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. 2013 May 8;135(18):6747-9.
doi: 10.1021/ja402893z. Epub 2013 Apr 24.

Enantioselective thiourea-catalyzed intramolecular cope-type hydroamination

Adam R Brown  1 , Christopher Uyeda, Carolyn A Brotherton, Eric N Jacobsen
Affiliations

Enantioselective thiourea-catalyzed intramolecular cope-type hydroamination

Adam R Brown et al. J Am Chem Soc. .

Abstract

Catalysis of Cope-type rearrangements of bis-homoallylic hydroxylamines is demonstrated using chiral thiourea derivatives. This formal intramolecular hydroamination reaction provides access to highly enantioenriched α-substituted pyrrolidine products and represents a complementary approach to metal-catalyzed methods.

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Figures

Figure 1
Figure 1
Calculated electronic energies for the optimized structures of the substrate, transition state, N-oxide intermediate, and product for both an uncatalyzed- (black, top) and a N,N'-dimethylthiourea-catalyzed (blue, bottom) Cope hydroamination reaction (B3LYP/6-331+G(d, p) level of DFT). Relative energies are in kcal/mol and key hydrogen bonding distances are shown in Angstroms.
Scheme 1
Scheme 1
Design Strategy for Enantioselective Cope-Type Hydroamination Catalyst
See this image and copyright information in PMC

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