962
J . Org. Chem. 1996, 61, 962-968
Br + a n d I+ Tr a n sfer fr om th e Ha lon iu m Ion s of
Ad a m a n tylid en ea d a m a n ta n e to Accep tor Olefin s. Ha locycliza tion
of 1,ω-Alk en ols a n d Alk en oic Acid s P r oceed s via Rever sibly
F or m ed In ter m ed ia tes
A. A. Neverov and R. S. Brown*,†
Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada
Received September 18, 1995X
The kinetics of the transfer of X+ from the bromonium and iodonium ions of adamantylideneada-
mantane (1-Br+ and 1-I+) to some 1,ω-alkenols and alkenoic acids in ClCH2CH2Cl at 25 °C was
investigated. In all cases, the expected products of halocyclization were observed. For the iodonium
ion transfer the reaction kinetics are second order overall, first order in both 1-I+ and acceptor
olefin. Transfer of the bromonium ion from 1-Br+ to these acceptor olefins exhibits different kinetic
characteristics. In most cases, the rate of the Br+ transfer is subject to strong retardation in the
presence of added parent olefin (AddAd), suggestive of a common species rate depression. In some
cases, such as 4-penten-1-ol (2b) and 4-pentenoic acid (4b), the reaction can be completely suppressed
at high [AddAd]. In other cases, such as 3-buten-1-ol (2a ), 5-hexen-1-ol (2c), cyclohexene,
4-(hydroxymethyl)cyclohexene (3), and 5-endo-carboxynorbornene (5), added AddAd does not
suppress the reaction completely. In the cases of the 1,ω-alkenols, the reactions appear to exhibit
kinetic terms that are greater than first order in alkenol. In these cases, alcohols such as 1-pentanol
also accelerate the reaction, pointing to the involvement of the hydroxyl group of the second alkenol
as a catalytic species. A unifying mechanism consistent with the data that involves two reversibly
formed intermediates is presented.
In tr od u ction
opinion, are the mechanistic details of these reactions,
although several early reports have delineated the overall
reaction rates for bromo- and iodocyclizations of 1-ω-
alkenols and 1-ω-alkenoic acids in various solvents.5 The
latter experimental work has been complemented by
theoretical work on the facial selectivity in electrophilic
addition to allylic alcohols and related amines,6a as well
as on the details for cyclization of what is considered to
be the Br+-Π complex of 4-penten-1-ol.6b
Electrophile-promoted cyclization of ω-substituted alk-
enes1 (eq 1) is an increasingly important method for
synthesis of heterocyclic ethers (X ) OH),2 lactones (X )
CO2H),3 and lactams (X ) C(O)NRH).4 Much recent work
(CH2)n
E+
+ H+
(CH2)n
(1)
Y
H
Y
E
Of interest in this work, particularly insofar as the
product stereochemistry is concerned, is the question of
reversibly-formed intermediates which could lead to
thermodynamically controlled products in competition
with kinetically controlled ones.2b,d Although the sug-
gestions of reversibly formed intermediates in these
cyclization reactions are reasonable and appealing, to our
knowledge there is scant hard evidence for this. In one
recent study, Rodebaugh and Fraser-Reid7 have shown,
on the basis of changing product ratios as a function of
initial substrate concentrations, that there is communi-
cation between the bromonium ion of an n-pentenyl or
n-hexenyl glycoside and the two parent olefins.7 Kinetic
evidence pertaining to this mechanistic question would
be invaluable, and this forms the subject of the present
report.
has centered on the well-known bromo- and iodocycliza-
tions of substituted pentenols, hexenols, or their unsatur-
ated acid counterparts which form cyclic 5- and 6-mem-
bered rings with defined stereochemical preferences for
the ring closures.2,3 Less comprehensively studied, in our
† Address correspondence to this author after J uly 1, 1995, at the
Department of Chemistry, Queen’s University, Kingston, Ontario, K7L
3N6, Canada.
X Abstract published in Advance ACS Abstracts, J anuary 1, 1996.
(1) For reviews on this subject see: (a) Staninets, V. I.; Shilov, E.
A. Russ. Chem. Rev. 1971, 40, 277. (b) Dowle, M. D.; Davies, D. I. Chem.
Soc. Rev. 1979, 171-197. (c) Bartlett, P. A. In Asymmetric Synthesis;
Morrison, J . D., Ed.; Academic Press: New York, 1984; Chapter 6,
Vol. 3.
(2) (a) Lipshutz, B. H.; Barton, J . C. J . Am. Chem. Soc. 1992, 114,
1084. (b) Reitz, A. B.; Norley, S. O.; Maryanoff, B. E.; Liotta, D.;
Monahan, R. J . Org. Chem. 1987, 52, 4191 and references therein. (c)
Cook, C. H.; Cho, Y. S.; J ew, S. S.; J ung, Y. H. Arch. Pharmacol. Res.
1985, 8, 39 and references therein. (d) Rychnovsky, S. D.; Bartlett, P.
A. J . Am. Chem. Soc. 1981, 103, 3963.
(3) (a) Corey, E. J .; Fleet, W. J .; Kato, M. Tetrahedron Lett. 1973,
3963. (b) Rengevitch, E. N.; Staninets, V. L.; Shilov, E. A. Proc. Natl.
Acad. Sci. USSR 1962, 146, 781. (c) Toshimitsu, A.; Teras, K.; Uemura,
S. Tetrahedron Lett. 1984, 5917. (d) Bartlett, P. A.; Richardson, D. P.;
Meyerson, J . Tetrahedron 1984, 40, 2317 and references therein. (e)
Collado, I. G.; Maders, J . G.; Massanet, G. M.; Luis, F. R. Tetrahedron
Lett. 1990, 563. (f) Cambie, R. C.; Rutledge, P. S.; Somerville, R. F.;
Woodgate, P. D. Synthesis 1988, 1009. (g) Davies, D. I.; Dowle, M. D.
J . Chem. Soc., Perkin Trans. 1 1976, 2267. (h) Evans, D.; Magee, J .
W.; Schauble, J . H. Synthesis 1988, 862.
(5) (a) Williams, D. L. H. Tetrahedron Let. 1967, 2001. (b) Rengevich,
E. N.; Staninets, V. I.; Shilov, E. A. Dokl. Akad. Nauk. 1962, 146, 111.
(c) Bienvenu¨e-Goetz, E.; Dubois, J . E.; Pearson, D. W.; Williams, D. L.
H. J . Chem. Soc. B 1969, 1275. (d) Williams, D. L. H.; Bienvenu¨e-
Goetz, E.; Dubois, J . E. Ibid. 1969, 517. (e) Hooley, S. R.; Williams, D.
L. H. J . Chem. Soc. B 1975, 503. (f) DoAmaral, L.; Melo, S. C. J . Org.
Chem. 1973, 38, 800. (g) Lown, J . W.; J oshua, A. V. Can. J . Chem.
1977, 55, 131.
(6) (a) Chamberlin, A. R.; Mulholland, R. L.; Kahn, S. D.; Hehre,
W. J . J . Am. Chem. Soc. 1987, 109, 672. (b) Sperka, J .; Liotta, D. C.
Heterocycles 1993, 35, 701. (c) Houk, K. N.; Moses, S. R.; Wu, Y.-D.;
Rondan, N. G.; J a¨ger, V.; Schohe, R.; Franczek, F. R. J . Am. Chem.
Soc. 1984, 106, 3880.
(4) (a) Balko, T. W.; Brinkmeyer, S.; Terando, N. H. Tetrahedron
Lett. 1989, 30, 2045. (b) Bilosk, A. J .; Wood, R. D.; Ganem, B. J . Am.
Chem. Soc. 1982, 104, 3233. (c) Knapp, S.; Levorse, A. T. J . Org. Chem.
1988, 53, 4006 and references therein.
(7) Rodebaugh, R.; Fraser-Reid, B. J . Am. Chem. Soc. 1994, 116,
3155.
0022-3263/96/1961-0962$12.00/0 © 1996 American Chemical Society