Chirality transfer in gold-catalyzed carbothiolation of o-alkynylphenyl 1-arylethyl sulfides

Article abstract of DOI:10.1021/ol8007556

(Chemical Equation Presented) 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-aryleth

Full text of DOI:10.1021/ol8007556

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
itaru-n@mail.tains.tohoku.ac.jp
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

Figure 1. ORTEP drawing of (R)-3.
the reaction of 1h having a bulky cyclohexyl group at R1
took 5 days to complete with a poor chirality transfer
(entry 9). In the reaction of 1h, we observed in situ
racemization of the starting material; when the reaction
was quenched at 1 day, the product 2h was obtained in
57% yield with 33% of chirality transfer along with 28%
of the recovered 1h of which the enatiomeric excess was
9%.
X-ray crystallographic analysis (Figure 1).6 The present
reaction is concluded to proceed with retention of the con-
figuration at the R-phenethyl group.
To know if the carbodemetalation process of the sulfonium
intermediate 4 to give the product 2 proceeded through direct
[1,3] shift of the R-phenethyl group (Scheme 2, route A) or
Next, we explored the substrate scope of the gold-catalyzed
chirality transfer reaction of 1 as summarized in Table 1.
The reaction of 1b having a p-anisyl group at the alkynyl
moiety at 25 °C proceeded with a high level of chirality
transfer (entry1). Among the solvents we examined, we
found that the use of CH2Cl2 gave the best result (see
Supporting Information). Decrease of the ee of 2b was
observed in the reaction at 50 °C (entry 2). The reaction
at 0 °C proceeded slowly, giving 2b with 71% of chirality
transfer (entry 3). The chirality of 1-(p-chlorophenyl)ethyl
group was transferred with a good level (entry 4). The
reaction of 2d, 2e, and 2f having an aromatic ring at R1
gave a good degree of chirality transfer, whereas that of
1g and 1h bearing an alkyl group at the alkynyl moiety
proceeded much more slowely and showed a decrease in
the level of chirality transfer (entries 5-9). Particularly,
Scheme 2
.
Carbodemetalation Process in the Au-Catalyzed
Carbothiolation
Scheme 1
[1,2] migration of the R-phenethyl group forming the gold-
carbenoid intermediate 5 followed by the second [1,2]
migration (route B),7 we carried out the labeling experiment
using the deuterated substrate 6 (eq 4). The reaction of 6
under the standard reaction conditions gave 7 in 89% yield;
only a trace of the [1,2] shift-derived product 8 was observed
1
in H NMR spectroscopy. This result clearly indicates that
the present reaction proceeds mainly through direct [1,3]
migration of the R-phenethyl group.
(6) CCDC-666893 contains the supplementary crystallographic data for
3. The data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/
retrieving.html (or from the Cambridge Crystallographic Data Centre, 12,
Union Road, Cambridge CB21EZ, U.K.; fax (+44)1223-336-033; or
deposit@ccdc.cam.ac.uk).
(7) (a) Kusama, H.; Miyashita, Y.; Takaya, J.; Iwasawa, N. Org. Lett.
2006, 8, 289–292. (b) Li, G.; Huang, X.; Zhang, L. Angew. Chem., Int.Ed.
2008, 47, 346–349.
2650
Org. Lett., Vol. 10, No. 13, 2008

Table 1. Chirality Transfer in Gold-Catalyzed Carbothiolation of o-Alkynylphenyl 1-Arylethyl Sulfides 1a
entry
1
R1
R2
ee of 1, %c temp, °C time, h
2
yield, %b ee of 2, %c chirality transfer,%
1
2
3
4
5
6
7
8
9
1b p-anisyl
1b p-anisyl
1b p-anisyl
1c p-anisyl
1d Ph
Ph
Ph
Ph
p-ClC6H4
Ph
97
97
97
98
98
95
99
>99
>99
25
50
0
25
25
25
25
25
25
0.5
0.5
4 days
0.5
2
2b
2b
2b
2c
2d
2e
2f
98
99
97
97
quant
87
93
82
92
88
79
69
79
78
72
82
38
22
91
52
71
81
79
76
82
38
23
1e p-F3CC6H4
Ph
2
2
1f
6-methoxy-2-naphthyl Ph
1g n-Pr
1h cyclohexyl
Ph
Ph
3 days
5 days
2g
2h
a The reaction of 1 (0.2 mmol) was carried out in the presence of 2 mol % of AuCl in 1 mL of CH2Cl2 at 25 °C. b Isolated yield. c Enantiomeric excess
was determined by chiral HPLC analysis.
Scheme 3
Retention of the stereocenter suggests that the [1,3]
migration of R-phenethyl group in the present chirality
In conclusion, we have found that the chirality transfer in
the gold-catalyzed carbothiolation of 1 proceeds with reten-
tion of the stereocenter at R-phenethyl group. Further mecha-
nistic investigations including chirality transfer in indole and
benzofuran synthesis are on going in our laboratory.
transfer reaction proceeds through generation of the contact
ion-pair B followed by C-C bond formation before race-
mization of the stereocenter (Scheme 3, path I).8 Decrease
of the level of chirality transfer in the reaction of 1b at 50
°C is probably because the separation of the ion-pair B occurs
faster at higher temperature, resulting in higher degree of
racemization (Table 1, entry 2). Obviously, an aryl group at
R1 plays an important role for rate acceleration (e.g., Table
1, entry 1 versus 8). Perhaps, interaction between the
π-electron of the aromatic ring at R1 and the R-phenethyl
cation facilitates migration of the R-phenethyl group. Since
the [1,3] sigmatropic rearrangement would proceed antarafa-
cially with inVersion of the stereocenter at the R-phenethyl
group,9 the possibility of concerted [1,3] migration is illogical
(path II).
Acknowledgment. This work was financially supported
by a Grant-in-Aid for Scientific Research from Japan Society
for Promotion in Science (JSPS).
Supporting Information Available: Experimental pro-
cedures and characterization of the products 1, 2, 3, 6, and
7. This material is available free of charge via the Internet
at http://pubs.acs.org.
OL8007556
(8) (a) Kawabata, T.; Fuji, K. Top. Stereochem. 2003, 23, 175–205. (b)
Goering, H. L.; Levy, J. F. J. Am. Chem. Soc. 1964, 86, 120–121. (c)
Decoret, C.; Royer, J.; Dannenberg, J. J. J. Org. Chem. 1981, 46, 4074–
4076.
(9) March, J. AdVanced Organic Chemistry, 4th ed.; John Wiley & Sons:
New York, 1992; pp 1126.
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