Catalytic Regio- and Enantioselective Proton Migration from Skipped Enynes to Allenes

• Published in: Chem Vol. 5; no. 3; pp. 585 - 599
• Main Authors: Wei, Xiao-Feng, Wakaki, Takayuki, Itoh, Taisuke, Li, Hong-Liang, Yoshimura, Takayoshi, Miyazaki, Aya, Oisaki, Kounosuke, Hatanaka, Miho, Shimizu, Yohei, Kanai, Motomu
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 14.03.2019
• Subjects: allene; asymmetric catalysis; copper catalysis; DFT calculation; enyne; hydrocarbon; ligand; proton migration; regioselectivity; SDG11: Sustainable cities and communities; SDG12: Responsible consumption and production; SDG9: Industry, innovation, and infrastructure; regioselectivity; allene; copper catalysis; DFT calculation; enyne; SDG12: Responsible consumption and production; proton migration; asymmetric catalysis; SDG11: Sustainable cities and communities; hydrocarbon; ligand; SDG9: Industry, innovation, and infrastructure
• ISSN: 2451-9294; 2451-9294
• DOI: 10.1016/j.chempr.2018.11.022

Chiral allenes are highly valuable as versatile synthetic intermediates and core skeletons of various functional organic molecules. Despite marked recent advances, the straightforward catalytic enantioselective synthesis of hydrocarbon allenes from readily available starting materials without relying on polar functional groups is still very challenging. Here, we report a copper(I)-catalyzed enantioselective proton migration from skipped enynes to allenes as an efficient approach in chiral allene synthesis. With catalyst loading as low as 0.5 mol %, the reaction proceeds smoothly under mild conditions without the need for additional stoichiometric reagents or generation of waste. Novel chiral ligand L6 plays a critical role in furnishing high catalyst activity, promoting regioselective protonation to produce allenes instead of conjugated enynes, and inducing axial chirality of allenes. The multiple roles of the chiral ligand are rationalized by density functional theory calculations. [Display omitted] •A catalytic conversion of achiral skipped enynes to chiral allenes is developed•Soft-soft interactions between the catalyst and the substrates play a key role•The chiral ligand of the catalyst controls both regio- and enantioselectivity•DFT calculations rationalize the ligand effects in reactivity and selectivity Catalytic conversions of readily available feedstock hydrocarbons to value-added fine chemicals will vastly expand the scope of organic molecules. Because of the lack of polar functional groups in hydrocarbons, however, conversions of hydrocarbons require activation of unactivated chemical bonds. Moreover, the control of various types of selectivity, including regio- and enantioselectivity, is extremely challenging. Here, we disclose a catalytic enantioselective proton migration of readily available achiral skipped enynes to chiral allenes. The product allenes are versatile chiral building blocks for value-added fine chemicals, such as drugs and advanced functional materials. Moreover, density functional theory calculations shed light on the origin of regio- and enantioselectivity control. The experimental and theoretical approaches to the one-step, catalyst-controlled reconstitution of the C–H bond connectivity in hydrocarbons will be a foundation for a large-scale production of value-added fine chemicals. A catalytic enantioselective proton migration of skipped enynes to allenes is developed. A newly identified chiral ferrocenyl phosphine ligand plays critical roles in controlling both regio- and enantioselectivity. The method offers a new concept to convert readily available and abundant feedstock hydrocarbons into high-value-added molecules by reconstituting C–H bond connectivity without relying on polar functional groups.