Development of Pd-Catalyzed Alkyne Dimerization and Enyne Benzannulation Methodologies
thesisposted on 2017-07-22, 00:00 authored by Olga V. Zatolochnaya
Dimerization of alkynes represents a fundamental reaction for a straightforward construction of carbon–carbon bonds in atom-economical manner. A general highly regio- and stereoselective palladium-catalyzed head-to-head dimerization reaction of terminal alkynes has been developed. This methodology allows for efficient synthesis of a variety of 1,4-enynes as single E-stereoisomers. Furthermore, an alternative head-to-tail regioselectivity has been observed upon addition of carboxylate salts to the catalytic system. Detailed computational studies revealed that head-to-head dimerization under neutral reaction conditions proceeds via the hydropalladation pathway. It was also found that the regioselectivity of the process in the presence of carboxylate anion switches due to the redirection of the reaction from hydropalladation to carbopalladation pathway and destabilization of intermediate palladium complexes. Based on the DFT calculations, a clear correlation between mechanistic path and the reaction selectivity has been established. These findings are essential for the design of novel synthetic methods based on hydroalkynylation strategy in which hydro- and carbometallation are the competing reaction pathways. Chemo- and regioselective palladium-catalyzed [4+2] benzannulation reaction of conjugated enynes with various alkyne-containing enynophiles represent a powerful atom-economical method for construction of the aromatic ring from easily accessible starting materials. A highly efficient catalytic system for the Pd-catalyzed [4+2] benzannulation of enynes with diynes has been developed. Newly found conditions enabled synthesis of variety of densely substituted arylacetylenes via the cross-benzannulation reaction with turnover number of the catalyst up to 1800. This catalytic system also allowed expanding the scope of homo-benzannulation reaction. Moreover, an efficient method toward fluorinated and perfluoroalkylated densely substituted benzene derivatives based on the Pd-catalyzed [4+2] cross-benzannulation reaction has been established. The utility of obtained products has been also demonstrated by efficient synthesis of various aromatic and heteroaromatic compounds. Thus, this strategy offers a viable and very general alternative to the existing fluorination and perfluoroalkylation methods.
Degree GrantorUniversity of Illinois at Chicago
Committee MemberLee, Daesung Wardrop, Duncan J. Mohr, Justin T. Ku, Yi-Yin