Table 2 Examination of solvent-free asymmetric Michael reaction of 1 with
2a using various bases
Fig. 2
due to the same face differentiation mentioned above, even in
solution.
In summary, it was found that modified guanidines effi-
ciently catalysed the asymmetric Michael reaction of a prochiral
glycine derivative with vinyl compounds either in solution or
without a solvent under simple and mild conditions. These
guanidine-catalysed asymmetric Michael reactions12 could
contribute to development of green chemistry,13 because
modified guanidines are considered to be re-useable (economi-
cally favored) and easily functionalizable (widely applicable)
artificial organic bases.
solvent (Table 1, run 4). A heterogeneous mixture of the two
components containing 4 was simply stirred at 20 °C for 3 d.10
Interestingly, both product formation and enantioselectivity
were dramatically improved to give an (R)-excess 3a with 97%
ee in quantitative yield. Similarly, remarkable rate acceleration
was observed on two other Michael acceptors 2b and 2c. In the
former case (Table 1, run 5), reaction was completed after 15 h,
in which relatively high enantioselctivity (80% ee) was kept. On
the other hand, in the latter case (Table 1, run 6), 1 disappeared
after 5 days to afford 3c with 55% ee in spite of no reaction in
solution (see Table 1, run 3). In addition, as expected, the use of
methyl acrylate (2d) as a Michael acceptor led to the same
satisfactory results obtained with 2a (Table 1, run 7).
Notes and references
1 M. Costa, G. P. Chiusoli, D. Taffurelli and G. Dalmonego, J. Chem.
Soc., Perkin Trans. 1, 1998, 1541.
2 Y. Yamamoto and S. Kojima, in The Chemistry of Amidines and
Imidates, Vol. 2, eds, S. Patai and Z. Rappoport, John Wiley and Sons
Inc., New York, 1991, pp. 485.
3 (a) T. Isobe, K. Fukuda and T. Ishikawa, J. Org. Chem., 2000, 65, 7770;
(b) T. Isobe, K. Fukuda, T. Tokunaga, H. Seki, K. Yamaguchi and T.
Ishikawa, J. Org. Chem., 2000, 65, 7774; (c) T. Isobe, K. Fukuda, K.
Yamaguchi, H. Seki, T. Tokunaga and T. Ishikawa, J. Org. Chem.,
2000, 65, 7779.
Thus, as a solvent-free reaction seems to be generally
effective in the guanidine-catalysed Michael reaction of 1,
optimization was tried using 2a as a Michael acceptor (Table 2).
The same high ee was achieved even on reduction of the catalyst
amount, albeit with lower chemical conversion (Table 2, run 2).
No reaction was observed in the absence of a guanidine or in the
presence of (2)-quinine (Table 2, runs 3 and 4). These facts
indicated that 4 effectively catalysed the solvent-free reaction of
1 with 2a in 20 mol% concentration.
4 T. Isobe, K. Fukuda and T. Ishikawa, Tetrahedron: Asymmetry, 1998, 9,
1729.
5 For the early work, see: M. J. O’Donnell, W. D. Bennett and S. Wu,
J. Am. Chem. Soc., 1989, 111, 2353; M. J. O’Donnell, I. A. Esikova, A.
Mi, D. F. Shullenberger and S. Wu in Phase-Transfer Catalysis (ACS
Symposium Series 659), ed. M. E. Halpern, ACS, Washington D. C.,
1997, Chapter 10; B. Lygo and P. G. Wainwright, Tetrahedron Lett.,
1997, 38, 8595. For recent work, see: A. Nelson, Angew. Chem., Int. Ed.,
1999, 38, 1583; J. Ezquerra, C. Pedregal, I. Merino, J. Florez, J.
Barluenga, S. G.-Granda and M.-A. Llorea, J. Org. Chem., 1999, 64,
6554; T. Ooi, M. Kameda and K. Maruoka, J. Am. Chem. Soc., 1999,
121, 6519; T. Abellan, R. Chinchilla, N. Galindo, G. Guillena, C. Najera
and J. M. Sansano, Eur. J. Org. Chem., 2000, 2689.
6 D. Ma and K. Cheng, Tetrahedron: Asymmetry, 1999, 10, 713.
7 Corey et al. reported the quaternary ammonium salt-catalysed asym-
metric Michael reaction: E. J. Corey, M. C. Noe and F. Xu, Tetrahedron
Lett., 1998, 39, 5347; F.-Y. Zhang and E. J. Corey, Org. Lett., 2000, 2,
1097.
8 Although Ma and Cheng6 had also tried the Michael reaction of 1 with
2b, the enantioselectivity was quite low (16.5% ee).
The use of ent-4,11 as expected, afforded an (S)-excess 3a in
quantitative yield with the same high enantioselectivity (Table
2, run 5). The (S)-excess 3a was also obtained when 8,3a
a
diastereomer of 4, was used as a catalyst, but both chemical
yield and asymmetric induction were lowered considerably
(Table 2, run 6). Replacement of an (R)-phenylalaninol unit in
4 to an (R)-phenylglycinol one in 93a afforded an (R)-excess 3a
with relatively high selectivity. However, chemical conversion
was not good (Table 2, run 7). On the other hand, the use of a
guanidine 104 lacking a hydroxyethyl function resulted in no
reaction (Table 2, run 8).
Experimental evidence obtained in the above solvent-free
reactions could be summarised as follows: (i) satisfactory
chemical conversion with high enantioselectivity in the use of
HOC2H4-substituted cyclic guanidines with (4S,5S,1AR or
4R,5R,1AS) configuration such as 4 indicates that the relative
configurations of these three chiral centers are very important
for effective asymmetric induction in addition to rate accelera-
tion; (ii) predominant production of (R)-3a with 4 and 9 [or (S)-
3a with ent-4 and 8] shows that a stereogenic center of the
adduct should be strictly reflected by the chirality of a
substituent at the external nitrogen; (iii) if the enolate of 1 could
be formed by action of 4, its re-face should be attacked by 2a to
yield an (R)-excess 3a, for which the opposite si-face is severely
blocked by the guanidine unit as shown in Fig. 2; (iv) although
the absolute configuration of an excess enantiomer obtained in
each reaction of 1 with 2b, 2c or 2d has not been determined, an
(R)-excess 3b, 3c or 3d should be given in the reaction using 4
9 For examples, see: K. Tanaka and F. Toda, Chem. Rev., 2000, 100,
1025; V. K. Aggarwal and A. Mereu, Chem. Commun., 2000, 2310; J. O.
Metzger, Angew. Chem., Int. Ed., 1998, 37, 2975.
10 A heterogeneous mixture turned into a homogeneous one after
completion of the reaction.
11 The guanidine was prepared from (R,R)-1,2-diphenylethylenediamine
according to the reported method.4
12 Some guanidines have been applied to asymmetric Michael reactions as
chiral bases, however low or no enantioselectivity had been observed in
the guanidine-catalysed reactions, see: V. Alcazar, J. R. Moran and J.
deMendoza, Tetrahedron Lett., 1995, 36, 3941; A. Howard-Jones, P. J.
Murphy, D. A. Thomas and P. W. R. Caulkett, J. Org. Chem., 1999, 64,
1039. During our research works an effective Strecker reaction
catalysed by a C2-symmetrical bicyclic guanidine was reported in spite
of the reaction in solution: E. J. Corey and M. J. Grogan, Org. Lett.,
1999, 1, 157.
13 P. T. Anastas and J. C. Warner in Green Chemistry: Theory and
Practice, Oxford University Press, Oxford, 1998.
246
Chem. Commun., 2001, 245–246