Diastereoselective synthesis of half-sandwich chiral-at-metal cobaltacycles by oxidative cyclisation

Article abstract of DOI:10.1039/c2cc34837c

Reaction of chiral ester linked diynes with chlorotris(triphenylphosphine) cobalt(i) and sodium cyclopentadienide gave (η⁵-cyclopentadienyl) (triphenylphosphine) cobaltacyclopentadiene complexes as single chiral-at-metal diastereoisomers, including a non-racemic example synthesised in three steps from (S)-3-butyn-2-ol.

Full text of DOI:10.1039/c2cc34837c

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COMMUNICATION
Diastereoselective synthesis of half-sandwich chiral-at-metal
cobaltacycles by oxidative cyclisationw
Jahangir Amin and Christopher J. Richards*
Received 6th July 2012, Accepted 9th August 2012
DOI: 10.1039/c2cc34837c
Reaction of chiral ester linked diynes with chlorotris(triphenyl-
phosphine)cobalt(I) and sodium cyclopentadienide gave (g5-cyclo-
pentadienyl)(triphenylphosphine) cobaltacyclopentadiene complexes
as single chiral-at-metal diastereoisomers, including a non-racemic
example synthesised in three steps from (S)-3-butyn-2-ol.
chiral ligand.3 Known examples of Z5-cyclopentadienyl cobalt(III)
complexes of type C have been generated by the latter procedure
following ligand substitution with both neutral and anionic
chiral ligands.7 In this Communication we report on an
alternative oxidative cyclisation protocol for the highly dia-
stereoselective and modular synthesis of cobalt-based
chiral half-sandwich complexes, and on the extension of
this methodology to the asymmetric synthesis of an air and
configurationally stable chiral-at-cobalt complex.
The variability in the structure of chiral organometallic complexes
provides novel opportunities for the synthesis of non-racemic
ligands, catalysts and materials. Ideally such complexes are
air-stable, configurationally-stable, and readily generated as single
enantiomers. Chiral organometallics result from the attachment
of a metal to a carbon based stereogenic centre (Fig. 1, A).1
Alternatively, differential di-substitution of metallocenes such
as ferrocene (B) gives rise to planar chirality, these and other
sandwich complexes having been exploited extensively in chiral
ligand syntheses.2 Pseudo tetrahedral half-sandwich complexes
containing three different additional ligands, with either an
Z5-cyclopentadienyl (C) or an Z6-arene ligand, contain a
stereogenic metal atom.3 Although such complexes have
not been utilised as building blocks for ligand synthesis, this
metal-focused chirality has been exploited extensively in
stoichiometric asymmetric synthesis (notably M = Re, Fe, Mo),4
and more recently in catalysis.5
Cobaltacyclopentadiene 1 is readily prepared from the
reaction of chlorotris(triphenylphosphine)cobalt(I) and sodium
cyclopentadienide with two equivalents of diphenylacetylene.8
The same reaction on a diyne containing a stereogenic centre
within an acetylene tether will result in a chiral-at-metal cobalta-
cycle 2 (Scheme 1). Provided the reaction is diastereoselective, and
the product configurationally stable, this will provide an accessible
route to novel chiral organometallic building blocks.
Non-terminal linked diynes were prepared in two steps by
an esterification and Sonogashira cross-coupling sequence;
starting either from propargylic alcohols 3 and introduction
of Ar2CRC– onto 4, or from 5 and introduction of Ar1
onto 6 (Scheme 2). Diynes 7 were chosen for this study because
of the simplicity and modularity of these procedures, and
also because they are known to react with (Z5-cyclopenta-
dienyl)cobaltdicarbonyl to give planar chiral (Z5-cyclopenta-
dienone)(Z5-cyclopentadienyl)cobalt metallocenes in moderate
diastereoselectivity.9
Reaction of 7a (R = Me, Ar1 = Ar2 = Ph) with
chlorotris(triphenylphosphine)cobalt(I) and sodium cyclopenta-
dienide in THF heated at reflux for 30 minutes resulted in a
new air-stable organometallic 8a isolated in 44% yield following
column chromatography (Scheme 3, Table 1, Method A – entry 1).
As the reaction likely proceeds via the in situ formation of
(Z5-cyclopentadienyl)cobaltbis(triphenylphosphine), pre-formation
and isolation of this complex10 was followed by addition of
Methods for the generation of enantiomerically pure chiral-at-
metal half-sandwich complexes began with resolution6 and have
been extended to diastereoselective protocols mediated either by
a chiral Z5 or Z6 p-ligand, or by an introduced mono or bidentate
Fig. 1 Representative chiral organometallic complexes.
School of Chemistry, University of East Anglia, Norwich Research
Park, Norwich, NR4 7TJ, UK. E-mail: Chris.Richards@uea.ac.uk;
Fax: +44 (0)1603 592003; Tel: +44 (0)1603 592003
w Electronic supplementary information (ESI) available: Experimental
procedures and characterisation data for 4c, 6, (S)-6, (S)-7a, 7c–g,
(S)-8a, 8b–g and 11a, c and d. CCDC 889207 (8a) and 889208 (8c). For
ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c2cc34837c
Scheme 1 Known (1) and proposed (2) products of oxidative cyclisation.
Reagents and conditions: (i) NaCp, CoCl(PPh3)3, D.
c
10192 Chem. Commun., 2012, 48, 10192–10194
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by phosphine dissociation and formation of a planar 16-electron
intermediate.12 Addition of 1.5 eq. of tri(p-tolyl)phosphine to 8a in
CDCl3 at room temperature and recording the 1H NMR spectrum
after 1 h revealed the presence of only 8a/tri(p-tolyl)phosphine
and no new ligand substitution complex. An X-ray structure
analysis of 8a confirmed the anticipated cobaltacycle half-
sandwich structure, and revealed the relative configuration as
S
Co*, SC* (Fig. 2).13
That facile phosphine substitution is not occurring with 8a
reveals that the SCo*, SC* configuration is maintained in solution
and that a single chiral-at-metal diastereoisomer results from
oxidative cyclisation via an intermediate planar14 16 electron
(Z5-cyclopentadienyl)cobaltacyclopentadiene. Coordination of
triphenylphosphine opposite the methyl group dictates the
configuration of the metal-based chirality.
Scheme 2 Diyne syntheses. Reagents and conditions: (i) 2-iodo-
benzoic acid (1.1 eq.), DCC (1.1 eq.), DMAP (0.2 eq.), CH2Cl2, RT,
48 h 92–99%. (ii) Ar2CCH (1.1 eq.), PdCl2(PPh3)2 (0.03 eq.), CuI
(0.1 eq.), NEt3, 60 1C, 24 h, 93–99%. (iii) 3-butyn-2-ol (1 eq.), DCC
(1.1 eq.), DMAP (0.2 eq.), CH2Cl2, RT, 48 h, 94%. (iv) Ar1I (1.1 eq.),
PdCl2(PPh3)2 (0.03 eq.), CuI (0.1 eq.), NEt3, 60 1C, 24 h, 99%.
The solution isomerism is ascribed to the two other elements
of chirality present in 8a. Three-atom linked biphenyls 9
interconvert rapidly between atropisomers15 containing either an
equatorial or axial R substituent, the lowest energy arrangement
being dependent upon the identity of X, Y and R (Scheme 4).16
The X-ray structure of 8a reveals an axial methyl group and an
Ra* configuration with the cobaltacyclopentadiene moiety
replacing the bottom phenyl group of 9. The propeller-like
arrangement of the phenyl rings of a metal-coordinated tri-
phenylphosphine complex 10 result in M and P-configurations
which give rise to diastereoisomers with chiral-at-metal half-
sandwich complexes.17 Although the barrier to intramolecular
interconversion is usually low, occurring by a two ring-flip
Scheme 3 Diastereoselective synthesis of half-sandwich complexes 8.
Table 1 Diastereoselective synthesis of half-sandwich complexes 8
Entry/
diyne
Product/
Method yielda (%)
R
Ar1
Ar2
1 7a
2 7a
3 7b
4 7b
5 7c
6 7d
7 7e
8 7f
9 7g
Me Ph
Me Ph
i-Pr Ph
i-Pr Ph
Me 4-CF3C6H4
Me Ph
Me Ph
Ph
Ph
Ph
Ph
A
B
A
B
A
A
B
A
B
8a 44
8a 75
8b 55
8b 79
8c 78
8d 72
8e 89
8f 73
8g 78
Ph
4-CF3C6H4
3-C5H4N
Ph
Me 2-BrC6H4
Me 2-Cl-5-C5H3N Ph
a
Isolated by column chromatography.
7a and heating in THF as before to give 8a in 75% yield
(Method B – entry 2).
Fig. 2 X-ray crystal structure of SCo*, SC* 8a.
Examination of both crude and column isolated 8a by
1H NMR spectroscopy revealed four sets of signals in a
11 : 1.5 : 1 : 1 ratio. Following recrystallisation of 8a the same
ratio of signals was observed when the spectrum was recorded
within minutes of dissolving the crystals in CDCl3 at room
temperature (20 1C). No change in this ratio was observed over
1
time. The multiplicity of signals in the H NMR pointed to the
possibility that these may, in part, result from rapid epimerisation
of the metal-based stereogenic centre.11 Stereochemical lability
in Z5-cyclopentadienyl piano-stool complexes C is a consequence
of facile ligand dissociation.3 For example, epimerisation of
the related isoelectronic chiral-at-metal complex (Z5-cyclopenta-
dienyl)FeCH3(CO)PPh2R* (half-life 70 min at 70 1C) proceeds
Scheme 4 Isomerism of 9, 10 and extension to SCo*, SC* 8a.
Chem. Commun., 2012, 48, 10192–10194 10193
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in phosphine dissociation and clean formation of (Z5-cyclo-
pentadienyl)(Z4-tetraphenylcyclobutadiene)cobalt.8
In conclusion, we have demonstrated a short highly diastereo-
selective modular synthesis of new air-stable cobalt-based
chiral-at-metal half-sandwich complexes obtained by oxidative
cyclisation. The methodology is applicable to both substituted
or unsubstituted cyclopentadienyl ligands and was readily
adapted to the synthesis of a configurationally stable single
enantiomer. These complexes provide an alternative to chiral
metallocene frameworks as the basis of novel ligands, catalysts
and materials.
Scheme 5 Diastereoselective synthesis of carbomethoxy substituted
half-sandwich complexes 11.
Table 2 Diastereoselective synthesis of carbomethoxy substituted
half-sandwich complexes 11
The EPSRC (JA) is thanked for financial support. We also
thank Caroline Taylor for some preliminary experiments, the
EPSRC National Crystallography Service (Southampton) and
the EPSRC National Mass Spectrometry Centre (Swansea).
Entry/diyne
R
Ar1
Ar2
Product/yielda (%)
1 7a
3 7c
4 7d
Me Ph
Me 4-CF3C6H4 Ph
Me Ph
Ph
11a 64
11c 49
4-CF3C6H4 11d 65
Notes and references
a
Isolated by column chromatography.
1 H. C. Malinakova, Chem.–Eur. J., 2004, 10, 2636.
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mechanism,17a,18 isolable M and P epimers have been obtained
with a bulky chiral bidentate ligand, epimerisation occurring
via reversible phosphine dissociation.19 Further examination
of the X-ray structure reveals an M* configuration,20 and
assuming the maintenance of this Ra*, M*-structure as the
dominant species in solution, isomerisation gives rise to the
three minor isomers listed in Scheme 4.21 In contrast, the
isopropyl substituted complex 8b, prepared by both Methods A
and B (entries 3 and 4), resulted in only a single observable
stereoisomer in solution, a consequence of the greater confor-
mational control imparted by the larger isopropyl group.
A number of other complexes were prepared in good yield
(8c–8g, entries 5–9), including examples with pyridyl ligand
substituents (8e, 8g), and a complex with a 2-bromophenyl
substituent (8f) with the potential for further functionalisation.
Like parent methyl substituted complex 8a, all of these gave
four solution species with one dominant (e.g. 11 : 1 : 1 : 1
for 8c – see ESIw), and the X-ray structure of 8c reveals
the same configuration for all four elements of chirality
(SCo*, SC*, Ra*, M*).
10 Y. Wakatsuki and H. Yamazaki, Inorg. Synth., 1989, 26, 189.
11 H. Brunner, Eur. J. Inorg. Chem., 2001, 905.
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prepared following in situ generation of sodium carbo-
methoxycyclopentadienide (Scheme 5, Table 2).22 As before,
these complexes containing a methyl substituted stereogenic
centre derived from 7a, 7c and 7d resulted in up to four solution
stereoisomers.
13 For extension of the Cahn-Ingold-Prelog system to polyhapto-ligands
see: C. Lecomte, Y. Dusausoy, J. Protas, J. Tirouflet and A. Dormond,
J. Organomet. Chem., 1974, 73, 67, and also ref. 5.
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15 An inversion barrier DGz for 9 of 56 kJ molꢀ1 has been estimated
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I. O. Sutherland and M. V. J. Ramsay, Tetrahedron, 1965,
21, 3401.
A non-racemic sample of 8a was synthesised starting with
commercially available (S)-3-butyn-2-ol. Following ester
formation with 5 as outlined in Scheme 2 (96%), followed
by Sonogashira coupling with iodobenzene (>99%), (S)-7a
was complexed by Method B to give (S)-8a in 74% yield.
Chiral HPLC analysis gave a single peak in contrast to the two
well separated peaks observed for racemic 8a. These results are
consistent with the observation of four solution species of 8a by
NMR spectroscopy at room temperature where interconversion
between these species is rapid. Essentially no difference was
observed in the 1H NMR of 8a recorded at 60 1C,23 and heating
at higher temperatures resulted in decomposition. This is in
marked contrast to 1 where heating at reflux in toluene results
16 S. L. Pira, T. W. Wallace and J. P. Graham, Org. Lett., 2009,
11, 1663, and references therein.
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1992, 11, 3724.
18 K. Mislow, Acc. Chem. Res., 1976, 9, 26.
19 H. Brunner, R. Oeschey and B. Nuber, Angew. Chem., Int. Ed. Engl.,
1994, 33, 866.
20 Relative to the Sc configuration the following torsions were
observed: o1 = 41.81, o2 = 53.41, o3 = 50.31.
21 J. W. Faller, J. Parr and A. R. Lavoie, New J. Chem., 2003, 27, 899.
22 W. P. Hart, D. Shihua and M. D. Rausch, J. Organomet. Chem.,
1985, 282, 111.
23 The energy barriers to interconverion of the isomers of 8a are
estimated as ca. 60–80 kJ molꢀ1
.
c
10194 Chem. Commun., 2012, 48, 10192–10194
This journal is The Royal Society of Chemistry 2012