Gold‐Catalyzed Stereoselective Domino Cyclization/Alkynylation of N‐Propargylcarboxamides with Benziodoxole Reagents for the Synthesis of Alkynyloxazolines

Abstract

A concise and highly stereoselective synthesis of alkynyloxazolines via a gold‐catalyzed domino cyclization‐alkynylation cascade of N‐propargylcarboxamides with benziodoxole reagents is reported. This new protocol, which represents an attractive alternative to two step sequences based on Sonagashira couplings, offers a broad substrate scope, excellent functional group tolerance, and perfect stereoselectivity. A comparison of the computed energies of the isomers of the product suggests kinetic control as the cause of the observed selectivity.

Dehydrogenative Cycloisomerization/Arylation Sequence ofN‐Propargyl Carboxamides with Arenes by Iodine(III)‐Catalysis

“…Nevertheless, the catalytic intermolecular arylation process has been limited to the cross‐coupling reactions between the arenes [14a–c] . Furthermore, the exo ‐cycloisomerization/carbon‐functionalization reactions of N ‐propargyl carboxamides have been developed for the effective and versatile synthesis of 2,5‐disubstituted oxazoles [15a–c,e] or 5‐alkylideneoxazolines, [15d–g] which are prevalent in many natural products and pharmaceutically active compounds [1c,d] . Unfortunately, except for the synthesis of dimeric ketones, [15e] only the tandem reaction via carbonylation step has been known as the dehydrogenative method for the formation of oxazolines [15d] .…”

Recent Advances in Gold(III) Chemistry: Structure, Bonding, Reactivity, and Role in Homogeneous Catalysis

“…[442][443][444][445][446] Various mechanistic possibilities have been proposed for these reactions, which either consider Au(I) as carbophilic Lewis acid forming alkyne π-complexes, or assume Au(I, III) redox cycles. 446 The reaction was extended to the coupling of TIPS-EBX with thiophenes through an AuCl / trifluoroacetic acid "cooperative effect", although the causes for this effect remained obscure. 447 N-allenamides react with EBX under AuCl catalysis in MeCN to give oxyalkynylation products 256 (Scheme 108 C).…”

“…A number of reactions have been reported where alkynyl-substituted iodine­(III) reagents (ethynylbenziodoxol­(on)­es, EBXs) are used as coupling partners in arene and alkyne alkynylations. Scheme shows some examples. − Various mechanistic possibilities have been proposed for these reactions, which either consider Au­(I) as carbophilic Lewis acid forming alkyne π-complexes or assume Au­(I, III) redox cycles . The reaction was extended to the coupling of TIPS-EBX with thiophenes through an AuCl/trifluoroacetic acid “cooperative effect”, although the causes for this effect remained obscure .…”

Gold and hypervalent iodine(iii): liaisons over a decade for electrophilic functional group transfer reactions

“…In another domino cyclization/alkynylation approach, where such interplay of activation modes is seen would be the highly stereoselective synthesis of (E)-alkynyloxazolines (113, up to 67% yields) by N-propargylcarboxamides 112 and benziodoxole reagents 3b (Scheme 18). 51 Mechanistically, the carbonyl oxygen atom attacks the alkyne, which is p-coordinated to Au(I), in a 5-exo-dig fashion to form vinylgold(I) intermediate 115. Next, the oxidative addition of intermediate 115 to 3b affords intermediate 116, which then undergoes ligand dissociation and reductive elimination to give the final product (E)-113 with the regeneration of the active Au(I)-catalyst.…”