past ten years. Beginning with the seminal reports from Saegusa and Tsuji in 1980, the decarboxylative allylation (DcA) of â-ketoesters remained relatively uninvestigated until the independent reports from Tunge and Stoltz in 2004. As part of the body of work produced during my tenure under the mentorship of Dr. Tunge, our group in 2011 compiled a comprehensive report published in Chemical Reviews highlighting the advancements of the DcA reaction. In addition, our group has also investigated the decarboxylative benzylation (DcB) of â-ketoesters and the reaction has shown to be an efficient method for the introduction of benzyl moieties. The enclosed dissertation thoroughly discusses my contribution to the advancement of palladium-catalyzed decarboxylative carbon-carbon bond forming reactions. As previously reported by the Tunge group, it was realized that, in addition to enolate nucleophiles derived from decarboxylation of â-ketoesters, various other nucleophiles were accessible via this path. In particular, my work involved the development of the palladium-catalyzed DcA, DcB, and decarboxylative arylation (DcAr) of cyanoacetic esters. Palladium-catalyzed ionization of allyl and benzyl cyanoacetic esters facilitates loss of carbon dioxide from cyanoacetate and is believed to allow access to the common intermediacy of non-stabilized metalated nitriles. In the course of our studies we discovered the DcA reaction to be regiospecific in C-C bond formation and to deliver enriched branched to linear allylation products. In addition, treatment of benzyl cyanoacetic esters with a palladium catalyst allows for access to newly benzylated acetonitrile molecules. However, in the case of furylmethyl cyanoesters choice of palladium catalyst determines the formation of benzylated and arylated products, representing the first reported examples for the addition of nitrile anions to Pd-ð-benzyl complexes.