Allylation of Aldehydes Promoted by Carboxylic Acids
SCHEME 2. Proposed Mechanism for the Regioselective Allylation Promoted by Carboxylic Acids
ppm; b in Figure 3). At the same time, allyltributyltin
disappeared gradually (as indicated by the disappearance
of the peaks at about δ 1.76, 4.6, and 4.7 ppm; c and e in
Figure 3, respectively). During this reaction, it was
observed that the heterogeneous reaction mixture (as
revealed in Table 1, p-nitrobenzoic acid is only slightly
soluble in CH3CN) gradually became homogeneous. Cor-
respondingly, as illustrated in Figure 3, new peaks at
about 8.2 ppm appeared gradually indicating the forma-
tion of tributyltin ester of p-nitrobenzoic acid (p-nitroben-
zoic acid is insoluble in CDCl3, as shown in Figure 3, (1)),
which is confirmed by comparison with the 1H NMR
spectrum of the tin ester prepared independently18
(Figure 3, (5)).
proceed by a S′E2 (open) mechanism to afford the γ-ad-
duct (7) exclusively.1,20 Therefore, it may be understood
that the carboxylic acids, as Lewis acids, could promote
the crotylation through a S′E2 mechanism predominantly
(III, path B, Scheme 2). This is observed in the case of
p-nitrobenzoic acid and the low distereoselectivity (syn/
anti) can be ascribed to its weak action toward the
aldehydes through hydrogen bonding (entry 1, Table 5).
On the other hand, the increasing acidity of carboxylic
acids was accompanied by an increase in the donor ability
of the carboxylate anion. It might facilitate the coordina-
tion to the Sn (the C-Sn bond fission under the nucleo-
philic attack of various carboxylic acids may throw light
on this).21 Therefore, 2b should be attacked by I on C1
involving a six-centered cyclic transition state (SE2,
closed) other than on C3 involving eight-centered ones
(S′E2, closed) (II, path A, Scheme 2). This is observed in
the cases of maleic acid and trifluoroacetic acid, in which
R-adducts are obtained as the major products (entries
3-7, Table 5). In addition, experiments22 proved that it
is impossible to produce the mixture of adducts by the
rearrangement23 between adducts 4 and 5 under these
reaction conditions.
At the same time, we performed another experiment
in which the allyltributyltin was stirred in the presence
of p-nitrobenzoic acid for about 21 h and monitored by
1H NMR. Only trace decomposition of the allyltributyltin
was observed. To further disclose the mechanism of the
allylation, the mixture of o-phthalic acid and allyltribu-
1
tyltin in acetonitrile was stirred and monitored by H
NMR as above. It was found that allyltributyltin had
decomposed completely within 230 min. In addition, in
the allylation promoted by maleic acid, allyltributyltin
disappeared within 1 h according to TLC. These facts
support the observation that the acidity of the carboxylic
acid plays an important role in weakening the C-Sn
bond, and this action makes the allyltributyltin more
nucleophilic and at the same time more susceptible to
decomposition.
At this time, the exact process of the regioselective
crotylation promoted by carboxylic acids is not very clear.
Based on the results of experiments, a possible mecha-
nism is proposed. First, the aldehyde (1) is activated by
the carboxylic acid through hydrogen bonding. Then, in
general, the resulting electrophile intermediate I could
attack 2b on C1 (adjoining tin atom) or C3 through two
pathways, namely SE2 and S′E2, respectively.19 It is
known that strong Lewis acids mediating crotylation
Conclusion
A novel, general, and practical method of allylation of
aldehydes promoted by carboxylic acids under mild
conditions has been developed. Under the promotion of
p-nitrobenzoic acid, the allylation of various aldehydes
with allytributyltin proceeded smoothly to provide high
to quantitative yields of the homoallylic alcohols. p-
Nitrobenzoic acid could be recovered by working up with
HCl (2 M). The regioselectivity of the crotylation of
aldehydes was also studied. The R-adduct could be
(20) Denmark, S. E.; Shinzo, H. J. Org. Chem. 1994, 59, 5133-5135.
(21) (a) Rappoport, Z. The Chemistry of Organic Germanium, Tin
and Lead; Wiley: New York, 2002; Vol. 2, Part 2, p 963. (b) If
benzaldehyde was added after the mixture of crotyltributyltin and
maleic acid in acetonitrile was stirred for 3 h, no desired product was
obtained. TLC indicated that crotyltributyltin was decomposed.
(22) (a) The mixture of the pure compound 7a (1.0 equiv), benzal-
dehyde (1.0 equiv), and trifluoroacetic acid (1.0 equiv) was stirred for
1.0 h in acetonitrile. And no 6a was produced. (b) No 6a was produced
after the mixture of the pure compound 7a (1.0 equiv), benzaldehyde
(0.5 equiv), CF3CO2SnBu3 (0.5 equiv), and trifluoroacetic acid (0.5
equiv) was stirred for 1.0 h in acetonitrile. (c) The 1H NMR study of
crotylation of benzaldehyde shows that adducts 6 and 7 are produced
simultaneously.
(16) (a) Hoffmann, R. W.; Feussner, G.; Zeiss, H.-J.; Schulz, S. J.
Organomet. Chem. 1980, 18, 321-329. (b) Alessandro, G.; Daniele, M.;
Valerio, P.; Giuseppe, T. J. Organomet. Chem. 1981, 204, 191-196.
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(18) Max, F.; David, G.; Daniel, W.; Albert, Z. J. Organomet. Chem.
1967, 9, 83-88 (tributyltin ester was prepared according to a similar
procedure in this literature).
(19) (a) Roberts, R. M. G. J. Organomet. Chem. 1970, 24, 675-685.
(b) Roberts, R. M. G. J. Organomet. Chem. 1969, 18, 307-319. (c)
Kuivila, H. G.; Verdone, J. A. Tetrahedron Lett. 1964, 2, 119-123. (d)
Verdone, J. A.; Mangravite, J. A.; Scarpa, N. M. J. Am. Chem. Soc.
1975, 97, 843-849.
(23) (a) Cheng, H.-S.; Loh, T.-P. J. Am. Chem. Soc. 2003, 125, 4990-
4991. (b) Hussain, I.; Komasaka, T.; Ohga, M.; Nokami, J. Synlett 2002,
640-642. (c) Nokami, J.; Anthony, L.; Sumida, S. Chem. Eur. J. 2000,
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