Synthesis of planar chiral ferrocenyl 1,3-diamines and 1,3-amino ethers

Article abstract of DOI:10.1039/b307014j

The efficient syntheses of novel planar chiral 1,3-diamines and 1,3-amino ethers with an oxy or amino function directly bound to the cyclopentadienyl ring of ferrocene has been developed. The key reaction is the Cu₂O promoted substitution of of (pR)-diisopropyl-2-iodoferrocenecarboxamide with either phthalimide or AcOH to introduce nitrogen or oxygen functionality onto the cyclopentadienyl ring. The enantiomerically pure iodoferrocene derivative is available from the known enantioselective ortho-lithiation of N,N-diisopropylferrocenecarboxamide with n-BuLi sparteine, In the course of these studies the synthesis of a novel C₂ symmetric C-2 dimer of N,N-dimethyl-1-ferrocenylethylamine was characterised by single crystal X-ray diffraction.

Full text of DOI:10.1039/b307014j

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Synthesis of planar chiral ferrocenyl 1,3-diamines and 1,3-amino
ethers
James C. Anderson,* Alexander J. Blake† and Jennifer C. Arnall-Culliford
School of Chemistry, University of Nottingham, Nottingham, UK NG7 2RD.
E-mail: j.anderson@nottingham.ac.uk
Received 24th June 2003, Accepted 15th August 2003
First published as an Advance Article on the web 11th September 2003
The efficient syntheses of novel planar chiral 1,3-diamines and 1,3-amino ethers with an oxy or amino function
directly bound to the cyclopentadienyl ring of ferrocene has been developed. The key reaction is the Cu2O promoted
substitution of (pR)-N,N-diisopropyl-2-iodoferrocenecarboxamide with either phthalimide or AcOH to introduce
nitrogen or oxygen functionality onto the cyclopentadienyl ring. The enantiomerically pure iodoferrocene derivative
is available from the known enantioselective ortho-lithiation of N,N-diisopropylferrocenecarboxamide with n-BuLi–
sparteine. In the course of these studies the synthesis of a novel C2 symmetric C-2 dimer of N,N-dimethyl-1-
ferrocenylethylamine was characterised by single crystal X-ray diffraction.
duced by Ugi and coworkers6,7 and has proven particularly
Introduction
effective for the synthesis of enantiomerically pure planar chiral
The development of asymmetric catalysis has relied in part on
the invention of unique ligand architectures ultimately to
control stereoselectivity. Planar chiral ligands used in metal
centred asymmetric catalysis have been shown to be a powerful
stereocontrol element in the efficient production of enantio-
enriched materials. The most well known planar chiral biden-
ferrocene ligands by resolution of 2.8
The most direct entry to an aminoferrocene derivative we
thought would be via electrophilic amination of ortho-lithiated
2. The diastereoselective ortho-lithiation of 2 is very reliable,7
but treatment with benzylhydroxylamine,9 N,N-dimethyl-O-
(methylsulfonyl)hydroxylamine,10 or N,O-bis(trimethylsilyl)-
tate chelate ligands at present are based upon the ferrocene
hydroxylamine (via the corresponding cyano cuprate),11 gave
motif.1,2 Since the first report of chelate ligands in this class
only recovered starting material. A three step synthesis of
aminoferrocene from ferrocene has been reported that proceeds
were shown to give modest enantioselectivities in rhodium-
catalysed hydrosilylations of ketones,3 numerous studies have
via the coupling of ferroceneboronic acid with copper
been undertaken to improve these results. These studies have
phthalimide in 13% overall yield.12 In addition the synthesis of
collectively investigated the diverse architecture and possible
the corresponding boronic acid of 2 would also allow invest-
permutations of functional groups around the ferrocene unit.1,4
igation of direct N-arylation.13 Despite following a procedure
We wish to investigate amino alcohol and diamine planar chiral
ligands, based on a ferrocene motif, which possesses an oxy or
amino function directly bound to a cyclopentadienyl ligand, in
various metal catalysed asymmetric processes. Although
hydroxy and amino ferrocene have been synthesised there are
no reports of chelate ligands based in part on these potential
donor sites. The amino ferrocene derivative in particular may
exhibit interesting donor capabilities based on a correlation
for the synthesis of 2-(N,N-dimethylaminomethyl)ferrocene-
boronic acid which proceeded in 64% yield14 we were unable to
synthesise the corresponding boronic acid of 2, again only
recovering starting material. The preparation of enantio-
merically pure 2-aminoferrocenecarboxylic acid via a 2-nitro-
ferrocenyloxazoline has been reported by Richards and
coworkers.15 Analogous nitration of lithiated 2 at a melting
THF/N2O4 interface16 gave an air unstable oil that by 1H
with its basicity which, due to opposing resonance stabilisation
and 13C NMR was consistent with a 1-ferrocenylethylamine
by the Cp ring and a positive inductive effect from the
ortho-substituted with an electron withdrawing group which we
ferrocenyl group, lies between that of aniline and 1-ferrocenyl-
tentatively assigned structure 3 (Scheme 1). The crude mixture
of 3 was hydrogenated to give an orange solid that displayed
new spectroscopic characteristics indicative of a mono-ortho-
substituted 2. Single crystal X-ray diffraction revealed the
ethylamine.5 In this publication we report our development of
the synthesis of planar chiral chelate ligands of amino and oxy
ferrocene with a pendant amino side chain. These new variants
have the flexibility to become platforms for other chiral ligands.
product to be the racemic C2 symmetric dimer (S*,pS*,S*,pS*)-
4‡ formed in 31% yield.
Compound (S*,pS*,S*,pS*)-4 is the homocoupled product
Results and discussion
arising from the dimerisation of identical enantiomers from the
Our initial attempts to access ligand systems of type 1 were
expected diastereoselective ortho-lithiation of ( )-2. The other
from the readily available racemic N,N-dimethyl-1-ferrocenyl-
expected (S*,pS*,R*,pR*)-diastereoisomer (formed from the
ethylamine (2, Fig. 1). This starting material had been intro-
dimerisation of opposite enantiomers from the diastereo-
selective ortho-lithiation of ( )-2) and a small amount of the
(R*,pR*,R,pS*)-diastereomer (formed from the minor dia-
stereoisomer of ortho-lithiated ( )-2 combining with the major
diastereoisomer of ortho-lithiated ( )-2) have been reported,17
but were not isolated in our experiment. We postulate that this
unique bis-ferrocenyl amine is formed from the ferrocenyl nitro
Fig. 1
‡ CCDC reference number 218360. See http://www.rsc.org/suppdata/
ob/b3/b307014j/ for crystallographic files in .cif or other electronic
format.
† Corresponding author for X-ray cyrstal structure.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 5 8 6 – 3 5 9 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
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Scheme 1
compound 3 which under the reducing conditions was
with MeCN, gave a 66% yield of 8 after refluxing overnight
transformed into azo compound 5.18 The azo compound might
then photolytically extrude nitrogen19 to yield the C2 symmetric
dimer 4. This dimer may exhibit interesting coordinating
properties like its bis-phosphine analogue20 and these studies
are underway.
(Scheme 3). Deprotection proceeded as before, but alkylation
of the primary amine could not be achieved by standard
reductive amination. Eschweiler–Clarke N,N-dimethylation28
gave only a low 14% yield of diamine 10. The mono-N-methyl
ligand 11 was achieved by first Boc protection and then
reduction with LiAlH4 which also reduced the amide to a
pendant diisopropylaminomethyl substituent.
The use of a Curtius rearrangement to introduce the desired
amino substituent21 was thwarted by our inability to form the
precursor amino amide from direct treatment of lithiated 2 with
TMS-isocyanate22 or via the amino acid with solid CO2.23 Our
attention briefly turned to the introduction of an ortho-hydroxy
group into 2. The synthesis of 2-(N,N-dimethylaminomethyl)-
ferrocenol had been reported from the corresponding iodide by
treatment with AcOH and Cu2O.24 Treatment of 2-iodo-N,N-
dimethyl-1-ferrocenylethylamine25 under identical conditions
led to an intractable mixture of products.
It became apparent that the popular starting material 2,
which has been used successfully for many planar chiral ligand
syntheses, was not going to be useful for the synthesis of ligands
1. However from our efforts we were able to conceive that the
introduction of amino and oxygen functionalities directly onto
the Cp ring of ferrocene looked most promising from the
treatment of a ferrocenyl boronic acid derivative with copper
phthalimide12 and treatment of an iodoferrocenyl derivative
with AcOH and Cu2O24 respectively. We concluded that our
lack of success in our previous efforts was due to the basic
amino side chain and that this could be remedied by using a
similar ferrocene starting material that possessed a much less
basic nitrogen side chain.
Scheme 3 Reagents and conditions: i, phthalimide, Cu2O, MeCN, 14 h,
82 ЊC; ii, H2NNH2ؒH2O, EtOH; iii, H2CO, HCO2H; iv, Boc2O, DMAP,
CH2Cl2, 60%; v, LiAlH4, THF, 67 ЊC, 91%.
Although this diamine is the first of its kind, its synthesis
is limited with respect to diversity. The exchange of the diiso-
propyl substituent would require selective activation,29 which is
hard to conceive. However the cyclopentadienyl amine was
unreactive towards alkylation. A more fruitful strategy in future
could be to use an ortho directing amide that possessed a
removable group.30
The enantiomerically pure boronic acid 6 and iodo derivative
7 of N,N-diisopropylferrocenecarboxamide have been prepared
by ortho-lithiation with n-butyllithium and (Ϫ)-sparteine and
quenching with a suitable electrophile in high enantio-
selectivity.26 We envisaged that the amide nitrogen would be less
likely to interfere in subsequent reactions due to the reduced
availability of its lone pair. Treatment of 626 with copper
phthalimide in refluxing acetone gave a disappointing 20% yield
of the desired substitution product 8 (Scheme 2). The phthalim-
ide was successfully deprotected to give the amine 9 in 83%
yield.
With respect to structural diversity, the synthesis of potential
chelate ligands based on oxy-substituted ferrocene derivatives
with a pendant amino side chain became more attractive.
Treatment of 7 with AcOH and Cu2O gave the acetate sub-
stitution product in 85% yield ( Scheme 4). Hydrolysis with
ethoxide ion gave the hydroxyferrocene derivative 12 (88%
yield), which was more stable than anticipated.31 This may be
attributed to a favourable hydrogen bond between the hydroxy
and the amide carbonyl group as evidenced by the hydroxy
group’s chemical shift of δ 9.68 in the 1H NMR spectrum.32 The
alcohol was smoothly methylated with NaH and MeI (80%)
and the amide successfully reduced with LiAlH4 (81%) to give
the desired oxyferrocene derivative with a pendant amino side
chain 13.
Scheme 2 Reagents: i, copper phthalimide, acetone; ii, H2NNH2ؒH2O,
EtOH.
The yield of this amination was not synthetically useful.
Attempts at Buchwald–Hartwig type palladium catalysed
amination27 of the corresponding iodide 7 were unfruitful.
However treatment of 726 with phthalimide and Cu2O under
modified reaction conditions, in which pyridine was replaced
Scheme 4 Reagents and conditions: i, AcOH, Cu2O, MeCN, 85%; ii,
aq. NaOH, EtOH, 88%; iii) NaH, THF, MeI, 80%; iv) LiAlH4, Et2O,
81%; v) MeI, MeCN; vi) RNH2, MeCN, R = n-Bu, 64%, R = c-Hex
72%, R = t-Bu, 49% over two steps.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 5 8 6 – 3 5 9 1
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We were also able to show that the pendant diisopropylamine
side chain could be substituted with other amines. Quaternis-
ation with MeI followed by treatment with n-butylamine,
cyclohexylamine or tert-butylamine gave the potential chelating
ligands 14–16 in good yields.
bath and agitated vigorously. The pale brown frozen solution
turned a deep red colour and the reaction was complete within
2 minutes. The excess dinitrogen tetraoxide and THF were
removed in vacuo and the residue was dissolved in CH2Cl2. The
CH2Cl2 solution was then filtered, washed with H2O, dried
(Na2SO4) and concentrated in vacuo yielding 1.04 g of red oil.
In one experiment this seemingly air unstable oil was purified
by flash column chromatography to give four main fractions.
All but the third fraction (in order of polarity) oxidised rapidly
and gave broad NMR spectra thought to be due to para-
magnetism. The third fraction (60 mg) was a 1 : 1 mixture of
3 with starting material from which NMR data was recorded
before decomposition. The data below is a listing of the peaks
assigned to 3. δH (400 MHz) 1.55 (3H, d, J 6.9, CH3), 2.08 (6H,
s, N(CH3)2), 4.11 (6H, s, CH5 Cp ϩ CH Cpsubs), 4.48 (1H, m,
CH Cpsubs), 4.63 (1H, q, J 6.9, CH), 5.25 (1H, s, CH Cpsubs);
δC (100 MHz) 15.5 (CH3), 40.4 (2C, N(CH3)2), 54.4 (CH), 68.0
(CH Cpsubs), 70.1 (CH Cpsubs), 72.3 (CH Cpsubs), 87.4 (C Cpsubs).
Conclusion
Efficient syntheses of novel planar chiral 1,3-diamines and 1,3-
amino alcohols with an oxy or amino function directly bound
to the cyclopentadienyl ring of ferrocene have been reported.
The enantiomerically pure ligands were derived from the
enantioselective ortho-lithiation of N,N-diisopropylferrocene-
carboxamide developed by Snieckus et.al.26 The enantiomeric
systems could be prepared by using a silicon blocking group
in the enantioselective ortho-lithiation reaction.26 These new
ligands are currently being assayed for effectiveness in
asymmetric catalytic processes and are being used as starting
materials for more complex planar chiral ligand systems.
Results from these studies will be reported in due course.
(S*,pS*,S*,pS*)-2,2Ј-Bis[1-(N,N-dimethylamino)ethyl]-1,1Ј-
biferrocene (S*,pS*,S*,pS*)-4
To a solution of the crude nitration reaction mixture (1.04 g,
theoretically 3.4 mmol) in EtOH (100 mL) was added PtO2
(0.099 g, 0.44 mmol). The reaction flask was stirred under H2 at
atmospheric pressure and rt for 2 h. The reaction mixture was
filtered through Celite and concentrated in vacuo, yielding
0.87 g of brown oil. Flash column chromatography (gradient
elution 4% CH2Cl2–1% Et3N–95% MeOH to 50% Et3N–
MeOH) gave ( )-2 (0.29 g) and the dimer (S*,pS*,S*,pS*)-4
(0.33 g, 31%) as a brown–orange solid. Mp = 145–147 ЊC; νmax
2933 (C–H), 2775, 1601, 1455, 1366, 1106 cmϪ1; δ H (400 MHz)
1.37 (6H, d, J 6.8, CH(NMe2)CH3), 1.80 (12H, s, N(CH3)2),
3.68 (2H, q, J 6.8, CH(NMe2)CH3), 4.15 (2H, s, CH Cpsubs),
4.24 (10H, s, CH Cpunsubs), 4.44 (2H, s, CH Cpsubs); δC (100
MHz) 14.5 (2C, CH(NMe2)CH3), 40.4 (4C, N(CH3)2), 55.7
(2C, CH(NMe2)CH3), 65.8 (2C, CH Cpsubs), 67.0 (2C, CH
Cpsubs), 69.7 (10C, CH Cpunsubs), 85.9, 90.4; HRMS (FABϩ)
C28H37Fe2N2 calcd. 513.1655, found 513.1651 (MHϩ); anal.
calcd. for C28H36Fe2N2: C, 65.65; H, 7.08; N, 5.47; found: C,
65.16; H, 7.11; N, 5.42%.
Experimental
Unless otherwise stated all reactions were carried out under an
atmosphere of nitrogen. All glassware was flame dried and
allowed to cool under a stream of nitrogen before use. THF was
distilled under an atmosphere of dry nitrogen from potassium
benzophenone ketyl. Diethyl ether was distilled under a dry
atmosphere of nitrogen from sodium benzophenone ketyl. All
other reagents were purified or dried according to standard liter-
ature methods. Solutions of alkyllithiums were standardised
with N-pivaloyl-o-toluidine.33 Water was distilled. Thin layer
chromatography was performed on Polygram® SIL G/UV254
0.25 mm silica gel precoated plastic sheets with fluorescent indi-
cator. Sheets were visualised using ultra violet light (254 nm)
and/or KMnO4 or anisaldehyde solutions. Flash column
chromatography was carried out using Fluorochem silica gel
60, 35–70 µ. Optical rotations were recorded on a Jasco DIP370
Digital Polarimeter and are reported in deg cm2 gϪ1. H NMR
1
and 13C NMR spectra were recorded as dilute solutions in
deuteriochloroform unless otherwise stated. All chemical shifts
(δ) are quoted in ppm and coupling constants (J) in Hz. Coup-
ling constants are recorded as observed in the spectrum without
averaging. 13C multiplicities were assigned using a DEPT
sequence. Residual signals from the solvents were used as
an internal reference. Mass spectra were acquired on a VG
micromass 70E, VG Autospec or Micromass LCTOF spectro-
meter. Melting points are uncorrected and were recorded on
a Reichert melting point apparatus. Elemental analyses were
performed by the microanalysis service of the School of
Chemistry, University of Nottingham on an Exeter Analytical
Inc. CE440 elemental analyzer.
Crystal structure determination of (S*,pS*,S*,pS*)-4‡
Crystal data: C28H36Fe2N2, M = 512.29, triclinic, a = 10.517(4),
b = 10.678(4), c = 12.532(5) Å, α = 104.199(4), β = 100.115(4),
3
¯
γ = 112.747(3)Њ, U = 1199.3(9) Å , T = 150(2) K, space group P1
(No. 2), Z = 2, Dc = 1.419 g cmϪ3, µ = 1.228 mmϪ1, 5358 unique
reflections measured, corrected for absorption (Rint 0.020) and
used in all calculations. Final R1 [4515F > 4σ(F)] = 0.0261 and
wR (all F 2) = 0.0694.
(pR)-2-[2-(N,N-Diisopropylcarbamoyl)ferrocenyl]phthalimide 8
from 6
( )-2-Nitro-N,N-dimethyl-1-ferrocenylethylamine ( )-3
A suspension of 626 (3.80 g, 10.6 mmol) and copper phthal-
imide12 (7.57 g, 21.3 mmol) in acetone (100 mL) was refluxed
for 2 h then allowed to cool to rt overnight. The reaction
mixture was concentrated in vacuo and the residue was taken up
in EtOAc. This solution was filtered in order to remove the
copper salts. The organic layer was then washed successively
with 10% KOH (2 × 50 mL), H2O (50 mL), 10% AcOH (2 × 50
mL), H2O (50 mL) then brine (2 × 50 mL). The organics were
then dried (MgSO4), and concentrated in vacuo to yield an
orange solid. Purification by column chromatography (10%
EtOAc–hexane) yielded 8 (0.960 g, 20%) as a pale brown solid.
To a solution of (ϩ)-2 (1.06 g, 4.1 mmol) in Et2O (40 mL) in a
500 mL Schlenk flask at Ϫ78 ЊC was added tert-butyllithium
(3.3 mL of a 1.6 M soln in hexane, 5.3 mmol) dropwise and the
reaction mixture left to stir for 1 h before being allowed to
warm to rt. The Et2O was removed in vacuo and the residue was
dissolved in THF (40 mL). The reaction mixture was then
frozen in as thin a layer as possible, around the walls of the
flask, using a liquid nitrogen bath and placed under a static
vacuum. Dinitrogen tetraoxide (0.38 g, 4.1 mmol, 1.0 equiv.)
was condensed, as a blue solid, into a pre-weighed, evacuated
Schlenk flask using an acetone–dry ice bath. The flask was then
allowed to warm to room temperature to give a brown gas. A
piece of Portex tubing fitted with a needle was attached to the
flask and used to condense the gas into the reaction vessel. The
reaction mixture was then warmed rapidly using a methanol
Mp = 218–220 ЊC; Rf = 0.40 (30% EtOAc–hexane); [α]D
=
ϩ146.3 (c = 1.08, CHCl3); νmax 1722 (C᎐O phthalimide), 1617
᎐
(C᎐O ferrocenyl amide), 1462, 1372, 1317 cmϪ1; δ (400 MHz)
᎐
H
1.23 (6H, br s, NCH(CH3)2), 1.40 (3H, br, NCH(CH3)2), 1.46
(3H, br, NCH(CH3)2), 3.40 (1H, br s, NCHMe2), 4.28 (1H, t,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 5 8 6 – 3 5 9 1
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J 2.6, CH Cpsubs), 4.39 (6H, s, 5CH Cpunsubs and CH Cpsubs),
4.52 (1H, dd, J 2.4, 1.4, CH Cpsubs), 4.60 (1H, br s, NCHMe2),
7.71 (2H, dd, J 5.4, 3.0, CH phthalimide), 7.85 (2H, dd, J 5.4,
3.0, CH phthalimide); δC (100 MHz) 20.6 (2C, br, NCH(CH3)2),
20.8 (1C, br, NCH(CH3)2), 21.6 (1C, br, NCH(CH3)2), 45.9
(1C, NCHMe2), 50.5 (1C, NCHMe2), 64.8 (1C, CH Cpsubs),
65.0 (1C, CH Cpsubs), 65.2 (1C, CH Cpsubs), 71.8 (5C, CH
Cpunsubs), 80.2 (1C, CC᎐ONiPr ), 88.8 (1C, CN Cpsubs), 123.2
J 6.8, NCHMe2), 3.82 (1H, dd, J 2.4, 1.6, CH Cpsubs), 3.87 (1H,
t, J 2.5, CH Cpsubs), 4.06 (1H, dd, J 2.5, 1.6, CH Cpsubs) 4.42
(5H, s, CH Cpunsubs); δC (100 MHz) 19.7 (NCH(CH3)2), 20.5
(NCH(CH3)2), 20.9 (NCH(CH3)2), 21.0 (NCH(CH3)2), 43.6
(2C, N(CH3)2), 45.7 (NCHMe2), 50.5 (NCHMe2), 56.9 (CH
Cpsubs), 61.3 (CH Cpsubs), 66.1 (CH Cpsubs), 68.4 (5C, CH
Cpunsubs), 75.9 (CC᎐ONiPr ), 111.7 (CNMe ), 168.4 (CC᎐
᎐
᎐
2
2
ONiPr2); m/z (FABϩ) 356 (100%, Mϩ), 256 (19%), 147 (13%), 73
(53%); HRMS C19H28FeN2O calcd. 356.1551, found 356.1559;
anal. calcd. for C19H28FeN2O: C, 64.05; H, 7.92; N, 7.86; found:
C, 64.20; H, 7.80; N, 7.82%.
᎐
2
(2C, CH phthalimide), 132.3 (2C, C phthalimide), 134.0 (2C
CH phthalimide), 166.9 (2C, C᎐O phthalimide), 167.2 (1C,
᎐
CC᎐ONiPr ); m/z (EIϩ) 458 (100%, Mϩ), 330 (10%), 266 (14%),
᎐
2
119 (12%); HRMS C25H20FeN2O3 calcd. 458.1293, found
458.1288; anal. calc. for C25H20FeN2O3: C, 65.51; H, 5.72; N,
6.11; found: C, 65.41; H, 5.53; N, 6.06%.
(pR)-N-tert-Butoxycarbonyl-2-(NЈ,NЈ-diisopropylcarbamoyl)-
ferrocenylamine
A mixture of 9 (0.378 g, 1.15 mmol), Boc2O (0.329 g, 1.50 mmol)
and DMAP (0.020 g, 0.16 mmol) in CH2Cl2 (4.0 mL) was
stirred at rt overnight. The reaction mixture was concentrated
in vacuo and purified by column chromatography (20% EtOAc–
hexane) to give Boc protected-9 (0.292 g, 60%) as an orange
(pR)-2-[2-(N,N-Diisopropylcarbamoyl)ferrocenyl]phthalimide 8
from 7
A stirred solution of 726 (4.94 g, 11.3 mmol), Cu2O (966 mg,
6.75 mmol) and phthalimide (1.99 g, 13.5 mmol) in MeCN
(68 mL) was refluxed for 14 h. The reaction mixture was
allowed to cool to rt and concentrated in vacuo. The residue was
taken up in EtOAc (70 mL) and filtered to remove copper salts.
The filtrate was washed with 2 M NaOH (2 × 50 mL), brine
(2 × 50 mL), then dried (MgSO4) and concentrated in vacuo.
Purification by flash column chromatography gave 8 (3.40 g,
66%) whose spectroscopic data were identical to that prepared
from 6.
solid. Mp = 132–134 ЊC; Rf = 0.35 (40% EtOAc–hexane); [α]D
ϩ505.6 (c = 0.99, CHCl3); νmax 3343 (N–H), 2973 (C–H), 1711
(C᎐O Boc), 1595 (C᎐O amide), 1454, 1369, 1346, 1315, 1159
=
᎐
᎐
cmϪ1; δH (400 MHz) 1.2–1.6 (12H, br, NCH(CH3)2), 1.51 (9H, s,
(C᎐O)OC(CH ) ), 3.2–3.8 (1H, br, N(CHMe ), 4.10 (2H, m,
᎐
3
3
2
CH Cpsubs), 4.17 (5H, s, CH Cpunsubs), 4.3–5.0 (1H, br,
NCHMe2), 5.33 (1H, s, CH Cpsubs), 8.18 (1H, s, NH ); δC (100
MHz) 21.4 (CH(CH3)2), 28.5 (C(CH3)3), 50 (br, CHMe2), 62.4
(CH Cpsubs), 63.7 (CH Cpsubs), 64.9 (CH Cpsubs), 66.5, 70.7
(CH Cpunsubs), 79.7, 100.6, 153.5 (C᎐O), 171.6 (C᎐O); m/z
᎐
᎐
(pR)-2-(N,N-Diisopropylcarbamoyl)ferrocenylamine 9
(FABϩ) 428 (100%, Mϩ), 328 (78%), 228 (19%); HRMS
C22H32FeN2O3 calcd. 428.1762, found 428.1752; anal. calcd. for
C22H32FeN2O3: C, 61.69; H, 7.53; N, 6.54; found: C, 61.53; H,
7.51; N, 6.42%.
To a solution of 8 (1.20 g, 2.62 mmol) in EtOH (50 mL) was
added NH2NH2ؒH2O (1.3 mL, 26 mmol). The reaction mixture
was refluxed for 30 min then allowed to cool to rt before being
quenched with H2O (50 mL). The reaction mixture was
extracted with Et2O (3 × 40 mL) and then the Et2O layer
was extracted with 15% HCl (3 × 30 mL). The aqueous layer
was basified with 2 M NaOH and extracted with Et2O (3 × 40
mL). The Et2O layer was then dried (MgSO4), and concentrated
in vacuo to yield 9 (0.860 g, 83%) as a dark brown crystalline
(pR)-2-(NЈ-Methylamino)-N,N-(diisopropyl)ferrocenylmethyl-
amine 11
To a stirred solution of Boc protected-9 (1.00 g, 2.33 mmol) in
THF (12 mL) was added a solution of LiAlH4 (9.3 mL of a 1 M
soln in THF, 9.3 mmol) at rt. The reaction mixture was refluxed
for 14 h before cooling to rt and quenched by the cautious
dropwise addition of H2O (0.5 mL), then 2 M NaOH (0.5 mL)
and a further portion of water (1.5 mL) with vigorous stirring.
The mixture was filtered, the filtrate washed with water (3 × 10
mL) and extracted with 1 M HCl. The acid layer was basified
with 2 M NaOH and extracted with Et2O (3 × 10 mL). The
Et2O layers were washed with brine (3 × 10 mL), dried (MgSO4)
and concentrated in vacuo. Purification by column chromato-
graphy (40% EtOAc–1% Et3N–59% hexane) gave 11 as an
orange oil (697 mg, 91%); Rf = 0.20 (50% EtOAc–1% Et3N–49%
hexane); [α]D = ϩ344.5 (c = 1.00, CHCl3); νmax 3370 (N–H), 2931
(C–H), 1731, 1364, 1118, 1046, 998 cmϪ1; δH (400 MHz) 0.96
(6H, d, J 6.6, NCH(CH3)2), 1.03 (6H, d, J 6.7, NCH(CH3)2),
2.73 (3H, d, J 5.8, NHCH3), 3.08 (2H, septet, J 6.6, NCHMe2),
3.30 (1H, d, J 5.7, NHMe), 3.37 (1H, d, J 14.0, CH2NiPr2), 3.74
(2H, s, 2 × CH Cpsubs), 3.76 (1H, d, J 14.4, CH2NiPr2), 3.86 (1H,
s, CCpsubs), 4.08 (5H, s, CH Cpunsubs); δC (100 MHz) 19.2
(NCH(CH3)2), 21.7 (NCH(CH3)2), 33.7 (NHCH3), 43.4 (CH2),
46.6 (2C, NCHMe2), 52.7 (CH Cpsubs), 60.2 (CH Cpsubs), 65.5
(CH Cpsubs), 68.4 (5C, CH Cpunsubs), 73.8 (CCH2), 113.1
(CNHMe); m/z (FABϩ) 328 (100%, Mϩ), 227 (58%), 114 (28%);
HRMS C18H28FeN2 calcd. 328.1602, found 328.1619.
solid. Mp = 125–127 ЊC; Rf = 0.20 (40% EtOAc–hexane); [α]D
=
Ϫ8.82 (c = 1.03, CHCl3); νmax 3419 and 3326 (N–H), 1581
(C᎐O), 1463, 1370, 1336 cmϪ1; δ (400 MHz) 1.4 (12H, br,
᎐
H
N(CH(CH3)2)2), 3.5–4.5 (2H, br, NCHMe2), 3.75 (2H, s, NH2),
3.90 (1H, t, J 2.6, CH Cpsubs), 4.08 (1H, dd, J 2.6, 1.4, CH
Cpsubs), 4.12 (5H, s, CH Cpunsubs), 4.17 (1H, dd, J 2.6, 1.4, CH
Cpsubs); δC (100 MHz) 21.3 (br, CH3), 21.7 (CH3), 45–50 (2C, br,
NCHMe2), 58.8 (1C, CH Cpsubs), 62.5 (1C, CH Cpsubs), 62.7
(1C, CH Cpsubs), 67.1 (1C, CC᎐ONiPr ), 70.8 (5C, CH Cpunsubs),
᎐
2
111.4 (1C, CNH2 Cpsubs), 171.3 (1C, CC᎐ONiPr ); m/z (FABϩ)
᎐
2
328 (100%, Mϩ), 228 (18%), 200 (8%); HRMS C17H24FeN2O
calcd. 328.1238, found 328.1247; anal. calcd. for C17H24FeN2O:
C, 62.17; H, 7.37; N, 8.54; found: C, 62.25; H, 7.21; N, 8.63%.
(pR)-N,N-Dimethyl-2-(NЈ,NЈ-diisopropylcarbamoyl)ferrocenyl-
amine 10
To a solution of ( )-9 (500 mg, 1.52 mmol) in formaldehyde
(1.1 mL of a 40% w/v aqueous solution, 15 mmol) was added
HCO2H (1.2 mL of a 98% aqueous solution, 30 mmol). The
reaction mixture was allowed to cool to rt and diluted with H2O
(5 mL), basified with 2 M NaOH and extracted with Et2O. The
Et2O layer was washed with brine, dried (MgSO4) and concen-
trated in vacuo. Purification by flash column chromatography
(10% EtOAc–1% Et3N–hexane) gave ( )-10 (75 mg, 14%) as a
pale brown crystalline solid. Mp = 115.9–17.2 ЊC; Rf = 0.68
(pR)-2-(N,N-Diisopropylcarbamoyl)ferrocenyl acetate
(40% EtOAc–petrol); νmax 2964 (C–H), 1621 (C᎐O), 1456, 1369,
To a flask containing Cu2O (0.694 g, 4.85 mmol) was added a
solution of 7 (3.38 g, 7.70 mmol) in MeCN (50 mL), AcOH
(0.53 mL, 9.2 mmol) and the mixture refluxed for 2.5 h. After
cooling to rt the reaction mixture was filtered and concentrated
in vacuo. The residue was dissolved in Et2O (50 mL) and washed
᎐
1320, 1039 cmϪ1; δH (400 MHz) 0.93 (3H, d, J 6.7, NCH(CH3)2),
1.08 (3H, d, J 6.6, NCH(CH3)2), 1.45 (3H, d, J 6.8,
NCH(CH3)2), 1.48 (3H, d, J 6.8, NCH(CH3)2), 2.59 (6H, s,
N(CH3)2), 3.39 (1H, septet, J 6.8, NCHMe2), 3.80 (1H, septet,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 5 8 6 – 3 5 9 1
3589

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with sat. aq. NH4Cl (2 × 50 mL) and brine (2 × 50 mL) then
dried (MgSO4) and concentrated in vacuo to yield a golden
brown oil. Purification by flash column chromatography (10%
EtOAc–hexane) gave a pale brown oil which solidified on
standing. Recrystallisation from hexane gave 2-(N,N-diisopro-
pylcarbamoyl)ferrocenyl acetate (2.44 g, 85%) as golden brown
br, NCHMe2), 52.7 (1C, OCH3), 58.2 (1C, CH Cpsubs), 60.3
(1C, CH Cpsubs), 64.3 (1C, CH Cpsubs), 70.2 (5C, CH Cpunsubs),
76.3 (1C, CC᎐ONiPr ), 125.0 (1C, COCH ), 167.1 (1C, CC᎐
᎐
᎐
2
3
ONiPr2); m/z (FABϩ) 343 (100%, Mϩ), 243 (6%), 86 (3%);
HRMS C18H25NO2Fe calcd. 343.1235, found 343.1219; anal.
calc. for C18H25FeNO2: C, 62.99; H, 7.34; N, 4.08; found: C,
62.90; H, 7.18; N, 4.03%.
crystals. Mp = 94–96 ЊC; Rf = 0.55 (30% EtOAc–hexane); [α]D
=
ϩ107.4 (c = 1.10, CHCl3); νmax 2968 (C–H), 1754 (C᎐O ferro-
᎐
cenyl acetate), 1620 (C᎐O ferrocenyl amide), 1462, 1370, 1322
᎐
(pR)-N,N-Diisopropyl-2-methoxyferrocenylmethylamine 13
cmϪ1; δH (400 MHz) 1.1 (6H, br s, NCH(CH3)2), 1.5 (6H, br s,
To a slurry of LiAlH4 (0.995 g, 26.2 mmol) in Et2O (15 mL) at
0 ЊC was added a solution of N,N-diisopropyl-2-methoxy-
ferrocenecarboxamide (3.00 g, 8.74 mmol) in Et2O (65 mL) and
the reaction refluxed for 14 h. The reaction mixture was then
cooled to 0 ЊC and H2O (1 mL) was added cautiously dropwise,
followed by 2 M NaOH (1 mL) then a further portion of water
(3 mL) with vigorous stirring. The granular precipitate was
filtered and washed with Et2O (10 mL). The organic layer was
extracted with a 10% solution of phosphoric acid (3 × 50 mL).
The acidic aqueous layer was basified with 2 M NaOH and
extracted with Et2O (3 × 50 mL). The Et2O layer was then
washed with brine (2 × 50 mL), dried (MgSO4), and concen-
trated in vacuo to give 13 (2.32 g, 81%) as an orange oil. Rf =
0.70 (50% EtOAc–1% Et3N–49% hexane); [α]D = ϩ182.7 (c =
1.04, CHCl3); νmax 2964 (C–H), 2820 (O–CH3), 1492, 1418,
1289, 1204, 1050 (C–O) cmϪ1; δH (400 MHz) 0.99 (6H, d, J 6.6,
NCH(CH3)2), 1.02 (6H, d, J 6.6, NCH(CH3)2), 3.04 (2H, septet,
J 6.6, N(CHMe2)2), 3.44 (1H, d, J 14.3, CpCH2NiPr2), 3.58 (1H,
d, J 14.3, CpCH2NiPr2), 3.66 (3H, s, OCH3), 3.71 (1H, t, J 2.6,
CH Cpsubs), 3.94 (1H, dd, J 2.5, 1.4, CH Cpsubs), 4.00 (1H, s, CH
Cpsubs), 4.12 (5H, s, CH Cpunsubs); δC (100 MHz) 20.5 (2C,
NCH(CH3)2), 21.5 (2C, N(CHCH3)2), 41.1 (1C, CH2), 47.6
(1C, OCH3), 52.3 (1C, CH Cpsubs), 58.0 (2C, CH), 59.7 (1C,
CH Cpsubs), 65.1 (1C, CH, Cpsubs), 69.0 (5C, CH Cpunsubs), 77.3
(1C, CCH2NiPr2), 126.0 (1C, COCH3); m/z (FABϩ) 329 (100%,
Mϩ), 229 (62%), 114 (11%); HRMS C18H27NOFe calcd.
329.1442, found 329.1443; anal. calcd. for C18H27FeNO: C,
65.66; H, 8.26; N, 4.25; found: C, 65.68; H, 8.26; N, 4.24%.
NCH(CH ) ), 2.18 (3H, s, C᎐OCH ), 3.39 (1H, br s, NCHMe ),
᎐
3
2
3
2
3.98 (1H, t, J 2.6, CH Cpsubs), 4.10 (2H, dd and br s, J 2.6, 1.4,
CH Cpsubs and NCHMe2), 4.36 (5H, s, CH Cpunsubs), 4.42 (1H,
dd, J 2.6, 1.4, CH Cpsubs); δ (100 MHz) 20.9 (4C, br,
NCH(CH ) ), 21.2 (1C, OC᎐OCH ), 46.0 (1C, br, NCHMe ),
᎐
3
2
3
2
50.6 (1C, br, NCHMe2), 61.0 (1C, CH Cpsubs), 61.9 (1C, CH
Cpsubs), 62.8 (1C, CH Cpsubs), 71.3 (5C, CH Cpunsubs), 79.3 (1C,
CC᎐ONiPr ), 115.2 (1C, COC᎐OCH ), 166.1 (1C, C᎐O), 169.9
᎐
᎐
᎐
2
3
(1C, C᎐O); m/z (FABϩ) 371 (100%, Mϩ), 329 (30%), 228 (12%);
᎐
HRMS C19H25FeNO3 calcd. 371.1184, found 371.1159; anal.
calcd. for C19H25NFeO3: C, 61.47; H, 6.79; N, 3.77; found: C,
61.58; H, 6.78; N, 3.58%.
(pR)-N,N-Diisopropyl-2-hydroxyferrocenecarboxamide 12
To a solution of 2-(N,N-diisopropylcarbamoyl)ferrocenyl acet-
ate (8.67 g, 23.3 mmol) in EtOH (230 mL) was added a solution
of NaOH (1.4 g, 35 mmol) in H2O (35 mL). The reaction
mixture was stirred at rt for 30 min before being quenched with
sat. aq. NH4Cl (200 mL). The resultant mixture was extracted
with CH2Cl2 (3 × 100 mL). The combined organics were
washed with H2O (2 × 100 mL) and then brine (2 × 100 mL)
before being dried (MgSO4). Concentration in vacuo gave 12
(6.74 g, 88%) as a dark brown solid. Mp = 104–106 ЊC; Rf = 0.65
(30% EtOAc–hexane); νmax 3196 (O–H, H-bonded), 2967
(C–H), 1588 (C᎐O), 1503, 1345, 1209, 816 cmϪ1; δ (400 MHz)
᎐
H
1.2–1.6 (12H, br, NCH(CH3)2), 3.4–3.6 (1H, br, NCHMe2), 3.93
(1H, t, J 2.8, CH Cpsubs), 4.04 (1H, s, CH Cpsubs), 4.17 (5H, s,
CH Cpunsubs), 4.45 (1H, s, CH Cpsubs), 4.7–4.8 (1H, br s,
NCHMe2), 9.68 (1H, s, exchanges with D2O, OH ); δC (100
MHz) 21.2 (4C, br, NCH(CH3)2), 46.9 (1C, br, NCHMe2), 49.2
General procedure for substitution of –NiPr2 for primary amine29
To a solution of tertiary ferrocenylamine in MeCN (5 mL
mmolϪ1) was added MeI (60 equiv.). The reaction mixture was
stirred at rt for 1.5 h before the volatiles were removed in vacuo.
The residue was dissolved in MeCN (5 mL mmolϪ1) and a
primary amine (30 equiv.) was added. The reaction mixture was
stirred at rt for 14 h before removal of the solvents in vacuo. The
residue was taken up in CH2Cl2 (5 mL mmolϪ1) and washed
with H2O (2 × 50 mL) and brine (2 × 50 mL) then dried
(MgSO4), and concentrated in vacuo.
(1C, br, NCHMe2), 58.0 (1C, CH Cpsubs), 59.6 (1C, CC᎐
᎐
ONiPr2), 61.8 (1C, CH Cpsubs), 62.6 (1C, CH Cpsubs), 70.3 (5C,
CH Cpunsubs), 128.8 (1C, COH), 174.9 (1C, CC᎐ONiPr ); m/z
᎐
2
(FABϩ) 329 (100%, Mϩ), 228 (15%), 200 (13%); HRMS
C17H23FeNO2 calcd. 329.1078, found 329.1105; anal. calcd. for
C17H23NFeO2: C, 62.04; H, 7.04; N, 4.26; found: C, 61.92; H,
7.04; N, 4.26%.
(pR)-N,N-Diisopropyl-2-methoxyferrocenecarboxamide
To a slurry of NaH (60% in mineral oil, 0.687 g, 17.1 mmol) in
THF (20 mL) at 0 ЊC was added a solution of 12 (3.77 g, 11.5
mmol) in THF (120 mL). The reaction mixture was stirred at
0 ЊC for 45 min before the addition of MeI (1.4 mL, 23 mmol).
The reaction mixture was allowed to warm slowly to rt over-
night. The solvents were removed in vacuo and the residue was
dissolved in Et2O (150 mL). The organics were washed with
H2O (3 × 100 mL) and the aqueous phase then extracted
with Et2O (2 × 50 mL). The combined Et2O layers were washed
with brine (2 × 150 mL) then dried (MgSO4). Concentration
in vacuo yielded N,N-diisopropyl-2-methoxyferrocenecarb-
oxamide (3.14 g, 80%) as a pale orange solid. Mp = 132–134 ЊC;
Rf = 0.60 (30% EtOAc–hexane); [α]D = ϩ210.4 (c = 0.96,
(pR)-N-Butyl-2-methoxyferrocenylmethylamine 14
Reaction of 13 (5.38 g, 16.3 mmol) with n-butylamine (48 mL,
490 mmol) according to the general procedure, after purifi-
cation by flash column chromatography (49% EtOAc–1%
Et3N–49% hexane) gave, in order of elution 13 (1.13 g, 21%)
followed by 14 (3.15 g, 64%) as a pale brown oil. Rf = 0.72 (49%
EtOAc–1% Et3N–49% hexane); [α]D = ϩ274.3 (c = 1.04,
CHCl3); νmax 3323 (N–H), 3096, 2925 (C–H), 2184, 1495, 1419,
1284, 1049 (C–O), 819 cmϪ1; δH (400 MHz) 0.90 (3H, t, J 7.3,
CH2CH3), 1.33 (3H, m, NH and CH2CH2CH3), 1.46 (2H, m,
CH2CH2CH3), 2.60 (2H, m, NHCH2CH2), 3.42 (1H, d, J 13.0,
CpCH2NiPr2), 3.65 (3H, s, OCH3), 3.74 (1H, t, J 2.6, CH
Cpsubs), 3.78 (1H, d, J 13.0, CpCHaHbNiPr2) 3.93 (1H, dd, J 2.6,
1.4, CH Cpsubs), 3.98 (1H, dd, J 2.6, 1.4, CH Cpsubs), 4.13 (5H, s,
CH Cpunsubs); δC (100 MHz) 14.2 (1C, CH2CH3), 20.7
(1C, CH2CH2CH3), 32.4 (1C, CH2CH2CH3), 46.5 (1C,
NHCH2CH2), 49.4 (1C, CpCH2NHnBu), 52.3 (1C, CH Cpsubs),
57.6 (1C, OCH3), 59.8 (1C, CH Cpsubs), 63.9 (1C, CH Cpsubs),
68.9 (5C, CH Cpunsubs), 75.4 (1C, CCH2NHnBu), 126.3 (1C,
CHCl3); νmax 2966 (C–H), 2234, 1616 (C᎐O), 1413, 1323, 1257,
᎐
1136, 1049, 819 cmϪ1; δH (400 MHz) 1.0–1.2 (6H, br d,
NCH(CH3)2), 1.49 (6H, br s, NCH(CH3)2), 3.40 (1H, br s,
N(CHMe2), 3.71 (3H, s, OCH3), 3.84 (1H, t, J 2.5, CH Cpsubs),
4.03 (2H, dd and br s, J 2.5, 1.5, CH Cpsubs and N(CHMe2),
4.11 (1H, dd, J 2.6, 1.5, CH Cpsubs), 4.34 (5H, s, CH Cpunsubs); δC
21.2 (4C, br, N(CH(CH3)2)2), 46.1 (1C, br, NCHMe2), 50.6 (1C,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 5 8 6 – 3 5 9 1
3590

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COCH3); m/z (FABϩ) 301 (34%, Mϩ), 243 (24%), 229 (100%),
73 (44%); HRMS C16H23FeNO calcd. 301.1129, found
301.1139; anal. calc. for C16H23FeNO: C, 63.76; H, 7.70; N,
4.65; found: C, 63.40; H, 7.59; N, 4.78%.
2 Other planar chiral bidentate ligands, again based upon
organometallic skeletons, are reviewed in O. Delacroix and
J. A. Gladysz, Chem. Commun., 2003, 665.
3 T. Hayashi, K. Yamamoto and M. Kumada, Tetrahedron Lett.,
1974, 15, 4405.
4 (a) D. A. Dobbs, K. P. M. Vanhessche, E. Brazi, V. Rautenstrauch,
J.-Y. Lenoir, J.-P. Genêt, J. Wiles and S. H. Bergens, Angew. Chem.,
Int. Ed. Engl., 2000, 39, 1992; (b) H.-U. Blaser, W. Brieden, B. Pugin,
F. Spindler, M. Studer and A. Togni, Top. Catal., 2002, 19, 3.
5 N. W. Duffy, J. Harper, P. Raman, R. Ranatunge-Bandarage,
B. H. Robinson and J. Simpson, J. Organomet. Chem., 1998, 564,
125.
6 G. Gokel, P. Hoffmann, H. Klusacek, D. Marquarding, E. Ruch and
I. Ugi, Angew. Chem., Int. Ed. Engl., 1970, 9, 64.
7 D. Marquarding, H. Klusacek, G. Gokel, P. Hoffmann and I. Ugi,
J. Am. Chem. Soc., 1970, 92, 5389.
(pR)-N-Cyclohexyl-2-methoxyferrocenylmethylamine 15
Reaction of 13 (500 mg, 1.52 mmol) with cyclohexylamine
(5.2 mL, 45 mmol) according to the general procedure, after
purification by flash column chromatography (30% EtOAc–1%
Et3N–69% hexane), gave 13 (81 mg, 16%) followed by 15 (360
mg, 72%) as an orange oil. Rf = 0.50 (50% EtOAc–1% Et3N–
49% hexane); νmax 3306 (N–H), 2841, (C–H), 2662, 2506, 1715,
1643, 1456, 1368, 1350, 1093, 1058, 996, 890 cmϪ1; δH 1.1–1.2
(5H, m, c-Hex), 1.27 (1H, br s, NH ), 1.60 (1H, m, c-Hex), 1.72
(2H, m, c-Hex), 1.88 (2H, m, c-Hex), 2.47 (1H, m, NHCHc-
Hex), 3.48 (1H, d, J 12.9, CpCH2NHc-Hex), 3.65 (3H, s,
OCH3), 3.74 (1H, t, J 2.6, CH Cpsubs), 3.78 (1H, d, J 12.9,
CpCH2NHc-Hex), 3.93 (1H, dd, J 2.6, 1.4, CH Cpsubs), 3.98
(1H, dd, J 2.6, 1.4, CH Cpsubs), 4.13 (5H, s, CH Cpunsubs); δC (400
MHz) 25.06 (CH2, c-Hex), 25.10 (CH2, c-Hex), 26.2 (CH2,
c-Hex), 33.4 (CH2, c-Hex), 33.6 (CH2, c-Hex), 43.3 (CH2NHc-
Hex), 52.2 (CH, c-Hex), 56.2 (CH Cpsubs), 57.5 (OCH3), 59.7
(CH Cpsubs), 63.6 (CH Cpsubs), 68.8 (5C, CH Cpunsubs), 75.5
(CCH2NHc-Hex), 126.1 (COCH3); m/z (FABϩ) 327 (100%,
Mϩ), 229 (97%), 73 (11%), 55 (11%); HRMS C18H25FeNO
calcd. 327.1286, found 327.1310.
8 Ferrocenes: Homogeneous Catalysis, Organic Synthesis, Material
Science, ed. A. Togni and T. Hayashi, VCH, Weinheim, Germany,
1995.
9 This reagent has been used to electrophilically aminate ferrocenyl-
lithium to give aminoferrocene in 13% yield. (a) A. N. Nesmeyanov,
E. G. Perevalova, R. V. Golovnya and L. S. Shilovtseva, Dokl. Akad.
Nauk. SSSR, 1955, 102, 353; (b) G. R. Knox, P. L. Pauson and
D. Willison, Organometallics, 1990, 9, 301 and references therein.
10 This reagent has been used to electrophilically aminate cyclopenta-
dienyllithium. M. Bernheim and G. Boche, Angew. Chem., Int. Ed.
Engl., 1980, 19, 1010.
11 O. Riant, S. Odile, T. Flessner, S. Taudien and H. Kagan, J. Org.
Chem., 1997, 62, 6733.
12 N. Montserrat, A. W. Parkins and A. R. Tomkins, J. Chem. Res. (S),
1995, 336.
13 D. M. T. Chan, K. L. Monaco, R.-P. Wang and M. P. Wimters,
Tetrahedron Lett., 1998, 39, 2933.
14 G. Marr, R. E. Moore and B. W. Rockett, J. Chem. Soc. (C), 1968,
24.
(pR)-N-tert-Butyl-2-methoxyferrocenylmethylamine 16
Reaction of 13 (883 mg, 2.68 mmol) with tert-butylamine (8.45
mL, 80.5 mmol) according to the general procedure, after
purification by flash column chromatography (20% EtOAc–1%
Et3N–79% hexane), gave 13 (115 mg, 13%) followed by 16 (398
mg, 49%) as an orange oil. Rf = 0.22 (50% EtOAc–1% Et3N–
49% hexane); [α]D = ϩ275.3 (c = 0.98, CHCl3); νmax 3307 (N–H),
2961 (C–H), 1490, 1364, 1130, 1104, 1050, 1000 cmϪ1; δH (400
MHz) 1.15 (9H, s, NHC(CH3)3), 1.25 (1H, br s, NHtBu), 3.41
(1H, d, J 11.8, CpCH2NHtBu), 3.65 (3H, s, OCH3), 3.67 (1H, d,
J 11.8, CpCH2NHtBu), 3.72 (1H, t, J 2.6, CH Cpsubs), 3.96 (2H,
m, CH Cpsubs), 4.12 (5H, s, CH Cpunsubs); δC (100 MHz) 29.1
(3C, C(CH3)3), 39.4 (CpCH2NHtBu), 50.6 (C(CH3)3), 52.3
(CH Cpsubs), 57.6 (OCH3), 59.7 (CH Cpsubs), 63.4 (CH Cpsubs),
68.8 (5C, CH Cpunsubs), 76.3 (CpCH2NHtBu), 126.0 (COCH3);
m/z (FABϩ) 301 (100%, Mϩ), 229 (80%), 57 (16%); HRMS
C16H23FeNO calcd. 301.1129, found 301.1150; anal. calc. for
C16H23FeNO: C, 63.76; H, 7.70; N, 4.65; found: C, 63.78; H,
7.58; N, 4.38%.
15 R. Salter, T. E. Pickett and C. J. Richards, Tetrahedron: Asymmetry,
1998, 9, 4239.
16 K. Tani, K. Lukin and P. E. Eaton, J. Am. Chem. Soc., 1997, 119,
1476.
17 P. Krajnik, Ch. Kratky, K. Schlögl and M. Widhalm, Monatsh.
Chem., 1990, 121, 945.
18 H. E. Bigelow and D. B. Robinson, Org. Synth., 1955, Coll Vol. 3,
103.
19 (a) P. G. Gassman and K. T. Mansfield, Org. Synth., 1973, Coll. Vol.
5, 96; (b) R. J. Peterson and P. S. Skell, Org. Synth., 1973, Coll. Vol. 5,
929.
20 M. Sawamura, H. Hamashima and I. Yoshihiko, Tetrahedron:
Asymmetry, 1991, 2, 593.
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Acknowledgements
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We would like to thank the EPSRC and GlaxoSmithKline for
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Mr T. Hollingworth and Mr D. Hooper for providing mass
spectra and Mr T. J. Spencer for micro analytical data.
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O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 5 8 6 – 3 5 9 1
3591