Magnesium hydride-promoted dearomatisation of pyridine

Article abstract of DOI:10.1039/c0dt01246g

Reaction of pyridine with well defined magnesium hydride species results in heterocycle dearomatisation by a hydride transfer which occurs with the formation of magnesium compounds containing 1,2- and 1,4-dihydropyridide anions as the respective kinetic a

Full text of DOI:10.1039/c0dt01246g

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Magnesium hydride-promoted dearomatisation of pyridine†
Michael S. Hill,* Dugald J. MacDougall and Mary F. Mahon
Received 16th September 2010, Accepted 4th October 2010
DOI: 10.1039/c0dt01246g
Reaction of pyridine with well defined magnesium hydride
species results in heterocycle dearomatisation by a hydride
transfer which occurs with the formation of magnesium
compounds containing 1,2- and 1,4-dihydropyridide anions
as the respective kinetic and thermodynamic products.
more wide-ranging exploration of reactivity inspired by the work
summarised in Scheme 1, we report herein our initial observations
of the behaviour of well defined magnesium alkyls and hydrides
with pyridine.
Although reaction of the b-diketiminato-supported n-butyl
magnesium complex [HC{(Me)CN(2,6-iPr2C6H3)}2MgnBu], I,9
with a single molar equivalent of pyridine on an NMR scale
in C6D6 produced a yellowing of the solution and a broad-
ening of the resonances in the 1H NMR spectrum attributed
to the methyl and methine resonances of the b-diketiminate
ligand, no alkylation or deprotonation of pyridine was apparent.
The origin of these observations was confirmed by a subse-
quent preparative-scale experiment, which allowed the isolation
and definitive identification of the colourless compound, 1, by
X-ray diffraction analysis after crystallisation from the toluene
reaction solvent.‡ The results of this analysis, shown in Fig. 1,
confirmed that compound 1 was simply a pyridine adduct of
the n-butylmagnesium starting material. Although a number of
mono- and dinuclear b-diketiminate magnesium alkyl species
have been previously characterised by crystallographic methods,10
compound 1 appears to be the first such example containing
an N-donor co-ligand. The structure is otherwise unremarkable,
however, and will not be discussed further here.
The ortho-metallation of N-heterocycles such as pyridine by
electrophilic d0 early transition metal complexes is one of the
archetypal reaction pathways of alkyl or hydride species.1 In
addition, albeit rather less commonly, heterocycle dearomatisation
by alkyl or hydride migration may occur, often with C–N
bond cleavage.2,3 While this latter reaction is also relevant to
hydrodenitrogenation,4 Diaconescu and co-workers have recently
shown that both heterocycle C–H activation and dearomatisation
may be combined into an elegant group 3-centred scheme which
results in C–C coupling reactivity between the two relevant
heterocycles (Scheme 1).5
Scheme 1
Our own research has sought to elaborate a more widespread
and generalised reaction chemistry for species derived from
similarly d0 M2+ alkaline earth dications (M = Mg, Ca, Sr and Ba).
Although a somewhat ‘lanthanide mimetic’ reactivity has emerged
from our studies of the group 2-catalysed hydroelementation
of C E multiple bonds (E = CR2, NR, O),6 and examples
of N-heterocycle dearomatisation are well precedented in the
chemistry of groups 1 and 13,7 examples of well-defined behaviour
comparable to the second reaction step depicted in Scheme 1 are
all but unexplored for group 2-based systems.8 As a prelude to a
Fig. 1 ORTEP representation (30% probability ellipsoids) of compound
1. H atoms and aryl iso-propyl carb◦on atoms are removed for clarity. Se-
˚
lected bond lengths (A) and angles ( ): N(1)–Mg(1) 2.062(2), N(2)–Mg(1)
2.057(2), N(3)–Mg(1) 2.174(3), C(30)–Mg(1) 2.130(3), N(2)–Mg(1)–N(1)
92.19(9), N(1)–Mg(1)–N(3) 101.70(10), N(2)–Mg(1)–N(3) 101.96(10).
Department of Chemistry, University of Bath, Claverton Down, Bath, BA2
7AY, UK. E-mail: msh27@bath.ac.uk; Fax: +44 (0)1225 386231; Tel: +44
(0)1225 383394
† Electronic supplementary information (ESI) available: Experimental
procedures, NMR spectra, crystallographic data for compounds 1–3, and
the complete citation for ref. 12. CCDC reference numbers 784396–784398.
For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c0dt01246g
The reaction of silanes with group 2 amides or alkyls has recently
been highlighted as an efficient route to well-defined magnesium
hydride species.11 Accordingly, addition of phenylsilane either to
a solution of compound 1 or to I in the presence of pyridine
produced a colour change from yellow to orange over the course
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of one hour. Monitoring of the 1H NMR spectra of these
reactions evidenced a depletion of the phenylsilane reagent and a
simultaneous formation of n-butylphenylsilane and di-n-
butylphenylsilane as indicated by the emergence of triplet reso-
nances centred at 4.48 and 4.43 ppm, respectively. Concurrent with
these processes, the b-diketiminate ligand methyl and iso-propyl
signals were observed to sharpen and evidenced the formation of
two sets of similar ligand environments. A signal consistent with
the formation of a long-lived magnesium hydride species (ca. 4.01
ppm) was not, however, observed at any point during the reaction.
Rather, a series of eight signals between 3.3 and 6.3 ppm were
observed, which were ascribed to a simultaneous dearomatisation
1
of the coordinated molecule of pyridine. Further analysis by H
COSY NMR spectroscopy allowed a complete assignment of these
signals to the presence of isomeric 1,2- and 1,4-dihydropyridide
fragments [1,2-isomer 6.20, 6.02, 5.03, 4.38 and 3.35 ppm: 1,4-
isomer 4.87, 4.09 and 3.56 ppm], while a further 1H EXSY NMR
experiment demonstrated that the two isomeric species were not
in chemical exchange. Heating a solution of the reaction mixtures
for 12 h at 60 ◦C resulted in complete conversion to the 1,4-
dihydropyridide isomer (Scheme 2).
Fig. 2 ORTEP representation (30% probability) of compound 3. H atoms
except for those attached to C(18) and aryl iso-propyl◦carbon atoms
˚
removed for clarity. Selected bond lengths (A) and angles ( ): Mg(1)–N(2)
1.993(2), Mg(1)–N(1) 2.0358(15), Mg(1)–N(3) 2.138(2), N(2)–C(16)
1.391(2), C(16)–C(17) 1.336(3), C(17)–C(18) 1.493(3), N(1)–Mg(1)–N(1)’
95.72(9), N(2)–Mg(1)–N(3) 103.65(10), N(1)–Mg(1)–N(2) 123.34(6),
N(1)–Mg(1)–N(3) 104.15(6). Symmetry transformations used to generate
equivalent atoms: x, y, -z + 1/2.
the b-diketiminate ligand, the 1,4-dihydropyridide anion and a fur-
ther equivalent of pyridine. The cyclic 1,4-dihydropyridide anion
is clearly defined and displays the expected variation in the C(16)–
˚
C(17)/C(16)¢–C(17)¢ [1.336(3) A] and C(17)–C(18)/C(17)¢–C(18)¢
˚
[1.493(3) A] consistent with the existence of double and single C–C
bonds around the C5N ring. The magnesium-bound N(2) centre is
also significantly pyramidalised [Rbond angles = 352.36◦] in compari-
son to the distorted trigonal planar N(3) atom [Rbond angles = 359.91◦]
contained within the neutral, datively coordinated molecule of
pyridine. The differing bonding modes (covalent/electrostatic
versus dative covalent) are also reflected in the respective Mg(1)–
˚
˚
N(2) [1.993(2) A] and Mg(1)–N(3) [2.138(2) A] distances linking
the Mg centre to the two heterocycles with the latter distance
˚
Scheme 2
effectively identical to the Mg–NDMAP distance [2.135(3) A] within
Jones’ recently reported and similarly four-coordinate magnesium
A preparative scale reaction performed in toluene after heating
to 60 ◦C allowed the isolation of compound 3 containing the 1,4-
dihydropyridide anion as a pale yellow crystalline compound. A
similar reaction performed without heating resulted in the co-
crystallisation of both compound 3 along with the analogous
compound, compound 2, containing the 1,2-dihydropyridide
anion. Although, in this latter case, the individual crystals of
compounds 2 and 3 were indistinguishable by the naked eye, the
compounds were not isostructural allowing the collection of a
unique X-ray crystallographic data set for compound 2 after a
trial and error selection process and comparison to the unit cell
parameters derived from analysis of a crystal selected from a pure
sample of compound 3.‡Compounds 2 and 3, which also contain a
further equivalent of coordinated neutral pyridine, crystallise with
these formulations, and as the sole dihydropyridide-containing
compounds, irrespective of the use of a single stoichiometric
amount of pyridine in the reaction.
hydride species, [HC{(tBu)CN(2,6-iPr2C6H3)}2Mg(H)(DMAP)]
(DMAP
=
4-dimethylaminopyridine) II, in which the
hydride maintains its integrity as
ligand.11c
a
terminally-bonded
The asymmetric unit of compound 2 consists of half of a
molecule, located on a mirror plane intrinsic to the space group
symmetry. Although a combination of symmetry within the
molecule, and possible disorder between the 2- and 6-positions
of the dihydropyridide unit, means that the dearomatised pyridine
could not be completely defined in terms of the expected alterna-
tion of double and single C–C bonds about the C5H6N ring, there
is ample crystallographic evidence for the dearomatisation. Larger
than normal anisotropic displacement parameters are recorded for
the carbon atoms (C16-C18) within the C5H6N unit as a result of
a combination of asymmetry about the ring and some disorder
(Fig. 3). The hydrogen atoms on the carbon centre bonded to the
˚
nitrogen atom (C16) were readily located, and refined at 0.98 A
The structure of compound 3 is illustrated in Fig. 2 while
selected bond length and angle data are provided in the figure cap-
tion. Compound 3 comprises a four-coordinate magnesium centre
in which pseudo-tetrahedral coordination geometry is provided by
from the parent atom. It was evident that one of these hydrogens
is present at full occupancy, and one at half-occupancy. The full
occupancy candidate (H16B) presents at an average position for an
aromatic CH, or one hydrogen of a CH2 pair. The half occupancy
11130 | Dalton Trans., 2010, 39, 11129–11131
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Notes and references
‡ X-Ray diffraction data for 1. C38H55MgN4, M = 579.16, monoclini◦c,
˚
˚
˚
P21/c, a = 12.7380(4) A, b = 12.9120(5) A, c = 22.1870(7) A, b = 90.308(2) ,
3
-3
˚
V = 3649.1(2) A , Z = 2, r = 1.052 g cm , R1 [I > 2s(I)] = 0.0801,
wR2 [I > 2s(I)] = 0.2098, R1 [all data] = 0.1312, wR2 [all data] = 0.2424,
measured reflections = 50 456, unique reflections = 8271, Rint = 0.1170. X-
Ray diffraction data for 2. C39H52MgN4, M = 601.16, monoclinic, P21/m,
3
˚
˚
˚
˚
a = 9.4213(2) A, b = 20.5902(6) A, c = 9.9732(2) A, V = 1819.79(8) A ,
b = 109.844(2)◦, Z = 2, r = 1.097 g cm-3, R1 [I > 2s(I)] = 0.0537, wR2
[I > 2s(I)] = 0.2192, R1 [all data] = 0.0806, wR2 [all data] = 0.1456,
measured reflections = 32 152, unique reflections = 4267, Rint = 0.0617. X-
Fig. 3 Numbering scheme employed in the refinement of the 1,2-dihy-
dropyridide anion within the X-ray structure of compound 2.
Ray diffraction data for 3. C39H52MgN4, M = 601.16, orthorhombic, Pbmn,
3
˚
˚
˚
˚
a = 9.6737(2) A, b = 18.2623(4) A, c = 20.6525(4) A, V = 3648.55(13) A ,
Z = 4, r = 1.094 g cm-3, R1 [I > 2s(I)] = 0.0476, wR2 [I > 2s(I)] = 0.1111, R1
[all data] = 0.0662, wR2 [all data] = 0.1268, measured reflections = 39 041,
unique reflections = 3303, Rint = 0.0918.
H16A is clearly only present half of the time i.e. only one half
of the pyridine ring has been reduced. H16A–H16B are closer to
each other than one would expect for a CH2 group. No additional
attempts were made to restrain the H ◊ ◊ ◊ H distance in this
moiety.
1 For a recent review, see: P. L. Diaconescu, Curr. Org. Chem., 2008, 12,
1388.
2 See, for example: (a) T. I. Gountchev and T. D. Tilley, Organometallics,
1999, 18, 2896; (b) E. Kirillov, C. W. Lehmann, A. Razavi and J.-F.
Carpentier, Eur. J. Inorg. Chem., 2004, 943.
The observation of both potential isomers during the early
stages of the reaction implies that the ultimate conversion to the
symmetrical 1,4-dihydropyridide-containing isomer, compound 3,
occurs under overall thermodynamic control. This observation
was borne out by calculations performed on model complexes of
compounds 2 and 3 in which the complete b-diketiminate ligand
was replaced by [HC{(H)CN(Me)}]- in the interests of computa-
tional expense. Despite this simplification, geometry optimisations
performed at the B3LYP density functional theory with LAN2DZ
pseudopotentials (and basis set) implemented in the Gaussian03
suite of programmes provided a good approximation of the local
bond lengths and angles about each Mg atom in comparison
to the crystallographically deduced structures.12 Consistent with
the experimentally observed transformation of compound 2 into
compound 3 the isomer containing the 1,4-dihydropyridide anion
was calculated to be some 3.48 kcal mol-1 lower in total energy than
its 1,2-dihydropyridide isomer, while both species are significantly
lower (1,2-isomer, 17.2 kcal mol-1; 1,4-isomer 20.7 kcal mol-1)
than the alternative pyridine-adducted magnesium hydride formu-
3 For example: J. A. Pool, B. L. Scott and J. L. Kiplinger, Chem.
Commun., 2005, 2591.
4 E. Furimsky and F. E. Massoth, Catal. Rev. Sci. Eng., 2005, 47, 297
and references therein.
5 (a) C. T. Carver and P. L. Diaconescu, J. Am. Chem. Soc., 2008, 130,
7558; (b) K. L. Miller, B. N. Williams, D. Benitez, C. T. Carver, K. R.
Ogilby, E. Tkatchouk, W. A. Goddard III and P. L. Diaconescu, J. Am.
Chem. Soc., 2010, 132, 342.
6 For a review, see: A. G. M. Barrett, M. R. Crimmin, M. S. Hill and P.
A. Procopiou, Proc. R. Soc. London, Ser. A, 2010, 466, 927.
7 (a) K. Ziegler and H. Zeiser, Chem. Ber., 1930, 63, 1847; (b) D.
R. Armstrong, R. E. Mulvey, D. Barr, R. Snaith and D. Reed, J.
Organomet. Chem., 1988, 350, 191; (c) W. Clegg, L. Dunbar, L.
Horsburgh and R. E. Mulvey, Angew. Chem., Int. Ed. Engl., 1996,
35, 753; (d) P. T. Lansbury and J. O. Peterson, J. Am. Chem. Soc., 1963,
85, 2236.
8 Addition reactions of Grignard and dialkylmagnesium reagents to
N-methoxycarbonyl pyridinium chlorides and N-silylpyridinium ions
have, however, been reported as methods for the selective synthesis
for N-methoxycarbonyl and N-silyl-1,4-dihydropyridines: (a) R. Yam-
aguchi, Y. Nakazono and M. Kawanisi, Tetrahedron Lett., 1983, 24,
1801; (b) J. Bra¨ckow and K. T. Wanner, Tetrahedron, 2005, 62, 2395.
9 A. P. Dove, V. C. Gibson, P. Hormnirum, E. L. Marshall, J. A. Segal,
A. J. P. White and D. J. Williams, Dalton Trans., 2003, 3088.
10 For example, see ref. 9 and (a) V. C. Gibson, J. A. Segal, A. J. P. White
and D. J. Williams, J. Am. Chem. Soc., 2000, 122, 7120; (b) P. J. Bailey,
R. A. Coxall, C. M. Dick, S. Fabre and S. Parsons, Organometallics,
2001, 20, 798.
11 (a) S. P. Green, C. Jones and A. Stasch, Angew. Chem., Int. Ed., 2008,
47, 9079; (b) M. Arrowsmith, M. S. Hill, D. J. MacDougall and M.
F. Mahon, Angew. Chem., Int. Ed., 2009, 48, 4013; (c) S. J. Bonyhady,
C. Jones, S. Nembenna, A. Stasch, A. J. Edwards and G. J. McIntyre,
Chem. Eur. J., 2010, 16, 938.
1
lation, [HC{(H)CN(Me)}Mg(H)-k -NC5H5]·C5H5N. We interpret
these results as a clear indication that compounds 2 and 3 may be
regarded as the respective kinetic and thermodynamic products
of the reaction of an initially formed magnesium hydride species
with pyridine. We are seeking to elaborate this reactivity in the
manner provided by the precedent illustrated in Scheme 1, to
incorporate further heterocyclic substrates and extend our studies
to the heavier and more electropositive members of the group 2
series of elements.
12 Gaussian 03, Revision C.02, M. J. Frisch et al. Gaussian, Inc.,
Wallingford CT, 2004.
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The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 11129–11131 | 11131
©