Highly efficient and diastereoselective gold(I)-catalyzed synthesis of tertiary amines from secondary amines and alkynes: substrate scope and mechanistic insights.
An efficient method for the synthesis of tertiary amines through a gold(I)-catalyzed tandem reaction of alkynes with secondary amines has been developed. In the presence of ethyl Hantzsch ester and [{(tBu)(2)(o-biphenyl)P}AuCl]/AgBF(4) (2 mol %), a variety of secondary amines bearing electron-deficient and electron-rich substituents and a wide range of alkynes, including terminal and internal aryl alkynes, aliphatic alkynes, and electron-deficient alkynes, underwent a tandem reaction to afford the corresponding tertiary amines in up to 99 % yield. For indolines bearing a preexisting chiral center, their reactions with alkynes in the presence of ethyl Hantzsch ester catalyzed by [{(tBu)(2)(o-biphenyl)P}AuCl]/AgBF(4) (2 mol %) afforded tertiary amines in excellent yields and with good to excellent diastereoselectivity. All of these organic transformations can be conducted as a one-pot reaction from simple and readily available starting materials without the need of isolation of air/moisture-sensitive enamine intermediates, and under mild reaction conditions (mostly room temperature and mild reducing agents). Mechanistic studies by NMR spectroscopy, ESI-MS, isotope labeling studies, and DFT calculations on this gold(I)-catalyzed tandem reaction reveal that the first step involving a monomeric cationic gold(I)-alkyne intermediate is more likely than a gold(I)-amine intermediate, a three-coordinate gold(I) intermediate, or a dinuclear gold(I)-alkyne intermediate. These studies also support the proposed reaction pathway, which involves a gold(I)-coordinated enamine complex as a key intermediate for the subsequent transfer hydrogenation with a hydride source, and reveal the intrinsic stereospecific nature of these transformations observed in the experiments.
Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong. PR China.
Xin-Yuan
XY
Liu
Zhen
Z
Guo
Sijia S
SS
Dong
Xiao-Hua
XH
Li
Chi-Ming
CM
Che
D000480:Alkynes / Q000737:chemistry*; D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D006046:Gold / Q000737:chemistry*; D006865:Hydrogenation; D015394:Molecular Structure; D013237:Stereoisomerism
D000480:Alkynes; D000588:Amines; D006046:Gold