Three‐Component [2+2+1] Gold(I)‐Catalyzed Oxidative Generation of Fully Substituted 1,3‐Oxazoles Involving Internal Alkynes

Abstract

Three‐component [2+2+1] gold(I)‐catalyzed reaction of internal alkynes (alkynyl esters or ‐ketones), nitriles, and 2‐chloropyridine N‐oxide led to a wide range of fully substituted 1,3‐oxazoles (32 examples; up to 92% isolated yields). Nitrile R3CN species, employed in the reaction as both reactants and solvents, comprise conventional nitriles (R3=Alk, Ar) and also push‐pull systems such as cyanamides (R3=NH2 and NAlk2) and the thiocyanate (R3=SPr). The advantages of the developed method include mild reaction conditions, high functional‐group tolerance, broad range of substituents R1/R3 along with a possibility of easy modification of COR2 or the amino group when R1=NH2.magnified image

Homogeneous Gold-Catalyzed Oxidation Reactions

“…In 2019, Dubovtsev and Kukushkin developed several conditions to expand the scope of this type of double oxidation to various terminal and internal alkynes − and further demonstrated the synthetic utilities of the glyoxal products. They can be converted into several types of heterocycles using one-pot transformations (Scheme B) .…”

“…The use of 2-picoline N -oxide necessitates the use of MsOH in order to prevent catalyst inhibition by 2-picoline. Later, ynoates were shown by Dubovtsev and Kukushkin to be suitable alkyne substrates in this annulation chemistry (Scheme C) . The reaction provides access to a range of fully substituted oxazole-4-carboxylates 33 .…”

Synthesis of densely substituted pyridine derivatives from nitriles by a non-classical [4+2] cycloaddition/1,5-hydrogen shift strategy

“…As illustrated in Fig. 2B, in the nucleophilic addition of nitriles, the most reported reaction partners have been focused on the highly reactive nitrogen, [44][45][46][47][48][49][50][51][52] oxygen, [53][54][55][56][57][58][59][60][61] and sulfur nucleophiles till now. [62][63][64] For carbon pronucleophiles, the related studies are only limited to sp, sp 2 , and sp 3 with α-electron withdrawing group (i.e.…”

A Gold‐Catalyzed Acid‐Assisted Regioselective Cyclization for the Synthesis of Polysubstituted Oxazoles

“…The solid‐state molecular structure of the desired product 3d is depicted in Figure . Based on the many applications of amide and ester groups in medical compounds, this protocol towards polysubstituted oxazoles offers a meaningful synthetic method.…”