Synthesis of stereochemically defined (E)-cinnamyl alcohol derivatives from the Baylis-Hillman adducts

Article abstract of DOI:10.1016/S0040-4039(00)00229-X

The reaction of the Baylis-Hillman adducts 1a-g and trifluoroacetic acid at 30-70°C gave the rearranged cinnamyl alcohols 2a-g stereoselectively in moderate yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00229-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2613–2616
Synthesis of stereochemically defined (E)-cinnamyl alcohol
derivatives from the Baylis–Hillman adducts
Hyoung Shik Kim, Tae Yi Kim, Ka Young Lee, Yun Mi Chung, Hong Jung Lee and
Jae Nyoung Kim ∗
Department of Chemistry, Chonnam National University, Kwangju 500-757, South Korea
Received 1 December 1999; revised 13 January 2000; accepted 4 February 2000
Abstract
The reaction of the Baylis–Hillman adducts 1a–g and trifluoroacetic acid at 30–70°C gave the rearranged
cinnamyl alcohols 2a–g stereoselectively in moderate yields. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: allylic alcohols; Baylis–Hillman adducts; trifluoroacetic acid.
The Baylis–Hillman reaction is one of the most powerful carbon–carbon bond-forming methods in
organic synthesis.1 The Baylis–Hillman adducts, which are allylic alcohol derivatives, can be formed
most often by the reaction of activated vinyls and carbonyl compounds.1 Besides the usefulness of these
Baylis–Hillman adducts themselves, further derivatization with various nucleophilic reagents toward
synthetically useful compounds has been studied in depth by us and other groups.2
Scheme 1.
The Baylis–Hillman adducts 1 have secondary allylic alcohol functionality, which can be rearranged
to the thermodynamically more stable primary allylic alcohols 2. The synthesis of 2 which has cinnamyl
alcohol moiety is important because it constitutes an important class of synthons for the synthesis
of various biologically active molecules.3 However, synthesis of 2 from 1 has been achieved by
indirect three step method, that is a tandem bromination–formylation–hydrolysis.4a–b The Mitsunobu
type reaction of the Baylis–Hillman adducts with appropriate carboxylic acid can also be used to form
esters of the rearranged allylic alcohols.4c Quite recently, Basavaiah et al. have reported an aqueous
sulfuric acid mediated isomerization of the nitrile-containing Baylis–Hillman adducts (vide infra).4d
∗
Corresponding author. Fax: +82-62-530-3389; e-mail: kimjn@chonnam.chonnam.ac.kr (J. Nyoung Kim)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00229-X
tetl 16509

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They obtained (E)-α-cyanocinnamyl alcohols in 52–68% isolated yields. However, there were no
comments on the reaction of ester-containing Baylis–Hillman adducts.
Table 1
Synthesis of allylic alcohols 2a–ga
In these contexts, we felt that it will be highly useful if the Baylis–Hillman adducts can be transformed
directly into α-ethoxycarbonylcinnamyl alcohols in a stereoselective manner. After some trials we were
able to develop a facile method using trifluoroacetic acid and report herein the preliminary results.
As shown in Scheme 1 and Table 1, the Baylis–Hillman adducts 1 in trifluoroacetic acid at 30–70°C
for 20 h gave the rearranged allylic alcohols 2a–d in 51–72% yields.5 The rearrangement might proceed
via the trifluoroacetate or its hydrate form as shown in Scheme 2. Subsequent in situ hydrolysis of the
trifluoroacetate of rearranged alcohols gave 2a–d.5 The reaction of 1a in acetic acid did not produce

2615
2a at all. The reaction of 1d in formic acid gave rearranged alcohol 2d (8%, E) and the corresponding
rearranged formate ester (75%, E) as the major products. The formate ester relative to the trifluoroacetate
ester is much more resistant to hydrolysis.6 Ester derivatives 1a–d gave E-form allylic alcohols 2a–d
stereoselectively. We could not isolate Z-form isomer which might be present in trace amounts in the
reaction mixtures.
Scheme 2.
1
The assignment of the E-Z stereochemistry was based on the H NMR and 13C NMR data of the
published ones.4,5
However, in the cases of nitrile derivatives 1e–g lower yields (27–40%) of 2e–g (again E-form due
to inversion of priority of the substituents) were obtained with some unidentified polar compounds. As
mentioned earlier, Basavaiah et al. have reported the aqueous sulfuric acid mediated rearrangement of
the nitrile-containing Baylis–Hillman adducts such as 1e and 1g.4d In order to compare the applicability
of these two methods (Basavaiah’s and ours), we examined the reaction of 1e and 1a in aqueous
sulfuric acid. The reaction of 1e in Basavaiah’s conditions (20% aq. sulfuric acid, reflux, 4 h) gave
72% yield of stereochemically pure E-allylic alcohol derivative 2e. However, ester derivative 1a in
aqueous sulfuric acid showed complex mixtures containing a low yield of 2a. From these results, we
think that the Basavaiah’s method works well in nitrile-containing adducts (for E-selective nitriles) while
the trifluoroacetic acid method works well with ester-containing adducts (for E-selective esters). Thus,

2616
these two methods are thought to be complementary to each other for the preparation of stereochemically
defined cinnamyl alcohols.
Acknowledgements
We wish to thank the Ministry of Education of Korea (BK-21 Project).
References
1. (a) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44, 4653. (b) Basavaiah, D.; Rao, P. D.; Hyma, R. S. Tetrahedron 1996,
52, 8001. (c) Brezezinski, L. J.; Rafel, S.; Leahy, J. W. J. Am. Chem. Soc. 1997, 119, 4317. (d) Rafel, S.; Leahy, J. W. J. Org.
Chem. 1997, 62, 1521.
2. (a) Lee, H. J.; Seong, M. R.; Kim, J. N. Tetrahedron Lett. 1998, 39, 6223. (b) Lee, H. J.; Kim, H. S.; Kim, J. N. Tetrahedron
Lett. 1999, 40, 4363. (c) Basavaiah, D.; Sarma, P. K. S. J. Chem. Soc., Chem. Commun. 1992, 955. (d) Charette, A. B.;
Cote, B.; Monroc, S.; Prescott, S. J. Org. Chem. 1995, 60, 6888. (e) Basavaiah, D.; Krishnamacharyulu, M.; Hyma, R. S.;
Pandiaraju, S. Tetrahedron Lett. 1997, 38, 2141. (f) Chavan, S. P.; Ethiraj, K. S.; Kamat, S. K. Tetrahedron Lett. 1997, 38,
7415. (g) Perlmutter, P.; Tabone, M. Tetrahedron Lett. 1988, 29, 949. (h) Lawrence, R. M.; Perlmutter, P. Chem. Lett. 1992,
305. (i) Foucaud, A.; El Guemmout, F. Bull. Soc. Chim. Fr. 1989, 403.
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Chu, C.-S.; Lee, T.-H.; Rao, P. D.; Song, L.-D.; Liao, C.-C. J. Org. Chem. 1999, 64, 4111. (d) Aiai, M.; Baudy-Floc’h, M.;
Robert, A.; Le Grel, P. Synthesis 1996, 403. (e) Takahashi, K.; Ogata, M. J. Org. Chem. 1987, 52, 1877. For further references,
see Refs 4b and 4d.
4. (a) Hbaieb, S.; Ben Ayed, T.; Amri, H. Synth. Commun. 1997, 27, 2825. (b) Beltaief, I.; Hbaieb, S.; Besbes, R.; Amri, H.;
Villieras, M.; Villieras, J. Synthesis 1998, 1765. (c) Charette, A. B.; Cote, B.; Monroc, S.; Prescott, S. J. Org. Chem. 1995,
60, 6888. (d) Basavaiah, D.; Kumaragurubaran, N.; Padmaja, K. Synlett 1999, 1630.
5. General procedure for the preparation of 2: a stirred solution of 1 (2 mmol) in CF3COOH (2 mL) was heated to 60–70°C
(30–40°C for 1d and 1g) during 20 h. The reaction mixture was poured into cold water and extracted with ether. The
organic layers were washed with water, dried with MgSO4, evaporated to dryness. Column chromatography on silica gel
(EtOAc:hexane, 1:10) of the crude product mixtures gave pure 2. Unhydrolyzed trifluoroacetate derivatives of 2 were
hydrolyzed readily to 2 during separation by column chromatography. Some selected spectroscopic data of 2a and 2e are
1
as follows. Compound 2a: clear oil; IR (neat) 3465, 1713, 1640, 1277 cm−1; H NMR (CDCl3) δ 1.30 (t, J=7.2 Hz, 3H),
2.62 (brs, 1H, OH), 4.25 (q, J=7.2 Hz, 2H), 4.41 (s, 2H), 7.30–7.42 (m, 5H), 7.76 (s, 1H); 13C NMR (CDCl3) δ 14.29, 57.97,
61.13, 128.55, 129.14, 129.54, 131.18, 134.56, 142.24, 167.97; mass (70 eV) m/z (rel. intensity) 55 (40), 77 (58), 131 (100),
132 (44), 133 (39), 160 (24), 177 (31), 206 (M+, 17). Compound 2e: clear oil; IR (neat) 3408, 2215, 1626, 1449, 1037 cm−1
;
1H NMR (CDCl3) δ 2.34 (brs, 1H, OH), 4.42 (d, J=1.2 Hz, 2H), 7.21 (s, 1H), 7.40–7.45 (m, 3H), 7.73–7.78 (m, 2H); 13C
NMR (CDCl3) δ 64.29, 110.53, 117.72, 128.84 (2C), 130.52, 132.95, 143.82; mass (70 eV) m/z (rel. intensity) 51 (51), 77
(50), 78 (55), 91 (60), 102 (31), 103 (36), 130 (100), 159 (M+, 76).
6. Kocienski, P. J. Protecting Groups; Thieme: New York, 1994; p. 22.