Nickel‐Catalyzed Asymmetric Reductive Carbo‐Carboxylation of Alkenes with CO₂

Abstract

Reductive carboxylation of organo (pseudo)halides with CO 2 is ap owerfulm ethod to providec arboxylic acids quickly.Notably,the catalytic reductive carbo-carboxylation of unsaturated hydrocarbons via CO 2 fixation is ah ighly challenging but desirable approach for structurally diverse carboxylic acids.T here are only af ew reports and no examples of alkenes via transition metal catalysis.W er eport the first asymmetric reductive carbo-carboxylation of alkenes with CO 2 via nickel catalysis.Avariety of aryl (pseudo)halides,s uch as aryl bromides,a ryl triflates and inert aryl chlorides of particular note,u ndergo the reaction smoothly to give important oxindole-3-acetic acid derivatives bearing aC3-quaternary stereocenter.T his transformation features mild reaction conditions,w ide substrate scope,f acile scalability,g ood to excellent chemo-, regio-and enantioselectivities.T he method highlights the formal synthesis of (À)-Esermethole, (À)-Physostigmine and (À)-Physovenine,a nd the total synthesis of (À)-Debromoflustramide B, (À)-Debromoflustramine Ba nd (+ +)-Coixspirolactam A; thereby, opening an avenue for the total synthesis of chiral natural products with CO 2 .

Challenges and recent advancements in the transformation of CO2into carboxylic acids: straightforward assembly with homogeneous 3d metals

“…With this in mind, in 2021, Yu and Kong together with their team realized this elegant nickel-catalyzed asymmetric reductive carbo-carboxylation for the synthesis of oxindole-3-acetic acid derivatives ( 138 ) bearing a C3-quaternary stereocenter with high chemo-, enantio-, and regioselectivities from 137 using (S,Sp)-iPr-FOXAP ( 139 ) as the ligand. 200 The developed method was implemented to achieve a broad substrate scope with substituted alkenes, arylbromides, aryl triflates and arylchlorides. Interestingly, the protocol was applied to furnish natural products such as (−)-debromoflustramide B, (−)-debromoflustramine B and (+)-coixspirolactam as well as the key intermediates (−)-esermethole and (−)-physovenine in good to excellent yields, 42–98% (Scheme 20).…”

“…Furthermore, Ar-Ni II L species 141 underwent 6-endo cyclization, which resulted in a relatively stable Ni II L enolate species ( 148 ), which can lead to the side product 149 (Scheme 21). 200 Ar-Ni II L species ( 142 ) can also undergo nucleophile attack with CO 2 to form the ipso -carboxylation byproduct 150 . The mentioned reaction mechanism indicates the possibility of the formation of side products ( 149 & 150 ), but in the present strategy, the authors became successful in achieving the desired product 147 .…”