Anti-Markovnikov alcohols via epoxide hydrogenation through cooperative catalysis

Abstract

The opening of epoxides typically requires electrophilic activation, and subsequent nucleophilic (SN2) attack on the less substituted carbon leads to alcohols with Markovnikov regioselectivity. We describe a cooperative catalysis approach to anti-Markovnikov alcohols by combining titanocene-catalyzed epoxide opening with chromium-catalyzed hydrogen activation and radical reduction. The titanocene enforces the anti-Markovnikov regioselectivity by forming the more highly substituted radical. The chromium catalyst sequentially transfers a hydrogen atom, proton, and electron from molecular hydrogen, avoiding a hydride transfer to the undesired site and resulting in 100% atom economy. Each step of the interconnected catalytic cycles was confirmed separately.

Using nature’s blueprint to expand catalysis with Earth-abundant metals

“…(88) Cooperative catalysis using EAM complexes of two metals, Ti and Cr, provided a highly selective route to anti-Markovnikov alcohols through ring-opening of epoxides. (89) This hydrogenation of epoxides is unusual since at different steps of the mechanism, a chromium complex transfers an electron, a hydrogen atom, and a proton.…”

Regiodivergent Hydroborative Ring Opening of Epoxides via Selective C–O Bond Activation

“… 3 One of the most employed catalytic methods for the ring-opening of epoxides is transition-metal-catalyzed hydrogenation, either by using heterogeneous or homogeneous catalysts. 4 In all cases, high temperatures and H 2 pressures are required, leading to poor selectivity along with the generation of oligomers or saturated hydrocarbons as byproducts ( Scheme 1 a). In recent years, the transition-metal-catalyzed hydroboration has appeared as a plausible alternative to the hydrogenation protocols.…”

Titanocene-Catalyzed Regiodivergent Epoxide Opening – From Desymmetrizing meso-Epoxides to Regiodivergent Arylation of Epoxides

“…It remains to be seen if the concept of regiodivergent epoxide opening can also be applied in other atom-economical reactions, such as epoxide hydrosilylation 32 or epoxide hydrogenation. 33 Scheme 7 Scope of the regiodivergent arylation of epoxides (rr and dr were determined by 13 C NMR spectroscopy of the crude reaction mixture). 29 All products are obtained as single enantiomers.…”