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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Tandem 1,3-Dipolar Cycloaddition/Rearrangement of Nitronates with Cyclooctyne for the Diastereoselective Synthesis of
Polina I Maksakova1,2, Roman S Malykhin1, Alexander A Lukoyanov1
1N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, Moscow 119334, Russian Federation.
Abstract:
The 1,3-dipolar cycloaddition of cyclic nitronates (5,6-dihydro-4H-1,2-oxazine N-oxides) with cyclooctyne affords oxazine-annulated spiroaziridine derivatives in mild conditions with high yields and diastereoselectivity via consecutive strain-promoted [3 + 2]-cycloaddition/ring contraction. Isoxazoline N-oxides and silyl nitronates also react smoothly, albeit with a lower diastereoselectivity. DFT calculations reveal key features, such as half-boat conformation of the oxazine ring during cycloaddition, and control of the stereoselectivity during ring contraction by an anomeric effect in the O-N-O moiety.
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