Researchers from Shanghai Institute of Organic Chemistry, CAS have developed the first Co-catalyzed protocol for catalytic generation of the nucleophilic allyl–Co(II) complexes from easily accessible and robust allylic alcohol derivatives followed by diastereo- and enantioselective addition to aldehydes with extremely broad scope of allyls and aldehydes in high efficiency and stereoselectivity, facilitating fast establishment of a library of enantioenriched homoallylic alcohols from common starting materials and catalyst.
Development of catalytic enantioselective transformations of ambiphilic-allyl–metal complexes has long been central to researchers in organic chemistry, as it enables installation of diversified allyl groups starting from easily accessible allylic alcohol derivatives, representing one of the most important and powerful carbon–carbon bond forming reac-tions. Although catalytic enantioselective allylic substitutions involving electrophilic-allyl–metal complexes have been well studied during the past few decades, the design and utility of the ambiphilic-allyl–metal complexes as nucleophiles for enantioselective transformations remain underdeveloped. In addition, enantioenriched homoallylic alcohols are important building blocks in complex molecule synthesis. Although catalytic enantioselective allyl additions to aldehydes promoted by various transition metal complexes have been established, there are significant limitations. No general method enabled diastereo- and enantioselective introduction of allyl groups containing both tertiary and quaternary centers promoted by a single catalytic system.
Researchers discovered that Co(I) species underwent either two-electron oxidative addition to afford allyl–Co(III) complex or single-electron oxidative addition, affording an equilibrium between allyl–Co(III) complex and Co(II) complex associated with an allyl radical. the chem-, regio-, diastereo-, and enantio-selectivity of the reaction can be accurately controlled by adjusting ligands. In addition, the reaction has high yield, wide substrate applicability and tolerance with a variety of sensitive functional groups. This reaction features diastereo- and enantioconvergent conversion of easily accessible allyl alcohol derivatives to diversified enantioenriched homoallylic alcohols with extremely broad scope of allyl groups that can be introduced. Mechanistic studies indicated that allyl radical intermediates were involved in this process.
The research findings have been published in the journal J. Am. Chem. Soc., 2021, DOI: 10.1021/jacs.1c05690 Fig.1 Cobalt-catalyzed enantioselective reductive allylation of aldehydes (Image by MENG Fanke)
Meng Fanke Ph.D.Professor Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences Ling Ling Road 345 Shanghai 200032 China Tel: 0086-21-54925203 Email: mengf@sioc.ac.cn |
