Molecules 2006, 11, 421-434
Hypervalent Iodine–Mediated Ring Contraction Reactions
Luiz F. Silva, Jr*
Instituto de Química, Universidade de São Paulo, CP 26077, CEP 05513-970, São Paulo SP, Brazil;
Tel. (+55)-11-3091-2388, Fax (+55)-11-3815-5579
* Author to whom correspondence should be addressed; e-mail: firstname.lastname@example.org
Received: 27 November 2005 / Accepted: 2 May 2006 / Published: 20 June 2006
Abstract: Hypervalent iodine reagents constitute a powerful tool in modern synthetic
organic chemistry, promoting several important reactions. One such reaction is the ring
contraction of cycloalkenes and cycloalkanones promoted by iodine(III) compounds, such
as iodobenzene diacetate, iodosylbenzene, iodotoluene difluoride, and [hydroxy(tosyloxy)-
iodo]benzene (Koser´s reagent). This review covers all the literature related to the ring
contraction of cyclic ketones and olefins promoted by iodine(III) species.
Keywords: Iodine(III), hypervalent iodine, ring contraction, oxidation, cycloalkenes,
Ring contraction reactions are an important method to increase molecular complexity in a single
step, because, in several cases, the reorganization of the bonds occurs with a high level of selectivity,
affording products not easily accessible by other approaches . Ring contraction reactions can be
effected by acids, by bases, by oxidizers or photochemically . Among the oxidizers, one of the most
used is thallium trinitrate (TTN) [2, 3].
In the last years, hypervalent iodine reagents have become an essential tool in synthetic organic
chemistry, due to the plethora of reactions that can be performed with them in excellent yield and
selectivity. One such reaction is the oxidative rearrangement of cycloalkenes and cycloalkanones,
which leads to a ring contraction. Although several reviews concerning hypervalent iodine chemistry
have been published [4-15], none of them covered ring contraction reactions in a comprehensive
manner. This review intends to cover the literature related to the ring contraction reaction of cyclic
Molecules 2006, 11
ketones and olefins promoted by hypervalent iodine. The definition of ring contraction through this
article follows that previously mentioned by Redmore and Gutsche [1, 16].
Ring Contractions of Cycloalkanones
Two articles concerning the ring contraction of steroidal ketones mediated by iodine(III) were
released nearly simultaneously in 1984. In the first paper, Daum reported that the reaction of the
androstan-3-one 1 with iodobenzene diacetate leads to a mixture of the ring contraction products 2 and
3 . After recrystallization, 2 was obtained in 65% yield. A similar result was obtained when the
reaction was performed with iodosobenzene, instead of iodobenzene diacetate. The configuration of
the major product 2 has been explained by the formation of the adduct 7, which bears the iodine group
at the equatorial position (Figure 1). The behavior of the 19-norandrostan-3-one 4 toward the oxidation
of iodobenzene diacetate was different from 1, because 4 gave as the major product the hydroxyketal 5.
In this case, the ring contraction product 6 was obtained in poor yield (Scheme 1). The author
suggested that for the nor-androstanone 4 formation of the adduct 8 bearing the iodine(III) group in the
axial position would occur, as shown in Figure 1. Thus, for substrates where there are no steric
restrictions, such as 4, the addition would lead to an intermediate with the iodine(III) group in the axial
position, as in 8. On the other hand, for cycloalkanones where an axial iodine(III) atom would lead to
strong 1,3-diaxial interactions, such as 1, the iodine(III) occupies the equatorial position, as in 7.
(a) i) 1 eq. PhI(OAc)2, KOH (excess),
MeOH, rt, overnight; ii) HCl
(b) i) 1 eq. PhIO, KOH (1 eq.),
MeOH, rt, overnight; ii) HCl
i) 1 eq. PhI(OAc)2
KOH (excess), MeOH
Figure 1. Structure of the Intermediates proposed by Daum.
Molecules 2006, 11
The first step is the electrophilic addition of the iodine(III) reagent to the unsaturation, giving the
oxonium ion 90. This intermediate would give the enone 80 through 91, by a reductive elimination.
Alternatively, the oxonium 90 may give, after addition of water, the adduct 92, on which would occur
the rearrangement leading to the tetrahydrofuran 82 or an intramolecular reductive displacement
The oxidative rearrangement of cyclic alkenes and ketones promoted by iodine(III) reagents can be
performed in an efficient manner under several different reaction conditions. However, considering the
potential of hypervalent iodine reagents in synthetic organic chemistry, as well as the usefulness of
ring contraction reactions to increase molecular complexity in a single step, we expect that
applications of iodine(III)-mediated ring contractions will rapidly increase in the next years.
We are grateful for the financial support provided by FAPESP and TWAS.
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