Using polymer-supported reagents and catalysts is a
popular tool in modern organic synthesis because the workup
of the reaction and the recovery of reagents and catalysts
are convenient.2 Recently, we have found that a series of
carboxylic acids are efficient promoters for allylation of
aldehydes with allyltributyltin under very mild conditions.5
In this allylation, the SnBu3 group is transferred to the
carboxylic acid, forming the tin ester (eq 1, Scheme 1). On
Table 1. Screening of R-Amino Acid and Their Derivatives as
Promoters for the Allylation of Benzaldehydes
entry
promoter
time, h
yield, % b
1
2
3
4
5
6
7
D-phenylalanine
72
23
23
55
23
23
23
5
84
74
51
80
40
92
N-tosyl-D-phenylalane
N-tosyl-L-proline
N-Cbz-L-proline
N-tosyl-L-valine
N-tosyl-L-2-phenylglycine
N-tosyl-glycine
Scheme 1
a 1a/2 ) 1.0 equiv (0.5 mmol)/1.2 equiv (0.6 mmol). b Isolated yield.
carbon (entries 5 and 6) were less active. The best result
was obtained from the simplest N-tosylglycine with a yield
up to 92% of 3a at room temperature in acetonitrile (entry
7). In addition, it needs to be noted that the corresponding
product of homoallyl alcohol 3a was racemic, although the
reactions used the pure optically active R-amino acid
derivatives as promoters (entries 1-6).
The polymer-supported sulfonamide of N-glycine (P4) was
prepared easily in three steps according to a similar method.3
As shown in Scheme 2, the beads of polystyrene (P1, 2%
the basis of these results, we think that if this allylation can
be promoted by polymer-supported carboxylic acids with a
certain acidic degree, we can allylate cleanly by transferring
the SnBu3 group to the polymer promoter (eq 2, Scheme 1).
In addition, after the tin ester of the polymer is treated with
aqueous HCl, the SnBu3 residue will be recovered as Bu3-
SnCl (eq 3, Scheme 1). In this Letter, we would like to
describe the results of this protocol.
We are interested in R-amino acids because of two
factors: (1) R-Amino acids have a good linking site, NH2,
which makes them convenient for being supported by
polymer. (2) The acidity of the N-protected R-amino acid is
tunable by using different protective groups, and thus the
excess allyltributyltin can be decomposed and removed if
polymer-supported R-amino acid was used. Therefore, first,
we screened various R-amino acids and their derivatives for
this allylation by employing benzaldehyde as a model
substrate. The results are summarized in Table 1. The
allylation promoted by D-phenylalanine was sluggish (entry
1). When D-phenylalanine was protected with a tosyl group,
which effectively enhanced the acidity of the carboxylic acid,
a good yield allylation was obtained (entry 2). Further
investigation revealed that R-amino acids with a weak
electronic-withdrawing protective group (e.g., Cbz) at the
amino group (entry 4) and more steric hindrance at the â
Scheme 2
divinylbenzene, 200-400 mesh) were treated with excess
chlorosulfonic acid to produce chlorosulfonylated polymer
(P2). The degree of chlorosulfonylation of P2 determined
by elemental analysis was about 4.61 mmol/g Cl and 4.80
mmol/g S. Next glycine ethyl ester was grafted onto P2 in
the presence of Et3N at room temperature over 4 days.
Elemental analysis showed that the percentage of remaining
Cl of P3 was less than 0.5%. Finally, P3 was saponified in
aqueous NaOH (3.0 M)7 and subsequently acidified under
HCl (2.0 M). After 48 h of stirring in distilled water to
remove the trace amount of hydrochloric acid and drying in
a vacuum (1 mmHg, P2O5, 50 °C overnight), the polymer-
supported sulfonamide of N-glycine (P4a) was obtained. The
polymer P4a was characterized by IR spectroscopy, which
(3) (a) Fouquet, E.; Pereyre, M.; Roulet, T. J. Chem. Soc., Chem.
Commun. 1995, 2387. (b) Fouquet, E.; Pereyre, M.; Rodriguez, A. L. J.
Org. Chem. 1997, 62, 5242. (c) Curran, D. P.; Hadida, S.; He, M. J. Org.
Chem. 1997, 62, 6714. (d) Olofsson, K.; Kim, S.-Y.; Larhed, M.; Curran,
D. P.; Hallberg, A. J. Org. Chem. 1999, 64, 4539. (e) Ryu, I.; Niguma, T.;
Minakata, S.; Komatsu, M.; Luo, Z.; Curran, D. P. Tetrahedron Lett. 1999,
40, 2367. (f) Cossy, J.; Rasamison, C.; Pardo, D. G. J. Org. Chem. 2001,
66, 7195. (g) McCluskey, A.; Muderawan, I. W.; Muntari; Young, D. J. J.
Org. Chem. 2001, 66, 7811. (h) Ryu, I.; Kreimerman, S.; Niguma, T.;
Minakata, S.; Komatsu, M.; Luo, Z.; Curran, D. P. Tetrahedron Lett. 2001,
42, 947. (i) Cossy, J.; Rasamison, C.; Pardo, D. G.; Marshall, J. A. Synlett
2001, 629.
(6) Hu, J.-B.; Zhao, G.; Ding, Z.-D. Angew. Chem., Int. Ed. 2001, 40,
1109.
(4) (a) An issue of Chemical Reviews (Chem. ReV. 2002, 102, 3215)
has been devoted to polymer-supported catalysts and reagents. (b) Maurizio,
B.; Alessandra, P.; Franco, C. Chem. ReV., 2003, 103, 3401.
(7) The strong IR absorption at 1747 cm-1(CdO of ethyl ester)
disappeared and was replaced by another strong band near 1601 cm-1 (Cd
O of sodium salt of the polymer). It suggests that the saponification was
completed.
(5) Li, G.-l.; Zhao, G. J. Org. Chem. 2005, 70, 4272.
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Org. Lett., Vol. 8, No. 4, 2006