Many pharmaceuticals, materials, and other chemicals important to modern society are procured by synthetic organic chemistry. The heart of this discipline is the construction of carbon?carbon bonds, yet reactions that achieve this goal often require undesirable starting materials or inefficient strategies. Alcohols are widely accessible compounds that are stable and minimally toxic, and would therefore be ideal reactants for many chemical transformations. The limited ability of modern technologies to engage alcohols, however, has severely restricted their direct use in these important reactions, particularly as latent alkylating agents. This proposal describes how the techniques of photoredox catalysis and organocatalysis, combined with a biologically-inspired chemical mechanism called spin-center shift, would enable the use of alcohols as alkylating agents in reactions that currently employ undesirable reagents or strategies. In particular, these respective reactions would produce versatile chiral compounds that are important synthons in pharmaceuticals, and ketones, which are also useful intermediates in the agrochemical, fragrance, and fine chemical industries. Furthermore, reaction conditions would be mild because visible light provides the driving force, and water would represent the only stoichiometric byproduct. Overall, the ability to employ alcohols directly as latent alkylating agents could improve the means by which a variety of important chemicals are accessed, which would impact public health as well as a number of other sectors that rely on fine chemicals.
The formation of carbon?carbon bonds is essential to the production of pharmaceuticals, materials, and many other important chemicals, but technologies that achieve this outcome often rely on undesirable starting materials or inefficient strategies. Alcohols are widely available, stable, and benign, and would be ideal latent alkylating agents for C?C construction, but conceptual challenges have severely limited success in realizing this goal. This proposal describes innovative catalytic platforms to enable these transformations and thus improve access to a range of useful organic compounds.
| Nacsa, Eric D; MacMillan, David W C (2018) Spin-Center Shift-Enabled Direct Enantioselective ?-Benzylation of Aldehydes with Alcohols. J Am Chem Soc 140:3322-3330 |
