Gold-catalyzed synthesis of N,O-heterocycles

Abstract

The selective synthesis of oxazoles, alkylidene oxazoles, and 1,3-oxazines from N-propargyl carboxamides by choosing gold(III) or gold(I) catalysts and selecting terminal or internal alkynes as substrates is discussed. The mechanistic studies based on labeling experiments and intensive in situ NMR studies indicate an anti-oxyauration step and a protodeauration with retention of the sterical arrangement at the double bond. The synthetic scope for gold(I) catalysts is very broad, allowing selective conversions to products with properties of chelate ligands, reactions of bromoarenes and the formation of acceptor-substituted oxazoles. With N-heterocyclic carbene (NHC) ligands in the presence of a base, even the vinylgold intermediates of the reactions leading to 1,3-oxazines could be isolated, a reaction with a great potential for future mechanistic studies and future applications of gold catalysis.

Gold Catalysis: Products and Intermediates Obtained from N‐Propargylcarboxamides Bearing Additional Substituents on Nitrogen

“…The gold‐catalysed synthesis of heterocycles is a highly useful tool 4. In this area we have developed a simple synthesis of oxazoles5 and alkylideneoxazolines6 from N ‐propargylcarboxamides 7. The same class of substrates then also allowed the isolation of vinylgold intermediates,8 a technique which subsequently proved to be of broad scope 9…”

Recent advances in the gold-catalyzed additions to C–C multiple bonds

“…This past decade has been the boom time for homogeneous gold catalysis, which was rather limited in organic synthesis until the advantages of gold complexes as catalysts were discovered [ 1 ]. In comparison to other transition-metal catalysts, most gold-catalyzed reactions are atom-economic, remarkably mild with regard to reaction conditions, and most importantly, have a different reaction scope [ 2 – 4 ].…”

“…One of the most important fundamental reactions in gold-catalyzed synthesis is the addition of X–H (X = O, N, C) bonds to C–C multiple bonds, which features diverse functional group tolerance and the easy formation of carbon–carbon and carbon–heteroatom bonds [ 1 , 4 – 5 ]. Furthermore, the rapid growing area of tandem reactions has allowed chemists to assemble diverse complex molecular frameworks more conveniently.…”

Diastereospecific Gold(I)‐Catalyzed Cyclization Cascade for the Controlled Preparation of N‐ and N,O‐Heterocycles

“…Gold(I) catalysis has been used to prepare N,O‐heterocycles by reaction of amides and hydroxylamine with alkynes and allenes and it is well recognized that electrophilic gold(I) catalysts are powerful mediators for the cycloisomerization of 1, n ‐enynes and their trapping with various nucleophiles . Although there is a wealth of work in this area, we identified that there were still untapped opportunities in the trapping of transient cyclopropyl‐gold(I) carbenes with oximes.…”