December 1998
SYNLETT
1321
Chemoselectivity of Tetrabutylammonium Borohydride towards Bifunctional Esters
a
b
S. Narasimhan , S. Swarnalakshmi , R. Balakumar, S. Velmathi
a
Centre for Agrochemical Research, SPIC Science Foundation, Guindy, Chennai 600032, India
b
Department of Chemistry, Guru Nanak College, Vellechery, Chennai 600032, India
Received 1 August 1998
Abstract: Chemoselective reduction of functional groups in the
presence of esters is observed with tetrabutylammonium borohydride in
chloro solvents.
Reduction of methyl cinnamate followed by protonolysis gave methyl
3-phenylpropionate due to the reduction of α:β unsaturation without
affecting the ester group.
Chemoselective reduction of esters in the presence of alkenes by metal
borohydrides has always resulted in the tandem reduction hydroboration
reaction. Significant differences in the reactivity has been observed with
different metal ions. Thus lithium borohydride in ether reacts faster and
Indeed the ester group in a number of substrates with other nucleophilic
functional groups remained unaffected. Reduction of acid esters like
methylhydrogen phthalate and monomethyl azelate in refluxing
chloroform yielded hydroxy esters indicating the selectivity of the
1
also hydroborates nearly three equivalents of alkenes per ester .
Calcium borohydride is less reactive and hydroborates only one
equivalent of alkene, and needs excess alkene to proceed to an uptake of
5
2
reagent .
two equivalents of the unsaturated compound . On the other hand zinc
3
borohydride exhibited borane like electrophilicity . Evidently
polarisability of the anion and the coordination of the cation are
responsible for the observed results.
Also, reduction of these acid esters followed by PCC oxidation yielded
the corresponding aldehyde esters which are useful intermediates in the
synthesis of insect sex pheromones.
In an attempt to find a suitable borohydride which would reduce the
ester chemoselectively, we chose tetrabutylammonium as the cation,
since its coordination ability is very poor. Interestingly, this reagent did
not reduce even the highly reactive methyl-10-undecenoate in THF.
However, in chlorinated solvents this resulted in the reversed selectivity
i.e., hydroboration of the double bond occurred in preference to the
reduction of the ester group. This prompted us to undertake a study on
the selective reduction /hydroboration using tetrabutyl ammonium
borohydride in chlorinated solvents.
The selectivity was also extended to amide esters. For example,
p-carbomethoxy acetanilide on reduction gave N-ethyl -p-methyl-
benzoate as the product.
Tetrabutylammonium borohydride was prepared as reported earlier by
the ion displacement reaction of sodium borohydride with
tetrabutylammonium hydrogen sulphate . The reagent undergoes slow
decomposition in chloro solvents at room temperature and reflux
temperature presumably due to the reduction of C-Cl bond by the
In an attempt to reduce imine esters to the corresponding secondary
amine esters while, borane undergoes complex formation with the basic
nitrogen thereby retarding the reduction reaction tetrabutylammonium
borohydride reduces the imine esters without the complex formation.
4
reagent in the order CH Cl <CHCl <CCl <CH Cl-CH Cl. Analysis of
2
2
3
4
2
2
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the chloroform solution by B NMR showed a peak around -27.4ppm
corresponding to B H species, indicating the availability of
-
2
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electrophilic borane like species for electrophilic reactions.
Reduction of various unsaturated esters like methyl-10-undecenoate,
methyl cinnamate, and methyl-10-undecynoate were carried out in
refluxing chloroform. Although several borohydride reagents including
borane reacted with methyl-10-undecenoate to produce the diol, under
the present conditions the ester group remained unaffected. Alkyne
function presumably undergoes dihydroboration since this produced
only the alcohol.
In conclusion, this reagent tolerates the presence of ester groups and
selectively reduces other functional groups including amides and imines
without the formation of amine borane complex, contrary to borane
Narasimhan
