Gold-catalyzed double migration-benzannulation cascade toward naphthalenes

Article abstract of DOI:10.1021/ol800229h

(Chemical Equation Presented) A novel gold(I)-catalyzed cycloisomerization of propargylic esters leading to unsymmetrically substituted naphthalenes has been developed. This cascade reaction involves an unprecedented tandem sequence of 1,3- and 1,2-migration of two different migrating groups. It is believed that this transformation likely proceeds via the formation of 1,3-diene intermediate or its precursor, which upon cyclization and aromatization steps transforms into the naphthalene core. 2008 American Chemical Society.

Full text of DOI:10.1021/ol800229h

ORGANIC
LETTERS
2008
Vol. 10, No. 7
1465-1468
Gold-Catalyzed Double
Migration-Benzannulation Cascade
toward Naphthalenes
Alexander S. Dudnik, Todd Schwier, and Vladimir Gevorgyan*
Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
Vlad@uic.edu
Received February 5, 2008
ABSTRACT
A novel gold(I)-catalyzed cycloisomerization of propargylic esters leading to unsymmetrically substituted naphthalenes has been developed.
This cascade reaction involves an unprecedented tandem sequence of 1,3- and 1,2-migration of two different migrating groups. It is believed
that this transformation likely proceeds via the formation of 1,3-diene intermediate or its precursor, which upon cyclization and aromatization
steps transforms into the naphthalene core.
In recent years, transition-metal-catalyzed transformations
of propargylic esters1 have received much attention. Par-
ticularly intriguing is reactivity of these easily accessible
compounds in the context of gold catalysis,2 which has been
reflected in the development of a variety of diverse and
elegant transformations leading to an immense array of
complex organic molecules. Remarkable propensity of pro-
pargylic esters 1 to undergo 1,3-acyl migration,1,2 through
the formation of an activated allene equivalent, intermediate
i,1 allowed for efficient and expeditious assembly of various
acyclic unsaturated synthons3 and complex carbo-4 and
heterocycles5 (eq 1). Herein, we wish to report a gold(I)-
catalyzed double 1,3-/1,2-migration-benzannulation cascade
of propargylic esters 1 into naphthalenes 2 (eq 2).
(1) For recent reviews, see: (a) Marco-Contelles, J.; Soriano, E. Chem.
Eur. J. 2007, 13, 1350. (b) Marion, N.; Nolan, S. P. Angew. Chem., Int.
Ed. 2007, 46, 2750.
Considering the enhanced electrophilicity of the sp3
center1b in intermediate i, we envisioned that incorporation
(2) For recent reviews, see: (a) Ma, S.; Yu, S.; Gu, Z. Angew. Chem.,
Int. Ed. 2006, 45, 200. (b) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2005,
44, 6990. (c) Hoffmann-Ro¨der, A.; Krause, N. Org. Biomol. Chem. 2005,
3, 387. (d) Echavarren, A. M.; Nevado, C. Chem. Soc. ReV. 2004, 33, 431.
(e) Dyker, G. Angew. Chem., Int. Ed. 2000, 39, 4237. (f) Hashmi, A. S. K.
Chem. ReV. 2007, 107, 3180. (g) Hashmi, A. S. K.; Hutchings, G. J. Angew.
Chem., Int. Ed. 2006, 45, 7896. (h) Fu¨rstner, A.; Davies, P. W. Angew.
Chem., Int. Ed. 2007, 46, 3410. (i) Yamamoto, Y. J. Org. Chem. 2007, 72,
7817. (j) Zhang, L.; Sun, J.; Kozmin, S. A. AdV. Synth. Catal. 2006, 348,
2271. (k) Widenhoefer, R. A.; Han, X. Eur. J. Org. Chem. 2006, 4555. (l)
Ishida, T.; Haruta, M. Angew. Chem., Int. Ed. 2007, 46, 7154. (m) Gorin,
D. J.; Toste, F. D. Nature 2007, 446, 395.
(3) (a) Amijs, C. H. M.; Lo´pez-Carrillo, V.; Echavarren, A. M. Org.
Lett. 2007, 9, 4021. (b) Yu, M.; Zhang, G.; Zhang, L. Org. Lett. 2007, 9,
2147. (c) Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128, 8414. (d)
Wang, S.; Zhang, L. Org. Lett. 2006, 8, 4585.
(4) (a) Lemie`re, G.; Gandon, V.; Cariou, K.; Fukuyama, T.; Dhimane,
A.-L.; Fensterbank, L.; Malacria, M. Org. Lett. 2007, 9, 2207. (b) Buzas,
A.; Gagosz, F. J. Am. Chem. Soc. 2006, 128, 12614. (c) Marion, N.; D´ıez-
Gonza´lez, S.; Fre´mont, P.; Noble, A. R.; Nolan, S. P. Angew. Chem., Int.
Ed. 2006, 45, 3647. (d) Zhang, L.; Wang, S. J. Am. Chem. Soc. 2006, 128,
1442.
10.1021/ol800229h CCC: $40.75
© 2008 American Chemical Society
Published on Web 03/01/2008

of a suitable 1,2-migrating group (MG) in ii would provoke
a subsequent 1,2-shift6 into iii, which upon proton loss and
protiodeauration would afford 1,3-diene7 3. It is reasonable
to propose that the latter may undergo 6π-electrocyclization
into naphthalene8,9 2, analogously to the known cyclization
of acyloxy-1,3,5-trienes10 (eq 3).
It deserves mentioning that the isomerization of acetates
1 into 1,3-dienes 5 in the presence of Ag-catalysts was
reported (eq 4).11 However, the nature of the second step
(1,2-H-shift or proton elimination) remained unclear. To
address this issue, we performed mechanistic studies12 for
MG ) H (eq 3) employing Au(I) catalyst. Experiments
revealed that the reaction proceeds exclusively via a 1,3-
shift13-15 -elimination16 sequence.
To this end, a possible isomerization of propargyl phos-
phate 1a (MG ) H) in the presence of different catalysts
has been tested (Table 1). It was found that employment of
Thus, we hypothesized that successful incorporation of a
1,2-migration into this cascade can only be achieved when
a migrating group resides at a “proton-free” quaternary C-4
center. Therefore, isomerization of acetate 1d, possessing a
strained cyclobutane ring, was examined. Indeed, a tandem
1,3-migration and ring expansion via a 1,2-shift occurred
leading to 1,3-diene 3d in a moderate yield (eq 5). Moreover,
isomerization of cyclopentyl homologs 1e and 1f afforded
target naphthalenes 3e and 3f respectively (eq 5), thus pro-
viding a proof of concept for this cascade transformation.17
Table 1. Optimization of Reaction Conditions
entry
catalyst
10% AgOTf
5% Ph3PAuCl, 5% AgOTf
5% AuCl3
5% AuCl3, 15% AgOTf
5% AuI
5% R3PAuCl (R ) Et, Ph)
yield 4a, %a yield 3a, %a
1
2
3
4
5
6
73
0
0
0
0
0
0
0
0
86
86
86
a Isolated yield of product for reaction performed on 0.1-0.2 mmol
scale.
Next, cycloisomerization of substrates possessing better
1,2-migrating groups was examined (Table 2). Thus, a
tandem acyloxy- or phosphatyloxy- and Ph-group migration/
benzannulation of propargylic esters 1g-n proceeded smoothly
Ag triflate gave corresponding allene 4a in good yield (entry
1). Remarkably, switching to cationic Au(I) triflate led to
the formation of target 1,3-diene 3a in 86% yield (entry 2).
Monitoring of the reaction course revealed that this trans-
formation proceeded through allenic intermediate 3a.12
Employment of Au(III) complexes (entries 3 and 4), non-
cationic Au(I) halides (entries 5 and 6), Cu(I) and Cu(II)
triflates, as well as Brønsted or Lewis acids, resulted in no
reaction.12
(11) (a) Saucy, G.; Marbet, R.; Lindlar, H.; Isler, O. HelV. Chim. Acta
1959, 42, 1945. (b) Schlossarczyk, H.; Sieber, W.; Hesse, M.; Hansen, H.-
J.; Schmid, H. HelV. Chim. Acta 1973, 56, 875. (c) Cookson, R. C.; Cramp,
M. C.; Parsons, P. J. J. Chem. Soc., Chem. Comm. 1980, 197.
(12) See Supporting Information for details.
(13) Direct observation of the allenes 4 supported 1,3-migration path.12
(14) For reviews, see: (a) Allin, S. M.; Baird, R. D. Curr. Org. Chem.
2001, 5, 395. (b) Nubbemeyer, U. Synthesis 2003, 7, 961. (c) Fanning, K.
N.; Jamieson, A. G.; Sutherland, A. Curr. Org. Chem. 2006, 10, 1007.
(15) D-Labeling studies on isomerization of 1a-d ruled out possible
involvement of alkyne-vinylidene isomerization path.
(5) (a) Buzas, A.; Istrate, F.; Gagosz, F. Org. Lett. 2006, 8, 1957. (b)
Zhang, L. J. Am. Chem. Soc. 2005, 127, 16804. (c) Luo, T.; Schreiber, S.
L. Angew. Chem., Int. Ed. 2007, 46, 8250. (d) Schwier, T.; Sromek, A.
W.; Yap, D. M. L.; Chernyak, D.; Gevorgyan, V. J. Am. Chem. Soc. 2007,
129, 9868.
(6) For general review, see: (a) Ducrot, P. H. In One or More CH and/
or CC Bond(s) Formed by Rearrangement; Katritzky, A. R., Taylor, R. J.
K., Eds.; Comprehensive Organic Functional Group Transformations II;
Elsevier: Oxford, UK, 2005; 1, pp 375-426.
(16) Significant loss of D-label, as well as scrambling of the latter
between C-1 and C-2, was observed for labeled phosphates 1b-d and 1c-d.
Reversible protonation at C-1 under the prolonged reaction times is most
likely the reason for the observed notable incorporation of D at C-1.
(7) For syntheses of 1,3-dienes employing Au catalysis, see: (a) Buzas,
A.; Istrate, F.; Gagosz, F. Org. Lett. 2007, 9, 985. (b) See also ref 3d.
(8) For a recent review on naphthalene syntheses, see: de Koning, C.
B.; Rousseau, A. L.; van Otterlo, W. A. L. Tetrahedron 2003, 59, 7.
(9) For selected examples, see: (a) Dyker, G.; Hilderbrandt, D.; Liu, J.;
Merz, K. Angew. Chem., Int. Ed. 2003, 42, 4399. (b) Zhao, J.; Hughes, C.
O.; Toste, F. D. J. Am. Chem. Soc. 2006, 128, 7436. (c) Asao, N.; Takahashi,
K.; Lee, S.; Kasahara, T.; Yamamoto, Y. J. Am. Chem. Soc. 2002, 124,
12650. See also: (d) Grise´, C. M.; Barriault, L. Org. Lett. 2006, 8, 5905.
(e) Asao, N.; Sato, K. Org. Lett. 2006, 8, 5361. (f) Wang, S.; Zhang, L. J.
Am. Chem. Soc. 2006, 128, 14274.
(10) Hamura, T.; Morita, M.; Matsumoto, T.; Suzuki, K. Tetrahedron
Lett. 2003, 44, 167 and references therein.
(17) For reasons, which are not clearly understood, 3d did not cyclize
into 2 even under forcing reaction conditions.
1466
Org. Lett., Vol. 10, No. 7, 2008

Scheme 1. Mechanistic Rationale for Au(I)-Catalyzed Cascade
to provide naphthalenes 2g-n in good to excellent yields.
an additional support for possible intermediacy of 1,3-dienes
in this transformation (eq 6).
Terminal, alkyl-, and aryl-substituted acetylenes were nearly
equally efficient in this transformation. Unexpectedly, cy-
clization of dimethylphenyl-substituted acetate 1k proceeded
via exclusive 1,2-Me-group migration to give 3k in good
yield (entry 5). Notably, a variety of substituents, such as
methoxy (entry 6), trifluoromethyl (entry 7), and 2-furyl
(entry 8), were perfectly tolerated under these reaction
conditions.
In summary, we have developed a novel gold(I)-catalyzed
approach toward polysubstituted naphthalenes, which features
an unprecedented tandem sequence of 1,3- and 1,2-migration
We propose the following plausible mechanisms for this
novel cascade transformation (Scheme 1). Au-catalyzed 1,3-
migration transforms 1 via cyclic intermediate1b,3c,5b iW into
allene 4.13 According to path A, 1,2-alkyl migration18 in iW
produces benzylic cation W. The latter gives diene 3 upon
protiodeauration or after proton transfer undergoes Friedel-
Crafts alkylation to furnish naphthalene 2. Alternatively, a
direct nucleophilic attack of vinyl-Au at the delocalized
benzyl cation in W19 gives carbenoid intermediate Wi, which
upon 1,2-H-shift20 and aromatization produces naphthalene
2 (Path B).21 According to path C, Au-catalyzed 6π-
electrocyclization14c,22 of 3 followed by elimination furnishes
2. In another scenario, direct intramolecular hydroarylation
of 4 followed by 1,2-shift and proton loss in Wii produces 2
(Path D). Unexpected exclusive Me- over Ph-migration in
1k is reasonably rationalized by stereoelectronic effect,
according to which Ph group cannot accommodate requisite
antiperiplanar orientation with the leaving group in iW.12,23,24
Successful cycloisomerization of 3e, obtained via 1,3-
migration/elimination cascade, into naphthalene 2e provided
Table 2. Gold(I)-Catalyzed Synthesis of Naphthalenes
(18) For selected examples, see: (a) Dudnik, A. S.; Gevorgyan, V.
Angew. Chem., Int. Ed. 2007, 46, 5195. (b) Kirsch, S. F.; Binder, J. T.;
Lie´bert, C.; Menz, H. Angew. Chem., Int. Ed. 2006, 45, 5878.
(19) See, for example: (a) Luzung, M. R.; Mauleo´n, P.; Toste, F. D. J.
Am. Chem. Soc. 2007, 129, 12402. (b) See also ref 4a,b.
(20) For selected examples, see: (a) Markham, J. P.; Staben, S. T.; Toste,
F. D. J. Am. Chem. Soc. 2005, 127, 9708. (b) Gorin, D. J.; Davis, N. R.;
Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260. (c) Sromek, A. W.;
Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc. 2005, 127, 10500.
(21) Path B involving clean 1,2-H-shift to Au-carbenoid is not supported
by the observed significant loss of D-label in cycloisomerization
of 1j-d.
a Isolated yield. b Reactions were performed on a 0.5 mmol scale. c 5%
Au-catalyst was used.
(22) See also: Menz, H.; Kirsch, S. F. Org. Lett. 2006, 8, 4795.
(23) For similar considerations, see: Aggarwal, V. K.; Sheldon, C. G.;
Macdonald, G. J.; Martin, W. P. J. Am. Chem. Soc. 2002, 124, 10300.
Org. Lett., Vol. 10, No. 7, 2008
1467

of different migrating groups in propargylic esters. A more
detailed investigation on the mechanism, as well as the
scope of this cascade, is ongoing and will be reported in
due course.
Acknowledgment. The support of the National Institutes
of Health (Grant GM-64444) is gratefully acknowledged.
Supporting Information Available: Preparative proce-
dures and analytical and spectral data. This material is
available free of charge via the Internet at http://pubs.acs.org.
(24) Obviously, exclusive Me- vs Ph-migration can also be explained
via Path D, according to which 1,2-migration occurs after cyclization step.
Alternatively, as proposed by the reviewer, migration of the Me group
leading to the more stable intermediate benzylic carbocation under
thermodynamic control can also account for the observed chemoselectivity.
OL800229H
1468
Org. Lett., Vol. 10, No. 7, 2008