A new type of C2-symmetric bisphospine ligands with a cyclobutane backbone: Practical synthesis and application

Article abstract of DOI:10.1021/ol034299c

(Matrix presented) A highly efficient and practical optical resolution of anti-head-to-head racemic coumarin dimer, (±)-5, by molecular complexation with TADDOL (6) through hydrogen bonding and a convenient transformation of enantiopure 5 to a new type of C₂-symmetric bisphosphine ligand (3) have been achieved. The asymmetric induction efficiency of these chiral bisphosphine ligands was evaluated in Pd-catalyzed asymmetric allylic substitution, affording the allylic substitution products in excellent yield (up to 99%) and enantioselectivity (up to 98.9% ee).

Full text of DOI:10.1021/ol034299c

ORGANIC
LETTERS
2003
Vol. 5, No. 8
1349-1351
A New Type of C -Symmetric
2
Bisphospine Ligands with a
Cyclobutane Backbone: Practical
Synthesis and Application
Dongbo Zhao and Kuiling Ding*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032,
The People’s Republic of China
kding@pub.sioc.ac.cn
Received February 20, 2003
ABSTRACT
A highly efficient and practical optical resolution of anti-head-to-head racemic coumarin dimer, (±)-5, by molecular complexation with TADDOL
(6) through hydrogen bonding and a convenient transformation of enantiopure 5 to a new type of C -symmetric bisphosphine ligand (3) have
2
been achieved. The asymmetric induction efficiency of these chiral bisphosphine ligands was evaluated in Pd-catalyzed asymmetric allylic
substitution, affording the allylic substitution products in excellent yield (up to 99%) and enantioselectivity (up to 98.9% ee).
Asymmetric catalysis of organic reactions to provide enan-
tiomerically enriched products is of central importance to
modern synthetic and pharmaceutical chemistry.1 Develop-
ment of chiral ligands is one of the most fascinating methods
to achieve high enantioselectivity of a given catalytic
asymmetric reaction.2 Therefore, the need for the design of
novel chiral ligands has been an eternal theme for organic
chemists. On the basis of the fact that some C2-symmetric
bisphosphine ligands (such as BINAP,3 Trost’s ligand (1),4
and so on) showed excellent asymmetric induction in many
kinds of asymmetric reactions, we are interested in the
development of a new-type of C2-symmetric bisphosphine
ligand (3) with a cyclobutane backbone, which can be
considered as an analogue of 1 and 2.5 In this paper, we
report the first synthesis of 3 and its application to Pd-
catalyzed asymmetric allylic substitution. An efficient and
practical resolution of anti-head-to-head racemic coumarin
dimer (()-5 has also been achieved by molecular complex-
ation with (R,R)-(-)-trans-bis(hydroxyldiphenylmethyl)-2,2-
dimethyl-1,3-dioxacyclopentane (TADDOL, 6) to give enan-
tiopure 5, a key intermediate for the synthesis of 3.
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley-
Interscience: New York, 1994. (b) Catalysis Asymmetric Synthesis, 2nd
ed; Ojima, I., Ed.; Wiley-VCH: New York, 2000. (c) ComprehensiVe
Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer, Berlin, 1999; Vols. I-III. (d) Lewis Acids in Organic Synthesis;
Yamamoto, H., Ed.; Wiley-VCH: New York, 2001.
(2) Brunner, H.; Zettlmeier, W. Handbook of EnantioselectiVe Catalysis
with Transition Metal Compounds; VCH: Weinheim, 1993; Vol. II.
(3) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40.
(4) Trost, B. M.; Van Vranken, D. L. Chem. ReV. 1996, 96, 395.
(5) (a) Hayashi, M.; Hashimoto, Y. Takezaki, H.; Watanabe, Y.; Saigo,
K. Tetrahedron: Asymmetry 1998, 9, 1863. For the examples of bisphosphine
ligands with five-membered ring backbones, see: (b) Fukuda, N.; Mashima,
K.; Matumura, Y.; Takaya, H. Tetrahedron Lett. 1990, 31, 7185. (c) Terfort,
A.; Brunner, H. J. Chem. Soc., Perkin Trans. 1 1996, 1467.
10.1021/ol034299c CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/27/2003

Scheme 1. Practical Optical Resolution of Coumarin Dimer
with TADDOL by Molecular Complexation
As shown in Scheme 1, the preparation of anti-head-to-
head racemic coumarin dimer (()-5 was carried out follow-
ing a literature method by irradiation of coumarin 4 in
benzene solution in the presence of benzophenone as a
sensitizer in >90% yield (0.2 mol scale).6 Although the
optical resolution of (()-5 could be achieved by stepwise
recrystallization of its diastereomers formed with enantiopure
R-phenylethamine, followed by acidic hydrolysis and recy-
clization of hydroxy acid,7 the process is somewhat long.
Direct synthesis of enantiopure 5 through a topochemical-
controlled [2 + 2] photodimerization of coumarin 4 included
in TADDOL (6) host in the solid state or in aqueous
suspension was recently reported by Toda, giving (-)-5 in
99% yield with 100% ee.8 Despite the difficulty of large-
scale preparation using this strategy, the perfect molecular
recognition between 6 and (-)-5 in the product prompted
us to utilize easily available 69 as a chiral host to resolve
two enantiomers of 5 by molecular complexation through
hydrogen bonding. Heating a mixture of an equal molar
amount of (()-5 and resolving agent 6 in ethyl acetate,
followed by cooling the homogeneous solution to room
temperature, resulted in the formation of molecular crystals
between 6 and (-)-5 with 88.3% ee of (-)-5. The precipi-
tated crystals were collected by filtration and washed with
ethyl acetate, which were characterized as 2:1 molecular
crystals of 6 and (-)-5 by 1H NMR. The enantiomeric excess
of the opposite enantiomer ((+)-5) that remained in mother
liquid was 81.7%. Further recrystallization of the molecular
crystals (-)-5‚[6]2 from ethyl acetate afforded enantiopure
(-)-5‚[6]2 in 70% yield. Decomposition of the molecular
crystals (-)-5‚[6]2 with DMF gave (-)-5 and 6‚DMF
complex in quantitative yields. The absolute configuration
of (-)-5 was assigned to be S,S,S,S by comparison of its
optical rotation with that reported in the literature.8a The
enantiomeric excess of (+)-5 in the mother liquid could be
further enriched to 99% by recrystallization from ethanol.
The resolving agent 6 could be recovered in >99% yield by
decomposition of molecular crystals, 6‚DMF, in water and
followed by extraction with ethyl acetate (see the Supporting
Information).
With enantiopure 5 in hand, we extended its application
to the synthesis of a new type of C2-symmetric bisphosphine
ligand 3. As shown in Scheme 2, refluxing ethanol solution
Scheme 2. Transformation of Enantiopure Coumarin Dimer
(5) to a New Type of Chiral Bisphosphine Ligands (3a-f)
of 5 resulted in the lactone ring opening to give ethyl ester
7 in quantitative yield. Treatment of 7 with (CF3SO2)2O in
the presence of Et3N gave its ditriflate derivative 8 quanti-
tatively. Compound 8 underwent a coupling reaction with
diarylphosphine oxides in the presence of Pd(OAc)2/dppp
(dppp ) 1,3-bis(diphenyl-phosphino)propane) and diiso-
propylethylamine to give corresponding 1,2-bis(2-diaryl-
phosphinylphenyl)cyclo-butane derivatives 9a-f in good to
excellent yields.10 The target bisphosphine ligands 3a-f were
easily obtained by the reduction of their oxides 9a-f with
HSiCl3 in the presence of N,N-dimethylaniline in 74-91%
yields.
(6) Krauch, C. H.; Farid, S.; Schenck, G. O. Chem. Ber. 1966, 99, 625.
(7) Saigo, K.; Yonezawa, N.; Sekimoto, K.; Hasegawa, M.; Ueno, K.;
Nakanishi, H. Bull. Chem. Soc. Jpn. 1985, 58, 1000.
(8) (a) Tanaka, K.; Toda, F.; Mochizuki, E.; Yasui, N.; Kai, Y.; Miyahara,
I.; Hirotsu, K. Angew. Chem., Int. Ed. 1999, 39, 3523. (b) Tanaka, K.; Toda,
F. J. Chem. Soc., Perkin Trans. 1 1992, 943.
Pd-catalyzed enantioselective allylic substitution is one of
the most important C-C or C-N bond forming reactions
(9) Seebach, D.; Beck, A. K.; Imwinkelried, R.; Roggo, S.; Wonnacott,
A. HelV. Chim. Acta 1987, 70, 954.
1350
Org. Lett., Vol. 5, No. 8, 2003

in modern asymmetric catalysis.11 To demonstrate the
asymmetric induction efficiency of the chiral ligands 3a-f,
Pd-catalyzed enantioselective allylic substitution was taken
as a model reaction. 1,3-Diphenylprop-2-enyl acetate (10)
was employed as the substrate, and dimethylmalonate 11a
and benzylamine 11b were utilized as nucleophiles, respec-
tively. As shown in Table 1, all of the chiral ligands (3a-f)
The extension of the present catalyst system to the allylic
substitution of cyclic substrate 1312 (Scheme 3) demonstrated
that the reaction proceeded smoothly to give the correspond-
ing cyclic allylation products 14a and 14b in good yields
(70-85%) and enantioselectivities (77.8-87.5% ee) using
5 mol % of the catalysts.
Scheme 3. Pd/3-Catalyzed Enantioselective Allylic
Table 1. Pd/3-Catalyzed Enantioselective Allylic Substitutionsa
Substitutions of Cyclic Substrate
entry ligand
base
NuH product yieldb (%) eec (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
3a
3b
3c
3d
3e
3f
BSA
11a
11a
11a
11a
11a
11a
11a
11b
11b
11b
11b
11b
11b
12a
12a
12a
12a
12a
12a
12a
12b
12b
12b
12b
12b
12b
99
99
99
99
99
99
99
99
94
91
96
91
97
96.8
97.3
95.8
96.1
98.0
97.5
98.9
95.6
96.7
97.5
96.4
96.2
96.2
BSAd
BSAd
BSAd
BSAd
BSAd
BSA
In summary, a highly efficient and practical optical
resolution of anti-head-to-head racemic coumarin dimer 5
by molecular complexation with TADDOL 6 through
hydrogen bonding and a convenient transformation of
enantiopure 5 to a new type of C2-symmetric bisphosphine
ligand 3, have been achieved.13 The asymmetric induction
efficiency of these chiral bisphosphine ligands was evaluated
in Pd-catalyzed asymmetric allylic substitution. Under the
experimental conditions, the allylic substitution products
could be obtained in excellent yield (up to 99%) and
enantioselectivity (up to 98.9% ee). The research on the
application of 3 to other asymmetric reactions and develop-
ment of polymer-supported bisphosphine ligands14 by taking
the advantage of easily derived carboxylate groups at the
backbone of cyclobutane is underway in this laboratory.
3f
3a
3b
3c
3d
3e
3f
a Molar ratio of 10/NuH/[η-allylPdCl]2/3 ) 1:2:0.025:0.06. b Isolated
yield. c Determined with HPLC on a Chiralcel OJ or AD column. d 2 equiv
of BSA was added in the presence of 5 mol % of LiOAc.
showed excellent asymmetric induction in the model reaction
to give corresponding allylation products in 91-99% yields
with 95.6-98.9% ee.
(10) For selected examples of C-P bond formation, see (a) Uozumi,
Y.; Takahashi, A.; Lee, S. Y.; Hayashi, T. J. Org. Chem. 1993, 58, 1945.
(b) Ding, K.; Wang, Y.; Yun, H.; Liu, J.; Wu, Y.; Terada, M.; Okubo, Y.;
Mikami, K. Chem. Eur. J. 1999, 5, 1734. (c) Vyskocil, S.; Smrcina, M.;
Hanus, V.; Polasek, M.; Kocovsky, P. J. Org. Chem. 1998, 63, 7738.
(11) For reviews, see: (a) Pfaltz, A.; Lautens, M. In ComprehensiVe
Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer, Berlin, 1999; Vol. II, pp 833-884. (b) Trost, B. M. Chem. Pharm.
Bull. 2002, 50, 1. (c) Trost, B. M. Acc. Chem. Res. 1996, 29, 355. (d) Trost,
B. M.; Van Vranken, D. L. Chem. ReV. 1996, 96, 395. (e) Hayashi, T. In
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH Publishers, Inc.: New
York, 1993. For selected examples, see: (f) Trost, B. M.; Van Vranken,
D. L.; Bingel, C. J. Am. Chem. Soc. 1992, 114, 9327. (g) Matt, P. V., Pfaltz,
A. Angew. Chem., Int. Ed. Engl. 1993, 32, 566. (h) Deng, W.-P.; You,
S.-L.; Hou, X.-L.; Dai, L.-X.; Yu, Y.-H.; Xia, W.; Sun, J. J. Am. Chem.
Soc. 2001, 123, 6508.
Acknowledgment. Financial support from the NSFC,
CAS, and the Major Basic Research Development Program
of China (Grant No. G2000077506) is gratefully acknowl-
edged.
Supporting Information Available: Spectral character-
ization of the products and experimental details for asym-
metric reactions. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL034299C
(12) For examples of reaction systems using cyclic substrates, see: (a)
Trost, B. M.; Bunt, R. C. J. Am. Chem. Soc. 1994, 116, 4089. (b) Kudis,
S.; Helmchen, G. Angew. Chem., Int. Ed. 1998, 37, 3047. (c) Gilbertson,
S. R.; Xie, D. Angew. Chem., Int. Ed. 1999, 38, 2750. (d) Evans, D. A.;
Campos, K. R.; Tedrow, J. S.; Michael, F. E.; Gagne, M. R. J. Am. Chem.
Soc. 2000, 122, 7905.
(13) Ding, K.; Zhao, D. Chinese Patent pending (01126762.6; 03115826.9).
(14) For recent examples of polymer-supported catalysts for asymmetric
allylation, see: (a) Uozumi, Y.; Shibatomi, K. J. Am. Chem. Soc. 2001,
123, 2919. (b) Song, C. E.; Yang, J. W.; Roh, E. J.; Lee, S.-G.; Ahn, J. H.;
Han, H. Angew. Chem., Int. Ed. 2002, 41, 3852. (c) Trost, B. M.; Pan, Z.;
Zambrano, J.; Kujat, C. Angew. Chem., Int. Ed. 2002, 41, 4691.
Org. Lett., Vol. 5, No. 8, 2003
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