Assessing the reactivity of sodium zincate [(TMEDA)Na(TMP)Zn tBu2] towards benzoylferrocene: Deprotonative metalation vs. alkylation reactions

Article abstract of DOI:10.1039/c1dt11465d

Exploring the reactivity of the mixed-metal reagent [(TMEDA)Na(TMP)Zn ^tBu₂] (1) towards substituted metallocene benzoylferrocene 2, this study has found that two competing reactivity pathways are available for the sodium TMP-zincate, namely (i) remote 1,6-nucleophilic addition of a tert-butyl group to the phenyl ring of 2, and (ii) simultaneous alpha-deprotonation of the substituted cyclopentadienyl ring of the metallocene and alkylation (1,2-addition) across the CO bond of the carbonyl group. A key organometallic intermediate [(TMEDA)Na(μ-TMP)Zn{OC(^tBu)(Ph) (η⁵-C₅H₃)Fe(η⁵-C ₅H₅)}] (3), resulting from the latter reaction has been trapped and characterised by X-ray crystallography and multinuclear ( ¹H and ¹³C) NMR spectroscopy. Its molecular structure revealed a unique two-fold activation of the tert-butyl groups bonded to zinc in the bimetallic base 1, showing for the first time that each alkyl group can exhibit markedly different reactivities (deprotonation vs. 1,2-addition) towards the same substrate molecule. Iodine interception of the organometallic intermediates of the reaction between 1 and 2 allowed the isolation and characterization (¹H, ¹³C NMR and X-ray crystallography) of the ferrocenyl derivatives [PhC(OH)(^tBu)(η⁵-C ₅H₃I)Fe(η⁵-C₅H₅)] (4) and [4-^tBu-C₆H₄C(O)(η⁵-C ₅H₄)Fe(η⁵-C₅H₅)] (5) in a 29% and 24% isolated yield respectively. The low yield observed for the formation of 5 (resulting from the 1,6-addition reaction followed by spontaneous aerobic oxidation during aqueous workup) could be increased to 41% when the reaction mixture was hydrolysed in the presence of the radical oxidant TEMPO. The Royal Society of Chemistry.

Full text of DOI:10.1039/c1dt11465d

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
Dalton
Transactions
Cite this: Dalton Trans., 2012, 41, 98
www.rsc.org/dalton
PAPER
Assessing the reactivity of sodium zincate [(TMEDA)Na(TMP)ZntBu2]
towards benzoylferrocene: deprotonative metalation vs. alkylation reactions†
Eva Hevia,* Alan R. Kennedy and Matthew D. McCall*
Received 3rd August 2011, Accepted 9th September 2011
DOI: 10.1039/c1dt11465d
Exploring the reactivity of the mixed-metal reagent [(TMEDA)Na(TMP)ZntBu2] (1) towards
substituted metallocene benzoylferrocene 2, this study has found that two competing reactivity
pathways are available for the sodium TMP-zincate, namely (i) remote 1,6-nucleophilic addition of a
tert-butyl group to the phenyl ring of 2, and (ii) simultaneous alpha-deprotonation of the substituted
cyclopentadienyl ring of the metallocene and alkylation (1,2-addition) across the C O bond of the
5
carbonyl group. A key organometallic intermediate [(TMEDA)Na(m-TMP)Zn{OC(tBu)(Ph)(h -C5H3)-
5
Fe(h -C5H5)}] (3), resulting from the latter reaction has been trapped and characterised by X-ray
crystallography and multinuclear (1H and 13C) NMR spectroscopy. Its molecular structure revealed a
unique two-fold activation of the tert-butyl groups bonded to zinc in the bimetallic base 1, showing for
the first time that each alkyl group can exhibit markedly different reactivities (deprotonation vs.
1,2-addition) towards the same substrate molecule. Iodine interception of the organometallic
intermediates of the reaction between 1 and 2 allowed the isolation and characterization (1H, 13C NMR
5
5
and X-ray crystallography) of the ferrocenyl derivatives [PhC(OH)(tBu)(h -C5H3I)Fe(h -C5H5)] (4) and
[4-tBu-C6H4C( O)(h -C5H4)Fe(h -C5H5)] (5) in a 29% and 24% isolated yield respectively. The low
yield observed for the formation of 5 (resulting from the 1,6-addition reaction followed by spontaneous
aerobic oxidation during aqueous workup) could be increased to 41% when the reaction mixture was
hydrolysed in the presence of the radical oxidant TEMPO.
5
5
tivities which cannot be replicated by classical metallating champi-
Introduction
ons such as organolithiums or lithium amides.13 An example of this
special regioselectivity is illustrated in Scheme 1(i) depicting the
meta-deprotonation of N,N-dimethylaniline by 1,14 contrasting
with conventional ortho-regioselectivity observed when nBuLi
is employed.15 As they require the presence of an alkali-metal
to proceed, although the departing hydrogen of the aromatic
molecule is replaced by a zinc atom, these deprotonations have
been designated as alkali-metal-mediated-zincations (AMMZn).16
Alkali-metal zincates have recently emerged as an impor-
tant family of organometallic reagents which can efficiently
be applied to a broad range of fundamental organic trans-
formations including metal–halogen exchange,1 deprotonative
metalation,2 nucleophilic addition3 or Negishi cross-coupling
reactions.4 Amongst this family of mixed-metal reagents,
sodium TMP-dialkyl zincate [(TMEDA)Na(TMP)ZntBu2] (1)5
(TMP = 2,2,6,6-tetramethylpiperidide, TMEDA = N,N,N¢,N¢-
tetramethylethylenediamine) stands out as an especially effective
and versatile base for executing direct zincation (C–H to C–
Zn exchange) on several different aromatic molecules (such as
benzene,5,6 toluene,7 benzonitriles,8 benzamides,2,9 naphthalene,10
aromatic ethers,11 carbamates,12 etc.) which are usually inert to-
wards conventional organozinc reagents. Outperforming existing
single-metal reagents, this bimetallic (alkali metal-zinc) approach
not only allows the use of milder reaction conditions (generally
room temperature) but also can enable unique synergic regioselec-
Scheme 1
Structural elucidation of key organometallic intermediates prior
to any electrophilic interception have demonstrated that these
deprotonations are genuine examples of zincations, where the
heteroleptic zincate 1 has displayed an overall alkyl basicity
(Scheme 1, i). Shedding new light on the mechanisms involved,
recent reactivity (in solution)17 and computational (in the gas
WestCHEM, Department of Pure and Applied Chemistry, University of
Strathclyde, Glasgow, UK, G1 1XL. E-mail: eva.hevia@strath.ac.uk
† Electronic supplementary information (ESI) available: Full experimental
details and NMR spectra. CCDC reference numbers 838243–838246. For
ESI and crystallographic data in CIF or other electronic format, see DOI:
10.1039/c1dt11465d
98 | Dalton Trans., 2012, 41, 98–103
This journal is
The Royal Society of Chemistry 2012
©

View Article Online
phase)18 studies have established that these TMP-dialkyl zincates
operate via a stepwise mechanism, where the mixed-metal reagent
acts first as an amide base (favoured by the greater kinetic
reactivity of the Zn–N bonds in comparison with Zn–C bonds),
metallating the aromatic substrate to generate a bisalkyl(aryl)
zincate [NaZn(arenide)tBu2] intermediate, with the concomitant
formation of TMP(H). In a second step, the acidic amine reacts
with this kinetic intermediate, to afford the final organometallic
product of the reaction containing the TMP anion releasing
isobutane.
Adding to this intriguing metallating ability, Mulvey has shown
that zincate 1 can also promote the remote addition of a tBu group
to benzophenone in a highly unusual 1,6-fashion (Scheme 1, ii).19
This alternative nucleophilic reactivity has recently been extended
to other ketones such as fluorenone and 2-benzoylpyridine,
demonstrating the versatility of 1 to prepare alkyl-substituted
arylketones.20
Results and discussion
In the experimental work a hexane solution of sodium zincate
[(TMEDA)Na(TMP)ZntBu2] (1) was mixed with one molar equiv-
alent of commercial benzoylferrocene (2) at room temperature
to afford a deep red suspension. Removal of hexane in vacuo
and addition of toluene gave a red solution which on cooling
deposited a batch of deep orange crystals of [(TMEDA)Na(m-
5
5
TMP)Zn{OC(tBu)(Ph)(h -C5H3)Fe(h -C5H5)}] (3) as determined
by X-ray crystallography and NMR spectroscopy in a modest
isolated yield of 12% (Scheme 2).
Herein, we extend for the first time our studies on sodium zincate
1 to their application in the area of metallocene functionalisation,
using metallocenyl-ketone benzoylferrocene (2) as a case study.
In general, the synthesis of functionalised ferrocene derivatives
attracts widespread interest from the synthetic community due to
their important applications in catalysis,21 materials science22 and
bioorganometallic chemistry.23 An invaluable synthetic tool which
facilitates the incorporation of ferrocenyl units into more complex
molecular scaffolds is deprotonative metalation, usually accom-
plished by polar organolithium reagents.24 Recent advances in
mixed-metal chemistry have revealed the selective deprotonation
of ferrocene can also be achieved using alkali-metal magnesiates,25
zincates,26 cadmates,26b,27 manganates,28 and cuprates.29 Further-
more, in certain cases, these bimetallic reagents can promote
unique polymetallations (as for example the spectacular four-
fold regioselective magnesiation of ferrocene performed by the
sodium tris(amido)magnesiate [NaMg(NiPr2)3])25b as well as the
efficient functionalisation of substituted ferrocenes bearing sensi-
tive organic functional groups (such as nitriles, esters or carboxylic
acids)25c,26b which are not compatible with traditional organo-
lithium reagents. Building on these precedents, the molecule cho-
sen for our study, benzoylferrocene (2), combines relatively acidic
hydrogen atoms of the Cp rings (therefore susceptible towards
C–H deprotonation) with an electrophilic benzoyl fragment
(which can undergo 1,2- or 1,6-addition reactions) (Fig. 1).
By trapping and structurally defining a new organometallic
intermediate from the reaction of 1 and 2 coupled with 1H NMR
monitoring of this reaction and carrying out subsequent elec-
trophilic interceptions, we provide new insights into the reactivity
of TMP-zincate 1, assessing its metallating power against its ability
to promote remote nucleophilic additions.
Scheme 2
The composition and molecular structure of 3 (Fig. 2)30 estab-
lished by X-ray crystallographic studies revealed an unprecedented
double activation of the tert-butyl groups bonded to Zn in
the bimetallic base 1 had taken place. Thus the benzoylfer-
rocene starting material has been simultaneously deprotonated
(zincated) at the alpha carbon position on the substituted Cp
ring (concomitantly releasing isobutane) and undergone a 1,2-
t
addition of the second Bu group across the C O bond of
the carbonyl group (Scheme 2 and Fig. 2). To the best of our
knowledge, 3 constitutes not only the first structurally defined
organometallic intermediate resulting from the reaction of 1 with
Fig. 2 Molecular structure of 3 with selective atom labelling and
40% probability ellipsoids. Hydrogen atoms and minor disordered
component of TMEDA have been omitted for clarity. Selected bond
◦
˚
lengths (A) and angles ( ): Zn(1)–N(1) 1.926(2), Zn(1)–C(9) 1.930(3),
Zn(1)–O(1) 1.9827(17), Na(1)–O(1) 2.229(2), Na(1)–N(1) 2.527(2),
O(1)–C(21) 1.415(3), N(1)–Zn(1)–C(9) 166.66(11), N(1)–Zn(1)–O(1)
104.30(8), C(9)–Zn(1)–O(1) 89.03(10), O(1)–Na(1)–N(1) 80.66(7),
Zn(1)–O(1)–Na(1) 90.26(7).
Fig. 1 Potential reactivity sites of benzoylferrocene (2).
This journal is
The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 98–103 | 99
©

View Article Online
a metallocene but also the first example where two alkyl groups
of a dialkylamidozincate exhibit strikingly different reactivities
(deprotonation vs. alkylation) towards a substrate.31 This double
activation is even more remarkable when compared with the lack
of reactivity of the homoleptic neutral zinc bis-alkyl tBu2Zn when
treated with 2, where neither addition nor deprotonation reactions
of the metallocene occur to any measurable extent.
the addition reactions (111.9 ppm for Zn–Ca and 81.3 ppm for
C–O in 3 vs. 72.3 ppm for Ca and 197.4 ppm for C O in 2).35
As mentioned above, 3 can only be isolated as a crystalline solid
in modest yields. Therefore in order to assess the selectivity and
the overall conversion of the reaction we then analysed by 1H and
13C NMR spectroscopy the constitution of the remaining filtrate
solution. To our surprise, we found that although no starting
1
Retaining the “[(TMEDA)-Na-(m-TMP)-Zn]2+” backbone of
reactant 1, the contacted ion pair structure of 3 (Fig. 2) is
material 2 was present in solution, the H NMR spectrum only
showed trace amounts of 3 along with a series of broad resonances
(ranging from 7.5 to 3.0 ppm) which were found to belong to
the same single species as evidenced by a 2D-[1H–1H] COSY
NMR experiment. Furthermore, it appears that this unknown
compound is the major product of the reaction of 1 with 2. Despite
several attempts this second intermediate could not be isolated as
a crystalline solid or any solid.
5
completed by a dianionic ferrocenyl fragment {OC(tBu)(Ph)(h -
5
2-
C5H3)Fe(h -C5H5)} which coordinates asymmetrically to the
bimetallic system, bridging Na and Zn through the oxygen (O1)
of the newly generated tertiary alkoxide and bonding exclusively
to Zn through ferrocenyl C9 (the carbon that has experienced the
deprotonation, which defines the reaction as a direct zincation).
This unique coordination mode led to the formation of two
fused metallocycles, a four-membered {NaNZnO} ring and a five-
membered {ZnOCCC} ring, with the latter subsequently fused
(through C9 and C10, Fig. 2) to the cyclopentadienyl ring of the
metallocene. The five-membered {ZnOCCC} ring lies essentially
co-planar with the C5H3 ring (maximum deviation from the mean
In order to shed some light on the overall outcome of the
reaction and the constitution of this species, we next probed the
electrophilic interception of the organometallic intermediates of
the reaction with iodine, an electrophile which has been previously
successfully used to trap magnesiated and zincated ferrocenyl
species.25c,26b Thus benzoylferrocene (2) was treated with one molar
equivalent of Na/Zn base 1 in toluene at room temperature for
2 h and subsequently reacted with a THF-solution of iodine to
˚
plane is 0.55 A for C10) whereas the {NaNZnO} ring is slightly
puckered (sum of internal angles, 358.38◦, torsion N1Na1O1Zn1,
8.49(7)◦). As a consequence of this rigid ring-fused framework, Zn
and O atoms adopt highly distorted trigonal planar geometries
(with angles ranging from 166.66(11) to 89.03(10)◦ and from
154.80(16) to 90.26 (7)◦ for Zn1 and O1 respectively). Despite
5
afford a mixture of the ferrocenyl derivatives [PhC(OH)(tBu)(h -
5
5
5
C5H3I)Fe(h -C5H5)] (4) and [4-tBu-C6H4C( O)(h -C5H4)Fe(h -
C5H5)] (5) in a 29% and 24% isolated yield respectively (Scheme 3).
˚
this distortion the Zn–Cferrocenyl distance in 3 (1.930(3) A) is similar
to those found in other related zincated ferrocenyl compounds
5
5
26a
˚
such as [(TMEDA)Zn{(h -C5H4)Fe(h -C5H5)}2] (1.9814(11) A)
5
5
and [{C,N-[Fe(h -C5H3-CH2NMe2)(h -C5H5)]}2Zn] (1.948(2) and
32
˚
˚
1.945(2) A). Similarly the Na–O (2.229(2) A) and Zn–O
˚
(1.9827(17) A) distances are within the same range as those
reported in the structurally elucidated compounds resulting from
1,6-addition reactions of 1 to aromatic ketones.19,20 Consistent with
the formation of a tertiary alkoxide resulting from a 1,2 addition
process, C21 (which originally in 2 had an sp2 hybridisation)
exhibits a distorted sp3 tetrahedral geometry (average bond angle
108.9◦), bonded to a tert-butyl group, a phenyl group and the
cyclopentadienyl fragment as well as forming a single C–O bond
33
˚
with O1 (C21–O1, 1.415(3) A).
Scheme 3
Being soluble in deuterated benzene, 3 was also characterized in
solution using 1H and 13C NMR spectroscopy (see Experimental
section and ESI† for full details). The most diagnostic resonances
The composition and structures of 4 and 5 were confirmed
by X-ray crystallographic studies (Fig. 3 and 4 respectively) and
1H and 13C NMR spectroscopy (see Experimental section for
1
in the H NMR spectrum were three broad singlets at 4.33, 4.63
and 4.70 ppm in a 1 : 1 : 1 ratio which can be assigned to the
three distinct hydrogens on the metallated cyclopentadienyl ring,34
and that differ significantly from the two multiplets present on
the mono-functionalised Cp ring of 2 (at 4.14 and 4.84 ppm).35
In addition, a sharp singlet at 1.07 ppm was observed for the
tert-butyl group of 3 which has added nucleophilically to the
electrophilic carbonyl group of 2. In the solid state structure of
3, the bulky amido group TMP acts as a bridge between the two
metals; this coordination mode must be retained in deuterated
benzene solution as evidenced by the inequivalence of the a-Me
groups of the TMP fragment in the 1H NMR spectrum (at 1.44 and
1.52 ppm). A comparison of the 13C NMR spectra of compounds
2 and 3 revealed large changes in the chemical shifts observed for
the distinct carbon atoms that have experienced the metalation or
Fig. 3 Molecular structures of 4 (a) and 6 (b) (present as a mixture in the
crystalline lattice in a relative ratio of 95 : 5) with selective atom labelling
and 40% probability ellipsoids. Hydrogen atoms (apart from in the OH
group) have been omitted for clarity.
100 | Dalton Trans., 2012, 41, 98–103
This journal is
The Royal Society of Chemistry 2012
©

View Article Online
leading to 4 after iodine interception. The close proximity between
t
the electrophilic C O group and the remaining Bu group on
the zincate must subsequently favour the 1,2-addition process to
form 3. Based on the previously structurally characterized 1,6-
addition products,19,20 I (Scheme 4) can be proposed as the second
organometallic intermediate of the reaction which, when treated
with I2 followed by an aqueous workup, is oxidised to 5.
The relatively modest yields obtained for 4 and 5 were somewhat
surprising considering that 1H NMR analysis of the reaction solu-
tion prior to the I2 quenching step showed no unreacted 2 present
in solution. Similar results were observed when the crude reaction
was treated with D2O (Scheme 5) which yielded 5 (1,6-addition
Fig. 4 Molecular structure of 5 with selective atom labelling and 40%
probability ellipsoids. Hydrogen atoms have been omitted for clarity.
product) and [PhC(OH)(tBu)(h -C5H3D)Fe(h -C5H5)] (7D) (zin-
cation, 1,2-addition product) in 27% and 32%, respectively, along
with the recovery of 41% of starting material 2. Previous studies
on the ring alkylation of benzophenone with tBuLi have revealed
that aqueous workups decompose the 1,6-addition intermediate
to regenerate benzophenone whilst if a strong oxidising agent such
as SOCl2 is used, it is possible to minimise this degradation route
and significantly increase the yield of tert-butylbenzophenone.37
A similar process could be taking place in the 1,6-alkylation of
2. In fact, supporting this hypothesis we found that when the
reaction mixture was quenched using radical oxidant TEMPO
[(2,2,6,6-tetramethylpiperidin-1-yl)oxyl]38 followed by an aqueous
work-up we could isolate 5 in an increased 41% yield, along with
5
5
full details). Disubstituted ferrocene 4 is the expected iodinated
species resulting from the electrophilic quenching of 3 with
I2, where the position previously filled by a Zn center in the
substituted pentadienyl ring in 3 is now occupied by an iodine
atom and the alkoxide group has been hydrolysed to a tertiary
alcohol (Fig. 3a). X-Ray crystallographic analysis revealed that a
5
mixture of compound 4 and the di-iodo analog [PhC(OH)(tBu)(h -
5
C5H3I)Fe(h -C5H4I)] (6) (Fig. 3b) in a respective ratio of 95 : 5%
was found in the crystal lattice. Initially the formation of 6 could be
attributed to a putative double zincation of 2, however considering
that the reaction when performed using D2O as an electrophile (see
below) does not show the formation of a related double deuterated
species and that the yield of 6 is extremely small, it seems more
plausible that 6 is the result of a side reaction of iodine (used in
excess) with compound 3. In this regard, selectivity problems using
I2 as a quenching agent for organometallic intermediates which can
lead to polysubstituted products have already been flagged up in
the literature.36
5
5
the 1,2-adduct [C6H5C(OH)tBu(h -C5H4)Fe(h -C5H5)] (7) (34%)
yield, and with the recovery of only 7% of unreacted 2 (Scheme 5).
Turning to compound 5 (Fig. 4) its formation must proceed
via a different organometallic intermediate to 3. Featuring a tert-
butyl substituent at the C3(para) position of the phenyl ring, 5
appears to be the oxidised product of an unusual 1,6-addition
t
of a Bu group from 1 to substrate 2 (Scheme 4). This unique
addition pattern has been previously reported for the reaction of
1 with other aromatic ketones,19 for which the relevant enolate
intermediates have been structurally characterized (Scheme 1,
ii). Contrasting with 2, when these substrates are examined no
products of aromatic metalation or 1,2-addition are observed.
This difference in reactivity can probably be explained in terms
of the enhanced acidity of the a-H’s on the (electron withdrawing
group)-substituted cyclopentadienyl ring, which must switch on a
competing reaction pathway promoting the alpha-zincation of 2
Scheme 5
Conclusions
By combining the trapping of a key organometallic intermediate
with subsequent electrophilic interceptions we have provided new
insights into the reactivity of sodium zincate 1 towards substituted
metallocene benzoylferrocene (2). Our study shows that at room
temperature two different reactivity pathways are available for
the bimetallic reagent: (i) remote 1,6-nucleophilic addition of a
tert-butyl group to the phenyl ring of 2 and (ii) simultaneous
alpha-deprotonation of the substituted cyclopentadienyl ring of
the metallocene and 1,2-addition of a tert-butyl anion to the elec-
trophilic carbonyl group of the ketone. The latter, involving two-
fold activation of the tert-butyl groups of bimetallic base 1 where
the two alkyl groups react strikingly differently (deprotonation
vs. alkylation) towards a substrate, is unprecedented in AMMZn
chemistry and it is in sharp contrast to the lack of reaction
Scheme 4
This journal is
The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 98–103 | 101
©

View Article Online
observed when 2 is treated with homometallic ZntBu2. NMR
analysis of the reaction mixture prior to electrophilic interception
suggests that the 1,6-addition product is the major product of
the reaction. Electrophilic interception of these species using I2
and D2O as quenching agents revealed that although the yield
of the deprotonated/1,2-addition product remains constant (29–
34%), the amounts of co-product resulting from the competing
1,6-addition reaction [which can only be isolated in its oxidised
parameters are given in the ESI† and full data has been deposited,
see CCDC reference numbers 838243–838246.
[(TMEDA)Na(l-TMP)Zn{OC(tBu)(Ph)(g5-C5H3)Fe(g5-
C5H5)}](3)
To a hexane solution of 1 (2 mmol scale, prepared as described
above) was added one molar equivalent of benzoylferrocene
(0.580 g, 2 mmol). The resulting deep red suspension was stirred for
2 h at room temperature, after which time the solvent was removed
in vacuo, and toluene (5 mL) added to give a dark red solution.
After 48 h in the freezer (-30 ◦C) a batch of orange, cubic crystals
form [tBu-C6H4CO(h -C5H4)Fe(h -C5H5)] (5)] seem to vary con-
siderably (from 24% to 41%) depending on the reaction conditions
employed. These variations can be due to a competing degradation
route taking place in the aqueous workup (previously reported for
5
5
t
the 1,6-addition of BuLi to benzophenone) which regenerates
1
of 3 were obtained (0.172 g, 12%). H NMR (400.13 MHz, 298
starting material 2. In our study we found that this process can be
minimised when the reaction is performed in the presence of the
radical oxidant TEMPO.
Overall we believe these findings highlight some of the complex-
ity of the organometallic species and the mechanisms involved in
the reactions of activated ferrocenes with alkali-metal zincates as
well as unveiling new reactivity patterns for these molecules which
are not available to any significant extent using more conventional
monometallic systems.
K, [D6]-benzene) d 8.19 (2H, doublet, CHortho), 7.38 (2H, triplet,
CHmeta), 7.26 (1H, triplet, CHpara), 4.71 (1H, broad singlet, C5H3),
4.65 (1H, broad singlet, C5H3), 4.34 (1H, broad singlet, C5H3),
3.85 (5H, singlet, C5H5), 1.94 (12H, singlet, CH3, TMEDA), 1.84
(2H, multiplet, g-CH2, TMP), 1.78 (4H, singlet, CH2, TMEDA),
1.53 (6H, singlet, a-CH3, TMP), 1.44 (6H, singlet, a-CH3, TMP),
1.40 (4H, multiplet, b-CH2, TMP), 1.07 (9H, singlet, C(CH3)3,
1
tBu). 13C{ H} NMR (100.62 MHz, 298 K, [D6]-benzene) d 154.5
(Cipso), 128.7 (Cortho), 126.0 (Cmeta), 125.9 (Cpara), 111.9 (Zn-Ca), 81.3
(C-O), 75.3 (OC-C5H3), 73.0 (C5H3), 70.9 (C5H3), 70.1 (C5H3),
68.0 (C5H5), 57.5 (CH2, TMEDA), 53.1 (a-TMP), 46.6 (CH3,
Experimental section
t
TMEDA), 41.2 (b-CH2, TMP), 40.6 (C(CH3)3, Bu), 36.8 and
General conditions
36.1 (a-CH3, TMP), 28.2 (C(CH3)3, tBu), 19.8 (g-CH2, TMP).
All reactions were performed under a protective argon atmo-
sphere using standard Schlenk techniques. Toluene and hexane,
purchased from Sigma Aldrich, were dried by heating to reflux
over sodium benzophenone ketyl and distilled under nitrogen
prior to use. NMR spectra were recorded on a Bruker DPX 400
MHz spectrometer, operating at 400.13 MHz for 1H, and 100.62
[PhC(OH)(tBu)(g5-C5H3I)Fe(g5-C5H5)] (4) and
[4-tBu-C6H4C(O)(g5-C5H4)Fe(g5-C5H5)] (5)
Benzoylferrocene (0.290 g, 1 mmol) was dissolved in toluene
(7 mL) and added via cannula to a second Schlenk tube containing
isolated crystals of 1 (0.460 g, 1 mmol, prepared as described
above). The resulting deep red solution was stirred for 2 h at room
temperature, after which time I2 solution (1 M in THF, 3 mL,
3 mmol) was added, and the reaction stirred for a further 4 h at
room temperature. The reaction was then quenched with saturated
Na2S2O3 solution (5 mL) and saturated NH4Cl solution (5 mL)
and then extracted with EtOAc (3 ¥ 15 mL). The combined organic
extracts were dried over MgSO4 and concentrated in vacuo. The
crude residue was purified by column chromatography (eluent:
hexane/diethyl ether, 1 : 0 to 9 : 1) affording 4 (0.1380 g, 29%) as
an orange solid and 5 (0.0845 g, 24%) as a red solid. NMR data
for 4: 1H NMR (400.13 MHz, 298 K, CDCl3) d 7.90 (2H, doublet,
CHortho), 7.42 (2H, triplet, CHmeta), 7.33 (1H, triplet, CHpara), 4.45
(2H, multiplet, C5H3), 4.30 (1H, triplet, C5H3), 3.74 (5H, singlet,
1
MHz for 13C{ H}. Sodium zincate 1 was prepared following the
previously published procedure.5
General crystallography
All data was collected at 123 K on Oxford-Diffraction CCD
˚
diffractometers using Mo-Ka radiation, l = 0.71073 A. All
refinements were to convergence on F2 and used all unique reflec-
tions and the program SHELXL-97.39‡ Selected crystallographic
‡ Crystal data for 3: C36H56FeN3NaOZn, Mr = 691.05, monoclinic, space
˚
group P21/c, a = 16.5928(8), b = 11.8192(4), c = 19.0005(8) A, b =
◦
3
111.772(5) , V = 3460.5(3) A , Z = 4, rc = 1.326 g cm-3, m = 1.157
˚
mm-1; Final refinement gave R = 0.0464 (F, 4235 obs. data only) and
Rw = 0.0771 (F2, 8165 unique data), GOF = 0.788, 395 refined parameters.
t
-3
˚
C5H5), 2.63 (1H, singlet, OH), 0.97 (9H, singlet, C(CH3)3, Bu).
Residual electron density max. and min. 0.818 and -0.479 e A . Crystal
1
13C{ H} NMR (100.62 MHz, 298 K, CDCl3) d 146.4 (Cipso), 127.2
data for cocrystal of 4 and 6: C21H22.95FeI1.05O, Mr = 480.44, monoclinic,
˚
space group P21/c, a = 9.6150(3), b = 11.7549(4), c = 17.2226(5) A, b =
(Cortho, Cmeta), 126.6 (Cpara), 89.9 (C–O), 81.1 (OC-CCp), 77.4 (C5H3),
71.7 (C5H5), 70.8 (C5H3), 69.2 (C5H3), 41.2 (C-I), 40.0 (C(CH3)3,
◦
3
-3
-1
˚
105.283(3) , V = 1877.72(10) A , Z = 4, rc = 1.699 g cm , m = 2.534 mm ;
Final refinement gave R = 0.0505 (F, 4244 obs. data only) and Rw = 0.1161
(F2, 5212 unique data), GOF = 1.129, 206 refined parameters. Residual
t
1
tBu), 27.0 (C(CH3)3, Bu). NMR data for 5: H NMR (400.13
MHz, 298 K, CDCl3) d 7.88 (2H, doublet, CHortho), 7.49 (2H,
doublet, CHmeta), 4.93 (2H, triplet, C5H4), 4.58 (2H, triplet, C5H4),
-3
˚
electron density max. and min. 1.336 and -0.621 e A . The ratio of 4
to 6 was measured by refining occupancies of separate C5H5 and C5H4I
fragments and setting their total occupancy to 1. This gave 5.03(8)% for the
di-iodo species. Crystal data for 5: C21H22FeO, Mr = 346.24, monoclinic,
4.23 (5H, singlet, C5H5), 1.38 (9H, singlet, C(CH3)3, tBu). 13C{ H}
1
˚
space gro◦up P21/n, a = 10.9164(6), b = 25.1685(13), c = 18.3340(11) A, b =
NMR (100.62 MHz, 298 K, CDCl3) d 198.7 (C-O), 155.1 (Cipso),
137.0 (Cpara), 128.2 (Cortho), 125.2 (Cmeta), 78.6 (C5H5), 72.3 (C5H4),
71.6 (C5H4), 70.2 (OC-CCp), 35.0 (C(CH3)3, tBu), 31.2 (C(CH3)3,
tBu).
3
-3
-1
˚
91.060(5) , V = 5036.4(5) A , Z = 12, rc = 1.370 g cm , m = 0.900 mm ;
Final refinement gave R = 0.0580 (F, 6409 obs. data only) and Rw = 0.1252
(F2, 10 967 unique data), GOF = 0.990, 631 refined parameters. Residual
-3
˚
electron density max. and min. 0.502 and -0.618 e A .
102 | Dalton Trans., 2012, 41, 98–103
This journal is
The Royal Society of Chemistry 2012
©

View Article Online
19 E. Hevia, G. W. Honeyman, A. R. Kennedy and R. E. Mulvey, J. Am.
Chem. Soc., 2005, 127, 13106.
Acknowledgements
20 J. J. Crawford, B. J. Fleming, A. R. Kennedy, J. Klett, C. T. O’Hara and
S. A. Orr, Chem. Commun., 2011, 47, 3772.
21 (a) A. Togni, Angew. Chem., Int. Ed. Engl., 1996, 35, 1475; (b) R. G.
Arrayas, J. Adrio and J. C. Carretero, Angew. Chem., Int. Ed., 2006, 45,
7674.
We thank the Royal Society (University Research Fellowship to
E. H.), and the EPSRC for their generous sponsorship of this
research.
22 (a) N. Long, Angew. Chem., Int. Ed. Engl., 1995, 34, 21; (b) Ferrocenes:
ˇ
Ligands, Materials and Biomolecules, ed. P. Steˇpnicˇka, Wiley, Chich-
Notes and references
ester, UK, 2008, pp. 279–641.
1 (a) T. Furuyama, M. Yonehara, S. Arimoto, M. Kobayashi, Y.
Matsumoto and M. Uchiyama, Chem.–Eur. J., 2008, 14, 10348; (b) Y.
Kondo, M. Fujinami, M. Uchiyama and T. Sakamoto, J. Chem. Soc.,
Perkin Trans. 1, 1997, 799; (c) M. Uchiyama, M. Koike, M. Kameda,
Y. Kondo and T. Sakamoto, J. Am. Chem. Soc., 1996, 118, 8733; (d) F.
Kneisel, M. Dochnahl and P. Knochel, Angew. Chem., Int. Ed., 2004,
43, 1017; (e) M. Uchiyama, T. Furuyama, M. Kobayashi, Y. Matsumoto
and K. Tanaka, J. Am. Chem. Soc., 2006, 128, 8404; (f) T. Harada, T.
Katsuhira and A. Oku, J. Org. Chem., 1992, 57, 5805.
2 (a) P. Knochel and P. Jones, in Organozinc Reagents: A Practical
Approach, ed. L. H. Harwood and C. J. Moody, Oxford University
Press, Oxford, 1999; (b) Y. Kondo, M. Shilai, M. Uchiyama and T.
Sakamoto, J. Am. Chem. Soc., 1999, 121, 3539; (c) K. Snegaroff,
S. Komagawa, F. Chevallier, P. C. Gros, S. Golhen, T. Roisnel, M.
Uchiyama and F. Mongin, Chem.–Eur. J., 2010, 16, 8191; (d) M. Mosrin
and P. Knochel, Org. Lett., 2009, 11, 1837.
23 D. R. van Staveren and N. Metzler-Nolte, Chem. Rev., 2004, 104, 5931.
24 First report on ferrocene lithiation: (a) R. A. Benkesser, D. Goggin and
G. Scholl, J. Am. Chem. Soc., 1954, 76, 4025; (b) F. Re´biere, O. Samuel
and H. B. Kaga, Tetrahedron Lett., 1990, 31, 3121; (c) R. Sanders and
U. T. Westerhoff, J. Organomet. Chem., 1996, 512, 219; (d) R. C. J.
Atkinson, V. C. Gibson and N. J. Long, Chem. Soc. Rev., 2004, 33, 313.
25 (a) W. Clegg, K. W. Henderson, A. R. Kennedy, R. E. Mulvey, C. T.
O’Hara, R. B. Rowlings and D. M. Tooke, Chem. Commun., 2001, 1049;
(b) P. C. Andrikopoulos, D. R. Armstrong, W. Clegg, C. J. Gilfillan, E.
Hevia, A. R. Kennedy, R. E. Mulvey, C. T. O’Hara, J. A. Parkinson
and D. M. Tooke, J. Am. Chem. Soc., 2004, 126, 11612; (c) A. H. Stoll,
P. Mayer and P. Knochel, Organometallics, 2007, 26, 6694.
26 (a) H. R. L. Barley, W. Clegg, S. H. Dale, E. Hevia, G. W. Honeyman,
A. R. Kennedy and R. E. Mulvey, Angew. Chem., Int. Ed., 2005, 44,
6018; (b) G. Dayaker, A. Sreeshailam, F. Chevallier, T. Roisnel, P. R.
Krishna and F. Mongin, Chem. Commun., 2010, 46, 2862.
3 (a) M. Uchiyama, S. Nakamura, T. Ohwada, M. Nakamura and E.
Nakamura, J. Am. Chem. Soc., 2004, 126, 10897; (b) M. Uchiyama, S.
Furumoto, M. Saito, Y. Kondo and T. Sakamoto, J. Am. Chem. Soc.,
1997, 119, 11425–11433.
4 (a) G. T. Achonduh, N. Hadei, C. Valente, S. Avola, C. J. O’Brien and
M. G. Organ, Chem. Commun., 2010, 46, 4109; (b) N. T. T. Chau, M.
Meyer, S. Komagawa, F. Chevallier, Y. Fort, M. Uchiyama, F. Mongin
and P. C. Gros, Chem.–Eur. J., 2010, 16, 12425; (c) Z. B. Dong, G.
Manolikakes, L. Shi, P. Knochel and H. Mayr, Chem.–Eur. J., 2010,
16, 248.
5 P. C. Andrikopoulos, D. R. Armstrong, H. R. L. Barley, W. Clegg, S. H.
Dale, E. Hevia, G. W. Honeyman, A. R. Kennedy and R. E. Mulvey,
J. Am. Chem. Soc., 2005, 127, 6184.
6 D. R. Armstrong, W. Clegg, S. H. Dale, D. V. Graham, E. Hevia, L.
M. Hogg, G. W. Honeyman, A. R. Kennedy and R. E. Mulvey, Chem.
Commun., 2007, 598.
7 D. R. Armstrong, J. Garcia-Alvarez, D. V. Graham, G. W. Honeyman,
E. Hevia and R. E. Mulvey, Chem.–Eur. J., 2009, 15, 3800.
8 (a) W. Clegg, S. H. Dale, E. Hevia, L. M. Hogg, G. W. Honeyman, R.
E. Mulvey, C. T. O’Hara and L. Russo, Angew. Chem., Int. Ed., 2008,
47, 731; (b) M. Uchiyama, Y. Matsumoto, S. Usui, Y. Hashimoto and
K. Morokuma, Angew. Chem., Int. Ed., 2007, 46, 926.
9 W. Clegg, S. H. Dale, R. W. Harrington, E. Hevia, G. W. Honeyman
and R. E. Mulvey, Angew. Chem., Int. Ed., 2006, 45, 2374.
10 W. Clegg, S. H. Dale, E. Hevia, L. M. Hogg, G. W. Honeyman,
R. E. Mulvey and C. T. O’Hara, Angew. Chem., Int. Ed., 2006, 45,
6548.
27 G. Dayaker, A. Sreeshailam, F. Chevallier, T. Roisnel, P. R. Krishna
and F. Mongin, Eur. J. Org. Chem., 2011, 3715.
28 (a) J. Garcia-Alvarez, A. R. Kennedy, J. Klett and R. E. Mulvey, Angew.
Chem., Int. Ed., 2007, 46, 1105; (b) V. L. Blair, L. M. Carella, W. Clegg,
J. Klett, R. E. Mulvey, E. Rentschler and L. Russo, Chem.–Eur. J., 2009,
15, 856.
29 R. Bomparola, R. P. Davies, T. Gray and A. J. P. White, Organometallics,
2009, 28, 4632.
30 An identical molecular structure to 3 was obtained when a second
batch of crystals was analysed by X-ray crystallography, which
contained a solvent molecule of crystallisation [(TMEDA)Na(m-
5
5
TMP)Zn{OC(tBu)(h -C5H3)Fe(h -C5H5)}·C7H8] (8) (see ESI†).
31 Although there are no examples of double activation of the tert-
butyl groups of 1, related lithium-zincate [(THF)Li(m-TMP)ZntBu2]
can exhibit polybasicity when reacted with two or three equivalents
of substituted aromatic molecules such as anisole or N,N-diisopropyl
benzamide, see ref. 9 and: (a) W. Clegg, S. H. Dale, A. M. Drummond,
E. Hevia, G. W. Honeyman and R. E. Mulvey, J. Am. Chem. Soc.,
2006, 128, 7434; (b) Y. Kondo, J. V. Morey, J. C. Morgan, H. Naka, D.
Nobuto, P. R. Raithby, M. Uchiyama and A. E. H. Wheatley, J. Am.
Chem. Soc., 2007, 129, 12734.
32 N. Seidel, K. Jacob, P. Zanello and M. Fontani, J. Organomet. Chem.,
2001, 620, 243.
33 Since C21 is bonded to four different substituents, it is a chiral centre,
however it must be pointed out that a racemic mixture of the two
enantiomers is obtained.
34 When the 1H NMR spectrum is recorded at a higher temperature
(343 K) a better defined splitting pattern can be observed for these
hydrogens, showing the following multiplicity: 4.70 ppm (doublet), 4.63
ppm (triplet) and 4.33 ppm (doublet).
11 L. Balloch, A. R. Kennedy, J. Klett, R. E. Mulvey and C. T. O’Hara,
Chem. Commun., 2010, 46, 2319.
12 L. Balloch, A. R. Kennedy, R. E. Mulvey, T. Rantanen, S. D. Robertson
and V. Snieckus, Organometallics, 2011, 30, 145.
13 J. Clayden, in Organolithiums: Selectivity for Synthesis, Pergamon,
Oxford, 2002, pp. 9–109.
14 D. R. Armstrong, W. Clegg, S. H. Dale, E. Hevia, L. M. Hogg, G. W.
Honeyman and R. E. Mulvey, Angew. Chem., Int. Ed., 2006, 45, 3775.
15 A. R. Lepley, W. A. Kahn, A. B. Giumanini and J. Giumanini, J. Org.
Chem., 1966, 31, 2047.
35 For a comparison of the chemical shifts in the 1H and 13C NMR spectra
of compounds 2 and 3 in C6D6 solutions see Table S2 in the ESI†.
36 (a) I. J. Blackmore, A. N. Boa, E. J. Murray, M. Dennis and S.
Woodward, Tetrahedron Lett., 1999, 40, 6671; (b) A. N. French, S.
Bissmire and T. Wirth, Chem. Soc. Rev., 2004, 33, 354.
37 (a) G. A. Olah, A. Wu and O. Farooq, Synthesis, 1991, 1179; (b) T. Holm
and I. Crossland, Acta Chem. Scand., 1971, 25, 59; (c) H. Yamataka,
N. Fujimura, Y. Kawafuji and T. Hanafusa, J. Am. Chem. Soc., 1987,
109, 4305.
38 (a) W. Peng, K. Ashida, T. Hirabaru, L. J. Ma and T. Inokuchi,
Tetrahedron, 2010, 66, 9714; (b) L. De Luca, G. Giacomelli, S. Masala
and A. Porcheddu, J. Org. Chem., 2003, 68, 4999. For reviews of
TEMPO oxidation see: (c) T. Vogler and A. Studer, Synthesis, 2008,
16 (a) R. E. Mulvey, Organometallics, 2006, 25, 1060; (b) R. E. Mulvey, F.
Mongin, M. Uchiyama and Y. Kondo, Angew. Chem., Int. Ed., 2007,
46, 3802; (c) R. E. Mulvey, Acc. Chem. Res., 2009, 42, 743.
17 (a) D. R. Armstrong, V. L. Blair, W. Clegg, S. H. Dale, J. Garcia-
Alvarez, G. W. Honeyman, E. Hevia, R. E. Mulvey and L. Russo, J.
Am. Chem. Soc., 2010, 132, 9480; (b) W. Clegg, B. Conway, E. Hevia,
M. D. McCall, L. Russo and R. E. Mulvey, J. Am. Chem. Soc., 2009,
131, 2375.
1979 (d) W. Adam, C. R. Saha-M
o¨ller and P. A. Ganeshpure, Chem.
Rev., 2001, 101, 3499.
18 D. Nobuto and M. Uchiyama, J. Org. Chem., 2008, 73, 1117–1120.
39 G. M. Sheldrick, Acta Crystallogr., 2008, A64, 112.
This journal is
The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 98–103 | 103
©