Facile and chemoselective cleavage of allyl carboxylic ester utilizing NaBH4 in DMSO

Article abstract of DOI:10.1080/00397910902963694

A new method for deprotection of allyl carboxylic ester has been observed by using the inexpensive reagent sodium borohydride in dimethyl sulfoxide (DMSO). Aliphatic and aromatic allyl carboxylic ester undergo deprotection smoothly. The allyl ester group can selectively deprotect better than phenol.

Full text of DOI:10.1080/00397910902963694

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Facile and Chemoselective
Cleavage of Allyl Carboxylic
Ester Utilizing NaBH4 in DMSO
Bharati V. Pawar a & Pradeep D. Lokhande a
a Center for Advanced Studies, Department of
Chemistry , University of Pune , Pune, India
Published online: 16 Jun 2009.
To cite this article: Bharati V. Pawar & Pradeep D. Lokhande (2009) Facile and
Chemoselective Cleavage of Allyl Carboxylic Ester Utilizing NaBH4 in DMSO, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:14, 2445-2453, DOI: 10.1080/00397910902963694
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Synthetic Communications1, 39: 2445–2453, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902963694
Facile and Chemoselective Cleavage of Allyl
Carboxylic Ester Utilizing NaBH4 in DMSO
Bharati V. Pawar and Pradeep D. Lokhande
Center for Advanced Studies, Department of Chemistry,
University of Pune, Pune, India
Abstract: A new method for deprotection of allyl carboxylic ester has been
observed by using the inexpensive reagent sodium borohydride in dimethyl sulfox-
ide (DMSO). Aliphatic and aromatic allyl carboxylic ester undergo deprotection
smoothly. The allyl ester group can selectively deprotect better than phenol.
Keywords: Allyl aryl ether, allyl ester, chemoselective, deallylation, sodium
borohydride
The allyl group is frequently used as a suitable protecting group for
acids,[1] alcohols,[2] and amines[3] in the synthesis of carbohydrates,[4] pep-
tides,[5] and nucleotides.[6] Because the reaction easily forms allyl ester
and is stabile under different conditions, it is now generally used in the
liquid- or solid-phase synthesis of a wide range of natural products.[7]
The reported method for deallylation is a two-step procedure that
includes isomerization to the more labile 1-propenyl group followed by
either acid hydrolysis or oxidation of the resulting ether. Isomerization
of the allyl to prop-1-enyl group has been classically achieved by potas-
sium tertiary-butoxide base.[8] The most frequently employed conditions
for deallylation are treatment of allyl carboxylic ester with palladium
complexes[9] and the use of a stoichiometric amount of nucleophiles,
including NaBH4,[10] HCOOH,[11] LiAlH4,[12] LiBHEt3,[13] and LiBH4.[14]
Received June 1, 2007.
Address correspondence to Pradeep D. Lokhande, Center for Advanced
Studies, Department of Chemistry, University of Pune, Pune 411007, India.
E-mail: pdlokhande@chem.unipune.ernet.in
2445

2446
B. V. Pawar and P. D. Lokhande
Excess nucleophile is required in this transition-metal-activated
deallylation procedure. In 1980, Hutchins and coworkers reported the
chemoselective cleavage of allylic acetate by hydride transfer from donors
[10]
such as NaBH4
and NaCNBH3 via catalytic activators.[15] The high
cost of transition-metal reagents, partial poisoning of the catalyst, competi-
tive reduction of the allyl to the propyl group, and other side reactions that
may occur during the isomerization process prompt our search for new
reagents. Several other one-step methods have been developed using
sodium borohydride reagent, including NaBH4=I2,[15] ZrCl4=NaBH4,[16]
NaBH4=PdPPh3,[17] NaCNBH3=TMSCl,[18] and NaBH4=EtOH=Ni
complex.[19]
Allylic esters (1) were prepared using conventional techniques (potas-
sium hydroxide [KOH], allyl bromide, dimethyl sulfoxide [DMSO]) in
70–90% yields at room temperature. The deprotection proceeded by the
treatment of the allyl esters (1) with excess of sodium borohydride in
DMSO at room temperature until thin-layer chromatography (TLC)
indicates that no starting material remains in the reaction mixture
(Scheme 1). The reaction was quenched by adding dilute hydrochloric
acid (1 N) to remove excess sodium borohydride. The reaction mixture
was extracted in an organic solvent and dried over anhydrous Na2SO4.
Removal of solvent afforded the desired acids (2). Results are summar-
ized in Table 1. This reaction requires anhydrous condition and an
inexpensive reagent. The reaction is performed at room temperature
and progresses well in all weather conditions. We applied the present
reaction to various types of substituted allylester for conformation of
scope and limitation. The allylesters were readily deprotected because
of the electron-withdrawing group on the benzene ring to give the corre-
sponding acid (2d, 2e). It is noteworthy that the amide, nitro, chloro,
bromo, and methyl ester groups in the substrates remain intact during
the reaction. In some of the deallylation procedures using NaBH4, it
was reported that some reducible functionality (such as cyanide, ester,
acetonitrile, and tetrahydropyranyl groups) was unaffected.[20]
When the same reaction conditions were applied to cinnamyl ester
deallylation, the reaction proceeded smoothly to give the corresponding
acid in good yield. Allyl cinnamate was deallylated without reducing
Scheme 1. Reagents and conditions: NaBH4 (2 eq), DMSO, rt, 10–25 h.

Cleavage of Allyl Carboxylic Ester
2447
Table 1. Deallylation of allyl esters
Yielda
(%)
No.
Reagent
Product
2a
92
2b
85
2c
2d
91
87
2e
89
2f
84
85
2g
2h
82
2i
2j
80
92
2k
No reaction
—
(Continued )

2448
B. V. Pawar and P. D. Lokhande
Table 1. Continued
Yielda
(%)
No.
Reagent
Product
2l
87
2m
2n
81
76
2o
2p
81
92
aYield of isolated purified product.
the alkene double bond. Aromatic and aliphatic allyl esters undergo
deprotection; however, aliphatic esters are relatively sluggish. All
compounds were isolated in moderate to good yield. Interestingly, in
the reaction of allyl-a-allylphenyl acetate (2p), which has two types of
allyl group, the allylester bond was selectively cleaved to give a-allyl
phenylacetic acid in the presence of NaBH4 at room temperature in 15 h.
The excellent results described here promoted us to examine the
possibility of applying the same cleavage condition to cleave the car-
bon–oxygen bond in allyl aryl ether. Literature search shows that allyl
O, S, and Se bonds are cleaved with various borohydrides such as
NaBH4,[10] NaCNBH3,[18] and LiBHEt3.[13] Also, NaBH4 is used for
regioselective deoxygenation of the allylic benzoates and desulfonation

Cleavage of Allyl Carboxylic Ester
2449
Scheme 2. Reagents and conditions: NaBH4 (3 eq), DMSO, rt, 48 h.
of 2-tosylhomoallylic alcohol using Pd0 complex.[21] Beside this, NaBH4=
MeOH has been used for reductive C-C bond cleavages of norborenyl
esters.[22] It has been reported that allylic ethers are converted to the cor-
responding alcohol by using nucleophile R-Li.[23]
Treatment of allyl salicylaldehyde 3 with sodium borohydride in
DMSO reduces the aldehyde group within 20–30 min. The allyloxy
salicylalcohol 4 was isolated and characterized by 1H NMR. It was
further stirred with NaBH4 for 48 h, but the desired product was not
obtained and compound 4 remained unreacted (Scheme 2). The same
reaction was observed in the cases of allyloxy vanillin and o-vanillin;
results are summarized in Table 2. Similarly, allyloxy p-chlorophenol,
allyloxy p-cresol, and allyloxyphenol ether were not deallylated even with
refluxing at 50–60ꢀC for 10 h. The results of deallylation of ally phenol
ether clearly indicate that NaBH4 in DMSO is a selective reagent for deal-
lylation of the carboxylic allyl ester group and not for the phenolic allyl
ether group. Allyl salicylate was prepared for confirmation of this possi-
bility, which under similar conditions deprotected to give salicylic acid.
Table 2. Deallylation of allyl aryl ethers
No.
Reagent
Product
Yielda (%)
87
3a
3b
3c
82
86
aYield of isolated purified product.

2450
B. V. Pawar and P. D. Lokhande
Although allyloxy allylsalicylate 2b underwent deallylation of only allyl
carboxylic ester and allyl aryl ether remained intact, allyloxy methylsali-
cylate 2g did not undergo the deallylation reaction.
Earlier, we reported our previous results on the deallylation of
2-allyloxychalcones[24] allyl carboxylic ester,[25] and allyl phenol ether
with iodine in DMSO.
In conclusion, this work provides a new deallylation procedure for a
variety of allyl carboxylic esters. Although the reaction is sluggish, it does
not require activation of expensive transition-metal complexes. However,
this methodology is incompatible with electrophilic aldehyde and
ketones. Moreover, the present reaction selectively cleaved the allyl ester
bond in the presence of allyl aryl ether.
GENERAL PROCEDURE FOR SYNTHESIS OF ACIDS (2)
FROM ALLYL ESTERS (1)
A solution of compound 1 (10 mmol) in DMSO (3 mL) was stirred at room
temperature for 30 min, and NaBH4 (20 mmol) was added in two steps.
The reaction mixture was stirred continuously at room temperature for
10–24 h. The excess of NaBH4 was destroyed by addition of HCl (1N),
and stirring continued for 30 min. The solvent was removed, and aqueous
solution was extracted with ether (2 ꢁ 10 mL). The combined organic
extracts were washed with brine and dried over anhydrous Na2SO4. The
crude product was purified by column chromatography on silica gel (60–
120 mesh) [eluent hexane–ethyl acetate (9:1)] to afford the pure product 2.
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