ORGANIC
LETTERS
2008
Vol. 10, No. 13
2649-2651
Chirality Transfer in Gold-Catalyzed
Carbothiolation of o-Alkynylphenyl
1-Arylethyl Sulfides
Itaru Nakamura,* Takuma Sato, Masahiro Terada, and Yoshinori Yamamoto
Department of Chemistry, Graduate School of Science, Tohoku UniVersity,
Sendai 980-8578 Japan
Received April 3, 2008
ABSTRACT
Chirality transfer in gold-catalyzed carbothiolation of o-alkynylphenyl 1-arylethyl sulfides 1 proceeded with retention of the configuration at
the 1-arylethyl group. This result suggests that the [1,3] migration of 1-arylethyl group proceeds through formation of the contact ion pair B
followed by C-C bond formation.
Catalytic cyclization is one of the most efficient methods to
synthesize 2-monosubstituted indoles and benzofurans from
o-alkynylanilines and -phenols (eq 1).1 Recently, transition-
metal-catalyzed cyclization of o-alkynylanilines, -phenyl ethers,
and -phenyl sulfides bearing a migration group (E) on the
heteroatom (Y) has attracted much attention as a direct method
to synthesize the 2,3-disubstituted indoles,2 benzofurans,2a,b,3
and benzo[b]thiophenes,4 which have been widely utilized
as medicines and organic materials (eq 2). It has been
proposed that this reaction proceeds through a [1,3] shift of
the migrating group on the heteroatom of the zwitterionic
intermediate A. However, the nature of this [1,3] migration
has rarely been elucidated to date. In this communication,
we report that chirality transfer in the gold-catalyzed car-
bothiolation of o-alkynylphenyl 1-arylethyl sulfides 1 pro-
ceeds with retention of stereocenter at the 1-arylethyl group
(eq 3).5
(1) For a review, see: (a) Cacchi, S.; Fabrizi, G. Chem. ReV. 2005, 105,
2873–2920. (b) Zeni, G.; Larock, R. C. Chem. ReV. 2004, 104, 2285–2309.
(c) Nakamura, I.; Yamamoto, Y. Chem. ReV. 2004, 104, 2127–2198.
(2) Migration of allyl groups: (a) Cacchi, S.; Fabrizi, G.; Pace, P. J.
Org. Chem. 1998, 63, 1001–1011. (b) Fu¨rstner, A.; Davies, P. W. J. Am.
Chem. Soc. 2005, 127, 15024–15025. (c) Istrate, F. M.; Gagosz, F. Org.
Lett. 2007, 9, 3181–3184. Propargyl groups: (d) Cacchi, S.; Fabrizi, G.;
Moro, L. Tetrahedron Lett. 1998, 39, 5101–5104. Acyl groups: (e) Shimada;
T.; Nakamura, I.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 10546–
10547. Sulfonyl groups: (f) Nakamura, I.; Yamagishi, U.; Song, D.; Konta,
S.; Yamamoto, Y. Angew. Chem., Int. Ed. 2007, 46, 2284–2287.
(R)-2-[{p-(tert-Butyldimethylsiloxy)phenyl}ethynyl]-phen-
yl 1-phenylethyl sulfide 1a, which was prepared from
Mitsunobu reaction of commercially available (S)-1-phe-
nylethanol with 2-bromobenzenethiol followed by Sono-
gashira coupling, was reacted in the presence of 2 mol % of
AuCl in toluene at 25 °C to afford 2a in 94% yield with
79% chirality transfer (Scheme 1). The product 2a was
converted to the brosylate 3, of which the absolute stereo
configuration was unambiguously determined to be R by
(3) Allyl groups: Arcadi, A.; Cacchi, S.; Del Rosario, M.; Fabrizi, G.;
Marinelli, F. J. Org. Chem. 1996, 61, 9280–9288. (b) Cacchi, S.; Fabrizi,
G.; Moro, L. Synlett 1998, 741–745. (c) Monterio, N.; Balme, G. Synlett
1998, 746–747. (d) Fu¨rstner, A.; Szillat, H.; Stelzer, F. J. Am. Chem. Soc.
2000, 122, 6785–6786. (e) Fu¨rstner, A.; Stelzer, F.; Szillat, H. J. Am. Chem.
Soc. 2001, 123, 11863–11869. R-Alkoxyalkyl groups: (f) Nakamura, I.;
Mizushima, Y.; Yamamoto, Y. J. Am. Chem. Soc. 2005, 127, 15022–15023.
(g) Fu¨rstner, A.; Heilmann, E. K.; Davies, P. W. Angew. Chem., Int. Ed.
(5) Au-catalyzed chirality transfer reactions: (a) Hoffmann-Ro¨der, A.;
Krause, N. Org. Lett. 2001, 3, 2537–2538. (b) Sherry, B. D.; Toste, F. D.
J. Am. Chem. Soc. 2004, 126, 15978–15979. (c) Nieto Faza, O.; Silva Lo´pez,
´
C.; Alvarez, R.; de Lera, A. R. J. Am. Chem. Soc. 2006, 128, 2434–2437.
2007, 46, 4760–4763
.
(d) Zhang, Z.; Liu, C.; Kinder, R. E.; Han, X.; Qian, H.; Widenhoefer,
R. A. J. Am. Chem. Soc. 2006, 128, 9066–9073. (e) Dube´, P.; Toste, F. D.
J. Am. Chem. Soc. 2006, 128, 12062–12063. (f) Nishina, N. Yamamoto,
Y. Angew. Chem., Int. Ed. 2006, 45, 3314–3317.
(4) (a) Nakamura, I.; Sato, T.; Yamamoto, Y. Angew. Chem., Int. Ed.
2006, 45, 4473–4475. (b) Nakamura, I.; Sato, T.; Terada, M.; Yamamoto,
Y. Org. Lett. 2007, 9, 4081–4083.
10.1021/ol8007556 CCC: $40.75
Published on Web 06/03/2008
2008 American Chemical Society