A new straightforward preparation of enantiopure 10-hydroxycamphor

Article abstract of DOI:10.1016/S0957-4166(00)00416-X

The enantiospecific preparation of the interesting chiral source 10-hydroxycamphor from commercially available camphor is described. The synthetic procedure takes place straightforwardly in only three synthetic steps with a high overall yield. The key step of the described route is based on the ability of a 2-methylenenorbornane intermediate to undergo an enantiospecific Wagner-Meerwein rearrangement under electrophilic treatment with m-CPBA.

Full text of DOI:10.1016/S0957-4166(00)00416-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 4437–4440
A new straightforward preparation of enantiopure
0-hydroxycamphor
1
a,
b
b
Antonio Garc ´ı a Mart ´ı nez, * Enrique Teso Vilar, Amelia Garc ´ı a Fraile,
a,
b
Santiago de la Moya Cerero * and Beatriz Lora Maroto
a
Departamento de Qu ´ı mica Org a´ nica I, Facultad de Ciencias Qu ´ı micas, Universidad Complutense de Madrid,
Ciudad Universitaria, 28040 Madrid, Spain
b
Departamento de Qu ´ı mica Org a´ nica y Biolog ´ı a, Facultad de Ciencias,
Universidad Nacional de Educaci o´ n a Distancia (UNED), Senda del Rey 9, 28040 Madrid, Spain
Received 9 October 2000; accepted 13 October 2000
Abstract
The enantiospecific preparation of the interesting chiral source 10-hydroxycamphor from commercially
available camphor is described. The synthetic procedure takes place straightforwardly in only three
synthetic steps with a high overall yield. The key step of the described route is based on the ability of a
2-methylenenorbornane intermediate to undergo an enantiospecific Wagner–Meerwein rearrangement
under electrophilic treatment with m-CPBA. © 2000 Elsevier Science Ltd. All rights reserved.
Enantiomerically pure C10-substituted camphor derivatives have found broad application as
1
chiral reagents, auxiliaries and catalysts in asymmetric synthesis, as well as versatile chiral
2
synthetic intermediates for the total synthesis of high-value molecules (e.g. natural products).
Most of the C10-substituted camphor derivatives present a sulfur atom attached to the C10
1
position (C10-S), because almost all of the synthetic routes described for the preparation of this
kind of compound use 10-camphorsulfonic acid (the first C10-substituted camphor derivative
3
1–3
obtained), or 10-camphorsulfonyl chloride, as starting material.
Nevertheless, some modern enantiopure camphors with a C10-substitution different from the
common C10-S, such as C10-O, C10-N, C10-halogen, C10-P or C10-Se, have been prepared and
4
tested as valuable chiral sources. Among them, C10-O derivatives (e.g. 1–4 in Fig. 1) must be
specially mentioned due to their application as chiral inducers (auxiliaries and reagents) in
4b,4d–f
several interesting asymmetric transformations.
In this sense, 10-hydroxycamphor 5 (Fig. 1) is a key intermediate (together with ketopinic
4a–g
acid) to C10-O-substituted camphor derivatives.
Unfortunately, 10-hydroxycamphor is pre-
pared from 10-camphorsulfonic acid in five steps with a low overall yield (12%), according to the
*
Corresponding authors.
0
957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00416-X

4438
A. Garc ´ı a Mart ´ı nez et al. / Tetrahedron: Asymmetry 11 (2000) 4437–4440
Figure 1. Some interesting C10-O-substituted camphors
4a
synthetic route described by Dallacker et al. in 1961. Due to this limitation, until now,
1
0-hydroxycamphor 5 has been used very rarely (in comparison to ketopinic acid) as starting
4a–g
precursor of other C10-O-substituted camphor derivatives.
Recently, we have described that reaction of enantiopure 3,3-dimethyl-2-methylenenorbornan-
1
-ol 6 with N-bromosuccinimide (NBS) as electrophilic reagent yields 10-bromocamphor 7
5
enantiospecifically. The process takes place through a regio- and enantiospecific tandem
electrophilic carbonꢀcarbon double bond addition—Wagner–Meerwein rearrangement on the
+
+
2
-methylenenorbornane 6 (Scheme 1, E =Br ). On the other hand, enantiopure precursor 6 can
be easily obtained from camphor 8 in two steps, in a high yield and under mild reaction
5
conditions (see Scheme 2). The use of 7 (obtained as described above) as an intermediate in the
Dallacker’s preparation of 10-hydroxycamphor 5 will improve the overall yield of that synthetic
6
route (ca. 58%).
Scheme 1. Tandem electrophilic carbonꢀcarbon double bond addition—Wagner–Meerwein rearrangement of 6
Now we have found that the treatment of (1R)-3,3-dimethyl-2-methylenenorbornan-1-ol 6
with meta-chloroperoxybenzoic acid (m-CPBA) as electrophile, instead of NBS, enantiospecifi-
cally yields (1R)-10-hydroxycamphor 5 as the only product (the corresponding expected
diastereomeric epoxides of 6 were not detected) (Scheme 2). The reaction takes place in high
yield (78%) under mild reaction conditions (methylene dichloride solution at room tempera-
7
ture). Triflate intermediate 9 does not react with m-CPBA under the same reaction conditions
as 6 does.

A. Garc ´ı a Mart ´ı nez et al. / Tetrahedron: Asymmetry 11 (2000) 4437–4440
4439
Scheme 2. New straightforward route to enantiopure 10-hydroxycamphor
Formation of 5 from 6 can be easily achieved according to the mechanism proposed in
+
+
Scheme 1 (E =OH ).
In conclusion, a new enantiospecific route to the interesting chiral intermediate 10-hydroxy-
camphor 5, based on the Wagner–Meerwein rearrangement of a convenient 2-methylenenorbor-
nane, has been described. 10-Hydroxycamphor 5 is now obtained in only three synthetic steps
starting from readily available enantiopure camphor 8. The complete synthetic route has an
overall yield of 70%. The availability of 5 following the procedure described will allow the
straightforward synthesis of other interesting enantiopure C10-O-substituted camphor-derived
chiral sources.
Acknowledgements
We would like to thank the Ministerio de Educaci o´ n y Ciencia (MEC) of Spain (DGICYT,
research project PB97-0264) for the financial support of this work. B.L.M. wishes to thank MEC
for a post graduate grant.
References
1
. For a review, see: (a) Oppolzer, W. Tetrahedron 1987, 1969. Some recent examples are described in: (b) Cermak,
D. M.; Du, Y.; Wiemer, D. F. J. Org. Chem. 1999, 64, 388. (c) Node, M.; Nishide, K.; Shigeta, Y.; Shiraki, H.;
Obata, K. J. Am. Chem. Soc. 2000, 122, 1927. (d) Ponsinet, R.; Chassaing, G.; Vaissermann, J.; Lavielle, S. Eur.
J. Org. Chem. 2000, 83. (e) Prieto, O.; Ramon, D. J.; Yus, M. Tetrahedron: Asymmetry 2000, 11, 1629. (f) Balint,
J.; Hell, Z.; Markovits, I.; Parkanyi, L.; Fogassy, E. Tetrahedron: Asymmetry 2000, 11, 1323. (g) Belzecki, C.;
Trojnar, J.; Chmielewski, M. Synth. Commun. 2000, 30, 2245.
2. For example, see: in the total synthesis of (+)-zizaanoic acid: (a) Liu, H. J.; Chan, W. H. Can. J. Chem. 1982, 60,
1081; in the total synthesis of (+)-taxuxina: (b) Paquette, L. A.; Zhao, M. J. Am. Chem. Soc. 1998, 120, 5203; in
the total synthesis of taxol: (c) Paquette, L. A.; Zhao, M.; Montgomery, F.; Zheng, Q.; Wang, T. Z.; Elmore, S.;
Combrink, K.; Wang, H.-L.; Bailey, S.; Su, Z. Pure Appl. Chem. 1998, 70, 1449.
3
4
. Reychler, A. Bull. Soc. Chim. Paris 1898, 19, 120.
. Referred to C10-O: (a) Dallacker, F.; Alroggen, I.; Krings, H.; Laurs, B.; Lipp, M. Liebigs Ann. Chem. 1961, 647,
2
3; (b) Ikota, N.; Sakai, H.; Shibata, H.; Koga, K. Chem. Pharm. Bull. 1986, 34, 1050; (c) Jingen, D.; Yaozong,
J.; Guilan, L.; Lanjun, W.; Aiqiao, M. Synthesis 1991, 963; (d) Ahn, K. H.; Lee, S.; Lim, A. J. Org. Chem. 1992,
7, 5065; (e) Ahn, K. H.; Lim, A.; Lee, S. Tetrahedron: Asymmetry 1993, 4, 2435; (f) Chu, Y.-Y.; Yu, C.-S.; Chen,
C.-J.; Yang, K.-S.; Lian, J.-C.; Lin, C.-H.; Chen, K. J. Org. Chem. 1999, 64, 6993; (g) Gaisina, I. N.;
5

4440
A. Garc ´ı a Mart ´ı nez et al. / Tetrahedron: Asymmetry 11 (2000) 4437–4440
Komissarova, N. G.; Selezneva, N. K.; Abutkov, A. V.; Spirikhin, L. V.; Muslukhov, R. R.; Miftakhov, M. S. Zh.
Org. Khim. 1999, 35, 1025; to C10-N: (h) Schenone, P.; Tasca, A.; Bignardi, G.; Mosti, L. Eur. J. Med.
Chem.—Chimica Therapeutica 1975, 10, 412; (i) Yang, K.-S.; Chen, K. Org. Lett. 2000, 2, 729; to C10-halogen: (j)
Oae, S.; Togo, H. Bull. Chem. Soc. Jpn. 1983, 56, 3802, see also Ref. 4a; to C10-Se: (k) Takahashi, T.; Nakao, N.;
Koizumi, T. Tetrahedron: Asymmetry 1997, 8, 3293; to C10-P: (l) Komarov, I. V.; Gorichko, M. V.; Kornilov, M.
Tetrahedron: Asymmetry 1997, 8, 435.
5
6
7
. Lora Maroto, B.; de la Moya Cerero, S.; Garc ´ı a Mart ´ı nez, A.; Garc ´ı a Fraile, A.; Teso Vilar, E. Tetrahedron:
Asymmetry 2000, 11, 3059.
. 10-Bromocamphor is enantiospecifically obtained from camphor in three steps with 95% overall yield (see Ref. 5).
10-Hydroxycamphor is obtained from 10-bromocamphor in two steps with 61% overall yield (see Ref. 4a).
. A solution of alcohol 6 and meta-chloroperoxybenzoic acid (57–86% purity) in CH Cl2 was stirred at room
2
2
0
temperature for 24 h. After usual work up, 5 was obtained as a white solid (78% yield). Mp 216–218°C. [h] +18.8
D
1
13
(
0.17, CH Cl ). The structure was confirmed by H, C NMR, IR, MS and HRMS.
2 2
.