402 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 402±403$
(Chlorosulfinyloxy)-N,N-dimethylmethaniminium
Chloride Mediated Direct and Chemoselective
Conversion of Carboxylic Acids into
Aldehydes$
R. H. Khan* and T. S. R. Prasada Rao
Indian Institute of Petroleum, Dehradun - 248 005, India
A new method for the direct conversion of carboxylic acids into aldehydes using (chlorosulfinyloxy)N,N-dimethylmetha-
niminium chloride and lithium triethylhydroborate (super-hydride) was established which provides a convenient way for
the chemoselective reduction of carboxylic acids even with such functional groups as halide, ester, nitrile, olefin and
ketone.
Aldehydes often play an important role in organic syn-
thesis. In general, carboxylic acids are transformed into
aldehydes after ®rst converting them into carboxylic acid
derivatives which are more easily reduced or designed
to produce stable intermediates of similar reducibility.
Several processes have been employed to eect aldehyde
synthesis: the Rosenmound reduction1 or hydride reduction
of acid halides,2 tertiary amides,3 esters and lactones4 and
other derivatives.5 It is very dicult to obtain aldehydes
by direct reduction of carboxylic acids6 because of the
easier reduction of the aldehydes. A few methods for
the direct reduction have been reported which use lithium
methylamide,7 bis(N-methylpiperidinyl)aluminium hydride,8
thexylborane9 or Grignard reagents catalysed by dichloro-
bis(Z-cyclopentadienyl)titanium.10 However, they seem to
be lacking in general applicability and chemoselectivity
because of the dierent reaction conditions. On the other
because of their solubility. Addition of lithium catalyst
hand a process which involves activation of carboxylic acids
increases the yield. The best solvent system was a mixture of
in situ and then attack of nucleophiles was used to give
the esters, amides and acid chlorides selectively. Accordingly
acetonitrile and THF; independent use of other solvents
resulted in decreased yield of the aldehydes. Other reduc-
the reduction of selectively activated intermediates of car-
tants such as NaBH4 and NaBH(OMe)3 resulted in further
boxylic acids in situ can provide a chemoselective synthetic
reduction to give alcohols. Both aliphatic and aromatic alde-
method for aldehydes by easier reduction of the activated
hydes were obtained in high yields from the corresponding
carboxylic acids than that of other functional groups. We
carboxylic acids in a one-pot operation. Aromatic carboxylic
report herein an example of a simple and chemoselective
acids with halogen, nitro or methoxy substituents were
method to convert carboxylic acids into aldehydes using
reduced chemoselectively to the corresponding aldehydes.
(chlorosul®nyloxy)N,N-dimethylmethaniminium chloride and
LiBEt3H in a one-pot operation, which enlarges the range
Although heteroaromatic carboxylic acids such as furoic
acid and nicotinic acid gave the corresponding aldehydes,
of application of this concept and suggests a variety of new
the yield was low in the case of the nicotinaldehyde due to
synthetic possibilities.
(Chlorosul®nyloxy)N,N-dimethylmethaniminium chloride11
is known to activate carboxylic acid groups for the prep-
poor solubility.
Ole®ns, which react with boron hydrides, are tolerant and
geranic acid was easily converted into geranial with reten-
tion of stereochemistry (experiment 16). The characteristics
of the reduction with the mild reductant LiBEt3H were
aration of acid chlorides,12 alkyl chlorides13 gem-dichlor-
ides14 and ketones.15 Accordingly chemoselective conversion
of carboxylic acids into aldehydes could be achieved when
also seen in the aliphatic series and other various type of
active carboxysul®nyloxymethaniminium chloride 1 derived
in situ from chlorosul®nyloxy-methaniminium chloride and
substituents can also be tolerated, even those which might
be considered susceptible to reduction by complex hydrides,
carboxylic acids was reduced with metal hydride to yield
such as bromo, cyano and ester groups. Carboxylic acids
a stable betaine 2 as an intermediate which was in turn
converted into aldehydes. Thus, a mixture of carboxylic
with such groups were converted chemoselectively into
the corresponding aldehydes in high yield. Furthermore,
6-oxooctanoic acid, a carboxylic acid with a second carbo-
nyl group, gave 6-oxooctanal in high yield. This result
shows that the carboxyiminium salt can be reduced more
easily than a carbonyl group and that this technique should
be useful for the reduction of complex molecules in natural
product synthesis.
acids and freshly prepared (chlorosul®nyloxy)N,N-dimethyl-
methaniminium chloride in the presence of triethylamine
was added 10 mol% LiI and LiBEt3H at 78 8C. Usual
work-up gave the corresponding aldehydes as shown in
Table 1.
When lithium carboxylates were used in place of the
carboxylic acid±triethylamine system the yields decreased
The good results obtained in the present method are
achieved by a combination of a reductant and the activation
of the carboxylic acids. The high chemoselectivity and easy
transformation into aldehydes by the reduction of carboxylic
acids using the iminium salt makes the method attractive
and widely applicable.
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
Khan
