J. Am. Chem. Soc. 2000, 122, 6775-6776
6775
Scheme 1
Diverse Reactivity Manifolds of Alkynyl Enone- and
Alkynyl Enal-Derived Nickelacycles: Discovery of
Nickel-Promoted [3+2] and [2+1] Cycloadditions
Sanjoy K. Chowdhury, Kande K. D. Amarasinghe,
Mary Jane Heeg,† and John Montgomery*
Department of Chemistry, Wayne State UniVersity
Detroit, Michigan 48202-3489
ReceiVed April 11, 2000
The nickel-catalyzed cyclization of alkynyl enones has been
extensively investigated in our laboratories over the past few
years.1 The reactions developed in this program include the
alkylative cyclization of alkynyl enones in the presence of
organozincs and Ni(COD)2 to produce 3,2,3 the reductive cycliza-
tion of alkynyl enones in the presence of organozincs and Ni-
(COD)2/PPh3 to produce 4,2 and the [2+2+2] cycloaddition of
alkynyl enones and simple enones in the presence of Ni(COD)2/
PPh3 to produce 5 (Scheme 1).4 We speculated that nickel
metallacycles 25 were common intermediates in each of these
pathways, although efforts to isolate or spectroscopically char-
acterize the proposed metallacycles were unsuccessful. The rapid
dimerization of alkynyl enones via the [2+2+2] cycloaddition
pathway to produce 6 is a major reason that the metallacycles
have proven to be elusive (Scheme 1).4
To explore this novel reaction in a synthetically useful context,
we examined the reactivity of simple alkynyl enones and alkynyl
enals that lacked the tethered diamine functionality. Whereas
monodentate (PPh3) and bidentate (Ph2PCH2CH2PPh2) phosphine
ligands led predominantly to substrate dimerization to afford 6,
treatment of alkynyl enones and alkynyl enals with 1 equiv of
the complex generated from Ni(COD)2 and tmeda afforded the
desired [3+2] cycloadducts (Table 1). Cyclization of enals 1a
and 1b that possess aliphatic or aromatic substituents on the alkyne
cleanly afforded bicyclooctenols 7a and 7b in 82% and 72%
isolated yields, respectively (entries 1 and 2). Six-membered-ring
product 7c was produced in 40% isolated yield, and 18% of
monocyclic product 4c was also obtained. Electron-deficient
alkyne 1d was much less efficient in the desired [3+2] cyclization,
and compound 7d was obtained in 15% isolated yield. Terminal
alkyne 1e was also a poor substrate, and only product 4e was
obtained in 27% isolated yield. Enones 1f and 1g also participated
in the [3+2] cycloadditions in similar fashion. However, upon
workup with dilute acid, rearranged tertiary alcohols 12f and 12g
were obtained in 53% and 52% isolated yields.
We envisioned that oxidative cyclization of an alkynyl enone
or alkynyl enal to metallacycle 2 could potentially provide a novel
entry to synthetically valuable nickel enolates if the facile
dimerization to 6 could be suppressed. To suppress the undesired
dimerization manifold, alkynyl enone 9, which possesses a
covalently tethered bidentate ligand, was prepared (eq 1). Upon
We speculate that the mechanism of this novel [3+2] cycload-
dition involves initial generation of nickelacycle 2 which could
exist as the O- or C-enolate tautomer 2a or 2b or in the
corresponding η3 form (Scheme 2). Double protonation of 2a or
2b would afford monocyclic product 14 (E ) H), which was
observed as a minor byproduct in two cases. However, the primary
pathway for the formal [3+2] cycloaddition likely involves
selective monoprotonation of 2 followed by carbonyl insertion
into the nickel-carbon bond of 13. The resulting nickel alkoxide
15 undergoes hydrolysis upon workup to produce the observed
bicyclooctenol 7 (E ) H).
The above experiments suggest that other enolate alkylation/
carbonyl insertion sequences could be accessed from metallacycle
2. Accordingly, the complex derived from Ni(COD)2, tmeda, and
enal 1a was treated with methyl iodide prior to aqueous workup
(eq 2). After the mixture was stirred at 0 °C for 1 h, compound
17 was produced as a single diastereomer in 68% yield,
presumably via C-alkylation of nickel enolate 2a or 2b with
methyl iodide followed by carbonyl insertion as described above
(Scheme 2). The enolate of metallacycle 2, derived from enal
treatment of 9 with a stoichiometric quantity of Ni(COD)2, a
homogeneous red solution resulted for which we tentatively
propose structure 10. The η1-C-enolate shown and the corre-
sponding η1-O-enolate and η3-enolate structures are all reasonable
formulations for 10. Although isolation of metallacycle 10 was
not achieved, bicyclooctenol 11 was obtained upon quenching
the reaction with aqueous Na2CO3. The process constitutes a
previously unknown formal [3+2] cycloaddition between an
enone and alkyne.6
† To whom correspondence regarding X-ray structure determinations should
be addressed.
(1) Montgomery, J. Acc. Chem. Res. 2000, in press.
(2) (a) Montgomery, J.; Savchenko, A. V. J. Am. Chem. Soc. 1996, 118,
2099-2100. (b) Montgomery, J.; Oblinger, E.; Savchenko, A. V. J. Am. Chem.
Soc. 1997, 119, 4911-4920. (c) Chevliakov, M. V.; Montgomery, J. J. Am.
Chem. Soc. 1999, 121, 11139.
(3) For related work from Ikeda and Sato, see: (a) Ikeda, S.; Sato, Y. J.
Am. Chem. Soc. 1994, 116, 5975-5976. (b) Ikeda, S.; Yamamoto, H.; Kondo,
K.; Sato, Y. Organometallics 1995, 14, 5015-5016. (c) Ikeda, S.; Kondo,
K.; Sato, Y. J. Org. Chem. 1996, 61, 8248-8255. (d) Ikeda, S.; Mori, N.;
Sato, Y. J. Am. Chem. Soc. 1997, 119, 4779-4780.
(4) Seo, J.; Chui, H. M. P.; Heeg, M. J.; Montgomery, J. J. Am. Chem.
Soc. 1999, 121, 476-477.
(5) For leading references to nickel metallacycles, see: (a) Grubbs, R. H.;
Miyashita, A.; Liu, M. M.; Burk, P. L. J. Am. Chem. Soc. 1977, 99, 3863-
3864. (b) Grubbs, R. H.; Miyashita, A. J. Am. Chem. Soc. 1978, 100, 1300-
1302.
(6) Related titanium-promoted [3+2] cycloadditions of enoate/alkyne
precursors have been reported. (a) Suzuki, K.; Urabe, H.; Sato, F. J. Am. Chem.
Soc. 1996, 118, 8729. (b) Urabe, H.; Suzuki, K.; Sato, F. J. Am. Chem. Soc.
1997, 119, 10014.
10.1021/ja0012624 CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/30/2000
Chowdhury, Sanjoy K.
