Divergent Synthesis of Oxa‐Cyclic Nitrones through Gold(I)‐Catalyzed 1,3‐Azaprotio Transfer of Propargylic α‐Ketocarboxylate Oximes: Experimental and DFT Studies

• Published in: Chemistry : a European journal 2019-07, Vol.25 (42), p.9821-9826
• Main Authors: Wang, Chunhong, Cui, Qi, Zhang, Zhixin, Yao, Zhu‐Jun, Wang, Shaozhong, Yu, Zhi‐Xiang
• Format: Article
• Language: English
• Subjects: 1,3-azaprotio transfer; Alkynes; Carbonyl groups; Carbonyls; Catalysis; Chemistry; Configurations; DFT calculations; Gold; gold catalysis; Migration; Nitrogen; organic synthesis; oxa-cyclic nitrones; Oximes; Oxygen
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201901522

1,3‐Azaprotio transfer of propargylic α‐ketocarboxylate oximes, a new type of alkynyl oximes featuring an ester tether, has been explored by taking advantage of gold catalysis. The incorporation of an oxygen atom to the chain of alkynyl oximes led to the formation of two different oxa‐cyclic nitrones. It was found that internal alkynyl oximes with an E‐configuration deliver five‐membered nitrones, whereas terminal alkynyl oximes with an E‐configuration afford six‐membered nitrones. DFT calculations on four possible pathways supported a stepwise formation of C−N and C−H bonds, in which a 1,3‐acyloxy‐migration competes with the 1,3‐azaprotio‐transfer, especially in the case of internal alkynyl oximes. The relative nucleophilic properties of oxygen in the carbonyl group and the nitrogen in the oxime, the electronic effects of alkynes, and the influence of the ring system have been investigated computationally. Regiodivergent C−N bond formation was observed in a gold‐catalyzed 1,3‐azaprotio‐transfer of alkynyl oximes, which makes controllable the synthesis of five‐ and six‐membered oxa‐cyclic nitrones. DFT calculations suggested that owing to the different electrophilicities of C1 and C2 caused by the R group, the oxime and the ester groups may compete initially as N‐ and O‐nucleophiles.