In Situ Kinetic Studies of Reactions Involving Dirhodium(II) Donor/Acceptor Carbenes.

摘要

The exceptional reactivity of dirhodium(II) donor/acceptor carbenes has made them key intermediates in organic synthesis. The breadth of transformations that can be conducted include C-H functionalization, ylide formation, cyclopropanation, N-H, O-H and Si-H insertion. Moreover, the advent of chiral catalysts has rendered many of these transformations asymmetric. These catalysts are extremely active and in special cases are capable of very high turnover numbers. However, the high turnover capability is very dependent on the substrates used, and a general problem is the occurrence of a major drop in the levels of enantioselectivity when low catalyst loadings are used. Research to date has not pinpointed the cause of the catalyst failure, and this seriously limits the practical utility of such an expensive catalyst and its application as an immobilized catalyst or in flow chemistry. The purpose of the work described in this thesis is to gain a better understanding of the factors that govern catalysts activity and stability, especially under high turnover conditions.;The two major goals of the thesis are to (1) explore modes of catalyst deactivation/ decomposition via kinetic analysis and (2) demonstrate how kinetic understanding can aid in natural product synthesis. These goals have been undertaken through detailed kinetic analysis for three classic dirhodium(II) carbenoid reactions and application of the kinetic knowledge gained to a synthetic approach for a complex natural product. Particular interest has focused on cyclopropanation of styrene. The selectivity of this standard reaction and ability for the catalyst to achieve high turnover numbers under solvent-free conditions has been extensively studied; however, the stability of the catalyst is not well understood. A more challenging reaction, C-H insertion into activated and unactivated C-H bonds was explored because high TONs have yet to be achieved for these reactions. Si-H insertion is a reaction that has shown to be very robust for dirhodium(II) carbenoid catalysis. Therefore, understanding factors attributing the high activity of the catalyst is integral. Finally, application of the kinetic analysis to address relative rate challenges in a project directed towards the synthesis of phorbol was undertaken.