Journal article

Causation in a Cascade: The Origins of Selectivities in Intramolecular Nitrone Cycloadditions

Elizabeth H Krenske, Sesil Agopcan, Viktorya Ayiyente, KN Houk, Brian A Johnson, Andrew B Holmes

Journal of the American Chemical Society | AMER CHEMICAL SOC | Published : 2012


The factors controlling chemo-, regio-, and stereoselectivity in a cascade of reactions starting from a bis(cyanoalkenyl)oxime and proceeding via nitrone cycloadditions have been unraveled through a series of density functional theory calculations with several different functionals. Both kinetic and thermodynamic control of the reaction cascade are important, depending upon the conditions. Kinetic control was analyzed by the distortion/interaction model and found to be dictated by differences in distortions of the cycloaddends in the transition states. A new mechanism competing with that originally proposed in the application of these reactions to the histrionicotoxin synthesis was discovere..

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University of Melbourne Researchers


Awarded by NIH (FIRCA)

Awarded by NSF

Awarded by Australian Research Council


Awarded by Division Of Chemistry

Funding Acknowledgements

We thank NIH (FIRCA Project 5R03TW007177-02 to V.A. and S.A.), NSF (CHE-0548209 to K.N.H.), the Australian Research Council (DP0985623 to E.H.K.), the ARC Centre of Excellence for Free Radical Chemistry and Biotechnology (funding to E.H.K.), and CSIRO (fellowship to A.B.H.) for generous financial support. Computing resources used in this work were provided by the National Center for High Performance Computing of Turkey UYBHM (Grants 20452008 and 11062010), UCLA Academic Technology Services/Institute for Digital Research and Education, the National Computational Infrastructure National Facility (Australia), and the University of Melbourne School of Chemistry .