Gold‐Catalyzed Iminations of Terminal Propargyl Alcohols with Anthranils with Atypical Chemoselectivity for C(1)‐Additions and 1,2‐Carbon Migration

Abstract

This work reports gold‐catalyzed iminations of terminal propargyl alcohols with anthranils or isoxazoles to yield E‐configured α‐amino‐2‐en‐1‐ones and ‐1‐als with complete chemoselectivity. These catalytic iminations occur exclusively with C(1)‐nucleophilic additions on terminal alkynes, in contrast to a typical C(2)‐route. For 3,3‐dialkylprop‐1‐yn‐3‐ols, a methyl substituent is superior to long alkyl chains as the 1,2‐migration groups toward α‐imino gold carbenes. For secondary prop‐1‐yn‐3‐ols, phenyl, vinyl, and cyclopropyl substituents are better than hydrogen as the migrating groups, obviating typical gold carbene reactions. DFT calculations have been performed to rationalize the observed C(1)‐regioselectivity and the preferable cyclopropyl migration based on gold carbene pathways.

Nitrene Transfer and Carbene Transfer in Gold Catalysis

“…102 The excellent diastereoselectivity observed for these products is believed to be an outcome of a stepwise formation of an eight-membered intermediate from a (5 + 3) annulation, followed by the cleavage of a ring in intermediate Extending the scope of these nitrene-transfer reactions of anthranils, Liu and co-workers reported a novel gold-catalyzed imination of terminal propargyl alcohols 201 with anthranils 202 and isoxazoles 204 to construct E-configured α-amino-2-en-1-ones or -1-als 203 and 205 with high chemoselectivity and a 1,2-carbon migration (Scheme 93). 103 This imination reaction preferred a terminal alkyne C(1) attack over the traditional C(2)-path. The protocol was catalyzed by JohnPhosAuCl/ AgNTf 2 (5 mol %) to allow a nucleophilic attack of both anthranils and isoxazoles toward 3,3-dialkyl propargyl alcohols or secondary propargyl alcohols.…”

Au(III) catalyzes the cross-coupling between activated methylenes and alkene derivatives

“…Gold catalysis is one of the most captivating topics in Organic Chemistry [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. In recent years, particular attention has been devoted to gold catalyzed CAH bond activations as a strategic tool for the formation of new CAC bonds.…”

1,2-Migrations onto Gold Carbene Centers

“…According to the to-date observed group migrations onto gold carbenes, the migratory aptitude of the groups is summarized as follows: (1) normally, 1,2-H migration is favored over 1,2-alkyl migration; (2) in the case of releasing ring strain, alkyl groups migrate prior to H; 101,102,117,125 (3) in most cases, sp-and sp 2hybridized carbon-based groups (alkynyl, aryl, alkenyl, allenyl) m i g r a t e s e l e c t i v e l y o v e r H a n d a l k y l groups; 112,113,131,134,137,150,151 (4) alkyl groups present a migratory aptitude as long-chain alkyl > short-chain alkyl; 82,116 (5) the migrations of OAc, OPiv, and OBn are favored over H; 62,87,98,108,126 (6) for heteroatoms, the order is S > N > O. 133 Although significant advances in developing new methodologies based on 1,2-migrations onto gold carbenes have been made, opportunities and challenges remain.…”

“…For instance, in most cases, the migrations are in accordance with the abovementioned migratory aptitudes; however, exceptions were observed in some reports. 82,151,114,127 The substitutents on the carbene and the ancillary ligand initially determine the reactivity of gold carbene and thus affect the selectivity of the 1,2migration. For example, a reverse selectivity of hydride and alkyl has been observed by switching the ancillary ligand from a sterically bulky phosphine ligand to an arylphosphite ligand.…”

“…Liu and co-workers found that the reaction between anthranils and terminal propargyl alcohols delivers E-configured 3-amino-2-en-1-ones (Scheme 71). 151 Various groups were observed to perform 1,2-migrations. All of the phenyl, 2-and 3thienyl, alkenyl, and cyclopropyl groups migrate prior to hydride.…”