C O M M U N I C A T I O N S
Table 3. Formation of 2-cycloalken-1-ones
of methanol onto the same activated allene. Subsequent basic
treatment of 13 afforded 2-cyclohexen-1-one 14 in 99% yield.
Furthermore, treatment of enantioenriched propargylic acetate 4j
furnished 15 in 72% yield as a 1:1.5 mixture of epimers under the
same experimental conditions (eq 4). A one-pot cycloisomerization
deprotection sequence was also attempted and led to the formation
of the corresponding 2-cyclohexen-1-one 16 with a complete
retention of the chiral information. Note that the cyclohexenones
obtained by that route (e.g., 16) are regioisomeric with those
generated by opening the cyclopropane as in Table 3.
a Isolated yields.
Scheme 1. Proposed Mechanism
In summary, we have developed an efficient gold(I) catalyzed
cycloisomerization of 5-en-2-yn-1-yl acetates that provides an
efficient access to acetoxy bicyclo[3.1.0]hexenes which can be
further transformed into 2-cycloalken-1-ones. Cyclohexenones are
key building blocks in numerous total syntheses. Further studies
related to this new gold(I)-catalyzed process as well as its
application to the synthesis of natural products are underway.
Acknowledgment. The authors wish to thank Prof. S. Z. Zard
for helpful discussions.
The aromatic ring could be substituted, but with a decrease in
efficiency when the 2,3-dichlorophenyl derivative 4f was used as
the substrate (entries 4 and 5). The rearrangement proceeded as
well when the propargylic position of the enyne was substituted
with an alkyl chain (entries 6-9). Various substituted bicyclo[3.1.0]-
hexenes 6g-j possessing two adjacent quaternary centers at the
ring junction were thus obtained in yields ranging from 72% to
99%. Finally, the cycloisomerization of enantioenriched substrate
4j was attempted. We were pleased to observe the rapid formation
of bicyclo[3.1.0]hexene 6j which was isolated in 92% yield.
Interestingly, the stereochemical information of the substrate was
nearly completely transferred to the final product.10
The functionalized acetoxy bicyclo[3.1.0]hexene products lend
themselves to a number of useful transformations. For example they
can be efficiently converted into 2-cycloalken-1-ones by simple
treatment with K2CO3 in methanol thus highlighting the general
utility of this transformation (Table 3). The cleavage of the
cyclopropane ring seems to be directed by the substitution pattern
of the cylopropyl ring. Bicyclo[3.1.0]hexenes 6a, 6c, and 6d
afforded the corresponding 2-cyclohexen-1-ones 7a, 7c, and 7d,
while bicyclo[3.1.0]hexene 6b bearing a methyl group at the ring
junction gave 2-cyclopenten-1-one 7b.
To account for these observations, a mechanistic manifold for
the formation of the bicyclo[3.1.0]hexenes is proposed in Scheme
1. Gold(I) activation of the triple bond in alkyne 8 promotes the
formation of allene 9 through a [3,3]-sigmatropic rearrangement.
A further gold(I) activation of the allene induces the nucleophilic
attack of the pendant alkene resulting in the formation of the cationic
vinyl-gold species 10.11 Subsequent formation of the cyclopropyl
ring assisted by electron donation from gold(I) affords gold(I)
carbene 11. A final 1,2-hydride shift regenerates the gold(I) catalyst
and produces bicyclo[3.1.0]hexene 12.
Supporting Information Available: Experimental procedures and
spectral data for new compounds. This material is available free of
References
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(6) Interestingly, aromatic groups do not interfere in the reaction (ref 3c).
(7) Allene 5a was obtained in 89% yield by reaction of 4a with 10% of
AgNTf2 in CH2Cl2 at room temperature for 30 min.
(8) In CH2Cl2 for 6 h; 5% AuBr3: 0% 4a, 0% 5a, 0% 6a. 5% PtCl2: 80%
4a, 17% 5a, 0% 6a. 10% AgNTf2: 0% 4a, 89% 5a, 0% 6a.
(9) The stereochemistry of the major endo isomer was assigned on the basis
of NMR experiments.
(10) The enantiomeric excess was determined by chiral HPLC analysis.
However, the configuration of the major enantiomer was not determined.
(11) A equilibrium between two conformers may explain the stereochemistry
observed for 6d:
The proposed mechanism suggests that intermediate 10 could
be trapped by a nucleophile. In agreement with this hypothesis,
cyclohexene 13 was formed in 81% yield as a 1:2 mixture of
diastereoisomers when the rearrangement of 4b was performed in
MeOH (eq 3). Interestingly, the nucleophilic addition of the alkene
onto the gold(I) activated allene seems to be faster than the addition
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