O–H hydrogen bonding promotes H-atom transfer from α C–H bonds for C-alkylation of alcohols

Abstract

The efficiency and selectivity of hydrogen atom transfer from organic molecules are often difficult to control in the presence of multiple potential hydrogen atom donors and acceptors. Here, we describe the mechanistic evaluation of a mode of catalytic activation that accomplishes the highly selective photoredox α-alkylation/lactonization of alcohols with methyl acrylate via a hydrogen atom transfer mechanism. Our studies indicate a particular role of tetra-n-butylammonium phosphate in enhancing the selectivity for α C–H bonds in alcohols in the presence of allylic, benzylic, α-C=O, and α-ether C–H bonds.

Photoredox Catalysis in Organic Chemistry

“…80 By leveraging photoredox, HAT, and hydrogen bonding catalysis, our laboratory has successfully developed a strategy for the selective alkylation of α-hydroxy C–H bonds with Michael acceptors (Scheme 18b). 81 In this protocol, both a quinuclidine HAT catalyst and a phosphate hydrogen bonding catalyst are required in order to achieve selective functionalization of α-hydroxy C–H bonds over other weaker C–H bonds. Here, a hydrogen bonding interaction between the phosphate and the alcohol induces a drastic weakening of the α-hydroxy C–H bonds and, in addition, increases the hydricity of the C–H bonds.…”

Strong Short‐Range Cooperativity in Hydrogen‐Bond Chains

“…Furthermore, the limited range of the cooperative effect was consistent with previous computations suggesting that polarization changes most rapidly at the ends of H‐bond chains 4c, 9b, 16, 17. Our findings have implications for the fundamental understanding, modeling, and exploitation of H‐bond chains particularly in regard to their role in catalysis,4d and in determining molecular structures and recognition properties 5a, 17c, 20. One might speculate that biology has already explored energetic cooperativity in phenolic H‐bond chains, considering that catechol, not pyrogallol, moieties (Figure 1 B) have been selected by evolution for their adhesive properties 11e, 11f…”

Native functionality in triple catalytic cross-coupling: sp 3 C–H bonds as latent nucleophiles

“…Recently, driven by developments in small-molecule catalyst design, general methods for C–H bond functionalization via HAT have begun to achieve levels of selectivity that were previously restricted to enzymatic systems (18, 19). In this context, our laboratory has demonstrated that photoredox-mediated HAT catalysis can exploit native sp 3 C–H bonds for a range of C–C bond constructions, such as Minisci reactions, conjugate additions, and radical–radical couplings (20–23). Nevertheless, a general strategy for functionalization of C–H bonds via HAT–transition metal cross-coupling has yet to be achieved (24, 25).…”

“…We recently questioned whether it would be possible to use a tertiary amine radical cation—generated via a photoredox-mediated single-electron transfer (SET) event (23, 26–28)—to accomplish H-atom abstraction from a diverse range of substrates (Fig. 1).…”