Metalated nitriles: N- and C-coordination preferences of Li, Mg, and Cu cations

Article abstract of DOI:10.1039/c3cc41703d

¹³C NMR analyses of a series of metalated arylacetonitriles and cyclohexanecarbonitriles with the synthetically relevant metals Li, Mg, and Cu identifies the influence of the carbon scaffold and the nature of the metal on the preference for N- or C-metalation. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3cc41703d

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Metalated nitriles: N- and C-coordination preferences
of Li, Mg, and Cu cations†
Cite this: Chem. Commun., 2013,
49, 4700
Matthew Purzycki,a Wang Liu,a Goran Hilmersson*b and Fraser F. Fleming*a
¨
Received 6th March 2013,
Accepted 4th April 2013
DOI: 10.1039/c3cc41703d
www.rsc.org/chemcomm
13C NMR analyses of a series of metalated arylacetonitriles and
cyclohexanecarbonitriles with the synthetically relevant metals Li,
Mg, and Cu identifies the influence of the carbon scaffold and the
nature of the metal on the preference for N- or C-metalation.
Metalated nitriles are chemical chameleons whose precise structural
identity depends upon the solvent, the carbon scaffold, the tem-
perature, and the metal.1 In general, electropositive metals, and
transition metals in high oxidation states, coordinate to metalated
nitriles through the electron-rich nitrile nitrogen whereas less
electropositive metals, and transition metals in low oxidation states,
preferentially coordinate to the nucleophilic carbon.2 Solid-state
structures of metalated nitriles containing transition metals are
roughly equally partitioned into N- and C-coordinated structures.2
Often the ligand dictates the metal coordination site as illustrated in
the ruthenium N- and C-phenylsulfonylacetonitriles 1 and 2 that can
be equilibrated upon heating (Fig. 1).3
Despite the seminal position of lithiated and magnesiated nitriles
in alkylations,1c,d significantly less structural information is available
than for comparable structures with transition metal cations.
Pioneering crystallographic4 and solution NMR analyses5 of
lithiated phenylacetonitrile identify the dimeric,6 N-lithiated struc-
ture 35 as the predominant structure in solution and in the solid
state (Fig. 1).7 Only in lithiated cyclopropanecarbonitriles such as 48
or in the presence of proximal, strong donor ligands9 are lithiated
nitriles coaxed into coordinating with the nucleophilic carbon.10
13C NMR provides an excellent method of determining the
metal coordination in metalated nitriles because the chemical
shift of the nitrile carbon is sensitive to the local environment.11
The 13C NMR signal for the nitrile carbon of N-metalated nitriles
containing a transition metal counter ion,2 resonates between
d = 140–157 whereas the corresponding C-metalated nitriles2
resonate between d = 115–138. The chemical shift ranges of the
ruthenium-complexed phenylsulfonylacetonitriles 1 and 2 are
Fig. 1 Comparison of N- and C-metalated nitrile structures.
illustrative (Fig. 1). Collectively, the chemical shift ranges for
N- and C-metalated nitriles provide diagnostic signals for identi-
fying the location of the metal in solution without the challenge
of crystallizing air and moisture sensitive organometallics.
Fewer 13C NMR chemical shifts are available for metalated
nitriles having Li, Mg, Zn, and Cu counter ions.5 For N-lithiated
phenylacetonitrile (3), the 13C NMR resonances of the nitrile carbon
vary modestly from d = 146.2 to 152.7 depending on the solvent.12 In
contrast, the chemical shifts of the nitrile carbon in the equilibrat-
ing lithiated acetonitriles 5 and 6 (À100 1C, Et2O) are d 155.3 for the
N-lithiated nitrile 5 and d 148.5 for the C-lithiated nitrile 6 (Fig. 1).9b
Solution and solid state structures of two zincated acetonitriles
show coordination of the metal to the nucleophilic carbon (Fig. 2). A
crystallographically determined structure of the zincated acetonitrile
7a bearing a pyrazolylborate ligand crystallizes with zinc bound to
the nucleophilic carbon.13 In solution, the parent C-zincated aceto-
a Department of Chemistry, Duquesne University, 600 Forbes Ave, Pittsburgh, USA
15282-1530. E-mail: flemingf@duq.edu; Fax: +1 412 396 5683; Tel: +1 412 396 6031
b
¨
¨
Department of Chemistry, Goteborg University, Goteborg, Sweden S-412 96.
E-mail: hilmers@chem.gu.se; Tel: +46 (0)31 786 90 22
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c3cc41703d nitrile 7b exhibits a 13C NMR chemical shift of d 131.8 for the nitrile
c
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Fig. 2 13C NMR of metalated nitriles containing Zn, Cu, and Mg.
Fig. 4 13C NMR Shifts of metalated 2-(2-methoxyphenyl)acetonitrile.
carbon (Fig. 2).14 The metal coordination site of cuprated nitriles is
less secure. The solution NMR of the C-cuprated nitrile 8 exhibits a
resonance for the nitrile carbon that lies toward the upper chemical
shift limit for C-metalated nitriles, at d 137.8.15
nucleophilic carbon 13C resonance for 12 was assigned to the
signal at d = 26.1 ppm in THF (and d = 25.9 in Et2O) through a
strong, single bond correlation with the signal for the methine
hydrogen at d = 2.86 ppm. In THF and Et2O the 6Li NMR shows a
single resonance consistent with formation of a symmetrical N-
lithiated dimer.
Structural analyses of magnesiated nitriles are lacking.16 A rare
exception is the magnesiated alkenenitrile 917 which exhibits a
13C NMR resonance for the nitrile carbon at d 129.6. In contrast
to the C-magnesiated nitrile 9, diphenylacetonitrile affords a
magnesiated nitrile whose infra-red signals are consistent with
an N-magnesiated nitrile structure.16 The ambiguity surrounding
the location of magnesium in magnesiated nitriles is compounded
by reactivity trends that correlate with C-magnesiation18 and a
configurationally labile C–Mg bond.19 The dearth of structural
information for metalated nitriles, and the structural ambiguity
of magnesiated nitriles, stimulated an NMR investigation into a
series of lithiated, magnesiated, and cuprated nitriles.
Deprotonating 2-(2-methoxyphenyl)acetonitrile with i-PrMgCl
affords 13 that has a 13C NMR signal for the nitrile carbon at
d 147.6 (Fig. 4). The 13C NMR chemical shifts of the magnesiated
nitrile 13 closely correlate with the analogous signals for the
magnesiated nitrile 10 and the lithiated nitriles 11 and 12.
Collectively the 13C chemical shift similarities between 10–13 imply
that the nitrile is N-metalated in each case. Extensive attempts to
crystallize 13 provided low quality crystals whose X-ray crystallo-
graphic structure was consistent with the N-magnesiated structure
13 but the R value was unable to be refined below 15%.20
Although the presence of the 2-methoxy group in 12 and 13
was insufficient to promote C-metalation, less electropositive
metals may prefer C-metalation. Consequently, the cuprated
nitrile 14 was prepared by adding CuI to the lithiated nitrile
12.21 Cuprated nitrile 14 has a diagnostic nitrile carbon reso-
nance at d 131.2 (Fig. 4), similar to that of the C-cuprated nitrile
8 and distinctly different from the N-lithiated nitriles 11 and 12,
and the N-magnesiated nitriles 10 and 13.22
Collectively, the metalations are consistent with lithiated and
magnesiated arylacetonitriles favoring N-metalated structures
whereas the less electropositive copper favors a C-cuprated nitrile.
Although magnesiated arylacetonitriles favor coordination of mag-
nesium to the nitrile nitrogen, the stereodivergent alkylations18
and cyclizations1a of some magnesiated and lithiated alkylnitriles
suggest that the preference for C- or N-metalation may be strongly
influenced by the carbon scaffold.
Cyclohexanecarbonitrile was chosen as a representative alkyl-
nitrile to investigate the influence of the carbon skeleton on the
coordination preferences of metalated nitriles because alkylations18
and cyclizations1a implicating C-metalated nitriles have featured in
mechanistic analyses of conformationally constrained, 6-membered
carbonitriles.19 As a point of reference, cyclohexanecarbonitrile was
deprotonated with LDA (1.1 equiv.) to afford the N-lithiated nitrile 15
(Fig. 5). Although the upfield signals of the ring carbons were
obscured by signals from other components, a broad signal for
the nitrile carbon was observed at d 163.6.23 The nitrile carbon
resonance is further upfield than the arylacetonitriles 11 and 12,
consistent with the influence of the aromatic system,24 and is similar
in frequency to the signal for lithiated acetonitrile in THF, d 157.3.10
Access to the corresponding magnesiated and cuprated nitriles
employed a facile bromine–metal exchange with 1-bromocyclo-
hexanecarbonitrile.25 Halogen–metal exchange methods carry the
Metalated arylacetonitriles are attractive for NMR analyses
because the highly acidic methylene protons are readily depro-
tonated by a range of bases.1 Phenylacetonitrile was readily
deprotonated by i-PrMgCl in THF to afford the corresponding
magnesiated nitrile 10. Spectra obtained at À20 1C show one
aliphatic resonance at d = 31.3 ppm and five resonances between
d = 113–148 ppm (Fig. 3). Comparing the 13C NMR chemical
shifts of 10 with those of N-lithiated phenylacetonitrile 1112
indicate a close structural correspondence consistent with 10
having magnesium coordinated to the nitrile nitrogen (Fig. 1).
Donor groups adjacent to the nitrile in lithiated alkylnitriles9 can
override the normal preference for lithium to coordinate to the
nitrile nitrogen to favour C-lithiated structures. If the coordination
of magnesium to the nitrile nitrogen in magnesiated phenylaceto-
nitrile and diphenylacetonitrile is weak, then C-magnesiated nitriles
might be accessed with an appropriately positioned chelating group.
2-(2-Methoxyphenyl)acetonitrile was selected for deprotonation to
determine whether an adjacent methoxy group could redirect the
preference of magnesium to coordinate to carbon instead of nitrogen.
As a point of reference, the lithiated nitrile was first generated from
2-(2-methoxyphenyl)acetonitrile (Fig. 4). Adding BuLi to a À78 1C,
THF solution of 2-(2-methoxyphenyl)acetonitrile readily afforded
the lithiated nitrile 12 which gave a resonance for the nitrile carbon
at d 142.1. In the 1H NMR, the methine proton at d 2.86 experiences
an upfield shift of d 0.84 which parallels a similar d 0.85 upfield
shift on deprotonating acetonitrile.6 An analogous deprotonation
in Et2O generates a signal for the nitrile carbon at d 151.9,
suggesting a tighter CN–Li association than in THF. The
Fig. 3 13C NMR shift comparison of metalated phenylacetonitrile.
c
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Financial support for this research from NSF (CHE 1111406,
0904393 and CHE 0614785 for NMR facilities) and the Swedish
research council (GH) are gratefully acknowledged.
Notes and references
Fig. 5 13C NMR chemical shifts of metalated cyclohexanecarbonitriles.
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2 See listing in ESI†.
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(1)
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20 Crystallographic data is provided in the ESI†.
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4702 Chem. Commun., 2013, 49, 4700--4702
This journal is The Royal Society of Chemistry 2013