Enantioselective synthesis and application to the allylic imidate rearrangement of amine-coordinated palladacycle catalysts of cobalt sandwich complexes

Article abstract of DOI:10.1002/chem.201302922

The reaction of (η⁵-(N,N-dimethylaminomethyl)cyclopentadien- yl)(η⁴-tetraphenylcyclobutadiene)cobalt with sodium tetrachloropalladate and (R)-N-acetylphenylalanine gave planar chiral palladacycle di-μ-chloridebis[(η⁵-(S

Full text of DOI:10.1002/chem.201302922

FULL PAPER
DOI: 10.1002/chem.201302922
Enantioselective Synthesis and Application to the Allylic Imidate
Rearrangement of Amine-Coordinated Palladacycle Catalysts of Cobalt
Sandwich Complexes
Doyle J. Cassar,[a] Gennadiy Ilyashenko,[a] Muhammad Ismail,[a, b] James Woods,[a]
David L. Hughes,[a] and Christopher J. Richards*[a]
Abstract: The reaction of (h5-(N,N-di-
methylaminomethyl)cyclopentadien-
yl)(h4-tetraphenylcyclobutadiene)cobalt
with sodium tetrachloropalladate and
(R)-N-acetylphenylalanine gave planar
ment with AgOAc gave (Sp)-Me2-CAP-
OAc which was applied to asymmetric
transcyclopalladation (up to 78% ee).
The (R)-N-acetylphenylalanine mediat-
ed palladation methodology was appli-
cable also to the corresponding N,N-di-
ethyl (82% ee, 39% yield) and pyrroli-
dinyl (>98% ee, 43% yield) cobalt
sandwich complexes. A combination of
5 mol% of the latter [(Sp)-Pyrr-CAP-
Cl] and AgNO3 (3.8 equiv) is a catalyst
for the allylic imidate rearrangement of
an (E)-N-aryltrifluoroacetimidate (up
to 83% ee), and this catalyst system is
also applicable to the rearrangement of
chiral palladacycle di-m-chloridebisACTHNUTRGNEUNG
[(h5-
(Sp)-2-(N,N-dimethylaminomethyl)cy-
clopentadienyl,1-C,3’-N)(h4-tetraphe-
nylcyclobutadiene)cobalt]dipalladium
[(Sp)-Me2-CAP-Cl] in 92% ee and 64%
yield. Enantiopurity (>98% ee) was
achieved by purification of the mono-
meric (R)-proline adducts and conver-
sion back to the chloride dimer. Treat-
a range of (E)-trichloroacetimidates
(up to 99% ee). This asymmetric effi-
ciency combined with the simplicity of
catalyst synthesis provides accessible
solutions to the generation of non-race-
mic allylic amine derivatives.
Keywords: asymmetric synthesis ·
catalysis · metallacycles · palladium ·
sandwich complexes
Introduction
There are three principal reasons to develop methods for
the asymmetric synthesis of chiral palladacycles,[1] an area in
which many examples are metallocene-based planar chiral
complexes.[2] First is the use of these metallacycles as cata-
lysts for the synthesis of non-racemic organic compounds.[3]
Conspicuous success has been achieved in catalysis of the
asymmetric allylic imidate rearrangement and closely relat-
ed reactions using planar chiral palladacycles based upon
bulky cobalt sandwich complexes (e.g., 1 and 2) or related
pentaphenylferrocene frameworks (Scheme 1).[4–6] In these
reactions the palladium-carbon palladacycle bond is main-
tained throughout the catalytic cycle. Numerous other exam-
ples of chiral palladacycle-catalysed asymmetric transforma-
tions have been reported also.[7] Second is the use of palla-
dacycles as precatalysts for the in situ generation of Pd0 spe-
Scheme 1. Diastereoselective synthesis of cobalt oxazoline palladacycle
1 [(S,Rp)-COP-OAc] and transformation into chloride-bridged dimer 2
[(S,Rp)-COP-Cl].[11]
cies.[8,9] Finally, the development of enantioselective meth-
À
ods for palladium catalysed asymmetric C H activation is
informed by the synthesis of complexes related closely to
the intermediate chiral palladacycles generated in these re-
actions.[10]
[a] D. J. Cassar, Dr. G. Ilyashenko, Dr. M. Ismail, J. Woods,
Dr. D. L. Hughes, Dr. C. J. Richards
Central to the synthesis of 1, as with many related planar
chiral metallocene-based palladacycles, is an auxiliary-medi-
School of Chemistry, University of East Anglia
Norwich Research Park, Norwich, NR4 7TJ (UK)
E-mail: Chris.Richards@uea.ac.uk
À
ated diastereoselective C H activation step resulting in
[2b,11]
À
a new carbon palladium bond.
There are far fewer ex-
[b] Dr. M. Ismail
amples of planar chiral palladacycles derived from enantio-
Current address: Department of Chemistry
Karakoram International University
University Road, Gilgit-15100 (Pakistan)
À
selective C H activation. Non-racemic planar chiral pallada-
cycles have been generated from a limited number of enan-
tioselective transcyclopalladation reactions,[12] and in 1979
Sokolov reported the N-acetyl amino acid mediated enantio-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201302922.
Chem. Eur. J. 2013, 19, 17951 – 17962
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
17951

Scheme 4. Enantioselective palladation of 8 and derivatisation with (S)-
proline.
Scheme 2. Application of enantioselective palladation to the synthesis of
planar chiral palladacycles.
selective palladation of N,N-dimethylaminomethylferrocene
(3).[13] Recent re-investigation of this latter chemistry within
our group identified conditions for the synthesis of pallada-
cycle (Sp)-4 in 96% ee using (R)-N-acetylphenylalanine
(5),[14] and an extension of the methodology to the kinetic
resolution of [2.2]paracyclophane (6) gave palladacycle (Sp)-
7 in more than 99% ee (Scheme 2).[15] In this study we
report on the application of enantioselective palladation to
the facile synthesis of non-racemic amine palladacycles con-
taining a cobalt sandwich complex, and on the application
of these to asymmetric transcyclopalladation and asymmet-
ric allylic imidate rearrangement.
plication of the room temperature conditions optimised pre-
viously for the enantioselective palladation of 3, with a reac-
tion time of 16 h, resulted in a new chloride bridged pallada-
cycle 11 in 64% yield (Scheme 4). The product was deter-
mined to have an enantiomeric excess of 92% following
treatment with (S)-proline and analysis of the resulting dia-
stereomeric adducts 12 and 13. Their ratio was determined
1
readily by H NMR spectroscopy, in particular by compari-
son of one of the base-line resolved methyl singlets [12:
2.31 ppm (3H, s), 13 2.36 ppm (3H, s)], or by comparison of
two of the signals arising from the cyclopentadienyl rings
[(12: 4.26 ppm (1H, brs), 13 4.30 ppm (2H, brs)]. Perform-
ing the palladation reaction at 08C resulted in no change in
enantioselectivity and a longer reaction time was required
to ensure complete palladation. A racemic acetate-bridged
palladacycle 14 was synthesised by heating together 8 and
palladium acetate in toluene at reflux for 2 h (Scheme 5).
Results and Discussion
Amine 8, a cobalt sandwich complex analogue of 3, was first
synthesised as previously reported from the Mannich-type
reaction of (h5-cyclopentadienyl)(h4-tetraphenylcyclobuta-
diene)cobalt with bis(dimethylamino)methane.[16] The low
yield of this reaction (typically ~40%) led us to an alterna-
tive and more productive procedure in which acid 9[11,17] was
converted to dimethylamide 10 followed by reduction
(Scheme 3).
Scheme 5. Non-enantioselective palladation of 8 with PdACTHNUTRGNEUNG(OAc)2.
Subsequent treatment with (S)-proline as before gave a 1:1
mixture of 12 and 13, confirming that these proline adducts
are planar chiral stereoisomers and not cis/trans coordina-
tion stereoisomers.
Scheme 3. Alternative synthesis of amine 8.
The palladation of amine 8 has been reported previously
with a mixture of lithium tetrachloropalladate and sodium
acetate in methanol.[18] This result suggested that the prochi-
ral cobalt complex 8 would be a suitable substrate for
a chiral carboxylate mediated asymmetric palladation. Ap-
Following recrystallisation from CH2Cl2/hexane of the
proline adducts derived from asymmetric palladation,
a small quantity of the major diastereoisomer was obtained
pure and the configuration of the element of planar chirality
was determined as Sp by X-ray crystallography (Figure 1).[19]
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Cobalt Sandwich Complexes
FULL PAPER
tition of the Na2PdCl4/N-acetyl amino acid palladation con-
ditions, with N-acetylglycine in place of (R)-N-acetylphe-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
(rac)-15/H-(rac)-15 (64% deuterium incorporation). The in-
tramolecular isotope effect of 2.5 is very similar to the value
of 2.3 determined for the palladation of the ferrocene ana-
logue 3 under the same conditions.[14] Furthermore, use of
the same sample of D-(rac)-8 in a reaction with palladium
acetate in toluene at reflux followed by ligand substitution
revealed an intramolecular isotope effect of 2.0 (D-(rac)-15/
H-(rac)-15=60:40). All of these values are consistent with
a carboxylate ligand accelerated CMD pathway, with the re-
actions containing (R)-N-acetylpheACTHNUTRGNEUNGnylalanine resulting in
the preferential formation of the (Sp)-palladacycle.
A pathway for the chiral carboxylate mediated pallada-
tion of 8 is outlined in Scheme 7. This is based on the DFT
calculated mechanism of dimethylbenzylamine cyclometala-
Figure 1. A molecule of (S,Sp)-12 from the X-ray analysis. Principal bond
À
À
À
lengths [ꢁ] include: Pd C(11) 1.973(4), Pd N(17) 2.092(4), Pd N(21)
À
À
À
2.023(4), Pd O(27) 2.082(4); mean Co CACHTUNTRGNEUNG(C4 ring) 1.991(5), mean Co
C(cp) 2.07(2). Principal angles [8] include: C(11)-Pd-N(17) 82.68(18),
N(21)-Pd-O(27) 82.50(16).
The pyrrolidine ring is disordered, with alternative sites for
one methylene group, at CACTHNUTRGNENG(U 24a) and CACHUTNGTRENN(GUN 24b). The other four
members of this ring are approximately co-planar, so that
the five-membered ring adopts an envelope shape with the
flap on one side, for example, CACHTNUTRGENN(UG 24a), or the other, CACHTUNGTERN(NUGN 24b).
Scheme 7. A possible pathway for the enantioselective palladation of 8.
The high enantioselectivity observed in the palladation re-
action points to the involvement of a palladium intermedi-
ate containing a coordinated carboxylate ligand obtained by
deprotonation of (R)-N-acetylphenylalanine. Palladation re-
actions with palladium acetate and other palladium(II)-car-
boxylate species have been shown to proceed by a concerted
metallation-deprotonation (CMD) pathway, a mechanism
consistent with a kinetic isotope effect of more than 1.[20] To
determine if this mechanism may be operating in the N-
acetyl amino acid mediated formation of 11, a racemic 2-
deutertated sample of the starting amine D-(rac)-8 (90%
deuterium incorporation) was synthesised by treatment of
the racemic palladacycle 14 with LiAlD4 (Scheme 6). Repe-
tion by palladium acetate,[21] and a suggested extension of
this process to the N-acetylphenylalanine mediated enantio-
selective palladation of phosphines containing a 2-phenylfer-
rocene substituent.[22] In this pathway an initially formed
amine and h2-carboxylate ligated complex 16 leads to transi-
tion state 17 with the carbonyl oxygen of the now h1-carbox-
ylate ligand participating in deprotonation simultaneously
À
with the formation of the new carbon palladium bond in
the vacant coordination site. Replacement of ligand X in 17
by the nitrogen of the amino acid derived ligand to give
a chelate would appear to be geometrically incompatible
with the participation of the carbonyl group of this ligand as
a base. Instead the conformational properties of the ligand
are controlled by its dipeptide-like properties.[22] Variation
of the ee of the (R)-N-acetylphenylalanine employed in cy-
clometallation resulted in a small positive non-linear effect
with respect to the ee of metallacycle (Sp)-11, an outcome
compatible with coordination of a second h1-carboxylate 18
and chirality matched rate accelerated cyclometallation
(Figure 2).
Separation of the diastereoisomeric proline adducts was
achieved readily by column chromatography. This was most
conveniently performed by first treating (Sp)-11 with (R)-
proline as the major diastereoisomer (R,Sp)-13 has a higher
Rf (0.24) than the minor diastereoisomer (R,Rp)-12 (0.16) in
Scheme 6. Determination of the intramolecular isotope effect for the N-
acetyl amino acid promoted palladation of 8.
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C. J. Richards et al.
Figure 2. An investigation into the relationship between the ee of N-ace-
tylphenylalanine and the ee of product palladacycle (Sp)-11.
2.5% MeOH/CH2Cl2, such that the majority of the former
can be eluted with little or no contamination from the latter.
If required, a subsequent recrystallisation can ensure diaste-
Figure 3. A molecule of (rac)-15 from X-ray analysis. Principal bond
lengths [ꢁ] and angles [8] [corresponding data for (S,Rp-COP-hfacac) in
1
reomeric purity (>99:1 as determined by H NMR spectros-
parenthesis][5c] include: C(5) Pd 1.955(3) [1.962(6)], N(1) Pd 2.085(3)
À
À
copy). The X-ray crystal structure of (R,Sp)-13 (see the Sup-
porting Information) confirmed further the absolute config-
uration and the trans nitrogen geometry.
À
À
[2.026(5)], O(1) Pd 2.046(2) [2.020(4)], O(2) Pd 2.119(2) [2.102(4)],
C(5)-Pd-N(1) 81.87(12) [80.8(2)], O(1)-Pd-O(2) 91.33(9) [92.77(15)].
Conversion back to the cobalt amine palladacycle (Sp)-11
[(Sp)-Me2-CAP-Cl] was carried out by stirring, overnight,
a biphasic mixture of (R,Sp)-13 in CH2Cl2 and aqueous 0.5m
HCl (Scheme 8).[23] The enantiopure chloride-bridged dimer
AHCTUNGTERN(GNUN hfacac)] gave (Sp)-15 [(Sp)-Me2-CAP-hfacac], although at-
tempts to synthesise this directly from proline adduct (R,Sp)-
13 were unsuccessful.
A representation of the X-ray crystal structure of (rac)-15
(obtained from (rac)-14 and NaACHTUNTRGNEUNG(hfacac)) is shown in
Figure 3.[25] The hfacac ligand allows comparison of this
structure with the hfacac derivative of palladacycles 1 and 2
[(S,Rp)-COP-hfacac].[5c] In common with that structure is the
À
À
longer length of the O(2) Pd bond compared to O(1) Pd,
indicative of the larger trans influence of the carbanion
ligand compared to nitrogen. That both these bond lengths
in 15 are longer than the corresponding bonds in the COP
derivative point to more electron density on the palladium
atom of 15 due to the greater basicity of the amine nitrogen
compared to the oxazoline nitrogen,[26] and the presence of
the electron-withdrawing oxazoline substituent in the COP
derivative. This is supported further by the larger chemical
shift of the methine proton in the hfacac ligand of the COP
derivative (5.95 ppm) compared to that in 15 (5.87 ppm).
A number of amines related to the N,N-dimethylamino
containing substrate 8 were synthesised to examine further
the asymmetric palladation methodology. Following reduc-
tion of methyl ester 19,[27] the alcohol 20 was converted in
situ with N-bromosuccinimide/triphenylphosphine into the
corresponding a-bromomethyl sandwich complex followed
by treatment with a variety of secondary amines to give
products 21a–e (Scheme 9).[28] Oxidation of alcohol 20 to al-
dehyde 22[27] followed by reductive amination with benzyl-
Scheme 8. Ligand exchange reactions starting from (R,Sp)-13.
is formed in good yield as an approximately 1:1 mixture of
isomers with respect to the cis/trans arrangements of the
À
two bridged C N chelates. Addition of silver acetate to
(Sp)-11 resulted in the clean formation of acetate bridged
dimer (Sp)-14 [(Sp)-Me2-CAP-OAc], and in common with
other examples of planar chiral acetate-bridged palladacy-
cles this is a single, presumably trans, stereoisomer.[24] Treat-
ment of (Sp)-11 with sodium hexafluoroacetylacetonate [Na-
ACHTUNGTRENaNUGN mine gave secondary amine 23. Hydrogenolysis of this re-
sulted only in debenzylation to give the primary amine 24
with no formation of (h5-methylcyclopentadienyl)(h4-tetra-
phenylcyclobutadiene)cobalt, an alternative reduction prod-
uct which would have resulted from hydrogenolysis of the
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Cobalt Sandwich Complexes
FULL PAPER
firmed by the correspondence between the CD spectra of
(Sp)-27 and (Sp)-28 with that of (Sp)-11 (see the Supporting
Information). That the diethylamine and pyrrolidine deriva-
tives are limiting substrates under these reaction conditions
is revealed by the reduced yield obtained. The N,N-dimeth-
yl, N,N-diethyl and pyrrolidinyl substrates appear to have
the correct balance of nitrogen basicity and steric accessibili-
ty to permit palladation. It is significant that treatment of
21c–e with PdACTHUNRGTNEUNG(OAc)2 in toluene at either 70–808C, or heat-
ing at reflux, also did not result in palladation.
Preliminary investigations into the use of these new CAP
complexes in asymmetric synthesis began with the N,N-di-
methylamino derivatives obtained following proline-mediat-
ed purification. Transcyclometallation is a term coined to
describe the exchange of cyclometalated ligands without the
formation of dissociated metal salts.[30] Following a demon-
stration of asymmetric transcyclopalladation using pallada-
cycles derived from (R)-3-amino-3-phenyl-2,2-dimethylpro-
pane,[12a] one of us reported that the reaction between
(S,Rp)-COP-OAc (1) and prochiral phosphines 33 or 34 re-
sulted in the clean formation of phosphapalladacycles 35
and 36 in up to 95% ee (R=Cy).[12b] The applicability of
CAP complexes to this reaction was investigated by combin-
ing (Sp)-Me2-CAP-OAc and phosphine 33 (R=Ph) followed
by heating at 708C in toluene for 24 h (Scheme 11). The ini-
Scheme 9. Synthesis of further amine substrates 21a–e, 23, 24 and 26.
nitrogen-C(a-sandwich complex) bond. Finally, introduction
of a Cbz group followed by reduction of 25 with lithium alu-
minium hydride gave the N-methyl amine 26.
Application to these new amines of the standard asym-
metric palladation conditions resulted in only two new palla-
dacycles, (Sp)-27 and (Sp)-28 derived from the N,N-diethyla-
mine 21a and pyrrolidinyl complex 21b, respectively
(Scheme 10). (S)-Proline derivatisation revealed the ee of 27
Scheme 11. Asymmetric transcyclopalladation and a phosphine addition
product.
tially formed acetate-bridged phosphapalladacycle was con-
verted into the monomeric acac ligated complex 35 for
which a 86:14 ratio of Rp and Sp enantiomers was deter-
mined by chiral HPLC analysis. In the same way phosphine
34 (R=Cy) gave a 89:11 ratio of Rp and Sp isomers of 36.
The initial reaction between a phosphine substrate and
the amine-coordinated palladacycle results in the formation
of a monomeric adduct, as revealed by the synthesis of (Sp)-
37 from 33 and (Sp)-11 (Scheme 11). A representation of
the X-ray crystal structure of (Sp)-37 is shown in Figure 4.[31]
In common with most other nitrogen ligand based pallada-
cycles, the added phosphine is incorporated trans to nitro-
gen, the thermodynamic ligand substitution product.[32] The
Scheme 10. Enantioselective palladation of additional amine substrates.
as 82% and 28 as more than 98%. In the latter case the
minor diastereoisomer (S,Rp)-32 could not be detected by
1H NMR spectroscopy. The determination of the ratio of
isomers as more than 100:1 was made following the synthe-
sis of (R,Sp)-32 from (R)-proline, and the use of this to
spike the 1H NMR sample. The absolute configuration of
these new palladacycles was assigned initially by the sign of
the specific rotation [(Sp)=Àve, (Rp)= +ve],[29] and con-
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17955

C. J. Richards et al.
Figure 4. A molecule of (Sp)-37 from X-ray analysis. Principal bond
À
À
À
lengths [ꢁ] include: Pd Cl 2.383(4), Pd C(51) 2.004(16), Pd NACTHNUTRGNEU(GN 522)
À
À
À
2.193(10), Pd P(6) 2.271(4), mean Co CACTHNUTRGNEUNG(C4 ring) 1.97(4), mean Co
Scheme 12. Mechanism and origin of enantioselection in asymmetric
transcyclopalladation.
À
À
C(cp) 2.05(7), mean Fe C(substd-cp) 2.00(4), Fe C(cp) 2.03(4). Principal
angles [8] include: C(51)-Pd-N
(522) 80.9(6), P(6)-Pd-Cl 87.8(2).
step.[5e] Given the similarity of the coordination site trans to
the amine nitrogen, it was anticipated that CAP catalysis of
the allylic imidate rearrangement by this pathway would
result in usable levels of enantioselectivity, and a predictable
correspondence between the configurations of planar and
product chirality (Sp gives R). This was investigated first
with the allylic imidate rearrangement of representative
(E)- and (Z)-N-(para-methoxyphenyl)trifluoroacetimidate
substrates 42 (Scheme 13, Table 1). The reactions were per-
triarylphosphine ligand displays an induced P configuration,
and the tetraphenylcyclobutadiene moiety is M. This latter
configuration is also displayed in the solid state structure of
(rac)-15 (relative to Sp), but (S,Sp)-12 and (R,Sp)-13 are P, re-
vealing no correlation between the planar and induced pro-
peller chirality of the h4-tetraphenylcyclobutadiene group.[33]
The X-ray crystal structure of (Sp)-37 also reveals the ori-
entation of the ferrocenyl group above the palladium cen-
tred square-plane, as beneath lie phenyl groups attached to
the h4-cyclobutadiene moiety. This and the trans to nitrogen
coordination geometry are instrumental in controlling the
enantioselectivity of palladium transfer. A pathway for this
process is outlined in Scheme 12 based, as before, on dime-
thylbenzylamine cyclopalladation and related studies.[21,22]
Following formation of 38, dissociation of the amine ligand
by formation of the h2-acetate complex 39 is followed by
acetate assisted concerted metalation-deprotonation (CMD)
via transition state 40 to give 41. Subsequent protonolysis of
Scheme 13. Use of (S)-CAP-Cl in catalysis of the rearrangement of (E)-
and (Z)-N-(para-methoxyphenyl)trifluoroacetimidates (42).
À
the cobalt complex carbon palladium bond by retro-CMD
releases amine 8 and gives an acetate ligated phosphapalla-
formed first with 5 mol% of (Sp)-11 at room temperature,
which resulted in modest conversions for the formation of
(R)-43 (75% ee) and (S)-43 (20% ee) from E and Z sub-
strates, respectively (entries 1 and 2). Similar results were
obtained with catalyst (Sp)-28, the E substrate also resulting
in higher conversion and enantioselectivity (entries 3 and 4).
Focusing on substrate (E)-42, and increasing the reaction
temperature to 388C with the addition of proton sponge, im-
proved the ee to 86% but the conversion was still modest
(entry 5). Under similar conditions 5 mol% of (S,Rp)-COP-
Cl (1) resulted in essentially complete conversion, and up to
92% ee.[5a]
dacycle, replacement of which on addition of NaACTHNUTRGENUG(N acac) re-
sults in isolated complexes (Rp)-35 or (Rp)-36. Although ro-
tation is possible about the carbon palladium bond in 39,
À
the conformer drawn is favoured by the orientation of the
coordinated phosphine away from the dimethylaminomethyl
moiety. Thus the planar chirality of this monodentate spe-
cies is also a factor in controlling the enantioselectivity.
Kinetic and molecular modelling studies on the COP-Cl
catalysed allylic imidate rearrangement revealed that the
planar chirality is also the key factor in controlling the facial
selectivity of nitrogen addition to the alkene moiety, this
being bound trans to the oxazoline nitrogen in the rate and
enantioselectivity determining anti-amino palladation
Assuming a correlation between conversion and the rate
of catalysis, the reduced activity observed with the CAP cat-
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Cobalt Sandwich Complexes
FULL PAPER
Table 1. Use of (Sp)-CAP-Cl in catalysis of the rearrangement of (E)-
and (Z)-N-(para-methoxyphenyl)trifluoroacetimidates (42).[a]
Table 2. Use of (Sp)-CAP-Cl in catalysis of the rearrangement of (E)-tri-
chloroacetimidates (44).[a]
Entry
Cat.
(Sp)
x
T
Config.
42
Conv.
[%][c]
ee 43
Config.
Entry Cat.
x
Substrate
Conv. [%][c] Product[d] ee
[mol%]
[8C]
[%][d]
43[d]
(Sp)
[mol%] (R)
(yield [%])
[%][d]
1
2
3
4
5
6
7
8
11[b]
11[b]
28
5
5
5
5
5
5
5
0.5
RT
RT
RT
RT
38
38
38
38
E
Z
E
Z
E
E
E
E
50
54
48
26
43
75
20
75
43
86
81
83
65
R
S
R
S
R
R
R
R
1
2
3
4
5
6
7
9
8
11[b]
11[b]
11[b]
28
1
2
5
5
5
5
44a (Pr)
44a (Pr)
44a (Pr)
44a (Pr)
44a (Pr)
44a (Pr)
44a (Pr)
44b (allyl)
44c (Me)
44d (Bn)
25
32
51
51
>99 (77)
>99 (78)
7
58 (55)
68 (66)
>99 (70)
(R)-45a
(R)-45a
(R)-45a
(R)-45a
(R)-45a
(R)-45a
(R)-45a
(R)-45b
(R)-45c
(R)-45d
51
68
72
86
73
99
64
71
91
87
28
28[e]
28[f]
28[e,f]
28[e,f]
28[e]
28[e,f]
>99[g]
>99[h]
33
28[e,f] 0.5
28[e,f]
28[e,f]
28[e,f]
5
5
5
[a] 0.6m 42 in CH2Cl2, reaction time 60 h at RT or 24 h at 388C. [b] Cata-
lyst ee more than 98%. [c] Determined by H NMR spectroscopy. [d] De-
10
1
termined by chiral HPLC of the secondary amine following trifluoroace-
tate removal. [e] With 4x mol% 1,8-bis(dimethylamino)naphthylene.
[f] With 3.8x mol% AgNO3. [g] Isolated yield=80%. [h] Isolated yield=
80%.
[a] 0.6m 44 in CH2Cl2, reaction time 39 h at 388C. [b] Catalyst ee more
than 98%. [c] Determined by 1H NMR spectroscopy; yield=isolated
yield. [d] Determined by chiral HPLC. [e] With 3.8x mol% AgNO3.
[f] With 4.0x mol% 1,8-bis(dimethylamino)naphthylene.
alysts is attributed to the increased electron density on the
palladium of the amine coordinated complex. Related chlo-
ride-bridged ferrocene imidazoline palladacycles are essen-
tially inactive as catalysts for the allylic imidate rearrange-
ment due the electron-donating properties of the iron con-
taining metallocene.[6] Activation is required by the addition
of silver salts, a recent study having identified the resultant
catalyst as a PdIII species obtained by initial chloride ligand
abstraction followed by oxidation.[34] Addition of 3.8 equiva-
lents with respect to (Sp)-28 of AgNO3 prior to the introduc-
tion of the substrate (E)-42 resulted in complete conversion
to give (R)-43 in 81% ee (entry 6). Essentially the same out-
come was obtained on addition of proton sponge (entry 7),
though a tenfold reduction in catalyst loading to 0.5 mol%
led to the erosion of enantioselectivity and yield (entry 8).
Encouraged by these results we applied the CAP catalysts
to the rearrangement of (E)-trichloroacetimidates 44
(Scheme 14). Compared to N-aryltrifluoroacetimidates these
(entry 5), which on repetition in the presence of proton
sponge increased to 99% ee (entry 6). Decreasing the cata-
lyst loading to 0.5 mol% again eroded significantly the ee
and yield (entry 7), and so a small range of additional sub-
strates were examined at 5 mol% loading (entries 8–10).
The allyl containing trichloroacetimidate 44b, which due to
the additional alkene functionality capable of competitive
palladium coordination is a challenging substrate for this re-
action, resulted in (R)-45b in 71% ee. In contrast, methyl
and benzyl containing substrates 44c/d reacted smoothly to
give (R)-45b and (R)-45c, in 91 and 87% ee, respectively.
These results are comparable to (S,Rp)-COP-Cl catalysed re-
arrangement of trichloroacetimidates,[5b,d] but now using
a catalyst available readily from highly enantioselective pal-
ladation of a simple prochiral substrate.
Conclusions
Enantioselective palladation of N,N-dimethylaminomethyl-
appended cobalt sandwich complex 8 with Na2PdCl4 mediat-
ed by (R)-N-acetylphenylalanine gave the chloride-bridged
palladacycle (Sp)-11 in 92% ee. The intramolecular isotope
effect (kH/kD =2.5) is consistent with a concerted metalla-
tion–deprotonation pathway mediated by a chiral h1-carbox-
ylate ligand. The enantiopurity of (Sp)-11 may be increased
to more than 98% ee by chromatographic separation of the
minor diastereoisomer formed on addition of (R)-proline
followed by treatment of the major diastereoisomer with
aqueous HCl. A number of related aminomethyl-substituted
cobalt complexes were synthesised readily, but this enantio-
selective palladation protocol is limited to N,N-diethyl-
(82% ee) and pyrrolidinyl (>98% ee) substituents. Combin-
ing this enantioselective palladation with subsequent enan-
tioselective transcyclopalladation enables the synthesis of
ferrocene-based phosphapalladacycles in up to 78% ee. The
activity and enantioselectivity of a cobalt amine palladacycle
catalyst for the allylic imidate rearrangement is increased
Scheme 14. Use of (Sp)-CAP-Cl in catalysis of the rearrangement of (E)-
trichloroacetimidates 44a–d.
are simpler to synthesise, and the products of rearrangement
require only a single deprotection step to release an allylic
amine building block. Initial experiments with 1, 2 and
5 mol% of (Sp)-11 gave a higher ee value with each increase
in catalyst loading (entries 1–3), and use of 5 mol% of (Sp)-
28 further increased the ee to 86% (Table 2). As these reac-
tions all resulted in incomplete conversion to the product,
the palladacycle (Sp)-28 was again activated by the addition
of 3.8 equivalents of AgNO3 prior to the addition of the sub-
strate. This gave complete conversion and an ee of 73%
Chem. Eur. J. 2013, 19, 17951 – 17962
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
17957

C. J. Richards et al.
Na2Pd2Cl4 (0.439 g, 1.49 mmol) in MeOH (50 mL). The pH of the mix-
ture was adjusted to 8.0 using either aqueous 50% NaOH(aq.) or conc.
HCl(aq.) as required and the mixture was allowed to stir for 20 min. A so-
lution of 8 (0.800 g, 1.49 mmol) in MeOH/CH2Cl2 (75/15 mL) was then
added in portions over 5 min. The solution was allowed to stir for 16 h at
RT. On completion, the reaction mixture was diluted with CH2Cl2
(150 mL) and washed with brine (2ꢂ100 mL). The organic phase was
dried over MgSO4, filtered and the solvent was removed in vacuo. Purifi-
cation by column chromatography (SiO2, 4:1 hexanes/EtOAc) gave the
product (Sp)-11 as an orange solid (0.650 g, 64%), ee=92% as deter-
mined by formation of the proline adducts. M.p. 143–1458C; [a]2D1 =À289
(c=1.1 mgmLÀ1 in CH2Cl2). Further characterisation data below.
significantly following the addition of 3.8 equivalents of
silver nitrate. The catalyst generated from (Sp)-28 results in
the rearrangement of (E)-trichloroacetimidates with high
enantioselectivity (up to 99% ee). Combined with the
simple highly enantioselective generation of (Sp)-28, this
methodology enables the straight-forward generation of
highly scalemic allylic amine derivatives for application in
organic synthesis.
Synthesis of proline adduct (S,Sp)-12: A solution of (Sp)-11 (0.050 g,
0.04 mmol) in acetone (1 mL) was added to a solution of NaHCO3
(0.031 g, 0.37 mmol) and (S)-proline (0.043 g, 0.37 mmol) in water
(0.5 mL). During the addition a copious amount of precipitate was
formed. The reaction was vigorously stirred for 16 h at RT and then dilut-
ed with CH2Cl2 (50 mL). The phases were separated and the aqueous
phase was washed with further portions of CH2Cl2 (2ꢂ25 mL). The or-
ganic phases were combined, dried over MgSO4, filtered and solvent was
removed in vacuo yielding the product as an orange solid (0.050 g, 90%).
Experimental Section
General: Thin layer chromatography (TLC) was performed on Merck
Silica Gel 60 F254 and was visualised with UV light, iodine or potassium
permanganate stain. NMR spectra were measured at 500 or 400 MHz for
1H and 126 or 100 MHz for 13C. The residual solvent protons (1H) or the
solvent carbons (13C) were used as internal standards for chemical shift
determinations. IR spectra were recorded on a Fourier transform inter-
ferometer; only diagnostic and/or intense peaks are reported. Melting
points were measured in a melting point apparatus and are uncorrected.
All reagents and solvents were purchased from commercial sources and
were purified using standard methods where required. Toluene and THF
were dried over sodium and benzophenone ketal. Dichloromethane was
dried over CaCl2. Methanol was dried over 4 ꢁ molecular sieves. Com-
plexes 9,[17] 19,[27] 20[27] and 22[27] were prepared as previously described.
All imidate substrates used were synthesised according to the literature
procedures from the corresponding allylic alcohols.[5a,b,d]
Ratio of (S,Sp)-12/ACHTNUTRGENGNU(S,Rp)-13=24:1. Crystals of (S,Sp)-12 suitable for X-ray
crystallography were obtained by slow diffusion of hexane into CH2Cl2
solution (~50:1 hexane/CH2Cl2). M.p. 190–1928C; [a]2D0 =À99 (c=
1.29 mgmLÀ1 in CH2Cl2); 1H NMR (400 MHz, CDCl3): d=7.58–7.56 (m,
8H, Ar-H), 7.26–7.22 (m, 12H, Ar-H), 4.36 (brs, 2H, Cp-H), 4.15 (t, J=
2 Hz, 1H, Cp-H), 3.93 (app. q, J=7.6 Hz, 1H, NHCH), 3.20 (d and brs,
J=13.2 Hz, 2H, CHHNMe2 and NH), 2.87 (d, J=13.2 Hz, 1H,
CHHNMe2), 2.65 (s, 3H, CH3), 2.50–2.40 (m, 1H, NHCHH), 2.38 (s, 3H,
CH3), 2.20–2.00 (m, 3H, 3ꢂCH), 1.60–1.50 (m, 1H, CHH), 1.24–
1.18 ppm (m, 1H, CHH); 13C NMR (100 MHz, CDCl3): d=136.72,
129.05, 128.23, 126.25, 103.75, 101.58, 84.33, 82.67, 77.85, 74.01, 64.28,
52.60, 51.70, 51.17, 29.89, 26.10 ppm (C=O not observed); IR (neat): n˜ =
2450, 2919, 1597, 1496, 1443, 1379, 1366, 1259, 1152, 1066, 1018, 845, 803,
740, 697 cmÀ1; HRMS (EI): m/z calcd for C41H40CoN2O2Pd: 757.1466
[M+H]+; found 757.1468.
Synthesis of (h5-N,N-dimethylcarboxamidocyclopentadienyl)(h4-tetraphe-
nylcyclobutadiene)cobalt (10):
A flask was charged with 9 (1.00 g,
1.91 mmol) and it was then dissolved in CH2Cl2 (20 mL). Oxalyl chloride
(0.33 mL, 3.8 mmol) and dimethylformamide (3 drops) were added se-
quentially. After 30 min the solution was concentrated in vacuo re-dis-
solved in CH2Cl2 and re-concentrated in vacuo to give the crude acid
chloride as a red/brown solid. A solution of the crude acid chloride in
CH2Cl2 (30 mL) was added via cannula to a solution of dimethylamine
hydrochloride (0.311 g, 3.81 mmol) and triethylamine (2.30 mL,
16.5 mmol) in CH2Cl2 (20 mL). The resulting solution was stirred at room
temperature. After 16 h the solution was washed with water (50 mL) and
brine (50 mL). The organic layer was dried over MgSO4, filtered, and
concentrated in vacuo. The residue was dissolved in a minimum volume
of CH2Cl2 and purified by column chromatography (SiO2, 7:3 hexanes/
ethyl acetate) to give the product 10 as an orange solid (1.01 g, 96%).
M.p. 2498C; 1H NMR (500 MHz, CDCl3): d=7.55–7.44 (m, 8H, Ar-H),
7.32–7.18 (m, 12H, Ar-H), 5.16 (brs, 2H, Cp-H), 4.75 (brs, 2H, Cp-H),
2.79 (brs, 3H, CH3), 2.64 ppm (brs, 3H, CH3); 13C NMR (126 MHz,
CDCl3): d=135.64, 129.04, 128.12, 126.64, 85.46, 84.89, 77.36, 76.26 ppm
(C=O and 2ꢂCH3 not observed); IR (neat): n˜ =3052, 2923, 1967, 1609,
1596, 1496, 1388, 1267, 1162, 1027 cmÀ1; HRMS (ESI+): m/z calcd for
C36H31CoNO: 552.1732 [M+H]+; found 552.1726.
Alternative synthesis of (h5-N,N-dimethylaminomethylcyclopentadie-
nyl)(h4-tetraphenylcyclobutadiene)cobalt (8):[16] A flask was charged with
10 (0.986 g, 1.78 mmol) and it was then dissolved in THF (20 mL). The
flask was cooled in an ice-water bath and lithium aluminium hydride
(0.214 g, 5.63 mmol) was added in two portions. The reaction was left to
stir, overnight. On completion, water (20 mL) was added and the aque-
ous layer was extracted with CH2Cl2 (3ꢂ20 mL). The organic layer was
dried over MgSO4, filtered and concentrated in vacuo to give the product
8 as an orange solid (0.959 g, 99%). 1H NMR (500 MHz, CDCl3): d=
7.51–7.40 (m, 8H, Ar-H), 7.33–7.21 (m, 12H, Ar-H), 4.73 (t, J=2.0 Hz,
2H, Cp-H), 4.68 (d, J=2.1 Hz, 2H, Cp-H), 2.90 (s, 2H, CH2), 2.24 ppm
(s, 6H, 2ꢂCH3); 13C NMR (126 MHz, CDCl3): d=136.42, 128.95, 128.10,
126.30, 93.84, 84.21, 83.66, 74.89, 56.53, 44.95 ppm.
Synthesis of proline adduct (R,Sp)-13: A solution of (Sp)-11 (0.050 g,
0.04 mmol) in acetone (10 mL) was added to a solution of NaHCO3
(0.088 g, 1.04 mmol) and (R)-proline (0.085 g, 0.74 mmol) in water
(5 mL). During the addition a copious amount of precipitate was formed.
The reaction was vigorously stirred for 16 h at RT and then diluted with
CH2Cl2 (50 mL). The phases were separated and the aqueous phase was
washed with further portions of CH2Cl2 (2ꢂ25 mL). The organic phases
were combined, dried over MgSO4, filtered and solvent was removed in
vacuo yielding the crude product. Ratio of (R,Rp)-12/ACTHNUGRTENUNG(R,Sp)-13=1:33. Pu-
rification by column chromatography eluting with (SiO2, 97:3 CH2Cl2/
MeOH) gave exclusively (R,Sp)-13 as an orange/red solid (0.045 g, 81%).
Crystals suitable for X-ray crystallography were obtained by slow diffu-
sion of hexane into CH2Cl2 solution (~50:1 hexane/CH2Cl2). M.p. 2368C;
[a]D21 = +26 (c=0.5 mgmLÀ1 in CH2Cl2); 1H NMR (500 MHz, CDCl3):
d=7.78–7.38 (m, 8H, Ar-H), 7.35–6.99 (m, 12H, Ar-H), 4.37 (t, J=
2.4 Hz, 1H, Cp-H), 4.26 (d, J=1.9 Hz, 1H, Cp-H), 4.11 (brs, 1H, Cp-H),
3.27 (dd, J=13.7, 8.6 Hz, 1H, NHCH), 3.10 (d, J=13.2 Hz, 1H,
CHHNMe2), 3.06–2.94 (m, 1H, NHCHH), 2.90–2.78 (m, 1H, NHCHH),
2.74 (d, J=13.2 Hz, 1H, CHHNMe2), 2.53 (s, 3H, CH3), 2.36 (s, 3H,
CH3), 2.15–1.96 (m, 2H, CHH and NH), 1.85 (ddt, J=13.3, 8.9, 4.7 Hz,
1H, CHH), 1.79–1.69 (m, 1H, CHH), 1.43–1.28 ppm (m, 1H, CHH);
13C NMR (126 MHz, CDCl3): d=180.42, 136.85, 128.96, 128.39, 126.26,
104.29, 97.65, 84.79, 84.03, 79.69, 73.86, 66.28, 63.57, 53.07, 51.43, 50.79,
29.74, 25.53 ppm; IR (neat): n˜ =3056, 2917, 2849, 2160, 1972, 1655, 1596,
1498, 1446, 1373, 1263, 1113, 1067, 1017, 823, 778, 694 cmÀ1; HRMS
(ESI): m/z calcd for C41H40O2N2PdCo: 757.1466 [M+H]+; found:
757.1467.
Conversion of (R,Sp)-13 into (Sp)-11: Dilute hydrochloric acid (0.64 mL
Synthesis of di-m-chlorobisACHTNUGRTNEUNG
[(h5-(Sp)-N,N-dimethylaminomethylcyclopen-
of
a 0.5m solution) was added to a solution of (R,Sp)-13 (0.100 g,
tadienyl,1-C,3’-N)(h4-tetraphenylcyclobutadiene)cobalt]dipalladium (11):
A solution of (R)-N-acetylphenylalanine (0.740 g, 3.57 mmol) and NaOH
0.13 mmol) in CH2Cl2 (2 mL) and the mixture was stirred vigorously for
16 h. The solution was diluted with CH2Cl2 (5 mL) and washed with
brine (3ꢂ5 mL). The organic layer was collected, dried over MgSO4, fil-
(0.066 g, 1.65 mmol) in water (15 mL) was added to
a solution of
17958
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 17951 – 17962

Cobalt Sandwich Complexes
FULL PAPER
tered and concentrated in vacuo. Purification by column chromatography
(SiO2, 4:1 hexanes/EtOAc) gave the product (Sp)-11 as an orange solid
(0.073 g, 82%). M.p. 1918C (decomp.); [a]2D1 =À310 (c=0.5 mgmLÀ1 in
portion. The reaction was then allowed to warm to RT and was then
heated at reflux for 1 h. The reaction mixture was cooled to RT and dilut-
ed with CH2Cl2 (15 mL). The mixture was washed with 10% HCl
(10 mL), dried over MgSO4, filtered and concentrated in vacuo. Purifica-
tion by column chromatography (SiO2, 19:1 CH2Cl2/MeOH) gave the
product 21a as a yellow solid (0.045 g, 41%). M.p. 140–1428C; 1H NMR
(300 MHz, CDCl3): d=7.52–7.40 (m, 8H, Ar-H), 7.31–7.18 (m, 12H, Ar-
H), 4.57 (s, 4H, Cp-H), 2.92 (s, 2H, CH2NEt2), 2.25 (q, J=7.2 Hz, 4H,
CH2CH3), 0.88 ppm (t, J=7.2 Hz, 6H, CH2CH3); 13C NMR (126 MHz,
CDCl3): d=136.34, 128.82, 127.98, 126.19, 84.14, 83.67, 74.74, 49.07,
11.84 ppm; IR (neat): n˜ =3057, 2966, 2921, 1597, 1499, 1446, 1068, 1020,
814, 780, 743, 698, 589, 564 cmÀ1; HRMS (ESI): m/z calcd for C38H36CoN:
565.2180 [M]+; found 565.2170.
1
CH2Cl2); H NMR (500 MHz, CDCl3), 1:0.9 mixture of isomers: d=7.77–
7.53 (m, 32H, Ar-H), 7.37–7.09 (m, 48H, Ar-H), 4.53 (d, J=1.2 Hz, 2H,
Cp-H), 4.38 (d, J=1.5 Hz, 2H, Cp-H), 4.33 (brs, 4H, Cp-H), 4.19 (t, J=
2.4 Hz, 2H, Cp-H), 4.09 (t, J=2.4 Hz, 2H, Cp-H), 3.18 (d, J=13.4 Hz,
2H, CHHNMe2), 3.13 (d, J=13.3 Hz, 2H, CHHNMe2), 2.81 (d, J=
13.4 Hz, 2H, CHHNMe2), 2.77 (d, J=13.2 Hz, 2H, CHHNMe2), 2.67 (s,
6H, CH3), 2.62 (s, 6H, CH3), 2.19 (s, 6H, CH3), 2.02 ppm (s, 6H, CH3);
13C NMR (126 MHz, CDCl3): d=136.83, 136.78, 129.42, 129.36, 128.09,
128.06, 125.95, 125.87, 103.09, 102.71, 102.31, 101.91, 85.03, 83.46, 81.07,
80.36, 77.73, 74.84, 74.81, 64.64, 64.55, 53.57, 52.21, 51.87, 51.52 ppm; IR
(neat): n˜ =3056, 2886, 1659, 1597, 1498, 1446, 1389, 1352, 1266, 1155,
1067, 1024, 984, 957, 910, 842, 809, 780, 739, 697, 563 cmÀ1; elemental
analysis calcd (%) for C72H62Cl2Co2N2Pd2: C 63.73, H 4.61, N 2.07; found
C 63.75, H 4.55, N 2.16.
Synthesis of (h5-(1-pyrrolidinyl)methylcyclopentadienyl)(h4-tetraphenyl-
cyclobutadiene)cobalt (21b): The same method as described for 21a was
followed starting with 20 (0.127 g, 0.25 mmol). The product was isolated
by column chromatography (SiO2, 19:1 CH2Cl2/MeOH) to give product
Synthesis of di-m-acetatobis
N
21b as a
yellow solid (0.100 g, 71%). M.p. 180–1828C; 1H NMR
(400 MHz, CDCl3): d=7.52–7.40 (m, 8H, Ar-H), 7.31–7.18 (m, 12H, Ar-
H), 4.75–4.70 (m, 2H, Cp-H), 4.62–4.58 (m, 2H, Cp-H), 2.84 (s, 2H,
CH2NMe2), 2.34–2.26 (m, 4H, N
ACHTUNGTRENNUNG
ACHTUGNTREN(NUNG CH2CH2)2), 1.70–1.64 ppm (m, 4H, N-
A
(CH2CH2)2); 13C NMR (126 MHz, CDCl3): d=136.35, 128.92, 128.08,
and eluted with CH2Cl2. The solvent was then removed in vacuo to give
the product (Sp)-14 as an orange solid (0.020 g, 97%). M.p. 162–1648C;
[a]D18 =À155 (c=2.6 mgmLÀ1, in CH2Cl2); 1H NMR (500 MHz, CDCl3):
d=7.71–7.60 (m, 16H, Ar-H), 7.25–7.14 (m, 24H, Ar-H), 4.22 (d, J=
1.3 Hz, 2H, Cp-H), 4.06 (t, J=2.2 Hz, 2H, Cp-H), 4.02 (brs, 2H, Cp-H),
3.05 (d, J=13.9 Hz, 2H, CHHNMe2), 2.76 (d, J=13.9 Hz, 2H,
CHHNMe2), 2.30 (s, 6H, NCH3), 2.15 (s, 6H, 2ꢂO2CCH3), 1.71 ppm (s,
6H, NCH3); 13C NMR (126 MHz, CDCl3): d=179.70, 135.96, 128.15,
126.78, 124.60, 102.08, 100.39, 83.06, 79.13, 74.10, 73.46, 64.11, 52.95,
50.78 24.14 ppm; IR (neat): n˜ =3055, 2920, 1577, 1498, 1412, 1261, 1176,
126.31, 84.06, 83.75, 74.93, 53.68, 52.60, 23.41 ppm; IR (neat): n˜ =2924,
1596, 1497, 1446, 1261, 1023, 816, 781, 746, 701, 589, 564 cmÀ1; HRMS
(ESI): m/z calcd for C38H35CoN: 564.2096 [M+H]+; found 564.2094.
Synthesis of (h5-N-benzylaminomethylcyclopentadienyl)(h4-tetraphenyl-
cyclobutadiene)cobalt (23): 1,2-Dichloroethane (35 mL) was added to
a mixture of 22 (2.61 g, 5.13 mmol) and benzylamine (0.55 g, 5.13 mmol)
and then sodium triacetoxyborohydride (1.72 g, 8.12 mmol) was added in
one portion. The mixture was stirred at room temperature for 1.5 h. On
completion, the reaction mixture was quenched by adding saturated
aqueous NaHCO3 solution (50 mL) and the product was extracted with
EtOAc (2ꢂ40 mL). The EtOAc extract was dried over MgSO4, filtered
and the solvent was removed in vacuo to give the crude product, which
was purified by column chromatography (SiO2, 19:1 CH2Cl2/EtOAc) to
give product 23 as a yellow solid (3.00 g, 4.45 mmol, 97%). M.p. 145–
1023, 957, 740, 692, 617 cmÀ1
; elemental analysis calcd (%) for
C76H68Co2N2O4Pd2: C 65.01, H 4.88, N 2.00; found C 65.18, H 4.96, N
2.04.
Synthesis of (rac)-14: A solution of 8 (0.050 g, 0.09 mmol) and PdACTHNUTRGNE(NUG OAc)2
1
(0.021 g, 0.09 mmol) in toluene (1 mL) was heated at reflux for 2 h. After
being cooled to room temperature the solvent was removed in vacuo to
give the product (rac)-14 as an orange solid (0.062 g, 95%). The spectral
data matched that of (Sp)-14.
1478C; H NMR (400 MHz, CDCl3): d=7.43 (dd, J=8.0, 1.4 Hz, 8H, Ar-
H), 7.33–7.11 (m, 17H, Ar-H), 4.66 (t, J=1.8 Hz, 2H, Cp-H), 4.57 (t, J=
1.9 Hz, 2H, Cp-H), 3.52 (s, 2H, CH2Ph), 3.13 ppm (s, 2H, CH2NH);
13C NMR (126 MHz, CDCl3): d=136.33, 135.43, 129.01, 128.88, 128.14,
128.10, 126.62, 83.68, 82.56, 74.89, 53.56, 45.38 ppm; IR (neat): n˜ =3080,
Synthesis of hexafluoroacetylacetonateACTHNUTRGNEUNG
[(h5-(Sp)-N,N-dimethylaminome-
3059, 3028, 2924, 2823, 2246, 1597, 1499, 1449, 1379, 909, 733, 697 cmÀ1
;
thylcyclopentadienyl,1-C,3’-N)(h4-tetraphenylcyclobutadiene)cobalt]pal-
ladium (15): Sodium hexafluoroacetylacetonate (0.007 g, 0.03 mmol) was
added to a solution of (Sp)-11 (0.020 g, 0.02 mmol) in acetone/water
(2:1 mL). The solution was stirred vigorously for 16 h. On completion,
the solution was diluted with CH2Cl2 (5 mL) and washed with water
(5 mL). The organic layer was collected, dried over MgSO4, filtered and
concentrated in vacuo to give the product (Sp)-15 as an orange solid
(0.012 g, 96%). M.p. 2198C; [a]1D9 =À160 (c=1.0 mgmLÀ1 in CH2Cl2);
1H NMR (500 MHz, CDCl3): d=7.71–7.47 (m, 8H, Ar-H), 7.34–7.08 (m,
12H, Ar-H), 5.87 (s, 1H, CHCO), 4.62 (dd, J=2.3, 1.0 Hz, 1H, Cp-H),
4.50 (d, J=1.5 Hz, 1H, Cp-H), 4.37 (t, J=2.4 Hz, 1H, Cp-H), 3.41 (d, J=
13.9 Hz, 1H, CHHNMe2), 2.92 (d, J=13.9 Hz, 1H, CHHNMe2), 2.76 (s,
3H, NCH3), 2.48 ppm (s, 3H, NCH3); 13C NMR (126 MHz, CDCl3): d=
174.40 (q, JCÀF =8.0 Hz), 174.12 (q, JCÀF =7.4 Hz), 136.77, 129.14, 127.92,
HRMS (ESI): m/z calcd for C41H35NCo: 600.2102 [M+H]+; found:
600.2093.
Synthesis of (h5-aminomethylcyclopentadienyl)(h4-tetraphenylcyclobuta-
diene)cobalt (24): Anhydrous ammonium formate (1.80 g, 28.5 mmol)
was added in a single portion to a stirred suspension of 23 (3.00 g,
5.00 mmol) and an equal weight of 10% Pd/C in methanol (20 mL). The
resulting reaction mixture was stirred at reflux for 2 h. On completion,
the solution was filtered through a pad of Celite and then washed with
chloroform (20 mL). The combined organic filtrate was evaporated in
vacuo and purified by column chromatography (SiO2, 3:2 CH2Cl2/
EtOAc) to give the product 24 as a yellow solid (1.09 g, 2.05 mmol,
43%). M.p. 1168C; 1H NMR (400 MHz, CDCl3): d=7.49–7.42 (m, 8H,
Ar-H), 7.25–7.18 (m, 12H, Ar-H), 4.63 (t, J=2.0 Hz, 2H, Cp-H), 4.57 (t,
J=2.0 Hz, 2H, Cp-H), 3.27 ppm (brs, 2H, CH2NH2); 13C NMR
(126 MHz, CDCl3): d=136.22, 128.75, 128.09, 126.37, 83.57, 81.84, 74.85,
53.54 ppm; IR (neat): n˜ =3052, 2923, 2162, 1610, 1596, 1573, 1453, 1497,
1453, 1387, 1267, 1231, 1106, 1054 cmÀ1; HRMS (ESI): m/z calcd for
C34H28NCoNa: 532.1451 [M+Na]+; found: 532.1438.
126.15, 118.95 (q,
JCÀF =38.9 Hz), 116.68 (q, JCÀF =38.6 Hz), 102.94,
101.83, 90.23, 84.49, 79.55, 75.44, 74.87, 65.71, 53.53, 51.12 ppm; IR
(neat): n˜ =3056, 2928, 2160, 1623, 1597, 1545, 1498, 1481, 1458, 1253,
1195, 1144, 1024, 950, 779, 695 cmÀ1; elemental analysis calcd (%) for
C41H32CoF6NO2Pd·2H2O: C 55.58, H 4.10, N 1.58; found C 55.54, H 3.90,
N 1.80. Crystals of (rac)-15 for X-ray analysis, generated in the same way
from (rac)-14, were obtained by slow diffusion of hexane into CH2Cl2 so-
lution (~50:1 hexane/CH2Cl2).
Synthesis of (h5-N,N-diethylaminomethylcyclopentadienyl)(h4-tetraphe-
nylcyclobutadiene)cobalt (21a): A solution of 20 (0.100 g, 0.20 mmol)
and PPh3 (0.051 g, 0.20 mmol) in THF (3 mL) was cooled to À208C and
NBS (0.035 g, 0.30 mmol) was added in one portion. The mixture was
stirred for 10–15 min and Et2NH (20 mL, 0.2 mmol) was added in one
Synthesis
of
(h5-N-(benzyloxycarbonyl)aminomethylcyclopentadie-
nyl)(h4-tetraphenylcyclobutadiene)cobalt
(25): Iodine (0.006 g,
0.02 mmol) was added to a stirred mixture of 24 (0.610 g, 1.20 mmol) and
benzylchloroformate (0.205 g, 1.20 mmol) in 1:1 methanol/dichlorome-
thane (5 mL). After being stirred for 2 h at RT, diethyl ether (10 mL)
was added. The reaction mixture was washed with 5% Na2S2O3 solution
(5 mL) and saturated NaHCO3 (5 mL), dried over MgSO4, filtered and
the solvent was removed in vacuo. Purification by column chromatogra-
Chem. Eur. J. 2013, 19, 17951 – 17962
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
17959

C. J. Richards et al.
phy (SiO2, CH2Cl2/EtOAc 4:1) gave the product as a yellow/brown solid
(0.750 g, 97%). M.p. 88–908C; 1H NMR (400 MHz, CDCl3): d=7.45 (d,
J=6.4 Hz, 8H, Ar-H), 7.41–7.17 (m, 17H, Ar-H), 5.03 (s, 2H, OCH2Ph),
4.63 (brs, 2H, Cp-H), 4.58 (d, J=1.8 Hz, 2H, Cp-H), 4.31 (brs, 1H,
NHCbz), 3.77 ppm (d, J=5.6 Hz, 2H, CH2NH); 13C NMR (126 MHz,
CDCl3): d=156.23, 136.78, 136.18, 128.77, 128.54, 128.27, 128.09, 127.09,
126.56, 96.05, 83.61, 81.87, 75.04, 69.75, 66.58, 65.46, 54.97 ppm; IR
(neat): n˜ =3416, 3080, 3059, 3030, 2954, 2247, 1723, 1597, 1499, 1444,
1269, 1026, 735, 697 cmÀ1; HRMS (ESI): m/z calcd for C42H35CoNO2:
644.2000 [M+H]+; found: 644.1990.
Synthesis of (h5-N-methylaminomethylcyclopentadienyl)(h4-tetraphenyl-
cyclobutadiene)cobalt (26): A stirred suspension of LiAlH4, (0.090 g,
2.37 mmol) in THF (30 mL) was cooled to 08C in an ice-water bath. To
this was added a solution of 25 (0.700 g, 1.09 mmol) in THF (40 mL) and
the mixture was heated to reflux for 1.5 h. After being cooled the reac-
tion was quenched with saturated Na2SO4 solution (5 mL), filtered
through a pad of Celite and extracted with EtOAc (2ꢂ30 mL). The com-
bined organic extracts were concentrated under reduced pressure to give
a crude solid, which was purified by column chromatography (SiO2,
CH2Cl2/EtOAc 7:3) to give the product 26 as yellow solid (0.560 g, 98%).
M.p. 177–1798C; 1H NMR (400 MHz, CDCl3): d=7.45 (dd, J=7.2,
1.9 Hz, 8H, Ar-H), 7.22–7.26 (m, 12H, Ar-H), 4.66 (s, 2H, Cp-H), 4.57 (s,
2H, Cp-H), 3.07 (s, 2H, CH2NHMe), 2.14 ppm (s, 3H, NHCH3);
13C NMR (126 MHz, CDCl3): d=136.29, 128.85, 128.19, 126.45, 84.26,
83.76, 83.64, 82.82, 74.99, 48.34 ppm; IR (neat): n˜ =3080, 3028, 2938,
2787, 1597, 1499, 1444, 1025, 909, 733, 697 cmÀ1; HRMS (ESI): m/z calcd
for C35H31CoN: 524.1778 [M+H]+; found: 524.1789.
H), 4.13 (d, J=1.5 Hz, 1H, Cp-H), 3.92 (dd, J=15.2, 7.6 Hz, 1H, NCH),
3.29 (d, J=13.9 Hz, 2H, 2ꢂCHH), 2.88 (d, J=13.7 Hz, 2H, 2ꢂCHH),
2.78–2.55 (m, 3H, 3ꢂCHH), 2.49–2.27 (m, 2H, 2ꢂCHH), 2.17–2.06 (m,
3H, CHH), 1.40–1.31 (m, 3H, CH2CH3), 0.94 ppm (t, J=7.4 Hz, 3H,
CH2CH3); 13C NMR (126 MHz, CDCl3): d=180.08, 136.79, 129.01,
128.20, 126.21, 84.38 84.0, 81.39, 79.62 74.82, 73.96, 66.17, 58.09, 54.23,
53.31, 52.52, 29.97, 26.07, 13.52, 9.84 ppm; IR (neat): n˜ =3453, 2929, 2852,
1725, 1594, 1492, 1446, 1381, 1255, 1179, 1156, 1122, 1071, 1021, 804, 778,
740, 699 cmÀ1; HRMS (ESI): m/z calcd for C43H44CoN2O2Pd: 785.1780
[M+H]+; found: 785.1773. Ratio of isomers obtained from integration of
signals at 4.40 (t, J=2.4 Hz, 1H, (S,Sp)-Cp-H) and 4.42 ppm (t, J=
2.4 Hz, 1H, (S,Rp)-Cp-H).
Synthesis of di-m-chlorobisACHTNUGRTNEUNG
[(h5-(Sp)-(1-pyrrolidinyl)methylcyclopentadien-
yl,1-C,3’-N)(h4-tetraphenylcyclobutadiene)cobalt]dipalladium (28): A so-
lution of (R)-N-acetylphenylalanine (0.251 g, 1.21 mmol) and NaOH
(0.039 g, 0.98 mmol) in water (15 mL) was added to
a solution of
Na2Pd2Cl4 (0.263 g, 0.89 mmol) in MeOH (50 mL). The pH of the mix-
ture was adjusted to 8.0 using either aqueous NaOH or HCl as required
and the mixture was allowed to stir for 20 min. A solution of 21b
(0.500 g, 0.89 mmol) in 5: 1 MeOH/CH2Cl2 (90 mL) was then added in
portions over 5 min. The solution was allowed to stir for 16 h at RT. On
completion, the reaction mixture was diluted with CH2Cl2 (150 mL) and
washed with brine (2ꢂ100 mL). The organic phase was dried over
MgSO4, filtered and the solvent was removed in vacuo. Purification by
column chromatography (SiO2, 4:1 hexanes/EtOAc) gave the product
(Sp)-28 as an orange solid (0.270 g, 43%), ee >98% as determined by
formation of the proline adducts M.p. >2008C (decomp); [a]2D4 =À266
(c=0.5 mgmLÀ1 in CH2Cl2); 1H NMR (500 MHz, CDCl3) 1:1 mixture of
isomers: d=7.72–7.63 (m, 32H, Ar-H), 7.28–7.16 (m, 48H, Ar-H), 4.53–
4.50 (m, 2H, Cp-H), 4.38–4.35 (m, 2H, Cp-H), 4.31 (d, J=1.5 Hz, 2H,
Cp-H), 4.26 (d, J=1.5 Hz, 2H, Cp-H), 4.23 (t, J=2.4 Hz, 2H, Cp-H),
4.15–4.09 (m, 2H, Cp-H), 3.44–3.32 (m, 4H, CpCHHN), 3.08–2.81 (m,
16H, CpCHHN and NCH2), 2.32–2.23 (m, 2H, NCH2), 2.08–2.03 (m, 2H,
NCH2), 1.81 (ddd, J=9.3, 6.2, 3.5 Hz, 4H, NCH2CH2), 1.76–1.60 (m, 8H,
NCH2CH2), 1.53–1.45 ppm (m, 4H, NCH2CH2); 13C NMR (126 MHz,
CDCl3): d=136.75, 136.68, 129.34, 129.28, 127.94, 125.79, 125.72, 103.20,
102.85, 102.75, 102.31, 84.84, 82.99, 80.55, 79.96, 77.60, 76.71, 75.25, 74.68,
74.66, 60.46, 60.38, 60.28, 60.22, 59.67, 30.95, 22.00, 21.65, 21.55,
Synthesis of di-m-chlorobisACHTNUGRTNEUNG
[(h5-(Sp)-N,N-diethylaminomethylcyclopenta-
dienyl,1-C,3’-N)(h4-tetraphenylcyclobutadiene)cobalt]dipalladium (27): A
solution of (R)-N-acetylphenylalanine (0.250 g, 1.21 mmol) and NaOH
(0.039 g, 0.98 mmol) in water (15 mL) was added to
a solution of
Na2Pd2Cl4 (0.263 g, 0.89 mmol) in MeOH (50 mL). The pH of the mix-
ture was adjusted to 8.0 using either aqueous NaOH or HCl as required
and the mixture was allowed to stir for 20 min. A solution of 21a
(0.500 g, 0.88 mmol) in 5:1 MeOH/CH2Cl2 (90 mL) was then added in
portions over 5 min. The solution was allowed to stir for 16 h at RT. On
completion, the reaction mixture was diluted with CH2Cl2 (100 mL) and
washed with brine (2ꢂ100 mL). The organic phase was dried over
MgSO4, filtered and the solvent was removed in vacuo. Purification by
column chromatography (SiO2, 4:1 hexanes/EtOAc) gave the product
(Sp)-27 as an orange solid (0.244 g, 39%), ee=82% as determined by for-
mation of the proline adducts. M.p. >2008C (decomp); [a]2D4 =À618 (c=
0.5 mgmLÀ1 in CH2Cl2); 1H NMR (500 MHz, CDCl3) 1:0.6 mixture of iso-
mers: d=7.70–7.60 (m, 32H, Ar-H), 7.29–7.15 (m, 48H, Ar-H), 4.47 (dd,
J=2.3, 1.1 Hz, 2H, Cp-H), 4.32 (t, J=2.2 Hz, 4H, Cp-H), 4.30–4.27 (m,
2H, Cp-H), 4.24 (t, J=2.4 Hz, 2H, Cp-H), 4.17 (t, J=2.4 Hz, 2H, Cp-H),
3.29 (d, J=13.9 Hz, 2H, CHHNEt2), 3.22 (d, J=13.9 Hz, 2H,
CHHNEt2), 2.75 (d, J=13.9 Hz, 4H, CHHNEt2), 2.68–2.43 (m, 16H,
CH2CH3), 1.52 (t, J=7.1, Hz, 6H, CH2CH3), 1.52 (t, J=7.1, Hz, 6H,
CH2CH3), 0.92–0.84 ppm (m, 12H, CH2CH3); 13C NMR (126 MHz,
CDCl3): d=136.74, 136.68, 129.32, 129.26, 127.95, 127.92, 129.79, 125.76,
84.27, 82.65, 79.50, 79.44, 77.24, 76.45, 75.55, 60.41, 57.44, 57.28, 55.39,
55.33, 54.32, 53.22, 14.53, 14.22, 10.01, 9.80 ppm; IR (neat): n˜ =3056,
2971, 2929, 1596, 1498, 1444, 1387, 909, 734, 695 cmÀ1; elemental analysis
calcd (%) for C76H70Cl2Co2N2Pd2: C 64.60, H 4.99, N 1.98; found C 64.70,
H 4.89, N 2.04.
21.30 ppm; IR (neat): n˜ =3056, 2966, 1596, 1498, 1443, 909, 734, 695 cmÀ1
;
elemental analysis calcd (%) for C76H66Cl2Co2N2Pd2: C 64.79, H 4.72, N
1.98; found C 64.81, H 4.60, N 2.07.
Synthesis of proline adduct (S,Sp)-31: A solution of (Sp)-28 (0.020 g,
0.014 mmol) in acetone (2 mL) was added to a solution of NaHCO3
(0.003 g, 0.04 mmol) and (S)-proline (0.003 g, 0.03 mmol) in water
(1 mL). During the addition a copious amount of precipitate was formed.
The reaction was then vigorously stirred for 16 h at RT and then diluted
with CH2Cl2 (5 mL). The phases were separated and the aqueous phase
was washed with further portions of CH2Cl2 (2ꢂ2 mL). The organic
phases were combined, dried over MgSO4, filtered and the solvent was
removed in vacuo yielding the product as an orange solid (0.020 g, 90%).
M.p. 206–2088C; [a]D21 =À37 (c=1.1 mgmLÀ1 in CH2Cl2); 1H NMR
(500 MHz, [D6]DMSO): d=7.52–7.46 (m, 8H, Ar-H), 7.28–7.20 (m, 12H,
Ar-H), 5.52–5.44 (m, 1H, NH), 4.36 (s, 2H, Cp-H), 4.25 (s, 1H, Cp-H),
3.56 (q, J=7.9 Hz, 1H, NHCH), 3.19–3.01 (m, 2H, NHCHH and
CpCHHN), 3.01–2.94 (m, 1H, NHCHH), 2.92–2.84 (m, 1H, NCH2), 2.79
(d, J=14.5 Hz, 1H, CpCHHN), 2.35–2.21 (m, 2H, CH2), 2.14–2.04 (m,
1H, CHH), 1.82–1.61 (m, 4H, CH2), 1.44–1.33 (m, 1H, CHH), 1.24–
1.16 ppm (m, 2H, CH2); 13C NMR: not obtained due to poor solubility in
CDCl3 and [D6]DMSO; IR (neat): n˜ =3444, 2925, 2855, 1733, 1623, 1590,
1497, 1459, 1378, 1259, 1170, 1070, 1023, 926, 782, 745, 702 cmÀ1; HRMS
(ESI): m/z calcd for C43H42CoN2O2Pd: 783.1623 [M+H]+; found:
783.1615.
Synthesis of proline adducts (S,Sp)-29 and (S,Rp)-30: A solution of (Sp)-27
(0.020 g, 0.014 mmol) in acetone (1 mL) was added to a solution of
NaHCO3 (0.003 g, 0.04 mmol) and (S)-proline (0.003 g, 0.03 mmol) in
water (0.5 mL). During the addition a copious amount of precipitate was
formed. The reaction was then vigorously stirred for 16 h at RT and then
diluted with CH2Cl2 (5 mL). The phases were separated and the aqueous
phase was washed with further portions of CH2Cl2 (2ꢂ2 mL). The organ-
ic phases were combined, dried over MgSO4, filtered and the solvent was
removed in vacuo yielding the product as an orange solid (0.021 g, 95%).
M.p. 206–2088C; [a]D21 =À104 (c=0.7 mgmLÀ1 in CH2Cl2); 1H NMR
(500 MHz, CDCl3): d=7.55 (dd, J=6.6, 3.0 Hz, 8H, Ar-H), 7.25–7.21 (m,
12H, Ar-H), 4.40 (t, J=2.4 Hz, 1H, Cp-H), 4.34 (d, J=1.6 Hz, 1H, Cp-
Synthesis of proline adduct (R,Sp)-32: Prepared in the same way as
(S,Sp)-31 from (Sp)-28 (0.020 g, 0.014 mmol) and (R)-proline (0.003 mg,
0.03 mmol) to give the product as an orange solid (0.011 g, 50%). M.p.
1
206–2088C; [a]2D3 = +72 (c=0.5 mgmLÀ1 in CH2Cl2); H NMR (500 MHz,
CDCl3): d=7.69 (d, J=6.4 Hz, 8H, Ar-H), 7.29–7.26 (m, 12H, Ar-H),
4.45 (t, J=2.3 Hz, 1H, Cp-H), 4.33 (d, J=2.6 Hz, 1H, Cp-H), 4.20 (d, J=
17960
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 17951 – 17962

Cobalt Sandwich Complexes
FULL PAPER
2.5 Hz, 1H, Cp-H), 3.44 (dt, J=11.5, 7.6 Hz, 1H, NHCH), 3.34 (ddt, J=
13.5, 9.1, 4.9 Hz, 2H, 2ꢂNHCHH), 3.13–2.91 (m, 4H, CH2), 2.71–2.61
(m, 1H, CHH), 2.47–2.35 (m, 1H, CHH), 2.18–2.10 (m, 1H, CHH), 2.05–
1.95 (m, 2H, CH2.), 1.94–1.89 (m, 2H, CH2), 1.88–1.79 (m, 1H, CHH),
1.78–1.72 (m, 1H, CHH), 1.64 (brs, 1H, NH), 1.51–1.38 ppm (m, 1H,
CHH); 13C NMR (126 MHz, CDCl3): d=180.32, 136.76, 128.87, 128.26,
126.09, 104.56, 97.53, 84.31, 83.78, 79.33, 73.73, 66.13, 59.97, 59.65, 59.13,
52.98, 29.60, 25.44, 22.06, 21.95 ppm; IR (neat): n˜ =3444, 2925, 2855,
1733, 1623, 1590, 1497, 1459, 1378, 1259, 1170, 1070, 1023, 926, 782, 745,
Acknowledgements
For financial support we thank the ISCE-Chem & INTERREGIVa pro-
gramme (D.C.), the EPSRC (G.I.), the Higher Education Commission
Pakistan (M.I.) and the Nuffield Foundation (J.W.). We also thank Myles
Cheesman for assistance with the CD spectra, the EPSRC National Mass
Spectrometry Centre (University of Wales, Swansea), and the EPSRC
National Crystallography Service (University of Southampton) for the
structure determination of (R,Sp)-13.
702 cmÀ1
[M+H]+; found: 783.1614.
Synthesis of chloroACHTUNGTRENNUNG
[(h5-(Sp)-N,N-dimethylaminomethylcyclopentadien-
; HRMS (ESI): m/z calcd for C43H42CoN2O2Pd: 783.1623
[1] Reviews: a) J. Dupont, C. S. Consorti, J. Spencer, Chem. Rev. 2005,
105, 2527–2571; b) Palladacycles: Synthesis Characterization and
Applications (Eds.: J. Dupont, M. Pfeffer), Wiley-VCH, Weinheim,
2008.
yl,1-C,3’-N)(h4-tetraphenylcyclobutadiene)cobalt]2-(diphenylphosphino)-
phenylferrocene-palladium (37): 2-(Diphenylphosphino)phenylferrocene
(0.007 g, 0.016 mmol) was added to
a solution of (Sp)-11 (0.010 g,
0.015 mmol) in CH2Cl2 (1 mL) and the solution was stirred for 16 h. The
solvent was removed in vacuo and the product was purified by column
chromatography (SiO2, 49:1 CH2Cl2/MeOH) to give the product (Sp)-35
as a red/orange solid (0.015 g, 88%). Crystals suitable for X-ray crystal-
lography were obtained by slow diffusion of hexane into a CH2Cl2 solu-
tion (~50:1 hexane/CH2Cl2). M.p. 1718C; [a]2D1 = +26 (c=0.5 mgmLÀ1 in
CH2Cl2); 1H NMR (500 MHz, CDCl3): d=7.90–7.80 (m, 2H, Ar-H),
7.48–7.10 (m, 28H, Ar-H), 7.00 (t, J=7.6 Hz, 1H, Ar-H), 6.90 (t, J=
6.8 Hz, 2H, Ar-H), 6.76 (dd, J=11.1, 7.5 Hz, 1H, Ar-H), 4.48 (brs, 1H,
Cp-H), 4.36 (brs, 1H, Cp-H), 4.12 (s, 1H, Cp-H), 4.07 (s, 1H, Cp-H),
4.00 (s, 1H, Cp-H), 3.93 (s, 5H, Cp-H), 3.84 (s, 1H, Cp-H), 3.22 (s, 1H,
Cp-H), 3.03 (d, J=14.1 Hz, 1H, CHHNMe2), 2.92 (dd, J=14.0, 2.5 Hz,
1H, CHHNMe2), 2.65 (s, 3H, CH3), 2.38 ppm (d, J=2.4 Hz, 3H, CH3);
13C NMR (126 MHz, CDCl3): d=136.66, 135.99, 132.84, 130.20, 129.42,
129.06, 128.05, 127.99, 127.95, 127.91, 127.52, 127.44, 125.89, 120.35, 80.82,
77.60, 77.29, 77.03, 76.78, 76.24, 73.82, 69.68, 61.90, 52.06 ppm; 31P NMR
(202 MHz, CDCl3): d=32.22 ppm; IR (neat): n˜ =3056, 2923, 1732, 1596,
1497, 1436, 1194, 911, 732, 695, 559 cmÀ1; elemental analysis calcd (%)
for C64H54ClCoFeNPPd: C 68.34, H 4.85, N 1.25; found C 66.35, H 5.05,
N 1.46.
[2] Reviews: a) J.-P. Djukic, A. Hijazi, H. D. Flack, G. Bernardinelli,
Chem. Soc. Rev. 2008, 37, 406–425; b) C. J. Richards, in Chiral Fer-
rocenes in Asymmetric Catalysis: Synthesis and Applications (Eds.:
L.-X. Dai, X.-L. Hou), Wiley-VCH, Weinheim, 2010, pp. 337–368.
[3] Review: V. V. Dunina, O. N. Gorunova, P. A. Zykov, K. A. Kochet-
kov, Russ. Chem. Rev. 2011, 80, 51–74.
[4] Review: H. Nomura, C. J. Richards, Chem. Asian J. 2010, 5, 1726–
1740.
[5] Bulky cobalt sandwich complex based palladacycle catalysis of allyl-
ic imidate rearrangements and related reactions: a) L. E. Overman,
C. E. Owen, M. M. Pavan, C. J. Richards, Org. Lett. 2003, 5, 1809–
1812; b) C. E. Anderson, L. E. Overman, J. Am. Chem. Soc. 2003,
125, 12412–12413; c) S. F. Kirsch, L. E. Overman, M. P. Watson, J.
Org. Chem. 2004, 69, 8101–8104; d) H. Nomura, C. J. Richards,
Chem. Eur. J. 2007, 13, 10216–10224; e) M. P. Watson, L. E. Over-
man, R. G. Bergman, J. Am. Chem. Soc. 2007, 129, 5031–5044;
f) M. D. Swift, A. Sutherland, Org. Lett. 2007, 9, 5239–5242;
g) M. D. Swift, A. Sutherland, Tetrahedron 2008, 64, 9521–9527;
h) A. M. Zaed, M. D. Swift, A. Sutherland, Org. Biomol. Chem.
2009, 7, 2678–2680; i) A. Maleckis, K. Klimovica, A. Jirgensons, J.
Org. Chem. 2010, 75, 7897–7900; j) S. Ahmad, L. H. Thomas, A. Su-
therland, Org. Biomol. Chem. 2011, 9, 2801–2808; k) S. Ahmad, A.
Sutherland, Org. Biomol. Chem. 2012, 10, 8251–8259. Related reac-
tions: l) S. F. Kirsch, L. E. Overman, J. Org. Chem. 2005, 70, 2859–
2861; m) E. E. Lee, R. A. Batey, J. Am. Chem. Soc. 2005, 127,
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General procedure for transcyclopalladation:
A mixture of (Sp)-14
(0.030 g, 0.02 mmol) and either 33 (0.019 g, 0.04 mmol) or 34 (0.020 g,
0.04 mmol) were heated in toluene (0.5 mL) under nitrogen for 24 h.
After being cooled the solvent was evaporated in vacuo and the residue
was re-dissolved in 2:1 acetone/water and sodium acetylacetonate
(0.005 g, 0.04 mmol) was added to it. After being stirred at room temper-
ature for 16 h the mixture was diluted with CH2Cl2, washed with water,
dried (MgSO4), filtered and the solvent was removed in vacuo. The ee
and absolute configuration of 35 and 36 were determined by HPLC
(Chiracel OD-H, 99.7:0.3 n-hexane/IPA, 0.8 mLminÀ1).
General procedure for catalysis: The required amount of imidate stock
solution was added to a flask charged with catalyst. If silver salts and/or
proton sponge was used this was subsequently added. The solution was
protected from light then heated to the desired temperature for the allot-
ted time. On completion, the solution was passed through a short pad of
Celite and the solvent was removed in vacuo. Purification by flash chro-
matography, eluting with 24:1 hexanes/EtOAc, yielded the product amide
2,2,2-trifluoro-N-(4-methoxyphenyl-N-(1-propylallyl)acetamide (43) as
a pale yellow oil. Chiral HPLC analysis was used to determine enantio-
meric excess after cleavage of the trifluoroacetate group[5a] (Chiracel
OD-H, 99.8:0.2 n-hexane/IPA, 0.8 mLminÀ1). In the same manner amides
44a–d were isolated as colourless oils and chiral HPLC analysis was used
to determine the enantiomeric excess (Chiracel OD-H, 99.5:0.5 n-
hexane/IPA, 0.8 mLminÀ1).[5b,d]
[6] Pentaphenylferrocene-based palladacycle catalysis of allylic imidate
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CCDC-931363 ((S,Sp)-12), 931364 (15) and 931365 ((Sp)-37) contain the
supplementary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
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ladacycle precatalyst for asymmetric synthesis through a Pd0/PdII
pathway has not been reported. However, for some of the reactions
listed in ref. [7] the nature of the palladium catalyst has not been es-
tablished.
[25] Crystal data for compound 15: C41H32CoF6NO2Pd, Mr =850.01; mon-
oclinic, space group P21/c (no. 14), a=14.0325(4), b=14.1479(4), c=
17.4222(5) ꢁ, b=91.776(2)8, V=3457.18(17) ꢁ3; Z=4, 1calcd
=
1.633 gcmÀ3
,
F
N
m
C
,
l-
AHCTUNGTRENNG(UN MoKa)=0.71073 ꢁ; 22534 reflections measured to q=27.58, 7849
unique (Rint =0.058), 6530 observed. Final R1 =0.062, wR2 =0.103
for all data; R1 =0.047 for the observed data.
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Chem. Sci. 2013, 4, 2675–2679.
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b) F. X. Roca, M. Motevalli, C. J. Richards, J. Am. Chem. Soc. 2005,
127, 2388–2389.
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Chem. Commun. 2012, 48, 1991–1993.
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4.4 compared to a value of about 10 for protonated trimethylamine:
M. A. Weinberger, R. Greenhalgh, Can. J. Chem. 1963, 41, 1038–
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planar chiral palladacycles that do not include additional elements
of chirality, see ref. [2b].
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[31] Crystal data for compound (Sp)-37: C64H54ClCoFeNPPd, C4H10O,
Mr =1198.8; orthorhombic, space group P212121 (no. 19), a=
11.1113(10), b=13.7443(14), c=36.309(4) ꢁ, V=5545.0(10) ꢁ3; Z=
4, 1calcd =1.436 gcmÀ3
,
F
G
mACHTUNGTRENNUNG(MoKa)=
10.0 cmÀ1, l
ACHTUNGTRENNUNG
21.38, 6133 unique (Rint =0.371), 2375 observed. Final R1 =0.184,
wR2 =0.082 for all data; R1 =0.070 for the observed data. Note: the
diffraction data here were generally weak and the value for qmax, the
limit for reliable data, was set at 21.38 resulting in a reduced dataset.
Flack x parameter=0.00(4).
[19] Crystal data for compound (S,Sp)-12: C41H39CoN2O2Pd, 2(CH2Cl2),
Mr =926.9; monoclinic, space group P21 (no. 4), a=14.4130(2), b=
9.8989(3), c=14.3763(9) ꢁ, b=96.5285(3)8, V=2037.81(14) ꢁ3; Z=
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217–227.
2, 1calcd =1.511 gcmÀ3
11.5 cmÀ1, l
,
F
N
mG
[33] The barrier to inversion of this propeller chirality is likely to be
ACHTUNGTRENNUNG
lower than the value of 11.7 kcalmolÀ1 determined for the propeller
27.58, 9334 unique (Rint =0.077), 6985 observed. Final R1 =0.072,
wR2 =0.093 for all data; R1 =0.048 for the observed data. Flack x
parameter=À0.01(2).
chiral epimerisation of (h5-C5Ph5)Fe(CO)
ACTHNGUTERN(NUG PMe3)ACHTNUGTREN(NUNG HC=O), which in
turn is lower than the value of about 17 kcalmolÀ1 determined as
the barrier to rotational isomerisation of meta-substituted hexaaryl-
benzenes; a) L. Li, A. Decken, B. G. Sayer, M. J. McGlinchey, P.
Brꢅgaint, J.-Y. Thꢅpot, L. Toupet, J.-R. Hamon, C. Lapinte, Organo-
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4683–4693.
Received: July 24, 2013
Published online: November 21, 2013
17962
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Chem. Eur. J. 2013, 19, 17951 – 17962