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

Abstract

The alkylative carboxylation of allenamide catalyzed by an N-heterocyclic carbene (NHC)-copper(I) complex [(IPr)CuCl] with CO2 and dialkylzinc reagents was investigated. The reaction of allenamides with dialkylzinc reagents (1.5 equiv) and CO2 (1 atm.) proceeded smoothly in the presence of a catalytic quantity of [(IPr)CuCl] to afford (Z)-α,β-dehydro-β-amino acid esters in good yields. The reaction is regioselective, with the alkyl group introduced onto the less hindered γ-carbon, and the carboxyl group introduced onto the β-carbon atom of the allenamides. The first step of the reaction was alkylative zincation of the allenamides to give an alkenylzinc intermediate followed by nucleophilic addition to CO2 . A variety of cyclic and acyclic allenamides were found to be applicable to this transformation. Dialkylzinc reagents bearing β-hydrogen atoms, such as Et2 Zn or Bu2 Zn, also gave the corresponding alkylative carboxylation products without β-hydride elimination. The present methodology provides an easy route to alkyl-substituted α,β-dehydro-β-amino acid ester derivatives under mild reaction conditions with high regio- and stereoselectivtiy.

Alkylative Carboxylation of Ynamides and Allenamides with Functionalized Alkylzinc Halides and Carbon Dioxide by a Copper Catalyst

“…The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3:1) to afford 12 af (colorless oil, 79.1 mg, 82 %). The spectral data of 12 af obtained by this protocol were fully consistent with those reported in the previous literature …”

“…Thus, the development of methods to synthesize dehydroamino acids and derivatives by carboxylation reactions using CO 2 is highly important. 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 . In this context, we have achieved the alkylative carboxylation of ynamides with dialkylzinc reagents (R 2 Zn) and CO 2 which affords α,β‐dehydro‐α‐amino acid esters bearing a branched alkyl group introduced by the addition of dialkylzinc reagents .…”

“…In this reaction, the alkylative carboxylation formally consists of Cu‐catalyzed carbozincation of ynamides and the subsequent carboxylation of resulting alkenylzinc species with CO 2 . More recently, we have developed also the alkylative carboxylation of allenamides with dialkylzinc reagents and CO 2 which affords α,β‐dehydro‐β‐amino acid esters through a similar reaction pathway . Although these methods can afford a variety of α,β‐dehydroamino acid esters with well‐controlled configurations, the introducible alkyl groups are limited to methyl, ethyl, or butyl due to the accessibility of dialkylzinc reagents.…”

Asymmetric Sulfinylations ofN‐Methylephedrine‐Modified Tri‐ or Tetraalkyl Zincates by Symmetric Diaryl Sulfoxides

“…Preparation of Bu 2 Zn and Hex 2 Zn: At 0 °C n BuLi or n HexLi (solutions in hexane, 18.7 mmol, 2.0 equiv.) was added dropwise to dry ZnCl 2 (1.28 g, 9.35 mmol) in Et 2 O (10 mL).…”

Carboxylation Reactions with Carbon Dioxide Using N‐Heterocyclic Carbene‐Copper Catalysts

“…The development of catalytic version of the carboxylation of allenamides with CO 2 is of interest . We have achieved a [(IPr)CuCl]‐catalyzed alkylative carboxylation of allenamides with CO 2 and dialkylzinc reagents, affording α,β ‐dehydro‐ β ‐amino acid esters with high regio‐ and stereoselectivity …”