Enantioselective CO₂ Fixation Via a Heck‐Coupling/Carboxylation Cascade Catalyzed by Nickel

Abstract

A novel asymmetric nickel‐based procedure has been developed in which CO2 fixation is achieved as a second step of a truncated Heck coupling. For this, a new chiral ligand has been prepared and shown to achieve enantiomeric excesses up to 99 %. The overall process efficiently furnishes chiral 2,3‐dihydrobenzofuran‐3‐ylacetic acids, an important class of bioactive products, from easy to prepare starting materials. A combined experimental and computational effort revealed the key steps of the catalytic cycle and suggested the unexpected participation of Ni(I) species in the coupling event.

Recent Advances Towards the Synthesis of Dihydrobenzofurans and Dihydroisobenzofurans

“…In 2021, M. Bandini and his research group unveiled a novel strategy for synthesizing chiral 2,3‐dihydrobenzofuran acetic acid scaffolds 108 via Ni‐catalyzed Heck cyclization followed by carboxylation of ortho ‐iodo allyl ether 35 [109] . The enantioselective carboxylation Heck coupling of 1‐iodo‐2‐((2‐methylallyl)oxy)benzene 35 occurs in the presence of carbon dioxide, pyridyl imidazoline ligand L , and zinc metal in DMF as a solvent at room temperature.…”

“…In 2021, M. Bandini and his research group unveiled a novel strategy for synthesizing chiral 2,3-dihydrobenzofuran acetic acid scaffolds 108 via Ni-catalyzed Heck cyclization followed by carboxylation of ortho-iodo allyl ether 35. [109] The enantioselec- the indoline and indene type moiety with moderate yield and good to excellent enantioselectivity (63%-98%). Additional, computational studies (DFT studies) are performed to the mechanistic approach for the synthesis of dihydrobenzofuran acetic acid derivatives 108.…”

Carbo-Carboxylation of Alkenes via Intramolecular Heck Carbonylation Utilizing CO2 and Hydrosilane

“…36 and tetrabutylammonium iodide as additives, producing a series of 2,3-dihydrobenzofuran-3-ylacetic acids as products in moderate yields (Scheme 1c, bottom). 37,38 These two reactions are examples of a direct carboxylation strategy and are similar to the form of the intramolecular carbo-carbonylation reactions. Up to now, there is no report on the participation of CO 2 in Heck carbonylation reactions as a CO surrogate.…”

Ni-Catalyzed Oxygen Transfer from N2O onto sp3-Hybridized Carbons

“…In this Communication, we demonstrate that this strategy can be extended to the catalytic synthesis of challenging C­(sp 3 )–O bonds (Figure D). The protocol developed herein forges an additional C–C bond via a carbometalation event, , which sets the stage for O insertion. Due to the resulting chiral quaternary center, we exploited a chiral bidentate ligand in the catalytic system to access enantioenriched indanols and benzofuran compounds, which are widespread motifs present in biologically relevant compounds …”

“…Inspired by similar precedents on carbocyclization and C–C and C–N bond formation, we selected aryl iodide compound 1a as the model substrate (Table ). The use of 10 mol % NiI 2 in combination with 15 mol % phenanthroline derivative L1 , activated Zn, and NaI in DMSO at 25 °C resulted in an 87% isolated yield of alkanol 2a (see the Supporting Information for full details of the reaction optimization) .…”