Lewis acid catalyzed protective opening of epoxides with pivaloyl halides

Article abstract of DOI:10.14233/ajchem.2015.18053

An efficient protocol of shorter reaction times for protective opening of epoxides (POE) with pivaloyl halides under solvent-free conditions in presence of Lewis acid catalysts has been developed.

Full text of DOI:10.14233/ajchem.2015.18053

Asian Journal of Chemistry; Vol. 27, No. 8 (2015), 2795-2797
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SIAN
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OURNAL OF HEMISTRY
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http://dx.doi.org/10.14233/ajchem.2015.18053
Lewis Acid Catalyzed Protective Opening of Epoxides with Pivaloyl Halides
1,*
2
2
1
TULAM VIJAYA KUMAR , T. VINAY BHARADWAJ , K. UKKANTI and PRATHAMA S. MAINKAR
1Evolva Biotech Private Limited, TICEL Bio Park Limited, Taramani, Chennai-600 113, India
2Centre for Chemical Sciences and Technology, IST, Jawaharlal Nehru Technological University-Hyderabad, Kukatpally, Hyderabad-500 085, India
*Corresponding author: Tel/Fax: +91 44 42971050/60, E-mail: vijaykumar.thulam@gmail.com
Received: 21 May 2014;
Accepted: 6 August 2014;
Published online: 27 April 2015;
AJC-17133
An efficient protocol of shorter reaction times for protective opening of epoxides (POE) with pivaloyl halides under solvent-free conditions
in presence of Lewis acid catalysts has been developed.
Keywords: Lewis acid, Epoxides, Protective opening, Pivaloyl halides.
INTRODUCTION
EXPERIMENTAL
Epoxides1 are well known most versatile compounds
in organic synthesis. Due to their ease of formation, wide
reactivity with nucleophiles and their ability to undergo region
selective ring opening2,3 reactions contributes their synthetic
value not only as final products but also as key intermediates4,5.
Preservation and protection of the oxirane ring is one of
the most important aspects during the many cases in total
synthesis6,7 of biologically active natural products8,9. Epoxides
due to their highly strained three-membered ring and
difficulties in the stability aspects they tend to react with a
wide variety of reagents such as electrophiles, nucleo-
philes10, acids, bases, some reducing agents and oxidizing
agents11,12. To side step these problems, there is a substantial
need for protective opening of the oxirane ring13 into its
derivatives from which it can be easily reconstructed with
consistent regio-selectivity and stereo-selectivity14,15. Green
chemical reactions have become more important in recent
decades. Reactions in solvent free conditions are considerably
safer, nontoxic, environmentally friendly and inexpensive.
The present needs for clean, fast, efficient and selective
processes have promoted the demand for metal-based
reaction promoters, especially the ones that can be applied in
catalytic amounts and/or that are recyclable. Shorter reaction
times are of utmost importance to make the synthetic chemistry
viable in many applications.Although there are many protocols
for epoxide ring opening, to the best of our knowledge only
one method is reported so far to prepare vic-halopivaloylates
with pivaloyl halides16. Here in we are reporting the Lewis
acid catalyzed protective opening of epoxides with pivaloyl
halides.
All the chemicals employed in this study were procured
from SigmaAldrich. In present study, all the synthetic reactions
were monitored by TLC. All the synthesized compounds were
confirmed by different spectroscopic methods. The IR spectra
were recorded using KBr pellets on a Perkin Elmer IR spec-
1
trophotometer. H NMR spectra were recorded on Brucker
300 MHz Avance NMR spectrophotometer using CdCl3 as
solvent and TMS as internal standard (chemical shifts in δ
ppm). The Mass spectra were recorded onAgilent 6300 series
ion trap.
General procedure: Epoxide (0.01 mmol) is treated with
pivaloyl halides (0.01 mmol) in presence of catalytic amount
of Lewis acid (a-i). The reaction was stirred for 5 to 10 min
and monitored the progress of the reaction by TLC.
RESULTS AND DISCUSSION
In order to find out the suitable conditions, the reaction
of glycidol 4-methoxyphenyl ether with pivaloyl chloride was
used as a model reaction for screening of different catalysts
under solvent free conditions and the results were presented
in the Table-1. All the catalysts used i.e. ZnCl2, FeCl3, MoCl5,
B(C6F5)3, SnCl4, TMS-OTf, Sn(OTf)2, Cu(OTf)2 and I2 were
found to be effective towards the protective opening of
epoxides with pivaloyl halides. It was observed that glycidol
4-methoxyphenyl ether (1a) reacts with pivaloyl iodide (2a)
to afford the product 3a in 99 % yield with high regio-selectivity
in presence of 5 mol % of iron chloride (Scheme-I and II).
Trimethyl silyl triflate, tin triflate, copper triflate gave the
desired products in 60 to 70 % yields in 5 to 10 min of the
time. Desired product was obtained after 12 h when the reaction

2796 Kumar et al.
Asian J. Chem.
OP iv
I
TABLE-1
O
SCREENING OF LEWIS ACID CATALYSTS FOR PROTECTIVE
O
O
OPENING OF EPOXIDES WITH PIVALOYL HALIDES
Piv-I/FeCl3 (5 mol %)
Lewis acid
(5 mol %)
FeCl3
SnCl4
MoCl5
B(C6F5)3
I2
Room temperature,
5 min, 99 %
MeO
MeO
Entry
Time (min)
Yield (%)
(
3a)
(
1a)
A
B
C
D
E
F
G
H
I
5
5
5
10
5
5
10
10
10
720
99
88
80
81
90
92
67
65
70
99
Scheme-I: Protective opening of epoxide with Piv-Cl in presence of Lewis
acid catalyst-under solvent free conditions
was carried out in the absence of catalyst. Although, most of
these Lewis acids provided good to better yields. Iron chloride,
for obvious reasons (being cheapest, milder conditions and
easy to handle) was chosen for further experiments and results
were mentioned in the Table-2. Epoxides from 7 to 9 were
ZnCl2
TMS-OTf
Sn(OTf)2
Cu(OTf)2
-
J
TABLE-2
LEWIS ACID CATALYZED PROTECTIVE OPENING OF EPOXIDES (POE)
WITH PIVALOYL HALIDES UNDER SOLVENT FREE CONDITIONS
Entry
Substrance
Pvi-X
Product
Reaction time (min)
Yield (%)
OPiv
OPiv
OPiv
OPiv
O
O
O
O
O
O
O
O
O
Cl
Cl
Cl
Cl
O
O
O
O
O
5
99
1
2
But
But
But
But
But
Cl
Cl
Cl
Cl
Cl
MeO
MeO
Cl
O
O
O
5
96
96
95
98
97
Cl
10
3
4
5
10
10
OPiv
O
O
Cl
OPiv
O
O
10
5
6
O
But
But
Cl
Cl
O
Cl
O
O
95
94
O
7
8
9
O
O
O
Cl
O
10
But
But
Cl
Cl
O
O
O
Cl
O
O
O
O
Cl
5
5
O
O
O
96
95
O
O
O
Cl
O
But
But
Cl
Br
10
11
O
OPiv
OPiv
OPiv
O
O
O
O
O
O
Br
Br
Br
O
O
O
5
5
5
99
99
98
MeO
MeO
O
O
12
13
But
But
Br
Br
Cl
Cl
OPiv
OPiv
O
O
O
O
O
I
I
I
O
O
O
O
99
94
5
5
14
15
16
But
I
MeO
MeO
O
O
But
But
I
I
OPiv
O
5
96
Cl
Cl

Vol. 27, No. 8 (2015)
Lewis Acid Catalyzed Protective Opening of Epoxides with Pivaloyl Halides 2797
FeIII
FeIII
ACKNOWLEDGEMENTS
O
O
O
The authors are thankful to management of Evolva
Biotech Pvt. ltd, India, Indian Institute of chemical Technology,
Hyderabad for their constant support and encouragement.
R
X
R
O
FeIII
FeIII
O
REFERENCES
O
O
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to 12 were treated with pivaloyl iodide. The rate of reaction
increased gradually from Cl to Br to I. In all attempts, the
reactions proceeded smoothly; the epoxide ring opening
appeared to be region specific. The corresponding vic-halo
pivaloylates were obtained in excellent yields in all cases. The
results were summarized in Table-2.
Conclusion
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reaction timings from hours to minutes. An efficient protocol
for protective opening of epoxide (POE) in presence of Lewis
acid catalysts under solvent free conditions with shorter
reaction timings was achieved.
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