Amide-Phosphonium Salt as Bifunctional Phase Transfer Catalyst for Asymmetric 1,6-Addition of Malonate Esters to para-Quinone Methides

• Published in: Journal of organic chemistry Vol. 81; no. 19; pp. 9315 - 9325
• Main Authors: Ge, Luo, Lu, Xuehe, Cheng, Cang, Chen, Jie, Cao, Weiguo, Wu, Xiaoyu, Zhao, Gang
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.10.2016; Amer Chemical Soc
• Subjects: agonists; amino acids; biphenyl; catalysts; Chemistry; Chemistry, Organic; esters; organic chemistry; Physical Sciences; salts; Science & Technology; 1,6-CONJUGATE ADDITION; AMINO-ACID; ENANTIOSELECTIVE SYNTHESIS; QUANTIFICATION; EXPEDIENT ACCESS; OXINDOLES; NUCLEOPHILIC REACTIVITIES; ALDEHYDES; QUATERNARY CENTERS; CONJUGATE ADDITION
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/acs.joc.6b01906

Asymmetric 1,6-addition of malonates to para-quinone methides has been developed by using amide-phosphonium salts derived from easily available chiral α-amino acids as bifunctional phase transfer catalysts. Stabilized para-quinone methides with various substituents on the phenyl ring were reacted with diphenyl malonates to give functionalized diaryl methines in excellent yields and high to excellent ee’s. Furthermore, to show the utility of this methodology, a gram scale synthesis of an 1,6-addition adduct and its further elaboration into the key intermediate for synthesis of GPR40 agonists were also described.