DOI: 10.1002/chem.201501072
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& Hydrosilylation | Hot Paper|
Calcium Hydride Catalyzed Highly 1,2-Selective Pyridine
Hydrosilylation
Julia Intemann,[a] Heiko Bauer,[b] Jìrgen Pahl,[b] Laurent Maron,[c] and Sjoerd Harder*[b]
Dedicated to Professor Manfred Scheer on the occasion of his 60th birthday
Abstract: Reaction of the calcium hydride complex (DIPPnacnac-CaH·THF)2 with pyridine is much faster and selective
than that of the corresponding magnesium hydride complex
(DIPPnacnac = [(2,6-iPr2C6H3)NC(Me)]2CH). With a range of
pyridine, picoline and quinoline substrates, exclusive transfer
of the hydride ligand to the 2-position is observed and also
at higher temperatures no 1,2!1,4 isomerization is found.
The heteroleptic product DIPPnacnac-Ca(1,2-dihydropyridide)·(pyridine) shows fast ligand exchange into homoleptic
calcium complexes and therefore could not be isolated. Calcium hydride reduction of isoquinoline gave well-defined
homoleptic products which could be characterized by X-ray
Introduction
Dihydropyridine, the reduced form of pyridine, represents an
important high-energy building block. For example, the dihydropyridine NADH (nicotinamide adenine dinucleotide) should
be regarded as the fuel of life and is responsible for biological
reduction processes.[1, 2] NADH as well as its mimics like the
Hantzsch ester[3, 4] belong to 1,4-dihydropyridines, a compound
class with widespread pharmalogical applications and research
interests.[5] Increasing attention for the somewhat less stable
1,2-dihydropyridine isomers[6] was triggered by their recognition as importance building blocks in the synthesis of alkaloids
and further pharmaceutical products such as Tamiflu,[7] a wellknown anti-influenza drug. Syntheses of these building blocks
rely heavily on routes for selective reduction of pyridines. Catalytic pyridine reduction/conversion processes are generally
[a] Dr. J. Intemann
Stratingh Institute for Chemistry, Nijenborgh 4
9747AG Groningen (The Netherlands)
[b] Dr. H. Bauer, M. Sc. J. Pahl, Prof. Dr. S. Harder
Friedrich-Alexander University Erlangen-Nìrnberg
Inorganic and Organometallic Chemistry
Egerlandstraße 1, 91058 Erlangen (Germany)
[c] Prof. Dr. L. Maron
Universit¦ de Toulouse et CNRS INSA, UPS, CNRS, UMR 5215, LPCNO
135 avenue de Rangueil, 31077 Toulouse (France)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201501072.
Chem. Eur. J. 2015, 21, 11452 – 11461
diffraction: Ca(1,2-dihydroisoquinolide)2·(isoquinoline)4 and
Ca3(1,2-dihydroisoquinolide)6·(isoquinoline)6. The striking selectivity difference in the dearomatization of pyridines by
Mg or Ca complexes could be explained by DFT theory and
was utilized in catalysis. Whereas hydroboration of pyridine
with pinacol borane with a calcium hydride catalyst gave
only minor conversion, the hydrosilylation of pyridine and
quinolines with PhSiH3 yields exclusively 1,2-dihydropyridine
and 1,2-dihydroquinoline silanes with 80–90 % conversion.
Similar results can be achieved with the catalyst Ca[N(SiMe3)2]2·(THF)2. These calcium complexes represent the first
catalysts for the 1,2-selective hydrosilylation of pyridines.
based on transition metal catalysts[8–17] and are usually not very
selective but recently 1,4-selective catalytic routes based on Ru
catalysts have been reported.[9, 14] Selective catalytic routes to
1,2-dihydropyridines have been described with Ni, Ag, Au, Cu
and Rh catalysts.[6, 16–17] Recently, a 1,2-selective catalytic route
for the hydroboration of pyridines with a La catalyst has been
reported.[18]
The last decade has seen rapid progress in early main group
metal catalyzed reactions.[19] Magnesium hydride based catalysts for pyridine dearomatization/hydroboration have been
employed but generate mixtures of 1,2- and 1,4-products.[20, 21]
Pyridine reduction by the magnesium hydride complex is suggested to be the first step in the catalytic cycle (Scheme 1,
top). Its regioselectivity may likely be decisive for product selectivity.
Early work by Ashby et al. showed that addition of MgH2 to
pyridine gives a mixture of 1,2- and 1,4-pyridides, abbreviated
in here as 1,2-DHP and 1,4-DHP (Scheme 2, left), but subsequent heating led to exclusive isomerization to 1,4-DHP.[22, 23]
Similar, dearomatization of pyridine by a b-diketiminate magnesium hydride intermediate, initially gives a mixture of 1,2and 1,4-DHP which after heating evolves to the pure 1,4-DHP
product (Scheme 2, middle).[24, 25] As 2,6-disubstituted pyridines
do not react with magnesium hydrides, it is assumed that 1,2DHP is the initially formed kinetic product whereas 1,4-DHP is
the final, more stable, thermodynamic product.[26] This is in line
with the thermodynamic preference for N-methyldihydropyridine: experimental data show that the 1,4-isomer is 2.3 kcal
mol¢1 more stable than the 1,2-isomer (DG8 at 90 8C).[27]
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ty for pyridine reduction promised considerable potential in
the selective catalytic hydroboration of pyridines, catalytic reactions only produced mixtures of 1,2- and 1,4-products. This
might be explained by assuming a mechanism without a magnesium hydride intermediate, for example, by direct transfer of
the hydride from R2BH(DHP)¢ to pyridine (Scheme 1, bottom).
Alternatively, pyridine aromatization is not selective under catalytic conditions.
Herein, we describe the highly 1,2-selective stoichiometric
reduction of pyridine by a hydrocarbon-soluble b-diketiminate
calcium hydride complex.[28] DFT calculations explain the unusual selectivity. In addition we discuss investigations towards
catalytic pyridine hydroboration and the first example of main
group metal catalyzed pyridine hydrosilylation which proceeds
with high 1,2-selectivity.
Scheme 1. Possible pathways for magnesium hydride catalyzed pyridine hydroboration (only 1,2-reduction is exemplary shown but usually mixtures of
1,2- and 1,4-products are found).
Experimental Section
All experiments were carried out in flame-dried glassware under an
inert atmosphere using standard Schlenk techniques and freshly
dried degassed solvents. Pyridine and all derivatives have been
dried by refluxing them overnight on freshly powdered CaH2 and
were distilled prior to use. Phenylsilane (PhSiH3) has been obtained
commercially, was stored over molecular sieves and used without
further purification. (DIPPnacnac-CaH·THF)2 has been prepared according to literature.[28] 1H and 13C NMR spectra have been recorded on Bruker 300 MHz, 400 MHz, 500 MHz or 600 MHz NMR spectrometer (specified at individual experiments). Crystal structures
were measured with an Agilent Supernova (Atlas S2) diffractometer
with microfocus source.
Scheme 2. Stoichiometric reduction of pyridine with MgH2 and complexes
thereof.
We recently found that a coupled b-diketiminate magnesium
hydride complex reacts with pyridine to give exclusively the
1,2-DHP product (Scheme 2, right).[21] Even after heating (60 8C,
2 days) less than 10 % was converted to 1,4-DHP. The unusual
stability of the 1,2-DHP product may be related to the bimetallic nature of the complex: careful analysis of its crystal structure shows that the pyridide CH2 group and the neutral pyridine ligands are involved in an extensive network of C¢H···C(p)
and p–p stacking interactions. Although this high 1,2-selectiviChem. Eur. J. 2015, 21, 11452 – 11461
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Reaction of (DIPPnacnac-CaH·THF)2 with pyridine: Pyridine
(20.0 mg, 0.25 mmol) was added to a solution of (DIPPnacnacCaH·THF)2 (21.2 mg, 0.020 mmol) in benzene (0.5 mL). Within 30
seconds the color of the solution changed from yellow to bright
orange. After 30 min at room temperature, the solvent was removed and the resulting orange-red solids were dissolved in C6D6
for 1H NMR analysis. This showed quantitative conversion of the
metal hydride complex into DIPPnacnac-Ca(1,2-DHP)·pyridine. The
complex is extremely air-sensitive and also unstable towards ligand
exchange reactions. Over the course of one hour major quantities
of the homoleptic species (DIPPnacnac)2Ca and Ca(1,2-DHP)2 were
detected. Although full NMR data for (DIPPnacnac)2Ca are
known,[29] 13C NMR analysis on the mixture of hetero- and homoleptic species remains difficult. Therefore 13C data for DIPPnacnacCa(1,2-DHP)·pyridine given below should be taken with care.
1
H NMR (400 MHz, C6D6, 25 8C): d = 0.99 (d, 3JHH = 6.9 Hz, 12 H, iPr),
1.19 (d, 3JHH = 6.9 Hz, 12 H, iPr), 1.79 (s, 6 H, CH3), 3.34 (sept, 3JHH =
6.9 Hz, 4 H, iPr), 3.81 (d, 3JHH = 4.1 Hz, 2 H, 1,2-DHP), 4.52 (m, 1 H,
1,2-DHP), 5.02 (s, 1 H, H backbone), 5.16 (m, 1 H, 1,2-DHP), 6.42 (m,
1 H, 1,2-DHP), 6.64 (d, 3JHH = 5.6 Hz, 1 H, 1,2-DHP), 6.72 (m, 2 H, pyr),
7.03–7.08 (m, 4 H, Ar + pyr), 8.48 ppm (d, 3JHH = 4.2 Hz, 2 H, pyr). It
is not clear from the pyridine signals (pyr) whether part of the
excess pyridine is coordinated to the metal or not (in the first case
chemical shifts would average out by fast exchange). Addition of
stoichiometric amounts of pyridine results in broad signals.
13
C NMR (600 MHz, C6D6, 25 8C): d = 24.4 (CH3 iPr), 24.6 (CH3), 25.2
(CH3 iPr), 28.2 (CH iPr), 48.5 (DHP NCH2), 92.3 (DHP NCH), 94.5 (CH
backbone), 122.9 (DHP CH), 123.5 (DIPP), 123.8 (pyridine), 123.9
(DHP CH), 125.2 (DHP CH), 125.3 (DIPP), 134.1 (pyridine), 141.0 (o-C,
DIPP), 148.8 (ipso-C, DIPP), 149.9 (pyridine), 168.2 ppm (C-N).
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Reaction of (DIPPnacnac-CaH·THF)2 with quinoline: Quinoline
(20.0 mg, 0.15 mmol) was added to a solution of (DIPPnacnacCaH·THF)2 (5.0 mg, 4.7 mmol) in C6D6 (0.5 mL). Within 30 seconds
the color of the solution changed from yellow to bright orange.
After 30 min at room temperature a 1H NMR of the complex was
recorded which showed quantitative conversion of the calcium hydride complex to DIPPnacnac-Ca(1,2-DHQ). The complex is extremely air-sensitive and also unstable towards ligand exchange reactions. Over the course of one hour major quantities of the homoleptic species (DIPPnacnac)2Ca and Ca(1,2-DHQ)2 were detected. Although full NMR data for (DIPPnacnac)2Ca are known,[29] 13C NMR
analysis on the mixture of hetero- and homoleptic species remains
difficult. Therefore 13C data for DIPPnacnac-Ca(1,2-DHQ)·quinoline
given below should be taken with care. 1H NMR (500 MHz, C6D6,
25 8C): d = 0.90 (m, 12 H, iPr), 1.08 (m, 12 H, iPr), 1.84 (s, 6 H, CH3),
3.26 (m, 4 H, iPr), 3.87 (br, 2 H, 1,2-DHQ), 5.15 (s, 1 H, H backbone),
5.34 (d, 3JHH = 7.7 Hz, 1 H, 1,2-DHQ), 6.20 (t, 3JHH = 7.0 Hz, 1 H, 1,2DHQ), 6.29 (dd, 3JHH = 7.2 Hz, 3JHH = 7.7 Hz, 1 H, 1,2-DHQ), 6.78 (m,
1 H, quin), 6.82 (d, 3JHH = 7.2 Hz, 1 H, 1,2-DHQ), 7.14–7.18 (m, 3 H, Ar
+ quin), 7.35–7.40 (m, 4 H, Ar + quin), 7.53 (d, 3JHH = 8.2 Hz, 1 H,
quin), 8.34 (d, 3JHH = 8.3 Hz, 1 H, quin), 8.78 ppm (br, 1 H, quin). It is
not clear from the quinoline signals (quin) whether part of the
quinoline is coordinated to the metal or not (in the first case chemical shifts would average out by fast exchange). 13C NMR (600 MHz,
C6D6, 25 8C): d = 24.5 (CH3 iPr), 24.6 (CH3), 25.6 (CH3 iPr), 28.5 (CH
iPr), 46.8 (DHQ NCH2), 94.5 (CH backbone), 107.2 (DHQ NC), 121.3
(quinoline), 123.4 (DHQ), 123.5 (DHQ), 124.0 (DHQ), 124.4 (DIPP),
125.2 (DIPP), 127.0 (quinoline), 127.9 (quinoline), 128.5 (DHQ),
128.6 (quinoline), 129.4 (quinoline), 130.1 (quinoline), 130.6 (DHQ),
131.1 (DHQ), 134.8 (DHQ), 136.8 (quinoline), 141.8 (o-C, DIPP),
146.2 (ipso-C, DIPP), 148.2 (quinoline), 150.9 (quinoline), 168.2 ppm
(C-N).
Reaction of (DIPPnacnac-CaH·THF)2 with isoquinoline: Isoquinoline (15.5 mg, 0.12 mmol) was added to a solution of (DIPPnacnacCaH·THF)2 (21.2 mg, 0.020 mmol) in C6D6 (0.6 mL) The color of the
solution changed immediately from yellow to orange and darkened rapidly. After 30 min of room temperature, a 1H NMR of the
reaction mixture was recorded, which show quantitative conversion of the calcium hydride complex to DIPPnacnac-Ca(1,2-DHiQ).
The complex is well soluble in benzene and quite stable towards
ligand exchange reactions according to the Schlenk equilibrium.
After 1 h at room temperature, only small amounts of homoleptic
species could be detected by 1H NMR (less than 5 %), but at elevated temperature (60 8C), the homoleptic complex forms much faster
(50 % in 2 h). The relative good stability towards Schlenk equilibria
allowed recording of 13C NMR data for DIPPnacnac-Ca(1,2-DHiQ).
1
H NMR (400 MHz, C6D6, 25 8C): d = 1.06 (d, 3JHH = 6.8 Hz, 12 H,
CH(CH3)2), 1.28 (d, 3JHH = 6.8 Hz, 12 H, CH(CH3)2), 1.97 (s, 6 H, backbone CH3), 3.52 (m, 4 H, CH(CH3)2), 4.51 (s, 2 H, 1,2-DHiQ, CH2), 5.27
(s, 1 H, H backbone), 5.68 (d, 3JHH = 5.9 Hz, 1 H, 1,2-DHiQ), 7.03–7.45
(m, 23 H, 1,2-DHiQ + Ar + iQ), 7.54 (d, 3JHH = 8.0 Hz, 3 H, iQ), 8.24 (d,
3
JHH = 5.9 Hz, 3 H, iQ), 8.90 ppm (s, 3 H, iQ); 13C NMR (400 MHz, C6D6,
25 8C): d = 24.5 (CH(CH3)2), 24.6 (CH(CH3)2), 25.7 (backbone CH3),
28.7 (CH(CH3)2), 47.3 (DHiQ NCH2), 94.6 (backbone CH), 105.7 (DHiQ
NCH), 120.9 (iQ CH), 123.2 (DHiQ CH), 123.6 (DHiQ CH), 124.1
(DHiQ CH), 124.5 (iQ C), 125.9 (Ar CH), 126.1 (iQ CH), 126.4 (Ar CH),
127.5 (iQ CH), 128.4 (DHiQ CH), 128.8 (iQ CH), 130.0 (iQ C), 130.5
(DHiQ C), 131.1 (DHiQ CH), 135.3 (iQ CH), 136.8 (DHiQ C), 142.6 (iQ
CH), 142.9 (Ar C), 148.8 (Ar C), 153.6 (iQ CH), 166.0 ppm (backbone
C).
Synthesis and crystallization of Ca(1,2-DHiQ)2·(iQ)4 : (DIPPnacnacCaH·THF)2 (21.0 mg, 0.020 mmol) was added to isoquinoline (2 mL)
and the red solution was heated to 60 8C for 2 h and slowly cooled
Chem. Eur. J. 2015, 21, 11452 – 11461
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to 20 8C. The product was isolated as a uniform batch of dark-red,
square-shaped crystals and characterized by X-ray diffraction as
Ca(1,2-DHiQ)2·(iQ)4, isolated yield: 24.0 mg, 57 %. The crystals show
an unexpectedly high air-sensitivity which is likely due to fast reaction with only slight traces of oxygen. This extreme sensitivity also
hindered the mounting of crystals on a diffractometer, which
needed numerous attempts. Elemental analysis calcd (%) for:
C54H44N6Ca (817.12): C 79.37 H 5.44 N 10.29; found C 77.75 H 5.31
N 10.18. The extreme air-sensitivity and potential formation of
stable calcium carbide are likely the cause for strong deviation in C
content. 1H NMR (400 MHz, C6D6, 25 8C): d = 4.69 (s, br, 2 H, DHiQ
NCH2), 5.50 (s, br, 1 H, DHiQ NCH), 6.67 (s, br, 2 H, DHiQ), 7.00 (s, br,
1 H, DHiQ), 7.07 (s, 1 H, DHiQ), 7.11 (t, 6 H, 3JHH = 7.1 Hz, iQ), 7.16 (s,
br, 1 H, DHiQ), 7.17–7.21 (m, 3 H, iQ), 7.30 (d, 3 H, 3JHH = 8.2 Hz, iQ),
7.42 (d, 3 H, 3JHH = 8.2 Hz, iQ), 8.49 (d, 3 H, 3JHH = 5.8 Hz, iQ),
9.20 ppm (s, 3 H, iQ); 13C NMR (400 MHz, C6D6, 25 8C): d = 54.3
(DHiQ NCH2), 91.1 (DHiQ NCH), 118.0 (DHiQ CH), 120.5 (DHiQ CH),
120.5 (iQ CH), 126.5 (iQ CH), 127.0 (DHiQ CH), 127.2 (iQ CH), 127.9
(iQ CH), 128.6 (DHiQ CH), 129.0 (iQ C), 130.3 (iQ CH), 136.0 (iQ C),
143.6 (iQ CH), 153.4 ppm (iQ CH). Signals for two quaternary C’s
and one CH in DHiQ could not unequivocally be detected due to
overlap with solvent signals and other ligand signals.
The same product can be obtained by reaction of Ca[N(SiMe3)2]2
(108.3 mg, 0.30 mmol) suspended in hexane (2 mL) with PhSiH3
(65.0 mg, 0.60 mmol) and isoquinoline (232.5 mg, 1.80 mmol). The
reaction mixture turned immediately orange-red and an insoluble
red residue formed. After 1 h at 60 8C, the nearly colorless hexane
solution was decanted and the red residue was washed with pentane (3 Õ 3 mL). The pentane/hexane extracts contain only PhSiH3
and isoquinoline as well as a small amount of well soluble byproducts according to 1H NMR. The red residue was dried in vacuo and
extracted with benzene (3 Õ 3 mL) to yield a red benzene solution
and a light-brownish residue. All solvents from the red benzene extract were removed under high vacuum giving a red powder that
shows the same NMR as those for Ca(1,2-DHiQ)2·(iQ)4. Isolated
yield: 50.3 mg (0.062 mmol, 21 %).
The light-brownish residue of the extraction with benzene (isolated
yield: 70.5 mg, 0.042 mmol, 42 %) could be dissolved in [D8]THF.
NMR data obtained fit very well with NMR data for the complex
Ca3(1,2-DHiQ)6(iQ)6 (vide infra).
Synthesis and crystallization of Ca3(1,2-DHiQ)6(iQ)6 : Ca[N(SiMe3)2]2 (36.1 mg, 0.10 mmol) was dissolved in C6D6 (0.5 mL) and
PhSiH3 (21.6 mg, 0.20 mmol) and isoquinoline (77.5 mg, 0.60 mmol)
were added. The reaction mixture turned dark orange immediately
and was heated for 2 h at 60 8C. After cooling to room temperature, a uniform batch of orange crystals suitable for X-ray diffraction was obtained. The product could be identified as Ca3(1,2DHiQ)6(iQ)6. Isolated yield: 11.5 mg (0.0066 mmol, 20 %). Elemental
analysis calcd (%) for: C108H90N12Ca3 (1676.34): C 77.38 H 5.42 N
10.03; found C 75.37 H 5.55 N 9.10. The extreme air-sensitivity and
potential formation of stable calcium carbide are likely the cause
for strong deviation in C content. The crystals show a high air-sensitivity and are poorly soluble in benzene and toluene but slightly
soluble in [D8]THF. 1H NMR (400 MHz, [D8]THF, 25 8C): d = 4.26 (s,
2 H, DHiQ NCH2), 4.88 (d, 1 H, 3JHH = 5.6 Hz, DHiQ NCH), 6.36 (d, 1 H,
3
JHH = 7.5 Hz, DHiQ), 6.48 (t, 1 H, 3JHH = 7.2 Hz, DHiQ), 6.64 (d, 1 H,
3
JHH = 7.0 Hz, DHiQ), 6.69 (t, 1 H, 3JHH = 7.4 Hz, DHiQ), 6.99 (d, 1 H,
3
JHH = 4.8 Hz, DHiQ), 7.60 (t, 1 H, 3JHH = 8.0 Hz, iQ), 7.65–7.70 (m, 2 H,
iQ), 7.85 (d, 1 H, 3JHH = 8.3 Hz, iQ), 7.99 (d, 1 H, 3JHH = 8.1 Hz, iQ), 8.46
(d, 1 H, 3JHH = 5.7 Hz, iQ), 9.21 ppm (s, 1 H, iQ); 13C NMR (400 MHz,
[D8]THF, 25 8C): d = 54.4 (DHiQ NCH2), 89.8 (DHiQ NCH), 117.6
(DHiQ CH), 119.5 (DHiQ CH), 120.9 (iQ, CH), 123.6 (DHiQ C), 124.9
(DHiQ CH), 126.4 (DHiQ CH), 127.4 (iQ CH), 128.1 (iQ CH), 128.5 (iQ
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CH), 130.0 (iQ C), 131.0 (iQ CH), 136.9 (iQ C), 141.3 (DHiQ C), 144.3
(iQ CH), 153.5 (iQ CH), 153.5 ppm (DHiQ CH). It is of interest to
note that at high isoquiniline concentrations crystals of Ca(1,2DHiQ)2·(iQ)4 are formed whereas at lower isoquinoline concentrations oligomeric Ca3(1,2-DHiQ)6(iQ)6 crystallized. It is likely that in
solution multiple species are in equilibrium.
General procedure for the hydrosilylation of pyridines catalyzed
by (DIPPnacnac-CaH·THF)2 (NMR scale): (DIPPnacnac-CaH·THF)2
(21.0 mg, 0.020 mmol; 0.040 mmol based on the monomer) was
added to a solution of the pyridine derivative (0.40 mmol) and
PhSiH3 (48.0 mg, 0.44 mmol) in C6D6 (0.5 mL) and the reaction mixture was heated to 60 8C for 24 h. 1H NMR spectra were recorded
after 5 h and after 24 h.
Preparative catalytic procedure for bis(1,2-dihydropyridine)phenylsilane, (1,2-DHP)2PhSiH: (DIPPnacnac-CaH·THF)2 (5.0 mg,
4.7 mmol; 9.4 mmol based on the monomer) was added to a solution of pyridine (310 mg, 3.90 mmol) and PhSiH3 (300 mg,
2.77 mmol) in toluene (2 mL) and the reaction mixture was stirred
at 60 8C for 30 h. The solvent was removed in vacuum and the
product was obtained as a yellow, viscous oil which is air-sensitive.
Isolated yield: 300 mg, 1.13 mmol, 41 %. Elemental analysis calcd
(%) for: C16H18N2Si (266.41): C 72.13 H 6.81 N 10.52; found C 73.05
H 7.31 N 10.23. 1H NMR (500 MHz, C6D6, 25 8C): d = 3.76 (m, 4 H,
1,2-DHP), 4.92 (s, 1 H, Si-H), 4.97 (m, 2 H, 1,2-DHP), 5.09 (m, 2 H, 1,2DHP), 5.86 (dd, 3JHH = 9.3 Hz, 3JHH = 5.4 Hz, 2 H, 1,2-DHP), 6.22 (d,
3
JHH = 7.1 Hz, 2 H, 1,2-DHP), 7.12–7.17 (m, 3 H, Ph), 7.53 ppm (d,
3
JHH = 7.7 Hz, 2 H, Ph); 13C NMR (75 MHz, C6D6, 25 8C): d = 43.6 (1,2DHP), 104.4 (1,2-DHP), 111.7 (1,2-DHP), 125.7 (1,2-DHP), 129.0 (Ph),
131.2 (Ph), 131.5 (Ph), 135.1 (1,2-DHP), 135.6 ppm (Ph).
Preparative catalytic procedure for mono(1,2-dihydroquinoline)phenylsilane, (1,2-DHQ)PhSiH2 : (DIPPnacnac-CaH·THF)2 (5.0 mg,
4.7 mmol; 9.4 mmol based on the monomer) was added to a mixture
of quinoline (205 mg, 1.59 mmol) and PhSiH3 (108 mg, 1.00 mmol)
and the reaction mixture was stirred at 25 8C for 16 h. Remaining
PhSiH3 and quinoline were removed in vacuum at 40 8C and the
product was obtained as a colorless viscous oil which is air-sensitive. Isolated yield: 152 mg, 0.64 mmol, 64 %. Elemental analysis
calcd (%) for: C24H22N2Si (366.53): C 78.64 H 6.05 N 7.64; found C
79.11 H 6.48 N 7.44. 1H NMR (500 MHz, C6D6, 25 8C): d = 3.81 (m,
2 H, 1,2-DHQ), 5.15 (s, 2 H, Si-H), 5.37 (dt, 3JHH = 9.5 Hz, 3JHH = 4.1 Hz,
1 H, 1,2-DHQ), 6.26 (d, 3JHH = 9.5 Hz, 1 H, 1,2-DHQ), 6.70 (m, 1 H, 1,2DHQ), 6.79 (m, 1 H, 1,2-DHQ), 7.09 (d, 3JHH = 7.2 Hz, 1 H, 1,2-DHQ),
7.13 (m, 3 H, Ph) 7.51 (m, 1 H, 1,2-DHQ), 7.51 ppm (d, 3JHH = 8.1 Hz,
2 H, Ph); 13C NMR (75 MHz, C6D6, 25 8C): d = 46.8 (1,2-DHQ), 117.5
(1,2-DHQ), 120.4 (1,2-DHQ), 122.8 (1,2-DHQ), 126.1 (1,2-DHQ), 126.5
(1,2-DHQ), 127.0 (1,2-DHQ), 127.4 (Ph), 128.6 (1,2-DHQ), 129.4 (Ph),
130.6 (Ph), 134.8 (Ph), 145.4 ppm (1,2-DHQ).
Preparative catalytic procedure for bis(1,2-dihydroisoquinoline)phenylsilane, (1,2-DHiQ)2PhSiH: (DIPPnacnac-CaH·THF)2 (11.0 mg,
1.0 mmol; 2.1 mmol based on the monomer) was added to a mixture
of isoquinoline (410 mg, 3.17 mmol) and PhSiH3 (108 mg,
1.00 mmol) and the reaction mixture was stirred at 25 8C for 16 h.
Remaining PhSiH3 and isoquinoline were removed in vacuum at
40 8C giving the product as a colorless viscous oil which is air-sensitive. Isolated yield: 226 mg, 0.62 mmol, 63 %. Elemental analysis
calcd (%) for: C24H22N2Si (366.53): C 78.64 H 6.05 N 7.64; found C
79.28 H 6.35 N 7.37; 1H NMR (500 MHz, C6D6, 25 8C): d = 4.25 (m,
4 H, 1,2-DHiQ), 5.08 (s, 1 H, Si-H), 5.64 (d, 3JHH = 7.3 Hz, 2 H, 1,2DHiQ), 6.34 (d, 3JHH = 7.3 Hz, 2 H, 1,2-DHiQ), 6.64 (d, 3JHH = 7.3 Hz,
2 H, 1,2-DHiQ), 6.87 (d, 3JHH = 7.3 Hz, 2 H, 1,2-DHiQ), 6.95 (m, 2 H,
1,2-DHiQ), 7.17–7.02 (m, 5 H, Ph + 1,2-DHiQ), 7.46 ppm (d, 3JHH =
6.7 Hz, 2 H, Ph); 13C NMR (75 MHz, C6D6, 25 8C): d = 47.6 (1,2-DHiQ),
105.2 (1,2-DHiQ), 123.6 (1,2-DHiQ), 125.7 (1,2-DHiQ), 126.4 (1,2Chem. Eur. J. 2015, 21, 11452 – 11461
www.chemeurj.org
DHiQ), 127.8 (1,2-DHiQ), 128.2 (Ph), 129.1 (1,2-DHiQ), 131.7 (Ph),
134.4 (1,2-DHiQ), 135.1 (1,2-DHiQ), 135.6 (1,2-DHiQ), 135.6 ppm
(Ph).
Single crystal X-ray structure determinations: Details on the crystal structures of Ca(1,2-DHiQ)2·(iQ)4 and Ca3(1,2-DHiQ)6·(iQ)6 can be
found in the Supporting Information. CCDC 1008317 for Ca(1,2DHiQ)2·(iQ)4 and 1052060 for Ca3(1,2-DHiQ)6·(iQ)6 contain the supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Results and Discussion
Stoichiometric pyridine reduction by a calcium hydride complex
Addition of an excess of pyridine to a solution of (DIPPnacnacCaH·THF)2 at room temperature led to a fast color change from
light yellow to dark-orange. Within 20–30 min the calcium hydride complex was fully converted to DIPPnacnac-Ca(1,2DHP)·pyridine (Scheme 3). The 1,2-DHP anion shows five signals in the 1H NMR at d = 3.81, 4.52, 5.16, 6.42 and 6.64 ppm
(cf. the Mg analogue: d = 3.35, 4.38, 5.03, 6.02 and
6.20 ppm).[24] The low-field doublet at 3.81 ppm integrates for
2 H’s and is typical for the CH2 group of 1,2-DHP. The reaction
is highly regioselective for the 2-position and no side reactions
like reduction at the 4-position or a deprotonation in 2-position[30] have been observed. It is also noteworthy that the hydride transfer from (DIPPnacnac-CaH·THF)2 to pyridine proceeds smoothly already at room temperature and is significantly faster than that for (DIPPnacnac-MgH·THF)2.[24]
In contrast to the comparable magnesium DHP complexes,
the resulting dihydropyridide complex DIPPnacnac-Ca(1,2DHP)·pyridine dissolved in C6D6 is not stable towards ligand exchange by the Schlenk equilibrium and considerable quantities
of the homoleptic complexes (DIPPnacnac)2Ca and Ca(1,2DHP)2 were observed already after 30 min. Use of the more
polar solvent [D8]THF led to immediate formation of homoleptic species. This observation hampered a more detailed characterization of the novel complex. In order to obtain a heterolep-
Scheme 3. Reaction of [DIPPnacnac-CaH·THF]2 with pyridines.
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tic calcium dihydropyridide complex that is stable towards
ligand exchange, a variety of pyridine derivatives were tested
(Scheme 3). In reaction with (DIPPnacnac-CaH·THF)2, all substrates showed a fast and selective hydride transfer to the 2position with 80–90 % conversion. The only exception is 2,6-lutidine which formed 1,4-dihydro-2,6-lutidide in very poor yields
(< 5 %). This is most likely due to the fact that formation of the
kinetic product, 1,2-dihydro-2,6-lutidide, is hindered by the Me
substituents. It is still noteworthy that the reaction of the calcium hydride complex with 2,6-lutidine gave minor amounts of
product. Previous attempts to react magnesium hydride complexes with 2,6-lutidine failed.[21, 25] Likewise, the transition
metal catalyzed hydrosilylation of 2,6-lutidine gave no conversion.[9, 10] These observations were taken as an indication that
the initial step in pyridine dearomatization is hydride transfer
to the 2-position. Equally unusual is the fact that the Me-substituent in 2-picoline, 4-picoline or 2,6-lutidine is not deprotonated by the calcium hydride complex (DIPPnacnac-CaH·THF)2.
It is known that reaction with scandium methyl and yttrium
benzyl complexes give deprotonation of the highly acidic Mesubstituent.[31, 32] Likewise, deprotonation of picoline and lutidine by organolithium reagents is a keystep in their functionalization.[33]
Despite the smooth and selective reactions, no well-defined
heteroleptic calcium dihydropyridide complexes could be isolated. This is due to fast Schlenk equilibria which produce mixtures of heteroleptic and homoleptic complexes (Scheme 3). In
the case of pyridine and quinoline, Schlenk equilibria were
slow enough to record 1H NMR data for the heteroleptic complexes but unambiguous 13C data could not be obtained. For
isoquinoline, Schlenk equilibria are sufficiently slow to record
1
H and 13C NMR spectra but crystals of a heteroleptic species
could not be obtained. However, the solvent-free reaction of
(DIPPnacnac-CaH·THF)2 in pure isoquinoline gave a batch of
dark red, extremely air-sensitive, square-shaped crystals. Single
crystal X-ray diffraction revealed crystallization of the homoleptic complex Ca(1,2-dihydroisoquinolide)2·(isoquinoline)4 in reasonable yield (57 %).
The complex Ca(1,2-dihydroisoquinolide)2·(isoquinoline)4,
which we abbreviate as Ca(1,2-DHiQ)·(iQ)4, crystallized as a centrosymmetric molecule in a triclinic lattice with space group P1̄
(Figure 1 a). Selected bond lengths and angles are shown in
Table 1 and Figure 1 b. The octahedral coordination sphere
around the Ca center is provided by the nitrogen atoms of
two DHiQ anions (N1, N1’) in trans-position and four neutral iQ
ligands (N2, N2’, N3, N3’) in a perpendicular plane. Differences
in the bonding between Ca2 + and anionic 1,2-DHiQ or neutral
iQ ligands are of electrostatic origin and reflected in their respective Ca–N distances (Figure 1). Both 1,2-DHiQ anions are
clearly defined (no disorder) and the N¢CH2 and C¢CH2 bonds
are significantly elongated which is in agreement with the
dearomatization of the isoquinoline moiety and hydride transfer to the 2-position (Figure 1 b). The bond lengths in the annulated phenyl ring of the 1,2-DHiQ anions do not differ significantly from each other, indicating largely delocalized double
bonds within this ring. On the contrary, the single and double
bonds in the neutral iQ units show alternating bond lengths
Chem. Eur. J. 2015, 21, 11452 – 11461
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and are considerably more localized (Figure 1 b). The nitrogen
atoms within the 1,2-DHiQ anions [—bond angles = 356.1(2)8] and
two of the neutral iQ ligands [—bond angles = 355.5(1)8] are slightly
pyramidalized while the remaining two neutral iQ ligands contain trigonal planar nitrogen atoms [—bond angles = 356.1(2)8]. A
similar pyramidalization at N has been observed in magnesium
pyridide complexes[21, 24] but there are also examples for planar
N geometries.[25] As the energy surface for pyramidalization is
very shallow, such effects are likely determined by intra- and
intermolecular interactions.
As heteroleptic calcium dihydropyridide complexes are
plagued by fast Schlenk equilibria we focused on the direct
synthesis of homoleptic calcium dihydropyride complexes. Reaction of Ca[N(SiMe3)2]2 with two equivalents of PhSiH3 and six
equivalents of isoquinoline in hexane gave immediate formation of a red precipitate which shows the composition Ca(1,2DHiQ)2·(iQ)4. Performing the same reaction in benzene gave
orange crystals with a higher 1:1 ratio of 1,2-DHiQ and isoquinoline. Crystal structure analysis revealed the trimeric complex
Ca3(1,2-DHiQ)6·(iQ)6 which crystallized in the trigonal lattice
with space group R3̄ (Figure 2). The highly symmetric complex
possesses a crystallographic three-fold inversion axis. Selected
Table 1. Selected bond lengths [æ] and angles [8] for Ca(1,2-DHiQ)2·(iQ)4
and Ca3(1,2-DHiQ)6·(iQ)6.
Ca(1,2-DHiQ)2·(iQ)4
Ca3(1,2-DHiQ)6·(iQ)6
Ca¢N1
Ca¢N2
Ca¢N3
N1-Ca-N2
N1-Ca-N2’
N1-Ca-N3
N1-Ca-N3’
Ca1¢N1
Ca2¢N1
Ca2¢N2
N1-Ca1-N1’
N1-Ca1-N1’’
N1-Ca1-N1’’’
N1-Ca2-N2
2.400(2)
2.523(2)
2.526(2)
89.51(6)
90.49(6)
87.21(6)
92.79(6)
2.550(2)
2.495(2)
2.574(2)
78.75(7)
101.25(7)
180
98.28(6)
N1-Ca2-N2’
N1-Ca2-N2’’
N1-Ca2-N1’
N2-Ca-N2’
Ca1-N1-Ca2
178.28(7)
97.58(6)
80.83(6)
83.29(7)
84.43(6)
Figure 1. a) Crystal structure of Ca(1,2-DHiQ)2·(iQ)4. b) C¢C and C¢N bond
lengths in the 1,2-DHiQ and iQ ligands (for the latter average values are
shown).
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gives 1,4-allylpyridide.[34] Another report addresses the reaction
of Ca(1,4-Ph3Si-pyridide)2 with pyridine which cleanly generates
the following products: Ca(1,4-pyridide)2 and 4-Ph3Si-pyridine.[35] It is suggested that this reaction goes through a CaH2
intermediate. In the light of the herein described 1,2-selective
reduction of pyridine by calcium hydride, it seems more likely
that there is direct H-transfer from 1,4-Ph3Si-pyridide to pyridine.
DFT calculations
Figure 2. a) Crystal structure of Ca3(1,2-DHiQ)6·(iQ)6 ; hydrogen atoms have
been omitted for clarity. b) The Ca-N framework.
bond lengths and angles are shown in Table 1. The complex
consists of a central Ca2 + ion (Ca1) bound to six negatively
charged 1,2-DHiQ anions that bridge to two terminal Ca2 + ions
(Ca2/Ca2’). Ca¢N bond distances to the central Ca2 + ion
(2.550(2) æ) are somewhat longer than those to the terminal
Ca2 + ions (2.495(2) æ). The longest Ca–N distances are observed for the neutral iQ ligands in terminal positions
(2.574(2) æ). The metal coordination geometries are slightly distorted from octahedral. All hydrogen atoms have been located
in the difference Fourier map and were refined isotropically.
Therefore the identities of dearomatized 1,2-DHiQ anions and
neutral isoquinoline ligands could be established unequivocally. Their geometries show similar C¢C and C¢N bond patterns
as discussed for Ca(1,2-DHiQ)2·(iQ)4 (Figure 1 b).
The high 1,2-selectivity for the addition of calcium hydride
complexes to pyridines and quinolines strongly contrasts to
that of the magnesium hydrides. Calcium 1,2-pyridides, 1,2-picolides and 1,2-quinolides are also thermally quite stable towards isomerization to 1,4-products. Although this unusual
preference may be exploited in catalytic regimes (vide infra),
the striking difference in selectivity between Mg and Ca hydride additions is still not understood. An unusual case for this
1,2-selectivity was previously reported for the reaction of a binuclear magnesium hydride complex with pyridine (Scheme 2).
Preference for 1,2-DHP was explained by weak intramolecular
C-H···C(p) and p–p stacking interactions in the product.[21] The
crystal structures of Ca(1,2-DHiQ)2·(iQ)4 and Ca3(1,2-DHiQ)6·(iQ)6,
however, do not show such interactions. This means that the
unusual preference for hydride transfer to the 2-position is inherent to calcium pyridide complexes.
It is unclear why calcium hydride complexes show highly selective 1,2-addition to pyridines (or why no 1,2 ! 1,4 isomerization takes place). This observation is also in striking contrast
with the superb 1,4-selectivity for dearomatization of pyridine
by Ca(h3-allyl)2 : it is claimed that the allyl anion initially attacks
at the 2-position and subsequent 1,2 ! 1,4 isomerization
Chem. Eur. J. 2015, 21, 11452 – 11461
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In order to gain insight in the unusually high preference for
1,2-addition of calcium hydrides to pyridines, we initiated a theoretical investigation.
In a first approach, the molecular structures of the 1,2-DHP
and 1,4-DHP anions as well as their b-diketiminate magnesium
and calcium complexes were optimized by DFT calculations at
the B3PW91/6-311G(d,p) level (Figures 3 and 4). The free 1,4DHP anion is 6.3 kcal mol¢1 more stable than the 1,2-DHP
anion. For Mg and Ca complexes a somewhat smaller but significant preference of 4.0 kcal mol¢1 for the 1,4-DHP isomers is
calculated. Although this is in line with experimental observations in Mg chemistry, it does not explain the highly selective
formation of 1,2-DHP complexes for Ca. The latter could only
be explained by assuming that the first step in the reaction of
the metal hydride with pyridine is a selective addition to form
the 1,2-DHP product and the second step is isomerization to
a 1,4-DHP product. An explanation for the striking differences
in Mg and Ca chemistry might then be explained by differences in the transition states of the final isomerization step.
An obvious transition state for the 1,2-DHP!1,4-DHP isomerization would be a direct transfer of H from 2- to 4-position. However, in all cases no transition state for direct H transfer through a four-membered ring as the transition state could
be found. This is likely due to immense strain in such a transition state and is in contrast with the relatively facile allyl shift
observed in transformation of the 2-allyl-pyridide anion to the
4-allyl-pyridide anion. The latter goes through a preferred 6membered ring as the transition state (DH … 25–30 kcal
mol¢1).[34] Attempts to find a pathway for the 1,2-DHP ! 1,4DHP isomerization through direct H-transfer from 1,2-DHP to
the 4-position of a coordinated pyridine also failed.
It was found that 1,2-DHP!1,4-DHP isomerization of the
free anions goes via the 1,3-DHP anion as a transition state
(NIMAG = 1). This isomer, for which no resonance structure
with negative charge on N can be written, is 5.2 kcal mol¢1
higher in energy than the 1,2-DHP anion. Also isomerization of
DIPPnacnac-Mg(1,2-DHP) to DIPPnacnac-Mg(1,4-DHP) proceeds
via the 1,3-DHP species as a transition state. The activation
energy of 14.8 kcal mol¢1 is considerably higher but explains
the observed isomerization of Mg complexes (Scheme 2).
Interestingly, the Ca complex DIPPnacnac-Ca(1,3-DHP)
turned out to be not a transition state but is a true minimum
on the potential surface (NIMAG = 0). This complex even represents the most stable isomer: it is 4.3 kcal mol¢1 more stable
than the 1,2-DHP complex. The reason for the unusual stability
of DIPPnacnac-Ca(1,3-DHP) may be due to a metal effect. The
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Figure 3. DFT optimized structures, B3PW91/6-311G(d,p), for the dihydropyridide anions and their Mg and Ca complexes. The 1,3-DHP anion and DIPPnacnacMg(1,3-DHP) are transition states and all others are true minima.
Figure 4. Energy profiles for the 1,2-DHP!1,4-DHP isomerization (DH in kcal
mol¢1, B3PW91/6-311G(d,p)).
Chem. Eur. J. 2015, 21, 11452 – 11461
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molecular structures of DIPPnacnac-Mg(1,3-DHP) and DIPPnacnac-Ca(1,3-DHP) show strikingly different coordination modes.
Whereas in the first case the 1,3-DHP anion is bound h2 to
Mg2 + , the latter structure shows a face-on h4-coordination of
the 1,3-DHP anion to Ca2 + . This is in line with the C¢C and C¢
N bond lengths in the 1,3-DHP anion which in the Mg complex
shows a more localized structure (strong alternation) whereas
that in the Ca complex is more delocalized (less alternation). It
is also in agreement with the charge distribution in the 1,3DHP anion (NPA charges see Supporting Information). Whereas
in the Mg complex most of the negative charge in the 1,3-DHP
anion is mainly localized on the N and 2-position, the Ca complex shows a more evenly distribution of negative charge in
the 1,3-DHP ring. The origin for these differences between the
Mg and Ca complexes is simply the larger size of Ca2 + (Mg2 + :
0.72 æ, Ca2 + : 1.00 æ; 6-coordinate)[36] which allows for a higher
hapticity in ligand binding.
In case of the Ca complex, we were able to locate the transition states for 1,2-DHP!1,3-DHP and 1,3-DHP!1,4-DHP isomerization (see Supporting Information). The activation enthalpies for these reactions are 74.9 kcal mol¢1 and 55.4 kcal mol¢1,
respectively, and both should be considered high enough to
make the reaction unlikely (Figure 4).
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Solvation by addition of an extra pyridine ligand is endothermic (1–2 kcal mol¢1) and due to entropy effects the free energies for solvation are clearly endergonic (9–10 kcal mol¢1; see
Supporting Information for details). It is therefore unlikely that
solvated structures play a role under dynamic conditions. Interestingly, the optimized structure for DIPPnacnac-Ca(1,3DHP)·pyridine also shows multi-hapto bonding between Ca
and 1,3-DHP. Therefore, solvation with pyridine was not further
considered.
Application in catalytic conversion of pyridine derivatives
The unique preference for formation of calcium 1,2-DHP complexes may be exploited in catalysis. In succession of earlier reports on magnesium hydride catalyzed hydroboration of pyriScheme 4. Proposed mechanism for the calcium catalyzed hydrosilylation of
pyridines; for clarity the reaction of only one equivalent of pyridine is
dines,[20, 21] we investigated the potential application of (DIPPshown.
nacnac-CaH·THF)2 as a catalyst. The calcium hydride species,
however, proved to be inactive
in the hydroboration of a range
Table 2. Hydrosilylation of pyridine derivatives with PhSiH3 catalyzed by (DIPPnacnac-CaH·THF)2.
of pyridine derivatives with pinacolborane (HBpin, 10 mol % cataSubstrate
Conditions[a]
Product
Conv.[%][b]
Yield [%][c]
lyst, C6D6, 25–60 8C) and instead
0.4 mmol, C6D6, 60 8C, 24 h; 5 mol %
(1,2-DHP)2PhSiH
80
–
B2(pin)3 was observed as the
I
3.9 mmol, toluene, 60 8C, 30 h; 0.12 mol %
(1,2-DHP)2PhSiH
–
41
major product. As catalytic decomposition of pinacolborane
0.4 mmol, C6D6, 60 8C, 24 h, 5
(1,2-DHQ)PhSiH2
90
–
VII
1.6 mmol, 25 8C, 16 h, 0.30 mol %
(1,2-DHQ)PhSiH2
–
64
seems to be faster than the hydroboration reaction, we re0.4 mmol, C6D6, 60 8C, 24 h, 5 mol %
(1,2-DHiQ)2 PhSiH
90
–
VIII
frained from further investiga3.2 mmol, 25 8C, 16 h, 0.32 mol %
(1,2-DHiQ)2 PhSiH
–
63
tions.
[a] Mol % catalyst based on dimer. [b] Conversion determined by 1H NMR. [c] Isolated yield.
A more challenging alternative
application is the hydrosilylation
of pyridines.[8–11, 14] A tentative
general catalytic cycle, based on earlier reported investigations
tones.[37] These differences in reactivity can be explained by
[11]
with a titanium hydride catalyst, is shown in Scheme 4. Previthe fact that, in contrast to PhSiH3, the product (1,2ous attempts to perform this transformation with magnesium
DHP)SiH2Ph is an amine and therefore a potential Lewis base.
Precoordination of this product to the Ca-(1,2-DHP) complex B
hydride catalysts failed on account of the low reactivity of
magnesium pyridide with PhSiH3, that is, the second step in
promotes fast conversion to the bis-substituted product (1,2the catalytic cycle (B!C).[20, 25] However, the much higher reacDHP)2PhSiH (Scheme 5). The higher reactivity of (1,2tivity of calcium complexes could be the key to such transition
DHP)SiH2Ph versus PhSiH3 is therefore due to a complex-inmetal-free catalysis.
duced proximity effect (CIPE).[38] Further conversion of the bisA number of pyridine derivatives (see Scheme 3) were
substituted product (1,2-DHP)2PhSiH to the tris-substituted
product PhSi(1,2-DHP)3 is most likely not possible for steric reascreened as substrates for the hydrosilylation with PhSiH3 at
the NMR scale (5 mol % catalyst). (DIPPnacnac-CaH·THF)2
sons. Similarly, also doubly aminated products are observed for
turned out to be an efficient catalyst for pyridine (I) and quinoisoquinoline (VII) but a single amination is observed for quinolines (VII and VIII) (Table 2) but performed poorly for alkylated
line (VIII). Sole formation of mono-substituted silanes in the
pyridines (II–VI, conversion: 10–20 %). Catalytic hydrosilylation
case of quinoline could be explained by steric hindrance. Quinoline (VIII) is an ortho-substituted pyridine which should be
of pyridine and quinolines led to the exclusive formation of silanes with 1,2-dihydropyridine and 1,2-quinoline substituents.
considered more sterically hindered than isoquinoline (VII) or
This means that in this case the unusual selectivity for hydride
pyridine (I).
transfer to the 2-position, as found in stoichiometric experiCatalytic runs that resulted in a reasonable conversion at the
ments, is also maintained in a catalytic regime.
NMR scale were repeated at a slightly larger scale resulting in
the isolation of products in reasonable to good isolated yields
Analysis of the products shows that PhSiH3 is doubly aminated in the cases of pyridine (I). As only bis(1,2-DHP)-silane and
(Table 2). The reduction of the catalyst loading could be lownot even traces of mono(1,2-DHP)-silane have been observed,
ered to the 0.12–0.32 mol % range. Lowering of the temperaaddition of the second pyridine moiety is significantly faster
ture to 25 8C in the reactions of quinoline and isoquinoline still
than that of the first equivalent. A similar observation has
gave reasonable isolated yields.
been reported for the Ca-catalyzed hydrosilylation of keChem. Eur. J. 2015, 21, 11452 – 11461
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Scheme 5. Proposed route for the double-hydrosilylation of pyridine derivatives by a Ca catalyst.
As observed in stoichiometric experiments, the heteroleptic
DIPPnacnac-Ca(1,2-DHP) complexes are subject to Schlenk
equilibria and cannot be regarded as well-defined single-site
catalysts. In situ preparation of “CaH2” as a homoleptic catalyst
from Ca[N(SiMe3)2]2·(THF)2 and PhSiH3 gave comparable results
in catalysis as (DIPPnacnac-CaH·THF)2. This means that simple,
readily prepared, homoleptic Ca amide reagents can also be
employed in these selective conversions.
In line with the excellent 1,2-selectivity for addition of (DIPPnacnac-CaH·THF)2 to pyridine derivatives, the catalytic hydrosilylation yielded in all cases 1,2-substituted products. This could
be an indication for a calcium hydride as the active species in
the catalytic cycle and would strongly support the earlier proposed cycle for Ti-mediated pyridine hydrosilylation
(Scheme 4).[11] In a first step, the [Ca]-H complex A reacts with
a pyridine molecule to form [Ca]-1,2-DHP (B). In contrast to
transition-metal catalyzed hydrosilylations, an ion-pair containing a hypervalent silicon species is proposed as the following
intermediate C. Especially under polar conditions (the presence
of strongly polar pyridine derivatives) such ion-pairs are feasible.[39] A subsequent hydride transfer to the cationic calcium
species releases the N-silylated product and regenerates the
[Ca]-H complex A. This mechanism is in line with Ca-catalyzed
alkene hydrosilylation.[40]
In contrast to magnesium pyridide products, the calcium
pyridides are more prone to Schlenk equilibria and conversion
to homoleptic species is generally fast (< 30 min, 20 8C). This
hinders the isolation of the heteroleptic complex DIPPnacnacCa(1,2-DHP). However, two homoleptic complexes could be
structurally characterized: Ca(1,2-DHiQ)2·(iQ)4 and Ca3(1,2DHiQ)6·(iQ)6.
The remarkable difference in selectivity for the addition of
magnesium and calcium hydride complexes to pyridines has
been investigated by DFT calculations. The first step is addition
to form the 1,2-DHP products. In case of Mg facile isomerization to the more stable 1,4-DHP product is possible. This process proceeds through a 1,3-DHP transition state and needs an
activation energy of 14.8 kcal mol¢1. For Ca the situation is different: DIPPnacnac-Ca(1,3-DHP) is a true minimum and the
most stable isomer. The activation energies for isomerization
of the initially formed DIPPnacnac-Ca(1,2-DHP) to the 1,3-DHP
and 1,4-DHP isomers are very high (55–75 kcal mol¢1) and explain the high 1,2-selectivity.
The high 1,2-selectivity for the addition of calcium hydride
complexes to pyridines and quinolines can be exploited in catalysis. Although there is precedence for catalytic pyridine hydroboration with magnesium hydride catalysts, the calcium hydride complex was found to be inactive for this transformation.
This is due to a Ca-catalyzed side reaction that converts pinacol borane (HBpin) into B2(pin)3. The more challenging hydrosilylation of pyridine and quinolines, which is not catalyzed by
magnesium hydride complexes, proceeds smoothly with the
calcium hydride catalysts (DIPPnacnac-CaH·THF)2 and Ca[N(SiMe3)2]2·(THF)2 (25–60 8C, 80–90 % conversion). This is likely due
to the much higher reactivity of calcium versus magnesium
amides. The exclusive formation of products with 1,2-dihydropyridine and 1,2-dihydroquinoline units suggests that calcium
hydride species are key intermediates in this transformation.
This unusual 1,2-selectivity in a calcium catalyzed hydrosilylation of pyridines amends the recently reported, highly 1,4-selective pyridine hydrosilylation by a Ru complex.[9, 14] The herein
presented contribution to the fast growing area of alkalineearth metal catalysis[19] is another illustrative example of how
this field complements rather than competes with transition
metal catalysis.
Acknowledgements
Conclusion
The DFG is gratefully acknowledged for financial support.
Reaction of the calcium hydride complex (DIPPnacnacCaH·THF)2 with pyridine is much faster and more selective than
that of the corresponding magnesium hydride complexes. The
hydride anion is exclusively transferred to the 2-position of
pyridine and at higher temperatures no 1,2!1,4 isomerization
is observed. The higher reactivity of calcium hydride complexes is exemplified by the reaction with 2,6-lutidine (VI),
a pyridine with blocked 2- and 6-positions: whereas magnesium hydride complexes showed no reaction, the more reactive
calcium hydride complex gave slow conversion to a 1,4-DHP
product.
Chem. Eur. J. 2015, 21, 11452 – 11461
www.chemeurj.org
Keywords: calcium · catalysis · hydride · hydrosilylation ·
reduction
[1] J. M. Berg, J. L. Tymoczko, L. Stryer, Biochemistry, 5th ed., 2002.
[2] M. Schramm, G. Thomas, R. Towart, G. Franckowiak, Nature 1983, 303,
535 – 537.
[3] M. Nasr-Esfahani, M. Moghadam, S. Tangestaninejad, V. Mirkhani, A. R.
Momeni, Bioorg. Med. Chem. 2006, 14, 2720 – 2724.
[4] M. Anniyappan, D. Muralidharan, P. T. Perumal, Tetrahedron 2002, 58,
5069 – 5073.
[5] N. Edraki, A. R. Mehdipour, M. Khoshneviszadeh, R. Miri, Drug Discovery
Today 2009, 14, 1058 – 1068.
11460
Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper
[6] E. M. P. Silva, P. A. M. M. Varandas, A. M. S. Silva, Synthesis 2013, 45,
3053 – 3089.
[7] C. Seki, M. Hirama, N. D. M. Romauli Hutabarat, J. Takada, C. Suttibut, H.
Takahashi, T. Takaguchi, Y. Kohari, H. Nakano, K. Uwai, N. Takano, M.
Yasui, Y. Okuyama, M. Takeshita, H. Matsuyama, Tetrahedron 2012, 68,
1774 – 1781.
[8] K. Osakada, Angew. Chem. Int. Ed. 2011, 50, 3845 – 3846; Angew. Chem.
2011, 123, 3929 – 3930.
[9] D. V. Gutsulyak, A. van der Est, G. I. Nikonov, Angew. Chem. Int. Ed. 2011,
50, 1384 – 1387; Angew. Chem. 2011, 123, 1420 – 1423.
[10] J. F. Harrod, R. Shu, H.-G. Woo, E. Samuel, Can. J. Chem. 2001, 79, 1075 –
1185.
[11] L. Hao, J. F. Harrod, A. M. Lebuis, Y. Mu, R. Shu, E. H. Samuel, H. G. Woo,
Angew. Chem. Int. Ed. 1998, 37, 3126 – 3129; Angew. Chem. 1998, 110,
3314 – 3318.
[12] K. Oshima, T. Ohmura, M. Suginome, Chem. Commun. 2012, 48, 8571 –
8573.
[13] K. Oshima, T. Ohmura, M. Suginome, J. Am. Chem. Soc. 2012, 134,
3699 – 3702.
[14] C. D. F. Kçnigs, H. F. T. Klare, M. Oestreich, Angew. Chem. Int. Ed. 2013,
52, 10076 – 10079; Angew. Chem. 2013, 125, 10260 – 10263.
[15] A. P. Shaw, B. L. Ryland, M. J. Franklin, J. R. Norton, J. Y.-C. Chen, M. Lynn
Hall, J. Org. Chem. 2008, 73, 9668 – 9674.
[16] D. A. Black, R. E. Beveridge, B. A. Arndtsen, J. Org. Chem. 2008, 73,
1906 – 1910.
[17] C. Nadeau, S. Aly, K. Belyk, J. Am. Chem. Soc. 2011, 133, 2878 – 2880.
[18] A. S. Dudnik, V. L. Weidner, A. Motta, M. Delferro, T. J. Marks, Nat. Chem.
2014, 6, 1100 – 1107.
[19] For reviews, see: a) S. Harder, Chem. Rev. 2010, 110, 3852; b) A. G. M.
Barrett, M. R. Crimmin, M. S. Hill, P. A. Procopiou, Proc. R. Soc. London
Ser. A 2010, 466, 927; c) M. R. Crimmin, M. S. Hill, Topics in Organometallic Chemistry, Ed. S. Harder, 2013, vol. 45, p. 191.
[20] M. Arrowsmith, M. S. Hill, T. Hadlington, G. Kociok-Kçhn, C. Weetman,
Organometallics 2011, 30, 5556 – 5559.
[21] J. Intemann, M. Lutz, S. Harder, Organometallics 2014, 33, 5722 – 5729.
Chem. Eur. J. 2015, 21, 11452 – 11461
www.chemeurj.org
[22] E. C. Ashby, A. B. Goel, J. Am. Chem. Soc. 1977, 99, 310 – 311.
[23] E. C. Ashby, A. B. Goel, J. Chem. Soc. Chem. Commun. 1977, 169 – 169.
[24] M. S. Hill, D. J. MacDougall, M. F. Mahon, Dalton Trans. 2010, 39, 11129 –
11131.
[25] M. S. Hill, G. Kociok-Kçhn, D. J. MacDougall, M. F. Mahon, C. Weetman,
Dalton Trans. 2011, 40, 12500 – 12509.
[26] J. G. Keay, Adv. Heterocycl. Chem. 1986, 39, 1 – 77.
[27] F. W. Fowler, J. Am. Chem. Soc. 1972, 94, 5926 – 5927.
[28] S. Harder, J. Brettar, Angew. Chem. Int. Ed. 2006, 45, 3474 – 3478; Angew.
Chem. 2006, 118, 3554 – 3558.
[29] S. Harder, Organometallics 2002, 21, 3782 – 3787.
[30] S. Jie, P. L. Diaconescu, Organometallics 2010, 29, 1222 – 1230.
[31] B.-T. Guan, B. Wang, M. Nishiura, Z. Hou, Angew. Chem. Int. Ed. 2013, 52,
4418 – 4421; Angew. Chem. 2013, 125, 4514 – 4517.
[32] B. F. Wicker, H. Fan, A. K. Hickey, M. G. Crestani, J. Scott, M. Pink, D. J.
Mindiola, J. Am. Chem. Soc. 2012, 134, 20081 – 20096.
[33] V. Mamane, E. Aubert, Y. Fort, J. Org. Chem. 2007, 72, 7294 – 7300.
[34] P. Jochmann, T. S. Dols, T. P. Spaniol, L. Perrin, L. Maron, J. Okuda,
Angew. Chem. Int. Ed. 2010, 49, 7795 – 7798; Angew. Chem. 2010, 122,
7962 – 7965.
[35] V. Leich, T. P. Spaniol, L. Maron, J. Okuda, Chem. Commun. 2014, 50,
2311 – 2314.
[36] R. D. Shannon, Acta Crystallogr. Sect. A 1976, 32, 751 – 767.
[37] J. Spielmann, S. Harder, Eur. J. Inorg. Chem. 2008, 1480 – 1486.
[38] B. Chauder, L. Green, V. Snieckus, Pure Appl. Chem. 1999, 71, 1521 –
1529.
[39] P. Jochmann, J. P. Davin, T. P. Spaniol, L. Maron, J. Okuda, Angew. Chem.
Int. Ed. 2012, 51, 4452 – 4455; Angew. Chem. 2012, 124, 4528 – 4531.
[40] F. Buch, J. Brettar, S. Harder, Angew. Chem. Int. Ed. 2006, 45, 2741 – 2745;
Angew. Chem. 2006, 118, 2807 – 2811.
Received: March 18, 2015
Published online on June 26, 2015
11461
Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim