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. 2017 Apr 7;82(7):3826-3843.
doi: 10.1021/acs.joc.7b00391. Epub 2017 Mar 15.

Catalytic, Enantioselective, Intramolecular Sulfenoamination of Alkenes with Anilines

Scott E Denmark  1 , Hyung Min Chi  1
Affiliations

Catalytic, Enantioselective, Intramolecular Sulfenoamination of Alkenes with Anilines

Scott E Denmark et al. J Org Chem. .

Abstract

A method for the catalytic, enantioselective, intramolecular sulfenoamination of alkenes with aniline nucleophiles has been developed. The method employs a chiral, Lewis basic selenophosphoramide catalyst and a Brønsted acid co-catalyst to promote stereocontrolled C-N and C-S bond formation by activation of an achiral sulfenylating agent. Benzoannulated nitrogen-containing heterocycles such as indolines, tetrahydroquinolines, and tetrahydrobenzazepines were prepared with high to excellent enantioselectivities. The impact of tether length and electron density of both the nucleophile and olefin on the reactivity, site selectivity, and enantioselectivity were investigated and interpreted in terms of substrate-dependent stereodetermining thiiranium ion formation or capture.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Chart 1
Chart 1. Tetrahydroquinolines in Natural and Synthetic Compounds
Figure 1
Figure 1
Three strategies for the synthesis of tetrahydroquinolines.
Figure 2
Figure 2
Different connectivity-based approaches to tetrahydroquinoline ring construction.
Scheme 1
Scheme 1. Example Reactions of Disconnections 1–4
Scheme 2
Scheme 2. Examples of Two-Bond-Forming Reactions
Scheme 3
Scheme 3. Zhou’s Two-Step Sequence Strategy
Scheme 4
Scheme 4. Intermediacy of the Thiiranium ions in Sulfenofunctionalization Reactions
Scheme 5
Scheme 5. Previously Reported Enantioselective Sulfenofunctionalization Reactions
Scheme 6
Scheme 6. Lewis Base Catalyzed Sulfenofunctionalization Reactions
Figure 3
Figure 3
Catalytic cycle for enantioselective sulfenofunctionalization reaction.
Scheme 7
Scheme 7. Sulfenoamination of Amines and Anilines
Scheme 8
Scheme 8. Three Main Routes for the Preparation of 2-Alkenylaniline Substrates
Scheme 9
Scheme 9. Reductive Cleavage of the Sulfide Moiety
Scheme 10
Scheme 10. Effect of the Electron Density of Nucleophile on Sulfenoamination
Figure 4
Figure 4
Unified mechanistic scheme for different TOLS.
Scheme 11
Scheme 11. Configurational Stability of N-Phenyl Thiiranium Ion
Scheme 12
Scheme 12. Shift in Turnover-Limiting Step of Substrate 2c
Scheme 13
Scheme 13. Sulfenofunctionalization of Phenol and Aniline
Figure 5
Figure 5
Two pathways for generation of the thiiranium ion intermediates.
Scheme 14
Scheme 14. Impact of Tether Length on Site Selectivity with Tosylamides
Scheme 15
Scheme 15. Effect of Olefin Substitution on Site Selectivity
Scheme 16
Scheme 16. Site Selectivity Following the Markovnikov Rule
See this image and copyright information in PMC

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