N-Heterocyclic carbene-catalyzed direct cross-aza-benzoin reaction: Efficient synthesis of α-amino-β-keto esters

Abstract

SummaryAn efficient catalytic synthesis of α-amino-β-keto esters has been newly developed. Cross-coupling of various aldehydes with α-imino ester, catalyzed by N-heterocyclic carbene, leads chemoselectively to α-amino-β-keto esters in moderate to good yields with high atom efficiency. The reaction mechanism is discussed, and it is proposed that the α-amino-β-keto esters are formed under thermodynamic control.

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

“…The NHC generated from the bicyclic pentafluoro triazolium salt promoted the chemoselective cross aza-benzoin reaction of aldehydes with N -PMP-imino esters to afford α-amino-β-keto esters in good yield ( Scheme 22 ) [ 38 ]. A range of functional groups are tolerated under the optimised reaction conditions.…”

Advancements in N-heterocyclic carbenes (NHCs) catalysis for benzoin reactions: A comprehensive review from past to present

“…The cross-aza-benzoin reaction between aldehydes and N-PMP-imino esters 126 was very well promoted by the NHC generated from bicyclic pentafluorotriazolium salt 15 to afford products of -amino--keto esters 127 in good yield, as investigated by Uno and colleagues in 2012 [93]. Scheme 8 depicts their findings.…”

α-Imino Esters in Organic Synthesis: Recent Advances

“…Takemoto et al have reported N -heterocyclic carbene (NHC)-catalyzed acylation of α-imino esers, to synthesize α-amino-β-keto esters. Reactions were carried out by stirring a solution of an aldehyde with 1.1 equiv of α-imino ester in the presence of NHC precatalyst 345a (20 mol %) and K 2 CO 3 (20 mol %) in THF at room temperature for 24 h. Various substituted aromatic aldehydes worked well in the reaction, affording corresponding acylated products 344 in 39–73% yields.…”

“…Takemoto et al 138 . 142 Examples of the addition of N, O, and S nucleophiles to αimino esters are rare, and corresponding addition products could be utilized in the heterocycles synthesis.…”