Chiral base-mediated benzylic functionalisation of tricarbonylchromium(0) complexes of benzylamine derivatives

Article abstract of DOI:10.1039/b211222c

The novel complex (η⁶-benzylamine)tricarbonylchromium(0) 11 was prepared in up to 66% yield by direct complexation with Cr(CO)₆ in refluxing 1,4-dioxane. Imine derivatives of this complex were readily deprotonated at the benzylic position by diamide 5, and the resultant anions reacted regioselectively with electrophiles (Me₃SiCl or Mel) to give fairly good yields of products substituted at the benzylic carbon. Products of up to 87% e.e. were obtained in these reactions, with the highest enantioselectivity being derived from the tert-butyl-substituted imine complex 25.

Full text of DOI:10.1039/b211222c

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Chiral base-mediated benzylic functionalisation of
tricarbonylchromium(0) complexes of benzylamine derivatives
Susan E. Gibson*a and Mark H. Smithb
a Department of Chemistry, King’s College London, Strand, London, UK WC2R 2LS
b Department of Chemistry, Imperial College of Science, Technology and Medicine,
South Kensington, London, UK SW7 2AY
Received 13th November 2002, Accepted 3rd January 2003
First published as an Advance Article on the web 23rd January 2003
The novel complex (η6-benzylamine)tricarbonylchromium(0) 11 was prepared in up to 66% yield by direct
complexation with Cr(CO)6 in refluxing 1,4-dioxane. Imine derivatives of this complex were readily deprotonated
at the benzylic position by diamide 5, and the resultant anions reacted regioselectively with electrophiles (Me3SiCl
or MeI) to give fairly good yields of products substituted at the benzylic carbon. Products of up to 87% e.e. were
obtained in these reactions, with the highest enantioselectivity being derived from the tert-butyl-substituted imine
complex 25.
Asymmetric functionalisation of the benzylic position of tri-
carbonylchromium(0) complexes of acyclic and cyclic benzyl
ethers 1 and 2 and thioethers 3 and 4 has been achieved using
chiral bases.1–6 In a typical example, chiral base 57 was used to
convert complex 6 into complex 7 in a yield of 96% and an
enantiomeric excess of 97% (Scheme 1).1 To date, however, the
Scheme 2
of the tricarbonylchromium(0) complex of N-methylisoindoline
with a monoamide chiral base did not result in clean
metallation.3
Activated systems
Scheme 1
It was decided that greater activation would be required for
benzylic deprotonation at low temperature. A wide range of
derivatives of purely organic amines have been employed to
promote metallation on carbon adjacent to nitrogen, including
imines, amides, carbamates, formamidines, nitrosamines and
amine–borane complexes.9,10 Davies achieved α-methylation of
chiral formamidine derivatives of N-methylbenzylamine-
Cr(CO)3, 10, using LDA as base at Ϫ48 ЊC (Scheme 3).11
asymmetric functionalisation of nitrogen analogues of 1–4
using chiral bases has remained elusive. In order to address this
issue, we initiated the study described below, the aim of which
was to achieve asymmetric functionalisation of complexes of
general structure 8.
Scheme 3
Although good diastereomeric excesses were attained (74–84%),
a disadvantage of using such formamidine derivatives for our
purposes was that they are only applicable to functionalisation
of a secondary amine, necessitating an additional alkyl group
on nitrogen in addition to the benzyl group. It was considered
to be of greater synthetic value if the parent benzylamine
complex could be functionalised.
Preliminary investigations
Our investigations began with a direct analogue of the oxygen
and sulfur systems that had given rise to successful asymmetric
benzylic functionalisations. The known N,N-dimethylbenzyl-
amine complex 98 was prepared by heating the ligand with
Cr(CO)6 in dibutyl ether–THF (Scheme 2). Treatment of this
complex with diamide 5 under the same conditions used
successfully with the ether substrates, followed by an iodo-
methane quench, gave only recovered starting material (81%).
This result was consistent with a literature report that treatment
Synthesis of (benzylamine)tricarbonylchromium(0)
An obvious starting point for preparation of suitable deriv-
atives of the benzylamine complex for benzylic deprotonation
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 6 7 6 – 6 8 3
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
676

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would be (benzylamine)tricarbonylchromium(0) itself. Surpris-
ingly, however, this was unknown in the literature. Wary that
this could have been due to difficulties in preparing the complex
via the usual routes, benzylamine and Cr(CO)6 were nonetheless
heated under reflux in dibutyl ether–THF (10 : 1) for 48 h
(Scheme 4). The crude reaction mixture contained a large
(10 : 1) would discourage σ-complex formation via the amine
group. This indeed proved to be the most satisfactory route
to (η6-benzylamine)tricarbonylchromium(0) 11, giving a 66%
yield, with very little precipitate formation, using just 0.5
equivalents of benzylamine (Scheme 6).
Scheme 6
Scheme 4
Carbamate-activated systems
amount of a dull yellow precipitate, in addition to a yellow
solution. The solute was purified by column chromatography
(elution with EtOH–CH2Cl2 mixtures was required owing to its
high polarity) and shown to indeed be the novel benzylamine
complex 11 by IR, 1H NMR, 13C NMR, MS and microanalysis.
The precipitate could not be identified, as it rapidly decom-
posed in the NMR solvents in which it was soluble (e.g.
CD3SOCD3), although an IR spectrum indicated the presence
of complexed carbonyl ligands (resonances at 1982 and 1876
cmϪ1). Possibly this was a σ-complex (or mixture of such com-
plexes), analogous to the tris(amine) complex Cr(CO)3(NH3)3
which is often used as a complexing agent.12 σ-Complex form-
ation would be expected to be more likely for benzylamine
compared to sterically more encumbered amines such as N,N-
dimethylbenzylamine 9. The quantity of precipitate produced
was minimised using a large excess (12 equivalents) of benzyl-
amine during complexation, giving complex 11 in up to 48%
yield. The benzylamine complex was a yellow oil which dark-
ened over several days storage under nitrogen. It was conven-
iently stockpiled as its trifluoroacetic acid salt 12, from which
the free amine could be regenerated by addition of aqueous
K2CO3.
Schlosser has shown that treatment of uncomplexed N-Boc-
benzylamine 13 with at least 2 equivalents of sec-butyllithium
in THF at Ϫ50 ЊC results in lithiation on both nitrogen and the
benzylic carbon.14 Subsequent addition of carbon dioxide gave
Boc-phenylglycine in 79% yield. Given that N-Boc-benzylamine
complex 14 had already been prepared, this seemed a good
initial candidate for benzylic lithiation using a chiral lithium
amide base.
In addition to complex 14, the N-Cbz-benzylamine complex
15 was targeted as an alternative substrate. This was synthesised
in 87% yield by treatment of (η6-benzylammonium)tricarb-
onylchromium(0) trifluoroacetate 12 with potassium hydrogen-
carbonate solution and benzyl chloroformate (Scheme 7).
Scheme 7
In view of the relatively low yields of benzylamine complex
11 obtained from this direct method, an alternative route was
investigated. Benzylamine was Boc-protected and the product
13 complexed to tricarbonylchromium in 69% yield, by heating
with Cr(CO)6 (Scheme 5). Treatment of the N-Boc-benzylamine
Anticipating the need to form a product for which the e.e.
could be measured (and the absolute configuration readily
established), 1-phenylethylamine complex 1615 was prepared by
reacting the ligand with Cr(CO)6. In contrast to benzylamine,
complexation of 1-phenylethylamine did not produce large
amounts of precipitate (presumably due to its more hindered
amino group) and a good yield of complex 16 was obtained
using either racemic or (S)-configured starting material
(Scheme 8). Like benzylamine complex 11, it was a yellow oil
Scheme 8
which darkened over a few days under nitrogen, but longer-
term storage could be effected by conversion to the solid
trifluoroacetic acid salt 17.
Racemic
(η6-1-phenylethylammonium)tricarbonylchrom-
Scheme 5
ium(0) trifluoroacetate 17 was converted to its N-Boc derivative
18 (the anticipated product of benzylic methylation of N-Boc-
benzylamine complex 14) by treatment with Boc2O and tri-
ethylamine in methanol (Scheme 9). Attempts to separate
the enantiomers of complex 18 by chiral HPLC, however,
proved unsuccessful. Neither could complete separation of the
enantiomers of the parent 1-phenylethylamine complex 16 be
achieved by HPLC methods. Fortunately, chiral HPLC analysis
did prove successful for the N-Cbz derivative 19, which had
been prepared from complex 17 using potassium hydrogen-
carbonate solution and benzyl chloroformate.
complex 14 with trifluoroacetic acid in CH2Cl2 directly gave
(η6-benzylammonium)tricarbonylchromium(0) trifluoroacetate
12 in 91% yield (55% overall from benzylamine). Boc-protected
benzylamine was identified by comparison of its mp and
spectroscopic data with literature values,13 whilst novel complex
14 was fully characterised by IR, 1H NMR, 13C NMR, MS and
elemental analysis.
Finally, a direct complexation of benzylamine was attempted
in 1,4-dioxane. It was hoped that the slightly stronger donor
characteristics of this solvent relative to dibutyl ether–THF
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 6 7 6 – 6 8 3
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Scheme 9
Treatment of either N-Boc- or N-Cbz-benzylamine complex
(14 or 15 respectively) with 0.95 equivalents n-butyllithium
(to deprotonate nitrogen), then diamide base 5 with LiCl in
THF at Ϫ78 ЊC followed by a MeI quench gave no identifiable
products other than starting material. A similar experiment
(using complex 15), but maintaining the reaction mixture at
Ϫ40 ЊC after addition of the diamide 5, produced an insepar-
able mixture of α-methylated complex 19 and starting material
15 (38 : 62), with only 69% overall recovery (Scheme 10). It was
Scheme 11
Scheme 10
thus apparent that deprotonation at the benzylic position of
carbamate complexes 14 and 15 by diamide 5 was relatively
sluggish. Rather than pursuing this strategy further, our atten-
tion then turned to another class of substrate with greater
activation of the benzylic protons.
Imine-activated systems
Deprotonation at the benzylic position of N-benzylimines may
be accomplished using LDA in THF at Ϫ78 ЊC.16 The 2-azaallyl
anions thus formed react with electrophiles to give products
of substitution α to nitrogen. Such a reaction was reported
by Solladie-Cavallo for the complexed imine 21, derived
from ortho-methylbenzaldehyde complex 20 and benzylamine
(Scheme 11).17
Scheme 12
THF at Ϫ78 ЊC, with an internal Me3SiCl quench gave the
novel silylated imine 26 in 71% yield. Complex 26 proved
remarkably resistant to hydrolysis (presumably for steric
reasons) with no reaction observed on stirring in 5% hydro-
chloric acid (r.t., 15 min), and purification by column chrom-
atography on silica was possible. Furthermore, its enantiomers
could be separated by chiral HPLC [Chiralcel OD-H, hexane–
propan-2-ol (1999 : 1)]. Formation of complex 26 was thus
a suitable method for probing asymmetric deprotonation of
complex 25.
Imine complex 25 was added to a solution of diamide 5, LiCl
and Me3SiCl (in situ quench) in THF at Ϫ78 ЊC (Scheme 13).
Silylated imine complex 26 was isolated in 89% yield, and with
[α]D Ϫ23 (c = 1, CH2Cl2). HPLC analysis of the product
revealed the e.e. to be 87%—substantial asymmetric induction
had been achieved.
The effect of using an external quench of iodomethane was
examined next. Benzylic methylation of the intermediate anion
occurred readily at Ϫ78 ЊC, but the imine product was readily
hydrolysed and unstable towards column chromatography,
preventing direct measurement of the product e.e. A protocol
was therefore developed for complete hydrolysis of the imine
product followed by Cbz-derivatisation of the resultant 1-
Although the deprotonation occurred adjacent to the
(uncomplexed) phenyl group, alkylation of the intermediate
delocalised anion 22 occurred predominantly α to the com-
plexed arene. This regioselectivity was ascribed to either a
greater charge density or a greater orbital coefficient at the
observed alkylation site. Hydrolysis and decomplexation of
the product 23 gave an α-alkyl benzylic amine 24. Since high
diastereoselectivities were achieved in the alkylation step,
starting with optically pure ortho-methylbenzaldehyde complex
20 provided access to chiral benzylic amines 24 with high e.e. In
view of these results, it seemed feasible that an imine derived
from benzylamine complex 11 could be deprotonated at the
benzylic position using a (chiral) lithium amide base, and that
attack of an electrophile on the resultant 2-azaallyl anion
would be regioselective for the carbon α to the complexed arene.
The novel imine complex 25 was prepared in 79% yield, on
a 2 g scale, by stirring benzylamine complex 11 with trimethyl-
acetaldehyde and silica gel at room temperature (Scheme 12). It
was hoped that the tert-butyl-substituted 2-azaallyl anion
derived from complex 25 would be less stabilised than an aryl-
substituted analogue and hence exhibit greater reactivity and
configurational stability. Treatment of complex 25 with LDA in
25
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 6 7 6 – 6 8 3
678

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lower configurational stability of the more stabilised 2-azaallyl
anion it forms. Thus, a better e.e. was obtained from the
para-dimethylaminophenyl-substituted imine 28 (80% e.e., 61%
yield), possibly due to the destabilising effect of the NMe2
group on the intermediate anion. Attempted deprotonation of
para-nitrophenyl-substituted imine 29, on the other hand,
resulted in complete decomposition of the complex.
Deprotonation of imine complexes 25, 27 and 28 using
diamide base 5 gave, in each case, (R)-19, the same product
configuration as obtained in deprotonations of the acyclic ether
complexes by this base.1 A reaction pathway similar to that
proposed for the ether complexes could therefore be operating.
Selective removal of the pro-R benzylic proton [antiperiplanar
to the tricarbonylchromium group] from the substrate 30 by
base 5 would give a configurationally stable anion 31 (Scheme
16). Electrophilic attack would then occur stereoselectively from
the exo face to give the (R)-configured product 32.
Scheme 13
phenylethylamine complex to produce complex 19, for which
the e.e. could easily be measured by chiral HPLC (vide supra).
This one-pot procedure was carried out using the crude product
formed after deprotonation–methylation of the imine substrate.
Imine hydrolysis was complete within 30 min using 6 M
HCl–MeOH at room temperature, and Cbz-derivatisation was
effected using benzyl chloroformate.
This method permitted use of substrates with an imine
substituent other than tert-butyl. A series of novel aryl-
substituted imine complexes 27–29 were prepared for this
purpose by stirring benzylamine complex 11 with an arylalde-
hyde and silica gel at room temperature (Scheme 14).
Scheme 16
Experimental
General details
All reactions and manipulations involving organometallic
compounds were performed under nitrogen using standard
vacuum line and Schlenk tube techniques.18 Reactions involving
(arene)tricarbonylchromium(0) complexes were performed with
the exclusion of light. Tetrahydrofuran was distilled from
sodium benzophenone ketyl. Diethyl ether was either distilled
from sodium benzophenone ketyl or dried over sodium wire.
1,4-Dioxane and dichloromethane were distilled from calcium
hydride. The concentrations of alkyllithiums were determined
by titration against diphenylacetic acid in THF.19 The precursor
to diamide 5 was prepared according to a literature method.7
All other reagents were used as obtained from commercial
sources, unless otherwise stated.
Scheme 14
Methylation of the tert-butyl-substituted imine 25 gave
complex (ϩ)-19 in 69% overall yield with 81% e.e. (Scheme 15),
Melting ponts were determined using either an Electro-
thermal IA9100 digital or Büchi 510 melting point apparatus,
and are uncorrected. Melting points of organometallic com-
pounds were determined in sealed capillaries under nitrogen.
IR spectra were obtained on Perkin-Elmer 1710 or Mattson
5000 FTIR spectrometers. Elemental analyses were performed
by Imperial College Microanalytical Service. Optical rotations
were recorded on a Perkin-Elmer 241 polarimeter with a 10 cm
path length. Concentrations for optical rotation measurements
are given in g/100 cm3. NMR spectra were recorded at room
1
temperature on JEOL GSX 270 (270 MHz H, 67.9 MHz 13C)
Scheme 15
or Bruker DRZ 300 (300 MHz 1H, 75.4 MHz 13C) instruments.
1H NMR chemical shifts are referenced with respect to residual
undeuterated solvent while 13C NMR shifts are referenced with
in reasonably good agreement with the e.e. obtained for silyl-
ation. As (S)-19 had been prepared previously and was laevo-
rotatory this product was clearly (R)-configured [the silylated
complex (Ϫ)-26 was tentatively assumed to be (R) based on this
reasoning]. Phenyl-substituted imine 27 gave product (R)-(ϩ)-
19 in 69% yield but only 55% e.e. The lower optical yield in this
case may be related to the greater acidity of complex 27 or
1
respect to deuterated solvent. Broadband H decoupling was
employed for 13C NMR spectra. J values are given in Hz. Mass
spectra were recorded on VG Micromass 7070E or Autospec-Q
instruments at Imperial College, or a VG Mass Lab 12/250
instrument at EPSRC Mass Spectrometry Service, Swansea,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 6 7 6 – 6 8 3
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using EI or CI techniques. Analytical HPLC was carried out
using a Unicam Crystal 200 pump with a Unicam Spectrea
100 uv-vis detector at Imperial College, or Waters 600E System
Controller with a Waters 455 uv-vis detector at Associated
Octel Company.
(4 H, m, Cr–CHortho/meta); δC (67.9 MHz; CDCl3) 44.8 (CH2),
᎐
91.3 and 93.4 (Cortho/meta/para), 114.2 (Cipso) and 233.0 (C᎐O); m/z
᎐
(EI) 243 (Mϩ, 10%), 215 (M Ϫ CO, 3), 187 (M Ϫ 2CO, 8), 159
(M Ϫ 3CO, 72) and 52 (Cr, 100). Complex 11 darkened over
several days storage under N2 and was conveniently stockpiled
as the trifluoroacetic acid salt. This was formed by addition of
trifluoroacetic acid (1.1 equiv.) to a CH2Cl2 solution of the
complex (0.2 M), followed by addition of an equal volume
of diethyl ether to induce precipitation. The precipitate was
filtered and washed with diethyl ether to give (η6-benzyl-
ammonium)tricarbonylchromium(0) trifluoroacetate 12 as a
yellow solid; δH (270 MHz; D2O) 3.73 (2 H, s, CH2) and 5.40–
5.53 (5 H, m, Cr–CH ). The free amine could be regenerated by
addition of saturated aqueous K2CO3, extraction into diethyl
ether and removal of the solvent in vacuo.
General procedure for complexation of arenes to
tricarbonylchromium(0)
A round-bottomed flask fitted with an air condenser below
a water condenser, connected in series (all joints B24), was
charged with arene, hexacarbonylchromium(0), dibutyl ether
and THF (Bu2O : THF, 10 : 1). The mixture was thoroughly
degassed and heated at reflux in the dark for 30–48 h (bath
temp. approx. 140 ЊC). The resulting solution/suspension was
cooled to room temperature, diluted with an equal volume of
diethyl ether, filtered through a short pad of silica or Celite
(elution with diethyl ether) and evaporated under reduced
pressure. The residue was purified by column chromatography
and/or recrystallisation.
N-(tert-Butoxycarbonyl)benzylamine 13
A solution of benzylamine (5.36 g, 50 mmol) and di-tert-butyl
dicarbonate (10.91 g, 50 mmol) in MeOH (25 cm3) was stirred
at room temperature for 2 h. The solvent was removed in vacuo
and the residue recrystallised from petroleum ether (bp 40–60
ЊC) to give the title compound 13 as colourless needles (9.13 g,
44.1 mmol, 88%), mp 53.5–55 ЊC (lit.13 mp 55.5–56.5 ЊC); νmax
(ꢀ6-Benzyldimethylamine)tricarbonylchromium(0) 98
Following the general procedure for complexation, benzyl-
dimethylamine(2.00 g, 14.8 mmol), hexacarbonylchromium(0)
(3.58 g, 16.2 mmol), dibutyl ether (60 cm3) and THF (6 cm3)
were heated for 46 h, and the mixture filtered through Celite.
Purification by flash column chromatography (SiO2; EtOAc–
Et2O, 1 : 4) and recrystallisation from CH2Cl2–petroleum ether
(bp 40–60 ЊC) gave the title complex 9 as a yellow crystalline
solid (3.08 g, 11.3 mmol, 77%), mp 44.5–45.5 ЊC (lit.8 mp 48–50
ЊC); δH (270 MHz; CDCl3) 2.29 (6 H, s, CH3), 3.14 (2 H, s, CH2),
(CH2Cl2)/cmϪ1 3448m (NH), 1713s (C᎐O), 1505s and 1159s;
᎐
δH (270 MHz; CDCl3) 1.46 [9 H, s, C(CH3)3], 4.31 (2 H, d, J5.3,
CH2), 4.85 (1 H, br s, NH ) and 7.23–7–36 (5 H, m, Ph).
[ꢀ6-N-(tert-Butoxycarbonyl)benzylamine]tricarbonyl-
chromium(0) 14
Following the general procedure for complexation, N-(tert-
butoxycarbonyl)benzylamine 13 (4.15 g, 20.0 mmol), hexacar-
bonylchromium(0) (4.40 g, 20.0 mmol), dibutyl ether (80 cm3)
and THF (8 cm3) were heated for 48 h, and the mixture filtered
through Celite. Purification by flash column chromatography
[SiO2; CH2Cl2–petroleum ether (bp 40–60 ЊC), 7 : 3] and re-
crystallisation from diethyl ether–petroleum ether (bp 40–60
ЊC) gave the title complex 14 as a yellow crystalline solid (4.73 g,
13.8 mmol, 69%), mp 97–98 ЊC (Found: C, 52.4; H, 4.9; N, 4.15.
C15H17CrNO5 requires C, 52.48; H, 4.99; N, 4.08%); νmax
5.23–5.28 (1 H, m, Cr–CHpara), 5.30–5.32 (2 H, m, Cr–CHortho
)
and 5.36–5.41 (2 H, m, Cr–CHmeta); δC (67.9 MHz; CDCl3) 45.2
(CH3), 62.8 (CH2), 91.3 (Cpara), 93.2 and 93.8 (Cortho and Cmeta),
ϩ
᎐
108.5 (Cipso) and 232.8 (C᎐O); m/z (EI) 271 (M , 77%), 215 (M
᎐
Ϫ 2CO, 85), 187 (M Ϫ 3CO, 96) and 91 (PhCH2, 100).
Attempted deprotonation of (ꢀ6-benzyldimethylamine)-
tricarbonylchromium(0) 9 using chiral lithium amide 5
(CH2Cl2)/cmϪ1 3449w (NH), 1969s and 1888s (C᎐O) and 1714m
᎐
᎐
A solution of lithium amide 5 was prepared by addition of
BuLi (1.6 M in hexanes, 0.55 cm3, 0.88 mmol) to a stirred
solution of the diamine precursor to 5 (185 mg, 0.44 mmol) in
THF (5 cm3) at Ϫ78 ЊC, followed by warming to room temper-
ature. The resulting pink solution was recooled to Ϫ78 ЊC and
a solution of flame-dried LiCl (17 mg, 0.40 mmol) in THF
(5 cm3) was added via a cannula. To this was added a solution
of complex 9 (108 mg, 0.40 mmol) in THF (5 cm3) via a cannula
over approximately 2 min. The solution was stirred at Ϫ78 ЊC
for 1 h after which MeI (0.10 cm3, 1.61 mmol) was added. After
a further 1 h at Ϫ78 ЊC, MeOH was added, the mixture allowed
to warm to room temperature and the solvents removed in
vacuo. The residue was purified by flash chromatography (SiO2;
EtOAc–Et2O, 1 : 4) which gave starting complex 9 (87 mg, 0.30
(C᎐O); δH (270 MHz; CDCl3) 1.47 [9 H, s, C(CH3)], 4.10 (2 H,
᎐
d, J 6.5, CH2), 5.00 (1 H, br m, NH ), 5.23–5.29 (3 H, m,
Cr–CHortho/para) and 5.40 (2 H, dd, J 6.0, 6.0, Cr–CHmeta);
δC (75.4 MHz; CDCl3) 28.4 [C(CH3)3], 43.2 (CH2), 80.4
[C(CH3)3], 91.2 (Cortho or Cmeta), 91.3 (Cpara), 93.4 (Cortho or
᎐
Cmeta), 110.3 (Cipso), 156.0 (C᎐O) and 232.8 (C᎐O); m/z (EI) 343
᎐
᎐
(Mϩ, 18%), 315 (M Ϫ CO, 18), 287 (M Ϫ 2CO, 50), 259
(M Ϫ 3CO, 85), 203 [M Ϫ 3CO Ϫ (CH ) C᎐CH , 97] and 91
᎐
3
2
2
(PhCH2, 100).
Boc deprotection of [ꢀ6-N-(tert-butoxycarbonyl)benzylamine]-
tricarbonylchromium(0) 14
A solution of complex 14 (3.43 g, 10.0 mmol) and tri-
fluoroacetic acid (2.0 cm3, 26 mmol) in CH2Cl2 (40 cm3) was
stirred at room temperature for 2 h. Diethyl ether (30 cm3) was
added and the resultant precipitate filtered and washed with
further diethyl ether to give (η6-benzylammonium)tricarb-
onylchromium(0) trifluoroacetate 12 as a yellow crystalline
solid (3.25 g, 9.1 mmol, 91%). A sample of free amine, formed
by addition of saturated aqueous K2CO3, extraction into
diethyl ether and removal of the solvent in vacuo, had identical
1H NMR and TLC data to those of authentic complex 12.
1
mmol, 81%). The H NMR spectrum and TLC of the product
were identical to those of authentic 9.
Complexation of benzylamine to tricarbonylchromium in Bu2O–
THF to give complex 11
Following the general procedure for complexation, benzyl-
amine (6.4 g, 60 mmol), hexacarbonylchromium(0) (1.10 g,
5.0 mmol), dibutyl ether (40 cm3) and THF (4 cm3) were heated
for 48 h to give, after filtration through Celite and flash column
chromatography (SiO2; CH2Cl2–EtOH, 1 : 0 to 9 : 1), (η6-ben-
zylamine)tricarbonylchromium() 11 as a yellow oil (0.58 g, 2.4
mmol, 48%) (Found: C, 49.2; H, 3.5; N, 5.6. C10H9CrNO3
Complexation of benzylamine to tricarbonylchromium in
1,4-dioxane to give complex 11
requires C, 49.39; H, 3.73; N, 5.76%); νmax (CH2Cl2)/cmϪ1 1963s
The general procedure for complexation was followed except
1,4-dioxane was used instead of dibutyl ether and THF, and
the bath temperature was 110 ЊC. Thus, benzylamine (0.268 g,
᎐
and 1890s (C᎐O); δH (270 MHz; CDCl3) 1.45 (2 H, br s, NH2),
᎐
3.68 (2 H, s, CH2), 5.23–5.28 (1 H, m, Cr–CHpara) and 5.39–5.43
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 6 7 6 – 6 8 3
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2.50 mmol), hexacarbonylchromium(0) (1.10 g, 5.00 mmol) and
1,4-dioxane were heated for 48 h to give, after filtration through
Celite and flash column chromatography (SiO2; CH2Cl2–EtOH,
1 : 0 to 9 : 1), (η6-benzylamine)tricarbonylchromium(0) 11 as a
yellow oil (0.403 g, 1.66 mmol, 66%). The H NMR and TLC
data of the product were identical to those of authentic 11.
( )-[ꢀ6-N-(tert-Butoxycarbonyl)-1-phenylethylamine]tricarbonyl-
chromium(0) ( )-18
A solution of (η6-1-phenylethylammonium)tricarbonylchrom-
ium(0) trifluoroacetate 17 (36 mg, 0.10 mmol), di-tert-butyl
dicarbonate (26 mg, 0.12 mmol) and triethylamine (20 µl,
0.14 mmol) in MeOH (1 cm3) was stirred at room temperature
for 2 h. The solvent was removed in vacuo and the residue
purified by flash chromatography [SiO2; CH2Cl2–petroleum
ether (bp 40–60 ЊC), 6 : 4] and recrystallisation from diethyl
ether–petroleum ether (bp 40–60 ЊC) to give the title complex
( )-18 as a yellow solid (26 mg, 0.073 mmol, 72%), mp 79–81
1
[ꢀ6-N-(Benzyloxycarbonyl)benzylamine]tricarbonylchromium(0)
15
(η6-Benzylammonium)tricarbonylchromium(0) trifluoroacetate
12 (0.500 g, 1.40 mmol), saturated aqueous KHCO3 (10 cm3)
and diethyl ether (10 cm3) were stirred at room temperature for
10 min. Benzyl chloroformate (0.22 cm3, 1.54 mmol) was added
and stirring continued for 0.5 h. The layers were separated and
the aqueous layer extracted with diethyl ether until no longer
yellow. The combined organic phase was washed with brine
(20 cm3), dried (Na2SO4) and the solvent removed in vacuo. The
residue was purified by flash chromatography [SiO2; CH2Cl2–
petroleum ether (bp 40–60 ЊC), 8 : 2] to give the title complex 15
as a yellow crystalline solid (0.461 g, 1.22 mmol, 87%), mp
105.5–107.5 ЊC (Found: C, 57.35; H, 4.1; N, 3.5. C18H15CrNO5
ЊC; νmax (CH2Cl2)/cmϪ1 3447w (NH), 1970s and 1892s (C᎐O)
᎐
᎐
and 1708m (C᎐O); δ (270 MHz; CDCl ) 1.46–1.48 [12 H, over-
᎐
H
3
lapping s and d, J ≈ 6, C(CH3)3 and CHCH3], 4.62–4.80 (2 H, br
m, CHNH ), 5.24–5.36 (3 H, m, Cr–CH ), 5.40–5.44 (1 H, m,
Cr–CH ) and 5.47–5.50 (1 H, m, Cr–CH ); δC (67.9 MHz;
CDCl3) 20.3 (CHCH3), 28.3 [C(CH3)3], 47.6 (CHNH), 80.2
[C(CH3)], 91.3, 91.4, 92.9 and 93.3 (Cortho/meta/para), 114.0 (Cipso),
ϩ
᎐
155.1 (C᎐O) and 232.7 (C᎐O); m/z (CI, NH ) 375 [(M ϩ NH ) ,
᎐
᎐
3
4
13%], 319 [M ϩ NH Ϫ (CH ) C᎐CH , 28], 239 [M ϩ NH Ϫ
᎐
4
3
2
2
4
Cr(CO) , 30] and 183 [M ϩ NH Ϫ Cr(CO) Ϫ (CH ) C᎐CH ,
᎐
3
4
3
3
2
2
100] [Found: (M ϩ NH4)ϩ; 375.1023. C16H23CrN2O5 requires
requires C, 57.30; H, 4.01; N, 3.71%); νmax (CH2Cl2)/cmϪ1 3443w
375.1012].
᎐
(NH), 1970s and 1895s (C᎐O) and 1725m (C᎐O); δ (270 MHz;
᎐
᎐
H
( )-[ꢀ6-N-(Benzyloxycarbonyl)-1-phenylethylamine]tricarbonyl-
chromium(0) 19
CDCl3) 4.15 (2 H, d, J 6.5, NHCH2), 5.15 (2 H, s, OCH2), 5.20–
5.40 (6 H, m, NH and Cr–CH ) and 7.35–7.39 (5 H, m, Ph);
δC (75.4 MHz; CDCl3) 43.6 (CH2NH), 67.2 (CH2O), 91.3 and
93.2 (Cr–Cortho/meta/para), 109.3 (Cr–Cipso), 128.1 (Ph–Cortho or Ph–
Cmeta), 128.2 (Ph–Cpara), 128.5 (Ph–Cortho or Ph–Cmeta), 136.0
Racemic (η6-1-Phenylethylammonium)tricarbonylchromium(0)
trifluoroacetate 17 (36 mg, 0.10 mmol), saturated aqueous
KHCO3 (2 cm3) and diethyl ether (2 cm3) were stirred at room
temperature for 10 min. Benzyl chloroformate (17 µl, 0.12
mmol) was added and stirring was continued for a further 0.5 h.
The layers were separated and the aqueous layer extracted with
diethyl ether until no longer yellow. The combined organic
phase was dried (Na2SO4) and the solvent removed in vacuo.
The residue was purified by flash chromatography [SiO2;
CH2Cl2–petroleum ether (bp 40–60 ЊC), 8 : 2] followed by
recrystallisation from diethyl ether–petroleum ether (bp 40–60
ЊC) to give the title complex 19 as a yellow solid (17 mg, 0.043
mmol, 43%), mp 86–87 ЊC (Found: C, 58.05; H, 4.1; N, 3.5.
C19H17CrNO5 requires C, 58.31; H, 4.38; N, 3.58%); νmax
ϩ
᎐
(Ph–Cipso), 156.5 (C᎐O) and 232.6 (C᎐O); m/z (EI) 377 (M ,
᎐
᎐
0.2%), 321 (M Ϫ 2CO, 1), 293 (M Ϫ 3CO, 10), 185 (M Ϫ 3CO
Ϫ PhCH2O, 41), 157 (M Ϫ 3CO Ϫ PhCH2OCO, 30) and 91
(PhCH2, 100).
( )-(ꢀ6–1-Phenylethylamine)tricarbonylchromium(0) ( )-1615
Following the general complexation procedure, ( )-1-phenyl-
ethylamine (0.60 g, 5.0 mmol), hexacarbonylchromium(0)
(1.1 g, 5.0 mmol), dibutyl ether (30 cm3) and THF (3 cm3) were
heated for 46 h to give, after filtration through Celite and flash
column chromatography (SiO2; CH2Cl2–EtOH, 1 : 0 to 19 : 1),
the title complex ( )-16 as a yellow oil (0.98 g, 3.8 mmol, 76%);
(CH2Cl2)/cmϪ1 3432w (NH), 1970s and 1888s (C᎐O) and 1716m
᎐
᎐
νmax (CH2Cl2)/cmϪ1 1966s and 1888s (C᎐O); δ (270 MHz;
᎐
(C᎐O); δ (270 MHz; CDCl ) 1.49 (3 H, d, J 6.7, CHCH ), 4.73
᎐
H
3
3
᎐
H
(1 H, br m, NHCH ), 4.95–5.02 (1 H, s, NH ), 5.07–5.18 (2 H,
m, OCH2), 5.25–5.30 (2 H, m, Cr–CH ), 5.33–5.41 (2 H,
Cr–CH ), 5.47–5.50 (1 H, m, Cr–CH ) and 7.29–7.40 (5 H, m,
Ph); δC (67.9 MHz; CDCl3) 20.2 (CH3), 48.4 (CHNH), 67.2
(CH2O), 91.3, 93.0 and 93.2 (Cr–Cortho/meta/para), 113.2 (Cr–Cipso),
128.2 (Ph–Cortho or Ph–Cmeta), 128.3 (Ph–Cpara), 128.6 (Ph–Cortho
CDCl3) 1.36 (3 H, d, J 6.7, CH3), 1.50 (2 H, br s, NH2), 3.84
(1 H, q, J 6.7, CHCH3), 5.27–5.41 (4 H, m, Cr–CH ), and 5.63
(1 H, d, J 6.5, Cr–CHortho); δC (75.4 MHz; CDCl3) 26.0 (CH3),
49.6 (CHCH3), 90.0, 91.8, 92.1, 92.9 and 93.0 (Cortho/meta/para),
ϩ
᎐
119.0 (Cipso) and 233.2 (C᎐O); m/z (EI) 257 (M , 72%), 229
᎐
(M Ϫ CO, 20), 201 (M Ϫ 2CO, 53), 173 (M Ϫ 3CO, 91), 156
(M Ϫ 3CO Ϫ NH3, 97) and 52 (Cr, 100). Complex 16 darkened
over several days storage under N2 and was conveniently
stockpiled as the trifluoroacetic acid salt, formed by addition
of trifluoroacetic acid (1.1 equiv.) to a CH2Cl2 solution of the
complex (0.2 M), followed by addition of an equal volume of
diethyl ether to induce precipitation. The precipitate was
filtered and washed with diethyl ether to give (η6-1-phenylethyl-
ammonium)tricarbonylchromium(0) trifluoroacetate 17 as a
yellow solid; δH (270 MHz; CD3SOCD3) 1.53 (3 H, d, J 6.7,
CH3), 4.21 (1 H, q, J 6.7, CHCH3), 5.74–5.80 (2 H, m,
Cr–CHmeta), 5.84–5.89 (1 H, m, Cr–CHpara), (2 H, d, J 6, Cr–
CHortho) and 8.44 (3 H, br s, NH3). The free amine could be
regenerated by addition of saturated aqueous K2CO3, extrac-
tion into diethyl ether and removal of the solvent in vacuo.
᎐
or Ph–Cmeta), 136.1 (Ph–Cipso), 155.7 (C᎐O) and 232.6 (C᎐O);
᎐
᎐
m/z (EI) 391 (Mϩ, 1%), 307 (M Ϫ 3CO, 15), 199 (M Ϫ 3CO Ϫ
PhCH2O, 61), 171 (M Ϫ 3CO Ϫ PhCH2OCO, 20) and 105
(PhCHCH3, 100).
(S )-(؊)-[ꢀ6-N-(Benzyloxycarbonyl)-1-phenylethylamine]-
tricarbonylchromium(0) (S )-19
A similar procedure to that for ( )-19 was followed using
(S)-(η6-1-phenylethylammonium)tricarbonylchromium(0) tri-
fluoroacetate (S)-17 (179 mg, 0.50 mmol), saturated aqueous
KHCO3 (5 cm3) and diethyl ether (5 cm3) and benzyl chloro-
formate (86 µl, 0.60 mmol) to give the title complex (S)-19 as a
25
yellow solid (147 mg, 0.376 mmol, 75%); [α]D Ϫ30 (c = 1,
CH2Cl2); 1H NMR and TLC were identical to those of racemic
complex 19; HPLC: Chiralcel OD-H column; eluent propan-2-
ol–hexane, 3 : 7; flow rate 1 cm3 minϪ1; detection 330 nm; (Ϫ)-19
RT 13.8 min, (ϩ)-19 RT 16.8 min; e.e. ≥ 99%.
(S )-(؉)-(ꢀ6–1-Phenylethylamine)tricarbonylchromium(0) (S )-16
Following the procedure used for ( )-16, except using (S)-(Ϫ)-
1-phenylethylamine instead of the racemate, complex (S)-16
was isolated as a yellow oil (1.02 g, 3.97 mmol, 79%); [α]D25 ϩ20
Attempted deprotonation of [ꢀ6-N-(benzyloxycarbonyl)benzyl-
amine]tricarbonylchromium(0) 15 using chiral lithium amide 5
1
(c = 1, CH2Cl2). The H NMR and TLC data were identical
A solution of lithium amide 5 was prepared by addition
to those of racemic complex 16.
of BuLi (1.6 M in hexanes, 0.55 cm3, 0.88 mmol) to a stirred
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 6 7 6 – 6 8 3
681

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solution of the precursor chiral diamine (185 mg, 0.44 mmol) in
THF (2 cm3) at Ϫ78 ЊC, followed by warming to room temper-
ature. The resulting pink solution was recooled to Ϫ78 ЊC and
a solution of flame-dried LiCl (17 mg, 0.40 mmol) in THF
(4 cm3) was added via a cannula. A stirred solution of complex
15 (151 mg, 0.40 mmol) in THF (3 cm3) at Ϫ78 ЊC was treated
with BuLi (1.6 M in hexanes, 0.24 cm3, 0.38 mmol) and the
resultant solution added via a cannula to the lithium amide–
LiCl solution at Ϫ40 ЊC over approximately 2 min. After 2.5 h
at Ϫ40 ЊC, MeI (0.10 cm3, 1.61 mmol) was added followed by,
after a further 1 h at Ϫ40 ЊC, MeOH (1 cm3). The mixture was
allowed to warm to room temperature, the solvents removed in
vacuo and the residue subjected to flash chromatography (SiO2;
toluene–diethyl ether, 50 : 1) to give an inseparable mixture of
methylated complex 19 and starting complex 15 (107 mg) in
38 : 62 ratio, as determined by integration of the methyl signal
for 19 and methylene signal for 15 in the 1H NMR spectrum.
0.44 mmol) in THF (6 cm3) at Ϫ78 ЊC, and the mixture warmed
to room temperature. The resulting pink solution was recooled
to Ϫ78 ЊC and a solution of flame-dried LiCl (17 mg, 0.40
mmol) in THF (4 cm3) was added via a cannula. Me3SiCl (0.13
cm3, 1.0 mmol) was added, followed by complex 25 (125 mg,
0.40 mmol) in THF (5 cm3) and the resulting red solution was
stirred at Ϫ78 ЊC for 0.5 h. MeOH (1 cm3) was added, the
mixture warmed to room temperature and the solvents removed
in vacuo. The residue was subjected to column chromatography
[SiO2; diethyl ether–petroleum ether (bp 40–60 ЊC), 1 : 19] to
give the title complex (Ϫ)-26 as a yellow crystalline solid
(137 mg, 0.357 mmol, 89%); [α]D25 Ϫ23 (c = 1, CH2Cl2); HPLC:
Chiralcel OD-H column; eluent propan-2-ol–hexane, 1 : 1999;
flow rate 1 cm3 minϪ1; detection 330 nm; (ϩ)-26 RT 10.4 min,
(Ϫ)-26 RT 11.4 min; e.e. 87%.
(ꢀ6-N-Benzylidenebenzylamine)tricarbonylchromium(0) 27
[ꢀ6-N-(2,2-Dimethylpropylidene)benzylamine]tricarbonyl-
chromium(0) 25
A mixture of benzylamine complex 11 (340 mg, 1.40 mmol),
benzaldehyde (0.20 cm3, 2.0 mmol) and silica gel (1 g) in CH2Cl2
(3 cm3) was stirred for 0.5 h at room temperature. The slurry
was transferred to a column with sintered glass fritt, with
residual material transferred in diethyl ether. The column was
eluted with diethyl ether, the solvents removed in vacuo and the
residue recrystallised from diethyl ether–petroleum ether (bp
40–60 ЊC) to give the title complex 27 as yellow crystals (375 mg,
1.13 mmol, 81%), mp 87–88 ЊC (Found: C, 61.4; H, 3.65; N, 4.1.
C17H13CrNO3 requires C, 61.63; H, 3.96; N, 4.23%); νmax
A mixture of benzylamine complex 11 (1.75 g, 7.20 mmol),
trimethylacetaldehyde (0.93 cm3, 8.6 mmol) and silica gel (3 g)
in CH2Cl2 (5 cm3) was stirred for 0.5 h at room temperature.
The slurry was transferred to a column with sintered glass fritt,
with residual material transferred in diethyl ether. The column
was eluted with diethyl ether, the solvents removed in vacuo and
the residue recrystallised from petroleum ether (bp 40–60 ЊC) to
give the title complex 25 as a yellow powder (1.78 g, 5.72 mmol,
79%), mp 62–62.5 ЊC (Found: C, 57.75; H, 5.45; N, 4.65.
C15H17CrNO3 requires C, 57.88; H, 5.50; N, 4.50%); νmax
(CH2Cl2)/cmϪ1 1968s and 1889s (C᎐O) and 1642m (C᎐N);
᎐
᎐
᎐
δH (300 MHz; CDCl3) 4.56 (2 H, s, CH2), 5.24–5.28 (1 H, m,
Cr–CHpara), 5.40–5.48 (4 H, m, Cr–CHortho/meta), 7.42–7.49 (3 H,
m, Ph–CHmeta/para), 7.80–7.84 (2 H, m, Ph–CHortho) and 8.42
(CH2Cl2)/cmϪ1 1967s and 1890s (C᎐O) and 1667m (C᎐N);
᎐
᎐
᎐
δH (270 MHz; CDCl3) 1.11 [9 H, s, C(CH3)3], 4.32 (2 H, d, J 1.2,
CH2), 5.22–5.26 (1 H, m, Cr–CHpara), 5.34–5.40 (4 H, m, Cr–
(1 H, s, CH᎐N); δ (75.4 MHz; CDCl ) 63.0 (CH ), 91.1 (Cr–
᎐
C
3
2
Cpara), 92.1 and 93.1 (Cr–Cortho and Cr–Cmeta), 110.6 (Cr–Cipso),
128.4 and 128.6 (Ph–Cortho and Ph–Cmeta), 131.2 (Ph–Cpara),
CHortho/meta) and 7.67 (1 H, t, J 1.2, CH᎐N); δ (75.4 MHz;
᎐
C
CDCl3) 26.7 [C(CH3)3], 36.6 [C(CH3)3], 62.4 (CH2), 91.5 (Cpara),
᎐
135.6 (Ph–Cipso), 163.3 (HC᎐N) and 232.8 (C᎐O); m/z (EI) 331
᎐
᎐
(Mϩ, 2%), 303 (M Ϫ CO, 3), 275 (M Ϫ 2CO, 11), 247
(M Ϫ 3CO, 47), 155 (CrNCPh, 47), 91 (PhCH2, 63) and 52 (Cr,
100).
92.1 and 93.0 (Cortho and Cmeta), 111.4 (Cipso), 175.1 (HC᎐N) and
᎐
ϩ
᎐
233.0 (C᎐O); m/z (EI) 311 (M , 19%), 255 (M Ϫ 2CO, 45), 227
᎐
(M Ϫ 3CO, 85), 143 (CrPhCH2, 96) and 135 [CrNCC(CH3)3,
100].
[ꢀ6-N-(4-Dimethylaminobenzylidene)benzylamine]tricarbonyl-
chromium(0) 28
( )-[ꢀ6-N-(2,2-Dimethylpropylidene)-ꢁ-(trimethylsilyl)benzyl-
amine]tricarbonylchromium(0) ( )-26
LDA (1.47 M in cyclohexane, 0.33 cm3, 0.49 mmol) was added
to THF (5 cm3) at Ϫ78 ЊC after which Me3SiCl (0.10 cm3,
0.8 mmol) was added, with stirring. A solution of complex
25 (125 mg, 0.40 mmol) in THF (5 cm3) was added via a
cannula. The resulting red solution was stirred for 0.5 h at
Ϫ78 ЊC, MeOH (1 cm3) was added, the mixture was allowed to
warm to room temperature and the solvents removed in vacuo.
The residue was subjected to column chromatography [SiO2;
diethyl ether–petroleum ether (bp 40–60 ЊC), 1 : 19] to give the
title complex ( )-26 as a yellow crystalline solid (109 mg, 0.285
mmol, 71%), mp 92–93 ЊC (Found: C, 56.3; H, 6.35; N, 3.65.
C18H25CrNO3Si requires C, 56.38; H, 6.57; N, 3.65%); νmax
A mixture of benzylamine complex 11 (340 mg, 1.40 mmol),
4-dimethylaminobenzaldehyde (209 mg, 1.40 mmol) and silica
gel (1 g) in CH2Cl2 (5 cm3) was stirred for 1 h at room temper-
ature. The slurry was transferred to a column with sintered
glass fritt, with residual material transferred in diethyl ether.
The column was eluted with diethyl ether, the solvents removed
in vacuo and the residue recrystallised from diethyl ether–
CH2Cl2 to give the title complex 28 as yellow plates (318 mg,
0.85 mmol, 61%), mp 109.5–110.5 ЊC (Found: C, 60.85; H, 4.65;
N, 7.35. C19H18CrN2O3 requires C, 60.96; H, 4.85; N, 7.48%);
νmax (CH2Cl2)/cmϪ1 1962s and 1888s (C᎐O), 1636m and 1607s
᎐
᎐
(C᎐N); δ (270 MHz; CDCl ) 3.03 [6 H, s, N(CH ) ], 4.47 (2 H,
᎐
H
3
3 2
(CH2Cl2)/cmϪ1 1962s and 1882s (C᎐O) and 1660w (C᎐N);
s, CH2), 5.20–5.25 (1 H, m, Cr–CHpara), 5.37–5.45 (4 H, m,
Cr–CHortho/meta), 6.70 (2 H, d, J 8.9, Me2NCCH ), 7.65 (2 H, d,
᎐
᎐
᎐
δH (300 MHz; CDCl3) 0.00 [9 H, s, Si(CH3)3], 1.12 [9 H, s,
C(CH3)3], 3.64 (1 H, s, CHSiMe3), 5.09 (1 H, d, J 6.5,
Cr–CHortho), 5.20 (1 H, m, Cr–CHmeta), 5.34 (1 H, m, Cr–
CHpara), 5.42 (1 H, m, Cr–CHmeta), 5.76 (1 H, d, J 6.5, Cr–
J 8.9, N᎐CHCCH ) and 8.24 (1 H, s, CH᎐N); δ (67.9 MHz;
᎐
᎐
C
CDCl3) 40.1 [N(CH3)2], 63.2 (CH2), 91.1 (Cr–Cpara), 92.4 and
93.2 (Cr–Cortho and Cr–Cmeta), 111.5 (Me2NCCH), 111.6
(Cr–Cipso), 123.7 (N᎐CHC), 129.9 (N᎐CHCCH), 152.4
᎐
᎐
CHortho) and 7.51 (1 H, s, CH᎐N); δ (67.9 MHz; CDCl ) Ϫ3.8
᎐
C
3
ϩ
᎐
(Me NC), 163.3 (HC᎐N) and 233.0 (C᎐O); m/z (EI) 374 (M ,
᎐
᎐
2
[Si(CH3)3], 27.0 [C(CH3)3], 36.6 [C(CH3)3], 67.2 (CHSiMe3),
90.2, 90.3, 90.6, 92.9 and 93.5 (Cortho/meta/para), 117.3 (Cipso), 169.6
4%), 318 (M Ϫ 2CO, 16), 290 (M Ϫ 3CO, 40), 198
[CrNC(C6H4)NMe2, 58], 91 (PhCH2, 100) and 52 (Cr, 79).
ϩ
᎐
(HC᎐N) and 233.6 (C᎐O); m/z (EI) 383 (M , 37%), 327 (M Ϫ
᎐
᎐
2CO, 17), 299 (M Ϫ 3CO, 82) and 135 [CrNCC(CH3)3, 100].
[ꢀ6-N-(4-Nitrobenzylidene)benzylamine]tricarbonylchromium(0)
29
(؊)-[ꢀ6-N-(2,2-Dimethylpropylidene)-ꢁ-(trimethylsilyl)benzyl-
amine]tricarbonylchromium(0) (؊)-26
BuLi (1.6 M in hexanes, 0.55 cm3, 0.88 mmol) was added to a
A mixture of benzylamine complex 11 (340 mg, 1.40 mmol),
4-nitrobenzaldehyde (212 mg, 1.40 mmol) and silica gel (1 g) in
CH2Cl2 (3 cm3) was stirred for 1 h at room temperature. The
stirred solution of the diamine precursor to diamide 5 (185 mg,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 6 7 6 – 6 8 3
682

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slurry was transferred to a column with sintered glass fritt, with
residual material transferred in diethyl ether. The column was
eluted with diethyl ether–CH2Cl2, 1 : 1, the solvents removed
in vacuo and the residue recrystallised from diethyl ether–
CH2Cl2 to give the title complex 29 as yellow-orange plates (363
mg, 0.965 mmol, 69%), mp 114.5–115.5 ЊC (Found: C, 53.95; H,
2.95; N, 7.2. C17H12CrN2O5 requires C, 54.26; H, 3.21; N,
onylchromium(0) 19 was isolated as a yellow solid (108 mg,
0.276 mmol, 69%); [α]D25 ϩ23 (c = 1, CH2Cl2); HPLC: as above
for the direct synthesis of 19; e.e. 55%.
Synthesis of complex (؉)-19 from [ꢀ6-N-(4-dimethylamino-
benzylidene)benzylamine]tricarbonylchromium(0) 28
The procedure given above was followed using BuLi (1.26 M,
0.70 cm3, 0.88 mmol) and complex 28 (150 mg, 0.40 mmol).
Imine hydrolysis was complete within 1 h at room temperature.
[η6-N-(Benzyloxycarbonyl)-1-phenylethylamine]tricarbonyl-
chromium(0) 19 was isolated as a yellow solid (96 mg, 0.245
mmol, 61%); [α]D26 ϩ26 (c = 1, CH2Cl2); HPLC: as above for the
direct synthesis of 19; e.e. 80%.
7.44%); νmax (CH2Cl2)/cmϪ1 1968s and 1886s (C᎐O), 1648w and
᎐
᎐
1603w (C᎐N), 1526m and 1347m (N–O); δ (300 MHz; CDCl )
᎐
H
3
4.63 (2 H, s, CH2), 5.28–5.33 (1 H, m, Cr–CHpara), 5.40–5.48
(4 H, m, Cr–CHortho/meta), 7.98 (2 H, ABd, J 8.8, O2NCCH ), 8.31
(2 H, ABd, J 8.8, N᎐CHCCH ) and 8.50 (1 H, s, CH᎐N); δ
᎐
᎐
C
(67.9 MHz; CDCl3) 63.0 (CH2), 91.5 (Cr–Cpara), 92.1 and 92.9
(Cr–Cortho and Cr–Cmeta), 109.7 (Cr–Cipso), 123.9 (O2NCCH),
129.1 (N᎐CHCCH), 141.0 (N᎐CHC), 149.3 (O NC), 161.0
᎐
᎐
Attempted deprotonation of [ꢀ6-N-(4-nitrobenzylidene)benzyl-
amine]tricarbonylchromium(0) 29 using chiral lithium amide 5
2
ϩ
᎐
(HC᎐N) and 232.8 (C᎐O); m/z (EI) 376 (M , 1%), 320 (M Ϫ
᎐
᎐
2CO, 3), 292 (M Ϫ 3CO, 13), 240 [M Ϫ Cr(CO)3, 24] and 91
(PhCH2, 100).
The procedure given above was initially followed using BuLi
(1.6 M, 0.55 cm3, 0.88 mmol) and complex 29 (150 mg,
0.40 mmol). On addition of the solution of complex 29 to the
lithium amide–LiCl solution, the mixture became deep purple
in colour with decomposition of the complex observed by TLC.
General procedure for the synthesis of [ꢀ6-N-(benzyloxycarb-
onyl)-1-phenylethylamine]tricarbonylchromium(0) 19 from
N-benzylimine complexes using chiral lithium amide 5
1
The H NMR spectrum (270 MHz; CDCl3) of the purple resi-
BuLi (1.26–1.6 M in hexanes, 0.88 mmol) was added to a stirred
solution of the chiral diamine precursor to 5 (185 mg, 0.44
mmol) in THF (6 cm3) at Ϫ78 ЊC, and the mixture warmed to
room temperature. The resulting pink solution was recooled
to Ϫ78 ЊC and a solution of flame-dried LiCl (17 mg,
0.40 mmol) in THF (4 cm3) was added via a cannula. The
N-benzylimine complex (0.40 mmol) in THF (5 cm3) was added
via a cannula over approximately 2 min and the resulting deep
orange to red solution stirred at Ϫ78 ЊC for 2 h. MeI (0.25 cm3,
4.0 mmol) was added followed by, after 1 h, MeOH (1 cm3). The
mixture was warmed to room temperature, the solvents
removed in vacuo, MeOH (10 cm3) was added, followed by 6 M
aqueous HCl (6 cm3) and the mixture stirred until imine
hydrolysis was complete by TLC. The mixture was cooled to
0 ЊC and saturated aqueous K2CO3 was added dropwise until
the pH was above 9. Diethyl ether (5 cm3) was added, followed
by benzyl chloroformate (70 µl, 0.49 mmol) and the mixture
stirred at room temperature for 0.5 h after which the layers were
separated and the aqueous layer extracted with further diethyl
ether until no longer yellow. The combined organic layers were
dried (Na2SO4), the solvent removed in vacuo and the residue
subjected to column chromatography (SiO2; diethyl ether–
due obtained after addition of MeI, followed by MeOH and
removal of the solvents in vacuo, revealed a complex mixture of
products. In particular, no resonances ascribable to complexed
arene ring protons (δ 5–6) were present.
Acknowledgements
We thank Associated Octel Ltd for a CASE studentship
(to M. H. S.).
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1
toluene, 3 : 97). H NMR and TLC were identical to those of
authentic complex 19.
Synthesis of complex (؉)-19 from [ꢀ6-N-(2,2-dimethylpropyl-
idene)benzylamine]tricarbonylchromium(0) 25
The general procedure given above was followed using BuLi
(1.6 M, 0.55 cm3, 0.88 mmol) and complex 25 (125 mg,
0.40 mmol). Imine hydrolysis was complete within 0.5 h at
room temperature. [η6-N-(Benzyloxycarbonyl)-1-phenylethyl-
amine]tricarbonylchromium(0) 19 was isolated as a yellow solid
(108 mg, 0.276 mmol, 69%); [α]D25 ϩ26 (c = 1, CH2Cl2); HPLC:
as above for the direct synthesis of 19; e.e. 81%.
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0.70 cm3, 0.88 mmol) and complex 27 (133 mg, 0.40 mmol).
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O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 6 7 6 – 6 8 3
683