Simple, one-pot procedure for the generation of homoallylic alcohols from barbier-type allylation of gem-diacetates in the presence of β-cyclodextrin in water

Article abstract of DOI:10.1080/00397910701356371

A novel and highly efficient allylation of gem-diacetates using allylbromide has been developed in aqueous medium catalyzed by β-cyclodextrin in the presence of Zn-mediated Barbier-type allylation to afford the corresponding homoallylic alcohols in good y

Full text of DOI:10.1080/00397910701356371

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Simple, One‐Pot Procedure for the
Generation of Homoallylic Alcohols from
Barbier‐Type Allylation of Gem‐diacetates in
the Presence of β‐Cyclodextrin in Water
a
a
a
a
M. Somi Reddy , M. Narender , Y. V. D. Nageswar & K. Rama Rao
a
Organic Chemistry Division I, Indian Institute of Chemical Technology,
Hyderabad, India
Available online: 22 Jun 2007
To cite this article: M. Somi Reddy, M. Narender, Y. V. D. Nageswar & K. Rama Rao (2007): Simple, One‐Pot
Procedure for the Generation of Homoallylic Alcohols from Barbier‐Type Allylation of Gem‐diacetates in
the Presence of β‐Cyclodextrin in Water, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 37:12, 1983-1988
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Synthetic Communications , 37: 1983–1988, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701356371
Simple, One-Pot Procedure for the
Generation of Homoallylic Alcohols from
Barbier-Type Allylation of Gem-diacetates
in the Presence of b-Cyclodextrin in Water
M. Somi Reddy, M. Narender, Y. V. D. Nageswar, and
K. Rama Rao
Organic Chemistry Division I, Indian Institute of Chemical Technology,
Hyderabad, India
Abstract: A novel and highly efficient allylation of gem-diacetates using allylbromide
has been developed in aqueous medium catalyzed by b-cyclodextrin in the presence of
Zn-mediated Barbier-type allylation to afford the corresponding homoallylic alcohols
in good yields. The b-cyclodextrin can be recovered and reused for a number of runs
without significant loss of activity.
Keywords: allylbromide, b-cyclodextrin, gem-diacetates, homoallylic alcohols, water
INTRODUCTION
The allylation of carbonyl compounds with allyl halides is a very important
reaction, and numerous reagents and methods have been developed to accom-
[
1]
plish this transformation. Homoallylic alcohols are useful tools for the
construction of complex molecules and important building blocks for
[
2]
the synthesis of natural products.
Among various protecting groups,
gem-diacetates have been recognized as the method of choice because of
their easy installation and removal and their stability in a variety of reaction
Received in the USA October 26, 2006
Communication no. 061015.
Address correspondence to K. Rama Rao, Organic Chemistry Division I, Indian
Institute of Chemical Technology, Hyderabad 500 007, India. E-mail: ramaraok@
iict.res.in
1
983

1
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M. S. Reddy et al.
conditions. Apart from this, these gem-diacetates are useful synthetic inter-
However, the methodology
[3,4]
mediates in various organic transformations.
involving direct allylation of gem-diacetates is highly advantageous over a
two-step procedure of converting gem-diacetates to carbonyl compounds and
then allylating later.
Most of the methods reported utilize different procedures and acid
catalysis for conversion of gem-diacetates to homoallylethers.
[5]
These
reactions are usually carried out under strictly anhydrous conditions with
various limitations such as hazardous organic solvents, tedious workup, low
yields, and moisture-sensitive reagents.
Hence, there is need to develop a new methodology for the allylation of
gem-diacetates, especially using water as the solvent with a recyclable catalyst
and without any organic solvents. Organic reactions in water have been widely
studied to minimize the use of organic solvents, most of which are flammable,
[
6]
toxic, or carcinogenic. Our earlier expertise in the biomimetic modeling of
[
7]
organic reactions, prompted us to attempt C-C bond formation, through
supramolecular catalysis involving cyclodextrin with Zn-mediated allylation
reaction in water. Zinc is commonly accepted as nontoxic and is usually
[8]
activated in aqueous Barbier reactions.
Cyclodextrins (CDs) are cyclic oligosaccharides, which exert a micro-
environmental effect. They catalyze reactions by supramolecular catalysis
through noncovalent bonding as in enzymes. These attractive features of
cyclodextrins in the biomimetic modeling of chemical reactions prompted
us to investigate the allylation of a variety of gem-diacetates.
RESULTS AND DISCUSSION
Herein, we describe an efficient method for the one-pot synthesis of homo-
allylic alcohols with deprotection followed by allylation of gem-diacetates
in the presence of b-cyclodextrin and Zn/allyl bromide/NH Cl under
4
biomimetic conditions with water as the solvent (Scheme 1).
These reactions were carried out by dissolving a catalytic amount of
b-CD (0.1 mmol of CD per 1 mmol of the substrate) in water at 608C,
followed by the addition of the substrate and Zn/allyl bromide/NH Cl and
4
stirring at that temperature until the reaction was complete. The yields of
the products were impressive, ranging from 80 to 85%. This method is
Scheme 1. R ¼ H, p-Cl, p-Me, p-OMe.

Synthesis of Homoallylic Alcohols
1985
Table 1. b-CD-catalyzed allylation of gem-diacetaes using Zn/allyl bromide in
aqueous media
Time
(h)
Yield
b
(%)
a
Entry
1
Substrate
Product
7
8
8
7
82
88
87
81
2
3
4
5
6
7
8
8
88
86
9
81
(
continued)

1
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M. S. Reddy et al.
Table 1. Continued
Time
(h)
Yield
b
(%)
a
Entry
8
Substrate
Product
8
82
9
10
84
1
0
1
9
9
84
85
1
1
1
1
2
3
4
8
8
8
85
80
82
a
b
1
All the products were characterized by MS, H NMR, and IR spectroscopy.
Isolated yields.

Synthesis of Homoallylic Alcohols
1987
compatable with functionalities such as hydroxy, methoxy, bromo, chloro,
nitro, and olefinic bonds. All the products reported are known and were
1
characterized by H NMR, MS, and IR and by comparison with known com-
[
9,7e]
pounds.
by the formation of hydrogen bonding, thereby facilating its cleavage
Here, the role of b-CD appears to be to activate the acetyl group
in
[10]
situ and also enhancing the activity of carbonyl oxygen for Barbier-type ally-
lation reaction. These reactions did not take place in the absence of CD. b-CD
was used as a catalyst because it is inexpensive and can also be recovered and
reused. Although these reactions do take place with aliphatic gem-diacetates,
the yields are less than satisfactory (10–15%).
In conclusion, we have developed a simple and efficient procedure for the
direct allylation of gem-diacetates with allylbromide and Zn-mediated Barbier
reaction in the presence of a reusable catalyst (b-CD) in water.
EXPERIMENTAL
Materials
All reactions were carried out without any special precautions in an atmos-
phere of air. Chemicals and solvents were purchased from Fluka and S. D.
1
Fine Chemicals and used as received. H NMR spectra were obtained
on a Gemini 200- or 300-MHz spectrometer; IR spectra were recorded on
a Nicolet FT-IR spectrometer and mass spectra on V. G. Auto spectrometer.
Typical Experimental Procedures (Scheme 1)
To a solution of b-CD (0.1 mmol) dissolved in distilled water (20 ml) by
heating at 608C, the substrate gem-diacetate (1.0 mmol) was added slowly
with stirring. After 15 min at this temperature, zinc powder (1.2 mmol),
allyl bromide (1.2 mmol), and NH Cl (2.0 mmol) were added sequentially,
4
and the mixture was stirred at 608C until the reaction was complete
(Table 1). The reaction mixture was cooled to room temperature, extracted
with ethyl acetate (3 Â 151), and washed with brine solution. The organic
phase was dried over anhydrous sodium sulfate and concentrated under
vacuum. The crude product thus obtained was purified by column chromato-
graphy on silica gel (60–20 mesh) using ethyl acetate–exane (2:8) as an
eluent. The aqueous layer was cooled to 58C to precipitate b-cyclodextrin,
which was recovered by filtration (95%).
ACKNOWLEDGMENT
We thank CSIR, New Delhi, India, for fellowships to M. S. R. and M. N.

1
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M. S. Reddy et al.
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