An efficient [4 + 2 + 1] entry to seven-membered rings

Article abstract of DOI:10.1021/ja046147y

A new nickel-catalyzed procedure for the [4 + 2 + 1] cycloaddition of trimethylsilyl diazomethane with alkynes tethered to dienes has been developed. A broad range of unsaturated substrates participate in the sequence, and stereoselectivities are generall

Full text of DOI:10.1021/ja046147y

Published on Web 08/20/2004
An Efficient [4 + 2 + 1] Entry to Seven-Membered Rings
Yike Ni and John Montgomery*
Department of Chemistry, Wayne State UniVersity, Detroit, Michigan 48202
Received June 29, 2004; E-mail: jwm@chem.wayne.edu
Table 1
Transition metal catalysis provides many elegant entries to
medium ring systems via cycloadditions that are either unavailable
or inefficient by noncatalyzed thermal counterparts. For example,
efficient metal-catalyzed or promoted [4 + 4], [5 + 2], [6 + 2],
[6 + 4], [4 + 2 + 2], [5 + 2 + 1], and [2 + 2 + 2 + 1] cyclo-
additions have been developed in recent years.1 Wender recently
reported the first examples of a new [4 + 2 + 1] cycloaddition
process involving alkynes, dienes, and carbon monoxide, although
yields were low since [4 + 2] and [2 + 2 + 1] pathways
predominated.2 The stoichiometric [4 + 2 + 1] cycloaddition of
molybdenum Fischer carbene complexes to dienes tethered with
alkynes is known, although there are considerable substrate
restrictions with both reaction partners.3 Related [4 + 3] catalytic
cycloadditions involving diazoacetates have been extensively
developed,4 and two examples of fully intramolecular catalytic
[4 + 2 + 1] diazoacetate-mediated cycloadditions have been
reported.5 To our knowledge, the only partially intermolecular,
catalytic [4 + 2 + 1] cycloadditions known are the studies from
Wender that afforded < 20% yield of seven-membered ring
products as minor components of the reaction mixture.2
To fill this void in the synthesis of seven-membered rings, we
have explored the development of catalytic [4 + 2 + 1] cycload-
ditions of diazoalkanes with dienes tethered to alkynes. Given our
longstanding interest in nickel chemistry6 and the paucity of useful
synthetic procedures that involve carbene insertions with nickel
catalysis,7-9 we examined the behavior of Ni(COD)2 in the desired
[4 + 2 + 1] transformation. Thus, exposure of a mixture of unsat-
urated precursor 1a and trimethylsilyldiazomethane (2 equiv) to
10 mol % Ni(COD)2 in THF at 60 °C led to the efficient production
of bicyclo-[3.5.0]-decane 2a in 76% yield as a 13:1 mixture of
diastereomers. Remarkable selectivity for production of the [4 + 2
+ 1] adduct over alternate [4 + 2], [4 + 1], [2 + 1], [2 + 2 + 1],
[2 + 2 + 2], [4 + 4], or [4 + 2 + 2] cycloaddition modes was
noted.1 Given the exquisite chemoselectivity of this transformation,
we have carried out a preliminary study of the scope of this new
reaction.
Our initial studies have focused exclusively on the use of TMS
diazomethane given its ease of handling and the synthetic utility
of the product allyl silanes (Table 1). In addition to a malonate-
derived substrate (entry 1), we examined the preparation of
heterocyclic structures. Nitrogen-containing substrate 1b generated
product 2b in 68% yield in greater than 95:5 dr (entry 2), and
oxygen-containing substrate 1c generated product 2c in 65% yield
as a 10:1 ratio of diastereomers (entry 3). Internal alkynes were
also effective participants, as evidenced by the generation of
products 2d, 2e, 2g, and 2h (entries 4, 5, 7, 8). Substitution on
either the diene terminus (entries 6 and 7) or an internal position
of the diene (entry 8) was acceptable. Substitution within the tether
chain was also tolerated with excellent resulting diastereoselectivity
(entry 8).
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10.1021/ja046147y CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1
preparatively useful, chemoselective entry to seven-membered rings
is provided. Although numerous mechanistic issues have yet to be
established, these studies suggest that nickel carbene intermediates
may be useful mediators of cascade metathesis entries to function-
alized medium rings. We are actively pursuing further developments
in this area.
Acknowledgment. We acknowledge receipt of NIH Grant GM-
57014 and a Johnson and Johnson Focused Giving Award in support
of this research. Prof. Jin Cha and Dr. Bashar Ksebati are thanked
for helpful discussions.
Supporting Information Available: Full experimental details and
copies of NMR spectral data. This material is available free of charge
via the Internet at http://pubs.acs.org.
References
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The mechanism of this novel cycloaddition process is unclear
at this stage. In analogy to stoichiometric molybdenum carbene-
mediated dienyne cyclizations3,11 and catalytic ruthenium-mediated
cyclizations of enynes,12 the mechanism could involve formation
of a nickel carbene intermediate 5, followed by a metathesis cascade
to generate metallacyclobutane 6. Rearrangement of 6 to 7 would
allow direct production of 2 upon reductive elimination. Alterna-
tively, reductive elimination of 6 to produce 8, followed by Cope
rearrangement, would afford product 2.3-5,13 In a completely distinct
mechanism, oxidative cyclization of nickel(0) with dienyne 1 could
allow production of metallacycloheptadiene 9.14 Carbene insertion
into either metal carbon bond of 9 to generate metallacycle 7 (or
its regioisomer) followed by reductive elimination would afford
product 2. Further study will be directed toward elucidating these
mechanistic issues.
In summary, a novel, nickel-catalyzed [4 + 2 + 1] cycloaddition
of a diazoalkane, diene, and alkyne has been developed, and a
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