Gold(I)-catalyzed formation of 4-alkylidene-1,3-dioxolan-2-ones from propargylic tert-butyl carbonates

Article abstract of DOI:10.1021/ol053100o

A study concerning the gold(I)-catalyzed rearrangement of propargylic tert-butyl carbonates into 4-alkylidene-1,3-dioxolan-2-ones is described. The mild reaction conditions employed allow the efficient synthesis of a variety of cyclic carbonates that would be less conveniently obtained using reported methods. Variability in the structure of the final product has been observed and is significantly dependent on the nature of the substituent attached to the alkyne moiety.

Full text of DOI:10.1021/ol053100o

ORGANIC
LETTERS
2006
Vol. 8, No. 3
515-518
Gold(I)-Catalyzed Formation of
4-Alkylidene-1,3-dioxolan-2-ones from
Propargylic tert-Butyl Carbonates
Andrea Buzas and Fabien Gagosz*
Laboratoire de Synthe`se Organique, UMR 7652 CNRS/Ecole Polytechnique,
Ecole Polytechnique, 91128 Palaiseau, France
gagosz@dcso.polytechnique.fr
Received December 21, 2005
ABSTRACT
A study concerning the gold(I)-catalyzed rearrangement of propargylic tert-butyl carbonates into 4-alkylidene-1,3-dioxolan-2-ones is described.
The mild reaction conditions employed allow the efficient synthesis of a variety of cyclic carbonates that would be less conveniently obtained
using reported methods. Variability in the structure of the final product has been observed and is significantly dependent on the nature of the
substituent attached to the alkyne moiety.
Derivatives of 4-methylene-1,3-dioxolan-2-ones 1 are at-
tractive building blocks for organic synthesis because they
represent a useful source of masked hydroxyketones, which
can be further transformed into a range of more elaborated
structures (Scheme 1).1 However, their use in synthesis
Following the recent developments in the field of gold-
catalyzed nucleophilic additions onto alkynes,3 we surmised
that a suitably selected propargylic carbonate 2 might be a
(1) (a) Toullec, C.; Martin, A. C.; Gio-Batta, M.; Bruneau, C. Dixneuf,
P. H. Tetrahedron Lett. 2000, 41, 5527-5531. (b) Le Gendre, P.; Thominot,
P.; Bruneau, C.; Dixneuf, P. H. J. Org. Chem. 1998, 63, 1806-1809; 1996,
61, 8453-8455. (c) Inoue, Y.; Matsushita, K. Yen, I-F.; Imaizumi, S.
Chem. Lett. 1991, 1377-1378. (d) Ohe, K.; Matsuda, H.; Ishihara, T.;
Ogoshi, S.; Chatani, N.; Murai, S. J. Org. Chem. 1993, 58, 1173-1177.
(e) Ohe, K.; Matsuda, H.; Morimoto, T.; Ogoshi, S.; Chatani, N.; Murai, S.
J. Am. Chem. Soc. 1994, 116, 4125-4126.
Scheme 1. Possible Transformations of
4-Methylene-1,3-dioxolan-2-ones 1
(2) 4-Methylene-1,3-dioxolan-2-ones are typically synthesized using
propargylic alcohols under CO2 pressure and in the presence of a catalyst.
The great majority of these methods are limited to the use of tertiary
propargylic alcohols. (a) Ru: Sazaki, Y. Tetrahedron Lett. 1986, 27, 1573-
1574. (b) Co: Inoue, Y.; Ishikawa, J.; Taniguchi, M.; Hashimoto, H. Bull.
Chem. Soc. Jpn. 1987, 60, 1204-1206. (c) Cu: Gu, Y.; Shi, F.; Deng, Y.
J. Org. Chem. 2004, 69, 391-394. Laas, H.; Nissen, A.; Nu¨rrenbach, A.
Synthesis 1981, 958-959. (d) PBu3: Joumier, J. M.; Bruneau, C.; Dixneuf,
P. H. Synlett 1992, 453-454. Joumier, J. M.; Fournier, J.; Bruneau, C.;
Dixneuf, P. H. J. Chem. Soc., Perkin. Trans. 1, 1991, 3271-3274. Fournier,
J.; Bruneau, C.; Dixneuf, P. H. Tetrahedron Lett. 1989, 30, 3981-3982.
(e) Pd: Jiang, Z.-X.; Qing, F.-L. J. Fluorine Chem. 2003, 123, 57-60.
Uemura, K., Kawaguchi, T.; Takayama, H. Nakamura, A. Inoue, Y. J. Mol.
Catal. A: Chem. 1999, 139, 1-9. Iritani, K.; Yanagihara, N.; Utimoto, K.
J. Org. Chem. 1986, 51, 5499-5501. (f) Inorganic base: see ref 2e.
remains largely unexplored due to a lack of efficient and
general methods to access them.2
10.1021/ol053100o CCC: $33.50
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valuable precursor for the gold-catalyzed synthesis of 1
(Scheme 2, eq 1). Compound 3a was first chosen as a model
Table 1. Au(I)-Catalyzed Transformations of Terminal
Alkynes 3b-j
Scheme 2. Synthetic Approach to
4-Methylene-1,3-dioxolan-2-ones from Propargylic Carbonates
substrate to validate this approach (Scheme 2, eq 2).4 We
were pleased to observe that the rearrangement of 3a,
5
catalyzed by 1% of (Ph3P)AuNTf2 in dichloromethane,
afforded the desired carbonate 4a in 83% yield.
The reaction proved to be quite general and various
substituted terminal alkynes reacted under the same condi-
tions to furnish the corresponding cyclic carbonates in yields
ranging from 40% to 98% (Table 1). The time required to
reach completion is generally less than 1 h with the exception
of tertiary tert-butyloxycarbonyl substrates 3f, 3j, and 3i,
which were less reactive. The reaction of androstene deriva-
tive 3h was exceptionally efficient and gave the correspond-
ing pure spirocyclic carbonate 4h in 90% yield after a simple
filtration of the crude reaction mixture. The moderate yield
obtained in the case of substrate 3i may be attributed to its
poor stability in acidic medium. Interestingly, the reaction
of diyne 3j selectively furnished 4j without formation of the
six-membered cyclic carbonate resulting from a 6-exo
cyclization. We next focused our attention on the reactivity
of internal alkynes. As attested by the results compiled in
Table 2, these were also reactive. Substrates 3k-n gave
exclusively the E-isomers of the corresponding cyclic
carbonates 4k-n in good yields. The valuable vinylbromide
4k was formed in 87% yield in 1 h, whereas masked
ketoester 4l was obtained in the same yield after 2 h of
reaction time.
a Isolated yields.
Interestingly, unsymmetrical substrate 3n selectively fur-
nished 4n in 77% yield as the result of a faster cyclization
of the more substituted tert-butyloxycarbonyl group.6 Curi-
ously, alkynes 3p-s were inert when (Ph3P)AuNTf2 was
used as the catalyst. Pleasingly, the more electrophilic catalyst
[(pCF3Ph)3P]AuNTf2 allowed the conversion of the substrates
into mainly the exo-methylene compounds 4p-s in moderate
to good yield.7,8
Surprisingly, in the case of substrates 3o-s, the cyclic
carbonate moiety was shifted by one carbon in comparison
with the structures of the products previously obtained. Thus,
N-alkynyl oxazolidinone 3o rapidly furnished 4o in 94%
yield. Alkyl substituted alkynes 3p-s reacted more slowly
to give the corresponding cyclic carbonates in approximately
60% yield. Alkynes 3r and 3s possessing an asymmetric
center at the propagylic position were slowly transformed
into a mixture of two isomers with a diastereoisomeric ratio
reaching 1:3.9 in the case of 3s.9
(3) Selection of recent developments: (a)Antoniotti, S.; Genin, E.;
Michelet, V.; Geneˆt, J.-P. J. Am. Chem. Soc. 2005, 127, 9976-9977. (b)
Casado, R.; Contel, M.; Laguna, M.; Romero, P.; Sanz, S. J. Am. Chem.
Soc. 2003, 125, 11925-11935. (c) Asao, N.; Sato, K.; Yamamoto, Y. J.
Org. Chem. 2005, 70, 3682-3685. (d) Hashmi, A. S. K.; Weyrauch, J. P.;
Frey, W.; Bats, J. W. Org. Lett. 2004, 6, 4391-4394. (e) Gorin, D. J.;
Davis, N. R.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260-11261. (f)
Nieto-Oberhuber, C.; Lopez, S.; Echavarren, A. M. J. Am. Chem. Soc. 2005,
127, 6178-6179. (g) Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2005,
127, 6962-6963. (h) Shi, X.; Gorin, D. J.; Toste, F. D. J. Am. Chem. Soc.
2005, 127, 5802-5803. (i) Mamane, V.; Gress, T.; Krause, H.; Fu¨rstner,
A. J. Am. Chem. Soc. 2004, 126, 8654-8655. (j) Nieto-Oberhuber, C.;
Mun˜oz, M.; Bun˜uel, E.; Nevado, C.; Ca´rdenas, D. J.; Echavarren, A. M.
Angew. Chem., Int. Ed. 2004, 43, 2402-2406.
To account for these observations, a mechanistic manifold
for the formation of the cyclic carbonates is proposed in
Scheme 3.10 Gold(I) activation of the triple bond in pro-
pargylic tert-butyl carbonate 5 promotes the formation of
(6) The observed selectivity may be the result of a Thorpe-Ingold effect
favoring the cyclisation of the more substituted Boc group.
(7) Around 10% of cyclic carbonates formed following path A (see
Scheme 3) was also observed.
(8) [(pCF3Ph)3P]AuNTf2 was also effective for the described transforma-
tion of substrates 3a-o.
(9) Studies towards the identification of the major isomer and diastereo-
selectivity rational are underway.
(4) By analogy with the well-documented iodine-mediated cyclization
of allylic and homoallylic tert-butyl carbonate. See: Duan, J.; Smith, A.
B., III J. Org. Chem. 1993, 58, 3703-3711. Madness, M. L.; Lautens, M.
Synthesis 2004, 1399-1408. No example of iodine-mediated cyclization
of propargylic tert-butyl carbonate has been reported.
(5) Mezailles, N.; Ricard, L.; Gagosz, F. Org. Lett. 2005, 7, 4133-4136.
516
Org. Lett., Vol. 8, No. 3, 2006

H) and more especially in the presence of electron-rich
groups (R ) alkyl).13
Table 2. Au(I)-Catalyzed Transformations of Alkynes 3k-s
Scheme 3. Proposed Mechanism for the Formations of Cyclic
Carbonates
To further highlight the potential of this new process, we
attempted to trap the intermediate vinyl-gold species 7 by a
source of electrophilic iodine prior to protonation. Such a
transformation would be of high synthetic interest since it
would lead to vinyl iodides. To this end, alkyne 3e was
treated with 1% (Ph3P)AuNTf2 and a slight excess of NIS
in acetone (Scheme 4). We were pleased to observe the rapid
a Isolated yields. b With (Ph3P)AuNTf2. c With [(pCF3Ph)3P]AuNTf2.
1
d Ratio determined by H NMR.
the stabilized cationic species 6.11 The latter may follow two
distinct reaction pathways depending on the nature of the
alkyne substituent R. Fragmentation of the C-O bond of
the tert-butyloxy group in 6 can lead to the formation of the
neutral vinyl-gold species 7, which is subsequently proto-
nated to finally furnish cyclic carbonate 8 (path A).12 This
pathway seems to be favored in the case of terminal alkynes
(R ) H) or alkynes bearing electron-withdrawing groups
(R ) ester, halogen). The internal allylic C-O bond in
intermediate 6 can alternatively fragment to give the
stabilized allylic cation 9 (path B). Cyclization of the tert-
butyloxycarbonyl group, followed by fragmentation and
protonation finally affords cyclic carbonate 10. This pathway
appears to be favored in the case of internal alkynes (R *
Scheme 4. Au(I)-Catalyzed Formations of Vinyl Iodides 4u
and 4t
and exclusive formation of Z-vinyliodide 4u, which was
isolated in 95% yield.14,15 Interestingly, the corresponding
E-isomer 4t was obtained in 83% yield when iodoalkyne 3t
was treated with the same quantity of catalyst in dichloro-
methane.
(10) For related Pt(II)-catalyzed cyclisation-fragmentation processes,
see: Davies, P. W.; Fu¨rstner, A. J. Am. Chem. Soc. 2005, 127, 15024-
15025. Nakamura, I.; Mizushima, Y.; Yamamoto, Y. J. Am. Chem. Soc.
2005, 127, 15022-15023.
(11) A similar intermediate was recently proposed by Toste and
co-workers for the gold(I)-catalyzed conversion of 1-ethynyl-2-propenyl
acetates into cyclopentenones (see ref 3h).
(13) Curiously, internal alkynes 3m and 3n are reacting following path
A. The reason for such a selectivity is still unclear, and studies to rationalize
this result are underway.
(12) Reaction of 80% deuterated 3a is in agreement with this mechanism.
(14) Reaction in a less polar solvent such as dichloromethane furnished
a 1:1 mixture of 4e and 4u as the result of a less efficient trapping.
(15) Treatment of 3e with a 2-fold excess of NIS and without Au+
catalyst slowly furnished 4u: 5% conversion after 3 h, 82% isolated yield
after 48 h.
Org. Lett., Vol. 8, No. 3, 2006
517

In summary, we have shown that highly active phosphine
gold(I) complexes we described recently5 efficiently catalyze
the formation of various 4-alkylidene-1,3-dioxolan-2-ones
from readily available propargylic tert-butyl carbonates.
Further studies relating to the use of this gold(I)-catalyzed
cyclization-fragmentation process to the synthesis of other
valuable synthons are underway and will be reported in due
course.
Acknowledgment. The author wishes to thank Prof. S.
Z. Zard, Dr. B. Quiclet-Sire, and Dr. I. Hanna for helpful
discussions and Rhodia Chimie Fine for a donation of HNTf2.
Supporting Information Available: Experimental pro-
cedures and spectral data for new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL053100O
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