Synthesis of α‐Amino Acids by Umpolung of Weinreb Amide Enolates

Abstract

An efficient and diastereoselective synthesis of α-amino acids from readily available starting materials has been developed. The key feature of this reaction is an umpolung of a glycinederived enolate, providing an alternative approach for the synthesis of α-amino acids.

Lithium Enolates Derived from Weinreb Amides: Insights into Five-Membered Chelate Rings

“…5,6,7 Evidence of an odd demethoxylation (eq 6) might preclude some applications, 7,9 but this outcome becomes significant only at elevated temperatures (above −30 °C). Possible advantages of Weinreb enolates relative to propionate ester enolates include total selectivity for Z enolate geometry 8 and formation of Weinreb amide products poised for further transformation (eq 1).…”

“…4,5,6,7 The potentially advantageous features of reactions with these compounds include the anticipated high Z -selective enolization characteristic of carboxamides 8 and the synthetic utility of the Weinreb amides (eq 2). Several strange observations are included in the reports.…”

“…Demethoxylation occasionally affords N -methyl carboxamides. 7,9 Davis and co-workers, 6 incredulously, metalated and functionalized a Weinreb amide by using lithium diisopropylamide (LDA) in the presence of 5 equiv of water. In general, applications of Weinreb enolates are rare, 5,6,7 and we can find no structural or mechanistic studies.…”

Nucleophilic Arylation of N,O‐Ketene Acetals with Triaryl Aluminum Reagents: Access to α‐Aryl Amides through an Umpolung Process

“…[10] To suppress this undesired retro-ene reaction and introduce the desired nucleophile at the C a position, we decided to use isoxazolidine amides 7 owing to the restricted rotation of the N À O bond (Table 1). [12] We initially investigated the phenylation of O-silyl N,Oketene acetal 9,which was generated in situ by the treatment of N-alkoxyamide 7a with as ilylating agent and an amine base through at wo-step,o ne-pot process (Table 1). [12] We initially investigated the phenylation of O-silyl N,Oketene acetal 9,which was generated in situ by the treatment of N-alkoxyamide 7a with as ilylating agent and an amine base through at wo-step,o ne-pot process (Table 1).…”

“…[11] We intended to use N-alkoxyamide 7a to investigate the possibility of the nucleophilic arylation of N,O-ketene acetal 9.F urthermore,a no rganoaluminum reagent with Lewis acidic characteristics was selected as the nucleophile because it would trigger the desired sequential coordination, N À Ob ond cleavage,a nd nucleophilic addition. [12] We initially investigated the phenylation of O-silyl N,Oketene acetal 9,which was generated in situ by the treatment of N-alkoxyamide 7a with as ilylating agent and an amine base through at wo-step,o ne-pot process (Table 1). [13] The nucleophilic phenylation of 7a was performed in CH 2 Cl 2 at ambient temperature with trimethylsilyl triflate (TMSOTf), iPr 2 NEt, and triphenylaluminum.…”