Variable structure diversification by multicatalysis: the case of alcohols

Abstract

Given that alcohol moieties are present in a great diversity of valuable fine chemicals from nature and synthesis, methods enabling their structure diversification are highly sought after. Catalysis proved to enable the development of new transformations that are beyond the inherent reactivity of alcohols. However, modifying the structure of alcohols at certain unbiased positions remains a major challenge or requires tedious multistep procedures. Recently, increased attention has been given to multicatalyis, which combines multiple reactions and catalysts within one system, creating room for discovering previously inaccessible reactivities or increasing the overall efficiency of multistep transformations. This feature article focuses on demonstrating various aspects of devising such multicatalytic systems that modify the structure of alcohol-containing compounds. Special attention is given to highlighting the challenges and advantages of multicatalysis, and in a broader context discussing how the field of catalysis may progress toward more complex systems.

Fig. 1. Multicatalytic approaches to modifying alcohols: α-functionalization of alcohols, β-functionalization of alcohols, α-hydro functionalization of allylic alcohols, γ-hydro functionalization of allylic alcohols, site-selective modifications of sugars.

Scheme 1. α-Arylation of alcohols with aryl bromides under the Ir/Ni/amine photoredox multicatalysis.

Scheme 2. α-Arylation of alcohols with aryl fluorides under the photoredox-hydrogen atom transfer multicatalysis.

Scheme 3. Enantioselective α-arylation of alcohols with boronic acids under the Ru/Ru sequential dual-catalytic relay.

Scheme 4. Enantioselective synthesis of secondary benzylic alcohols starting from unsaturated alcohols and boronic acids under the Ir/Ru sequential dual-catalytic relay.

Scheme 5. Access to enantioenriched secondary benzylic alcohols starting from alkenes, a TMS-protected diol, and boronic acids under the Ru/Acid/Ru/Ru sequential quadruple-catalytic relay.

Scheme 6. Enantioselective and diasterodivergent synthesis of secondary benzylic alcohols bearing 1,3-adjacent stereocentres from readily available allylic alcohols bearing a prochiral double bond under the Ru/Ru sequential dual-catalytic relay catalysis.

Scheme 7. Direct β-arylation of alcohols with aryl bromides under the dual-catalytic Ru/Pd relay.

Scheme 8. Enantioselective Michael-type addition of keto-esters to allylic alcohols under the dual iron-/organocatalytic system.

Scheme 9. Enantioselective Michael-type addition of boronic acids to allylic alcohols under the dual-catalytic Fe/Rh relay.

Scheme 10. Stereodivergent synthesis of alcohols bearing 1,4-stereocentres from allylic alcohols and ketimine esters under the dual-catalytic Ru/Cu system.

Scheme 11. Site-selective epimerization of sugars operating under photocatalysis with two hydrogen atom transfer processes.