Direct and highly enantioselective synthesis of ferrocenes with planar chirality by (-)-sparteine-mediated lithiation

Full text of DOI:10.1021/ja953246q

J. Am. Chem. Soc. 1996, 118, 685-686
685
Communications to the Editor
Scheme 1
Direct and Highly Enantioselective Synthesis of
Ferrocenes with Planar Chirality by
(-)-Sparteine-Mediated Lithiation
M. Tsukazaki,† M. Tinkl, A. Roglans, B. J. Chapell,
N. J. Taylor, and V. Snieckus*,‡
The Guelph-Waterloo Centre for
Graduate Work in Chemistry
UniVersity of Waterloo, Waterloo,
Ontario N2L 3G1, Canada
Scheme 2
ReceiVed September 22, 1995
We report the first direct and highly enantioselective synthesis
of ferrocenyl derivatives with planar chirality Via a (-)-
sparteine-mediated Directed ortho Metalation (DoM) process
(1 f 2, Scheme 1). Although reports for the effective
diastereoselective preparation of chiral 1,2-disubstituted fer-
rocenes using chiral Directed Metalation Group (DMG) auxil-
iaries have been rapidly accumulating (Scheme 2),1 direct
methods to obtain enantiomerically pure ferrocenyls,2 unre-
stricted by requirement for substrate-specific resolution1a,3 and
chiral auxiliary removal,1b-f have not been hitherto described.
Our work is a rational extension of DoM strategies4 and is
stimulated by the results of Hoppe5a and Beak,5b demonstrating
that (-)-sparteine is an effective ligand for high asymmetric
induction in lithiation-substitution reactions. In view of the
increasing importance of ferrocenes with planar chirality6a in
asymmetric catalysis,6b enantioselective synthesis,6c and diverse
material science areas,6d significant utility and broad application
of the present methodology may be anticipated.
Table 1. n-BuLi/(-)-Sparteine-Induced Metalation of
N,N-Diisopropyl Ferrocenecarboxamide (1): Electrophiles, Yields,
and Enantioselectivities
E+ a
E
product
yield, %b
ee, %
TMSCl
MeI
Et2CO
Ph2CO
ClCH2OCH3
I2
(PhS)2
(PhSe)2
Ph2PCl
B(OMe)3
TMS
Me
Et2C(OH)
Ph2C(OH)
CH2OCH3
I
PhS
PhSe
Ph2P
B(OH)2
2a
2b
2c
2d
2e
2f
2g
2h
2i
96
91
45
91
62
85
90
92
82
89
98
94
99
99
81
96
98c
93c
90c
85
† Monsanto Scholar, 1992-1995.
‡ FAX: 519-746-5884. E-mail: snieckus@buli.uwaterloo.ca.
(1) Pioneering study: (a) Marquarding, D.; Klusacek, H.; Gokel, G.;
Hoffmann, P.; Ugi, I. J. Am. Chem. Soc. 1970, 92, 5389. Battelle, L. F.;
Bau, R.; Gokel, G. W.; Oyakawa, R. T.; Ugi, I. K. J. Am. Chem. Soc. 1973,
95, 482. Recent work: (b) Rebie`re, F.; Riant, O.; Ricard, L.; Kagan, H.
B. Angew. Chem., Int. Ed. Engl. 1993, 32, 568. (c) Riant, O.; Samuel, O.;
Kagan, H. B. J. Am. Chem. Soc. 1993, 115, 5835. (d) Nishibayashi, Y.;
Uemura, S. Synlett 1995, 79. (e) Sammakia, T.; Latham, H. A.; Schaad,
D. R. J. Org. Chem. 1995, 60, 10. (f) Richards, C. J.; Damalidis, T.; Hibbs,
D. E.; Hursthouse, M. B. Synlett 1995, 74.
2j
a 2.2 equiv of n-BuLi/(-)-sparteine was used with the exception of
E+ ) TMSCl, Et2CO, and Ph2CO (1.2 equiv of n-BuLi/(-)-sparteine).
b All yields refer to isolated and purified (chromatographed) materials.
c Compounds 2g-i undergo slow racemization at room temperature
(ref 12). Therefore, ee determination was carried out immediately after
purification.
(2) After the submission of this manuscript, a report appeared describing
the asymmetric metalation of diphenylphosphinylferrocene with chiral
lithium amide bases, resulting in moderate enantioinduction (55% ee): Price,
D.; Simpkins, N. S. Tetrahedron Lett. 1995, 36, 6135.
Deprotonation (1.2 equiv of n-BuLi/(-)-sparteine/Et2O/-78
°C) of N,N-diisopropyl ferrocenecarboxamide (1)7,8 followed
byquenching with TMSCl, warming to room temperature, and
standard aqueous NH4Cl workup afforded the silylated product
2a in 96% chemical yield and 98% ee (Table 1).9 Similarly,
sequential DoM and electrophile quench produced a variety of
substituted ferrocenes 2b-j in high yield and excellent enan-
tioselectivity. For compounds 2b,e-j, 2.2 equiv of n-BuLi/
sparteine was required to achieve optimum chemical yield; in
these cases, the change of stoichiometry did not lead to erosion
of ee. Enantiomeric excess was established by comparison with
racemic products, prepared by deprotonation with n-BuLi/
TMEDA/Et2O/-78 °C, using chiral HPLC.10 The (S) absolute
configuration of 2c was established by single-crystal X-ray
(3) Schlo¨gl, K. Top. Stereochem. 1967, 1, 39. See, inter alia: Hayashi,
T.; Kumada, M. Acc. Chem. Res. 1982, 15, 395. Sawamura, M.;
Hamashima, H.; Ito, Y. Tetrahedron: Asymmetry 1991, 2, 593. For other
methods to obtain ferrocenes with planar chirality, see: Ratajczak, A.;
Misterkiewicz, B. J. Organomet. Chem. 1975, 91, 73. Hayashi, T.; Mise,
T.; Kumada, M. Tetrahedron Lett. 1976, 4351. Wang, Y.-F.; Lalonde, J.
J.; Momongan, M.; Bergbreiter, D. E.; Wong, C.-H. J. Am. Chem. Soc.
1988, 110, 7200. Boaz, N. W. Tetrahedron Lett. 1989, 30, 2061. David,
D. M.; Kane-Maguire, L. A. P.; Pyne, S. G. J. Chem. Soc., Chem. Commun.
1990, 888. Nicolosi, G.; Patti, A.; Morrone, R.; Piattelli, M. Tetrahedron:
Asymmetry 1994, 5, 1275.
(4) Snieckus, V. Chem. ReV. 1990, 90, 879.
(5) (a) Hoppe, D.; Hintze, F.; Tebben, P.; Paetow, M.; Ahrens, H.;
Schwerdtfeger, J.; Sommerfeld, P.; Haller, J.; Guarnieri, W.; Kolczewski,
S.; Hense, T.; Hoppe, I. Pure Appl. Chem. 1994, 66, 1479. (b) Thayumana-
van, S.; Lee, S.; Liu, C.; Beak, P. J. Am. Chem. Soc. 1994, 116, 9755.
Beak, P.; Kerrick, S. T.; Wu, S.; Chu, J. J. Am. Chem. Soc. 1994, 116,
3231 and references cited therein. For original observations: (c) Aratani,
T.; Gonda, T.; Nozaki, H. Tetrahedron Lett. 1969, 2265; Tetrahedron 1970,
26, 5453.
(7) Prepared from ferrocenecarboxylic acid (Aldrich) by sequential
treatment with COCl2/cat. DMF/CH2Cl2 and HN(i-Pr)2 in 74% yield after
recrystallization (hexane).
(6) (a) Togni, A., Hayashi, T., Eds. Ferrocenes: Homogeneous Catalysis,
Organic Synthesis, Materials Science; VCH: Weinheim, 1995. Illustrative
examples: (b) Sawamura, M.; Ito, Y. Chem. ReV. 1992, 92, 857. (c)
Nicolosi, G.; Patti, A.; Morrone, R.; Piattelli, M. Tetrahedron: Asymmetry
1994, 5, 1639. (d) Lion-Dagan, M.; Marx-Tibbon, S.; Katz, E.; Willner, I.
Angew. Chem., Int. Ed. Engl. 1995, 34, 1604.
(8) For DoM chemistry of ferrocenes, see ref 1f.
(9) Metalation with s-BuLi/(-)-sparteine in Et2O and t-BuOMe produced
94% and 97% yields and 74% and 67% ee, respectively.
(10) CHIRALCEL OD, CHIRALCEL OK, and CHIRALCEL OJ chiral
columns were used. For details, see supporting information.
0002-7863/96/1518-0685$12.00/0 © 1996 American Chemical Society

686 J. Am. Chem. Soc., Vol. 118, No. 3, 1996
Communications to the Editor
Scheme 3
and benzophenone quench resulted in exclusive formation of 4
(Scheme 3), a result suggesting that the amide DMG effect is
overridden by steric hindrance factors in the substituted Cp
ring.14 In order to show the combined potential of DoM-cross-
coupling reactions, a powerful strategy in aromatic and het-
eroaromatic chemistry,15 the iodoferrocenyl amide 2f was
subjected to the Suzuki procedure with (2,4-dimethoxyphenyl)-
boronic acid to afford 5 in low yield but unchanged enantiomeric
excess together with the dehalogenation product 1 (Scheme 3).16
The present results demonstrate the first direct and highly
efficient enantioselective synthesis of ferrocenyl carboxamide
derivatives with planar chirality using sparteine-mediated DoM.
Enantiomerically pure ferrocenes are thus available from achiral
precursors without recourse to tedious methods of resolution
and chemical manipulation of chiral DMG auxiliaries. Fur-
thermore, aryl-substituted systems may be prepared by a
combined DoM-cross-coupling regimen (2f f 5). The ready
availability of diverse DMG-bearing ferrocenes,6 the rich
functional group chemistry of ferrocenes, and the flourishing
use of these ligands in asymmetric catalysis and synthesis
suggest considerable utility of these findings.
crystallographic analysis.11 In view of the configurational
stability of the sp2-hybridized ferrocenyl carbanion, enantiose-
lective induction must occur at the deprotonation and not
electrophile substitution step.5b On this basis, the corresponding
configurational outcome can be provisionally assigned to all
1,2-disubstituted ferrocenes 2a,b,d-j.
Acknowledgment. We are grateful to NSERC Canada for financial
support through Research and Industrial Chair awards and to “Gener-
alitat de Catalunya” (Spain) for a postdoctoral fellowship (A.R.). We
acknowledge R. Laufer for early studies and warmly thank Dr. A. Mical
(Dupont Merck) for rapid and dedicated assistance with chiral HPLC
analysis.
As depicted in Table 1, the electrophiles introduced provide
diverse carbon (2b-e) and heteroatom (2a,f-j)-based12 chiral
ferrocenes, some of which (2c,d,i) are related to popular ligands
for enantioselective catalysis.6 In fact, reduction (BH3/THF)
of 2d (Scheme 3) furnished 3, whose use in asymmetric
synthesis is under study.13 Subsequent metalation of 2a under
achiral conditions (1.2 equiv of n-BuLi/THF or s-BuLi/Et2O)
Supporting Information Available: Detailed description of ex-
perimental procedures for the preparation and reactions of 1-5 (12
pages). This material is contained in many libraries on microfiche,
immediately follows this article in the microfilm version of the journal,
can be ordered from the ACS, and can be downloaded from the Internet;
see any current masthead page for ordering information and Internet
access instructions.
(11) Crystal data for 2c, C22H23FeNO2, Mr ) 399.36, orthorhombic,
P212121, a ) 7.4383(7) Å, b ) 9.8099(8) Å, c ) 28.763(2) Å, V )
2098.8(3) Å3, Z ) 4, Dc ) 1.264 g/cm3, µ(Mo KR) ) 7.33 cm-1, F(000)
) 856, T ) 200 K. Data were collected on a Siemens P4 diffractometer
with Mo KR radiation (λ ) 0.710 73 Å); 6866 reflections were measured
giving 6130 independent reflections (unmerged Friedel opposites). The
structure was solved using Patterson and Fourier routines (SHELXTL IRIS)
and refined by full-matrix least squares on F resulting in final R, Rw and
GOF (for 5006 data with F > 6.0σ(F)) of 0.0283, 0.0298, and 1.59,
respectively, for solution using the S model. The corresponding values for
solution of the R model were 0.0430, 0.0467, and 2.49.
(12) Compounds 2g, 2h, and 2i undergo complete racemization in hexane:
i-PrOH (98:2) at room temperature: e.g., 2g (t1/2 ≈ 24 h); 2h (t1/2 ≈ 60 h).
This intriguing observation may be tentatively rationalized by substituted
Cp-aryl ligand exchange. For similar examples, see: Slocum, D. W.;
Tucker, S. P.; Engelmann, T. R. Tetrahedron Lett. 1970, 621. Roman, E.;
Astruc, D.; des Abbayes, H. J. Organomet. Chem. 1981, 219, 211.
JA953246Q
(13) Related chiral ferrocenyl amino alcohols are very efficient catalysts
for the enantioselective addition of diethylzinc to aldehydes: Butsugan,
Y.; Araki, S.; Watanabe, M. In Ferrocenes: Homogeneous Catalysis,
Organic Synthesis, Materials Science; Togni, A., Hayashi, T., Eds.; VCH:
Weinheim, 1995; pp 143-169. See also ref 6c.
(14) Similar behavior with parallel implications has been observed in
deprotonations of the TMS derivative of a chiral ferrocenyloxazoline (ref
1f).
(15) Quesnelle, C. A.; Familoni, O. B.; Snieckus, V. Synlett 1994, 349
and references cited therein.
(16) Unoptimized yield. For similar dehalogenations observed during
cross-coupling reactions, see: Nguyen, P.; Yuan, Z.; Agocs, L.; Lesley,
G.; Marder, T. B. Inorg. Chim. Acta 1994, 220, 289 and references cited
therein.