En Route to a Practical Primary Alcohol Deoxygenation

Abstract

A long-standing scientific challenge in the field of alcohol deoxygenation has been direct catalytic sp 3 C−O defunctionalization with high selectivity and efficiency, in the presence of other functionalities, such as free hydroxyl groups and amines widely present in biological molecules. Previously, the selectivity issue had been only addressed by classic multistep deoxygenation strategies with stoichiometric reagents. Herein, we propose a catalytic late-transition-metal-catalyzed redox design, on the basis of dehydrogenation/Wolff−Kishner (WK) reduction, to simultaneously tackle the challenges regarding step economy and selectivity. The early development of our hypothesis focuses on an iridium-catalyzed process efficient mainly with activated alcohols, which dictates harsh reaction conditions and thus limits its synthetic utility. Later, a significant advancement has been made on aliphatic primary alcohol deoxygenation by employing a ruthenium complex, with good functional group tolerance and exclusive selectivity under practical reaction conditions. Its synthetic utility is further illustrated by excellent efficiency as well as complete chemo-and regioselectivity in both simple and complex molecular settings. Mechanistic discussion is also included with experimental supports. Overall, our current method successfully addresses the aforementioned challenges in the pertinent field, providing a practical redox-based approach to the direct sp 3 C−O defunctionalization of aliphatic primary alcohols.

Manganese‐Catalyzed Dual‐Deoxygenative Coupling of Primary Alcohols with 2‐Arylethanols

“…[7] However,t he substrate scope is restricted to benzylic and allylic alcohols.Recently,Liand coworkers reported amore efficient deoxygenation of alcohols by at andem reaction that involves dehydrogenation and Wolff-Kishner reduction, catalyzed by either aR uo rI r catalyst. [8] Later on, Milsteinsg roup developed am ore sustainable version of the same transformation by using anon-noble-metal catalyst. [9] Despite significant advances such as those mentioned above,t he alcohol deoxygenation reaction is still limited to C À Oc leavage of one alcohol-containing molecule.D irect coupling of two alcohol molecules by ad ual-deoxygenation process could be an ideal approach for the production of highenergy-density hydrocarbons from oxygen-rich biomass feed-stocks.S uch transformations,w hich involve simultaneous cleavage of two inert CÀOb onds,a re very challenging, [10] although the corresponding mono-deoxygenation of alcohols with primary alcohols by ah ydrogen-borrowing strategy has been well developed.…”

Direct Synthesis of Symmetrical Azines from Alcohols and Hydrazine Catalyzed by a Ruthenium Pincer Complex: Effect of Hydrogen Bonding

“…Very recently, Ru-catalyzed reaction of primary alcohols with hydrazine resulted in alcohol deoxygenation. 25 …”

Advances in the Synthesis of Methylated Products through Indirect Approaches

“…In biological molecules, free hydroxy groups and amines are widely presented, and alcohol deoxygenation has been a long‐standing scientific challenge. Recently, Li and Dai proposed a catalytic late transition metal‐catalyzed redox design, on the basis of dehydrogenation/Wolff–Kishner reduction, to simultaneously tackle this challenge (Table ) …”