Ruthenium catalyzed asymmetric dihydroxylation with sultams as chiral auxiliaries

Article abstract of DOI:10.1016/S0957-4166(99)00121-4

Ruthenium catalyzed asymmetric dihydroxylations of α,β-unsaturated carbonyl compounds with sultams 4, 5 and 6 as chiral auxiliaries are reported.

Full text of DOI:10.1016/S0957-4166(99)00121-4

Pergamon
Tetrahedron: Asymmetry 10 (1999) 1421–1424
Ruthenium catalyzed asymmetric dihydroxylation with sultams as
chiral auxiliaries
Albert W. M. Lee,∗ W. H. Chan, W. H. Yuen, P. F. Xia and W. Y. Wong
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong, People’s Republic of China
Received 12 February 1999; accepted 24 March 1999
Abstract
Ruthenium catalyzed asymmetric dihydroxylations of α,β-unsaturated carbonyl compounds with sultams 4, 5
and 6 as chiral auxiliaries are reported. © 1999 Elsevier Science Ltd. All rights reserved.
Stereoselective OsO4 mediated dihydroxylation of alkene moieties has always attracted considerable
interest from synthetic chemists because of its role in the construction of valuable diol building blocks
for the syntheses of polyoxygenated compounds and natural products. Both stoichiometric and catalytic
OsO4 based asymmetric dihydroxylation are well known in the literature including the extremely well
received Sharpless asymmetric dihydroxlation.1,2 A few reports on using chiral auxiliaries such as the
Oppolzer’s camphorsultam in OsO4 asymmetric dihydroxylation have also appeared in the literature.3
Despite its popularity and reliability as an oxidizing reagent, osmium tetraoxide is highly toxic
and relatively expensive. Recently, Shing et al. demonstrated a procedure for the highly efficient
dihydroxylation of olefins catalyzed by ruthenium tetraoxide.4 Because of its low toxicity, affordable
price, and accelerated rate of reaction, the use of ruthenium tetraoxide has certain advantages over
osmium tetraoxide in dihydroxylation reactions. However, no asymmetric version of the ruthenium
catalyzed reaction has yet been reported. Recently, we reported a practical synthesis of α,β-unsaturated
γ-sultone 1 and its application as a dienophile in Diels–Alder reactions.5 We also demonstrated that
homochiral sultams such as compounds 2 and 3 can be derived from the Diels–Alder cycloadducts of
sultone 1. These synthetic sultams can serve as chiral auxiliaries in several asymmetric processes such
as Diels–Alder reactions and alkylations.6 In this report, we discuss our results using Oppolzer’s and our
synthetic sultams as chiral auxiliaries in ruthenium catalyzed asymmetric dihydroxylations.
∗
Corresponding author. Tel: (852) 2339 7064; fax: (852) 2339 7348; e-mail: alee@hkbu.edu.hk
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00121-4

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Our original homochiral sultams 2 and 3 derived from the exo- and endo-Diels–Alder cycloadducts
of 1 with cyclopentadiene contain olefinic moieties and therefore are not suitable for dihydroxylation
reactions. They were modified to the saturated series 4 and 5 through hydrogenation. All the N-enoyl
sultams 7–16 were then prepared in quantitative yields from the corresponding chiral sultam auxiliaries
(4, 5, 6) and acyl chlorides using n-butyl lithium as the base. Dihydroxylation of the N-enoyl sultams
(7–16) were carried out in 1:1 CH3CN:EtOAc for 2 to 5 hours after the Shing’s protocol (0.07 mol equiv.
RuCl3, 1.5 equiv. NaIO4). The resulting diols were converted in situ to the corresponding dimethyl acetals
(7a–16a and 7b–16b) in good overall yields (Scheme 1).
Scheme 1.
Our results on ruthenium catalyzed dihydroxylation, as depicted in Table 1, indicated that the π-facial
diastereoselectivity is highly dependent on the kind of auxiliary used. For the Oppolzer’s camphorsultam
6, good selectivities up to 9:1 were observed (entries 1–4). The sense of diastereoselectivity in these cases
is the same as in the OsO4 catalyzed reaction3 with 7a–16a as the major products with R configuration
at C(α).
The diastereoselectivities with synthetic sultams 4 and 5 as chiral auxiliaries (entries 5–10) were
poorer. Around 4:6 selectivities were observed for sultam 4, and basically no selectivity was afforded
by sultam 5. Furthermore, the sense of diastereoselectivity in sultam 4 is just opposite to that of sultam
Table 1
Ruthenium catalyzed asymmetric dihydroxylation7

A. W. M. Lee et al. / Tetrahedron: Asymmetry 10 (1999) 1421–1424
1423
6 with 7b–16b as the major products. X-Ray crystallographic analyses of 11b and 12b unambiguously
confirmed that the C(α) centers have the S configuration (Scheme 2).
Scheme 2.
The poorer and opposite diastereoselectivity observed for sultam 4 and 5 can be explained as follows.
Based on the model proposed by Oppolzer3c featuring a syn-orientation of the C_O and SO2 groups (a
chelation by a Ru-atom) and S-cis-related C_O/C(α)–(β) bonds, models of the enoylsultams of chiral
auxiliaries 4 and 5 are depicted in Scheme 2. As pointed out by Oppolzer, it is obvious that for the enoyl
derivatives of camphorsultam 6, the bottom face attack is more favorable as the top face is shielded by the
gem-dimethyl groups of the [2.2.1] bicyclic ring structure. For the enoyl derivatives of the endo-sultam
4, model 17 shows that it has a bent conformation: the bottom face is slightly shielded. A more favorable
attack from the top face afforded opposite selectivity as compared with sultam 6. For the exo-sultam 5,
model 18 shows that a rather flat conformation is adopted. The steric demand from either the top or the
bottom faces are almost the same: therefore, no diastereoselectivity was observed.
In summary, this is the first report of ruthenium catalyzed asymmetric hydroxylation using sultams as
chiral auxiliaries. Facial selectivities were highly dependent on the type of chiral sultams used. Financial
support from the Hong Kong Research Grant Council (HKBU 136/94P) and the Faculty Research Grant
are gratefully acknowledged.
References
1. Lohray, B. B. Tetrahedron: Asymmetry 1992, 3, 1317–1349.
2. Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: Weinheim, 1993.
3. (a) Colombo, L.; Gennari, C.; Poli, G.; Scolastico, C. Tetrahedron Lett. 1985, 26, 5459. (b) Hatakeyama, S.; Matsui, Y.;
Suzuki, M.; Sakurai, K.; Takano, S. Tetrahedron Lett. 1985, 26, 6485. (c) Oppolzer, W.; Barras, J. P. Helv. Chim. Acta
1987, 70, 1666.

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4. (a) Shing, T. K. M.; Tai, V. W.-F.; Tam, E. K. W. Angew. Chem., Int. Ed. Engl. 1994, 33, 2312. (b) Shing, T. K. M.; Tam,
E. K. W.; Chung, W.-F.; Chung, I. H. F.; Jiang, Q. Chem. Eur. J. 1996, 2, 50–57.
5. (a) Lee, A. W. M.; Chan, W. H.; Jiang L. S.; Poon, K. W. Chem. Commun. 1997, 611–612. (b) Lee, A. W. M.; Chan, W.
H. In Topics in Current Chemistry; Metz, P., Ed.; Springer–Verlag: Berlin, 1997; Vol. 190, pp. 103–129.
6. Chan, W. H.; Lee, A. W. M.; Jiang, L. S.; Mak, T. C. W. Tetrahedron: Asymmetry 1997, 8, 2501–2504.
7. All new compounds were characterized by spectroscopic methods (IR, 1H, 13C NMR, HRMS and/or elemental analysis).
Typical procedure: to a vigorously stirred solution of N-enoylsultam 11 (1.0 mmol) in EtOAc:CH3CN (10 ml:10 ml) at
−20°C was slowly added a solution of RuCl3·(H2O)x (0.1 mmol) and NaIO4 (1.5 mmol) in water (2 ml). The two-phase
mixture was stirred vigorously for 2 h and monitored by TLC. When the reaction was almost completed, it was gradually
warmed up to −10°C for 15 min. A saturated aqueous solution of Na2S2O3 (10 ml) was then added. The aqueous phase
was separated and extracted with EtOAc (3×20 ml). The combined organic extracts were then dried (Na2SO4) and filtered.
Concentration of the dried (Na2SO4) organic extracts provided a crude mixture of the diols. The crude diols was stirred in
1:1 CH3COCH3:(CH3)2C(OCH3)2 mixture (8 ml) in the presence of TsOH (1 mg) at rt for 2 h. Saturated NaHCO3 solution
was added followed by extraction with CH2Cl2. After passing through a short silica gel column, 0.274 g (83%) of 11a
and 11b was obtained. The two diastereomers can be further purified by silica gel column chromatography eluted with 1:4
EtOAc:pet-ether. 11b: m.p. 111–113°C; [α]2D3=+54.8 (c=0.17, CHCl3); 1H NMR (CDCl3, 270 MHz) δ 1.47–1.63 (14H,
m), 2.12 (1H, m), 2.51 (1H, s), 2.80 (1H, s), 2.85–2.94 (1H, m), 3.50 (1H, dd, J=8 and 13 Hz), 3.62 (1H, dd, J=4.6 and
10.8 Hz), 4.34 (1H, d, J=13 Hz), 4.40 (1H, t, J=6.21 Hz), 4.98 (1H, d, J=6.5 Hz); 13C NMR (CDCl3, 67.8 MHz) δ 18.69,
21.88, 22.32, 26.38, 27.95, 37.59, 40.78, 40.83, 41.63, 42.67, 63.72, 76.27, 79.54, 111.3 and 169; IR (KBr) ν/cm−1 1694
(C_O). Anal. calcd for C15H23NO5S: C, 54.69; H, 7.04; N, 4.25; found: C, 54.79; H, 7.12; N, 4.38.