Cu‐Catalyzed Formal Methylative and Hydrogenative Carboxylation of Alkynes with Carbon Dioxide: Efficient Synthesis of α,β‐Unsaturated Carboxylic Acids

Abstract

The sequential hydroalumination or methylalumination of various alkynes catalyzed by different catalyst systems, such those based on Sc, Zr, and Ni complexes, and the subsequent carboxylation of the resulting alkenylaluminum species with CO2 catalyzed by an N-heterocyclic carbene (NHC)-copper catalyst have been examined in detail. The regio- and stereoselectivity of the overall reaction relied largely on the hydroalumination or methylalumination reactions, which significantly depended on the catalyst and alkyne substrates. The subsequent Cu-catalyzed carboxylation proceeded with retention of the stereoconfiguration of the alkenylaluminum species. All the reactions could be carried out in one-pot to afford efficiently a variety of α,β-unsaturated carboxylic acids with well-controlled configurations, which are difficult to construct by previously reported methods. This protocol could be practically useful and attractive because of its high regio- and stereoselectivity, simple one-pot reaction operation, and the use of CO2 as a starting material.

Copper–NHC complexes in catalysis

“…After the previously described reactions (hydrocarboxylation or boracarboxylation), it became of great interest to develop new methodologies based on CO 2 insertion and functionalization [77]. In 2013, Hou reported a copper catalyzed methylative and hydrogenative carboxylation (Scheme 2.3.3.1) [78]. First the examination of the alkenylaluminium intermediate in the absence of the copper source did not afford the carboxylate species.…”

Cu‐Catalyzed Alkylative Carboxylation of Ynamides with Dialkylzinc Reagents and Carbon Dioxide

“…Initially, we tried carbometalation of ynamide 1 a by using Me 3 Al as the alkylating reagent as we have previously demonstrated for the formal methylative carboxylation of alkynes 13. However, such attempts failed possibly due to the high reactivity of Me 3 Al towards the carbonyl group of ynamide 1 a providing complex reaction mixtures.…”

“…Our group has recently shown that N‐heterocyclic carbene (NHC) copper complexes can serve as excellent catalysts for the carboxylation of various organic substrates with CO 2 5c. e, 6h, 7b, 12, 13 In this context, we have achieved the borocarboxylation of alkynes with this substrate, CO 2 , and a diboron compound 12. More recently, we developed the regio‐ and stereoselective formal methylative carboxylation and hydrocarboxylation of alkynes with CO 2 , which afforded a variety of α,β‐unsaturated carboxylic acids with well‐controlled configurations 13.…”

“…e, 6h, 7b, 12, 13 In this context, we have achieved the borocarboxylation of alkynes with this substrate, CO 2 , and a diboron compound 12. More recently, we developed the regio‐ and stereoselective formal methylative carboxylation and hydrocarboxylation of alkynes with CO 2 , which afforded a variety of α,β‐unsaturated carboxylic acids with well‐controlled configurations 13. Despite these recent advances, the substrate scope remains limited to relatively simple terminal‐ and internal alkynes.…”

Regioselective Alkylative Carboxylation of Allenamides with Carbon Dioxide and Dialkylzinc Reagents Catalyzed by an N‐Heterocyclic Carbene–Copper Complex

“…In recent years, N‐heterocyclic carbene (NHC)–copper complexes have been proved to be excellent catalysts for the carboxylation of various organic compounds with CO 2 to give the corresponding carboxylic acids or their derivatives . As part of our studies on the use of CO 2 as a building block for organic synthesis, we recently reported the NHC‐copper‐catalyzed alkylative carboxylation of ynamides with CO 2 and dialkylzinc reagents, which afforded the corresponding α,β‐dehydro‐α‐amino acid derivatives .…”