Novel iodine reagent system for regioselective cleavage of epoxides to alcohols

Article abstract of DOI:10.1080/00397910903219492

Epoxides are converted regioselectively to corresponding higher substituted alcohols with greater yields using diphosphorus tetraiodide (P ₂I₄) as a reducing agent and a catalytic amount of tetraethylammonium bromide at room temperature. Copyright Taylor & Francis Group, LLC.

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Novel Iodine Reagent System for
Regioselective Cleavage of Epoxides to
Alcohols
Vikas N. Telvekar a & Rajesh A. Rane a
a Department of Pharmaceutical Sciences and Technology ,
University Institute of Chemical Technology , Matunga, Mumbai,
India
Published online: 17 Jun 2010.
To cite this article: Vikas N. Telvekar & Rajesh A. Rane (2010) Novel Iodine Reagent System for
Regioselective Cleavage of Epoxides to Alcohols, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 40:14, 2108-2112, DOI:
10.1080/00397910903219492
To link to this article: http://dx.doi.org/10.1080/00397910903219492
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Synthetic Communications1, 40: 2108–2112, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903219492
NOVEL IODINE REAGENT SYSTEM FOR
REGIOSELECTIVE CLEAVAGE OF
EPOXIDES TO ALCOHOLS
Vikas N. Telvekar and Rajesh A. Rane
Department of Pharmaceutical Sciences and Technology, University Institute
of Chemical Technology, Matunga, Mumbai, India
Epoxides are converted regioselectively to corresponding higher substituted alcohols with
greater yields using diphosphorus tetraiodide (P2I4) as a reducing agent and a catalytic
amount of tetraethylammonium bromide at room temperature.
Keywords: Alcohols; diphosphorus tetraiodide; epoxides; reduction; tetraethylammonium bromide
INTRODUCTION
The reductive cleavage of epoxides to alcohols is one of the most important
reactions in organic synthesis. In principle, an unsymmetrical alkyl-substituted
epoxide can produce the more substituted carbinol by reduction of epoxides with
nucleophilic hydride transferring reagents or less substituted alcohol with elcetro-
philic hydride reagents,[1–5] depending on the cleavage of the C–O bond to the
less-substituted or more-substituted carbon atom. Drawbacks of most of these avail-
able methods are formation of mixtures of more- and less-substituted alcohols,
which means that there is still scope for alternative reagent systems for regioselective
preparation of alcohols from epoxides.
Our group is developing new methodologies using an iodine reagent system.[6]
Diphosphorus tetraiodide (P2I4) is an orange crystalline solid and is commercially
available. It exhibits a high affinity for oxygen and acts as a unique reagent to pro-
mote reduction reactions. It is known that P2I4 reduces, under mild conditions,
aminoxides, sulfoxides, and selenoxides to amines, sulfides, and selenides, respect-
ively,[7] as well as reducing diols at room temperature in the presence of a base to
corresponding alkenes.[8]
During our study, we proposed that diphosphorus tetraiodide in combination
with tetraethylammonium bromide (TEAB) might be advantageous for regioselec-
tive opening of epoxides in which the more substituted alcohol would be preferen-
tially produced by trapping the hydride at the site best able to accommodate a
Received April 27, 2009.
Address correspondence to Vikas N. Telvekar, Department of Pharmaceutical Sciences and
Technology, University Institute of Chemical Technology, Matunga, Mumbai 400 019, India. E-mail:
vikastelvekar@rediffmail.com
2108

NOVEL IODINE REAGENT SYSTEM
2109
Scheme 1. Transformation of epoxide to alcohol.
carbonium ion. After considerable exploration, a combination of diphosphorus
tetraiodide and a catalytical amount of tetraethyl ammonium bromide was demon-
strated to offer the most reliable and convenient reductive system. To the best of our
knowledge, there are no reports on P2I4-mediated regioselective reductive transform-
ation of epoxides to alcohols (Scheme 1).
In this communication, we report on our preliminary result on regioselective
cleavage of epoxides using P2I4 and TEAB to form higher substituted alcohols.
RESULTS AND DISCUSSION
For initial studies, we selected styrene epoxide as a model substrate. We
observed that without TEAB, the reaction does not take place. Instead of
TEAB, we tried other quaternary ammonium salts such as tetraethylammonium
chloride and tetraethylammonium iodide as catalyst, but no reaction was observed.
Screening with alternative solvents led us to conclude that dichloromethane was
the most suitable solvent for the conversion. Although complete conversion was
also observed in carbon disulfide, it was not selected because of its toxicity and
flammability.
It has been well studied for reduction of cyclic and acyclic dithioacetals using
P2I4 and found that the proton required for the reduction comes from the moisture
present in the solvent.[9,10] In this case, the transformation required traces of moist-
ure, which comes from solvent used in the reaction mixture. We confirmed this by
conducting the reaction in absolute dry conditions, where reduction to correspond-
ing alcohol was not observed in either dry carbon disulfide or dry dichloromethane.
To explore the reaction scope, a variety of aromatic, aliphatic epoxides were
converted into alcohols, and results are presented in Table 1. Table 1 clearly shows
that reactions completed within 5–6 h with good yield. It was found that either
electron-rich or electron-deficient aromatic epoxides were suitable for this reaction,
giving desired alcohols in good yield (Table 1, entries 2–7). It was noted that a
variety of functional group tolerated these reaction conditions (Table 1, entries 8
and 9). Reductive cleavage of epoxide occurs with retention of configuration, pro-
ducing (1R)-1-phenylehtanol exclusively from (2R)-2-phenyloxirane and (1R)-1-
(4-chlorophenyl) ethanol from (2R)-2-(4-chlorophenyl)oxirane (Table 1, entries 10
and 11).
The major advantages of this methodology are availability of this reagent, safer
reaction conditions, and complete regioselectivity in the reductive cleavage of
epoxide compared with existing reagents. Moreover, with the combination of the
excellent methods available for the synthesis of optically active epoxides, the present
method can provide easy access to optically active alcohols with retention of
configuration.

2110
V. N. TELVEKAR AND R. A. RANE
Table 1. Synthesis of alcohols from epoxides using P2I4 and catalytical TEABa
Entry
1
Substrateb
Product
Time (h)
Yieldc (%)
5
90
2
3
4
5
6
5
87
84
83
5
6
5
6
80
84
7
6
85
8
9
6
7
6
6
88
86
10
11
87d
85d
(Continued )

NOVEL IODINE REAGENT SYSTEM
2111
Table 1. Continued
Entry
12
Substrateb
Product
Time (h)
6
Yieldc (%)
80
13
6
82
aTypically, P2I4 (0.01 mol) reacted with epoxide (0.01 mol) in dichloromethane (50 ml, 1–3% moisture) in
the presence of a catalytic amount of TEAB at room temperature.
bStarting compounds were prepared by standard literature procedures.
cIsolated yields after column chromatography and structure confirmed by comparison of IR and
1H NMR with those of authentic materials.
dOptical purity was confirmed by chiral HPLC and optical rotation matches with literature values.[11,12]
GENERAL PROCEDURE
Preparation of Alcohols
Epoxide (0.01 mol) was added to a stirred solution of diphosphorus tetraiodide
(0.01 mole) and a catalytical amount of TEAB in dichloromethane (50 mL contains
1–3% moisture). The resultant mixture was stirred at rt until the starting material
had been completely consumed (thin-layer chromatography, TLC). The reaction
mixture was filtered, and the filtrate was washed successively with saturated aq.
NaHCO3 (2 Â 20 mL) and H2O (1 Â 20 mL). The organic layer was separated, dried
over Na2SO4, and concentrated in vacuo. The residue obtained was purified by
silica-gel column chromatography (15% EtOAc–hexane) to afford pure alcohols.
ACKNOWLEDGMENT
V. N. T. and R. A. R. gratefully acknowledge the University Grants
Commission, India, for financial support.
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2112
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