Dearomatization and C-H deprotonation with heavier group 2 alkyls: Does size matter?

Article abstract of DOI:10.1021/om100649z

We report that reaction of group 2 dialkyl compounds, [M{CH(SiMe ₃)₂}₂(THF)_n] [M = Mg, Ca, n = 2; M = Sr, Ba, n = 3] with a bis(imino)pyridine ligand ultimately results in deprotonation of both methyl groups attached to the imine carbon center. The resulting compounds are mononuclear for M = Mg or Ca, but assemble into cyclic hexameric arrays when M = Sr or Ba. In all four cases deprotonation appears to occur by a common pathway involving pyridine dearomatization and subsequent deprotonation of a single imine-bound methyl substituent. Monitoring of each reaction has revealed that the efficacy of the transformation, as well as the stability of each intermediate, is dependent upon the identity, ionic radius, and resultant charge density of the alkaline earth reagent employed.

Full text of DOI:10.1021/om100649z

Organometallics 2010, 29, 4203–4206 4203
DOI: 10.1021/om100649z
Dearomatization and C-H Deprotonation with Heavier Group 2 Alkyls:
Does Size Matter?
€
Merle Arrowsmith, Michael S. Hill,* and Gabriele Kociok-Kohn
Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, U.K.
Received July 5, 2010
Summary: We report that reaction of group 2 dialkyl com-
Maron have also calculated that the larger, early lanthanides
provide the lowest activation energies with a smooth pro-
gression toward decreasing activity across the 4f series.5
Although the relative facility toward related C-H reactivity
of the group 2 elements may be underpinned by a similar
interplay of charge density and polarization effects, consid-
eration of the lower intrinsic charge and increasing radii (six-
coordinate radii: Ca2þ, 114; Sr2þ, 132; Ba2þ, 149 pm)6 of the
electropositive alkaline earth series has led us to tentatively
suggest that any discerned reactivity series is as likely to
be marked by gross discontinuities as by smooth trends.7 We
have recently reported a series of heavier alkaline earth
dialkyl derivatives [M{CH(SiMe3)2}2(THF)n] [1: M = Ca,
n = 2; 2: M = Sr, n = 3; 3: M = Ba, n = 3],8 which have the
potential to operate as readily available reagents for further
explorations of the reaction chemistry of both homo- and
heteroleptic alkaline earth alkyl derivatives. Reactions of
these species with the β-diketiminate ligand precursor
[DippNC(Me)CHC(Me)NHDipp] (Dipp =2,6-di-isopro-
pylphenyl) did not provide straightforward access to the
desired heteroleptic alkyl compounds.9 Rather, the predo-
minant reaction product in all three cases was shown to be a
dimeric species in which a dianionic ligand had been formed
by deprotonation of the peripheral methyl substituents of the
monoanionic β-diketiminate. Although the insolubility of
the strontium and barium derivatives hindered a quantitative
analysis of this reactivity, the ease of formation and, by
inference, the ability to effect methyl deprotonation ap-
peared to vary in the order Ca < Sr < Ba. The methyl-
substituted bis(imino)pyridine, 4 (Scheme 1), has been ob-
served to possess a remarkable capacity either to function as a
passive ancillary ligand or to undergo anionization either via
hydrogen abstraction at one or both of the methyl groups
attached to the imine carbon atoms or through direct alkyl-
ation.10 In the latter case C-alkylation may occur not only
at the imine function but also at the C2 and, less commonly,
the C3, C4, and N1 positions of a dearomatized pyridine ring.
In this contribution we report that reactions of the heavier
group 2 dialkyls, 1-3, and the analogous magnesium species
pounds, [M{CH(SiMe3)2}2(THF)n] [M = Mg, Ca, n = 2; M =
Sr, Ba, n = 3] with a bis(imino)pyridine ligand ultimately
results in deprotonation of both methyl groups attached to the
imine carbon center. The resulting compounds are mononu-
clear for M = Mg or Ca, but assemble into cyclic hexameric
arrays when M = Sr or Ba. In all four cases deprotonation
appears to occur by a common pathway involving pyridine
dearomatization and subsequent deprotonation of a single
imine-bound methyl substituent. Monitoring of each reaction
has revealed that the efficacy of the transformation, as well as
the stability of each intermediate, is dependent upon the identity,
ionic radius, and resultant charge density of the alkaline earth
reagent employed.
The deprotonation and selective metalation of organic
substrates is one of the main uses of organometallic deriva-
tives of the s-block metals.1 While lithium and, to a lesser
extent, magnesium compounds are likely to maintain their
pre-eminence as the organic chemist’s reagents of choice,
there is a growing awareness that either greater selectivity or
deprotonating power may be achieved through the use of
reagents containing heavier elements from groups 1 and 2 of
the periodic table. While there have been rapid advances in
related applications of multicomponent and mixed metal
bases,2 our primary interest lies in the development of a more
widespread stoichiometric and catalytic reaction chemistry
based upon combinations of σ-bond metathesis and polar-
ized insertion pathways for the heavier members of group 2,
Ca, Sr, and Ba.3 Polarized metathesis reactivity without
adjustment to the metal oxidation state is especially preva-
lent for electrophilic d0 and d0fn complexes of the early
transition elements and lanthanides in their highest oxida-
tion states, and it is noteworthy that the relative rates of
reaction for degenerate methyl/methane exchange with
Cp*2M-CH3 complexes have been observed to decrease in
the order M = Y > Lu > Sc.4 In DFT studies Eisenstein and
*To whom correspondence should be addressed. E-mail: m.s.hill@
bath.ac.uk.
(1) (a) Schlosser, M., Organometallics in Synthesis-A Manual, 2nd
ed.; Wiley: New York, 2002. (b) Clayden, J. Organolithiums: Selectivity for
Synthesis; Elsevier: New York, 2002.
(2) (a) Mulvey, R. E.; Mongin, F; Uchiyama, M.; Kondo, Y. Angew.
Chem., Int. Ed. 2007, 46, 3802. (b) Snegaroff, K.; L’Helgoual’ch, J.-M.;
Bentabed-Ababsa, C.; Nguyen, T. T.; Chevallier, F.; Yonehara, M.; Uchiyama,
M.; Derdour, A.; Mongin, F. Chem.;Eur. J. 2009, 15, 10280. (c) Mulvey, R. E.
Acc. Chem. Res. 2009, 42, 743. (d) Mulvey, R. E. Organometallics 2006, 25,
1060.
(3) For general reviews, see: (a) Barrett, A. G. M.; Crimmin, M. R.;
Hill, M. S.; Procopiou, P. A. Proc. R. Soc., A 2010, 466, 927. (b) Harder, S.
Chem. Rev. 2010, 110, 3852.
(4) (a) Watson, P. L. J. Am. Chem. Soc. 1983, 105, 6491. (b) Watson,
P. L.; Parshall, G. W. Acc. Chem. Res. 1985, 18, 51.
(5) Barros, N.; Eisenstein, O.; Maron, L. Dalton Trans. 2006, 3052.
(6) Shannon, R. D. Acta Crystallogr. A 1976, 32, 751.
(7) Barrett, A. G. M.; Brinkmann, C.; Crimmin, M. R.; Hill, M. S.;
Hunt, P.; Procopiou, P. A. J. Am. Chem. Soc. 2009, 131, 12906.
(8) Barrett, A. G. M.; Crimmin, M. R.; Hill, M. S.; MacDougall,
D. J.; Mahon, M. F.; Procopiou, P. A. Chem.-Eur. J. 2008, 14, 11292.
(9) (a) Barrett, A. G. M.; Crimmin, M. R.; Hill, M. S.; MacDougall,
D. J.; Mahon, M. F.; Procopiou, P. A., Dalton Trans. 2009, 9715. The Ca
derivative had been reported previously. (b) Harder, S. Angew. Chem., Int.
Ed. 2003, 42, 3430.
(10) For reviews, see: (a) Knijnenburg, Q.; Gambarotta, S.; Budzelaar,
P. H. M. Dalton Trans. 2006, 5442. (b) Gibson, V. C.; Redshaw, C.; Solan,
G. A. Chem. Rev. 2007, 107, 1745.
r
2010 American Chemical Society
Published on Web 09/10/2010
pubs.acs.org/Organometallics

4204 Organometallics, Vol. 29, No. 19, 2010
Arrowsmith et al.
Scheme 1
observed as the only intermediate products throughout the
course of reaction. Although the C3 dearomatized com-
pounds 10, 12, and 14 were present in excess (C3:C4 ratios,
ca. 2:1-3:1) during the course of the respective reactions,
continued NMR monitoring indicated progressive con-
sumption of all intermediate species accompanied by a
gradual fading of the blue color of the solutions into green-
brown over several hours (Ca 36 h, Sr 2 h, Ba 8 h). At this
point the NMR spectra for all three reactions were reminis-
cent of those obtained during the synthesis of compound 7
and indicated a stoichiometric formation of calcium, stron-
tium, and barium complexes, 16, 17, and 18, containing an
identical pyridine-based ene-diamido ligand. An annotated
spectrum obtained from the reaction of 2 and 4, but per-
formed at a lower (ca. 0.04 M) concentration, is provided as
Figure 1 and illustrates the clean formation of each of the
intermediate species, 9, 12, and 13.
Compounds 16-18 were isolated as orange, bright red,
and dark red crystals, respectively, which were suitable for
X-ray diffraction analyses. The calcium compound 16 was
found to be mononuclear and isostructural to the Mg
derivative 7 and to contain a five-coordinate Ca center
comprising the tridentate ene-diamide ligand and two mole-
cules of THF. This structure is illustrated in Figure 2a.
Although compounds 17 and 18 were found to crystallize
with only a single molecule of coordinated THF, the coordi-
nation number of the strontium and barium centers is main-
tained through an additional intermolecular (methylene)
C(14)-to-group 2 element interaction such that the com-
pounds assemble into 6-fold symmetric cyclic arrays. The
hexameric unit of compound 17 is illustrated in Figure 2b,
while a similar depiction of compound 18 is provided in the
[Mg{CH(SiMe3)2}2(THF)2], compound 5, with 4 undergo
related reaction pathways involving pyridine dearomatization
at the less common C3 and C4 positions as a preface to com-
plete methyl deprotonation. The tractable nature of the reac-
tion products allows for an initial quantitative comparison of
the relative ability of alkyl group 2 species to engage in both
dearomatization and directed C-H activation reactivity.
Addition of the magnesium dialkyl, compound 5 (see
Figure S1 for an ORTEP representation resulting from
X-ray analysis of this compound), to a C6D6 solution of
[2,6-{(Dipp)NC(CH3)}2C5H3N], 4, caused an instantaneous
formation of an orange solution, which, from the simplicity
1
of its H NMR spectrum, was inferred to contain a C2-
symmetric bis(imino)pyridine adduct of the dialkyl species as
the only magnesium-containing compound. Monitoring of
this solution heated at 60 °C by 1H NMR spectroscopy for
24 h indicated conversion of this species to a single product,
compound 7, the result of deprotonation of both of the methyl
groups attached to the imine substituents of the bis(imino)-
pyridine unit. Compound 7 was isolated as a yellow crystalline
bis-THF adduct, and the structure implied from the solu-
tion-state NMR data was confirmed by an X-ray diffraction
analysis (Figure S2). In contrast to the analogous reactivity
observed with 1-3 (vide infra), the only identifiable inter-
mediate species during the course of this reaction was the
monodeprotonated species, compound 6, and the reac-
tion mixture remained red-brown in color throughout the
reaction.
The latter observation contrasts markedly with analogous
reactions performed with the heavier alkaline earth com-
pounds 1-3 (0.17-0.20 M concentrations). Combination of
the relevant metal dialkyl with 4 in C6D6 provided, in each
case, the instantaneous formation of a deep blue solution.
Analysis of the calcium- and strontium-based reactions by
1H NMR spectroscopy revealed the presence of singly
deprotonated species analogous to 6, compounds 8 and 9,
which appeared as 20-40% of the total bis(imino)pyridine-
derived species in solution at the first point of analysis
(Scheme 1). Further monitoring of both these reactions at
298 K indicated that 8 and 9 were consumed during the
course of the continued reactions over periods of 12 and 1.5 h,
respectively. The signals in the 1H NMR spectra attributed to
compounds 8 and 9 appeared in both reactions alongside two
further isomeric species, which were identified as the dear-
omatized metal alkyl compounds 10 and 11 (calcium) and 12
and 13 (strontium) formed by migration of a single alkyl
residue to either the C3 or C4 positions of the pyridine ring. In
contrast to these observations, the barium dialkyl 3 provided
no evidence for any singly deprotonated species. Rather, the
respective C3 and C4 dearomatized species, 14 and 15, were
Supporting Information. The intermolecular M CH2 con-
tacts between the alkaline earth centers and the methylene
3 3 3
unit of the adjacent molecule within compounds 17 and 18
0
0
˚
[Sr-C(14) 2.942(3); Ba-C(14) 3.142(8) A] are significantly
longer than either of the M CH2 contacts within the
3 3 3
recently reported products resulting from β-diketiminate
methyl deprotonation [Sr-CH2 2.759(3), 2.815(3); Ba-CH2
2.966(2), 3.001(2) A]. The group 2 center within each of the
9
˚
four complexes, 7 and 16 -18, adopts a distorted square-
pyramidal coordination geometry. Unlike other compounds
bearing the same ene-diamido ligand in which the pyridine
ring,10 the two ene-amide functions, and the metal center are
more or less coplanar, the ligand in all four alkaline earth
complexes is distorted from planarity, displaying an angle
ranging from 9.31° (18, Ba) to 22.52° (16, Ca) between the
least-squares plane of the pyridine backbone and that
formed by the ene-amide functionalities. Furthermore, the
˚
metal centers are situated at a distance of 0.645-1.220 A
above the pyridine plane, the distance increasing with the size
of the alkaline earth metal. The deprotonation of the two
former methyl groups is apparent from the values of the
˚
C-C distances [1.354(10) to 1.381(5) A], as expected for a
conjugated double bond, while the short C-N single-bond
distances [1.341(4) to 1.376(3) A] indicate some degree of
delocalization over the ene-amide system.
˚
Kinetic data relating to the relative abilities of heavier
group 2 organometallic compounds to participate in even ap-
parently simple deprotonation chemistries are, to date, non-
existent. We undertook, therefore, to place our understanding
of the course of the reactions to produce compounds 16, 17,
and 18 on a more quantitative foundation. The appearance
and decay of each intermediate identified in Scheme 1 as

Communication
Organometallics, Vol. 29, No. 19, 2010 4205
Figure 1. Annotated (2 h) spectrum ((a) -2 to 2.5 ppm region; (b) 3.5 to 8.5 region) obtained from the reaction of 2 and 4 (0.04 M)
illustrating the formation of 17 and each of the intermediate species. The numbers in the colored boxes refer to the assignments
indicated for 4 (yellow), 12 (green), 13 (blue), 9 (orange), and 17 (red).
well as the consumption of the ligand precursor 4 and the
production of the final doubly deprotonated products were
readily monitored and evidenced some rather complex metal-
dependent behavior. From experiments undertaken at 298 K
and with 0.10 M concentrations of the reagents, it was
apparent that although the barium dialkyl provided the most
rapid, effectively instantaneous, consumption of 4 (Figure 3),
this did not translate to the most facile formation of the final
doubly deprotonated product. In addition, the failure to
observe a barium-centered analogue of the singly deproto-
nated complexes, 6, 8, and 9, indicated that the dearomatized
intermediate species 14 and 15 possess enhanced stability for
this heaviest and most electropositive member of the group 2
series. This observation was further borne out by direct
monitoring of the total concentration of the two dearoma-
tized species for each metal (Figure 4). Although the appear-
ance and decline of each of these species could not be fitted to
any simple rate dependence, it may be inferred that the
subsequent proposed intermediate, a singly deprotonated
barium complex analogous to 8 and 9, is consumed imme-
diately to form the ultimate reaction product, compound 18.
Monitoring of the consumption of compound 4 in reactions
with compound 1 or 2 provided an apparent first-order
dependence upon both [4] and [1 or 2] such that -d[4]/dt =
k[4][1 or 2] and provided k = 0.0713 mol-1 min-1 for 1 and
k = 0.468 mol-1 min-1 for 2. From these data it is further

4206 Organometallics, Vol. 29, No. 19, 2010
Arrowsmith et al.
Figure 4. Total concentration of dearomatized intermediates
(i.e., 10 þ 11, 12 þ 13, 14 þ 15) observed during reactions of
ligand precursor 4 with 1 (green), 2 (red), and 3 (blue).
Figure 2. (a) ORTEP representation of compound 16. (b) Hex-
americ unit of compound 17. Thermal ellipsoids are set at 25%
probability, and H atoms, except for the methylene protons
within 16, and isopropyl methyl groups are removed for clarity.
Figure 5. Formation of products 16 (9), 17 (2), and 18 (().
reaction products, 16 to 18 (Figure 5), is then a more
complex interplay of the stability of the various dearoma-
tized and deprotonated intermediate species that varies in
the order Sr > Ba > Ca.
Although complex, and sharing common features, these
data illustrate that it is a likely fallacy to consider the
reactivity of the heavier members of group 2 as identical. It
is apparent that the activation barriers toward the individual
molecular steps encountered in the construction of a typical
catalytic cycle will also show a more nuanced dependence
upon the identity of the alkaline earth cation. In summary,
gross variation of M2þ cation size may be the most conspicuous
consequence of increasing atomic weight, but not the sole
consideration.
Acknowledgment. We thank the Engineering and Phys-
ical Sciences Research Council for a project studentship
(M.A., EP/E03117X/1).
Figure 3. Disappearance of ligand precursor 4 in reaction with
1 (green), 2 (red), and 3 (blue) (Ba . Sr > Ca).
apparent that the reactivity series of the metal dialkyl toward
an initial reaction with 4 vary in the order Ba > Sr > Ca,
which may be a simple reflection of the increasing M2þ
radii and access to the metal center on descending the
group. Conversely, the rate of formation of the final
Supporting Information Available: Experimental procedures,
compound characterization data, X-ray analyses, and kinetic
data. This material is available free of charge via the Internet at
http://pubs.acs.org.