A new class of planar-chiral ligands: Synthesis of a C2-symmetric bisazaferrocene and its application in the enantioselective Cu(I)-catalyzed cyclopropanation of olefins

Full text of DOI:10.1021/ja982488y

10270
J. Am. Chem. Soc. 1998, 120, 10270-10271
A New Class of Planar-Chiral Ligands: Synthesis of
a C2-Symmetric Bisazaferrocene and Its Application
in the Enantioselective Cu(I)-Catalyzed
Cyclopropanation of Olefins
Michael M.-C. Lo and Gregory C. Fu*
Department of Chemistry
Massachusetts Institute of Technology
Cambridge, Massachusetts 02139
Bisazaferrocene 1 bears a resemblance to semicorrins and to
bisoxazolines, insofar as they are all bidentate ligands in which
the ligating sites are sp2-hybridized nitrogen atoms. Pfaltz,
Masamune, and Evans have established that copper complexes
of C2-symmetric semicorrins and bisoxazolines function as highly
efficient catalysts for the enantioselective cyclopropanation of
olefins by diazoacetates.8-11 In view of these reports, we decided
that an investigation of copper-catalyzed cyclopropanation would
provide a suitable testing ground for determining the effectiveness
of our ligand design.
Treatment of styrene with ethyl diazoacetate in the presence
of 1% CuOTf‚(R,R)-1 furnishes the desired cyclopropane with
modest diastereo- and enantioselectivity (Table 1, entry 1).12 When
chiral semicorrins or bisoxazolines are employed as ligands in
copper-catalyzed cyclopropanation, increasing the steric demand
of the diazo ester can lead to a significant improvement in
stereoselectivity.4,8-10 We have observed parallel behavior with
bisazaferrocene ligand 1 (Table 1, entries 1-5). Thus, in the
presence of 1% CuOTf‚(R,R)-1, styrene reacts with the BHT ester
of diazoacetic acid to produce trans-cyclopropane with excellent
diastereo- and enantioselectivity (Table 1, entry 5).13
ReceiVed July 15, 1998
Prior to 1996, there had been no reports of applications of
planar-chiral heterocycles in asymmetric catalysis. Several years
ago, we initiated a program directed at the development of this
family of compounds as enantioselective nucleophilic catalysts1
and as chiral ligands for transition metals.2 Our early work in
the area of ligand design focused on complexes with C1-
symmetry,2 but we have recently expanded the scope of our
investigation to include C2-symmetric systems. In this paper, we
describe the synthesis and resolution of a new bidentate, C2-
symmetric planar-chiral bisazaferrocene (1), and we establish
The use of the more hindered diazo ester provides the added
bonus of an increased yield of cyclopropane, due to decreased
formation of maleates and fumarates from copper-catalyzed
coupling of the diazo ester.14 The data in entries 3 and 4 indicate
that the stereochemistry of a chiral diazo ester has little impact
on the selectivity established by ligand 1.15
its effectiveness as a chiral ligand in the Cu(I)-catalyzed enan-
tioselective cyclopropanation of olefins (eq 1).3,4
With the BHT ester of diazoacetic acid as the carbene source,
we investigated the [CuOTf‚(R,R)-1]-catalyzed asymmetric cy-
clopropanation of an array of monosubstituted olefins (Table
2).16,17 For styrene derivatives, we have determined that the
The synthesis of bisazaferrocene 1 is quite straightforward;
treatment of FeCl2 first with Cp*Li and then with the dilithio
salt of di(2-pyrrolyl)methane5 in the presence of AgCN provides
(()-1 in 66% yield (eq 2; separated from the meso diastereomer
by flash chromatography).6 The enantiomeric ligands can be
separated readily by chiral HPLC (Daicel Chiraldex OD).7 We
have determined the absolute configuration of (S,S)-1 by X-ray
crystallography (vide infra).
(8) (a) Fritschi, H.; Leutenegger, U.; Pfaltz, A. Angew. Chem., Int. Ed.
Engl. 1986, 25, 1005-1006. (b) Mu¨ller, D.; Umbricht, G.; Weber, B.; Pfaltz,
A. HelV. Chim. Acta 1991, 74, 232-240. (c) Pfaltz, A. AdV. Catal. Proc.
1995, 1, 61-94.
(9) Lowenthal, R. E.; Abiko, A.; Masamune, S. Tetrahedron Lett. 1990,
31, 6005-6008.
(10) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J. Am.
Chem. Soc. 1991, 113, 726-728.
(11) Bisazaferrocene 1 also bears a resemblance to chiral bipyridine and
to chiral pyrazole-derived ligands. (a) For applications of bipyridines in
catalytic asymmetric cyclopropanation, see: Ito, K.; Tabuchi, S.; Katsuki, T.
Synlett 1992, 575-576. Chelucci, G.; Cabras, M. A.; Saba, A. J. Mol. Catal.
A: Chem. 1995, 95, L7-L10. Kwong, H.-L.; Lee, W.-S.; Ng, H.-F.; Chiu,
W.-H.; Wong, W.-T. J. Chem. Soc., Dalton Trans. 1998, 1043-1046. For a
review of applications of bipyridines in asymmetric catalysis, see: Chelucci,
G. Gazz. Chim. Ital. 1992, 122, 89-98. (b) For applications of pyrazole-
derived ligands in catalytic asymmetric cyclopropanation, see: Brunner, H.;
Singh, U. P.; Boeck, T.; Altmann, S.; Scheck, T.; Wrackmeyer, B. J.
Organomet. Chem. 1993, 443, C16-C18. Christenson, D. L.; Tokar, C. J.;
Tolman, W. B. Organometallics 1995, 14, 2148-2150.
(1) (a) Ruble, J. C.; Fu, G. C. J. Org. Chem. 1996, 61, 7230-7231. (b)
Ruble, J. C.; Latham, H. A.; Fu, G. C. J. Am. Chem. Soc. 1997, 119, 1492-
1493. (c) Ruble, J. C.; Tweddell, J.; Fu, G. C. J. Org. Chem. 1998, 63, 2794-
2795. (d) Liang, J.; Ruble, J. C.; Fu, G. C. J. Org. Chem. 1998, 63, 3154-
3155. (e) Garrett, C. E.; Lo, M. M.-C.; Fu, G. C. J. Am. Chem. Soc., 1998,
120, 7479-7483.
(2) (a) Dosa, P. I.; Ruble, J. C.; Fu, G. C. J. Org. Chem. 1997, 62, 444-
445. (b) Qiao, S.; Fu, G. C. J. Org. Chem. 1998, 63, 4168-4169.
(3) (a) Nozaki, H.; Moriuti, S.; Takaya, H.; Noyori, A. Tetrahedron Lett.
1966, 5239-5244. (b) Aratani, T. Pure Appl. Chem. 1985, 57, 1839-1844.
(4) For reviews, see: (a) Doyle, M. P.; Forbes, D. C. Chem. ReV. 1998,
98, 911-935. (b) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds; Wiley: New York,
1998. (c) Singh, V. K.; DattaGupta, A.; Sekar, G. Synthesis 1997, 137-149.
(d) Calter, M. A. Curr. Org. Chem. 1997, 1, 37-70.
(5) Di(2-pyrrolyl)methane can be synthesized in one step from pyrrole and
formaldehyde: Wang, Q. M.; Bruce, D. W. Synlett 1995, 1267-1268.
(6) In the absence of AgCN, (()-1 is generated with poor diastereoselec-
tivity and in low yield.
(12) CuOTf (Salomon, R. G.; Kochi, J. K. J. Am. Chem. Soc. 1973, 95,
3300-3310) was the most effective of the copper complexes that were
surveyed.
(13) For the first report of use of the BHT ester of diazoacetic acid to
control trans:cis selectivity in metal-catalyzed cyclopropanations, see: Doyle,
M. P.; Bagheri, V.; Wandless, T. J.; Harn, N. K.; Brinker, D. A.; Eagle, C.
T.; Loh, K.-L. J. Am. Chem. Soc. 1990, 112, 1906-1912.
(14) Other workers have minimized this deleterious coupling reaction by
employing a large excess of olefin in their cyclopropanations; under these
conditions, the diazo ester is the limiting reagent. In our procedure, on the
other hand, we use the olefin as the limiting reagent.
(7) Solvent system: 0.1/5/95 Et2NH/i-PrOH/hexanes; retention time of (+)-
1: 6.6-7.8 min; retention time of (-)-1: 9.0-10.8 min.
(15) For similar observations by others, see ref 4.
S0002-7863(98)02488-3 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/19/1998

Communications to the Editor
J. Am. Chem. Soc., Vol. 120, No. 39, 1998 10271
Table 1. Catalytic Enantioselective Cyclopropanation of Styrene:
Stereoselectivity as a Function of Diazo Estera
% ee
isolated yield,
entry
OR
trans:cis
trans
cis
trans (%)
1
2
3
4
5
OEt
O-t-Bu
(+)-menthyl
(-)-menthyl
O-BHT
76:24
86:14
88:12
85:15
96:4
73
87
87
89
94
44
82
81
84
39
63
67
66
79
a All data represent the average of two runs.
Figure 1. ORTEP illustration, with thermal ellipsoids drawn at the 35%
probability level, of [Cu((S,S)-1)(styrene)]OTf (the triflate is noncoor-
dinating and is not included).
Table 2. Catalytic Enantioselective Cyclopropanation of
Monosubstituted Olefinsa
Finally, we have obtained an X-ray crystal structure of [Cu-
((S,S)-1)(styrene)]OTf (Figure 1).19,20 Ligand 1 binds to copper
to provide an adduct with approximate C2-symmetry. Complex-
ation of the olefin leads to a square-planar geometry, and the
phenyl substituent occupies one of the two quadrants left open
by the bisazaferrocene. While this crystal structure nicely reveals
the effective chiral environment generated by ligand 1, it is
interesting to note from a mechanistic point of view that the olefin
face that is bound to copper in this structure is not the face that
undergoes cyclopropanation.
In summary, we have developed a straightforward synthesis
and resolution of bisazaferrocene 1, a member of a new class of
bidentate, C2-symmetric ligands based on planar-chiral hetero-
cycles. Furthermore, we have established that ligand 1 can
effectively mediate the enantioselective Cu(I)-catalyzed cyclo-
propanation of an array of olefins. In future work, we intend to
tune the stereoselection of this new family of ligands by changing
the metal (Fe), the ligand on the metal (Cp*), and the linker (CH2)
between the heterocycles.
entry
R
trans:cis
% ee, trans
yield (%)b
1
2
3
4
5
6c
Ph
96:4
94:6
94:6
94:6
93:7
99:1
94
96
87
91
90
95
79
81
90
78
80
64
p-(F3C)C6H4
p-(MeO)C6H4
PhCH2
n-Hex
Et3Si
a All data represent the average of two runs. b For entries 1, 4, 5,
and 6, the yield refers to the isolated yield of the trans diastereomer.
For entries 2 and 3, the yield refers to the isolated yield of a mixture
of cis and trans isomers. c 2% CuOTf/2.4% (R,R)-1 was used.
enantioselectivity is moderately sensitive to electronic effects.
Thus, electron-poor p-trifluoromethylstyrene (entry 2) undergoes
addition with greater enantiomeric excess than does either styrene
(entry 1) or electron-rich p-methoxystyrene (entry 3).
Importantly, CuOTf‚(R,R)-1 is an efficient catalyst not only
for the asymmetric cyclopropanation of aryl-substituted olefins
but also for alkyl- and silyl-substituted olefins. Thus, allylbenzene
and 1-octene react with the diazoester to produce the trans-
cyclopropane in high enantiomeric excess (entries 4 and 5).
Furthermore, vinyltrimethylsilane undergoes addition with excel-
lent diastereo- and enantioselectivity (entry 6).18
Acknowledgment. We thank the Buchwald group (MIT) for gener-
ously sharing their GC and HPLC equipment and Mr. Diego A. Hoic
and Dr. William M. Davis for X-ray crystallographic assistance. Support
has been provided by the Alfred P. Sloan Foundation, the American
Cancer Society, Bristol-Myers Squibb, the Camille and Henry Dreyfus
Foundation, Eli Lilly, Firmenich, Glaxo Wellcome, the National Science
Foundation (Young Investigator Award, with funding from Merck,
Pharmacia & Upjohn, DuPont, Bayer, and Novartis), Pfizer, Procter &
Gamble, and the Research Corporation.
(16) Sample experimental (Table 2, entry 1): A solution of CuOTf‚0.5
C6H6 (1.4 mg, 0.0056 mmol) and (R,R)-1 (3.6 mg, 0.0067 mmol) in 1.0 mL
of CH2Cl2 was transferred to a vessel containing styrene (59.6 mg, 0.570
mmol). The resulting solution was stirred for five min, and then the BHT
ester of diazoacetic acid (68.5 mg, 0.240 mmol, 0.42 equiv) was added. TLC
analysis after 10 h showed that the diazo ester had been completely consumed.
Additional diazo ester (0.40 equiv) was then added, and the resulting mixture
was stirred for 10 h. The final batch of diazo ester (0.40 equiv) was then
added, and the reaction mixture was stirred for 16 h, at which time TLC
analysis showed no residual styrene or diazo ester. The reaction mixture was
filtered through a plug of silica gel, and an aliquot was analyzed by GC, which
revealed a 96:4 trans:cis mixture. The product was purified by chromatography,
which afforded the trans-cyclopropane as a colorless liquid (154 mg, 74%;
chiral GC w 95% ee).
Supporting Information Available: Experimental procedures, com-
pound characterization data, and X-ray crystal structure data (20 pages).
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JA982488Y
(18) We have begun to explore reactions of more highly substituted olefins.
For example, in preliminary experiments we have found that CuOTf‚(R,R)-1
catalyzes the cyclopropanation of trans-â-methylstyrene with good diastereo-
and enantioselectivity (94% de; 87% ee (trans)).
(19) We have also obtained an X-ray crystal structure of [Cu((S,S)-1)-
(allylbenzene)]OTf.
(17) The absolute stereochemistry of the product cyclopropanes is the
“expected” one, based on the structural and steric analogy between bisaza-
ferrocene 1 and semicorrins/bisoxazolines.
(20) For a previous study of a [Cu(chiral diimine)(olefin)]+ complex, see:
Quan, R. W.; Li, Z.; Jacobsen, E. N. J. Am. Chem. Soc. 1996, 118, 8156-
8157.