Palladium-catalyzed kinetic resolution of racemic cyclic and acyclic allylic carbonates with sulfur nucleophiles

Article abstract of DOI:10.1016/S0040-4039(00)00523-2

A chiral Pd(0) complex bearing the Trost ligand in combination with S- nucleophiles effects the kinetic resolution of cyclic and acyclic allylic carbonates with excellent levels of enantioselectivity to give enantiomerically highly enriched allylic carbonates as well as allylic sulfones and sulfides. This method allows also for a new access to enantiopure cyclic allylic alcohols. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00523-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3809–3812
Palladium-catalyzed kinetic resolution of racemic cyclic and
acyclic allylic carbonates with sulfur nucleophiles
∗
Hans-Joachim Gais, Nicole Spalthoff, Thomas Jagusch, Michael Frank and Gerhard Raabe
Institut für Organische Chemie der RWTH Aachen, Professor-Pirlet-Straße 1, 52056 Aachen, Germany
Received 29 February 2000; accepted 23 March 2000
Abstract
A chiral Pd(0) complex bearing the Trost ligand in combination with S-nucleophiles effects the kinetic resolution
of cyclic and acyclic allylic carbonates with excellent levels of enantioselectivity to give enantiomerically highly
enriched allylic carbonates as well as allylic sulfones and sulfides. This method allows also for a new access to
enantiopure cyclic allylic alcohols. © 2000 Elsevier Science Ltd. All rights reserved.
1
Catalytic kinetic resolution is an important method for the attainment of chiral compounds. While
2
numerous highly efficient examples using enzymes have been described, those involving abiotic
3
chiral catalysts are much less abundant. Therefore, the development of highly selective kinetic re-
4
solutions with the latter type of catalysts continues to be a topic of considerable interest. During
5
our investigations of the Pd-catalyzed asymmetric synthesis of allylic S-derivatives by using a chiral
6
7
5a,b
Helmchen–Pfaltz–Williams ligand and the Trost ligand (R,R)-3 we had encountered
a kinetic resolu-
8
,9
tion of allylic acetates and carbonates. We now report that a highly selective kinetic resolution of cyclic
and acyclic allylic carbonates is achieved through the Pd-catalyzed substitution with S-nucleophiles in
the presence of (R,R)-3.
Reaction of the racemic six-ring allylic carbonate rac-1a on a 10 mmol scale with two equivalents of
5
a
sulfinate 2 at 0°C in a 1:1 mixture of water and methylene chloride in the presence of 1.5 mol% of
[
Pd dba ·CHCl ] (dba=dibenylideneacetone), 4.5 mol% of (R,R)-3 and tetrahexylammonium bromide
2
3
3
as a phase transfer catalyst gave after termination of the reaction at 54% conversion and chromatography
the sulfone (S)-4a with 98% ee in 49% yield and the carbonate (R)-1a with ≥99% ee in 34% yield
1
0
(
Table 1). The similar Pd-catalyzed substitution of the racemic seven-ring allylic carbonate rac-1b
with sulfinate 2 furnished, at 53% conversion, the sulfone (S)-4b with 95% ee in 46% yield and the
carbonate (R)-1b with 94% ee in 33% yield. The Pd-catalyzed substitution of the racemic eight-ring
allylic carbonate rac-1c with sulfinate 2 proceeded under these conditions equally effective and delivered
at 52% conversion the sulfone (S)-4c with 96% ee in 48% yield and the carbonate (R)-1c with ≥99% ee
in 34% yield. The reaction rate decreased with increasing ring size of the allylic carbonate necessitating
the reaction of rac-1c to be carried out at room temperature. According to GC and NMR spectroscopic
∗
Corresponding author. Fax: +49 (0) 241/8888665; e-mail: gais@rwth-aachen.de (H.-J. Gais)
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00523-2
tetl 16802

3
810
analyses formation of side products was negligible, and the chemical yield of the carbonates approached
1
0
in all cases the theoretical values. Thus, an optimization of the yields of the recovered educts should be
possible. The absolute configurations of the carbonates (R)-1a–c were established by chemical correlation
through hydrolysis to the corresponding cyclic allylic alcohols4
a,b,11
and comparison of their chiroptical
data with those reported in the literature. The absolute configuration of sulfone (S)-4c was confirmed by
12
X-ray structure analysis using anomalous X-ray scattering (Fig. 1). On the basis of these results and by
assuming that the reactions of the intermediate allyl–Pd complexes (vide infra) derived from carbonates
rac-1a–c and ‘[Pd(R,R)-3]’ with sulfinate 2 proceed all with the same sense of asymmetric induction the
absolute configurations of sulfones (S)-4a and (S)-4b were also assigned to be S.
Table 1
a,b
‘
[Pd(R,R)-3]’-catalyzed kinetic resolution of carbonates rac-1a–c with sulfinate 2
Fig. 1. Structure of sulfone (S)-4c in the crystal.
Monitoring the Pd-catalyzed reaction of carbonate rac-1a with sulfinate 2 under the above conditions
by GC and NMR spectroscopy revealed that the ee value of the sulfone (S)-4a did practically not change
during the course of the reaction (Fig. 2) and that the ee value of the carbonate (R)-1a increased at higher
conversion. On the basis of the conversion and the ee values of carbonate (R)-1a the lower limit of the
3
a
k /k value was estimated to be 40.
f
s
The ‘[Pd(R,R)-3]’-catalyzed kinetic resolution could be extended to acyclic and cyclic carbonates as
substrates and thiols as nucleophiles as well. Thus, reaction of carbonate rac-5 on a 10 mmol scale with
one equivalent of thiol 6 at 22°C in methylene chloride in the presence of 2.5 mol% of [Pd dba ·CHCl ]
2
3
3
and 5.5 mol% of (R,R)-3 gave after termination of the reaction at 55% conversion and chromatography
5
b
the sulfide (R)-7 with 93% ee in 36% yield while 36% of the carbonate (S)-5 with ≥99% ee were
recovered (Table 2). The similar ‘[Pd(R,R)-3]’-catalyzed substitution of carbonate rac-1a with thiol 6
furnished at 56% conversion the sulfide (S)-85b with 92% ee in 29% yield and the carbonate (R)-1a with
≥99% ee in 35% yield.

3
811
Fig. 2. ‘[Pd(R,R)-3]’-catalyzed reaction of carbonate rac-1a with sulfinate 2 (left) and with thiol 6 (right)
Table 2
a,b
‘
[Pd(R,R)-3]’-catalyzed kinetic resolution of carbonates rac-3 and rac-1a with thiol 6
The Pd-catalyzed reaction of carbonate rac-1a with thiol 6 was followed by GC (Fig. 2). The ee value
of sulfide (S)-8 did practically not change during the course of the reaction, but the ee value of the
carbonate (R)-1a increased at higher conversion. On the basis of the conversion and the ee values of
3
a
carbonate (R)-1a the lower limit of the k /k value was estimated to be 40.
f
s
A characteristic feature of the above Pd-catalyzed kinetic resolutions not shared by other kinetic reso-
lutions is that the ee values of the recovered substrate and of the product are dependent on the selectivities
of two different steps (Fig. 3). While the enantiomer selectivity (k /k ) of the ionization determines the
1
2
ee value of the recovered educt that of the product is defined by the enantioselectivity (k /k ) of the
3
4
substitution of the allyl–Pd complex, and the fastest reacting enantiomer of the allylic carbonate and
the fastest forming enantiomer of the sulfone and sulfide have the same absolute configuration.5
a,b
A
rationalization of the selectivities is hampered at present because of the unknown structures of ‘[Pd(R,R)-
]’ and the allyl–Pd complexes derived thereof.9
c
3
In summary, complex ‘[Pd(R,R)-3]’ in combination with S-nucleophiles allows for a catalytic kinetic
resolution of racemic cyclic and acyclic allylic carbonates with levels of enantioselectivity not observed
5
a,8,9
in the previous cases
to give enantiomerically highly enriched allylic carbonates, sulfones and
sulfides. Although the parent cyclic allylic alcohols of carbonates (R)-1a–c, which have found use as

3
812
Fig. 3. ‘[Pd(R,R)-3]’-catalyzed kinetic resolution and asymmetric substitution
chiral synthetic intermediates, can be obtained by several methods4a,b,11 the kinetic resolution alluded to
allows for the attainment of each alcohol in very high enantiomeric purity.13
Acknowledgements
Financial support of this work by the Deutsche Forschungsgemeinschaft (SFB 380) is gratefully
acknowledged.
References
1
2
. Collins, A. N.; Sheldrake, G. N.; Crosby, J. Chirality in Industry; Wiley: New York, 1992.
. (a) Gais, H.-J. In Enzymes in Organic Synthesis (Drauz, K.; Waldmann, H., Eds.), VCH: Weinheim, 1995; Vol. 1, p 165.
(b) Bornscheuer, U. T.; Kazlauskas, R. J. Hydrolases in Organic Synthesis; Wiley-VCH: Weinheim, 1999. (c) For a recent
example, see: Gais, H.-J.; Griebel, C.; Buschmann, H. Tetrahedron: Asymmetry 2000, 11, 917.
3
. For reviews, see: (a) Kagan, H. B.; Fiaud, J. C. Top. Stereochem. 1988, 18, 249. (b) Eliel, E. L.; Wilen, S. H. Stereochemistry
of Organic Compounds; Wiley: New York, 1994. (c) Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; VCH: Weinheim, 1993; p. 101. (d) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994,
9
4, 2483.
4
. For recent examples, see: (a) Kashiwagi, Y.; Yanagisawa, Y.; Kurashima, F.; Anzai, J.; Osa, T.; Bobbit, J. M. Chem.
Commun. 1996, 2745. (b) Hashiguchi, S.; Fujii, A.; Haack, K.-J.; Matsumura, K.; Ikariya, T.; Noyori, R. Angew. Chem.
Int. Ed. Engl. 1997, 36, 288. (c) Alexander, J. B.; La, D. S.; Cefalo, D. R.; Hoveyda, A. H.; Schrock, R. R. J. Am. Chem.
Soc. 1998, 120, 4041. (d) Ready, J. M.; Jacobson, E. N. J. Am. Chem. Soc. 1999, 121, 6086. (e) Feng, X.; Shu, L.; Shi, Y.
J. Am. Chem. Soc. 1999, 121, 11002. (f) Vedejs, E.; Daugulis, O. J. Am. Chem. Soc. 1999, 121, 5813. (g) Frohn, M.; Zhou,
X.; Zhang, J.-R.; Tang, Y.; Shi, Y. J. Am. Chem. Soc. 1999, 121, 7718.
5
6
. (a) Gais, H.-J.; Eichelmann, H.; Spalthoff, N.; Gerhards, F.; Frank, M.; Raabe, G. Tetrahedron Asymmetry 1998, 9, 235. (b)
Frank, M.; Gais, H.-J. Tetrahedron: Asymmetry 1998, 9, 3353. (c) Böhme, A.; Gais, H.-J. Tetrahedron: Asymmetry 1999,
1
0, 2511.
. Sprinz, J.; Helmchen, G. Tetrahedron Lett. 1993, 34, 1769. von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32,
66. Dawson, G. J.; Frost, C. G.; Williams, J. M. J.; Coote, S. J. Tetrahedron Lett. 1993, 34, 3149.
5
7
8
9
. Trost, B. M.; van Vranken, D. L.; Bingel, C. J. Am. Chem. Soc. 1992, 114, 9327.
. For a previous example, see: Hayashi, T.; Yamamoto, A.; Ito, Y. J. Chem. Soc. Chem. Commun. 1986, 1090.
. For subsequent observations and an application, see: (a) Ramdeehul, S.; Dierkes, P.; Aguado, R.; Kamer, P. C. J.; van
Leeuwen, P. W. N. M.; Osborn, J. A. Angew. Chem., Int. Ed. Engl. 1998, 37, 3118. (b) Lloyd-Jones, G. C.; Stephen, S. C.
Chem. Commun. 1998, 2321. (c) Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 1999, 121, 3543. (d) Trost, B. M.; Hembre,
E. J. Tetrahedron Lett. 1999, 40, 219.
1
1
0. The maximum yield of the remaining carbonate is 50% and that of the sulfone(sulfide) is 100%.
1. Gupta, A. K.; Kazlauskas, R. J. Tetrahedron: Asymmetry 1993, 4, 879. Södergren, M. J.; Andersson, P. G. J. Am. Chem.
Soc. 1998, 120, 10760.
1
2. Crystallographic data for the structure reported in this paper have been deposited with the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK, as supplementary publication no. CCDC-142405.
3. All compounds were fully characterized including elemental analysis.
1