Highly active Au(I) catalyst for the intramolecular exo- hydrofunctionalization of allenes with carbon, nitrogen, and oxygen nucleophiles

Article abstract of DOI:10.1021/ja062045r

Reaction of benzyl (2,2-diphenyl-4,5-hexadienyl)carbamate (4) with a catalytic 1:1 mixture of Au[P(t-Bu)₂(o-biphenyl)]CI (2) and AgOTf (5 mol %) in dioxane at 25 °C for 45 min led to isolation of benzyl 4,4-diphenyl-2-vinylpyrrolidine-1-carboxylate (5) in 95% yield. The Au(l)-catalyzed intramolecular hydroamination of N-allenyl carbamates tolerated substitution at the alkyl and allenyl carbon atoms and was effective for the formation of piperidine derivatives, γ-Hydroxy and δ-hydroxy allenes also underwent Au-catalyzed intramolecular hydroalkoxylation within minutes at room temperature to form the corresponding oxygen heterocycles in good yield with high exoselectivity. 2-Allenyl indoles underwent Au-catalyzed intramolecular hydroarylation within minutes at room temperature to form 4-vinyl tetrahydrocarbazoles in good yield. Au-catalyzed cyclization of N-allenyl carbamates, allenyl alcohols, and 2-allenyl indoles that possessed an axially chiral allenyl moiety occurred with transfer of chirality from the allenyl moiety to the newly formed stereogenic tetrahedral carbon atom.

Full text of DOI:10.1021/ja062045r

Published on Web 06/20/2006
Highly Active Au(I) Catalyst for the Intramolecular
exo-Hydrofunctionalization of Allenes with Carbon, Nitrogen,
and Oxygen Nucleophiles
Zhibin Zhang, Cong Liu, Robert E. Kinder, Xiaoqing Han, Hua Qian, and
Ross A. Widenhoefer*
Contribution from the P. M. Gross Chemical Laboratory, Duke UniVersity,
Durham, North Carolina 27708-0346
Received March 24, 2006; E-mail: rwidenho@chem.duke.edu
Abstract: Reaction of benzyl (2,2-diphenyl-4,5-hexadienyl)carbamate (4) with a catalytic 1:1 mixture of
Au[P(t-Bu)2(o-biphenyl)]Cl (2) and AgOTf (5 mol %) in dioxane at 25 °C for 45 min led to isolation of benzyl
4,4-diphenyl-2-vinylpyrrolidine-1-carboxylate (5) in 95% yield. The Au(I)-catalyzed intramolecular hydroami-
nation of N-allenyl carbamates tolerated substitution at the alkyl and allenyl carbon atoms and was effective
for the formation of piperidine derivatives. γ-Hydroxy and δ-hydroxy allenes also underwent Au-catalyzed
intramolecular hydroalkoxylation within minutes at room temperature to form the corresponding oxygen
heterocycles in good yield with high exo-selectivity. 2-Allenyl indoles underwent Au-catalyzed intramolecular
hydroarylation within minutes at room temperature to form 4-vinyl tetrahydrocarbazoles in good yield. Au-
catalyzed cyclization of N-allenyl carbamates, allenyl alcohols, and 2-allenyl indoles that possessed an
axially chiral allenyl moiety occurred with transfer of chirality from the allenyl moiety to the newly formed
stereogenic tetrahedral carbon atom.
Introduction
the transition metal-catalyzed hydrofunctionalization of allenes
with carbon and heteroatom nucleophiles has been investigated
Nitrogen1 and oxygen2 heterocycles are common structural
components of a wide range of naturally occurring and biologi-
cally active molecules. Therefore, the development of new and
efficient methods for the synthesis of heterocyclic compounds
is of central importance in organic synthesis.3 An attractive and
atom-economical route to the synthesis of functionalized
heterocycles is via the transition metal-catalyzed addition of the
X-H bond of a carbon, nitrogen, or oxygen nucleophile across
the CdC bond of a pendant alkene (hydrofunctionalization).
Unfortunately, due to a number of factors including the high
thermodynamic stability of most X-H σ-bonds and the inherent
nucleophilicity of simple alkenes, effective transition metal-
catalyzed protocols for the intramolecular hydrofunctionalization
of unactivated alkenes with C-,4,5 N-,6-9 or O-nucleophiles10,11
remain scarce.
(4) (a) Tan, K. L.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2001,
123, 2685. (b) Thalji, R. K.; Ahrendt, K. A.; Bergman, R. G.; Ellman, J.
A. J. Am. Chem. Soc. 2001, 123, 9692. (c) Ahrendt, K. A.; Bergman, R.
G.; Ellman, J. A. Org. Lett. 2003, 5, 1301. (d) Fairlie, D. P.; Bosnich, B.
Oranometallics 1988, 7, 936. (e) Tan, K. L.; Vasudevan, A.; Bergman, R.
G.; Ellman, J. A.; Souers, A. J. Org. Lett. 2003, 5, 2131. (f) Youn, S. W.;
Pastine, S. J.; Sames, D. Org. Lett. 2004, 6, 581. (g) Yao, X.; Li, C.-J. J.
Am. Chem. Soc. 2004, 126, 6884.
(5) (a) Widenhoefer, R. A. Pure Appl. Chem. 2004, 76, 671, and references
therein. (b) Liu, C.; Han, X.; Wang, X.; Widenhoefer, R. A. J. Am. Chem.
Soc. 2004, 126, 3700. (c) Han, X.; Wang, X.; Pei, T.; Widenhoefer, R. A.
Chem. Eur J. 2004, 10, 6343. (d) Qian, H.; Pei, T.; Widenhoefer, R. A.
Organometallics 2005, 24, 287. (e) Liu, C.; Widenhoefer, R. A. Tetrahedron
Lett. 2005, 46, 285.
(6) (a) Beller, M.; Tillack, A.; Seauyad, J. in Transition Metals for Organic
Synthesis; 2nd ed.; Wiley-VCH: Weinheim, 2004; pp 403-414. (b) Brunet,
J. J.; Neibecker, D. In Catalytic Heterofunctionalization; Togni, A.,
Gru¨tzmacher, H. Eds.; Wiley-VCH: Weinheim, 2001; pp 91-142. (c)
Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673. (d) Michael, F. E.;
Cochran, B. M. J. Am. Chem. Soc. 2006, 128, 4246. (e) Riegert, D.; Collin,
J.; Meddour, A.; Schulz, E.; Trifonov, A. J. Org. Chem. 2006, 71, 2514.
(f) Gribkov, D. V.; Hultzsch, K. C.; Hampel, F. J. Am. Chem. Soc. 2006,
128, 3748. (g) Kim, J. Y.; Livinghouse, T. Org. Lett. 2005, 7, 4391. (h)
Bexrud, J. A.; Beard, J. D.; Leitch, D. C.; Schafer, L. L. Org. Lett. 2005,
7, 1959. (i) Kim, J. Y.; Livinghouse, T. Org. Lett. 2005, 7, 1737. (j)
Crimmin, M. R.; Casely, I. J.; Hill, M. S. J. Am. Chem. Soc. 2005, 127,
2042. (k) Zulys, A.; Dochnahl, M.; Hollmann, D.; Lo¨hnwitz, K.; Herrmann,
J.-S.; Roesky, P. W.; Blechert, S. Angew. Chem. Int. Ed. 2005, 44, 7794.
(l) Karshtedt, D.; Bell, A. T.; Tilley, T. D. J. Am. Chem. Soc. 2005, 127,
12640.
The CdC π-bond of an allene is ∼10 kcal/mol less stable
than is the CdC π-bond of a simple alkene.12 For this reason,
(1) (a) O’Hagan, D. Nat. Prod. Rep. 2000, 17, 435. (b) Mitchinson, A.; Nadin,
A. J. Chem. Soc., Perkin Trans. 1 2000, 2862. (c) Liddell, J. R. Nat. Prod.
Rep. 2002, 19, 773. (d) Michael, J. P. Nat. Prod. Rep. 2001, 18, 520. (e)
Saxton, J. E. Nat. Prod. Rep. 1997, 14, 559. (f) Sundberg, R. J. Indoles;
Academic Press: San Diego, 1996.
(2) (a) Elliot, M. C. J. Chem. Soc., Perkin Trans. 1 2000, 1291. (b) Elliot, M.
C.; Williams, E. J. Chem. Soc., Perkin Trans. 1 2001, 2303. (c) Alali, F.
Q.; Liu, X. X.; McLaughlin, J. L. J. Nat. Prod. 1999, 62, 504. (d) Boivin,
T. L. B. Tetrahedron 1987, 43, 3309.
(3) (a) Bird, C. W.; Cheeseman, G. W. H. In ComprehensiVe Heterocyclic
Chemistry; Katrinsky, A. R., Rees, C. W., Eds.; Pergamon Press: Oxford,
1984; Vol. 4, pp 89-154. (b) McKillop, A.; Boulton, A. J. In Compre-
hensiVe Heterocyclic Chemistry; Katrinsky, A. R., Rees, C. W., Eds.;
Pergamon Press: Oxford, 1984; Vol. 2, pp 67-98. (c) Cardillo, G.; Orena,
M. Tetrahedron 1990, 46, 3321. (d) Bartlett, P. A. in Asymmetric Synthesis;
Morrison, J. D.; Ed.; Academic Press: New York; 1984; Vol. 3; pp 411-
454. (e) Cox, E. D.; Cook, J. M. Chem. ReV. 1995, 95, 1797.
(7) Zhang, J.; Yang, C.-G.; He, C. J. Am. Chem. Soc. 2006, 128, 1798.
(8) (a) Bender, C. F.; Widenhoefer, R. A. J. Am. Chem. Soc. 2005, 127, 1070.
(b) Wang, X.; Widenhoefer, R. A. Organometallics 2004, 23, 1649. (c)
Qian, H.; Widenhoefer, R. A. Org. Lett. 2005, 7, 2635.
(9) Han, X.; Widenhoefer, R. A. Angew. Chem. Int. Ed. 2006, 45, 1747.
(10) (a) Hori, K.; Kitagawa, H.; Miyoshi, A.; Ohta, T.; Furukawa, I. Chem.
Lett. 1998, 1083. (b) Yang, C.-G.; He, C. J. Am. Chem. Soc. 2005, 127,
6966. (c) Oe, Y.; Ohta, T.; Ito, Y. Chem. Commun. 2004, 1620. (d) Oe,
Y.; Ohta, T.; Ito, Y. Synlett 2005, 179. (e) Grant, V. H.; Liu, B. Tetrahedron
Lett. 2005, 46, 1237. (f) Tani, K.; Kataoka, Y. In Catalytic Heterofunc-
tionalization; Togni, A., Gru¨tzmacher, H. Eds.; Wiley-VCH: Weinheim,
2001; pp 171-216.
9
9066
J. AM. CHEM. SOC. 2006, 128, 9066-9073
10.1021/ja062045r CCC: $33.50 © 2006 American Chemical Society

Highly Active Au(I) Catalyst
A R T I C L E S
as a means to circumvent some of the difficulties associated
with catalytic alkene hydrofunctionalization.13 However, whereas
Ag(I), Au(III), and Cu(I) complexes catalyze the endo-hydro-
functionalization of allenes with N-,14 O-,15,16 and S-17 nucleo-
philes, the exo-hydrofunctionalization of allenes with carbon
and heteroatom nucleophiles remains problematic. Although the
Ag(I)-catalyzed exo-hydroamination18 and exo-hydroalkoxyla-
tion19 of allenes and the Pd(II)-catalyzed exo-hydroamination20,21
and exo-hydroalkylation21,22 of allenes have been reported, these
protocols suffer from a number of shortcomings including
limited substrate scope, low reactivity, and/or modest turnover
numbers.23,24 Similarly, d0-lanthanide complexes are active
catalysts for the exo-hydroamination of γ- and δ-amino al-
lenes,25,26 but the synthetic utility of these protocols is com-
promised by the poor functional group compatibility and
excessive air- and moisture-sensitivity of the oxophilic catalyst.
As part of a program directed toward the development of
new catalytic methods for the transition metal-catalyzed hy-
drofunctionalization of unactivated alkenes with carbon,5 ni-
trogen,8,9 and oxygen11 nucleophiles, we recently reported the
gold-catalyzed intramolecular exo-hydroamination of N-alkenyl
carbamates.9,27-33 As an example of this protocol, treatment of
the N-5-hexenyl carbamate 1 with a catalytic 1:1 mixture of
Au[P(t-Bu)2(o-biphenyl)]Cl (2) and AgOTf (5 mol %) in
dioxane at 60 °C for 18 h led to isolation of protected pyrrolidine
3 in 97% yield (eq 1). Employment of the sterically hindered
o-biphenyl ligand was crucial for high activity; cyclization of
1 catalyzed by a 1:1 mixture of Au(PPh3)Cl and AgOTf (5 mol
%) reached only 75% conversion after 24 h at 100 °C. The
high activity of the 2/AgOTf catalyst system with respect to
the exo-hydroamination of N-alkenyl carbamates suggested that
2/AgOTf might also catalyze the exo-hydroamination of N-
allenyl carbamates under mild conditions. Indeed, here we report
that a 1:1 mixture of 2 and AgX (X ) OTf, OTs) is an
exceptionally active catalyst system for the exo-hydroamination
of N-allenyl carbamates and also for the exo-hydroalkoxylation
of allenyl alcohols and the exo-hydroarylation of 2-allenyl
indoles.
(11) Qian, H.; Han, X.; Widenhoefer, R. A. J. Am. Chem. Soc. 2004, 126, 9536.
(12) Padwa, A.; Filipkowski, M. A.; Meske, M.; Murphree, S. S.; Watterson,
S, H.; Ni, Z. J. Org. Chem. 1994, 59, 588.
(13) Bates, R. W.; Satcharoen, V. Chem. Soc. ReV. 2002, 31, 12.
(14) (a) Lee, P. H.; Kim, H.; Lee, K.; Kim, M.; Noh, K.; Kim, H.; Seomoon,
D. Angew. Chem. Int. Ed. 2005, 44, 1840. (b) Ohno, H.; Toda, A.; Miwa,
Y.; Taga, T.; Osawa, E.; Yamaoka, Y.; Fujii, N.; Ibuka, T. J. Org. Chem.
1999, 64, 2992. (c) Dieter, R. K.; Yu, H. Org. Lett. 2001, 3, 3855. (d)
Morita, N.; Krause, N. Org. Lett. 2004, 6, 4121. (e) Prasad, J. S.; Liebeskind,
L. S. Tetrahedron Lett. 1988, 29, 4253. (f) Claesson, A.; Sahlberg, C.;
Luthman, K. Acta Chem. Scand. 1979, 309.
(15) (a) Ma, S.; Yu, Z.; Wu, S. Tetrahedron 2001, 57, 1585. (b) Hoffmann-
Ro¨der, A.; Krause, N. Org. Lett. 2001, 3, 2537. (c) Young, J.-j.; Jung,
L.-j.; Cheng, K.-m. Tetrahedron Lett. 2000, 41, 3411. (d) Young, J.-j.; Jung,
L.-j.; Cheng, K.-m. Tetrahedron Lett. 2000, 41, 3415. (e) Marshall, J. A.;
Wang, X. J. Org. Chem. 1991, 56, 4913. (f) Marshall, J. A.; Pinney, K. G.
J. Org. Chem. 1993, 58, 7180. (g) Marshall, J. A.; Bartley, G. S. J. Org.
Chem. 1994, 59, 7169. (h) Olsson, L.-I.; Claesson, A. Synthesis 1979, 743.
(i) Nikam, S. S.; Chu, K.-H.; Wang, K. K. J. Org. Chem. 1986, 51, 745.
(j) Walkup, R. D.; Park, G. Tetrahedron Lett. 1987, 28, 1023. (k) VanBrunt,
M. P.; Standaert, R. F. Org. Lett. 2000, 2, 705. (l) Lepage, O.; Kattnig, E.;
Furstner, A. J. Am. Chem. Soc. 2004, 126, 15970. (m) Marshall, J. A.;
Wolf, M. A.; Wallace, E. M. J. Org. Chem. 1997, 62, 367.
(16) For examples of the catalytic cyclization of allenyl ketones see: (a) Hashmi,
A. S. K.; Schwarz, L.; Choi, J.-H.; Frost, T. M. Angew. Chem. Int. Ed.
2000, 39, 2285. (b) Hashmi, A. S. K.; Ruppert, T. L.; Knofel, T.; Bats, J.
W. J. Org. Chem. 1997, 62, 7295. (c) Marshall, J. A.; Robinson, E. D. J.
Org. Chem. 1990, 55, 3450. (d) Marshall, J. A.; Wang, X. J. Org. Chem.
1991, 56, 960. (e) Marshall, J. A.; Wang, X. J. Org. Chem. 1992, 57, 3387.
(f) Marshall, J. A.; Wallace, E. M.; Coan, P. S. J. Org. Chem. 1995, 60,
796. (g) Marshall, J. A.; Sehon, C. A. J. Org. Chem. 1995, 60, 5966. (h)
Sromek, A. W.; Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc. 2005, 127,
10500.
(17) Morita, N.; Krause, N. Angew. Chem. Int. Eng. 2006, 45, 1897.
(18) (a) Huby, N. J. S.; Kinsman, R. G.; Lathbury, D.; Vernon, P. G.; Gallagher,
T. J. Chem. Soc., Perkin Trans. 1 1991, 145. (b) Gallagher, T.; Jones, S.
W.; Mahon, M. F.; Molloy, K. C. J. Chem. Soc., Perkin Trans. 1 1991,
2193. (c) Arseniyadis, S.; Sartoretti, J. Tetrahedron Lett. 1985, 26, 729.
(d) Fox, D. N. A.; Lathbury, D.; Mahon, M. F.; Molloy, K. C.; Gallagher,
T. J. Chem. Soc., Chem. Commun. 1989, 1073. (e) Ha, J. D.; Cha, J. K. J.
Am. Chem. Soc. 1999, 121, 10012. (f) Kinsman, R.; Lathbury, D.; Vernon,
P.; Gallagher, T. J. Chem. Soc., Chem. Commun. 1987, 243. (g) Lathbury,
D.; Gallagher, T. J. Chem. Soc., Chem. Commun. 1986, 114. (h) Lathbury,
D. C.; Shaw, R. W.; Bates, P. A.; Hursthouse, M. B.; Gallagher, T. J.
Chem. Soc., Perkin Trans. 1 1989, 2415.
(19) (a) Gallagher, T. J. Chem. Soc., Chem. Commun. 1984, 1554. (b) Audin,
P.; Doutheau, A.; Ruest, L.; Gore, J. Bull. Chem. Soc. Fr. 1981, 313. (c)
Audin, P.; Doutheau, A.; Gore, J. Bull. Chem. Soc. Fr. 1984, 297. (d) Audin,
P.; Dutheau, A.; Gore, J. Tetrahedron Lett. 1982, 23, 4337. (e) Chilot,
J.-J.; Doutheau, A.; Gore, J. Bull. Chem. Soc. Fr. 1984, 307.
Results and Discussion
exo-Hydroamination of N-Allenyl Carbamates. Mixtures
of 2 and AgOTf in dioxane catalyzed the exo-hydroamination
of 4,5-hexadienyl carbamates within minutes at room temper-
ature. For example, reaction of N-allenyl carbamate 4 with a
(24) For examples of the Pd(II)-catalyzed intermolecular hydrofunctionalization
of allenes with carbon and heteroatom nucleophiles see: (a) Al-Masum,
M.; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 3809. (b) Yamamoto,
Y.; Al-Masum, M.; Asao, N. J. Am. Chem. Soc. 1994, 116, 6019. (c) Trost,
B. M.; Gerusz, V. J. J. Am. Chem. Soc. 1995, 117, 5156. (d) Zhao, C.-Q.;
Han, L.-B.; Tanaka, M. Organometallics 2000, 19, 4196. (e) Yamamoto,
Y.; Al-Masum, M.; Fujiwara, N.; Asao, N. Tetrahedron Lett. 1995, 36,
2811. (f) Ogawa, A.; Kudo, A.; Hirao, T. Tetrahedron Lett. 1998, 39, 5213.
(g) Kamijo, S.; Al-Masum, M.; Yamamoto, Y. Tetrahedron Lett. 1998,
39, 691. (h) Al-Masum, M.; Meguro, M.; Yamamoto, Y. Tetrahedron Lett.
1997, 38, 6071. (i) Besson, L.; Gore´, J.; Cazes, B. Tetrahedron Lett. 1995,
36, 3853-3857.
(25) (a) Arredondo, V. M.; McDonald, F. E.; Marks, T. J. J. Am. Chem. Soc.
1998, 120, 4871. (b) Arredondo, V. M.; McDonald, F. E.; Marks, T. J.
Organometallics 1999, 18, 1949. (c) Hong, S.; Kawaoka, A. M.; Marks,
T. J. J. Am. Chem. Soc. 2003, 125, 15878.
(26) For the Ti(IV)-catalyzed hydroamination of allenylamines to form cyclic
imines see: (a) Ackermann, L.; Bergman, R. G. Org. Lett. 2002, 4, 1475.
(b) Ackermann, L.; Bergman, R. G.; Loy, R. N. J. Am. Chem. Soc. 2003,
125, 11956. (c) Hoover, J. M.; Petersen, J. R.; Pikul, J. H.; Johnson, A. R.
Organometallics 2004, 23, 4614.
(27) Examples of the Au(I) catalyzed hydrofunctionalization of alkynes with
C,28 N30, and O31, nucleophiles have appeared recently.
(28) Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2004,
126, 4526.
,
29
32
(29) (a) Ferrer, C.; Echavarren, A. M. Angew. Chem. Int. Ed. 2006, 45, 1105.
(b) Staben, S. T.; Kennedy-Smith, J. J.; Toste, F. D. Angew. Chem. Int.
Ed. 2004, 43, 5350. (c) Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2005,
127, 6962.
(20) Meguro, M.; Yamamoto, Y. Tetrahedron Lett. 1998, 39, 5421.
(21) (a) Ma, S. Chem. ReV. 2005, 105, 2829. (b) Zimmer, R.; Dinesh, C. U.;
Nandanan, E.; Khan, F. A. Chem. ReV. 2000, 100, 3067. (c) Yamamoto,
Y.; Radhakrishnan, U. Chem. Soc. ReV. 1999, 28, 199.
(30) (a) Mizushima, E.; Hayashi, T.; Tanaka, M. Org. Lett. 2003, 5, 3349. (b)
Gorin, D. J.; Davis, N. R.; Toste, F. D. J. Am. Chem. Soc. 2005, 127,
11260.
(31) (a) Genin, E.; Toullec, P. Y.; Antoniotti, S.; Brancour, C.; Genet, J.-P.;
Michelet, V. J. Am. Chem. Soc. 2006, 128, 3112. (b) Buzas, A.; Gagosz,
F. Org. Lett. 2006, 8, 515. (c) Mizushima, E.; Sato, K.; Hayashi, T.; Tanaka,
M. Angew. Chem. Int. Ed. 2002, 41, 4563. (d) Casado, R.; Contel, M.;
Laguna, M.; Romero, P.; Sanz, S. J. Am. Chem. Soc. 2003, 125, 11925.
(e) Roembke, P.; Schmidvaur, H.; Cronje, S.; Raubenheimer, H. J. Mol.
Catal. A 2004, 212, 35.
(22) (a) Meguro, M.; Kamijo, S.; Yamamoto, Y. Tetrahedron Lett. 1996, 37,
7453. (b) Trost, B. M.; Michellys, P.-Y.; Gerusz, V. J. Angew. Chem., Int.
Ed. Engl. 1997, 36, 1750.
(23) High activity in the Pd-catalyzed hydrofunctionalization is realized only
in the cases of allenes activated by an aryl group or a heteroatom. (a)
Kamijo, S.; Yamamoto, Y. Tetrahedron Lett. 1999, 40, 1747. (b) Trost, B.
M.; Ja¨kel, C.; Plietker, B. J. Am. Chem. Soc. 2003, 125, 4438.
(32) Liu, Y.; Song, F.; Song, Z.; Liu, M.; Yan, B. Org. Lett. 2005, 7, 5409.
9
J. AM. CHEM. SOC. VOL. 128, NO. 28, 2006 9067

A R T I C L E S
Zhang et al.
Table 1. Intramolecular Hydroamination of N-Allenyl Carbamates
Catalyzed by a 1:1 Mixture of Au[P(t-Bu)2(o-biphenyl)]Cl (2) and
AgOTf in Dioxane at 25 °C for 5-180 min
catalytic 1:1 mixture of 2 and AgOTf (5 mol %) in dioxane at
room temperature for 45 min led to isolation of 2-vinyl
pyrrolidine 5 in 95% yield (eq 2). In comparison, treatment of
4 with a catalytic amount of AgOTf (5 mol %) at room
temperature for 2 days led to no detectable consumption of 4.34
Gold-catalyzed exo-hydroamination was also effective for Boc
and Fmoc-substituted N-allenyl carbamates (Table 1, entries 1
and 2). The protocol tolerated substitution at the C(1) or C(3)
position of the 4,5-hexadienyl chain with modest to good levels
of diastereoselectivity (Table 1, entries 3 and 4). The protocol
tolerated substitution at the internal and terminal allenyl carbon
atoms and was also effective for the formation of piperidine
derivatives via cyclization of protected δ-amino allenes (Table
1, entries 5-10). N-Allenyl carbamates 6, 8, and 12, which
possessed an axially chiral allenyl moiety, underwent Au-
catalyzed cyclization to form heterocycles 7, 9, and 13,
respectively, with selective (g50:1) formation of the E-alkene
(Table 1, entries 6, 7, and 10). Noteworthy was that the Au-
catalyzed intramolecular hydroamination of 10 to form pyrro-
lidine 11 was run under ambient atmosphere without any
apparent decrease in rate or efficiency (Table 1, entry 8).
Although relatively high catalyst loadings (5 mol %) were
employed in the preparative-scale reactions described above,
efficient hydroamination was realized with significantly lower
catalyst loading. In one experiment, a concentrated solution of
N-allenyl carbamate 10 (0.64 mmol, 1.3 M) in dioxane was
treated with a catalytic 1:1 mixture of 2 and AgOTf (1 mol %)
and stirred for 25 min at room temperature. GC analysis revealed
complete consumption of 10 to form 11 as the exclusive product.
A second portion of 10 (0.64 mmol) was added, the reaction
mixture was stirred for 25 min at room temperature, and
subsequent GC analysis again revealed complete consumption
of 10 with formation of 11 as the exclusive product. Chroma-
tography of the reaction mixture gave 11 in 96% isolated yield.
Likewise, reaction of 10 (0.5 M) with a catalytic 1:1 mixture
of 2 and AgOTf (0.5 mol %) at room temperature for 14 h led
to isolation of 11 in 96% yield.
a Isolated material of >95% purity. b Reaction run at 25 °C for 22 h.
Table 2. Intramolecular Hydroalkoxylation of 14 as a Function of
Catalyst
exo-Hydroalkoxylation of Allenyl Alcohols. In contrast to
the hydroamination of 4,5-hexadienyl carbamates, the hy-
entry
catalyst
time
conv.
yield 15a
yield 16a
1
2
3
4
5
2/AgOTf
2/AgOTs
AgNO3
AgOTs
[PtCl(H2CdCH2)]2/
P(C6H5CF3)3
5 min
3 min
16 h
48 h
5 min
>99%
>99%
17%
0%
>99%
48%
96%
14%
37%
e1%
0%
(33) For recent examples of the Au(I)-catalyzed cyclization of enynes and related
substrates see: (a) Nieto-Oberhuber, C.; Lopez, S.; Echavarren, A. M. J.
Am. Chem. Soc. 2005, 127, 6178. (b) Luzung, M. R.; Markham, J. P.; Toste,
F. D. J. Am. Chem. Soc. 2004, 126, 10858. (c) Mamane, V.; Gress, T.;
Krause, H.; Furstner, A. J. Am. Chem. Soc. 2004, 126, 8654. (d) Nieto-
Oberhuber, C.; Munoz, M. P.; Bunuel, E.; Nevado, C.; Cardenas, D. J.;
Echavarren, A. M. Angew. Chem. Int. Ed. 2004, 43, 2402. (e) Sherry, B.
D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978. (f) Faza, O. N.;
Lopez, C. S.; Alvarez, R.; de Lera, A. R. J. Am. Chem. Soc. 2006, 128,
2434. (g) Mezailles, N.; Ricard, L.; Gagosz, F. Org. Lett. 2005, 7, 4133.
(h) Gagosz, F. Org. Lett. 2005, 7, 4129. (i) Suhre, M. H.; Reif, M.; Kirsch,
S. F. Org. Lett. 2005, 7, 3925. (j) Shi, X.; Gorin, D. J.; Toste, F. D. J. Am.
Chem. Soc. 2005, 127, 5802. (k) Zhang, L.; Wang, S. J. Am. Chem. Soc.
2006, 128, 1442. (l) Ma, S.; Yu, S.; Gu, Z. Angew. Chem. Int. Ed. 2006,
45, 200.
(34) The presence of significant acid-catalyzed background reactions in the Au-
catalyzed exo-hydrofunctionalization of allenes was ruled out by the
following control experiments: Treatment of 10 with a catalytic amount
of HOTf (5 mol %) in dioxane at room temperature for 2 h led to no
detectable formation of 11. Treatment of 14 with a catalytic amount of
HOTs (10 mol %) in toluene at room temperature for 1 h led to no detectable
formation of 15. Treatment of 21 with a catalytic amount of HOTf (10
mol %) in dioxane at room temperature for 2 h led to no detectable
formation of 22.
0%
49%
a Yield determined by GC analysis vs internal standard.
droalkoxylation of 4,5-hexadienyl alcohols catalyzed by 2/Ag-
OTf occurred rapidly but with poor regioselectivity. For
example, reaction of 2,2-diphenyl-4,5-hexadienol (14) catalyzed
by a 1:1 mixture of 2 and AgOTf at room temperature for 5
min led to complete consumption of 14 to form a 1.3:1 mixture
of tetrahydrofuran 15 and dihydropyran 16 in 85% combined
yield by GC (Table 2, entry 1). However, subsequent experi-
mentation revealed that the regioselectivity of Au-catalyzed
hydroalkoxylation depended strongly on the nature of the
9
9068 J. AM. CHEM. SOC. VOL. 128, NO. 28, 2006

Highly Active Au(I) Catalyst
A R T I C L E S
Table 4. Intramolecular Hydroarylation of 21 as a Function of
Table 3. Intramolecular Hydroalkoxylation of Allenyl Alcohols
Catalyzed by a 1:1 Mixture of Au[P(t-Bu)2(o-biphenyl)]Cl (2) and
AgOTs in Toluene at 25 °C for 5-75 min
Catalyst
conversion
(%)a
yield 22
(%)a
yield 23
(%)a
entry
catalyst
time (h)
1
2
2/AgOTf
AgBF4
0.25
2
>99
0
>99
0
0
0
3
4
PdCl2(MeCN)2
Pd(OAc)2
2
2
19
15
0
0
0
0
5
6
7
8
9
10
Pd(OAc)2/dppb
[Pd(allyl)Cl]2/dppf
PtCl2
PtCl4
AuCl3/AgOTf
AuCl/AgOTf
2
2
2
2
2
2
17
14
20
92
68
>99
0
0
10
44
40
25
0
0
14
26
15
56
a Conversion and yield determined by GC analysis vs internal standard.
tion of 14 to form 16 in 49% yield without formation of
detectable amounts of 15 (Table 2, entry 5).34
5,6-Heptadien-1-ols also underwent efficient exo-hydroalkox-
ylation within minutes at room temperature in the presence of
catalytic amount of 2/AgOTs to form the corresponding
2-alkenyl tetrahydropyran derivatives in good yield (Table 3,
entries 2-12). Gold-catalyzed hydroalkoxylation tolerated
substitution at the C(1), C(2), or C(4) position of the 5,6-
heptadienyl chain and was effective for the cyclization of
unsubstituted 5,6-heptadienol (Table 3, entries 2-7). 5,6-
Heptadien-1-ols that possessed a single substituent at either the
C(1) or C(4) position underwent Au-catalyzed hydroalkoxylation
with good diastereoselectivity (Table 3, entries 5 and 6).
Furthermore, both the 5-exo hydroalkoxylation of γ-hydroxy
allenes and the 6-exo hydroalkoxylation of δ-hydroxy allenes
tolerated substitution at the terminal allenyl carbon atom (Table
3, entries 8-12). Noteworthy was that the gold-catalyzed
hydroalkoxylation of the axially chiral γ-hydroxy allenes 17a-c
formed tetrahydrofurans 18a-c, respectively, in g90% yield
with g5.3:1 E:Z selectivity (Table 3, entries 9-11). Likewise,
gold-catalyzed hydroalkoxylation of the axially chiral δ-hydroxy
allene 19 formed tetrahydropyran 20 in 99% yield with 20:1
E:Z selectivity (Table 3, entry 12).
a Isolated material of >95% purity. b H NMR yield; reaction run in
dioxane-d8.
exo-Hydroarylation of Allenyl Indoles. Mixtures of 2 and
AgOTf catalyzed the room-temperature intramolecular exo-
hydroarylation of 2-allenyl indoles to form functionalized
tetrahydrocarbazoles. As an example, treatment of the 2-(4,5-
hexadienyl)indole 21 with a catalytic 1:1 mixture of 2 and
AgOTf in dioxane at 25 °C for 15 min led to complete
consumption of 21 to form tetrahydrocarbazole 22 in >99%
yield by GC analysis of the crude reaction mixture (Table 4,
entry 1). A number of complexes were screened as catalysts
for the conversion of 21 to 22, but none proved as active or as
selective as was the catalyst generated from 2 and AgOTf (Table
4). Silver(I) and Pd(II) complexes displayed no catalytic activity
with respect to the conversion of 21 to 22 (Table 4, entries 2-6).
Platinum dichloride, which catalyzes the hydroarylation of 2-
and 3-alkenyl indoles,5b displayed little catalytic activity for the
intramolecular hydroarylation of 21 (Table 4, entry 7). Neutral
Pt(IV) complexes and cationic, “ligandless” Au(III) and Au(I)
counterion. In an optimized procedure, reaction of 14 with a
catalytic 1:1 mixture of 2 and AgOTs in toluene at room
temperature for 3 min led to complete consumption of 14 to
form 15 in 96% yield (GC) without formation of significant
amounts (e1%) of 16 (Table 2, entry 2). Subsequent chroma-
tography gave 15 in 91% isolated yield (Table 3, entry 1).
In contrast to mixtures of 2 and AgOTs, Ag(I) salts alone
displayed little activity for the exo-hydroalkoxylation of 14.
Reaction of 14 with a catalytic amount of AgNO3 at room
temperature led to only 17% conversion after 16 h to form 15
in 14% yield (Table 2, entry 3). Treatment of 14 with a catalytic
amount of AgOTs led to no detectable consumption of 14 after
48 h at room temperature (Table 2, entry 4). Reaction of 14
with a catalytic 1:1 mixture of [PtCl(H2CdCH2)]2 and P(C6H5-
CF3)3, previously employed as a catalyst for the intramolecular
hydroalkoxylation of alkenyl alcohols,11 led to rapid consump-
9
J. AM. CHEM. SOC. VOL. 128, NO. 28, 2006 9069

A R T I C L E S
Zhang et al.
Table 5. Intramolecular Hydroarylation of 2-Allenyl Indoles
Catalyzed by a 1:1 Mixture of Au[P(t-Bu)2(o-biphenyl)]Cl (2) and
AgOTf in Dioxane at 25 °C for 30 min
complexes displayed considerably greater catalytic activity than
did PtCl2 but also displayed poor regioselectivity for hydroary-
lation (Table 4, entries 8-10).34
Gold-catalyzed hydroarylation was effective for allenyl
indoles that possessed either an electron-donating or an electron-
withdrawing group on the indole moiety and the protocol
tolerated substitution at either the internal or terminal allenyl
carbon atom (Table 5, entries 2-6). From this group of
examples, several points are worth noting. First, the axially chiral
2-allenylindole 24 underwent Au-catalyzed cyclization to form
tetrahydrocarbazole 25 with exclusive (g 50:1) formation of
the E-alkene (Table 5, entry 5). Second, allenyl indole 26, which
possessed a single carbomethoxy group at the C(2) position of
the 4,5-hexadienyl chain, cyclized in good yield to form
tetrahydrocarbazole 27 as a 5:1 mixture of cis:trans diastereo-
mers (Table 5, entry 7). Third, reaction of the bis(hydroxy-
methyl) substituted indole 28 with a catalytic 1:1 mixture of
2/AgOTf led to formation of tetrahydrocarbazole 29 via 6-exo
hydroarylation without formation of detectable amounts of the
corresponding tetrahydrofuran via 5-exo hydroalkoxylation
(Table 5, entry 8). The 2-(5,6-heptadienyl) indole 30 underwent
Au-catalyzed cyclization at room temperature to form the seven-
membered ring derivative 31 in good yield, although longer
reaction time was required (Table 5, entry 9). In comparison,
allenyl carboxamide 32 underwent gold-catalyzed hydroarylation
at 60 °C to form a ∼1:1 mixture of dihydro-â-carbolinone 33
and dihydroazepinoindolone 34 in 72% combined yield (Table
5, entry 10).
Axial to Tetrahedral Chirality Transfer. Transfer of
chirality from an axially chiral allenyl moiety to a tetrahedral
stereogenic carbon atom has been observed for a number of
catalytic and noncatalytic reactions including the intramolecular
[4+2] cycloaddition of allenyl propargyl alcohols,35 the inter-
molecular [4+2] cycloaddition of allene-1,3-dicarboxylates,36
the [2+2] cycloaddition of allenylsilanes,37 the Nazarov-type
cyclization of allenyl alkenes,38 the Mo- and Zr-mediated
carbonylative bicyclization of ynallenes,39 the Ni-catalyzed
coupling of an allene, aldehyde, and a silane,40 the Rh(I)-
catalyzed cycloisomerization of allenyl cyclopropylalkenes,41
the iodohydroxylation of allenylsulfoxides,42 and the meth-
oxymercuration and halogenation of 1,3-dimethylallenes.43
Because the Au-catalyzed hydroamination of axially chiral
N-allenyl carbamates 6, 8, and 12 occurred with exclusive
formation of the E-alkene, we considered that the Au-catalyzed
hydroamination of N-allenyl carbamates might also occur with
transfer of chirality from the allenyl moiety to the newly formed
stereogenic carbon atom. Indeed, treatment of the enantiomeri-
cally enriched N-allenyl carbamate (S)-8 (e84% ee)44 with a
catalytic 1:1 mixture of 2 and AgOTf led to isolation of (R)-9
in 96% yield with 74% ee (eq 3). Gold-catalyzed hydroarylation
(35) Gibbs, R. A.; Bartels, K.; Lee, R. W. K.; Okamura, W. H. J. Am. Chem.
Soc. 1989, 111, 3717.
(36) Ikeda, I.; Honda, K.; Osawa, E.; Shiro, M.; Aso, M.; Kanematsu, K. J.
Org. Chem. 1996, 61, 2031.
(37) Shepard, M. S.; Carreira, E. M. J. Am. Chem. Soc. 1997, 119, 2597.
(38) Hu, H.; Smith, D.; Cramer, R. E.; Tius, M. A. J. Am. Chem. Soc. 1999,
121, 9895.
(39) Brummond, K. M.; Kerekes, A. D.; Wan, H. J. Org. Chem. 2002, 67, 5156.
(40) (a) Ng, S.-S.; Jamison, T. F. J. Am. Chem. Soc. 2005, 127, 7320. (b) Ng,
S.-S.; Jamison, T. F. Tetrahedron 2005, 61, 11405.
(41) Wender, P. A.; Glorius, F.; Husfeld, C. O.; Langkopf, E.; Love, J. A. J.
Am. Chem. Soc. 1999, 121, 5348.
(42) Ma, S.; Ren, H.; Wei, Q. J. Am. Chem. Soc. 2003, 125, 4817.
(43) Waters, W. L.; Linn, W. S.; Caserio, M. C. J. Am. Chem. Soc. 1968, 90,
6741.
a E ) CO2Me. b Isolated material of >95% purity. c Reaction run for
22 h. d Reaction run at 60 °C for 1 h.
of axially chiral allenyl indoles also occurred with transfer of
chirality from the allenyl moiety to the newly formed stereogenic
carbon atom. For example, reaction of enantiomerically enriched
9
9070 J. AM. CHEM. SOC. VOL. 128, NO. 28, 2006

Highly Active Au(I) Catalyst
A R T I C L E S
(R)-24 (52% ee) with a catalytic 1:1 mixture of 2 and AgOTf
led to isolation of 25 in 86% yield with 52% ee (eq 4).
mixture of enantiomerically enriched (E)-18b and (Z)-18b
formed 2-n-heptyl-4,4-diphenyltetrahydrofuran (35) in 86% yield
with 67% ee (er ) 5.1:1).
An additional experiment was performed to assign the
absolute stereochemistry to the E and Z-isomers formed via the
gold-catalyzed hydroalkoxylation of an axially chrial allenyl
alcohol. To this end, reaction of the enantiomerically enriched
allenyl alcohol (S)-17a (84% ee) with a catalytic 1:1 mixture
of 2 and AgOTs led to formation of a 5.3:1 mixture of (R),(E)-
18a (81% ee) and (S),(Z)-18a (84% ee) in 87% combined yield
1
by H NMR analysis (eq 5). The absolute stereochemistry of
(R),(E)-18a and (S),(Z)-18a was assigned by comparison to an
authentic sample of a 25:1 mixture of (R),(Z)-18a and (R),(E)-
18a synthesized in two steps from commercially available (R)-
2-hydroxymethyltetrahydrofuran.46
In contrast to Au-catalyzed hydroarylation and hydroamina-
tion, the Au-catalyzed hydroalkoxylation of axially chiral allenyl
alcohols 17 formed mixtures of E and Z-alkenes (Table 3, entries
9-11). Nevertheless, the Au-catalyzed hydroalkoxylation of
axially chiral allenyl alcohols also occurred with transfer of
chirality from the allenyl moiety to the newly formed stereogenic
carbon atom. For example, treatment of the enantiomerically
enriched allenyl alcohol (R)-17b (94% ( 3% ee) with a catalytic
1:1 mixture of 2 and AgOTs led to isolation of a 5.5:1 mixture
of (E)-18b (g90% ee) and (Z)-18b (g90% ee) in 92% combined
yield (Scheme 1).45 Noteworthy was that (E)-18b and (Z)-18b
Mechanism. Both inner-sphere47 and outer-sphere7,16a,28,32
mechanisms have been suggested for the gold-catalyzed addition
of C-, N-, and O-nucleophiles to alkenes and alkynes. However,
stereochemical analysis of the Au(I)-catalyzed hydroalkylation
of 4-pentynyl â-keto esters,28 the hydroamination of 4-pentenyl
sulfonamides,7 and the hydroalkoxylation of (Z)-2-en-4-yne-1-
ols32 in each case established the anti-addition of the nucleophile
and Au atom across the C-C multiple bond, consistent with
outer-sphere C-X bond formation. Similarly, the stereospecific
conversion of (S)-8 to (R)-9 (eq 3) directly implicates a
mechanism involving nucleophilic anti-attack of the carbamate
nitrogen atom on the Au-complexed allene of intermediate cis-I
to form the ammonium intermediate II (Scheme 2). Deproto-
Scheme 1
Scheme 2
possessed opposite stereochemistry at the stereogenic C(2)
carbon atom. Catalytic hydrogenation of the aforementioned
(44) (a) We were unable to determine directly the enantiomeric purity of (S)-8.
Rather, the enantiomeric purity of (S)-9-(tetrahydropyran-2-yloxy)-5-nonyn-
4-ol [(S)-36] was determined (84% ee) by 19F NMR analysis of the
corresponding Mosher ester. Compound (S)-36 was deprotected to give
(S)-17a, which was then converted to (S)-2-(3,4-octadienyloxy)tetrahydro-
pyran employing the method of Myers44b and subsequently converted to
(S)-8 without further manipulation of the chiral allenyl moiety (See
Supporting Information). (b) Myers, A. G.; Zheng, B. J. Am. Chem. Soc.
1996, 118, 4492.
nation of II followed by protonolysis of the Au-C bond48 of
the neutral gold alkenyl complex III with retention of stereo-
(46) (a) Bianchi, P.; Roda, G.; Riva, S.; Danieli, B.; Zabelinskaja-Mackova,
A.; Griengl, H. Tetrahedron 2001, 57, 2213. (b) Cominetti, F.; Deagostino,
A.; Prandi, C.; Venturello, P. Tetrahedron 1998, 54, 14603.
(47) Teles, J. H.; Brode, S.; Chabanas, M. Angew. Chem. Int. Ed. 1998, 37,
1415.
(45) Determination of the enantiomeric purity of (E)-18b and (Z)-18b was
complicated by coelution of one enantiomer of (E)-18b with one enantiomer
of (Z)-18b on HPLC (see Supporting Information).
9
J. AM. CHEM. SOC. VOL. 128, NO. 28, 2006 9071

A R T I C L E S
Scheme 3
Zhang et al.
chemistry49 would release (R)-9 with regeneration of the
catalytically active cationic gold phosphine complex.50
sion of (S)-8 to (R)-9 supported a mechanism for the gold-
catalyzed hydroamination of N-allenyl carbamates involving
outer-sphere, anti-attack of the carbamate nitrogen atom on the
allenyl group of a gold allene complex in which the gold atom
is complexed to the allene π-face cis to the proximal allenyl
substituent.
Formation of the E-alkene moiety of (R)-9 requires selective
cyclization of gold-allene intermediate cis-I, in which the gold
atom is cis to the proximal n-propyl group, in preference to
cyclization of trans-I, in which the gold atom is trans to the
proximal n-propyl group (Scheme 2). Because it appears likely
that cis-I is less stable than is trans-I, Au-catalyzed conversion
of (S)-8 to (R)-9 presumably involves rapid and reversible
formation of trans-I followed by irreversible cyclization of cis-I
to form II (Scheme 2). It follows that the transition state for
C-N bond formation is destabilized to a greater extent by a
cis arrangement of the carbamate moiety and n-propyl group
(trans-I f II) than by a cis arrangement of the Au[P(t-Bu)2-
(o-biphenyl)] moiety and the n-propyl group (cis-I f II).
The high selectivity for transfer of chirality and the high
diastereoselectivity of the Au-catalyzed hydroarylation of allenyl
indole (R)-24 strongly suggest that conversion of (R)-24 to 25
also occurs via outer-sphere attack of the indole moiety on a
cis Au-allene complex. In comparison, Au-catalyzed hy-
droalkoxylation of the axially chiral allenyl alcohol (S)-17a
formed a 5.3:1 mixture of (R),(E)-18a and (S),(Z)-18a. This
result is in accord with a mechanism involving competitive
outer-sphere attack of the hydroxyl group on the diastereomeric
gold allene complexes cis-Ia and trans-Ia to form IIa and IIb,
respectively (Scheme 3). Deprotonation/protonolysis of IIa and
IIb would then form tetrahydrofurans (R),(E)-18a and (S),(Z)-
18a, respectively (Scheme 3). Destabilization of the transition
state for conversion of trans-Ia f IIb is presumably attenuated
relative to the corresponding processes involving C-N or C-C
bond formation due to the smaller size of the hydroxyl group
relative to a carbamate or indole group.
Experimental Section
Benzyl 4,4-diphenyl-2-vinylpyrrolidine-1-carboxylate (5). A sus-
pension of 4 (96 mg, 0.25 mmol), 2 (6.9 mg, 1.3 × 10-2 mmol), and
AgOTf (3.3 mg, 1.3 × 10-2 mmol) in dioxane (2.00 mL) was stirred
at 25 °C for 45 min. The crude reaction mixture was chromatographed
(SiO2; hexanes-EtOAc ) 4:1) to give 5 (91 mg, 95%) as a viscous,
colorless oil. TLC (SiO2; hexanes-EtOAc ) 4:1): Rf ) 0.34. 1H NMR
(1:1 ratio of rotamers): δ 7.46-7.11 (m, 15 H), 5.87-5.70 (m, 1 H),
5.37-4.99 (m, 4 H), [4.77 (d, J ) 11.6 Hz), 4.61 (d, J ) 11.3 Hz),
1:1, 1 H], 4.24-4.02 (m, 1 H), 3.71 (dd, J ) 7.3, 11.5 Hz, 1 H), 2.90-
2.79 (m, 1 H), 2.51-2.38 (m, 1 H). 13C{1H} NMR (1:1 ratio of
rotamers): δ 155.6, 154.8, 145.4, 144.8, 139.2, 138.5, 137.1, 136.9,
128.7, 128.6, 128.4, 128.2, 128.1, 127.8, 127.6, 126.9, 126.7, 126.5,
115.8, 115.2, 66.9, 59.5, 59.1, 56.2, 53.1, 52.8, 45.7, 44.7. IR (neat,
cm-1): 3060, 3030, 2976, 2881, 1698, 1598, 1493, 1446, 1408, 1353,
1313, 1202, 1105, 979, 918, 750, 697. Anal. calcd. (found) for C26H25-
NO2: C, 81.43 (81.18); H, 6.57 (6.54); N, 3.65 (3.66).
The remaining nitrogen heterocycles derivatives depicted in Table
1 were synthesized employing a procedure similar to that used to
synthesize 5.
4,4-Diphenyl-2-vinyltetrahydrofuran (15). A mixture of 2 (3.3 mg,
6.25 × 10-3 mmol) and AgOTs (1.7 mg, 6.25 × 10-3 mmol) in toluene
(0.4 mL) was stirred at room temperature for 10 min and then treated
with a solution of 14 (31.3 mg, 0.125 mmol) in toluene (0.6 mL). The
resulting suspension was stirred at room temperature for 3 min and
then chromatographed (SiO2; hexanes-EtOAc ) 50:1 f 20:1) to give
15 (28.4 mg, 91%) as a colorless oil. TLC (hexanes-EtOAc ) 5:1):
Rf ) 0.57. 1H NMR: δ 7.34-7.17 (m, 10 H), 5.90 (ddd, J ) 6.8, 10.0,
17.2 Hz, 1 H), 5.24 (d, J ) 16.8 Hz, 1 H), 5.10 (d, J ) 10.0 Hz, 1 H),
4.67 (d, J ) 8.4 Hz, 1 H), 4.43 (td, J ) 6.4, 10.0 Hz, 1 H), 4.15 (d, J
) 8.4 Hz, 1 H), 2.66 (ddd, J ) 0.8, 6.0, 12.4 Hz, 1 H), 2.44 (dd, J )
9.6, 12.0 Hz, 1 H). 13C{1H} NMR: δ 146.2, 145.8, 139.0, 128.7, 128.6,
127.4, 127.3, 126.7, 126.5, 116.1, 79.9, 56.4, 45.3. IR (neat, cm-1):
3056, 2973, 2866, 1650, 1499, 1445, 1056, 926, 757, 699. Anal. Calcd
(found) for C18H18NO4: C, 86.53 (86.36); H, 7.18 (7.25).
Conclusions
We have found that Au[P(t-Bu)2(o-biphenyl)]Cl (2) activated
by either AgOTf or AgOTs is a highly active and highly
selective precatalyst for the intramolecular exo-hydroamination
of N-allenyl carbamates, the intramolecular exo-hydroalkoxy-
lation of allenyl alcohols, and the intramolecular exo-hydroary-
lation of 2-allenyl indoles. N-Allenyl carbamates, allenyl
alcohols, and allenyl indoles that possessed an axially chiral
allenyl moiety underwent cyclization with transfer of chirality
from the allene to the newly formed stereogenic carbon atom
with selective formation of the E-alkene. The selective conver-
The remaining oxygen heterocycles depicted in Table 3 were
synthesized employing a procedure similar to that used to synthesize
15.
2,2-Dicarbomethoxy-9-methyl-4-vinyl-2,3,4,9-tetrahydrocarba-
zole (22). A mixture of 2 (6.6 mg, 1.3 × 10-2 mmol) and AgOTf (3.2
mg, 1.3 × 10-2 mmol) in dioxane (0.1 mL) was stirred for 10 min at
room temperature. To this, a solution of 21 (82 mg, 0.25 mmol) in
dioxane (0.4 mL) was added and the resulting solution was stirred for
30 min. Column chromatography of the reaction mixture (SiO2;
hexanes-EtOAc ) 10:1 f 5:1) gave 22 (71 mg, 87%) as a pale yellow
oil. TLC (SiO2; hexanes-EtOAc ) 2:1): Rf ) 0.56. 1H NMR: δ 7.53
(48) (a) Mitchell, C. M.; Stone, F. G. A. J. Chem. Soc. Dalton Trans. 1972,
102. (b) Johnson, A.; Pudephatt, R. J. J. Chem. Soc. Dalton Trans. 1977,
1384.
(49) Johnson, A.; Pudephatt, R. J. J. Chem. Soc. Dalton Trans. 1978, 980.
(50) An analogous mechanism involving intermolecular protonolysis of a Pt-C
bond has been established for the Pt-catalyzed hydroamination of
alkenylamines.8a.
9
9072 J. AM. CHEM. SOC. VOL. 128, NO. 28, 2006

Highly Active Au(I) Catalyst
A R T I C L E S
(d, J ) 8.0 Hz, 1 H), 7.24 (d, J ) 8.0 Hz, 1 H), 7.14 (t, J ) 7.6 Hz,
1 H), 7.00 (t, J ) 7.2 Hz, 1 H), 5.83 (ddd, J ) 8.0, 9.6, 17.6 Hz, 1 H),
5.30-5.14 (m, 2 H), 3.76 (s, 3 H), 3.71-3.69 (m, 1 H), 3.69 (s, 3 H),
3.66 (s, 3 H), 3.45 (d, J ) 8.0 Hz, 1 H), 3.15 (dd, J ) 2.0, 8.0 Hz, 1
H), 2.65 (ddd, J ) 0.8, 6.0, 13.2 Hz, 1 H), 2.05 (dd, J ) 10.0, 13.2
Hz, 1 H). 13C{1H} NMR: δ 172.2, 171.1, 141.8, 137.8, 133.0, 126.9,
121.2, 119.9, 119.1, 115.8, 109.2, 109.0, 54.5, 53.3, 36.7, 36.3, 29.6,
28.3. IR (neat, cm-1): 2952, 1731, 1469, 1373, 1319, 1289, 1250, 1083,
916, 743. Anal. Calcd. (found) for C18H21NO4: C, 69.71 (69.50); H,
6.47 (6.55).
Acknowledgment. We thank the NSF (CHE-0304994 and
CHE-0555425), the PRF (43636-AC1), administered by the
American Chemical Society, the Camille and Henry Dreyfus
Foundation, and GlaxoSmithKline for support of this research.
We thank Mr. Robert Jones for performing some initial
experiments.
Supporting Information Available: Experimental procedures,
analytical and spectroscopic data for new compounds, and copies
of pertinent spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
The remaining tricyclic indoles depicted in Table 5 were synthesized
employing a procedure similar to that used to synthesize 22.
JA062045R
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J. AM. CHEM. SOC. VOL. 128, NO. 28, 2006 9073