Optically Active 1,2-Ferrocenyldiamine Ligands
FULL PAPER
= 50:1 as eluent) to give pure (R,R)-1,2-bis(1-azido-1-phen-
ylmethyl)ferrocene (4). Total yield of the mixture of 4 and 5: 42 mg
(0.095 mmol, 95%).
para-Substituted acetophenones and 1- and 2-acetonaph-
thones were similarly reduced to the corresponding op-
tically active 1-arylethanols with 14–75% ee. The ee value
in the reduction with o-methylacetophenone was as high as
that with acetophenone (entry 6), and the reduction with p-
fluoroacetophenone and 1- and 2-acetonaphthone gave
moderate ee values (entries 8, 10, and 11). These results
show that 2 is a promising chiral ligand for asymmetric syn-
thesis. A detailed study of the design and application of
this 1,2-ferrocenyldiamine as a ligand for metal-catalyzed
asymmetric syntheses is now in progress.
Major Isomer 4: Yellow oil. [α]2D5 = –60.3 (c = 0.524, CHCl3). IR
1
(neat): ν = 2160 cm–1. H NMR (CDCl , 300 MHz): δ = 3.99 (m,
˜
3
1 H), 4.14 (s, 5 H), 4.20 (m, 1 H), 4.36 (m, 1 H), 5.48 (s, 1 H), 5.75
(s, 1 H), 7.2–7.3 (m, 10 H) ppm. 13C NMR (CDCl3): δ = 64.3, 64.9,
67.1, 68.3, 68.7, 69.9, 85.3, 87.5, 127.2, 127.6, 128.0, 128.2, 128.3,
128.5, 138.8, 139.2 ppm. C24H20FeN6 (448.30): calcd. C 64.30, H
4.50, N 18.75; found C 64.14, H 4.58, N 18.55.
Minor Isomer meso-(R,S)-5: [α]2D5 = 0 (c = 0.884, CHCl3). 1H NMR
(CDCl3, 300 MHz): δ = 3.78 (s, 5 H), 3.99 (m, 1 H), 4.14 (m, 1 H),
4.36 (m, 1 H), 5.68 (s, 1 H), 7.20–7.50 (m, 10 H) ppm. 13C NMR
δ = 64.5 67.9, 68.8, 69.9, 86.8, 127.5, 128.2, 128.5, 139.6 ppm.
Experimental Section
1
General: The H and 13C NMR spectra were recorded with a Var-
Preparation of (R,R,Sp)-[1-(1-Acetoxy-1-phenylmethyl)-2-(1-azido-
1-phenylmethyl)]ferrocene (6): The title compound was obtained by
the Y(OTf)3-catalyzed reaction of 1 with TMSN3 for 48 h. Yield:
44 mg (0.096 mmol, 96%). Yellow oil. [α]2D5 = –31.3 (c = 0.16,
ian Mercury 300 (300 MHz) spectrometer as solutions in CDCl3.
The chemical shifts are reported in δ units downfield from the in-
ternal reference (SiMe4). The IR spectra were obtained with a JA-
SCO Herschel FT/IR-230A spectrometer, and the optical rotations
were determined with a JASCO DIP-370 instrument. The HPLC
analyses were carried out with a Hitachi L-7100 apparatus
equipped with a UV detector and using chiral columns (Chiralcel
OD-H, AS-H, OB). The GC/MS analyses were carried out on a
Hewlett–Packard 5980/5972 instrument equipped with a chiral cap-
illary column (Chiraldex GT-A) using helium as carrier gas. Col-
umn chromatography was performed using a Yamazen YFLC-254
and a Michael Miller column equipped with a UV detector using
Merck Silica Gel 60. Preparative TLC was conducted using a
20×20 cm2 glass sheet coated with a 2-mm-thick layer of Merck
Kieselgel 60 PF254
Crystallography: The diffraction data were collected at room tem-
perature using Rigaku AFC7R four-circle automated dif-
fractometer with graphite-monochromated Mo-Kα radiation and
the ω–2θ scan technique to a maximum 2θ value of 50° or 55°.
The structure solution and refinements were carried out using the
CrystalStructure crystallographic software packages.[10] The posi-
tions of the non-hydrogen atoms were determined by Patterson
methods (DIRDIF PATTY)[11] and expanded using Fourier tech-
niques (DIRDIF94 or -99).[12] The carbon atoms of the solvate
CH2Cl2 molecules were refined isotropically.
CHCl ). IR (neat): ν = 2095, 1734 cm–1. 1H NMR (CDCl3,
˜
3
300 MHz): δ = 2.23 (s, 3 H), 4.00 (s, 6 H), 4.21 (m, 1 H), 4.40 (m,
1 H), 5.48 (s, 1 H), 7.06 (s, 1 H), 7.2–7.4 (m, 10 H) ppm. 13C NMR
δ = 21.2 64.5, 67.4, 67.8, 68.3 69.7, 72.3, 85.5, 87.3, 127.4, 127.5,
127.6, 128.1, 128.3, 128.4, 139.3, 140.1, 169.7 ppm. C26H23FeN3O2
(465.32): calcd. C 67.11, H 4.98, N 9.03; found C 66.97, H 5.13, N
8.96.
Preparation of (R,R)-1,2-Bis(1-amino-1-phenylmethyl)ferrocene (2):
A 50-mL Schlenk tube containing a magnetic stirring bar was
charged with 4 (500 mg, 1.12 mmol) and dry diethyl ether (30 mL)
under a slight pressure of nitrogen. LiAlH4 (100 mg, 2.8 mmol) was
then added in small portions with magnetic stirring at 0 °C. The
resulting mixture was stirred at the same temperature for 20 min
and then warmed to room temperature over a period of 4 h. The
reaction was subsequently quenched with saturated Na2SO4
(0.5 mL), the resulting solution was stirred for 10 min, and then
diethyl ether (3×20 mL) was added. The ethereal solution was
dried (Na2SO4), filtered, and then the solvent was removed on a
rotary evaporator to leave a brown oil. Crude yield: 420 mg
(1.03 mmol, 92%). [α]2D5 = –139.7 (c = 0.58, CHCl3). 1H NMR
(CDCl3, 300 MHz): δ = 1.80 (br. s, 4 H), 4.00 (s, 6 H), 4.13 (m, 1
H), 4.38 (m, 1 H), 4.94 (s, 1 H), 5.17 (s, 1 H), 7.2–7.5 (m, 10 H)
ppm. 13C NMR (CDCl3): δ = 54.0, 54.1, 65.8, 66.3. 67.6, 68.9,
91.6 ppm; aromatic signals are not listed here. Compound 3 is not
partucularly stable and decomposed into a black oil within a few
days, so it was stored as the corresponding ditosylamide 8a.
.
a
CCDC-274906 (for 8a) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Center via
www.ccdc.cam.ac.uk/data_request/cif.
Reaction of (R,R)-1,2-Bis(1-acetoxy-1-phenylmethyl)ferrocene (1)
with TMSN3 in the Presence of a Lewis Acid. Typical Procedure:[13]
A 50-mL Schlenk tube containing a magnetic stirring bar was
charged with 1 (50 mg, 0.1 mmol), anhydrous Cu(OTf)2 (4 mg,
0.01 mmol, 10 mol-%), and dry CH2Cl2 (10 mL) under a slight
pressure of nitrogen. TMSN3 (35 mg, 0.30 mmol) was then added
from a syringe, with magnetic stirring, at –40 °C and the resulting
mixture was stirred at the same temperature for 24 h. The reaction
was subsequently quenched with water and the resulting solution
was extracted with CH2Cl2 (3×15 mL). The combined extracts
were washed (brine), dried (MgSO4), and the solvent was removed
Preparation of (R,R)-1,2-Bis[1-phenyl-1-(p-tosylamido)methyl]ferro-
cene (8a): A mixture of crude 2 (420 mg, 1.03 mmol), tosyl chloride
(510 mg, 2.65 mmol), and pyridine (250 mg, 3.20 mmol) in CH2Cl2
(30 mL) was stirred at room temperature for 16–20 h. The solvent
was then removed under reduced pressure to give crude 8a as a
brown oil. This oil was washed with diethyl ether to give a yellow
solid. Yield: 700 mg (0.996 mmol, 98%); m.p. Ͼ 167 °C (dec).
[α]2D5 = +55.0 (c = 0.180, CHCl3). H NMR (CDCl3, 300 MHz): δ
1
= 2.29 (s, 3 H), 2.39 (s, 3 H), 3.90 (s, 5 H), 3.95 (br. s, 1 H), 4.05
(t, J = 2.60 Hz, 1 H), 4.11 (br. s, 1 H), 4.56 (d, J = 5.27 Hz, 1 H),
5.37 (d, J = 4.59 Hz, 1 H), 5.48 (d, J = 5.27 Hz, 1 H), 5.68 (d, J =
4.59 Hz, 1 H), 6.8–7.3 (m, 14 H), 7.29 (d, J = 8.20 Hz, 2 H), 7.61
(d, J = 8.20 Hz, 2 H) ppm. 13C NMR (CDCl3): δ = 21.3, 21.5, 54.6,
56.1, 66.5, 67.5, 67.6, 69.8, 87.3, 91.6 ppm; aromatic signals are not
listed here. C38H36FeN2O4S2 (704.68): calcd. C 64.77, H 5.15, N
3.98; found C 64.62, H 5.22, N 4.16. Crystals suitable for X-ray
analysis were obtained by recrystallization from hexane/CH2Cl2.
1
on a rotary evaporator to leave a yellow oil. H NMR analysis of
the crude product revealed the presence of two isomers of the 1,2-
ferrocenyldiazides, with 4 as the major product and 5 as the minor
product. The isomer ratio was determined by 1H NMR integration
of the benzylic protons (4/5 = 80:20). The crude product was sub-
jected to column chromatography on silica gel (hexane/diethyl ether
Eur. J. Org. Chem. 2006, 1012–1016
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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