DOI: 10.1002/chem.201501929
Communication
&
Epoxidation
N-Methylpyrrolidone Hydroperoxide/Cs2CO3 as an Excellent
Reagent System for the Hydroxy-Directed Diastereoselective
Epoxidation of Electron-Deficient Olefins
Napoleon John Victor, Janardhanan Gana, and Kannoth Manheri Muraleedharan *[a]
sulfonylation of alkenes and alkynes,[5] CÀH trifluoromethyla-
tion,[6] hydroxylation,[7] amidation of aldehydes,[8] and others
Abstract: This report introduces N-methylpyrrolidone hy-
droperoxide (NMPOOH)/base as an excellent reagent
like arene oxidation.[1b] Choice of a particular reagent is based
system for hydroxy-directed syn selective epoxidation of
electron-deficient olefins, characterized by high diastereo-
selectivity, short reaction times and remarkable chemose-
lectivity, especially in presence of oxidatively labile nitro-
gen or sulfur atoms. NMPOOH also proves efficient in the
oxidation of electron-deficient aromatic aldehydes, in the
removal of oxazolidinone chiral auxiliary, and in the func-
tionalization of alkenes and alkynes, showing wide appli-
cation potential.
on the electronic characteristics of the olefin, regio- or stereo-
chemical requirements, and substrate compatibility.
The observed selectivity during the epoxidation of allylic-
and homoallylic alcohols, and allylamines with peracids is at-
tributable to the directing effect of hydroxy or amino groups
through hydrogen bonding.[9] When the double bond in such
systems is also bonded to an electron-withdrawing group, as
in a-methylene-b-hydroxycarboxylates, the reactivity and ste-
reochemical preferences differ markedly. Despite the high syn-
thetic value of epoxides from such substrates,[10] not many ste-
reoselective methods are available for this transformation.
Bailey et al. have used VO(acac)2/TBHP or Ti(OiPr4)/TBHP to ach-
ieve syn-selective epoxidation of various cyclic and acyclic
Baylis–Hillman (BH) adducts.[11] Alkaline H2O2, which is generally
used for the epoxidation of enones, did not work well with
such substrates, and the selectivity was also very low.[11c]
Construction of complex organic frameworks always involves
the logical assembly of properly functionalized building blocks.
Amongst others, epoxides constitute one of the most impor-
tant groups of intermediates in organic synthesis. Presence of
this moiety in various natural products, as well as feasibility of
its further synthetic elaboration to key structural units in target
molecules has motivated researchers to develop efficient ste-
reoselective strategies for epoxidation, of which, protocols by
Sharpless, Jacobsen, and Shi are classical examples.[1] In gener-
al, peracids, dioxiranes, or hydroperoxides are part of the re-
agent system for epoxidation; the former two are efficient on
isolated double bonds, whereas hydroperoxides are used in
combination with metal salts/complexes or base to get wider
substrate scope, including enones.[1a,2a] Notable developments
in this area include high asymmetric induction in electron-defi-
cient systems with H2O2 or tBuOOH (TBHP) in the presence of
chiral phase-transfer catalysts, polyamino acids, lanthanide–
BINOL complexes, bovine serum albumin or chiral base, and
similar outcomes on using Et2Zn, chiral alcohol, and O2.[2] Apart
from these peroxides (H2O2 and TBHP), sugar-, perhydrate-, ox-
aziridine-, and flavin-based hydroperoxides have also been
used in epoxidation reactions.[3] In addition, hydroperoxides
are useful in the oxidation of aldehydes and heteroatoms,[4]
ˇ
Svenda and Myers were successful in getting anti-epoxides of
a-methylene-b-tert-butyldimethyl silyloxycarboxylate esters
with a TBHP/KOtBu system.[12] High diastereoselectivity in this
case is explained by considering a ‘concerted-like’ oxygen-
transfer step. Recently, Latorre et al. reported the syn-selective
epoxidation of a-methylene-b-hydroxycarboxylate esters using
lithium tert-butylperoxide.[13] With the exception of b-alkenyl
substitution, all groups, including alkyl, aryl, and arylalkyl, at
this position favored syn epoxidation (d.r. up to 93:7), with
yields ranging from 38 to 85%. These prior studies all suggest
that development of a new, efficient, and easily accessible re-
agent that can offer high diastereoselectivity under mild condi-
tions is highly warranted. Our development of such a reagent,
based on one of the most familiar solvents, N-methyl-2-pyrroli-
dinone (NMP), is discussed below.
During our attempt to synthesize the hydroxyacridone deriv-
ative 2 (Scheme 1) through reaction of 1 with n-propylamine
using K2CO3 in NMP, we serendipitously observed the forma-
tion of epoxide 3 in 40% yield, which was characterized by
various spectroscopic methods including X-ray diffraction anal-
ysis. Since repeating the reaction with a fresh bottle of NMP
did not give the same epoxide, the involvement of 5-hydroper-
oxy-N-methylpyrrolidin-2-one (NMPOOH)—an oxidation prod-
uct of NMP—was suspected. This became more evident when
we found that epoxide 4 formed on simple stirring of 1 in an
old sample of NMP in the presence of K2CO3 (Scheme 1). Re-
markably, the reaction was completed in less than five mi-
[a] Dr. N. J. Victor, J. Gana, Dr. K. M. Muraleedharan
Department of Chemistry
Indian Institute of Technology Madras,
Chennai 600 036, India
Fax: (+91)-44 2257 4202
Supporting information for this article is available on the WWW under
Chem. Eur. J. 2015, 21, 14742 – 14747
14742
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