The proposed research involves the development of synthetic methods that utilizes the copper-catalyzed diboration of aldehydes, ketones, and imines. The resulting ?-heteroatom- substituted boronate esters have known pharmaceutical properties and potential applications in target-directed synthesis. One advantage of the proposed methodology is to provide access to new -aminoboronate esters and acids, known serine protease inhibitors and an essential component of Bortezomib (Velcade), an FDA-approved treatment of multiple myeloma. The proposed synthetic methodology would simplify access to additional ?-heteroatom-substituted boronate esters that could be used in the pursuit of new pharmaceutical targets with increased potency and unrealized medicinal applications. The objective of the outlined research plan is to develop the diboration of carbonyl compounds and imines and to exploit the synthetic utility of the resulting products for target- directed synthesis. To achieve this goal, the specific aims of the research plan include: 1) Establish general reaction conditions that mediate the diboration of aldehydes, ketones, and imines. 2) Develop asymmetric diboration reaction conditions using chiral diboron reagents or chiral ligands. 3) Develop synthetic applications involving the diboration products including Matteson-type homologation reactions and formation of branched vinyl boronate esters.
The synthetic versatility of the C-B bond has led to its use in the synthesis of countless natural products and pharmaceutical targets. New methods to incorporate boron substituents into organic substrates would increase the types of molecules that could be accessed through these transformations. The proposed research plan involves the copper-catalyzed diboration of carbonyl compounds and imines, and the development of the resulting products into synthetically viable intermediates in organic synthesis.
|Moore, Cameron M; Medina, Casey R; Cannamela, Peter C et al. (2014) Facile formation of ?-hydroxyboronate esters by a Cu-catalyzed diboration/Matteson homologation sequence. Org Lett 16:6056-9|
|Guan, Weiye; Michael, Alicia K; McIntosh, Melissa L et al. (2014) Stereoselective formation of trisubstituted vinyl boronate esters by the acid-mediated elimination of ?-hydroxyboronate esters. J Org Chem 79:7199-204|
|Medina, Casey; Carter, Kyle P; Miller, Michael et al. (2013) Stereocontrolled synthesis of 1,3-diols from enones: cooperative Lewis base-mediated intramolecular carbonyl hydrosilylations. J Org Chem 78:9093-101|