A simple and facile method for regio- and stereoselective bromoformyloxylation and bromoacetoxylation of olefins using NH4Br and oxone

Article abstract of DOI:10.1016/j.tetlet.2014.04.103

A mild and efficient protocol for the preparation of bromoformates as well as bromoacetates from olefins using NH₄Br and oxone in nucleophile sources (DMF or DMA) without employing catalyst at room temperature is described. This method is facile, environmentally friendly and cost effective. A variety of terminal, internal and cyclic alkenes reacted smoothly to give the corresponding bromoformate and acetate products in good to excellent yields. Moreover, 1,2-disubstituted olefins provided moderate to excellent diastereoselectivity.

Full text of DOI:10.1016/j.tetlet.2014.04.103

Accepted Manuscript
A simple and facile method for regio- and stereoselective bromoformyloxylation
and bromoacetoxylation of olefins using NH4Br and oxone ®
Mameda Naresh, Peraka Swamy, Macharla Arun Kumar, Marri Mahender
Reddy, Kodumuri Srujana, Nama Narender
PII:
S0040-4039(14)00740-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.04.103
TETL 44565
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
24 February 2014
28 April 2014
29 April 2014
Please cite this article as: Naresh, M., Swamy, P., Kumar, M.A., Reddy, M.M., Srujana, K., Narender, N., A simple
and facile method for regio- and stereoselective bromoformyloxylation and bromoacetoxylation of olefins using
NH4Br and oxone ® , Tetrahedron Letters (2014), doi: http://dx.doi.org/10.1016/j.tetlet.2014.04.103
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Graphical Abstract
A simple and facile method for regio- and stereoselective
bromoformyloxylation and bromoacetoxylation of olefins using
NH4Br and oxone®
Mameda Naresh, Peraka Swamy, Macharla Arun Kumar, Marri Mahender Reddy,
Kodumuri Srujana, Nama Narender*

A simple and facile method for regio- and stereoselective
bromoformyloxylation and bromoacetoxylation of olefins using
NH4Br and oxone®
Mameda Naresh, Peraka Swamy, Macharla Arun Kumar, Marri Mahender Reddy,
Kodumuri Srujana, Nama Narender*
Inorganic and Physical Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad
500 007, India
ABSTRACT
A mild and efficient protocol for the preparation of bromoformates as well as
bromoacetates from olefins using NH4Br and oxone® in nucleophile sources (DMF or
DMA) without employing catalyst at room temperature is described. This method is
facile, environmentally friendly and cost effective. A variety of terminal, internal, and
cyclic alkenes reacted smoothly to give the corresponding bromoformate and acetate
products in good to excellent yields. Moreover, 1,2-disubstituted olefins provided
moderate to excellent diastereoselectivity.
Keywords: Alkenes, Cohalogenation, NH4Br, Oxone®, Regioselectivity,
Diastereoselectivity
Vicinal difunctionalization (simultaneous installation of two different
functional groups into the organic structure) is a remarkable fundamental process in
organic synthesis as it can be used to transform simple and readily available alkenes
into value added products in regio- and stereoselective manner.1 Among them, the co-
halogenation of olefins is a valuable synthetic method to prepare the vicinal halo-
functionalized synthons (halohydrins, β-haloethers and β-haloesters) regioselectively
which are useful for various synthetic applications2 and as building blocks for the
preparation of epoxides.3 Bromoformyloxylation and bromoacetoxylation of olefins
are synthetically useful transformations in order to obtain bifunctionalities
regioselectively.
Literature survey revealed that, in spite of its synthetic potential,
bromoformyloxylation has received little attention and only a few methods using
* Corresponding author. Tel.: +91–40-27191703; Fax: +91-40-27160387/27160757.
E-mail address: narendern33@yahoo.co.in; nama@iict.res.in (N. Narender)

NBS/DMF,4 N-bromosuccharin/DMF,5 dibromoamine-b/HCOOH,6 have been
reported. However, most of these methods suffer from one or more disadvantages,
such as unsatisfactory product yields, prolonged reaction times, use of moisture
sensitive reagents and tedious work-up procedures. Another difunctionalization
reaction is the bromoacetoxylation of olefins, which also has only a few literature
reports and employs tribromoisocyanuric acid (TBCA),7 NBS-AcOH/molecular
sieves,8 NaBr/PhI(OAc)2/CTAB,9 tetrabutyl ammonium dichlorobromate/AcOH,10
NBS-AcOH/organocatalysts,11 TsNBr2/AcOH/DMF.12 But, most of these methods
have some disadvantages. For instance, prolonged reaction times, necessity of dark,
inert conditions, high catalyst loading, low yields and exothermic process. Halohydrin
esters are also synthesized from haloesterfication of diols13 and acetylation of
corresponding halohydrins.14 However, these approaches need the prior synthesis of
diols or halo hydrin precursors from respective olefins. Therefore, replacement of
such reagents by non-toxic, mild, selective and easy-to-handle reagents is very
desirable and represents an important goal in the context of clean synthesis.
Oxone® (2KHSO5.KHSO4.K2SO4), a potassium triple salt containing
potassium peroxymonosulfate is a white crystalline solid, easy to handle, soluble in
water and yields non-polluting byproducts. Moreover, oxone® is an inexpensive and
readily accessible oxidizing agent, which have been used for the oxidation of
numerous functional groups.15 In continuation of our interest on the halogenation
reactions using environmentally benign, easy to handle and relatively inexpensive
reagents16 we wish to report herein a very simple, mild and efficient method for the
direct synthesis of bromoformates and bromoacetates from olefins using NH4Br as a
bromine source, oxone® as an oxidant and N,N-dimethyl formamide (DMF)/N,N-
dimethyl acetamide (DMA) as nucleophile sources without employing a catalyst
(Scheme 1)
Earlier we reported a method for the bromohydroxylation of olefins using
NH4Br and oxone® in CH3CN/H2O (1:1) reaction medium.16e Under similar reaction
conditions, the reaction was investigated with a variety of solvents using styrene as a
model substrate. When DMF was used as a reaction medium, instead of bromohydrin,
the bromoformyloxylation product was observed. Stimulated by these affirmative
preliminary results, subsequently, we considered to develop a methodology for
bromoformyloxylation of olefins.

Having optimized the reaction conditions, we subjected a variety of olefins
(terminal aromatic, heteroaromatic, polyaromatic, aliphatic, 1,2-disubstituted
unsymmetrical and symmetrical alkenes) to the bromoformyloxylation process to
explore its scope and generality. The results are summarized in Table 2. Aromatic
terminal alkenes with activated phenyl ring including 4-methylstyrene (1b) and 2,4-
dimethylstyrene (1c) afforded the respective bromoformate products 2b and 2c in
87% and 90% yields, respectively (Table 2), whereas, 3-nitrostyrene (1f) provided the
corresponding product in 73% yield (Table 2, entry 6). Halo substituted styrenes such
as 4-chlorostyrene (1d) and 4-bromostyrene (1e) generated the corresponding
bromoformate products 2d and 2e in excellent yields due to inductive and resonance
effect of halogen (Cl, Br) groups (Table 2). Heteroaromatic alkene 1g and
polyaromatic alkene 1h also reacted smoothly and provided the respective vicinal
bromoformate products 2g and 2h in 83% and 84% yields, respectively (Table 2). The
above results indicate that, there is no significant effect of the electronic nature of
aromatic ring on the bromoformyloxylation of terminal aromatic olefins.
Subsequently, 1,2-disubstituted unsymmetrical and symmetrical olefins were
submitted to the vicinal bromoformyloxylation and obtained the corresponding
products 2i-2q in good to excellent yields with moderate to excellent
diastereoselectivity (Table 2). In all cases complete regio- and predominant trans-
diastereoselective addition was observed. Unsymmetrical and symmetrical trans-
alkenes (1i-1m) yielded the corresponding erythro bromoformate products 2i-2m in
72-90% yields (Table 2). Whilst, symmetrical cis-alkene i.e. cis-stilbene (1n)
proceeded to give the diastereomeric mixture of bromoformates 2n in 93% (dr 3.65:1)
yield
(Table
2),
unsymmetrical
cyclic
olefins,
such
as
indene (1o) and 1,2-dihydronaphthalene (1p) reacted smoothly and furnished the
vicinal bromoformate products 2o and 2p in 89% (dr 9.99:1) and 85% (dr 44.45:1)
yields, respectively (Table 2). Similarly, symmetrical cyclic olefin 1q produced the
respective vicinal bromoformate product 2q in 70% (dr 5.99:1) yield (Table 2). In
case of aliphatic linear olefins regioselectivity was not observed, for example 1-octene
(1r) and trans-2-octene (1s) gave the corresponding Markovnikov’s products (2r and
2s) as well as anti-Markovnikov’s products (2r1 and 2s1) (Table 2, entries 18 and 19).
Encouraged by these results, we also successfully carried out the
bromoacetoxylation of various olefins by using DMA as a nucleophilic solvent under
similar reaction conditions and obtained the corresponding products in moderate to

excellent yields (Table 3). Olefins having either moderately activated (1b-1c) or
inactivated arenes (1d-1f) reacted smoothly and rendered the respective vicinal
bromoacetate products 3b-3f in 52-80% yields (Tables 3). Heteroaromatic olefin (1g)
and 2-vinylnaphthalene (1h) also furnished the corresponding bromoacetate products
3g and 3h in 62% and 82% yields, respectively (Tables 3). Unsymmetrical trans-
alkenes 1i-1k selectively formed the corresponding erythro isomers 3i-3k (Table 3).
In case of symmetrical olefins, such as trans- and cis-stilbenes 1l-1m, gave a
diastereomeric mixture of bromoacetates 3l and 3m in 82% (dr 2.8:1) and 88% (dr
1.51:1) yields, respectively (Table 3). Similarly, cyclic olefins including indene (1n)
and cyclohexene (1o), afforded the respective vicinal bromoacetate products 3n and
3o in 63% (dr 11.6:1) and 58% (dr 10:1) yields, respectively (Table 3). Moreover, the
aliphatic terminal and internal alkenes such as 1-octene (1p) and trans-2-octene (1q)
produced the corresponding vicinal bromoacetate products in 71% (as a mixture of
regioisomers 3p and 3p1) and 94% (as a mixture of regioisomers 3q and 3q1) yields,
respectively, (Table 3, entries 16 and 17). 1,4-Naphthoquinone (1v) furnished the 2-
bromo-1,4-naphthoquinone (2v) instead of the expected bromoformate/bromoacetate
products in 40% yield (Scheme 2). Bromoformyloxylation/bromoacetoxylation of
electron deficient double bond in coumarin failed to react (Table 2, entry 20 and
Table 3, entry 18). In case of benzofuran, a complex mixture of products was obtained
which contained virtually no bromoformate/bromoacetate products (Table 2, entry 21
and Table 3, entry 19).
In the case of aromatic olefins, the incoming nucleophile attacks exclusively at
the benzylic position of cyclic intermediate.17 The regioselectivity of aromatic olefins
can be explained by considering the fact that the α-position (benzylic) is more positive
than the β-position due to the presence of the aromatic ring. As seen from Tables 2
and 3, it is evident that, the bromoformyloxylation and acetoxylation of 1,2-
disubstituted alkenes provided the corresponding bromoformate and acetate products
with predominant anti-stereoselectivity. The stereochemistry of the vicinal
1
bromoformate and acetate products was established based on H NMR spectroscopy
by comparing chemical shift (δ) and coupling constant (J) values of protons attached
to the carbons bearing –OCHO/–OCOCH3 and -Br groups with previously reported
data (see Supporting Information).

A probable mechanistic pathway to explain the regio- and stereoselectivity of
the bromoformyloxylation and bromoacetoxylation of olefins is depicted in Scheme 3.
It is assumed that oxidation of bromide ion (Br-) by oxone could generate the
hypobromite ion (HO-Br+) in situ, which further reacts (electrophilic addition) with
olefin I to give a three-membered cyclic bromonium ion intermediate II. The cyclic
2
intermediate II undergoes ring opening by the oxygen of DMF or DMA via SN
pathway to produce an iminium ion III intermediate, which upon hydrolysis gave the
vicinal bromoformate/acetate product IV.
In conclusion, we have reported a selective, highly efficient and convenient
protocol for the regio- and stereoselective bromoformyloxylation as well as
bromoacetoxylation of olefins using NH4Br/oxone in DMF/ DMA (nucleophile
sources) without employing catalyst. This method is applicable to different kinds of
olefins, such as terminal aromatic, 1,2-disubstituted unsymmetrical and symmetrical
olefins. The noteworthy feature of the present method is the use of NH4Br/oxone
system as a mild, non-toxic, economically acceptable and inexpensive reagent system
coupled with simple operation and formation of cleaner products with high yields.
Acknowledgments
We thank CSIR Network project CSC-0125 for financial support. M.N,
M.A.K and M.M.R acknowledge the financial support from CSIR, India in the form
of fellowship. P.S and K.S acknowledge the financial support from UGC, India in the
form of fellowship.
Supplementary data
General procedure, spectroscopic data, and copies of 1H and 13C NMR spectra.
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Scheme 1. Synthesis of vicinal bromoformates and acetates
Scheme 2.
Br+
Oxone®
R1
R1
R
R
II
NH4Br
X = H, CH3
I
O
X
N
O
R
N
X
O
III
X
O
H2O
R1
R1
R
-C2H7N
Br
Br
IV
Scheme 3. Plausible reaction mechanism