Unlocking Hydrogenation for C–C Bond Formation: A Brief Overview of Enantioselective Methods

Abstract

Hydrogenation of π-unsaturated reactants in the presence of carbonyl compounds or imines promotes reductive C-C coupling, providing a byproduct-free alternative to stoichiometric organometallic reagents in an ever-increasing range of C=X (X = O, NR) additions. Under transfer hydrogenation conditions, hydrogen exchange between alcohols and π-unsaturated reactants triggers generation of electrophile-nucleophile pairs, enabling carbonyl addition directly from the alcohol oxidation level, bypassing discrete alcohol oxidation and generation of stoichiometric byproducts.

Alkynes as Allylmetal Equivalents in Redox-Triggered C–C Couplings to Primary Alcohols: (Z)-Homoallylic Alcohols via Ruthenium-Catalyzed Propargyl C–H Oxidative Addition

“…1). 3 In the course of our studies, Obora and Ishii reported a remarkable iridium catalyzed C-C coupling of 1-aryl-1-propynes to furnish branched products of carbonyl allylation (Scheme 1, eq. 2).…”

“…These studies contribute to the growing body of redox-triggered alcohol C-C couplings; new carbonyl addition chemistry that extends beyond the use of premetallated reagents. 3 …”

Ruthenium-Catalyzed Transfer Hydrogenation for C–C Bond Formation: Hydrohydroxyalkylation and Hydroaminoalkylation via Reactant Redox Pairs

“…25,26 As documented in this account, ruthenium catalyzed transfer hydrogenation now serves as the basis for C-C bond constructions that directly convert lower alcohols to higher alcohols. [16][17][18][19][20] This body of work was preceded by studies on metal catalyzed carbonyl reductive couplings mediated by elemental hydrogen, as initially described in 2002 by the present author, 27 and as documented in the review literature. 28,29 …”

“…14,15 The purpose of this review is to provide a comprehensive summary of ruthenium catalyzed C-C couplings induced via alcohol-mediated transfer hydrogenation. [16][17][18][19][20] These studies build on several important milestones in the area of ruthenium catalyzed hydrogenation and transfer hydrogenation (Scheme 1). In 1971, one decade beyond the seminal work of Halpern on ruthenium catalyzed hydrogenation, 6 transfer hydrogenations employing ruthenium catalysts were described.…”

Efficient, divergent synthesis of cryptophycin unit A analogues

“…Recent advances in crotylation technology pioneered in the Krische laboratory 14-17 created the opportunity for a catalytic process with the potential for recovery and recycling of the expensive iridium-based reactive complex. 18 This crotylation was also highly efficient, as it eliminated the need for a separate aldehyde generation and isolation step. Furthermore, an Eli Lilly process chemistry report 19 suggested that tedious protection and deprotection steps through the final alcohol oxidation would not be necessary, and that an in situ olefination could further shorten the synthetic route.…”