The utilization of transition metal complexes as catalysts for the formation of C-C bonds has emerged as a widely exploited synthetic strategy, both in the construction of pharmaceutical agents and small molecule natural products. However, a common prerequisite is that the molecular components are prefunctionalized, thus leading to wasteful byproducts and additional synthetic sequences. Recently, transition metals such as rhodium have found application in directed C-H functionalization reactions. These reactions make unnecessary the prior functionalization of the molecule, thus streamlining syntheses and decreasing chemical waste. With these considerations in mind, this proposal aims to study three aspects of the Rh(III)-catalyzed arylation of imines recently developed in the Ellman laboratory. This research project will encompass the (1) exploration of directing groups that would serve as versatile synthons in organic synthesis, (2) construction of complex ring systems via C-H functionalization, and (3) development of an asymmetric approach to the Rh(III) C-H functionalization using both a chiral auxiliary and a chiral counterion strategy. These studies will culminate in the synthesis of a number of enantioenriched ?-amino acid and isoindolinone derivatives.
Directed C-H functionalization has emerged as a promising alternative to traditional C-C bond forming cross-coupling reactions. C-H functionalization provides a strategy to simplify syntheses and minimize wasteful byproducts. Further, this concept has been applied in the synthesis of biologically active natural products. This investigation aims to expand on the synthetic potential of C-H functionalization through the streamlined enantioselective synthesis of gamma-amino acids and isoindolinones. These known pharmaceutical subclasses possess vital neurological applications and have been used in the treatment of epilepsy, neuropathic pain, and fibromyalgia.