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The Cyclization of Allenyl‐Substituted Hydroxylamines to 1,2‐Oxazines: an Experimental and Computational Study
Author(s) -
UtechtJarzyńska Greta,
Jasiński Marcin,
Würthwein ErnstUlrich,
Reissig HansUlrich
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202001147
Subject(s) - chemistry , hydroxylamine , zwitterion , nitroso , protonation , deuterium , solvent , medicinal chemistry , computational chemistry , organic chemistry , molecule , ion , physics , quantum mechanics
To gain a deeper understanding of the formation of the synthetically important 3,6‐dihydro‐2 H ‐1,2‐oxazines, the 6‐ endo‐trig cyclization of allenyl‐substituted hydroxylamines was experimentally investigated in detail employing a model compound. The solvent effect was moderate with respect to the rate, but crucial to suppress side‐product formation. Surprisingly, acids or bases had no big influence on the cyclization rate. With O‐deuterated allenyl hydroxylamine a high primary isotope effect was found, indicating that the proton transfer is crucial in the rate‐determining step. DFT calculations evidence that the allenyl‐substituted hydroxylamine is converted into an energetically similar zwitterionic intermediate with an allyl cation subunit. It cyclizes to the 1,2‐oxazine as the most stable species. Alternative pathways starting from the zwitterion were computationally investigated. Interestingly, it can also undergo a fragmentation to give a pentadiene derivative and a nitroso compound. The hetero Diels–Alder reaction of these components may also deliver the 1,2‐oxazine. To evaluate an alternative mechanistic scenario, calculations of the protonated allenyl‐substituted hydroxylamine were also performed.