Nitrone Cycloadditions of 1,2-Cyclohexadiene

We report the first 1,3-dipolar cycloadditions of 1,2-cyclohexadiene, a rarely exploited strained allene. 1,2-Cyclohexadiene is generated in situ under mild conditions and trapped with nitrones to give isoxazolidine products in synthetically useful yields. The reactions occur regioselectively and ex...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2016-03, Vol.138 (8), p.2512-2515
Main Authors: Barber, Joyann S, Styduhar, Evan D, Pham, Hung V, McMahon, Travis C, Houk, K. N, Garg, Neil K
Format: Article
Language:English
Subjects:
Allyl Compounds - chemistry
Cycloaddition Reaction
Cyclohexenes - chemistry
Heterocyclic Compounds - chemical synthesis
Nitrogen Oxides - chemistry
Stereoisomerism
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Summary:We report the first 1,3-dipolar cycloadditions of 1,2-cyclohexadiene, a rarely exploited strained allene. 1,2-Cyclohexadiene is generated in situ under mild conditions and trapped with nitrones to give isoxazolidine products in synthetically useful yields. The reactions occur regioselectively and exhibit a notable endo preference, thus resulting in the controlled formation of two new bonds and two stereogenic centers. DFT calculations of stepwise and concerted reaction pathways are used to rationalize the observed selectivities. Moreover, the strategic manipulation of nitrone cycloadducts demonstrates the utility of this methodology for the assembly of compounds bearing multiple heterocyclic units. These studies showcase the exploitation of a traditionally avoided reactive intermediate in chemical synthesis.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.5b13304