C O M M U N I C A T I O N S
Scheme 2. Proposed Mechanism for the Rh-Catalyzed
Alkylation-Cycloaddition of 3-Haloalkyl-1,6-enynes
In summary, we have developed a rhodium-catalyzed tandem
cyclization of alkynes. The reaction allows for the rapid assembly
of various fused ring systems from terminal alkyne derivatives in
a single step under mild conditions through a novel mechanism
that merges transition metal alkynyl and alkenylidene chemistry.
The findings described in this paper suggest that the uniquely unified
catalytic cycle may be permuted in many ways for further
development of new methods of alkyne functionalization.
Acknowledgment. We thank the NSF (CHE 0518559) and the
NIH-NIGMS (GM 073065) for support of this research, Princeton
University for a Hugh Stott Taylor fellowship (J.M.J.), and FMC
Corporation for a graduate fellowship (Y.Y.).
carried out with substrates bearing bromide (1b) and tosylate (1c)
leaving groups, albeit with diminished yields (entries 11 and 12).
Reaction scope was probed with a range of substrates (Table 2).
Similar to the model study, hydrindene ring systems possessing
substituents of differential positions and stereochemistry (entries
1-3) as well as a spirotricyclic derivative (entry 4) were accessed
from the corresponding enynes. In addition to these carbocycles,
the Rh(I)-catalyzed tandem cyclization proved feasible for the
preparation of various aza- (entry 5) and oxacycles (entries 6-9),
including the tricyclic hydrofurodecaline 18. For the reaction of
19, the use of [Rh(C2H4)2Cl]2 was found to be effective inducing
the cyclization at 25 °C (entry 9). Interestingly, the simple enyne
cycloisomerization without alkylation of the iodide took place when
the reaction was performed in THF instead of DMF (entry 10).
This dichotomy of reaction pathways suggests the presence of a
subtle kinetic balance in the catalytic cycle (vide infra).
The mechanism of the present tandem cyclization is proposed
to involve a reversible formation of rhodium alkynyl complex B
(Scheme 2). Subsequent to an irreversible alkylation with the
pendent alkyl halide, the resultant â,â-substituted alkenylidene C
undergoes a [2 + 2] cycloaddition to accomplish an additional ring
closure via D and E.10 When the alkylation step is slow or infeasible,
intermediate A, existing in equilibrium with B,11 may directly enter
on the cycloisomerization course to give rise to a monocyclization
product such as 21.
On the basis of the intermediacy of an alkenylidene complex of
type C, we hypothesized that the alkylative approach might be
extended to construct other ring structures by replacing the alkene
with other reactive components such as hydroxyl (22) and phenyl
(26) groups. Under the same reaction conditions employed for the
alkylation-cycloaddition, alcohol 22 was converted to enol ether
24 in 52% yield, presumably through â-alkylation followed by
addition of the hydroxyl group to the rhodium alkenylidene 23,
and the simple cycloisomerization product 25 in 15% yield (eq
1).7c,12 A tandem cyclization took place in the reaction of 26, which
afforded the tetracyclic naphthalene 28 in 83% yield (eq 2). In this
case, the incipient alkenylidene 27 is believed to follow a
6π-electrocyclization process,13 leading to aromatization.14
Supporting Information Available: Experimental details and NMR
spectra. This material is available free of charge via the Internet at
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