Gold-catalyzed formation of oxonium ions from enynes and their intra- and intermolecular trapping with allylsilanes

Article abstract of DOI:10.1021/ol203206k

Gold-catalyzed ring closure of 1,5-enyne containing a silyl ether at the allylic position induces a skeletal rearrangement to form an oxonium intermediate, which then undergoes a smooth allylation in both an intra- and intermolecular manner. In the intram

Full text of DOI:10.1021/ol203206k

ORGANIC
LETTERS
2012
Vol. 14, No. 1
410–413
Gold-Catalyzed Formation of Oxonium
Ions from Enynes and Their Intra- and
Intermolecular Trapping with Allylsilanes
Jingwei Li, Xiaoguang Liu, and Daesung Lee*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607, United States
dsunglee@uic.edu
Received December 1, 2011
ABSTRACT
Gold-catalyzed ring closure of 1,5-enyne containing a silyl ether at the allylic position induces a skeletal rearrangement to form an oxonium
intermediate, which then undergoes a smooth allylation in both an intra- and intermolecular manner. In the intramolecular allyl transfer, the
additive alcohol becomes positioned on the silicon of the silyl ether by forming a new SiꢀOR bond, whereas, in the intermolecular allylation, the
alcohol is incorporated in the homoallylic carbon by forming a CꢀOR bond.
Gold complexes are powerful carbophilic Lewis acids
that activate alkynes to generate cationic or carbenoid
intermediates depending on the functional groups within
the molecules containing the alkyne. These reactive inter-
mediates are known to undergo an array of transforma-
tions to engender diverse carbon frameworks.1
It has been shown that gold-catalyzed activation of
1-hexen-5-yn-3-ol or its silyl ether affords a cyclopentene
carboxaldehyde (Scheme 1).2 This reaction is believed to
proceed via an intermediate I arising from a nucleophilic
attack of the alkene to the activited alkynyl functionality
in a 6-endo-dig carbocyclization mode, which then under-
goes an irriversible pinacol-type rearrangement to another
intermediate II followed by loss of a proton or a silyl
group, yielding III. We envisaged that a carbocationic
intermediate I could be intercepted by an allylsilane,
before it undergoes a skeletal rearrangement to II, to gen-
erate a [5.4.0]bicyclic intermediate IV, which then would
undergo CꢀSi bond cleavage to deliver a cyclohexene
derivative V.3 On the other hand, if the formation of re-
arranged oxonium intermediate II still takes precedence
over the direct trapping of I by the allyl group,4 an
alternative carbocationic intermediate VI would arise.
Finally, the CꢀSi bond cleavage next to the carbocationic
center would lead to a cyclopentene derivative VII. Here-
in we describe an efficient and general allylation reaction
to form cyclopentene derivatives VII exclusively over
cyclohexene structures V in both an intra- and intermo-
lecular manner.
(1) For selected reviews on gold catalysis, see: (a) Hashmi, A. S. K.
Chem. Rev. 2007, 107, 3180. (b) Gorin, D. J.; Toste, F. D. Nature 2007,
446, 395. (c) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239.
ꢀ
ꢀ~
(d) Jimenez-Nunez, E.; Echavarren, A. M. Chem. Rev. 2008, 108, 3326.
(e) Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem. Rev. 2008, 108, 3351.
€
(f) Furstner, A. Chem. Soc. Rev. 2009, 38, 3208. (g) Corma, A.; Leyva-
Perez, A.; Sabater, M. J. Chem. Rev. 2011, 111, 1657.
(2) (a) Kirsch, S. F.; Binder, J. T.; Crone, B.; Duschek, A.; Haug,
(3) (a) Lim, C.; Kang, J.-E.; Lee, J.-E.; Shin, S. Org. Lett. 2007, 9,
3539. (b) Lim, C.; Rao, M. S.; Shin, S. Synlett 2010, 368. (c) Lee, Y.; Lim,
C.; Kim, S.; Shin, S. Bull. Korean Chem. Soc. 2010, 31, 670.
(4) Examples of oxonium species trapped by allylsilanes: (a) Nishiyama,
Y.; Shimoura, K.; Sonoda, N. Tetrahedron Lett. 2008, 49, 6533. (b) Jung,
M. E.; Maderna, A. J. Org. Chem. 2004, 69, 7755.
ꢀ
ꢀ
T. T.; Liebert, C.; Menz, H. Angew. Chem., Int. Ed. 2007, 46, 2310.
(b) Menz, H.; Binder, J. T.; Crone, B.; Duschek, A.; Haug, T. T.; Kirsch,
ꢀ
S. F.; Klahn, P.; Liebert, C. Tetrahedron 2009, 65, 1880.
r
10.1021/ol203206k
Published on Web 12/21/2011
2011 American Chemical Society

Table 1. Au(I)-Catalyzed Tandem Reaction with Intramolecu-
lar Allylationa
Scheme 1. Intramolecular Trapping of Oxonium Intermediates
in Au(I)-Catalyzed Tandem Reaction Sequence
To examine the behavior of the carbocationic inter-
mediates toward trapping with an allylsilane moiety,
2-methylhex-1-en-5-yn-3-yloxy allyldimethylsilyl ether
2a was prepared via propargylation of methacrolein
(propargyl bromide, Zn, aq NH4ClꢀDMF)5 followed
by silylation. With cationic gold complex 1 (1 mol %),6 re-
action of 2a in the presence of tert-butanol (1.1 equiv) in
dichloromethane provided cyclopentene derivative 3a in
86% yield (entry 1 in Table 1). The corresponding cyclo-
hexene derivative was not observed, but a nonnegligible
amount of cyclopentene caboxaldehyde (III) was isolated.
However, it was found that the combined use of allyldi-
phenylsilyl ether7 and phenol as opposed to allyldimethyl-
silyl ether and tert-butanol could minimize the formation
of the cyclopentene carboxaldehyde byproduct.8 Under
the optimized conditions, various enyne substrates 2bꢀf
afforded homoallylic silxoane 3bꢀf in good yields. Com-
pound 3cꢀe derived from internal alkynes 2cꢀe provided
mixtures of diastereomers (entries 3ꢀ5), but products
3b and 3f derived from terminal alkyne are single diastereo-
mers because the quaternary carbon center is not stereo-
genic (entries 2). Similarly, relatively complex substrate 4
containing an aromatic moiety with oxygen substituents
afforded 5 in good yield (76%) without complication.9
Although the gold-catalyzed tandem ring closure of
enynes followed by intramolecular allylation was an effi-
cient process, the preparation of a substrate containing
a 1 (1 mol %), PhOH (1.1 equiv). b Isolated yield. c tert-Butanol
(1.1 equiv) was used instead of phenol.
the allyldiphenylsilyl moiety was found to be tedious. To
remove this inconvenience, we envisaged an intermolecu-
lar trapping of the oxonium intermediate with externally
added allyltrimethylsilane. Initially, triethylsilyl protected
2-methyl-1-hexen-5-yn-3-ol 6a was employed. But under
the typical reaction conditions with allyltrimethylsilane,
6a provided only 1-methylcyclopent-3-ene carbaldehyde
without any allylation (Scheme 2). To diminish the OꢀSi
bond cleavage by the attack of the additive alcohol
on the silicon center, a more sterically hindered silyl
(10) For related seminal publications on the Sakurai reaction, see:
(a) Hosomi, A.; Endo, M.; Sakurai, H. Chem. Lett. 1976, 5, 941–942.
(b) Sakurai, H. Pure Appl. Chem. 1982, 54, 1. For in situ generated
oxoniums from alkoxysilanes and carbonyl compounds and their trap-
ping by allylic silanes, see: (c) Mukaiyama, T.; Ohshima, M.; Miyoshi,
ꢀ
N. Chem. Lett. 1987, 16, 1121. (d) Marko, I. E.; Mekhalfia, A.; Bayston,
D. J.; Adams, H. J. Org. Chem. 1992, 57, 2211. (e) Panek, J. S.; Yang, M.;
Xu, F. J. Org. Chem. 1992, 57, 5790. (f) Lipshutz, B. H.; Burgess-Henry,
J.; Roth, G. P. Tetrahedron Lett. 1993, 34, 995. (g) Tietze, L. F.; Wulff,
C.; Wegner, C.; Schuffenhauer, A.; Schiemann, K. J. Am. Chem. Soc.
1998, 120, 4276. (h) Cossrow, J.; Rychnovsky, S. D. Org. Lett. 2002, 4,
147. (i) Watahiki, T.; Akabane, Y.; Mori, S.; Oriyama, T. Org. Lett.
2003, 5, 3045. (j) Lowe, J. T.; Panek, J. S. Org. Lett. 2005, 7, 3231.
(k) Anzalone, P. W.; Baru, A. R.; Danielson, E. M.; Hayes, P. D.;
Nguyen, M. P.; Panico, A. F.; Smith, R. C.; Mohan, R. S. J. Org. Chem.
(5) Barbier, P. Compt. Rend. 1899, 128, 110.
ꢀ
ꢀ
ꢀ
(6) Nieto-Oberhuber, C.; Perez-Galan, P.; Herrero-Gomez, E.;
ꢁ
ꢀ
2005, 70, 2091. (l) Pospısil, J.; Kumamoto, T.; Marko, I. E. Angew.
Chem., Int. Ed. 2006, 45, 3357. (m) Spafford, M. J.; Anderson, E. D.;
Lacey, J. R.; Palma, A. C.; Mohan, R. S. Tetrahedron Lett. 2007, 48,
ꢀ
ꢀ
ꢀ
Lauterbach, T.; Rodrıguez, C.; Lopez, S.; Bour, C.; Rosellon, A.;Cardenas,
D. J.; Echavarren, A. M. J. Am. Chem. Soc. 2008, 130, 269.
(7) (a) Ito, H.; Saito, T.; Miyahara, T.; Zhong, C.; Sawamurat, M.
Organometallics 2009, 28, 4829. (b) Ito, H.; Takagi, K.; Miyahara, T.;
Sawamura, M. Org. Lett. 2005, 7, 3001.
ꢀ ^
8665. (n) Kampen, D.; Ladepeche, A.; Claßen, G.; List, B. Adv. Synth.
Catal. 2008, 350, 962. (o) Kataki, D.; Phukan, P. Tetrahedron Lett. 2009,
50, 1958. For allenylsilane trappings, see: (p) Brawn, R. A.; Panek, J. S.
Org. Lett. 2007, 9, 2689. For in situ generated oxoniums from alcohol
and carbonyl compounds and their trapping by allylic silanes, see:
(q) Sakurai, H.; Sasaki, K.; Hayashi, J.; Hosomi, A. J. Org. Chem.
1984, 49, 2808. (r) Imwinkelried, R.; Seebach, D. Angew. Chem., Int. Ed.
(8) For the effect of additive alcohols, see: (a) Horino, Y.; Luzung,
M. R.; Toste, F. D. J. Am. Chem. Soc. 2006, 128, 11364. (b) Park, S.; Lee,
D. J. Am. Chem. Soc. 2006, 128, 10664.
(9) Compared to tert-butyldimethylsilyl phenyl ether 4, a related
methoxymethyl phenyl ether provided an acetal product due to a
neighboring oxygen atom participation with intermediate II.
€
Engl. 1985, 24, 765. (s) Tietze, L. F.; Dolle, A.; Schiemann, K. Angew.
Chem., Int. Ed. Engl. 1992, 31, 1372.
Org. Lett., Vol. 14, No. 1, 2012
411

protecting group was empolyed. When tert-butyldi-
methyl silyl protected enyne substrate 6b was treated
with gold complex 1 (1 mol %) in the presence of benzyl
alcohol (1.1 equiv) and allyltrimethylsilane (3 equiv), an
efficient allylation took place. However, the isolated
product was not the expected silyl ether 7b0 but the
additive alcohol-incorporated ether 7b. This suggests
that the initially formed oxonium intermediate II re-
acted with the added alcohol instead of allylsilane to
generate a new oxonium species IX via an acetal inter-
mediate VIII, which then reacted with allylsilane to
provide the observed allylated product (Scheme 2).10
Table 2. Au(I)-Catalyzed Tandem Reaction Alkoxy Allylation
with Different Alcoholsa
Scheme 2. Au(I)-Catalyzed Formation of an Oxonium Inter-
mediate and Its Intermolecular Allylationa
a 1 (1 mol %), allyltrimethylsilane (3.0 equiv), ROH (1.1 equiv).
b Isolated yields.
a 1 (1 mol %), allyltrimethylsilane (3.0 equiv), BnOH (1.1 equiv).
With the involvement of carbocationic intermediates
along the reaction sequence, we predicted that the initially
formed oxonium species could be intercepted by suitably
tethered heteroatom-based nucleophiles such as alcohols,
ethers, and amides to form a new oxonium or iminium
species after elimination of silanol, which then undergoes
the expected final allylation, providing the corresponding
spirobicyclic products.11 As expected, a tethered alcohol-
containing substrate 8 provided an allylated spirobicyclic
ether 9 in good yield (Scheme 3). However, substrate 10
containing a three-carbon tether between the incipient
carbocation and a hydroxyl group provided spirobicyclic
ether 11 without allylation. This implies that the intramo-
lecular trapping of the initially formed carbocation I by a
tethered nucleophile to form a five-membered ring should
be more favorable than its skeletal rearrangement to an
oxonium species II. An altered pairing of reacting counter-
parts, such that the trapping of the cationic intermediate
with an alcohol additive would be intermolecular but the
subsequent allylation would be intramolecular, would gen-
erate a product of different connectivity. Indeed, when the
mixture of 6b and 5-trimethylsilyl-pent-3-en-1-ol was trea-
ted with catalyst 1, cycylopentene derivative 12 containing
To test the generality of the Au(I)-catalyzed tandem
cyclization of an enyneꢀalkoxy exchangeꢀintermolecular
allylation sequence, we examined the reaction of enyne sub-
strate 6b in the presence of a variety of additive alcohols
(Table 2). It was found that most alcohols could participate
in this reaction in roughly the same efficiency except tert-
butanol (entry 3). Water and acetic acid were found to be
unsuitable as an additive for this reaction. Not surprisingly,
both 3-buten-2-ol and (S)-5-hexen-2-ol gave diastereomeric
mixtures (entries 8 and 9), and cholesterol provided dia-
stereomers in a 15:1 ratio (entry 10). In the presence of
isopropanol, substrate 6c containing a brominated alkyne
efficiently generatedthe corresponding diastereomeric mix-
ture of isopropyl ethers in a 1:1 ratio (entry 11).
(11) For gold-catalyzed formation of oxonium ions and their intra-
molecular trapping by a hydroxyl group, see: (a) Sherry, B. D.; Maus, L.;
Laforteza, B. N.; Toste, F. D. J. Am. Chem. Soc. 2006, 128, 8132. For
gold-catalyzed formation of carbocations and their intramolecular
trapping by nucleophiles, see: (b) Zhang, L.; Kozmin, S. A. J. Am.
Chem. Soc. 2005, 127, 6962. (c) Toullec, P. Y.; Blarre, T.; Michelet, V.
Org. Lett. 2009, 11, 2888. (d) Tarselli, M. A.; Zuccarello, J. L.; Lee, S. J.;
ꢀ
Gagne, M. R. Org. Lett. 2009, 11, 3490. (e) Sethofer, S. G.; Mayer, T.;
Toste, F. D. J. Am. Chem. Soc. 2010, 132, 8276.
412
Org. Lett., Vol. 14, No. 1, 2012

an alternative substituent pattern was obtained in good
yield (87%).
Scheme 4. Reactivity Difference between Intra- And Intermo-
lecular Allyl Transfer
Scheme 3. Intramolecular Trapping of an Oxonium Intermedi-
ate with a Tethered Hydroxy Group
These reactions provide a rapid access to cyclopentene
derivatives containing a quaternary carbon center and a
homoallyl ether moiety. Further exploration of this meth-
odology in the context of natural product synthesis will be
reported in due course.
A subtle influence of substituents on the reactivity of
enynes toward gold-catalyzed ring closure was observed
(Scheme 4). Enyne substrate 13 with a phenyl substituent
on the internal position of the alkene moiety was inert
under the intermolecular allyl transfer conditions and re-
covered intact. On the other hand, the reaction of closely
related enyne 15 containing an allyl-transferring silyl ether
moiety delivered allylated product 16 in 85% yield.
Unambiguous structural determination of 16 was reali-
zed by X-ray crystallographic analysis of its p-nitrobenzo-
ate derivative 17.
Acknowledgment. L.J. is grateful for the Moriarty Fel-
lowship at UIC. Wethank Mr. Rodger F. HenryofAbbott
Laboratories for the structure elucidation of 17 by X-ray
crystallographic analysis. Mr. Furong Sun of the Univer-
sity of Illinois at UrbanaꢀChampaign is greatly acknowl-
edged for high resolution mass spectrometry data.
In conclusion, we demonstrated two efficient gold(I)-
catalyzed tandem reactions of 3-silyloxy-1,5-enynes, which
involves an initial carbocyclization of an enyne moiety,
pinacol-type skeletal reorganization, and intra- or inter-
molecular allyl transfer induced by an additive alcohol.
Supporting Information Available. General procedures
and characterization data of new compounds. This ma-
terial is available free of charge via the Internet at http://
pubs.acs.org.
Org. Lett., Vol. 14, No. 1, 2012
413