Fast Pd- and Pd/Cu-Catalyzed Direct C–H Arylation of Cyclic Nitrones. Application to the Synthesis of Enantiopure Quaternary α-Amino Esters

Abstract

Cocatalysis by pivalic acid or copper bromide allows a very fast, clean, and high-yielding palladium-catalyzed coupling of a large array of aryl, thienyl, and pyridyl halides with cyclic nitrones, including DMPO. The study of the reaction conditions, scope, and mechanism is presented. Applied to the chiral nitrone MiPNO, this transformation provides a straightforward access to enantiopure α-methyl α-arylglycine esters.

Pseudoephedrine‐Directed Asymmetric α‐Arylation of α‐Amino Acid Derivatives

“…There are far fewer options for the asymmetric introduction of aryl rings10, 11 to the α‐carbon atom of α‐amino acids to make quaternary α‐arylated amino acids, and those that exist suffer from severe limitations in scope. Racemic α‐arylations have been achieved through Pd12–14 or Fe15 catalyzed reactions of enolates to form heterocyclic amino acid derivatives, with an asymmetric version requiring a complex multi‐step sequence 16. Electron‐deficient rings may be introduced intra‐17–20 or intermolecularly21–23 by stereoselective aryne or S N Ar chemistry.…”

Pseudoephedrine‐Directed Asymmetric α‐Arylation of α‐Amino Acid Derivatives

“…[2] Ar ange of methods for the asymmetric a-alkylation of readily available amino acids makes simple quaternary amino acids bearing a-alkyl groups readily accessible. [16] Electron-deficient rings may be introduced intra- [17][18][19][20] or intermolecularly [21][22][23] by stereoselective aryne or S N Ar chemistry.Maruoka et al [24] achieved an asymmetric phase-transfer arylation with Cr complexes of electron-rich arenes.We previously reported [25] ar acemic approach to the synthesis of a-aryl amino acids that makes use of the rearrangement of N-aryl urea derivatives [26][27][28][29][30] of amino acid enolates with migration of an aromatic ring from NtoC.The reaction formally involves an intramolecular nucleophilic aromatic substitution reaction, [31,32] but is much more general with regard to ring electronics than atypical S N Ar reaction. [16] Electron-deficient rings may be introduced intra- [17][18][19][20] or intermolecularly [21][22][23] by stereoselective aryne or S N Ar chemistry.Maruoka et al [24] achieved an asymmetric phase-transfer arylation with Cr complexes of electron-rich arenes.…”

“…[2] Ar ange of methods for the asymmetric a-alkylation of readily available amino acids makes simple quaternary amino acids bearing a-alkyl groups readily accessible. [16] Electron-deficient rings may be introduced intra- [17][18][19][20] or intermolecularly [21][22][23] by stereoselective aryne or S N Ar chemistry.Maruoka et al [24] achieved an asymmetric phase-transfer arylation with Cr complexes of electron-rich arenes. [16] Electron-deficient rings may be introduced intra- [17][18][19][20] or intermolecularly [21][22][23] by stereoselective aryne or S N Ar chemistry.Maruoka et al [24] achieved an asymmetric phase-transfer arylation with Cr complexes of electron-rich arenes.…”

“…[3][4][5][6][7][8][9] There are far fewer options for the asymmetric introduction of aryl rings [10,11] to the a-carbon atom of a-amino acids to make quaternary a-arylated amino acids,and those that exist suffer from severe limitations in scope.R acemic a-arylations have been achieved through Pd [12][13][14] or Fe [15] catalyzed reactions of enolates to form heterocyclicamino acid derivatives,with an asymmetric version requiring ac omplex multi-step sequence. [16] Electron-deficient rings may be introduced intra- [17][18][19][20] or intermolecularly [21][22][23] by stereoselective aryne or S N Ar chemistry.Maruoka et al [24] achieved an asymmetric phase-transfer arylation with Cr complexes of electron-rich arenes.We previously reported [25] ar acemic approach to the synthesis of a-aryl amino acids that makes use of the rearrangement of N-aryl urea derivatives [26][27][28][29][30] of amino acid enolates with migration of an aromatic ring from NtoC.The reaction formally involves an intramolecular nucleophilic aromatic substitution reaction, [31,32] but is much more general with regard to ring electronics than atypical S N Ar reaction. [33] Kawabata et al [34] simultaneously reported ac hiral memory effect in ar elated reaction that allowed certain members of the class of a-aryl a-amino acid derivatives to be prepared with good enantioselectivity.Aiming to solve the problem of asymmetric arylation of amino acids,particularly with electron-rich rings,wedecided to start from Myers very general methods for asymmetric alkylation, [8,9,35,…”

“…[3][4][5][6][7][8][9] There are far fewer options for the asymmetric introduction of aryl rings [10,11] to the a-carbon atom of a-amino acids to make quaternary a-arylated amino acids,and those that exist suffer from severe limitations in scope.R acemic a-arylations have been achieved through Pd [12][13][14] or Fe [15] catalyzed reactions of enolates to form heterocyclicamino acid derivatives,with an asymmetric version requiring ac omplex multi-step sequence. [16] Electron-deficient rings may be introduced intra- [17][18][19][20] or intermolecularly [21][22][23] by stereoselective aryne or S N Ar chemistry.Maruoka et al [24] achieved an asymmetric phase-transfer arylation with Cr complexes of electron-rich arenes.…”