Developing Lithium Chemistry of 1,2-Dihydropyridines: From Kinetic Intermediates to Isolable Characterized Compounds

Article abstract of DOI:10.1002/chem.201501880

Generally considered kinetic intermediates in addition reactions of alkyllithiums to pyridine1-lithio-2-alkyl-1,2-dihydropyridines have been rarely isolated or characterized. This study develops their "isolated" chemistry. By a unique stoichiometric (that is1:1alkyllithium/pyridine ratios) synthetic approach using tridentate donors we show it is possible to stabilize and hence crystallize monomeric complexes where alkyl is tert-butyl. Theoretical calculations probing the donor-free parent tert-butyl species reveal 12 energetically similar stereoisomers in two distinct cyclotrimeric (LiN)₃ conformations. NMR spectroscopy studies (including DOSY spectra) and thermal volatility analysis compare new sec-butyl and iso-butyl isomers showing the former is a hexane soluble efficient hydrolithiation agent converting benzophenone to lithium diphenylmethoxide. Emphasizing the criticalness of stoichiometryreaction of nBuLi/Me₆TREN with two equivalents of pyridine results in non-alkylated 1-lithio-1,4-dihydropyridine·Me₆TREN and 2-n-butylpyridineimplying mechanistically the kinetic 1,2-n-butyl intermediate hydrolithiates the second pyridine.

Full text of DOI:10.1002/chem.201501880

DOI: 10.1002/chem.201501880
Full Paper
&
Dihydropyridyl Complexes
Developing Lithium Chemistry of 1,2-Dihydropyridines:
From Kinetic Intermediates to Isolable Characterized Compounds
David R. Armstrong, Catriona M. M. Harris, Alan R. Kennedy, John J. Liggat, Ross McLellan,
Robert E. Mulvey,* Matthew D. T. Urquhart, and Stuart D. Robertson*[a]
Dedicated to Professor Manfred Scheer on the happy occasion of his 60th birthday
Abstract: Generally considered kinetic intermediates in addi-
tion reactions of alkyllithiums to pyridine, 1-lithio-2-alkyl-1,2-
dihydropyridines have been rarely isolated or characterized.
This study develops their “isolated” chemistry. By a unique
stoichiometric (that is, 1:1, alkyllithium/pyridine ratios) syn-
thetic approach using tridentate donors we show it is possi-
ble to stabilize and hence crystallize monomeric complexes
where alkyl is tert-butyl. Theoretical calculations probing the
donor-free parent tert-butyl species reveal 12 energetically
similar stereoisomers in two distinct cyclotrimeric (LiN)3 con-
formations. NMR spectroscopy studies (including DOSY spec-
tra) and thermal volatility analysis compare new sec-butyl
and iso-butyl isomers showing the former is a hexane solu-
ble efficient hydrolithiation agent converting benzophenone
to lithium diphenylmethoxide. Emphasizing the criticalness
of stoichiometry, reaction of nBuLi/Me6TREN with two equiv-
alents of pyridine results in non-alkylated 1-lithio-1,4-dihy-
dropyridine·Me6TREN and 2-n-butylpyridine, implying mecha-
nistically the kinetic 1,2-n-butyl intermediate hydrolithiates
the second pyridine.
Introduction
The dihydropyridyl unit[1] is prev-
alent in both biological[2] and
medicinal chemistry[3] as a trans-
fer hydrogenation (reduction)
agent. In the former case this
takes the form of naturally oc-
curring nicotinamide adenine di-
nucleotide (NADH) or its phos-
phorylated derivative NADPH
Figure 1. Structures of biochemically relevant dihydropyridyl containing compounds.
(Figure 1), which act as cofactors
for mediating redox processes
such as photosynthesis. In the
latter case, Hantzsch esters (Figure 1) can be utilized as calcium
antagonists to treat hypertension (high blood pressure). Dihy-
dropyridyl units have also been comprehensively studied in or-
ganic chemistry for asymmetric transfer hydrogenation purpos-
es[4] as well as for pyridine functionalization.[5]
reactive species has been identified as the 1,4-dihydropyridyl
isomer. Closely related to this work, the N-metallo dihydropyr-
idyls, with greater negative charge, would appear to be ideal
hydrometallation reagents operating under the same principles
with a rearomatization engine driving their reductive capability.
This logic has indeed been proved correct with for example
Lansbury’s reagent,[6] generated from lithium aluminum hy-
dride LiAlH4 and excess pyridine and formulated as the pyri-
dine-solvent-separated ion pair [Li(NC5H5)4]+[Al(1,4-NC5H6)4]À
(Figure 2, top),[7] which acts as a selective reducing agent for
aldehyde or ketone functionalities in the presence of carboxyl-
ic acid or ester groups. This 1-aluminato-1,4-dihydropyridyl
complex (along with other related metallo-1,4-dihydropyridyl
complexes including those of lithium,[8] magnesium,[9] zinc[9a,10]
and other aluminum complexes[11]) is generally accepted as
being the thermodynamically controlled isomer with the kinet-
The driving force behind the utility of dihydropyridyl sys-
tems is the rearomatization of the ring to give an aromatic pyr-
idine derivative. In both of the cases depicted in Figure 1 the
[a] Dr. D. R. Armstrong, C. M. M. Harris, Dr. A. R. Kennedy, Dr. J. J. Liggat,
Dr. R. McLellan, Prof. R. E. Mulvey, M. D. T. Urquhart, Dr. S. D. Robertson
WestCHEM, Department of Pure and Applied Chemistry
University of Strathclyde, Glasgow, G1 1XL (UK)
E-mail: r.e.mulvey@strath.ac.uk
stuart.d.robertson@strath.ac.uk
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201501880.
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ic intermediate being a 1,2-dihydropyridyl isomer, leaving only
limited synthetic access to the 1,2-isomer.[12] 1-Metallo-1,2-dihy-
dropyridines have been implicated as the active intermediates
in the metal catalyzed 1,2-hydroboration of pyridine,[13] while
the presence of a metal salt such as a zinc or magnesium diha-
lide is known to activate the reduction of unactivated ketones
and aldehydes by 1-methyl-1,4-dihydropyridines.[14]
commercially available polydentate donors for similar mono-
mer stabilization and also synthetically safer alkyllithium re-
agents in the pursuit of alternative soluble sources of lithium
hydride. Their solubility, thermal robustness and utility as hy-
drolithiation reagents have been appraised. The importance of
utilizing stoichiometric pyridine in the pursuit of a 1,2-dihydro-
pyridyl complex is also emphasized by our findings. All com-
plexes have been compared in solution by multinuclear NMR
spectroscopy and in the solid state by X-ray crystallography
where possible, while a theoretical study of the trimeric com-
plex 1t has also been carried out.
Results and Discussion
Donor stabilized monomers of 1-lithio-2-tert-butyl-1,2-dihy-
dropyridine
Noting the incomplete h3 coordination of tetradentate
Me6TREN to lithium in 1t·Me6TREN, we began by studying
more readily available tridentate ligands in its place for oligo-
mer to monomer deaggregation and stabilization. Although
Me6TREN has a proven record for stabilizing sensitive mono-
mers,[24] it is time-consuming to prepare and expensive to pur-
chase commercially (£111 mL),[25] meaning that a commercially
available, cheaper alternative would be more practical and
economical. To explore this possibility experimentally, equimo-
lar amounts of commercially available PMDETA (N,N,N’,N’’,N’’-
pentamethyldiethylenetriamine, 24 pence per mL)[25] and
Me4AEE (bis-[2-(N,N-dimethylamino)ethyl]ether, 23 pence per
mL)[25] were introduced to a yellow hexane solution of 1t and
cooled in a freezer to afford crystalline complexes identified
by X-ray crystallographic analyses as monomeric 2-
tBuC5H5NLi·PMDETA (1t·PMDETA) and 2-tBuC5H5NLi·Me4AEE
(1t·Me4AEE), respectively (Figure 3). Only the former crystal
structure determination was of sufficient quality to discuss
bond parameters although the latter unambiguously confirms
the molecular connectivity and oligomerization state. In each
case the structure is mononuclear, with the tBu group and one
donor atom lying below the plane of the pyridyl ring and the
other two donor atoms lying above to minimize steric repul-
sion (Figure 3, right-hand side).
Figure 2. Molecular structure of Lansbury’s reagent and general synthetic
protocol for preparation of 1-lithio-2-butyl-1,2-dihydropyridines.
The addition of metalÀcarbon bonds to pyridines gives
either the 1,2- or 1,4-addition product (e.g., organoanion=
allyl, M=K;[15] K/Zn;[15] Ca;[16] Al[17]). Steric blocking at the 2 and
6 positions of the pyridine ring for example with imino sub-
stituents, does not necessarily promote 1,4 addition.[18] A ring
substituent may be susceptible to deprotonative attack if it
contains hydrogen atoms which are sufficiently inductively
acidified by the pyridyl ring, for example a methyl group, as in
picoline.[16,19]
Recently, we revisited the well known 1,2-nucleophilic addi-
tion reaction of alkyllithium reagents to pyridine,[20] albeit by
employing a stoichiometric volume of pyridine rather than the
typical excess (Figure 2, bottom).[21] This new approach allowed
us to isolate and characterize some pure 1-lithio-2-alkyl-1,2-di-
hydropyridine (2-nBuC5H5NLi, 1, Figure 2, bottom) complexes
(that is suspected kinetic intermediates), normally utilized in
situ for the purpose of pyridine functionalization, which some-
what surprisingly were thermally robust and in the case of the
tert-butyl example 2-tBuC5H5NLi (1t) was hexane soluble. This
solubility, which was attributed to the steric effect of the tert-
butyl arm alpha to the NÀLi bond and its consequent molecu-
lar constitution since in contrast the n-butyl isomer 2-
nBuC5H5NLi (1n) is a hexane-insoluble polymer, makes it an ex-
cellent LiH surrogate complex, as exemplified by its hydroli-
thiation of benzophenone.[22] Practical soluble sources of
alkali–metal hydrides are coveted with only a select few exam-
ples reported.[23] Furthermore, it was possible to characterize
this 1,2-dihydropyridyl complex crystallographically as a mono-
mer, presumably a more reactive form than an aggregated
type, by coordinatively saturating the lithium with a polyden-
tate neutral donor in 2-tBuC5H5NLi·Me6TREN, 1t·Me6TREN. We
have now extended this work here to look at both cheaper,
Comparison of the pertinent bond parameters presented in
Table 1 confirms that the bonding between the polydentate
donor and lithium-dihydropyridyl moiety is very similar in each
case and that as with Me6TREN, the three N donor atoms of
PMDETA are sufficient for stabilization of the reactive mono-
mer. In particular, the conjugated double bond system is evi-
dent by the alternating short and long bonds in the C1ÀC2À
C3ÀC4ÀC5 unit [1.378(2)/1.424(2)/1.341(2)/1.510(2) Š] while C5
is again clearly sp3 hybridized with a distorted tetrahedral coor-
dination sphere, lying 0.387(1) Š outside of the mean plane of
the C1=C2ÀC3=C4 unit.
1
The H and 13C NMR spectra of 1t·PMDETA in C6D12 solution
closely resemble those of 1t·Me6TREN with all corresponding
resonances appearing within 0.1 ppm (1H) or 1 ppm (13C,
Table 2), which may be expected given the close similarities
between their molecular structures. The 7Li resonances and
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Next we turned to the
common and inexpensive bi-
functional donor N,N,N’,N’-tetra-
methylethylenediamine (TMEDA,
11 pence per mL),[25] which when
added to 1t in hexane and
cooled, afforded
a non-X-ray
quality crystalline product [2-
tBuC5H5NLi·TMEDA]2.
1H and 13C NMR analysis of
1t·TMEDA in C6D12 solution un-
equivocally confirmed the regio-
selective 1,2 alkyllithium addition
to pyridine and that the result-
ing dihydropyridyl/TMEDA ratio
was 1:1. The 1H NMR spectro-
scopic resonances of the ring hy-
drogen atoms appeared at
values intermediate between
those of monomeric, N-solvated
complexes 1t·Me6TREN and
1t·PMDETA and of unsolvated
trimeric complex 1t (for example
H5 resonates at 4.58 ppm in
1t·TMEDA, c.f. 4.07 in 1t·PMDE-
TA and 4.92 in 1t; see Table 2
for full details), perhaps sug-
gesting an intermediate aggre-
gation scenario (that is, dimeric
as postulated in Figure 4:
Figure 3. Molecular structure of 2-tBuC5H5NLi·PMDETA (1t·PMDETA, top) and 2-tBuC5H5NLi·Me4AEE (1t·Me4AEE,
bottom). Ellipsoids are displayed at 50% probability and all hydrogen atoms except that on the saturated C5 of
the dihydropyridyl ring are omitted for clarity.
their half height line widths are virtually identical at 0.81
(5.94 Hz) and 0.82 ppm (6.09 Hz). On moving to 1t·Me4AEE,
there is a more pronounced shielding of the H2/C2 resonances
(3.46/66.9 ppm; c.f. 3.54/69.5 and 3.62/69.0 ppm for PMDETA
and Me6TREN solvates, respectively) and also a deshielding of
the H3/C3 (4.18/97.2, c.f. 3.95/95.2; 4.03/95.7) and H5/C5 reso-
nances (4.36/91.6, c.f. 4.07/87.4; 4.09/88.2) with respect to the
N”3 donor solvated derivatives, most likely as a consequence
of changing one of the Lewis donating atoms to more electro-
negative oxygen which will in turn subtly alter the electronics
of the dihydropyridyl ring. Likewise, the 7Li resonance is notice-
ably shifted to 0.34 ppm (c.f. 1t·Me6TREN, 0.81 ppm).
a common bonding scenario seen previously in TMEDA solvat-
ed lithium amides,[26] including those formed through the
alpha metalation of functionalized pyridines[27]) although this
could also be due to the fewer number of Lewis basic nitrogen
atoms solvating the lithium atom. Cooling of a [D14]hexane so-
lution of 1t·TMEDA to À708C resulted in a broadening of the
TMEDA resonances but no splitting of them, meaning we were
unable to infer whether the dimer adopts a cisoid or transoid
conformation with respect to the two tBu groups (that is C2v or
C2h symmetry) in the manner described previously by Harder.[28]
In the absence of a solid-state structure for 1t·TMEDA, we
turned to a 1H DOSY NMR spectroscopy study,[29] which has
Table 1. Selected bond lengths [Š] and angles [o] for complexes
1t·PMDETA and 1t·Me6TREN.[21]
1t·PMDETA 1t·Me6TREN
1t·PMDETA 1t·Me6TREN
Li1ÀN1 1.976(2)
1.971(2)
2.137(2)
2.197(3)
2.178(3)
1.336(2)
1.378(2)
1.424(2)
1.341(2)
1.510(2)
1.479(2)
N1-Li1-N2 122.4(1)
120.6(1)
125.4(1)
114.9(1)
84.9(1)
117.8(1)
85.0(1)
Li1ÀN2 2.153(2)
Li1ÀN3 2.180(2)
Li1ÀN4 2.194(3)
N1ÀC1 1.332(2)
C1ÀC2 1.379(2)
C2ÀC3 1.421(2)
C3ÀC4 1.345(2)
C4ÀC5 1.516(2)
C5ÀN1 1.483(2)
N1-Li1-N3 123.4(1)
N1-Li1-N4 115.1(1)
N2-Li1-N3 84.6(1)
N2-Li1-N4 116.7(1)
N3-Li1-N4 85.2(1)
Figure 4. Proposed molecular structure of complex [2-tBuC5H5NLi·TMEDA]2,
1t·TMEDA.
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Theoretical calculations on
oligomeric 2-tBuC5H5NLi
Table 2. Comparison of 1H, 13C and 7Li NMR spectroscopic data for solvated complexes of 1t in C6D12 solution, of
unsolvated complexes 1t and 1s in C6D12 solution, and of complexes 1n and 1i in [D8]THF solution.
Having postulated that un-
solvated complex 1t is a cy-
clotrimer, we turned to DFT
calculations using the B3LYP
density functional and 6-
311(d, p) basis set, to probe
if such oligomerization is
reasonable. Such a motif is
well-documented in struc-
tural lithium amide chemis-
try,[34] including the syntheti-
1t·Me6TREN[21] 1t·PMDETA 1t·Me4AEE 1t·TMEDA 1t[21]
1s
1n[21]
1i
H2/C2
H3/C3
H4/C4
H5/C5
H6/C6
quaternary
C
3.62/69.0
4.03/95.7
5.88/128.7
4.09/88.2
6.53/151.1
42.1
3.54/69.5
3.95/95.2
3.46/66.9
4.18/97.2
3.30/66.2
4.07/94.4
3.12/66.1
4.37/95.1
3.10/60.6 3.54/57.6 3.63/53.3
4.40/95.1 4.08/96.7 3.97/95.1
5.85/128.8 5.92/128.2 6.04/127.0 6.12/127.9 6.04/125.7 5.72/126.4 5.71/126.5
4.07/87.4 4.36/91.6 4.58/93.8 4.92/95.1 5.08/96.6 4.29/90.0 4.25/89.2
6.56/150.8 6.62/151.0 6.71/151.3 6.85/150.0 6.73/147.7 6.55/150.0 6.54/150.0
41.1
40.9
41.6
39.3
–
–
–
tBu (H/C)
Li
0.86/25.4
0.81
0.87/25.7
0.82
0.84/25.7
0.34
0.82/26.0
À1.67
0.83/25.6
À1.79
–
–
2.17
–
0.29
À1.97
cally
important
utility
amides[35] LiHMDS[36] and
been used effectively in organometallic chemistry for solution
state molecular weight determination,[30] again in C6D12, to esti-
mate its aggregation state (n) in solution of [2-
tBuC5H5NLi·TMEDA]n, the results of which suggested an esti-
mated molecular weight of 420 at 0.2 molLÀ1 (refer to the Sup-
porting Information for details). This value lies intermediate be-
tween the calculated molecular weights of a monomer (n=1;
259) and dimer (n=2; 518). While considerably removed from
either value, this result is possibly indicative of a dimer in solu-
tion as it has previously been noted[31] that coordinated Lewis
donors can undergo a rapid coordination/de-coordination
event [Eq. (1)] which can be seen on the DOSY NMR timescale,
resulting in an estimated molecular weight value intermediate
between the solvated (518) and unsolvated (286) aggregate.
Typically, further evidence for this is an estimated molecular
weight for the coordinating Lewis donor lower than that of
the complex but higher than that of the free Lewis donor
itself. In this example we note the estimated molecular weight
for TMEDA as calculated using the resonances at 2.25 and
2.34 ppm is 169 (TMEDA itself has a significantly lower molecu-
lar weight of 116):
LiTMP.[37] Because of the tetrahedral nature of the nitrogen
atoms we modeled two distinct ring types, namely those with
the tBu groups on the same side of the ring (type A, Figure 5a)
or those with two on one side and one on the other (type B,
Figure 5a). The calculations revealed that the dihydropyridyl
rings did not lie perfectly perpendicular to the Li3N3 plane but
rather tilted towards one of the neighboring lithium atoms
due to a slight interaction of the p electron density with the
Lewis acidic lithium neighbor. This resulted in a shorter (s-
bonded) neighbor and a longer (p-bonded) neighbor (illustrat-
ed through single and dashed lines, respectively, in Figure 5b)
giving axial chirality and meaning that the S,S,S system
(entry 1) is not the same as the R,R,R system (entry 4) as might
have been thought originally. Table 3 summarizes the findings
of this study.
We considered a second hypothesis for this DOSY result,
namely that a complex of formula [2-tBuC5H5NLi]2·TMEDA is
present in solution, that is an asymmetric structure in which
only one of the lithium cations is solvated by TMEDA (such
a complex would have a molecular weight of 402, much closer
to the experimentally determined MWDOSY, <5% error). Asym-
metrically monosolvated dinuclear alkali–metal amides have
been crystallographically characterized previously, for example
the THF-solvated sodium 1,1,1,3,3,3-hexamethyldisilazide[32] or
the TMEDA-solvated heterometallic lithium/sodium 2,2,6,6-tet-
ramethylpiperidide.[33] However, we consider this reduced
solvation to be unlikely in this instance since the tBuC5H5N/
TMEDA ratio is unity as determined by integration of the
1H NMR spectrum.
Figure 5. a) Possible variable structural conformations for cyclotrimeric 1-
lithio-2-tert-butyl-1,2-dihydropyridine complexes (C2 atoms also bear a hydro-
gen atom which has been omitted for clarity); b) tilting movement of the
NC5 dihydropyridyl ring towards one of the adjacent lithium atoms resulting
in a stereogenic nitrogen and a shorter (s) and longer (p) Li-dihydropyridyl
interaction (tBu groups and H atoms have been omitted for clarity); c) cyclic
structure with butyl groups included to emphasize difference between R,R,R
and S,S,S enantiomers due to axial chirality.
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quantitative and that therefore any pre-prepared solutions
could be used in situ with confidence in their molarity for sub-
sequent stoichiometric reactions. The filtered product ap-
peared to start degrading on the filter stick upon prolonged
application of dynamic vacuum, although if collected in an
inert atmosphere after only a short period of vacuum applica-
tion then the product appeared to have a longer lifespan.
Soluble in C6D12 after a few seconds of gentle heating of the
Table 3. Calculated energies of different possible configuration sets of
complex 1t.
Entry
Model
C2
C2’
C2’’
Absolute energy
[kcalmolÀ1
Relative energy
[kcalmolÀ1
]
]
1
2
3
4
5
6
7
8
A
A
A
A
B
B
B
B
B
B
B
B
S
R
R
R
S
S
R
R
S
S
R
R
S
S
R
R
S
S
S
S
R
R
R
R
S
S
S
R
S
R
S
R
S
R
S
R
À1240.806479
À1240.804562
À1240.801927
À1240.798594
À1240.804711
À1240.806342
À1240.801909
À1240.804633
À1240.802243
À1240.804634
À1240.798526
À1240.802058
0.000
+1.203
+2.856
+4.948
+1.109
+0.086
+2.868
+1.158
+2.658
+1.158
+4.991
+2.774
1
mixture, complex 1s displayed H and 13C NMR spectra consis-
tent with 1,2 addition of the alkyllithium to pyridine, specifical-
ly via shielding of the five pyridyl resonances consistent with
loss of both aromaticity and symmetry (Table 2). However, the
presence of other small resonances indicated that this was not
the only species present in solution, specifically four extra reso-
nances were evident in the aromatic region of the spectrum
indicative of aromaticity and more specifically a 2-substituted
pyridine.
9
10
11
12
The study showed that the approximately C3 symmetric
structure (entry 1 in Table 3, for full structural parameters see
the Supporting Information) was the lowest energy conforma-
tion. Crucially, however, it showed that all twelve modeled
structures came within 5 kcalmolÀ1 of each other and indeed
nine of the remaining eleven were less than 3 kcalmolÀ1
higher in energy than the energy minimum (entry 1). This
narrow range of energies for the different conformations sug-
gests the possibility that multiple conformations might be
present in a sample and can potentially also explain why
single crystals of the trimeric complex 1t (or indeed 2-
sBuC5H5NLi, 1s, vide infra) cannot be obtained.
The deterioration issue under vacuum coupled with this
NMR evidence hinted that LiH was being extruded from com-
plex 1s under only mild (ambient) conditions and that 1s is
therefore potentially more reactive than its tBu isomer 1t,
which, in contrast, is thermally robust in C6D12 solution. This
conversion from the 1,2-dihydropyridyl complex to a substitut-
ed pyridine was monitored with 1H NMR spectroscopy over
time (see Figure 6a for full details) which confirmed that com-
plex 1s converts cleanly to 2-s-butylpyridine in cyclohexane at
558C in less than a day.
To study the conversion of 1s to LiH and 2-s-butylpyridine
1
further we repeated the H NMR spectroscopy study over time
at a constant temperature (218C) in the presence of the inert
standard hexamethylbenzene to allow accurate concentration
determination at each interval. After almost two weeks the
conversion was virtually complete. A plot of 1s and 2-s-butyl-
pyridine concentration versus time (Figure 6b) showed that
the conversion appears to follow two distinct phases. The first,
which occurs over a time period of approximately two days,
behaves according to zero order kinetics. The data following
this are then consistent with a first order process. This can per-
haps be attributed to the preparation of Lewis donor sec-butyl-
pyridine as part of the conversion process which will be avail-
able to solvate the lithium center of 1s, reducing its oligomeri-
zation to first dimeric (similar to complex 1t·TMEDA) and then
to monomeric (similar to complex 1t·PMDETA) as its relative
concentration increases.
Searching for an alternative hexane soluble 1-lithio-2-alkyl-
1,2-dihydropyridine
In order to minimize the usage of highly pyrophoric tert-butyl-
lithium in the laboratory, our next aim was to ascertain wheth-
er an equally reactive congener of 1t could be prepared using
an alternative but less pyrophoric alkyllithium reagent.[38] Given
that the n-butyl adduct 1n is hexane insoluble (and presuma-
bly polymeric) we immediately ruled out other straight chain
alkyl groups such as those from commercially available methyl-
or ethyllithium. The good solubility of complex 1t was attribut-
ed to the steric effects of the tert-butyl group inhibiting poly-
merization and so we logically considered the branched i- and
sec-butyl isomers. Like the n-butyl derivative, the iso-butyl
complex 2-iBuC5H5NLi (1i) precipitated from solution almost
immediately, even under dilute conditions, implying that
To ascertain the aggregation state of 1s in solution, we
again turned to 1H DOSY NMR spectroscopy. Unfortunately,
due to the conversion of 1s to 2-s-butylpyridine it was impos-
sible to quantify the estimated molecular weight since the res-
onances of the developing aromatic species coincided with
those of the aromatic standards 1-phenylnaphthalene (PhN)
and 1,2,3,4-tetraphenylnaphthalene (TPhN) and thus interfered
with their integration, which is necessary for the calculation of
diffusion coefficients. However, qualitative perusal of the re-
sulting spectrum (Figure 7) certainly supports the suggestion
that 1s is trimeric in solution since its resonances appear in
line with those of TPhN, which has a molecular weight of
432.55 (the molecular weight of a trimer would be 429.47).
1
a polymeric complex akin to 1n was being produced. H and
13C NMR spectroscopy in [D8]THF solution confirmed this prod-
uct to be the desired one, with the chemical shifts indicating
loss of aromaticity and the presence of five distinct ring reso-
nances indicating loss of symmetry and thus 1,2 addition of
the alkyllithium reagent. Moving to sec-butyllithium, the result-
ing yellow product 1s remained in solution for a prolonged
period of time, with a yellow microcrystalline product precipi-
tating upon cooling to À308C. Although the recrystallized ma-
terial represented a fairly moderate yield of 44%, 1H NMR inter-
rogation of the filtrate suggested the reaction was virtually
Chem. Eur. J. 2015, 21, 14410 – 14420
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mately 608C) than for 1n or 1t (both approximately 1008C)
with a maximum pressure seen just below 110 8C. In compari-
son, 1i did not start to liberate volatiles until 708C and this lib-
eration was not complete until almost 1308C. In each case
there was no sign of non-condensable volatile products. The
condensable products were identified as the appropriate 2-bu-
1
tylpyridine by H and 13C NMR spectroscopy and their IR spec-
tra were obtained (see the Supporting Information).
1
Figure 6. Top: section of H NMR spectra over time of a 1s sample in C6D12
solution showing loss of five dihydropyridyl (non-aromatic) resonances and
concomitant growth of four 2-substituted pyridyl (aromatic) resonances.
Bottom: plot of concentration of 1s and 2-s-butylpyridine as a function of
time, carried out at 218C.
Figure 8. Thermal volatility analysis thermograms for 1s (top) and 1i
(bottom). The solid line represents total volatile products, and the dashed
line non-condensable volatile products.
With a hexane soluble complex in hand, we next studied its
ability to operate as a lithium hydride transfer reagent. Mirror-
ing our recent studies of 1-lithio-2-tert-butyl-1,2-dihydropyri-
dine 1t for consistency and comparison, we prepared
a sample of 1s in hexane and introduced benzophenone. After
approximately 10 min, a white precipitate formed which was
1
isolated and confirmed by H NMR spectroscopy as the antici-
Figure 7. 1H DOSY NMR spectrum of 1s in C6D12 solution at 300 K containing
the inert standards 1,2,3,4-tetraphenylnaphthalene (TPhN), 1-phenylnaphtha-
lene (PhN) and tetramethylsilane (TMS).
pated lithium alkoxide LiOCH(Ph)2. A total isolated yield of
71% was comparable with that obtained using 1t (83%), sug-
gesting that this synthetically safer sBu isomer is essentially as
efficient a hydrolithiation agent as its tBu isomer. The marginal-
ly lower yield might be due to 1s starting to degrade partially
to sec-butylpyridine prior to the addition of benzophenone.
To further study the ease with which LiH is liberated from
a solid sample of 1s (and 1i for comparison) we turned to
thermal volatility analysis (TVA).[39] This showed (Figure 8) that
evolution of a volatile material from 1s commences close to
608C and occurs over a narrower temperature range (approxi-
Chem. Eur. J. 2015, 21, 14410 – 14420
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Assessing the importance of pyridine stoichiometry
mode is unlikely to be purely steric in origin since Me6TREN
has previously been shown to bind in a h4 fashion in the relat-
ed complex 4-picolyllithium which has a virtually identical local
environment around the anionic nitrogen atom (Figure 10).[19]
The six membered dihydropyridyl ring of 2 is clearly planar [C4
lies only 0.055(3) Š outside the plane of the remaining C4N
unit] with the shorter CaÀCb bonds [1.340(4)/1.343(4) Š] and
longer CbÀCg bonds [1.503(4)/1.501(4) Š] indicative of double
and single bonds, respectively. The hydrogen atoms at the 4-
position were located and refined, confirming this carbon is
sp3 hybridized and that the ligand is a dihydropyridyl anion.
The Li-N5(pyr) distance [1.969(5) Š] is consistent with other
crystallographically characterized monomeric, four-coordinate
lithium secondary amides such as PMDETA-solvated lithium a-
(methylbenzyl)benzylamide [1.959(7) Š],[40] lithium bis(a-meth-
ylbenzyl)amide [1.949(6) Š][41] and lithium 3,6-diethoxy-2,5-di-
hydro-2-isopropylpyrazide [1.965(3) Š][42] reported by Andrews
et al., while the Li-N(Me6TREN) distances [2.105(5)–2.139(5) Š]
are longer reflecting the weaker donor acceptor nature of
these interactions.
Finally, we carried out the reaction of pyridine with nBuLi in
the presence of Me6TREN in hexane solution but this time in-
creasing the number of pyridine equivalents from one to two
in order to judge the importance of keeping the ratio at unity
for the synthesis of a 1,2-dihydropyridyl complex capable of
acting as a LiH transfer reagent. This mixture was heated for
1 hour at 508C then allowed to cool slowly, resulting in a red
oily product from which a small crop of crystals developed.
These crystals were identified by X-ray crystallography to be
the
non-alkylated
1-lithio-1,4-dihydropyridine
complex
H6C5NLi·Me6TREN, 2 (Figure 9), that is the expected “added” n-
butyl ligand has been replaced by a hydride anion.
Presumably, 1n·Me6TREN is formed first in situ and then an
intermolecular 1,4-addition of LiH to the extra pyridine mole-
cule occurs to give 2 with 2-n-butylpyridine being the other
product [Eq. (2)]. Complex 2 can be considered a monomeric
variant of the previously reported pyridine solvate of 1-lithio-
1,4-dihydropyridine which is dimeric in the solid state and is
made in a similar fashion.[8c] As in 1t·Me6TREN, the donor binds
to lithium in a hypodentate h3 fashion with one arm free,
giving lithium an overall coordination number of four within
a distorted tetrahedral geometry. This hypodentate binding
Figure 10. Molecular structures of 2 (left) and 4-picolyllithium·Me6TREN.
Unlike the 2-alkyl-1,2-dihydropyridyl complexes mentioned
thus far (1t·donor), 2 is insoluble in aliphatic cyclohexane and
thus its NMR spectra were collected in C6D6 solution. These
spectra confirm that mirroring the molecular structure, the di-
hydropyridyl anion is in its 1,4 isomeric form and not the 1,2.
Specifically, there are only three dihydropyridyl resonances of
equal intensity (located at 6.50, 4.58 and 4.36 ppm), consistent
with a symmetric, non-aromatic 1,4 isomer. 13C and 7Li NMR
spectra corroborated this regiochemistry. Although the isolated
1
yield of 2 was low, a H NMR spectrum of the filtrate confirmed
that this was the exclusive lithium-containing product, with no
evidence of a 1,2 isomer. The by-product, 2-n-butylpyridine
was also clearly present along with some free uncoordinated
Me6TREN.
Conclusion
This study has advanced the chemistry of 1-lithio-2-alkyl-1,2-di-
hydropyridines. The key to this progress has been to use stoi-
chiometric amounts of pyridine in reactions with alkyllithium
compounds as opposed to the more common usage of excess
pyridine. Three new crystalline complexes have emerged from
this study in the 1,2-alkyl complexes 2-tBuC5H5NLi·PMDETA
(1t·PMDETA) and 2-tBuC5H5NLi·Me4AEE (1t·Me4AEE) both of
which show these kinetic intermediates can be stabilized in
monomeric form using polydentate donor supports, as well as
Figure 9. Molecular structure of monomeric 1,4-dihydropyridylLi·Me6TREN
(2). Ellipsoids are displayed at 50% probability and all hydrogen atoms
except those on C15 are omitted for clarity. Selected bond lengths [Š] and
angles [o]: Li1ÀN1 2.139(5); Li1ÀN2 2.108(4); Li1ÀN3 2.105(5); Li1ÀN4
4.604(5); Li1ÀN5 1.969(5); N5ÀC13 1.385(3); C13ÀC14 1.340(4); C14ÀC15
1.503(4); C15ÀC16 1.501(4); C16ÀC17 1.343(4); C17-N5 1.375(3); N1-Li1-N2,
85.2(2); N1-Li1-N3, 88.7(2); N1-Li1-N5, 132.1(2); N2-Li1-N3, 119.2(2); N2-Li1-
N5, 118.2(2); N3-Li1-N5, 110.1(2).
Chem. Eur. J. 2015, 21, 14410 – 14420
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domain data. DOSY plots were generated by use of the DOSY proc-
essing module of TopSpin. Parameters were optimized empirically
to find the best quality of data for presentation purposes. Diffusion
coefficients were calculated by fitting intensity data to the Stej-
skal–Tanner expression.
the non-alkyl complex 1,4-H6C5NLi·Me6TREN (2), which demon-
strate that 1,2-alkyl isomers can react with any available excess
pyridine to generate thermodynamic lithio 1,4-dihydropyri-
dines and 2-alkylpyridine byproducts. The study also brings to
the fore the subtle effect the alkyl substituent can have on the
solubility of the complex, with the tert-butyl and sec-butyl iso-
mers showing excellent solubility in aliphatic hydrocarbon sol-
vents; whereas the n-butyl and iso-butyl isomers are essentially
insoluble. These differences appear to reflect the different ag-
gregation states involved with the former pair molecular and
the latter pair probably polymeric. Though the hydrolithiation
properties of these new isolated lithio dihydropyridines have
been touched upon here, the fact that these complexes are
easily synthesized and (some) exhibit excellent solubility, sug-
gest their application as transporters of molecular LiH will in-
crease in the future.
Samples were prepared by introducing the desired complex
(0.1 mmol) to a NMR tube containing 1,2,3,4-tetraphenylnaphtha-
lene (TPhN, 15 mg), 1-phenylnaphthalene (PhN, 13.2 mL) and tetra-
methylsilane (TMS, 19.1 mL) as inert internal reference standards in
0.5 mL of the desired solvent for a concentration of 0.2 molLÀ1
.
1
The H DOSY NMR data were recorded at 300 K. From the diffusion
coefficients of the internal standards, linear calibration graphs were
obtained by plotting logD versus logFW. Using the diffusion coeffi-
cients for the signals corresponding to the species under study an
estimate of FW in solution was obtained.
X-ray crystallography
Crystallographic data were collected on Oxford Diffraction instru-
ments with Mo or CuKa radiation. Structures were solved using
SHELXS-97,[44] while refinement was carried out on F2 against all in-
dependent reflections by the full-matrix least-squares method
using the SHELXL-97 program.[44] All non-hydrogen atoms were re-
fined using anisotropic thermal parameters. Selected crystallo-
graphic details and refinement details are provided in Table 4.
1t·Me4AEE was treated as a twin. A hklf 5 formatted reflection file
was created with the two twin components related by matrix À1 0
À0.03 0 À1 0 0 0 1. The twin ratio refined to 0.618(4):0.382(4).
CCDC 1061251–1061253 contain the supplementary crystallo-
graphic data for this structure. These data are provided free of
charge by The Cambridge Crystallographic Data Centre.
Experimental Section
General
All reactions and manipulations were carried out under a protective
dry argon atmosphere using standard Schlenk techniques. Prod-
ucts were isolated and NMR samples pre-prepared in an argon-
filled glove box. Hexane and THF were dried by heating to reflux
over sodium-benzophenone and distilled under nitrogen prior to
use. Me6TREN was prepared according to a literature method.[43]
TMEDA, Me4AEE and PMDETA were distilled over CaH2 and stored
over 4 Š molecular sieves prior to use. Pyridine (anhydrous, 99.8%),
benzophenone, nBuLi (1.6m in hexanes), iBuLi (1.7m in heptane),
sBuLi (1.4m in cyclohexane), and tBuLi (1.7m in pentane) were pur-
chased from Aldrich and used as received. NMR spectra were re-
corded on a Bruker AVANCE 400 NMR spectrometer, operating at
Theoretical calculations
1
7
400.13 MHz for H, 155.50 MHz for Li and 100.62 MHz for 13C. All
DFT calculations were performed using the Gaussian03[45] package
using the B3LYP[46] density functional and the 6–311(d, p)[47] basis
set. After each geometry optimization a frequency analysis was
13C spectra were proton decoupled. H and 13C spectra were refer-
1
7
enced to the appropriate solvent signal and Li spectra were refer-
enced against LiCl in D2O at 0.00 ppm. Elemental analyses were
carried out on a PerkinElmer 2400 elemental analyzer. Satisfactory
elemental analyses could not be obtained for 1s (due to its high
reactivity and conversion into sec-butylpyridine and LiH, vide
supra), 1i (presumably as a result of its sensitive nature) and 2
(which is predominantly an oil). 1H NMR spectra of all new com-
plexes are therefore provided in the Supporting Information as an
alternative proof of purity.
Table 4. Crystallographic data and refinement details for complexes
1t·PMDETA, 1t·Me4AEE and 2.
Compound
1t·PMDETA
1t·Me4AEE
2
formula
C18H37N4Li
316.46
monoclinic
P21/c
0.71073
9.1578(2)
13.9331(3)
16.2095(4)
105.925(2)
1988.90(8)
4
C17H34N3LiO C17H36N5Li
303.41 314.45
monoclinic orthorhombic
formula weight
crystal system
space group
wavelength [Š]
a [Š]
DOSY NMR spectroscopy
P21/c
Pca21
0.71073
1.54180
Diffusion-ordered spectroscopy (DOSY) NMR experiments were per-
formed on a Bruker AVANCE 400 NMR spectrometer operating at
400.13 MHz for proton resonance under TopSpin (version 2.0,
Bruker Biospin, Karslruhe) and equipped with a BBFO-z-atm probe
with actively shielded z-gradient coil capable of delivering a maxi-
mum gradient strength of 54 GcmÀ1. Diffusion-ordered NMR data
were acquired using the Bruker pulse program dstegp3s employ-
ing a double stimulated echo with three spoiling gradients. Sine-
shaped gradient pulses were used with a duration of 4 ms togeth-
er with a diffusion period of 100 ms. Gradient recovery delays of
200 ms followed the application of each gradient pulse. Data were
systematically accumulated by linearly varying the diffusion encod-
ing gradients over a range of 2 to 95% of maximum for 64 gradi-
ent increment values. The signal decay dimension on the pseudo-
2D data was generated by Fourier transformation of the time-
12.6639(19) 13.4284(4)
b [Š]
c [Š]
9.5511(16)
16.073(3)
90.848(15)
1943.8(6)
4
10.5694(3)
14.1379(4)
90
2006.6(1)
4
b [8]
V [Š3]
Z
reflns. collected
unique reflns.
Rint
obs. reflns. [I>2s(I)]
goodness of fit
R[F2 >2s], F
Rw (all data), F2
largest diff. peak/hole e [Š3] 0.277/À0.178 0.366/À0.92 0.371/À0.187
[a] Twinned sample refined against a hklf 5 formatted reflection file.
39810
4732
0.0469
3410
1.017
0.0492
0.1152
4860[a]
4860[a]
0.0573
2278
1.018
0.0937
0.2486
7712
3270
0.0218
3047
1.046
0.0570
0.1600
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performed. The energy values quoted include the zero point
energy contribution.
tate formed almost immediately after the addition of iBuLi which
1
was filtered and collected (yield 0.66 g, 4.62 mmol, 92%). H NMR
(400.1 MHz, [D8]THF, 300 K): d=6.54 (1H, d, 3JH–H =5.39 Hz, H6),
3
3
5.71 (1H, t, JH–H =5.59 Hz, H4), 4.25 (1H, t, JH–H =5.49 Hz, H5), 3.97
Synthesis of 2-tBu(C5H5N)Li·PMDETA (1t·PMDETA)
3
3
(1H, t, JH–H =5.59 Hz, H3), 3.63 (1H, quin, JH–H =4.51 Hz, H2), 1.84
(2H, m, JH–H =5.30 Hz, a-CH2), 1.29 (1H, brs, CH), 0.83 ppm (6H, d,
3
A sample of 1t (143 mg, 1 mmol) was added to a Schlenk flask and
dissolved in hexane (5 mL) by gently warming with a heat gun for
a few seconds. PMDETA (0.21 mL, 1 mmol) was added via syringe
producing a thick oil. THF was slowly added dropwise with stirring
until a homogeneous yellow solution was obtained. Yellow crystals
formed after standing the solution at À308C for one week (yield
0.211 g, 67%). 1H NMR (400.1 MHz, C6D12, 300 K): d=6.56 (1H, d,
3JH–H =6.57 Hz, CH3); 13C NMR (100.6 MHz, [D8]THF, 300 K): d=150.0
(C6), 126.5 (C4), 95.1 (C3), 89.2 (C5), 53.3 (C2), 43.9 (a-CH2), 23.8
(CH3), 22.8 ppm (CH); 7Li NMR (155.5 MHz, [D8]THF, 300 K): d=
0.29 ppm.
3
3
3JH–H =4.70 Hz, H6), 5.85 (1H, t, JH–H =5.82 Hz, H4), 4.07 (1H, t, JH–
H =5.29 Hz, H5), 3.95 (1H, brs, H3), 3.54 (1H, brd, 3JH–H =4.56 Hz,
H2), 2.46 (4H, brs, 2”CH2 PMDETA), 2.38 (7H, brs, CH3 +2”CH2
PMDETA), 2.32 (12H, s, 4”Me PMDETA), 0.87 ppm (9H, s, CH3);
13C NMR (100.6 MHz, C6D12, 300 K): d=150.8 (C6), 128.8 (C4), 95.2
(C3), 87.4 (C5), 69.5 (C2), 58.1 (CH3 PMDETA), 55.0 (CH2 PMDETA),
46.0 (4”Me PMDETA), 45.2 (CH2 PMDETA), 41.1 (tBu quaternary),
25.7 ppm (CH3); 7Li NMR (155.5 MHz, C6D12, 300 K): d=0.82 ppm;
elemental analysis (%) for C18H37N4Li: calcd: C 68.31, H 11.78, N
17.70; found: C 67.64, H 11.85, N 17.33.
Synthesis of 2-sBu(C5H5N)Li (1s)
Pyridine (1.12 mL, 14 mmol) was added to a Schlenk flask contain-
ing hexane (10 mL). sBuLi (10 mL, 1.4m in hexane, 14 mmol) was
added via syringe, giving a yellow solution. A pale yellow precipi-
tate formed upon cooling the solution to À308C which was fil-
tered and collected (yield 0.88 g, 6.16 mmol, 44%). 1H NMR
3
(400.1 MHz, C6D12, 300 K): d=6.73 (1H, d, JH–H =5.25 Hz, H6), 6.04
3
(1H, m, H4), 5.08 (1H, brt, JH–H =5.25 Hz, H5), 4.40 (1H, brm, H3),
3.10 (1H, brm, H2), 1.55 (2H, m, a-CH+1 from CH2), 0.97 (1H, m,
1 from CH2), 0.85 (3H, m, CH3), 0.77 ppm (3H, m, CH3); 13C NMR
(100.6 MHz, C6D12, 300 K): d=147.7 (C6), 125.7 (C4), 96.6 (C5), 95.1
(C3), 60.6 (C2), 37.2 (CH), 24.8 (CH2), 15.0 (CH3), 11.4 ppm (CH3);
7Li NMR (155.5 MHz, C6D12, 300 K): d=À1.97 ppm.
Synthesis of 2-tBu(C5H5N)Li·Me4AEE (1t·Me4AEE)
A sample of 1t (143 mg, 1 mmol) was added to a Schlenk flask and
dissolved in hexane (5 mL) by gently warming with a heat gun for
a few seconds. Me4AEE (0.19 mL, 1 mmol) was added via syringe
producing a thick oil. THF was slowly added dropwise with stirring
until a homogeneous yellow solution was obtained. Yellow crystals
formed after standing the solution at À308C for one week (yield
0.097 g, 32%). 1H NMR (400.1 MHz, C6D12, 300 K): d=6.62 (1H, d,
Synthesis of 1,4-dihydropyridylLi·Me6TREN (2)
Pyridine (0.32 mL, 4 mmol) and Me6TREN (0.52 mL, 2 mmol) were
added to a Schlenk flask containing hexane (5 mL). nBuLi (1.25 mL,
1.6m in hexane, 2 mmol) was added via syringe, giving an orange
solution. This solution was heated at 508C for one hour then al-
lowed to slowly cool, depositing an orange-red oil which con-
tained a small crop of crystalline material. The oil and solvent mix-
ture was decanted off and the sticky crystals dried and collected
3
3JH–H =5.60 Hz, H6), 5.92 (1H, dq, JH–H =5.60, 1.23 Hz, H4), 4.36 (1H,
3
3
dt, JH–H =5.60, 1.34 Hz, H5), 4.18 (1H, dd, JH–H =4.89 Hz, H3), 3.55
(4H, t, 3JH–H =5.52 Hz, O-CH2 Me4AEE), 3.46 (1H, d, 3JH–H =5.00 Hz,
3
H2), 2.50 (4H, t, JH–H =5.55 Hz, CH2-N Me4AEE), 2.24 (s, 12H, N-CH3
Me4AEE), 0.84 ppm (s, 9H, CH3); 13C NMR (100.6 MHz, C6D12, 300 K):
d=151.0 (C6), 128.2 (C4), 97.2 (C3), 91.6 (C5), 69.4 (O-CH2 Me4AEE),
66.9 (C2), 59.4 (CH2-N Me4AEE), 45.8 (N-CH3 Me4AEE), 40.9 (tBu qua-
ternary), 25.7 ppm (CH3); 7Li NMR (155.5 MHz, C6D12, 300 K): d=
0.34 ppm; elemental analysis (%) for C17H34N3LiO: calcd: C 67.29, H
11.29, N 13.85; found: C 66.67, H 11.22, N 14.10.
1
(yield 0.121 g, 19%). H NMR (400.1 MHz, C6D6, 300 K): d=6.50 (2H,
d, 3JH–H =7.27 Hz, H2), 4.56 (2H, m, H3), 4.38 (2H, brt, H4), 2.01–
1.91 ppm (brs with shoulder, 30H, Me6TREN); 13C NMR (100.6 MHz,
C6D6, 300 K): d=143.5 (C2), 89.4 (C3), 57.5 (CH2 Me6TREN), 51.9
(CH2 Me6TREN), 45.6 (Me Me6TREN), 27.9 ppm (C4); 7Li NMR
(155.5 MHz, C6D6, 300 K): d=0.68 ppm.
Synthesis of 2-tBu(C5H5N)Li·TMEDA (1t·TMEDA)
2-i-Butylpyridine
A sample of 1t (143 mg, 1 mmol) was added to a Schlenk flask and
dissolved in hexane (5 mL) by gently warming with a heat gun for
a few seconds. TMEDA (0.15 mL, 1 mmol) was added via syringe
giving a homogeneous yellow solution. Orange crystals formed
1H NMR (400.1 MHz, CDCl3, 300 K): d=8.53 (1H, brs, H6), 7.59 (1H,
t, 3JH–H =7.64 Hz, H4), 7.11 (2H, brt, H3+H5), 2.66 (2H, d, JH–H
7.30 Hz, a-CH2), 2.11 (1H, m, JH–H =6.87 Hz, b-CH), 0.93 ppm (6H,
d, 3JH–H =6.61 Hz, CH3); 13C NMR (400.1 MHz, CDCl3, 300 K): d=
161.6 (C2), 149.1 (C6), 136.3 (C4), 123.7 (C3), 121.0 (C5), 47.6 (CH2),
29.3 (CH), 22.5 ppm (CH3).
3
=
3
after standing the solution at À308C for one week (yield 0.212 g,
3
82%). 1H NMR (400.1 MHz, C6D12, 300 K): d=6.70 (1H, d, JH–H
=
=
=
3
5.19 Hz, H6), 6.04 (1H, t, 3JH–H =5.54 Hz, H4), 4.58 (1H, t, JH–H
3
5.19 Hz, H5), 4.07 (1H, m, 3JH–H =5.19 Hz, H3), 3.30 (1H, d, JH–H
4.67 Hz, H2), 2.34 (4H, s, CH2 TMEDA), 2.26 (12H, s, Me TMEDA),
0.82 ppm (9H, s, CH3); 13C NMR (100.6 MHz, C6D12, 300 K): d=151.3
(C6), 127.0 (C4), 94.4 (C3), 93.8 (C5), 66.2 (C2), 58.9 (CH2 TMEDA),
46.8 (Me TMEDA), 41.6 (tBu quaternary), 26.0 ppm (CH3); 7Li NMR
(155.5 MHz, C6D12, 300 K): d=À1.67 ppm.
2-s-Butylpyridine
1H NMR (400.1 MHz, CDCl3, 300 K): d=8.56 (1H, d, 3JH–H =5.05 Hz,
H6), 7.65 (1H, t, 3JH–H =7.46 Hz, H4), 7.15 (2H, m, H3+H5), 2.87
(1H, m, 3JH–H =6.80 Hz, a-CH), 1.78 (1H, m, 3JH–H =7.46 Hz, CH2),
1.65 (1H, m, 3JH–H =7.02 Hz, CH2), 1.29 (3H, d, 3JH–H =7.02 Hz,
CHCH3), 0.87 ppm (3H, t, 3JH–H =7.46 Hz, CH2CH3); 13C NMR
(400.1 MHz, CDCl3, 300 K): d=165.7 (C2), 147.9 (C6), 136.4 (C4),
121.3 (C3), 121.7 (C5), 42.8 (CH), 29.4 (CH2), 19.8 (CHCH3), 11.5 ppm
(CH2CH3).
Synthesis of 2-iBu(C5H5N)Li (1i)
Pyridine (0.40 mL, 5 mmol) was added to a Schlenk flask containing
hexane (10 mL). iBuLi (3.12 mL, 1.6m in hexane, 5 mmol) was
added via syringe, giving a yellow solution. A pale yellow precipi-
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Acknowledgements
We would like to thank the Royal Society of Edinburgh (BP
Trust Fellowship to SDR), the EPSRC (grant award nos. EP/
L027313/1 and EP/K001183/1), the Royal Society (Wolfson re-
search merit award to R.E.M.) and the Nuffield Foundation for
an undergraduate Science Bursary (C.M.M.H.).
Keywords: hydrides
· lithium · nucleophilic addition ·
pyridine · structure elucidation
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