Catalytic asymmetric intermolecular C-H activation adjacent to nitrogen

Recently, the rhodium carbenoids derived from aryldiazoacetates have been demonstrated to be exceptional at intermolecular C-H insertion. The primary objective of this work is to explore the scope and limitations of the catalytic asymmetric intermolecular C-H activation adjacent to nitrogen.; The first area of investigation was to explore the double stereodifferentiation and kinetic resolution in the intermolecular C-H insertion reaction into substituted Boc protected pyrrolidines using dirhodium tetrakis(S-(N-dodecylbenzenesulfonyl)prolinate) (Rh₂(S-DOSP)₄). Intermolecular C-H insertion reactions of 2-substituted pyrrolidines using Rh₂( S-DOSP)₄ as catalyst showed impressive levels of kinetic resolution and double stereodifferentiation. This allows for three or even four stereogenic centers to be controlled during the C-H insertion generating highly functionalized products with high diastereoselectivity. Intermolecular C-H insertion reactions were effectively carried out into 3-substituted pyrrolidines and using the appropriate chiral catalyst the regioselectivity was altered. In addition to the excellent regiocontrol that is possible with this chemistry, the reaction can be extended to a system that allows double stereodifferentiation and kinetic resolution to occur.; The second area of investigation was to explore the intermolecular C-H insertion reaction into acyclic amines. The C-H insertion studies represent the first chemoselective C-H activation occurring at a methyl site. One of the direct applications of this chemistry is the catalytic asymmetric synthesis of substituted β-amino acids. The reaction proceeded with good chemo- and enantioselectivity and demonstrated the remarkable steric control that is possible with these rhodium-carbenoid intermediates.; In the final part of the work, studies to optimize the catalyst loading for the asymmetric cyclopropanation were carried out. The results show that the rigid bridged prolinate complex, Rh₂(S-biTISP) ₂ is an excellent catalyst for asymmetric cyclopropanation. Cyclopropanation of alkenes with the diazo compounds occurred in high yields and enantioselectivity with 0.001mol% catalyst, under mild conditions. This reaction provides turnover numbers of 100,000 and turnover frequencies of 4000 h−1 at room temperature.