Addition of halide to π-bond directly from aqueous NaX solution: A general strategy for installation of two different functional groups

Article abstract of DOI:10.1039/c1cc11685a

Activation of π-bond with organic Lewis acid and cationic surfactant mediated direct transfer of halides to alkyne and alkene are demonstrated to afford α,α-dihaloketones and other valuable synthons with outstanding selectivities.

Full text of DOI:10.1039/c1cc11685a

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COMMUNICATION
Addition of halide to p-bond directly from aqueous NaX solution: a
general strategy for installation of two different functional groupsw
Palash Pandit, Krishnanka S. Gayen, Saikat Khamarui, Nirbhik Chatterjee and
Dilip K. Maiti*
Received 24th March 2011, Accepted 4th May 2011
DOI: 10.1039/c1cc11685a
Activation of p-bond with organic Lewis acid and cationic
surfactant mediated direct transfer of halides to alkyne and
alkene are demonstrated to afford a,a-dihaloketones and other
valuable synthons with outstanding selectivities.
microwave7a are employed. Thus, a general method is required
under homogeneous and mild reaction conditions especially to
achieve a single regio- and stereochemical outcome typically
being possible in the fascinating intermolecular approach.
Currently, intensive research is devoted to metal catalyzed
activation of C–C triple and double bonds and their transfor-
mation.8 Organic Lewis acid9-like hypervalent iodane10 can
also be used to activate p-bond which opens up the opportu-
nity for direct transfer of halide. We disclose herein the first
ever breakthrough for simultaneous incorporation of halide
and ketone/hydroxyl/acetoxy group to CRC and CQC
bonds with complete regio- and stereoselectivity.
Simultaneous installation of two different functional groups
into the organic framework is a remarkable fundamental
process in organic synthesis.1 Vicinal difunctionalization offers
ease of access to halogen containing attractive substrates,
key intermediates, versatile building blocks2 and valuable
bioactive materials3 with introduction of new bonds and
stereocenters. However, production of these halogenated
synthons utilizing volatile molecular halogens is unsafe for
human health and the environment. Extensive research is
devoted toward in situ generation of halogen or halogen-
equivalents from halides. There are a few interesting reagents
PhI(OAc)2 has displayed (Scheme 1) exceptional chemo-
and regioselectivity in the difunctionalization of alkyne (1a)
with sodium halides (NaX) at the interface between cetyltri-
methylammonium bromide (CTAB)-assembled lipophilic
nanoreactor11 (ESI) and water to afford a,a-dibromoketone
(3a, entry 1, Table 1). Herein, attempts are also made for the
difunctionalization reaction utilizing anionic (SDS), neutral
(Tween 80), acidic (DBSA) and basic (TPAOH) surfactant
(entries 2–5), and also g3-hypervalent iodanes like PhIO12 and
PhIF210 (entries 7,8) in vain. Presence of cationic surfactant is
essential because the reaction does not proceed in absence of
CTAB (entry 6). Gratifyingly, changeover of the surfactant
CTAB to aliquat has efficiently transferred both bromide and
like NH4Br–LDH–WO4 ,
2ꢀ 4a HBr–H2O2,4b,d,e NaBr–NaIO4,4c
4g
KBr–selectfluoro4f and NaBr–NaBrO3 which have been
developed to afford halohydrins and their derivatives from
olefins. Unfortunately, water–organic combo solvents, strong
acid or alkali and also high temperature are usually employed
to achieve the desired transformations. Br+ is the active
species for the difunctionalization of olefin involving a three-
membered cyclic bromonium cation. However, the protocol is
not successful with the triple bond because of large strain in
the cationic species. For example, Floris et al. have studied the
oxobromination of ethynylbenzene using H2O2–KBr–HClO4
(pH B1) in presence of molybdenum(VI) catalyst which has
shown poor selectivities and formation of byproducts like two
diastereomeric 1,2-dibromo alkene, a-bromoketone along
with the desired a,a-dibromoketones.5 There are only two
other methods toward the synthesis of the significant
synthons5–7 with simultaneous formation of the monobromo
compound. Aqueous HBr (48%)–O2–hn to alkyne7b and
molecular bromine–dioxane–silica to acetophenone under
Department of Chemistry, University of Calcutta,
University College of Science, 92, A. P. C. Road, Kolkata-700009,
India. E-mail: maitidk@yahoo.com; Fax: +91-33-2351-9755;
Tel: +91-33-2350-9937
w Electronic supplementary information (ESI) available: Experimental
procedures, characterization data, NMR spectra, and CIF file. CCDC
799249. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c1cc11685a
Scheme 1 Difunctionalization of alkyne inside the nanoreactor.
Chem. Commun., 2011, 47, 6933–6935 6933
c
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Table 1 Development and optimization of the reaction
Time Conversion Yielda
Entry Reagentb
(h)
(%)
(%)
1
2
3
4
5
6
7
8
PhI(OAc)2, CTAB, NaBr
PhI(OAc)2, SDS, NaBr
PhI(OAc)2, Tween-80, NaBr
PhI(OAc)2, DBSA, NaBr
PhI(OAc)2, n-Pr4NOH, NaBr 20
PhI(OAc)2, NaBr
PhIO, CTAB, NaBr
PhIF2, CTAB, NaBr
PhI(OAc)2, aliquat, NaBr
PhI(OAc)2, aliquat, NaCl
PhICl2, CTAB, NaBr
3.5
24
24
25
100
3a, 83
no reaction 3a, —
no reaction 3a, —
no reaction 3a, —
no reaction 3a, —
no reaction 3a, —
no reaction 3a, —
no reaction 3a, —
100
100
100
24
24
22
4.5
4.0
5.0
9
10
11
3a, 82
3b, 65
3a, 61
a
b
Isolated yield. Surfactant (10 mol%), g3-hypervalent iodanes
(two mole).
Table 2 Substrate scope toward synthesis of a,a-dihaloketone
Entry Starting material Product
Time (h) Yield (%)
Scheme 2 Diastereoselective vicinal difunctionalization of olefin.
1
3.5
4.5
83
65
The useful building blocks are normally accessed by stepwise
processes involving metal catalysts. For example, 1,2-halohydrins
are obtained with moderate to good selectivities via ring opening
of epoxides by Ce(OTf)4,15 followed by nucleophilic addition.
The direct addition approach is equally effective for activation of
double bonds and their vicinal difunctionalization to afford
synthon 5. Versatility of the reaction is examined utilizing
functionalized unactivated, activated and sugar-based olefins
toward rapidly (1.0–2.0 h) accessed valuable building blocks
(5a–g) with good yield (70–87%). Surprisingly, complete
regio- and trans-diastereoselective addition is accomplished.
The cationic surfactant can also transfer iodine with desired
selectivities (5h). The structure is confirmed by means of single
crystal X-ray diffraction data (5a) and spectroscopic analyses
(ESI). Recently, g3-hypervalent iodanes mediated diamination14a
and diacetoxylation16 have been reported where metal catalysts
are essential.
2
3
1a
3.0
2.5
80
82
4
5
6
4.0
3.5
78
75
We have found a pronounced effect on changing the reaction
from water to organic media where OAc group is transferred
along with the halogen (7, Scheme 3). The reaction is also
successfully extended with NaI, NaCl and sugar substrates
toward synthesis of valuable 1,2-difunctionalized synthons 7d–f.
A probable reaction path is depicted in eqn (1). Organic
substrate (1a) and reagent remain inside the CTAB-assembled
chloride (entries 9,10) to furnish corresponding a,a-dibromo-
and a,a-dichloroketone (3a,b, Table 2, entries 1,2). PhICl2 is also
active for the reaction to produce 3a with lower yield (entry 11).
With this optimization study, the substrate scope for synthesis
of a,a-dibromoketone is illustrated utilizing various unactivated
and functionalized alkynes possessing electron donating and
electron withdrawing substituents (1b–e, Table 2) toward rapidly
(2.5–4.5 h) accessed valuable synthons (3c–f). Only one product
is found in each reaction with two bromine atoms at the terminal
position. The synthetic process often necessitates sugar-based
chiral synthons13 for construction of chiral heterocycles. It led us
to examine the synthesis of a new chiral synthon 3f (entry 6).
Recent studies on palladium-catalyzed difunctionalization of
olefin with similar groups like diarylation, diamination etc.14
have prompted us to examine the scope of the metal-free mild
heterofunctionalization approach toward synthesis of halo-
hydrins and also evaluate the capability of the reagent to afford
a possible single stereochemical outcome (5, 6, Scheme 2).
Scheme 3 Solvent dependent 1,2-heterofunctionalization of olefin.
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6934 Chem. Commun., 2011, 47, 6933–6935
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Interestingly, dynamic light scattering data of the aqueous
CTAB solution (Fig. 1) have supported the formation of
spherical nanoreactors (polarized optical microscope image,
ESI) with maximum population at 183 nm. However, there is
an equilibration between the spherical and small amount
(B10%) of ultralong cylindrical nanoreactor (B7500 nm).17
Fig. 1 Size and intensity data of the nanoreactor in DLS.
lipophilic nanoreactor and sodium bromide in the aqueous
surroundings. Addition of cationic surfactant bearing bromide
anion to PhI(OAc)2-polarized alkyne takes place at the interface
involving a six-membered transition state (A). The AcO: group
of the modified surfactant CTAA is immediately exchanged with
the more polarizable halide anion (B). A second bromide anion is
transferred to the putative intermediate through coordination of
the cationic nitrogen of CTAB to form C. Its solvolysis with
water (D) and simultaneous reductive elimination of hypervalent
iodane afford 3a. Complete regioselectivity of the reaction can be
explained due to placement of the relatively smaller and larger
organic part of the substrate directed toward the interface and
strongly lipophilic micellar core respectively. To understand the
reaction path, we have studied the reaction in ethylene glycol
media (eqn (2)) which probably progresses through formation
of intermediate E and subsequent solvolysis (F) to afford
keto-protected 3g. Indeed, a-bromoketone (8) is not found in
our experiments but is obtained in the commonly used Br+
addition method involving formation of bromonium species4
(G, eqn (3)).
ð4Þ
Financial support from DST (SR/NM/NS-29/2010 and
SR/S1/OC-22/2006), CRNN (C.U.) and CSIR (JRF and SRF),
India is gratefully acknowledged.
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Similarly, difunctionalization of olefin involves syn-addition
of PhI(OAc)2 and halide ion (X:, I, eqn (4)) and subsequent
reductive elimination (J) in a stereoelectronically anti fashion.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 6933–6935 6935