Work

Rotational Isomers of N-Methyl-N-arylacetamides and Their Derived Enolates: Implications for Asymmetric Hartwig Oxindole Cyclizations

Year: 2013

Type: article

Abstract: The rotational preferences of N-(2-bromo-4,6-dimethylphenyl)-N-methyl 2-phenylpropanamide were studied as a model of precursors for Hartwig asymmetric oxindole cyclizations. The atropisomers of this compound were separated by flash chromatography, and then the enantiomers were resolved and the interconversions of the stereocenter and the N-Ar axis were studied. Under thermal conditions, the axis is very stable. Under the basic conditions of the Hartwig cyclization, both the stereocenter and the chiral axis equilibrate via enolate formation. The N-Ar rotation barrier of a 2-phenylacetamide analogue was reduced from 31 kcal mol(-1) in the precursor to 17 kcal mol(-1) in the enolate. Reasons for this dramatic barrier reduction and implications of both N-Ar and amide C-N rotations for Hartwig cyclizations are discussed.

Source: The Journal of Organic Chemistry

DOI: 10.1021/jo400385t

Authors: Jérémie Mandel, Xiaohong Pan, E. Ben Hay, Steven J. Geib, Craig S. Wilcox, Dennis P. Curran

Institution: University of Pittsburgh

Language: English

Topic: Axial and Atropisomeric Chirality Synthesis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Center for Research Resources

Awards: Purchase of a Single Crystal Defractometer for Use with Small Crystals, Purchase of a 600 MHz NMR Spectrometer with Cryoprobe, Fluorous Mixture Synthesis of Natural Product Libraries