Facile synthesis of spirocyclic ketones via gold(I)-catalyzed claisen-type rearrangement of cyclic 8-aryl-2,7-enyn-l-ols

Article abstract of DOI:10.1021/om900833k

The gold(I)-catalyzed Claisen-type rearrangement of cyclic 8-aryl-2,7-enyn-l-ols proceeds via a cationic allylic vinyl ether gold intermediate to give spirocyclic ketones. The reaction proceeded via attack of the hydroxyl group onto the gold-activated alkynes followed by [3,3]-sigmatropic rearrangement to generate the spirocyclic ketones. This transformation can be applied to the synthesis of aza- and oxaspirocyclic ketones from cyclic 8-aryl-2,7-enyn-l-ols bearing an N-sulfonamide or an oxygen atom linkage in the tether and the gold(I) catalyst.

Full text of DOI:10.1021/om900833k

160 Organometallics 2010, 29, 160–166
DOI: 10.1021/om900833k
Facile Synthesis of Spirocyclic Ketones via Gold(I)-Catalyzed
Claisen-Type Rearrangement of Cyclic 8-Aryl-2,7-enyn-1-ols
Ming-Chang P. Yeh,* Hui-Fen Pai, Chuen-Yo Hsiow, and Yan-Rong Wang
Department of Chemistry, National Taiwan Normal University, 88 Ding-Jou Road Section 4, Taipei 11677,
Taiwan, Republic of China
Received September 27, 2009
The gold(I)-catalyzed Claisen-type rearrangement of cyclic 8-aryl-2,7-enyn-1-ols proceeds via
a cationic allylic vinyl ether gold intermediate to give spirocyclic ketones. The reaction proceeded
via attack of the hydroxyl group onto the gold-activated alkynes followed by [3,3]-sigmatropic
rearrangement to generate the spirocyclic ketones. This transformation can be applied to the
synthesis of aza- and oxaspirocyclic ketones from cyclic 8-aryl-2,7-enyn-1-ols bearing an
N-sulfonamide or an oxygen atom linkage in the tether and the gold(I) catalyst.
Introduction
availability of functionalized spirocyclic building blocks
could greatly facilitate the elaboration of more complex
target molecules, the design of expedient synthetic routes
to such intermediates has been actively pursued.2-7 Many
synthetic methods, as the key step, have been developed in
pursuit of this structure, including intramolecular alkyla-
tion,2 radical cyclization,3 [3,3]-sigmatropic rearrangement,4
ring closure of geminal-disubstituted alkenes,5 cycloaddi-
tion,6 and transition-metal-mediated cyclization.7 Among
these, Claisen rearrangement is generally regarded as a high-
performance method for diastereoselective C-C bond for-
mation from an easily accessible C-O single bond, thereby
generating two stereogenic centers and a double bond.8
Metal-catalyzed Claisen-type rearrangement has shown sig-
nificant impact due to the catalysis needing milder reaction
conditions and providing better stereoselectivities compared
to their thermal counterparts.9 Recently, cationic phosphine
The construction of spirocyclic building blocks is an
important synthetic goal because such ring skeletons have
interesting conformational features and are present in nu-
merous natural products of biological interest.1 Because the
*Corresponding author. Fax: 886-2-29324249. E-mail: cheyeh@scc.
ntnu.edu.tw.
(1) (a) Srivastav, N.; Mittal, A.; Kumar, A. J. Chem. Soc., Chem.
Commun. 1992, 493. (b) Kobayashi, J.; Tsuda, M.; Agemi, K.; Shigemiri, H.;
Ishibashi, M.; Sasaki, T.; Mikami, Y. Tetrahedron 1991, 47, 6617. (c) James,
D. M.; Kunze, H. B.; Faulkner, D. J. J. Nat. Prod. 1991, 54, 113. (d) Posner,
G. H.; Hamill, T. G. J. Org. Chem. 1988, 53, 6031. (e) Stork, G.; Danheser,
R. L.; Ganem, B. J. Am. Chem. Soc. 1973, 95, 3414. (f) Huang, H.; Forsyth,
C. J. J. Org. Chem. 1995, 60, 2773. (g) Yamamoto, Y.; Furuta, T. J. Org.
Chem. 1990, 55, 3971.
(2) (a) Pigge, F. C.; Coniglio, J. J.; Dalvi, R. J. Am. Chem. Soc. 2006,
128, 3498. (b) Chande, M. S.; Khanwelkar, R. R. Tetrahedron Lett. 2005,
46, 7787. (c) Kotha, S.; Manivannan, E. Arkivoc 2003, 67. (d) Huang, A.;
Kodanko, J. J.; Overman, L. E. J. Am. Chem. Soc. 2004, 126, 14043.
(e) Bagul, T. D.; Lakshmaiah, G.; Kawabata, T.; Fuji, K. Org. Lett. 2002, 4,
249. (f) Takasu, K.; Ohsato, H.; Ihara, M. Org. Lett. 2003, 5, 3017.
(3) (a) Inui, M.; Nakazaki, A.; Kobayashi, S. Org. Lett. 2007, 9, 469.
(b) Takasu, K.; Ohsato, H.; Ihara, M. Org. Lett. 2003, 5, 3017. (c) Parsons, P.
J.; Caddick, S. Tetrahedron 1994, 50, 13523. (d) Ladlow, M.; Pattenden, G.
Tetrahedron Lett. 1984, 25, 4317. (e) Lee, E.; Tae, J. S.; Lee, C.; Park, C. M.
Tetrahedron Lett. 1993, 34, 4831.
(4) (a) Miyamoto, H.; Okawa, Y.; Nakazaki, A.; Kobayashi, S.
Angew. Chem., Int. Ed. 2006, 45, 2274. (b) Kawasaki, T.; Ogawa, A.;
Terashima, R.; Saheki, T.; Ban, N.; Sekiguchi, H.; Sakaguchi, K.; Sakamoto,
M. J. Org. Chem. 2005, 70, 2957. (c) Mao, Z.; Baldwin, S. W. Org. Lett.
2004, 6, 2425.
(5) (a) Fedouloff, M.; Paknoham, S. J.; Strachan, J. B.; Melville, J.
L.; Voyle, M. Tetrahedron Lett. 2000, 41, 4657. (b) Somei, M.;
Yamada, F.; Izumi, T.; Nakajou, M. Heterocycles 1997, 45, 2327.
(c) Nakazaki, A.; Miyamoto, H.; Henmi, K.; Kobayashi, S. Synlett
2005, 1417. (d) For a related example of the construction of spirocyclic
compounds based on a Claisen rearrangement, see: Miyamoto, H.;
Okawa, Y.; Nakazaki, A.; Kobayashi, S. Angew. Chem., Int. Ed. 2006,
45, 2274. (e) Nakazaki, A.; Era, T.; Numada, Y.; Kobayashi, S. Tetra-
hedron 2006, 62, 6264.
(7) (a) Pearson, A. J.; Alimardonov, A.; Pinkerton, A. A.; Parrish,
D. A. J. Org. Chem. 1998, 63, 6601. (b) Pearson, A. J.; Zettler, M. W.
J. Chem. Soc., Chem. Commun. 1987, 1243. (c) Kido, S.; Abiko, P.;
Kato, M. J. Chem. Soc., Perkin Trans. 1 1992, 229. (d) Cossy, J.;
Bouzide, A.; Leblanc, C. Synlett 1993, 202. (e) Tanaka, M.; Takahashi,
M.; Sakamoto, E.; Imail, M.; Matsui, A.; Fujio, M.; Funakoshi, K.; Sakai,
K.; Suemune, H. Tetrahedron 2001, 57, 1197. (f) Semmelhack, M. F.;
Yamashita, A. J. J. Am. Chem. Soc. 1980, 102, 5924. (g) Trost, B. M.;
Shi, Y. J. Am. Chem. Soc. 1991, 113, 701. (h) Villar, J. M.; Delgado, A.;
Llebaria, A.; Moreto, J. M.; Molins, E.; Miravitlles, C. Tetrahedron
1996, 52, 10525. (i) Pages, L.; Llebaria, A.; Camps, F.; Molins, E.;
Miravitlles, C.; Moreto, J. M. J. Am. Chem. Soc. 1992, 114, 10449.
(j) Casaschi, A.; Grigg, R.; Sansano, J. M.; Vilson, D.; Redpath, J.
Tetrahedron 2000, 56, 7541.
(8) For reviews on catalysis of the Claisenrearrangement, see: (a) Lutz,
R. P. Chem. Rev. 1984, 84, 205. (b) Ito, H.; Taguchi, T. Chem. Soc. Rev.
1999, 28, 43. (c) Hiersemann, M.; Abraham, L. Eur. J. Org. Chem. 2002,
1461.
(9) For Lewis acid catalysis of the Claisen rearrangement see:
(a) Takai, K.; Mori, I.; Oshima, K.; Nozaki, H. Tetrahedron Lett.
1981, 22, 3985. (b) Nonoshita, K.; Banno, H.; Maruoka, K.; Yamamoto, H.
J. Am. Chem. Soc. 1990, 112, 316. (c) Trost, B. M.; Schroeder, G. M. J. Am.
Chem. Soc. 2000, 122, 3785. (d) Hiersemann, M.; Abraham, L. Org. Lett.
2001, 3, 4952. For metal catalysis of the Claisen rearrangement see: (e) van
der Baan, J. L.; Bickelhaupt, F. Tetrahedron Lett. 1986, 27, 6267.
(f) Sugiura, M.; Yanagisawa, M.; Nakai, T. Synlett 1995, 447. (g) Overman,
L. E. Angew. Chem., Int. Ed. 1984, 23, 579.
(6) (a) Yong, S. R.; Williams, M. C.; Pyne, S. G.; Ung, A. T.; Skelton,
B. W.; White, A. H.; Turner, P. Tetrahedron 2005, 61, 8120. (b) Beccalli,
E. M.; Clerici, F.; Gelmi, M. L. Tetrahedron 2003, 59, 4615. (c) Okada, K.;
Kondo, M.; Tanino, H.; Inoue, S. Heterocycles 1992, 34, 589. (d) Barluenga,
J.; Aznar, F.; Barluenga, S.; Garcia-Granda, S.; Alvarez-Rua, C. Synlett
1997, 1040. (e) Marx, J.; Norman, L. R. J. Org. Chem. 1975, 40, 1602.
r
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2009 American Chemical Society

Article
Organometallics, Vol. 29, No. 1, 2010 161
gold(I) complexes have emerged as versatile catalysts
for electrophilic activation of alkynes toward a variety
of nucleophiles under mild reaction conditions, allowing
numerous synthetic transformations of unsaturated
systems into useful structure motifs.10 Although gold(I)-
catalyzed Claisen-type rearrangement of propagylic vinyl
ethers and 3-methoxy-1,6-enynes has been reported to give
homoallenic alcohols11 and cycloheptenones,12 respec-
tively, a general gold(I)-catalyzed Claisen-type rearrange-
ment of cyclic 8-aryl-2,7-enyn-1-ols to give spirocycles
has yet to be developed. We have now demonstrated
that phosphine gold(I) can be applied toward the syn-
thesis of spirocycles by treatment of cyclic 8-aryl-2,7-enyn-
1-ols with a catalytic amount of Ph3PAuCl/AgOTf. In
this transformation, a nucleophilic 9-endo-dig addi-
tion of the hydroxyl group onto the gold(I)-activated
alkyne generated a cationic allylic vinyl ether gold inter-
mediate. A subsequent Claisen-type rearrangement of
the cyclic transient cationic gold intermediate pro-
duced a spirocyclic ketone. Moreover, the gold(I)-cata-
lyzed Claisen-type rearrangement of cylic 8-aryl-2,7-
enyn-1-ols containing a N-sulfonamide or an oxygen
atom linkage in the tether afforded aza- and oxaspirocycles,
respectively.
both Ph3PAuCl and AgOTf are required for the rearran-
gement.
Recently, the Yamamoto group has reported a trifluoro-
methanesulfonic acid (TfOH)-catalyzed cyclization of alkynyl
cyclic tertiary alcohol 4 to form the spirocyclic ketone 5 as a
mixture of diastereomers in 80% yield.14 The reaction path
leading to 5 started with the formation of the tertiary carboca-
tion (6a) followed by addition of the alkynyl moiety onto the
cation to give a benzylidene cation (6b). Trapping of the
reactive cation with H2O afforded the spirocyclic ketone 5.
To investigate the possibility of an ionization pathway by the
gold catalyst, the non-allylic tertiary alcohol 4 was treated
with the gold(I) cation. Thus, treatment of 4 with 5 mol % of
Ph3PAuCl/AgOTf in CH2Cl2 at 25 °C for 45 min produced
cyclohexenylketone 7 in 68% isolated yield (Scheme 1). The
formation of 7 may start with a 6-exo-dig cyclization to afford
8a followed by proton transfer to give the cyclic vinyl ether 8b.
Deprotonation of 8b produced the cyclohexenyl ketone 7. On
the basis of two different rearrangement products (5 vs 7)
obtained from TfOH and the gold catalyst, it is reasonable to
state that the cationic pathway suggested by Yamamoto does
not apply to the gold-catalyzed transformation of 4. More-
over, Rhee has reported that the tertiary allylic alcohol 9,
containing a carbocation-stabilizing phenyl group at the
allylic position, converted quantitatively into 1-methoxy-5-
phenyl-1,4-cycoheptadiene (10) using 2 mol % of Ph3PAuCl/
AgSbF6.12 The formation of 10 was suggested via a 5-exo-dig
cyclization (to give 11) followed by a [3,3]-sigmatropic rear-
rangement. The ionic intermediate 12, however, would lead to
six- or eight-membered carbocycles. Therefore, a concerted
reaction pathway for rearrangement of 1a is likely to proceed
under the gold-catalyzed reaction conditions.
Results and Discussion
The requisite 8-arylcyclohex-2-en-7-yn-1-ol 1 was pre-
pared by addition of the corresponding 5-lithio-1-aryl-
pent-1-yne to 3-methoxycyclohex-2-en-1-one followed by
reduction of the resulting enones with NaBH4 in MeOH to
afford 8-arylcyclohex-2-en-7-yn-1-ol 1 in good overall
yields. Our study of gold(I)-catalyzed Claisen-type rear-
rangement of 8-arylcyclohex-2-en-7-yn-1-ols began with
the parent compound 1a. Treatment of 1a with 5 mol % of
Ph3PAuCl/AgOTf in CH2Cl2 at 25 °C for 3 min produced
phenyl(spiro[4.5]dec-6-en-1-yl)methanone (2a) in 90%
isolated yield as a 1:1 mixture of two diastereomers
(eq 1). Attempts to separate isomers using flash column
chromatography on silica gel failed. A Pd/C-catalyzed
chemoselective hydrogenation of 2a employing diphenyl-
sulfide as a catalyst poison produced the spirocyclic
ketone 3a.13 Thus, the crude mixture of isomer 2a, 10
mol % Pd/C, and 10 mol % diphenylsulfide in ethanol was
allowed to stir at room temperature under 1 atm of
hydrogen for 24 h to provide the spirocyclic ketone 3a in
85% isolated yield in two steps (eq 1). Decreasing the
catalyst loading for the [3,3]-sigmatropic rearrangement
of 1a to 0.1 mol % slowed the reaction (90 min) but still
produced 2a in 90% yield. In contrast, when 1a was
treated with 5 mol % PtCl2 in fluxing toluene, the reaction
failed to give the desired spirocyclic ketone 2a. Moreover,
(10) (a) Toste, F. D.; Gorin, D. J. Nature 2007, 446, 395. (b) F€urstner,
A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410. (c) Nieto-
~
~
ꢀ
Oberhuber, C.; Munoz, M. P.; Bunuel, E.; Nevado, C.; Cardenas, D. J.;
Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 2402. (d) Yeh, M. C. P.;
Tsao, W. C.; Lee, B. J.; Lin, T. L. Organometallics 2008, 27, 5326. For
reviews on gold catalysts in organic synthesis, see: (e) Patil, N. T.;
Yamamoto, Y. Chem. Rev. 2008, 108, 3395.
A reaction pathway was suggested in Scheme 2. Unlike
addition of the olefin to the gold-activated alkyne in most
(11) Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978.
(12) Bae, H. J.; Baskar, B.; An, S. E.; Cheong, J. Y.; Thangadurai, D.
T.; Hwang, I. C.; Rhee, Y. H. Angew. Chem., Int. Ed. 2008, 47, 2263.
(13) Mori, A.; Miyakawa, Y.; Ohashi, E.; Haga, T.; Maegawa, T.;
Sajiki, H. Org. Lett. 2006, 8, 3279.
(14) Jin, T.; Himuro, M.; Yamamoto, Y. Angew. Chem., Int. Ed.
2009, 48, 5893.

162 Organometallics, Vol. 29, No. 1, 2010
Yeh et al.
Scheme 1
mention that an acyclic analogue of 1a, for example the
acyclic 2,7-enyn-1-ol 16, underwent addition of alkene to the
gold-activated alkyne in a 5-exo-dig fashion using 2 mol % of
Ph3PAuCl/AgOTf to afford a gold cyclopropylcarbene fol-
lowed by skeletal rearrangement to give 1,3-diene 17.16 In
this case, the hydroxyl group did not participate as a
competing nucleophile in the addition to the gold-activated
terminal alkyne. Moreover, a gold(I)-catalyzed aza-Claisen-
type rearrangement of pentenynyl allyl tosylamides to afford
pyrroles only occurred with terminal alkynes,17 and sub-
strates bearing a phenyl group at the terminal position of the
alkyne failed to generate the corresponding pyrrole using a
high loading of the gold catalyst ((pCF3Ph)3PAuNTf2). The
failure of the cyclization may be due to an increased steric
hindrance during the nucleophilic addition step of the tosy-
lamide moiety onto the gold(I)-activated alkyne, while in the
case of 1 the hydroxyl group added efficiently to the gold(I)-
activated phenyl-substituted alkyne to generate the cationic
allylic vinyl gold intermediate 13 (Scheme 2).
Scheme 2
Results of gold-catalyzed Claisen-type rearrangements of
cyclic 8-aryl-2,7-enyn-1-ols 1a-e, followed by olefin hydro-
genation to produce spirocyclic ketones 3a-e, are listed in
Table 1. Electron-neutral and -rich arenes were proven to
be good substrates, as the yields of desired spiroketones 3a-e
ranged from 60% to 85% in two steps (Table 1, entries 1-5).
However, substrate 1f, possessing a para bromine atom at the
phenyl ring, was less effective and provided 2f in 60% yield
(Table 1, entry 6). To rule out the possibility of forming an
allyl cationic intermediate catalyzed by gold(I) followed by
attack of the pendant alkynyl group onto the allylic cation
generating the spirocyclic ketones, the hydroxyl group was
changed to the O-TBDMS (tert-butyldimethylsilyl) group,
for example 1g (Table 1, entry 7). The possible coordination
of gold(I) to the oxygen atom should be prevented by the
presence of the sterically demanding TBDMS group. The
comparative isolated yields of 2a, obtained from transfor-
mation of 1a (90%) and the TBDMS ether 1g (70%),
respectively, may rule out the possible formation of highly
reactive allyl cations and call for a coordination of the gold(I)
to the pendant C-C triple bond, which is active during the
ring-closing event (Scheme 2).18 Moreover, the tertiary
allylic alcohol with an ethyl group on the C-1 position, for
example 1h, also provided the spirocyclic ketone 2h in 40%
yield in 20 min under the standard reaction conditions
(Table 1, entry 8). The low yield might be attributed to an
increased steric hindrance during the nucleophilic addition
step of the hydroxyl group onto the gold(I)-activated alkyne.
This result may further indicate that the formation of a more
stable tertiary carbocation by reaction of the gold(I) catalyst
with 1h did not occur. Therefore, these two examples
gold(I)-catalyzed cyclization of simple 1,6-enynes, a 9-endo-
dig addition of the alcohol oxygen onto the gold-activated
alkyne occurred. Coordination of the alkene to the gold
center formed the cationic allylic vinyl gold intermediate 13.
In this way, it aligns two alkenyl moieties for further
conversions. Moreover, the intermediate 13, containing an
oxonium ion, could greatly facilitate the key [3,3]-sigmatro-
pic rearrangement. A similar allylic vinyl gold was suggested
in the literature as a low-energy intermediate in the gold-
catalyzed rearrangement of allenynes and N-allylic aminoni-
triles.15 A subsequent Claisen-type rearrangement of the
cyclic transient intermediate 13 produced the spirocyclic
intermediate 14, with a newly formed quarternary carbon
center and a carbon-gold bond at the R-position of the
carbonyl group. Attack of the triflate at the gold center of 14
furnished the spirocyclic enol 15 and release of the gold(I)
catalyst into the catalytic cycle. Enol 15 led to spirocyclic
ketone 2 as a 1:1 mixture of diastereomers. It is important to
ꢀ
ꢀ~
(16) (a) Jimenez-Nunez, E.; Echavarren, A. M. Chem. Rev. 2008, 108,
~
ꢀ
ꢀ
~
3326. (b) Nieto-Oberhuber, C.; Munoz, M. P.; Lopez, S.; Jimenez-Nꢀunez, E.;
ꢀ
Nevado, C.; Herrero-Gomez, E.; Raducan, M.; Echavarren, A. M. Chem.;
(15) (a) Heugebaert, T. S. A.; Stevens, C. V. Org. Lett. 2009, 11, 5018.
(b) Lemiere, G.; Gandon, V.; Agenet, N.; Goddard, J.-P.; de Kozak, A.;
Aubert, C.; Fensterbank, L.; Malacria, M. Angew. Chem., Int. Ed. 2006, 45,
7596.
Eur. J. 2006, 12, 1677.
(17) Istrate, F. M.; Gagosz, F. Org. Lett. 2007, 9, 3181.
(18) Bandini, M.; Eichholzer, A.; Kotrusz, P.; Tragni, M.; Troisi, S.;
Umani-Ronchi, A. Adv. Synth. Catal. 2009, 351, 319.

Article
Table 1. Gold(I)-Catalyzed Synthesis of Spiroketones 2 and
Hydrogenation of 2 to Give Spiroketones 3
Organometallics, Vol. 29, No. 1, 2010 163
saturated azaspirocycles 23a-e in 52-85% yields in two steps.
Moreover, substrate 24, containing two oxygen atoms at both
allylic positions, was investigated. Compound 24 was prepared
starting from addition of sodium hydride to the mixture of
3-(hydroxymethyl)cyclohex-2-en-1-one and 1-bromo-3-phenyl-
2-propyne in tetrahydrofuran to give the enone 25. Reduc-
tion of 25 with sodium borohydride in methanol afforded 24.
The cyclic enynol 24 was transformed into the expected
oxaspirocyclic ketone 26 as a mixture of diastereomers in
62% yield using 5 mol % of the gold(I) catalyst in CH2Cl2 at
25 °C for 2 h. The oxaspirocycle 26 was selectively hydro-
genated by the Wilkinson catalyst (10 mol % Rh(PPh3)3Cl/H2)
in ethanol at room temperature for 12 h to provide the
oxaspirocycle 27 in 78% isolated yield. However, when treated
with TfOH, compound 24 decomposed immediately. There-
fore, the isolation of 26 may further provide evidence that the
gold-catalyzed reaction did not proceed via an ionic pathway
even when compound 24 contains a very sensitive allyl propa-
gyl ether moiety.
(Table 1, entries 7, 8) may serve as mechanistic probes
indicating a more concerted Claisen-type mechanism in the
present case and exclude the possibility of the formation of
allylic carbocationic intermediates. To further highlight the
synthetic potential of the present catalytic cyclization, cyclic
2,7-enyn-1-ols with a methyl group or a hydrogen atom at
the alkyne terminus were attempted. Unfortunately, both
substrates failed to give the corresponding spirocycles even
in the presence of 10 mol % of the catalyst, but instead
resulted in the formation of unidentified products.
Five-membered-ring substrates 18a-e also underwent
Claisen-type rearrangement to provide spiro[4.4]nonenones
19a-e, respectively, as a mixture of diastereomers in each
case and in good yields (Table 1, entries 9-13). Upon use of
10 mol % Pd/C in the presence of Ph2S, the hydrogenation of
19a-e readily proceeded to give spirocyclic ketones 20a-e in
64-80% yields in two steps.
We have described here a highly efficient gold(I)-catalyzed
cycloisomerization of cyclic 8-aryl-2,7-enyn-1-ols featuring a
Claisen-type rearrangement as the key step. The transforma-
tion is characterized by its efficiency, the mild conditions
employed, and the easy formation of spiro[4.5]decane and
spiro[4.4]nonane skeletons. This catalytic cyclization was
applied to the formation of aza- and oxaspirocycles. The
easy formation of spirocycles in an efficient way under mild
reaction conditions may have further applications.
Experimental Section
The chemistry is general for the synthesis of nitrogen spiro-
cycles. Substrates 21a-e, containing an N-sulfonamide linkage
in the tether, were prepared from treatment of 3-(bromo-
methyl)cyclohex-2-en-1-one with respective N-sulfonated aryl-
propagyl amines. In general, substrates 21a-e, bearing an
N-sulfonamide in the tether, reacted with the catalyst less effi-
ciently at room temperature. Thus, the reaction was performed
in refluxing CH2Cl2 for 15 min to give azaspirocycles 22a-e as
a 1:1 unseparable diastereomeric mixture (eq 2). These azas-
pirocycles were further hydrogenated (Pd/C/PhS2/H2) to give
General Considerations. All reactions were performed in oven-
dried glassware under a nitrogen atmosphere unless otherwise
indicated. Anhydrous solvents or reaction mixtures were trans-
ferred via an oven-dried syringe or cannula. Methylene chloride
was predried by molecular sieves and then by passing through an
Al2O3 column.18 Flash column chromatography, following the
method of Still, was carried out with E. Merck silica gel (Kieselgel
60, 230-400 mesh) using the indicated solvents.19 1H nuclear
(19) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.;
Timmers, F. J. Organometallics 1996, 15, 1518.

164 Organometallics, Vol. 29, No. 1, 2010
Yeh et al.
magnetic resonance (NMR) spectra were obtained with Bruker-
AC 400 (400 MHz) and 500 (500 MHz) spectrometers. The
chemical shifts are reported in parts per million with either
tetramethylsilane (0.00 ppm) or CDCl3 (7.26 ppm) as internal
standard. 13C NMR spectra were recorded with Bruker-AC 400
(100 MHz) and 500 (125 MHz) spectrometers with CDCl3 (77.0
ppm) as the internal standard. Infrared (IR) spectra were
recorded with a JASCO IR-700 spectrometer. Mass spectra
were acquired on a JEOL JMS-D 100 spectrometer at an
ionization potential of 70 eV and were reported as mass/charge
(m/e) with percent relative abundance. High-resolution mass
spectra were obtained with an AEI MS-9 double-focusing mass
spectrometer and a JEOL JMS-HX 110 spectrometer at the
Department of Chemistry, Central Instrument Center, Tai-
chung, Taiwan.
126.1, 124.5, 60.0, 48.9, 38.7, 36.1, 33.5, 28.6, 26.3, 23.8, 23.5,
23.0; MS (EI) m/e (%) 292.3 (Mþ, 29), 196.1 (20), 183.1 (14),
170.1 (27), 156.1 (15), 155.1 (100), 127.1 (49); HRMS (EI) m/e
calcd for C21H24O 292.1819, found 292.1827.
Phenanthren-9-yl(spiro[4.5]decan-1-yl)methanone (3c). The
crude mixture obtained from gold(I)-catalyzed Claisen-type
rearrangement of 1c (0.68 g, 2.0 mmol) followed by hydrogena-
tion was purified by flash column chromatography (silica gel,
gradient elution: 5% to 20% ethyl acetate/hexanes) to give 3c
(0.56 g, 1.64 mmol, 82%) as a yellow oil: IR (CH2Cl2) 2925,
2856, 1670, 1529, 1495, 1451 cm-1; 1H NMR (400 MHz, CDCl3)
δ 8.71 (d, J = 7.8 Hz, 1 H), 8.67 (d, J = 8.3 Hz, 1 H), 8.49 (d, J =
7.8 Hz, 1 H), 8.06 (s, 1 H), 7.95 (d, J = 7.8 Hz, 1 H), 7.74-7.60
(m, 4 H), 3.68 (t, J = 7.8 Hz, 1 H), 2.31 (m, 1 H), 2.02 (m, 1 H),
1.98-1.83 (m, 2 H), 1.73 (m, 1 H), 1.64-1.57 (m, 2 H),
1.46-1.23 (m, 8 H), 0.90 (m, 1 H); 13C NMR(100 MHz, CDCl3)
δ 207.69, 137.89, 131.62, 130.89 130.08, 129.68, 128.99, 128.48,
128.36, 127.26, 126.97, 126.78, 122.84, 122.62, 59.85, 48.76,
38.59, 35.88, 33.26, 28.36, 26.03, 23.65, 23.23, 22.76; MS (EI)
m/e (rel intensity) 342.4 (Mþ, 32), 220.2 (27), 206.2 (28), 205.2
(100), 177.1 (55), 176.1 (23); HRMS (EI) m/e calcd for C25H26O
342.1989, found 342.1984.
Biphenyl-4-yl(spiro[4.5]decan-1-yl)methanone (3d). The crude
mixture obtained from gold(I)-catalyzed Claisen-type rearran-
gement of 1d (0.94 g, 3.0 mmol) followed by hydrogenation was
purified by flash column chromatography (silica gel, gradient
elution: 5% to 20% ethyl acetate/hexanes) to give 3d (0.63 g,
0.19 mmol, 66%) as a yellow oil: IR (CH2Cl2) 3054, 2985, 2931,
2858, 2305, 1669, 1602, 1422, 1265 cm-1; 1H NMR (400 MHz,
CDCl3) δ 8.02, (d, J = 8.3 Hz, 2 H), 7.68 (d, J = 8.3 Hz, 2 H),
7.64 (d, J = 7.4 Hz, 2 H), 7.47 (t, J = 7.5 Hz, 2 H), 7.39 (t, J =
7.3 Hz, 1 H), 3.61 (t, J = 7.4 Hz, 1 H), 2.13 (m, 1 H), 1.91-1.85
(m, 2 H), 1.76 (m, 1 H), 1.71-1.64 (m, 2 H), 1.58-1.50 (m, 3 H),
1.44-1.40 (m, 4 H), 1.28 (m, 1 H), 1.10-1.03 (m, 2 H); 13C NMR
(100 MHz, CDCl3) δ 203.6, 145.4, 140.2, 138.1, 129.2, 129.1,
128.3, 127.5, 127.3, 56.0, 48.2, 38.8, 35.9, 33.9, 29.0, 26.3, 23.9,
23.5, 23.4; MS (EI) m/e (%) 318.3 (Mþ, 34), 196.1 (86), 182.1
(15), 181.1 (100), 153.1 (24), 152.1 (41), 55.1 (19); HRMS (EI) m/
e calcd for C23H26O 318.1977, found 318.1984.
(4-Methoxyphenyl)(spiro[4.5]decan-1-yl)methanone (3e). The
crude mixture obtained from gold(I)-catalyzed Claisen-type
rearrangement of 1e (0.81 g, 3.0 mmol) followed by hydrogena-
tion was purified by flash column chromatography (silica gel,
gradient elution: 5% to 20% ethyl acetate/hexanes) to give 3e
(0.66 g, 2.43 mmol, 81%) as a yellow oil: IR (CH2Cl2) 2934,
2856, 1664, 1600, 1576, 1508, 1450, 1418, 1364, 1306, 1261, 1236,
1170, 1112, 1031 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.95 (d,
J = 8.8 Hz, 2 H), 6.93 (d, J = 8.8 Hz, 2 H), 3.85 (s, 3 H), 3.52 (t,
J = 7.3 Hz, 1 H), 2.11 (m, 1 H), 1.88-1.79 (m, 2 H), 1.74 (m, 1
H), 1.69-1.63 (m, 2 H), 1.53-1.48 (m, 3 H), 1.43-1.37 (m, 4 H),
1.25 (m, 1 H), 1.05-0.99 (m, 2 H); 13C NMR (100 MHz, CDCl3)
δ 202.2, 163.3, 132.3, 130.7, 113.7, 55.5, 55.4, 47.9, 38.6, 35.7,
33.7, 28.8, 26.2, 23.8, 23.4, 23.3; MS (EI) m/e (%) 272.3 (Mþ,
13), 176.1 (12), 163.1 (40), 135.1 (100), 107.1 (10), 92.1 (10), 77.1
(17), 55.1 (11); HRMS (EI) m/e calcd for C18H24O2 272.1770,
found 272.1776.
General Procedure for Gold(I)-Catalyzed Claisen-Type Rear-
rangement of Cyclic 8-Aryl-2,7-enyn-1-ols Followed by Hydro-
genation. Synthesis of Spirocyclic Ketones 3. To an oven-dried
50 mL round-bottom flask equipped with a stirrer bar and
capped with a rubber septum was added AgOTf (12 mg, 0.05
mmol). The apparatus was evacuated (oil pump) and filled with
nitrogen three times. To the reaction mixture were then added
via syringe 8-phenyl-2-cyclohex-1-ol (1a) (0.24 g, 1.0 mmol) and
PPh3AuCl (24 mg, 0.05 mmol) in 10 mL of CH2Cl2. The
resulting mixture was stirred at room temperature for 3 min.
The resulting dark blue solution was filtered through a bed of
Celite. The filtrate was concentrated in vacuo to give the crude
mixture. The residue was purified by flash column chromatog-
raphy (silica gel, gradient elution: 5% to 10% ethyl acetate/
hexanes) to give phenyl(spiro[4.5]dec-6-en-1-yl)methanone (2a)
(0.22 g, 0.9 mmol, 90%) as a yellow oil. To an oven-dried 50 mL
round-bottom flask equipped with a stirrer bar and capped with
a rubber septum was added 2a (0.22 g, 0.9 mmol) in 18 mL of
ethanol at room temperature (ca. 30 °C) followed by addition
of Pd/C (96 mg, 0.09 mmol) and diphenylsulfide (9 mg, 0.045
mmol). The air inside the reaction flask was evacuated and filled
with a balloon of hydrogen twice. The reaction was vigorously
stirred under 1 atm of hydrogen for 24 h. The crude mixture was
filtered through a bed of Celite and eluted with dichloromethane
(30 mL). The filtrate was concentrated to give the crude mixture.
Phenyl(spiro[4.5]decan-1-yl)methanone (3a). The crude mix-
ture obtained from gold(I)-catalyzed Claisen-type rearrange-
ment of 1a (0.24 g, 1.0 mmol) followed by hydrogenation was
purified by flash column chromatography (silica gel, gradient
elution: 5% to 20% ethyl acetate/hexanes) to give 3a (0.21 g,
0.85 mmol, 85%) as a yellow oil: IR (CH2Cl2) 2925, 2854, 1673,
1596, 1447, 1363, 1231, 1201 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.94 (d, J = 7.5 Hz, 2 H), 7.52 (t, J = 7.3 Hz, 1 H), 7.43 (t, J =
7.6 Hz, 2 H), 3.57 (t, J = 7.4 Hz, 1 H), 2.11 (m, 1 H), 1.89-1.82
(m, 2 H), 1.74 (m, 1 H), 1.70-1.62 (m, 2 H), 1.54-1.47 (m, 3 H),
1.41-1.37 (m, 4 H), 1.23 (m, 1 H), 1.07-0.98 (m, 2 H); 13C NMR
(100 MHz, CDCl3) δ 203.8, 139.3, 132.6, 128.5, 128.4, 55.7, 48.0,
38.5, 35.7, 33.7, 28.8, 26.1, 23.8, 23.4, 23.2; MS (EI) m/e (%)
242.2 (Mþ, 40), 146.1 (86), 145.1 (23), 133.1 (93), 122.2 (77) 120.1
(39), 105.1 (100), 81.1 (25), 77.1 (64), 55.1 (28); HRMS (EI) m/e
calcd for C17H22O 242.1672, found 242.1670.
Naphthalen-1-yl(spiro[4.5]decan-1-yl)methanone (3b). The
crude mixture obtained from gold(I)-catalyzed Claisen-type
rearrangement of 1b (0.87 g, 3.0 mmol) followed by hydrogena-
tion was purified by flash column chromatography (silica gel,
gradient elution: 5% to 20% ethyl acetate/hexanes) to give
naphthalen-1-yl(spiro[4.5]decan-1-yl)methanone 3b (0.52 g,
1.8 mmol, 60%) as a yellow oil: IR (CH2Cl2) 2925, 2854, 1672,
1593, 1574, 1508, 1449, 1352, 1269, 1233, 1173 cm-1; 1H NMR
(400 MHz, CDCl3) δ 8.48 (d, J = 8.4 Hz, 1 H), 7.95 (d, J = 8.2
Hz, 1 H), 7.87 (d, J = 8.0 Hz, 1 H), 7.81 (d, J = 7.2 Hz, 1 H),
7.59-7.46 (m, 3 H), 3.58 (t, J = 7.7 Hz, 1 H), 2.25 (m, 1 H),
2.01-1.82 (m, 3 H), 1.70 (m, 1 H), 1.62-1.57 (m, 2 H),
1.46-1.23 (m, 8 H), 0.92 (m, 1 H); 13C NMR (100 MHz, CDCl3)
δ 208.1, 139.1, 134.3, 132.2, 130.2, 128.6, 127.8, 127.4, 126.5,
(4-Bromophenyl)((1S,5R)-spiro[4.5]dec-6-en-1-yl)methanone
(2f). The crude mixture obtained from gold(I)-catalyzed Clai-
sen-type rearrangement of 1f (0.95 g, 3.0 mmol) was purified by
flash column chromatography (silica gel, gradient elution: 5%
to 10% ethyl acetate/hexanes) to give 2f (0.57 g, 1.80 mmol,
60%) as a yellow oil: dr = 1:1; IR (CH2Cl2) 2090, 1639, 1395,
1071, 1004 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.4
Hz, 2 H), 7.35 (d, J = 8.8 Hz, 2 H), 7.56 (d, J = 8.4 Hz, 4 H),
5.59-5.57 (m, 2 H), 5.48 (dt, J = 10.4, 3.6 Hz, 1 H), 5.36 (d, J =
10 Hz, 1 H), 3.64-3.57 (m, 2 H), 2.28-1.93 (m, 2 H), 1.93-1.39
(m, 22 H); 13C NMR (100 MHz, CDCl3) δ 202.89, 202.09,
137.63, 137.57, 135.69, 132.41, 131.60, 131.58, 130.09, 130.00,
127.70, 127.58, 126.95, 126.90, 55.79, 55.70, 48.50, 48.07, 41.89,
40.62, 35.92, 30.46, 29.70, 28.76, 28.56, 24.96, 24.85, 23.27,

Article
Organometallics, Vol. 29, No. 1, 2010 165
22.99, 20.43, 20.18; MS (EI) m/e (%); HRMS (EI) m/e calcd for
C17H19BrO 318.0619, found 318.0623.
purified by flash column chromatography (silica gel, gradient
elution:5% to20% ethylacetate/hexanes) togive 20c (0.39g, 1.28
mmol, 64%) as a yellow oil: IR (CH2Cl2) 2938, 2869, 1670, 1601,
1448, 1402 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.4
Hz, 2 H), 7.69 (d, J = 8.3 Hz, 2 H), 7.65 (d, J = 7.3 Hz, 2 H), 7.48
(d, J = 7.2 Hz, 2 H), 7.41 (t, J = 7.3 Hz, 1 H), 3.77 (t, J = 7.8 Hz,
1 H), 2.16-2.05(m, 1 H), 2.02-1.92 (m, 1 H), 1.91-1.85 (m, 1 H),
1.80-1.69 (m, 2 H), 1.62-1.54 (m, 6 H), 1.51-1.44 (m, 2 H),
1.43-1.37 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 203.74,
145.25, 139.96, 137.52, 128.92, 128.12, 127.25, 127.16, 55.60,
53.23, 39.70, 39.12, 34.19, 29.53, 24.31, 23.81, 23.26; MS (EI)
m/e (%) 304.3 (Mþ, 42), 209.1 (43), 196.1 (82), 181.1 (100), 153.1
(40), 152.1 (63); HRMS (EI) m/e calcd for C22H24O 304.1825,
found 304.1827. Crystals suitable for X-ray diffraction analysis
were grown from CH2Cl2 and hexanes.
Phenanthren-9-yl(spiro[4.4]nonan-1-yl)methanone (20d). The
crude mixture obtained from gold(I)-catalyzed Claisen-type
rearrangement of 18d (0.65 g, 2.0 mmol) followed by hydro-
genation was purified by flash column chromatography (silica
gel, gradient elution: 5% to 20% ethyl acetate/hexanes) to give
20d (0.50 g, 1.51 mmol, 76%) as a yellow oil: IR (CH2Cl2) 2950,
2869, 1670, 1529, 1492, 1445 cm-1; 1H NMR (400 MHz, CDCl3)
δ 8.72 (d, J = 7.8 Hz, 1 H), 8.68 (d, J = 8.3 Hz, 1 H), 8.44 (d, J =
8.0 Hz, 1 H), 8.04 (s, 1 H), 7.93 (d, J = 11.4 Hz, 1 H), 7.75-7.61
(m, 4 H), 3.83 (dd, J = 7.7, 6.3 Hz, 1 H), 2.32-2.21 (m, 1 H),
2.11-2.01 (m, 1 H), 1.99-1.89 (m, 1 H), 1.88-1.72 (m, 2 H),
1.68-1.55 (m, 4 H), 1.54-1.45 (m, 5 H); 13C NMR (100 MHz,
CDCl3) δ 208.08, 137.74, 131.60, 130.87, 130.08, 129.66, 128.84,
128.50, 128.42, 127.29, 127.00, 126.75, 122.84, 122.64, 57.57,
55.99, 39.65, 39.14, 33.96, 29.10, 24.51, 23.71, 22.98; MS (EI) m/
e (%) 328.2 (Mþ, 15), 311.2 (27), 205.1 (100), 191.1 (88), 177.1
(43); HRMS (EI) m/e calcd for C24H24O 328.1820, found
328.1827.
(4-Methoxyphenyl)(spiro[4.4]nonan-1-yl)methanone (20e).
The crude mixture obtained from gold(I)-catalyzed Claisen-type
rearrangement of 18e (0.51 g, 2.0 mmol) followed by hydro-
genation was purified by flash column chromatography (silica
gel, gradient elution: 5% to 20% ethyl acetate/hexanes) to give
20e (0.39 g, 1.51 mmol, 76%) as a yellow oil: IR (CH2Cl2) 2393,
2865, 1663, 1601, 1511, 1261, 1233, 1168, 1031 cm-1; 1H NMR
(400 MHz, CDCl3) δ 7.93 (d, J = 8.9 Hz, 2 H), 6.93 (d, J = 8.8
Hz, 2 H), 3.86 (s, 3 H), 3.67 (dd, J = 7.8, 6.3 Hz, 1 H), 2.15-2.03
(m, 1 H), 1.95-1.80 (m, 2 H), 1.78-1.67 (m, 2 H), 1.60-1.35 (m,
9 H); 13C NMR (100 MHz, CDCl3) δ 202.54, 163.13, 131.87,
130.52,113.59, 55.44, 55.37, 52.71, 39.63, 39.11, 34.07, 29.45,
24.23, 23.76, 23.22 ; MS (EI) m/e (%) 258.2 (Mþ, 7), 163.1 (36),
150.1 (61), 135.0 (100); HRMS (EI) m/e calcd for C17H22O2
258.1624, found 258.1620.
Phenyl(2-tosyl-2-azaspiro[4.5]decan-4-yl)methanone (23a).
The crude mixture obtained from gold(I)-catalyzed Claisen-type
rearrangement of 21a (0.12 g, 0.5 mmol) followed by hydrogena-
tion was purified by flash column chromatography (silica gel,
gradient elution: 10% to 50% ethyl acetate/hexanes) to give 23a
(0.1 g, 0.25 mmol, 52%) as a yellow solid: mp 128-130 °C; IR
(CH2Cl2) 2931, 1673, 1596, 1343, 1162 cm-1; 1H NMR (400 MHz,
CDCl3) δ 7.83 (d, J = 8.5 Hz, 2 H), 7.81 (d, J = 8.2 Hz, 2 H), 7.57
(t, J = 7.4Hz, 1 H), 7.45 (t, J = 7.5 Hz, 2 H), 7.36 (d, J = 8.0Hz, 2
H), 3.81 (t, J = 7.2 Hz, 1 H), 3.60 (dd, J = 10.0, 9.9 Hz, 2 H), 3.40
(d, J = 9.8 Hz, 1 H), 3.27 (d, J = 9.9 Hz, 1 H), 2.46 (s, 3 H),
1.62-1.51 (m, 3 H), 1.34-1.29 (m, 3 H), 1.09-0.90 (m, 4 H); 13C
NMR (100 MHz, CDCl3) δ199.43, 143.39, 137.96, 133.91, 133.39,
129.61, 128.71, 128.32, 127.55, 55.44, 53.34 49.19, 46.75, 36.49,
30.89, 25.41, 23.41, 22.97, 21.53; MS (EI) m/e (%) 397.2 (Mþ, 0.1),
243.2 (17), 242.2 (100), 110.1 (23). 105.1 (57), 91.1 (25), 77.1 (18);
HRMS (EI) m/e calcd for C23H27NO3S 397.1715, found 397.1711.
Crystals suitable for X-ray diffraction analysis were grown from
CH2Cl2 and hexanes.
Biphenyl-4-yl(7-ethylspiro[4.5]dec-6-en-1-yl)methanone (2h).
The crude mixture obtained from gold(I)-catalyzed Claisen-type
rearrangement of 1h (0.72 g, 2.0 mmol) was purified by flash
column chromatography (silica gel, gradient elution: 5% to
10% ethyl acetate/hexanes) to give 2h (0.13 g, 0.4 mmol, 40%)
as a yellow oil: dr = 1:1; IR (CH2Cl2) 2961, 2093, 1664, 1187,
1005 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.4 Hz, 4
H), 7.92 (d, J = 8.4 Hz, 2 H), 7.63-7.57 (m, 12 H), 7.46 (t, J =
7.1 Hz, 6 H), 7.39 (d, J = 7.3 Hz, 3 H), 5.31 (s, 2 H), 4.99 (s, 1 H),
3.71 (t, J = 6.4 Hz, 1 H), 3.67 (t, J = 8.6 Hz, 3 H), 2.33-2.14 (m,
3 H), 1.8-1.6 (m, 38 H), 0.82 (t, J = 7.2 Hz, 6 H), 0.65 (t, J = 7.2
Hz, 3 H), 13C NMR (100 MHz, CDCl3) δ 203.92, 202.97, 145.03,
144.82, 140.15, 140.12, 139.53, 139.38, 137.94, 137.84, 129.13,
129.03, 128.89, 128.73, 128.03, 127.24, 127.22, 126.80, 126.51,
125.71, 56.55, 55.93, 48.66, 48.26, 42.06, 40.48, 35.93, 30.51,
30.45, 30.21, 28.29, 28.14, 28.08, 28.04, 23.50, 22.82, 20.74,
20.56, 12.23, 12.06; MS (EI) m/e (%) 344 (Mþ, 100), 209 (100),
181 (61), 136 (95), 110 (61); HRMS (EI) m/e calcd for C25H28O
344.2140, found 344.2135.
5-Cyclohexenyl-1-phenylpentan-2-one (7). The crude mixture
obtained from gold(I)-catalyzed rearrangement of 4 (0.17 g, 1.0
mmol) was purified by flash column chromatography (silica gel,
gradient elution: hexanes to 2% ethyl acetate/hexanes) to give 7
(0.17 g, 0.07 mmol, 68%) as a colorless oil: IR (CH2Cl2) 2923,
2856, 1712, 1635, 1495, 1443, 1362 cm-1; 1H NMR (500 MHz,
CDCl3) δ 7.34-7.30 (m, 2 H), 7.27-7.23 (m, 1 H), 7.21-7.18 (m,
2 H), 5.33-5.31 (m, 1 H), 3.67 (s, 2 H), 2.41 (t, J = 7.4 Hz, 2 H),
1.98-1.91 (m, 2 H), 1.90-1.81 (m, 3 H), 1.70-1.60 (m, 3 H),
1.60-1.55 (m, 2 H), 1.55-1.48 (m, 2 H); 13C NMR (125 MHz,
CDCl3) δ 208.5, 136.84, 134.39, 129.38, 128.65 126.91, 121.66,
50.18, 41.29, 37.19, 27.97, 25.19, 22.91, 22.48, 21.56; MS (EI)
m/e (%) 242.2 (Mþ, 14), 151.1 (100), 133.1 (26), 108.2 (20),
67.1 (18).
Phenyl(spiro[4.4]nonan-1-yl)methanone (20a). The crude mix-
ture obtained from gold(I)-catalyzed Claisen-type rearrange-
ment of 18a (0.45 g, 2.0 mmol) followed by hydrogenation was
purified by flash column chromatography (silica gel, gradient
elution: 5% to 20% ethyl acetate/hexanes) to give 20a (0.35 g,
1.53 mmol, 77%) as a yellow oil: IR (CH2Cl2) 2863, 1676, 1445,
1361, 1224 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 7.2
Hz, 2 H), 7.54 (t, J = 7.2 Hz, 1 H), 7.45 (t, J = 7.2 Hz, 2 H), 3.73
(t, J = 6.8 Hz, 1 H), 2.19-2.08 (m, 1 H), 1.97-1.79 (m, 2 H),
1.77-1.66 (m, 2 H), 1.57-1.28 (m, 9 H); 13C NMR (100 MHz,
CDCl3) δ 204.20, 138.90, 132.56, 128.49, 128.29, 55.53, 53.23,
39.66, 39.12, 34.15, 29.49, 24.29, 23.78, 22.22; MS (EI) m/e (%)
228.2 (Mþ, 39), 146.1 (52), 133.1 (84), 108.1 (69), 106.1 (31),
105.0 (100), 81.1 (29), 77.0 (84), 67.0 (22); HRMS (EI) m/e calcd
for C16H20O 228.1507, found 228.1514.
Naphthalen-1-yl(spiro[4.4]nonan-1-yl)methanone (20b). The
crude mixture obtained from gold(I)-catalyzed Claisen-type
rearrangement of 18b (0.55 g, 2.0 mmol) followed by hydro-
genation was purified by flash column chromatography (silica
gel, gradient elution: 5% to 20% ethyl acetate/hexanes) to give
20b (0.45 g, 1.6 mmol, 80%) as a yellow oil: IR (CH2Cl2) 2944,
2875, 1673, 1595, 1573, 1511 cm-1; 1H NMR (400 MHz, CDCl3)
δ 8.44 (d, J = 8.6 Hz, 1 H), 7.94 (d, J = 8.2 Hz, 1 H), 7.86 (d, J =
7.9 Hz, 1 H), 7.78 (d, J = 7.16 Hz, 1 H), 7.58-7.45 (m, 3 H), 3.72
(dd, J = 7.5, 6.4 Hz, 1 H), 2.27-2.15 (m, 1 H), 2.05-1.96 (m, 1
H), 1.95-1.87 (m, 1 H), 1.85-1.77 (m, 1 H), 1.77-1.66 (m, 1 H),
1.59-1.39 (m, 9 H); 13C NMR (100 MHz, CDCl3) δ 208.25,
138.65, 134.02, 131.93, 130.04, 128.38, 127.54, 127.05, 126.29,
125.88, 124.26, 57.55, 55.93, 39.62, 39.15, 33.95, 29.19, 24.43,
23.68, 23.01; MS (EI) m/e (%) 278.2 (Mþ, 54), 170.1 (41), 156.1
(23), 155.1 (100), 127.1 (67), 83.9 (21); HRMS (EI) m/e calcd for
C20H22O 278.1662, found 278.1670.
Biphenyl-4-yl(spiro[4.4]nonan-1-yl)methanone (20c). The crude
mixture obtained from gold(I)-catalyzed Claisen-type rearrange-
ment of 18c (0.61 g, 2.0 mmol) followed by hydrogenation was
Naphthalen-1-yl(2-tosyl-2-azaspiro[4.5]decan-4-yl)methanone
(23b). The crude mixture obtained from gold(I)-catalyzed Clai-
sen-type rearrangement of 21b (0.22 g, 0.5 mmol) followed by

166 Organometallics, Vol. 29, No. 1, 2010
Yeh et al.
hydrogenation was purified by flash column chromatography
(silica gel, gradient elution: 10% to 50% ethyl acetate/hexanes)
to give 23b (0.14 g, 0.3 mmol, 62%) as a white solid: mp 165-167
°C; IR (CH2Cl2) 2913, 1673, 1597, 1340, 1162 cm-1; 1H NMR
(400 MHz, CDCl3) δ 8.33 (m, 1 H), 7.99 (d, J = 8.2 Hz, 1 H),
7.83 (m, 1 H), 7.81 (d, J = 8.2 Hz, 2 H), 7.73 (d, J = 7.0 Hz, 1 H),
7.58-7.46 (m, 3 H), 7.38 (d, J = 8.1 Hz, 2 H), 3.83 (t, J = 7.3 Hz,
1 H), 3.71 (d, J = 7.4 Hz, 2 H), 3.42 (d, J = 9.9 Hz, 1 H), 3.34 (d,
J = 9.9 Hz, 1 H), 2.47 (s, 3 H), 1.47-1.40 (m, 3 H), 1.33-1.02
(m, 7 H); 13C NMR (100 MHz, CDCl3) δ 202.89, 143.42, 136.93,
134.08, 133.06, 129.82, 129.66, 128.62, 128.06, 127.80, 127.62,
126.63, 125.42, 124.20, 56.96, 55.91, 48.94, 47.28, 36.49, 30.52,
25.44, 23.40, 22.95, 21.57; MS (EI) m/e (%) 447.3 (Mþ, 0.4),
293.2 (20), 292.2 (100), 265.2 (16), 263.2 (19), 183.1 (12), 165.1
(11), 156.1 (13), 155.1 (99), 128.1 (11), 127.1 (63). 110.1 (26), 91.1
(34), 67.1 (11); HRMS (EI) m/e calcd for C27H29NO3S 447.1859,
found 447.1860.
Phenanthren-9-yl(2-tosyl-2-azaspiro[4.5]decan-4-yl)metha-
none (23c). The crude mixture obtained from gold(I)-catalyzed
Claisen-type rearrangement of 21c (0.25 g, 0.5 mmol) followed
by hydrogenation was purified by flash column chromatogra-
phy (silica gel, gradient elution: 10% to 50% ethyl acetate/
hexanes) to give 23c (0.18 g, 0.36 mmol, 76%) as a white solid:
mp 187-189 °C; IR (CH2Cl2) 2931, 1731, 1668, 1598, 1338, 1161
cm-1; 1H NMR (400 MHz, CDCl3) δ 8.67 (dd, J = 19.0, 8.3 Hz,
2 H), 8.33 (d, J = 7.8 Hz, 1 H), 8.00 (s, 1 H), 7.93 (d, J = 7.8 Hz,
1 H), 7.83 (d, J = 8.0 Hz, 2 H), 7.74 (t, J = 7.8 Hz, 1 H),
7.69-7.58 (m, 3 H), 7.37 (d, J = 8.0 Hz, 2 H), 3.94 (t, J = 7.4 Hz,
1 H), 3.76 (t, J = 7.4 Hz, 2 H), 3.44 (d, J = 9.9 Hz, 1 H), 3.36 (d,
J = 10.0 Hz, 1 H), 2.46 (s, 3 H), 1.49-1.06 (m, 9 H), 0.83 (m, 1
H); 13C NMR (100 MHz, CDCl3) δ 202.69, 143.40, 135.98,
134.01, 131.85, 130.88, 129.98, 129.84, 129.62, 129.11, 127.82,
127.55, 127.48, 127.26, 127.21, 126.24, 122.96, 122.64, 56.92,
55.84, 48.85, 47.32, 36.44, 30.50, 25.36, 23.34, 22.90, 21.51; MS
(EI) m/e (%) 497.3 (Mþ, 0.6), 343.3 (20), 342.3 (75), 313.2 (21),
265.2 (13), 233.2 (12), 232.1 (16). 215.1 (13), 206.1 (20), 205.1
(100), 191.1 (10). 178.1 (20), 177.1 (62), 176.1 (21), 110.1 (20),
91.1 (26), 67.1 (10); HRMS (EI) m/e calcd for C31H31NO3S
497.2030, found 497.2024.
MS (EI) m/e (%) 412.3 (Mþ, 0.1), 257.2 (17), 256.2 (100),
147.1 (14), 119.1 (96), 110.1 (23). 91.1 (53), 65.1 (11); HRMS
(FABþ) m/e calcd for C24H30NO3S 412.1952, found 412.1958.
Crystals suitable for X-ray diffraction analysis were grown from
CH2Cl2 and hexanes.
(4-Methoxyphenyl)(2-tosyl-2-azaspiro[4.5]decan-4-yl)metha-
none (23e). The crude mixture obtained from gold(I)-catalyzed
Claisen-type rearrangement of 21e (0.21 g, 0.5 mmol) followed
by hydrogenation was purified by flash column chromatogra-
phy (silica gel, gradient elution: 10% to 50% ethyl acetate/
hexanes) to give 23e (0.18 g, 0.42 mmol, 85%) as a white solid:
mp 108-110 °C; IR (CH2Cl2) 1734, 1667, 1599, 1343, 1164
cm-1; 1H NMR (500 MHz, CDCl3) δ 7.83 (d, J = 8.9 Hz, 2 H),
7.78 (d, J = 8.2 Hz, 2 H), 7.35 (d, J = 8.1 Hz, 2 H), 6.92 (d, J =
8.9 Hz, 2 H), 3.86 (s, 3 H), 3.76 (t, J = 7.3 Hz, 1 H), 3.60 (dd, J =
9.9, 9.8 Hz, 2 H), 3.39 (d, J = 9.85 Hz, 1 H), 3.26 (d, J = 9.85 Hz,
1 H), 2.45 (s, 3 H), 1.64-1.62 (m, 1 H), 1.55-1.53 (m, 2 H),
1.36-1.27 (m, 3 H), 1.1-0.87 (m, 4 H); 13C NMR (100 MHz,
CDCl3) δ 197.48, 163.74, 143.29, 133.92, 130.88, 130.68, 129.54,
127.47, 113.81, 55.43, 52.92, 49.24, 46.57, 36.47, 30.79, 25.39,
23.41, 22.93, 21.46; MS (EI) m/e (%) 426.3 (Mþ, 0.1), 273.2 (16),
272.2 (92), 163.1 (11), 136.1 (12), 135.1 (100), 110.1 (11). 91.1
(21); HRMS (EI) m/e calcd for C24H29NO4S 427.1816, found
427.1818.
Phenyl(2-oxaspiro[4.5]decan-4-yl)methanone (27). The crude
mixture obtained from gold(I)-catalyzed Claisen-type rearran-
gement of 24 (0.12 g, 0.5 mmol) followed by hydrogenation with
the Wilkinson catalyst20 was purified by flash column chroma-
tography (silica gel, gradient elution: 10% to 50% ethyl acetate/
hexanes) to give 27 (0.059 g, 0.24 mmol, 48%) as a yellow liquid:
mp 108-110 °C; IR (CH2Cl2) 1731, 1673, 1447, 1372, 1220
cm-1; 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 7.9 Hz, 2 H),
7.59 (m, 1 H), 7.51-7.4 (m, 2 H), 4.22 (dd, J = 8.4, 6.7 Hz, 1 H),
4.11 (dd, J = 8.2, 7.9 Hz, 1 H), 3.88-3.83 (m, 2 H), 3.76 (d, J =
8.5 Hz, 1 H), 1.79 (m, 1 H), 1.57-1.35 (m, 6 H), 1.17-1.06 (m, 3
H); 13C NMR (100 MHz, CDCl3) δ 200.67, 138.47, 133.15,
128.72, 128.38, 76.18, 70.46, 55.20, 48.63, 36.77, 31.20, 25.61,
23.87, 23.72; MS (EI) m/e (%) 244.2 (Mþ, 14), 151.1 (10), 149.1
(51), 148.1 (14), 147.1 (30), 134.1 (12), 133.1 (74), 112.1 (27),
106.1 (11), 105.1 (100), 95.1 (13). 81.1 (14), 79.1 (13), 77.1 (62),
67.1 (17), 55.1 (22); HRMS (EI) m/e calcd for C16H20O2
244.1470, found 244.1463.
p-Tolyl(2-tosyl-2-azaspiro[4.5]decan-4-yl)methanone (23d).
The crude mixture obtained from gold(I)-catalyzed Claisen-type
rearrangement of 21d (0.2 g, 0.5 mmol) followed by hydrogena-
tion was purified by flash column chromatography (silica gel,
gradient elution: 10% to 50% ethyl acetate/hexanes) to give 23d
(0.14 g, 0.33 mmol, 65%) as a white solid: mp 194-196 °C; IR
Acknowledgment. This work was supported by grants
from the National Science Council (NSC 98-2119-M-003-
004-MY3).
1
(CH2Cl2) 2933, 1735, 1671, 1605, 1342, 1161 cm-1; H NMR
(400 MHz, CDCl3) δ 7.78 (d, J = 8.2 Hz, 2 H), 7.74 (d, J = 8.2
Hz, 2 H), 7.35 (d, J = 8.0 Hz, 2 H), 7.25 (d, J = 8.3 Hz, 2 H), 3.78
(t, J = 7.3 Hz, 1 H), 3.64-3.54 (m, 2 H), 3.40 (d, J = 9.8 Hz, 1
H), 3.25 (d, J = 9.8 Hz, 1 H), 2.46 (s, 3 H), 2.41 (s, 3 H), 1.64 (m,
1 H), 1.55-1.53 (m, 2 H), 1.36-1.26 (m, 3 H), 1.11-0.89 (m, 4
H); 13C NMR (100 MHz, CDCl3) δ 198.81, 144.28, 143.29,
135.45, 133.96, 129.54, 129.34, 128.43, 127.48, 55.41, 53.14,
49.18, 46.62, 36.43, 30.81, 25.38, 23.38, 22.93, 21.51, 21.46;
Supporting Information Available: 1H NMR and 13C NMR
spectra of compounds 2f, 2h, 3a-e, 7, 20a-e, 23a-e, and 27 and
X-ray crystallographic information files for compounds 20c,
23a, and 23d. This material is available free of charge via the
Internet at http://pubs.acs.org.
(20) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.