Tempering the Reactivities of Postulated α-Oxo Gold Carbenes Using Bidentate Ligands: Implication of Tricoordinated Gold Intermediates and the Development of an Expedient Bimolecular Assembly of 2,4-Disubstituted Oxazoles

Abstract

2,4-Oxazole is an important structural motif in various natural products. An efficient modular synthesis of this structure is achieved via a [3+2] annulation between a terminal alkyne and a carboxamide by using a gold-catalyzed oxidation strategy. The postulated reactive intermediate, a terminal α-oxo gold carbene, previously known to be highly electrophilic and hence impropable to be trapped by stoichiometric external nucleophiles, is coerced to react smoothly with a carboxamide en route to the oxazole ring by a P,N- or P,S-bidentate ligand such as Mor-DalPhos; in stark contrast, often used ligands including monodentate phosphines and NHCs are totally ineffective. The role of these bidentate phosphines in this reaction is attributed to the formation of a tricoordinated gold carbene intermediate, which is less electrophilic and hence more chemoselective when reacting with nucleophiles. The success in using bidentate phosphine ligands to temper the reactivities of in-situ generated gold carbenes would likely open many new opportunities to apply the oxidative gold catalysis to the development of novel methods, and the implication of tricoordinated gold intermediates in homogeneous gold catalysis should stimulate further advance in gold catalysis.

Highly Efficient One-Pot Synthesis of 2,4-Disubstituted Thiazoles Using Au(I) Catalyzed Oxidation System at Room Temperature

“…It can be seen that Mor-DalPhosAuCl exhibited the good yield of 58% with the presence of AgNTf 2 , and Me-DalPhosAuCl showed the slightly inferior yield of 53%, due to the steric size of the pendant secondary amine [28]. These prospective results were consistent with our previous works, which further supported the accepted viewpoint that P,N-bidentate ligands could attenuate the strong electrophilicity of the a-oxo gold carbene via the formation of a tricoordinated metal center [29,30]. L1AuCl and L2AuCl, with the more rigid cyclic structure, displayed less-efficient yield in this reaction.…”

One-Step Synthesis of 2,4-Disubstituted Thiazoles in Au(I) Complex/Zinc Salt Catalytic System

“…Hashmi 等 [4g,6] 报道了 Au(III)配合物催化体 系在五元杂环合成中显示了较高的催化活性. Zhang 等 [7] 利用 Au(I)配合物催化体系高效地合成了噁唑类化 167.39, 158.92, 133.92, 129.67, 128.77, 126.42, 112.60, 31.90, 31.72, 29.60, 29.58, 29.45, 29.32, 29.21, 22.67, 14.10;IR (neat) ν: 2924IR (neat) ν: , 2853IR (neat) ν: , 1516IR (neat) ν: , 1499IR (neat) ν: , 1461IR (neat) ν: , 1436IR (neat) ν: , 1245IR (neat) ν: , 1002 165.12, 157.36, 111.70, 31.90, 31.55, 29.59, 29.57, 29.43, 29.33, 29.31, 29.25, 22.67, 19.10, 14.10;IR (neat) ν: 2955IR (neat) ν: , 2924IR (neat) ν: , 2854IR (neat) ν: , 1524IR (neat) ν: , 1465IR (neat) ν: , 1376IR (neat) ν: , 1180IR (neat) ν: , 1131 156.79, 110.68, 44.81, 35.85, 31.89, 31.64, 29.58, 29.56, 29.42, 29.34, 29.31, 29.21, 27.99, 26.42, 22.66, 14.09;IR (neat) ν: 2924IR (neat) ν: , 2854IR (neat) ν: , 1522IR (neat) ν: , 1460IR (neat) ν: , 1377IR (neat) ν: , 1321IR (neat) ν: , 1130 8.28 (td,J＝7.7,1.8 Hz,1H),7.36 (dddd,J＝8.3,7.1,5.2,1.8 Hz,1H),7.26～7.21 (m,1H),7.17 (ddd,J＝11.2,8.3,1.1 Hz,1H),7.00 (s,1H),…”

Optimizing P,N‐Bidentate Ligands for Oxidative Gold Catalysis: Efficient Intermolecular Trapping of α‐Oxo Gold Carbenes by Carboxylic Acids

“…Earlier we reported for the first time that the reactivity of the gold carbene could be attenuated by using bidentate phosphine ligands so that it reacted with carboxamides efficiently, leading to a one-step synthesis of 2,4-disubstituted oxazoles. [6] Mor-DalPhos (see Scheme 1B), [7] a bulky P,N -bidentate ligand, was found as a uniquely effective ligand, and its role is proposed to enable the formation of a tris-coordinated gold carbene (e.g., A ) instead of the typical bis-coordinated one (e.g., A’ ), leading to attenuated electrophilicity at the carbene center (Scheme 1B). …”