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. 2014 Mar 5;136(9):3655-63.
doi: 10.1021/ja413270h. Epub 2014 Feb 18.

Catalytic, enantioselective, intramolecular carbosulfenylation of olefins. Mechanistic aspects: a remarkable case of negative catalysis

Scott E Denmark  1 , Hyung Min Chi
Affiliations

Catalytic, enantioselective, intramolecular carbosulfenylation of olefins. Mechanistic aspects: a remarkable case of negative catalysis

Scott E Denmark et al. J Am Chem Soc. .

Abstract

In the course of developing an enantioselective, Lewis base/Brønsted acid co-catalyzed carbosulfenylation of alkenes, a seemingly impossible conundrum arose: How could a catalyst inhibit a stoichiometric reaction? Despite the observation of very good enantioselectivities, the rate of the uncatalyzed reaction (i.e., no Lewis base) was found to be comparable to or slightly faster than that of the catalyzed process. A combination of detailed kinetic and spectroscopic studies revealed that the answer is not the direct involvement of the Lewis base catalyst, but rather the secondary consequences of its conversion to the catalytically active sulfenylating agent. Generation of the chiral sulfenylating species is accompanied by the formation of equimolar amounts of sulfonate ion and phthalimide which serve to buffer the remaining Brønsted acid and thus inhibit the racemic background reaction. Thus, the actual background reaction operative under catalytic conditions is not well mimicked by simply removing the catalyst.

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Figures

Scheme 1
Scheme 1
Figure 1
Figure 1
Reactions with MsOH (1.0 equiv). (a) Rate profile for catalyzed cyclization with 0.1 equiv of (S)-1. (b) Rate profile for uncatalyzed cyclization.
Figure 2
Figure 2
Reactions with EtSO3H (X equiv). (a) Rate profile for catalyzed cyclization with 0.1 equiv of (S)-1. (b) Rate profile for formation of 4 in the uncatalyzed cyclization. (c) Rate profile for formation of 5 in the uncatalyzed cyclization.
Figure 3
Figure 3
Calculation of Keq for 6 assuming solvent-separated ion pair structure.
Figure 4
Figure 4
Calculation of Keq for 6 assuming intimate ion pair structure.
Figure 5
Figure 5
Titration curves for protonation of 2 with MsOH and EtSO3H.
Figure 6
Figure 6
Reactions with MsOH (1.0 equiv) and Bu4N+OMs–. (a) Rate profile for formation of 4 in the uncatalyzed cyclization. (b) Rate profile for formation of 5 in the uncatalyzed cyclization.
Figure 7
Figure 7
(a) Rate profile for the uncatalyzed reaction with 0.9 equiv of MsOH and 0.1 equiv of Bu4N+OMs–. (b) Rate profile for the uncatalyzed reaction with 0.9 equiv of MsOH, 0.1 equiv of Bu4N+OMs–, and 0.1 equiv of phthalimide. (c) Superposition of all reactions with MsOH; only formation of 4 is depicted.
Scheme 2
Scheme 2
Scheme 3
Scheme 3
Scheme 4
Scheme 4
See this image and copyright information in PMC

References

    1. Denmark S. E.; Jaunet A. J. Org. Chem. 2014, 79, 140–171. - PMC - PubMed
    2. Denmark S. E.; Jaunet A. J. Am. Chem. Soc. 2013, 135, 6419–6422. - PMC - PubMed
    1. Denmark S. E.; Kornfilt D. J.-P.; Vogler T. J. Am. Chem. Soc. 2011, 133, 15308–15311. - PMC - PubMed
    2. Denmark S. E.; Kalyani D.; Collins W. R. J. Am. Chem. Soc. 2010, 132, 15752–15765. - PMC - PubMed
    3. Denmark S. E.; Collins W. R. Org. Lett. 2007, 9, 3801–3804. - PubMed

    1. A parallel set of experiments run at 0.1 M concentration displayed dramatically different behavior than those run at 0.2 M. For example, with MsOH (1.0 equiv), the catalyzed reaction showed an induction period of ca. 6 h before the rapid onset of reaction, approximating an autocatalytic process. Moreover, with EtSO3H, the uncatalyzed reaction afforded only 5, the product of proton-initiated cyclization. These results, while intriguing and potentially informative, did not represent the preparative-scale reactions and as such were not further investigated or analyzed. See Supporting Information for details.

    1. The enantiomeric ratio (er) for 4 in this run using purified MsOH was only 75:25.

    1. Enantiomeric ratios: 1.00 equiv, 86.9:13.1; 0.75 equiv, 90.2:9.8; 0.50 equiv, 92.6:7.4; 0.25 equiv, 92.9:7.1.

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