Organic Letters
Letter
These reactions probably occur by ionic mechanisms
(negative radical probe; no acceleration by light; large polar
solvent effect); hence, we call them nucleophilic substitutions.
Three limiting mechanisms can be considered based on timing
of events: two with two steps and one concerted. In the first
two-step mechanism (not shown), the boryl sulfide could
dissociate to a thiolate/borenium ion pair (RS− and [BH2-
NHC]+), then the thiolate ion is the nucleophile that reacts
with the bromide or acid chloride. This “thiolate release”
mechanism seems unlikely because borenium ions are
unstable.11 Substituted NHC-boranes can express borenium-
like reactivity, but far better leaving groups than thiolates are
needed.12
only nucleophile that can be delivered from neutral NHC-
boranes. Sulfur groups can now be delivered, so perhaps other
groups will be subject to similar chemistry.
ASSOCIATED CONTENT
* Supporting Information
■
S
Contains experimental and compound characterization details
and copies of spectra of isolated products. This material is
AUTHOR INFORMATION
Corresponding Author
■
Notes
The other two-step mechanism is illustrated in the upper
path of Figure 7 with a monosulfide NHC-BH2SAr and benzyl
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the National Science Foundation for funding. We
■
thank Dr. E. Laco
discussions.
̂
te (CNRS/University of Lyon I) for helpful
REFERENCES
■
(1) The Chemistry of Sulfur-Containing Functional Groups; Patai, S.,
Rappoport, Z., Eds.; Wiley: Chichester, U.K., 1993.
(2) (a) Eichman, C. C.; Stambuli, J. P. Molecules 2011, 16, 590−608.
(b) Nishimoto, Y.; Okita, A.; Yasuda, M.; Baba, A. Org. Lett. 2012, 14,
1846−1849.
Figure 7. Possible two-step (top) and one-step (bottom) ionic
mechanisms.
(3) (a) Chu, Q.; Makhlouf Brahmi, M.; Solovyev, A.; Ueng, S.-H.;
Curran, D.; Malacria, M.; Fensterbank, L.; Laco
2009, 15, 12937−12940. (b) Horn, M.; Mayr, H.; Laco
̂
te, E. Chem.Eur. J.
bromide. Here, the order of the steps is reversed. First, the
sulfur of the boryl sulfide displaces the leaving group to give a
transient boryl sulfonium bromide intermediate 12. This
quickly collapses by attack of bromide at boron with liberation
of the thioether. (Or, the thioether can leave to form a
borenium ion that is trapped by bromide.) Such nucleophilic
attacks at NHC-boranes bearing good leaving groups have solid
precedent.9 Here, the neutral thioether in 12 is an outstanding
leaving group for the substitution in the second step. Finally, in
the concerted mechanism, Figure 7, lower path, these two
processes take place simultaneously through a four-centered
transition state like 13 that is polarized in a fashion similar to
the intermediates in both of the two-step mechanisms.
Regardless of the mechanism, the immediate boron-
containing products of these reactions are presumably boryl
bromides or chlorides. To show this, several 11B NMR spectra
of a reaction mixture containing benzyl bromide and 3 were
recorded a various intervals. The doublet from 3 gradually
yielded to two new doublets assigned to NHC-BHBrSPh
(−11.5 ppm, major) and NHC-BHBr2 (−15.6 ppm, minor).
In summary, we have shown that NHC-boryl sulfides and
related N-boryl thioamides are neutral reagents that deliver a
nucleophilic sulfur group to provide neutral products such as
thioethers and thioesters. Such neutral products are usually
made from anionic sulfur nucleophiles (thiolates), while most
nucleophilic substitution reactions at neutral sulfur result in
cationic products (sulfonium ions, for example).
̂
te, E.; Merling,
E.; Deaner, J.; Wells, S.; McFadden, T.; Curran, D. P. Org. Lett. 2012,
14, 82−85. (c) Lamm, V.; Pan, X.; Taniguchi, T.; Curran, D. P.
Beilstein J. Org. Chem. 2013, 9, 675−680.
(4) Curran, D. P.; Solovyev, A.; Makhlouf Brahmi, M.; Fensterbank,
L.; Malacria, M.; Laco
10317.
(5) Pan, X.; Vallet, A.-L.; Schweizer, S.; Dahbi, K.; Delpech, B.;
Blanchard, N.; Graff, B.; Geib, S. J.; Curran, D. P.; Lalevee, J.; Lacote,
E. J. Am. Chem. Soc. 2013, 135, 10484−10491.
(6) Telitel, S.; Vallet, A.-L.; Schweizer, S.; Delpech, B.; Blanchard, N.;
Morlet-Savary, F.; Graff, B.; Curran, D. P.; Robert, M.; Lacote, E.;
Lalevee, J. J. Am. Chem. Soc. 2013, 135, 16938−16947.
(7) (a) Pan, X.; Lalevee, J.; Lacote, E.; Curran, D. P. Adv. Synth.
Catal. 2013, 355, 3522−3526. (b) Pan, X.; Lacote, E.; Lalevee, J.;
̂
te, E. Angew. Chem., Int. Ed. 2011, 50, 10294−
́
̂
̂
́
́
̂
̂
́
Curran, D. P. J. Am. Chem. Soc. 2012, 134, 5669−5675.
(8) Blakemore, P. R. J. Chem. Soc., Perkin Trans. 1 2002, 2563−2585.
(9) Solovyev, A.; Chu, Q.; Geib, S. J.; Fensterbank, L.; Malacria, M.;
̂
Lacote, E.; Curran, D. P. J. Am. Chem. Soc. 2010, 132, 15072−15080.
(10) Lindsay, D. M.; McArthur, D. Chem. Commun. 2010, 46, 2474−
2476.
(11) De Vries, T. S.; Prokofjevs, A.; Vedejs, E. Chem. Rev. 2012, 112,
4246−4282.
(12) (a) Pan, X.; Boussonnier
2013, 135, 14433−14437. (b) Boussonnier
Curran, D. P. Organometallics 2013, 32, 7445−7450. (c) Prokofjevs,
A.; Boussonniere, A.; Li, L.; Bonin, H.; Lacote, E.; Curran, D. P.;
Vedejs, E. J. Am. Chem. Soc. 2012, 134, 12281−12288.
̀
e, A.; Curran, D. P. J. Am. Chem. Soc.
̀
e, A.; Pan, X.; Geib, S. J.;
̀
̂
The procedures are convenient, and the synthesis of the
sulfur nucleophile reagent and its onward substitution reaction
are easily telescoped to a one-pot process. Only two
representative S-nucleophiles were used in this work, but
many related analogues are known.5 So many kinds of
thioethers and thioesters can potentially be made by using
this method. Finally, the results show that hydride is not the
2731
dx.doi.org/10.1021/ol5010164 | Org. Lett. 2014, 16, 2728−2731