ORGANIC
LETTERS
2011
Vol. 13, No. 9
2220–2223
Iodobenzene-Catalyzed Intramolecular
Oxidative Cyclization Reactions of
δ-Alkynyl β-Ketoesters
´
Arantxa Rodrıguez and Wesley J. Moran*
Department of Chemical & Biological Sciences, University of Huddersfield, Queensgate,
Huddersfield HD1 3DH, U.K.
Received February 21, 2011
ABSTRACT
Iodobenzene is shown to catalyze the 5-exo-dig cyclization of δ-alkynyl β-ketoesters under oxidative conditions that generate hypervalent iodine
species in situ. The cyclopentane products contain adjacent quaternary and tertiary stereocenters which are generated with excellent
diastereoselectivity.
The catalytic activation of alkynes to nucleophilic
addition by π-acidic metal complexes has received
considerable attention from the synthetic community;1
however there are almost no examples of such activa-
tion by organocatalysts.2 Molecular iodine has been
shown to activate alkynes to nucleophilic attack, but
stoichiometric quantities of iodine are required in these
cases.3 Stoichiometric quantities of hypervalent iodine
reagents are also known to activate alkynes to nucleophilic
attack by heteroatoms.4 Considering the low cost, as well
as the ease of use and handling, of hypervalent iodine
species compared to noble metals, the development of
novel reactions utilizing these compounds is of increasing
interest to synthetic chemists.5 Notably, over the past few
years, reports have appeared demonstrating the use of
hypervalent iodine compounds prepared in situ from
aryliodides and used as catalysts in various oxidation
reactions.6
Considering that molecular iodine and hypervalent
iodine mediated cyclization reactions bear similarities
to gold catalysis, we reasoned that 5-exo-dig cyclizations
onto alkynes, promoted by iodine(III) species, to generate
carbonÀcarbon bonds should be feasible. To this end, we
prepared alkyne 1a and surveyed hypervalent iodine re-
agents as mediators for intramolecular cyclization. Upon
stirring with PhI(OAc)2 (PIDA) or PhI(OCOCF3)2 (PIFA)
inacetonitrileatroomtemperature, oratrefluxwithPIFA,
no reaction took place (Table 1, entries 1 and 2). Stirring
with Koser’s reagent (PhI(OH)OTs) returned ∼95% of 1a,
but some unidentifiable products (at that point) were
evident in the 1H NMR spectrum (entry 3). At this stage,
we decided to generate the hypervalent iodine species in
situ from iodobenzene with p-toluenesulfonic acid and
m-chloroperbenzoic acid, and we were delighted to find that
(5) For reviews on hypervalent iodine chemistry, see: (a) Zhdankin,
V. V. J. Org. Chem. 2011, 76, 1185–1197. (b) Zhdankin, V. V. Arkivoc
2009, 1–62. (c) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299–
5358. (d) Wirth, T. Angew. Chem., Int. Ed. 2005, 44, 3656–3665. (e)
French, A. N.; Bissmire, S.; Wirth, T. Chem. Soc. Rev. 2004, 33, 354–362.
(f) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523–2584. (g)
Koser, G. F. Aldrichimica Acta 2001, 34, 89–102. (h) Stang, P. J.;
Zhdankin, V. V. Chem. Rev. 1996, 96, 1123–1178.
(6) (a) Uyanik, M.; Ishihara, K. Chem. Commun. 2009, 2086–2099.
(b) Dohi, T.; Kita, Y. Chem. Commun. 2009, 2073–2085. (c) Ochiai, M.;
Miyamoto, K. Eur. J. Org. Chem. 2008, 4229–4239. (d) Richardson,
R. D.; Wirth, T. Angew. Chem., Int. Ed. 2006, 45, 4402–4404.
(1) For an excellent review, see: Furstner, A.; Davies, P. W. Angew.
Chem., Int. Ed. 2007, 46, 3410–3449.
(2) Miyamoto, K.; Sei, Y.; Yamaguchi, K.; Ochiai, M. J. Am. Chem.
Soc. 2009, 131, 1382–1383.
(3) For a selected example, see: Bi, H.-P.; Guo, L.-N.; Duan, X.-H.;
Gou, F.-R.; Huang, S.-H.; Liu, X.-Y.; Liang, Y.-M. Org. Lett. 2007, 9,
397–400.
(4) (a) Pardo, L. M.; Tellitu, I.; Domı
978. (b) Tellitu, I.; Serna, S.; Herrero, M. T.; Moreno, I.; Domı
SanMartin, R. J. Org. Chem. 2007, 72, 1526–1529.
´
nguez, E. Synthesis 2010, 971–
´
nguez, E.;
r
10.1021/ol200471w
Published on Web 04/01/2011
2011 American Chemical Society