Synthesis of hemilabile P,N ligands: ω-2-pyridyl-n-alkylphosphines

Article abstract of DOI:10.1007/pl00010260

A series of P,N ligands of the general formula (2-py)-(CH₂)_n-PR₂ (2-py: 2-pyridyl; R: i-Pr (n = 1, 4-7), Ph (n = 5-7)) 4a g and 6a has been synthesized. Starting from 2-picoline (1), 2-(ω-chloroalkyl)pyridines 3a-d are prepared. The reactions of 3a-d with (i-Pr)₂PLi and Ph₂PLi, respectively, result in the title compounds 4a-g in up to 89percent yield. Reaction of Cl-(CH₂)₃-P(i-Pr)₂ with 2-picolyllithium (2) is an alternative route to 4a. Additionally, P,P,N ligands 7a and 9 are synthesized by similar methods. All new compounds were fully characterized. The formation of cyclic pyridinium derivatives 5a and 5b from intramolecular S_N reactions of 3a and 3b is discussed in detail.

Full text of DOI:10.1007/pl00010260

Monatshefte f uÈ r Chemie 130, 783±794 (1999)
Synthesis of Hemilabile P,N Ligands:
x-2-Pyridyl-n-alkylphosphines
Achim Jansen and Stephan PitterÃ
Projektgruppe CO -Chemie, Friedrich-Schiller-Universit aÈ t Jena, D-07743 Jena, Germany
2
Summary. A series of P,N ligands of the general formula (2-py)-(CH )n-PR (2-py: 2-pyridyl; R: i-Pr
2
2
(
n ˆ 1, 4±7), Ph (n ˆ 5±7)) 4a±g and 6a has been synthesized. Starting from 2-picoline (1), 2-(!-
chloroalkyl)pyridines 3a±d are prepared. The reactions of 3a±d with (i-Pr) PLi and Ph PLi,
2
2
respectively, result in the title compounds 4a±g in up to 89% yield. Reaction of Cl-(CH ) -P(i-Pr)
2
2
3
with 2-picolyllithium (2) is an alternative route to 4a. Additionally, P,P,N ligands 7a and 9 are
synthesized by similar methods. All new compounds were fully characterized. The formation of
cyclic pyridinium derivatives 5a and 5b from intramolecular SN reactions of 3a and 3b is discussed
in detail.
Keywords. Hemilabile ligand; P,N Ligand.
Synthese hemilabiler P,N-Liganden: x-2-Pyridyl-n-alkylphosphine
Zusammenfassung. Ausgehend von 2-Picolin (1) werden die homologen P,N-Liganden (2-py)-
È
(
CH )n-PR (2-py: 2-Pyridyl; R: i-Pr (n ˆ 1, 4±7), Ph (n ˆ 5±7) 4a±g und 6a dargestellt. Uber die
2
2
entsprechenden 2-(!-Chloralkyl)pyridine 3a±d erh aÈ lt man durch nachfolgende Umsetzung mit
i-Pr) PLi bzw. Ph PLi die Titelverbindungen 4a±g in bis zu 89% Ausbeute. Alternativ erh aÈ lt man
(
2
2
È
Verbindung 4a durch Umsetzung von Cl-(CH ) -P(i-Pr) mit 2-Picolyllithium (2). Ahnliche
2
3
2
Synthesemethoden er oÈ ffnen einen einfachen Zugang zu den P,P,N-Liganden 7a und 9. Alle neuen
Verbindungen wurden vollst aÈ ndig charakterisiert. Die Bildung der zyklischen Pyridiniumderivate 5a
und 5b durch intramolekulare SN-Reaktionen von 3a bzw. 3b wird im Detail diskutiert.
Introduction
Bidentate ligands which offer two different coordination sites are termed to be
hemilabile [1]. They provide interesting properties in catalytic reactions: Fixed at
the metal centre by one strong donor group, the number of coordination sites may
be varied by addition or removal of the weaker donor group. This hemilability may
play an important role during a catalytic cycle because key intermediates are often
stabilized by weaker donor ligands, e.g. solvent molecules. Most recently, we were
able to show that !-cyano-n-alkylphosphines exhibit an extraordinary effect on the
cooligomerization of 1,3-butadiene and carbon dioxide due to labile bonding of the
nitrile backbone to the active centre [2, 3]. Consequently, catalysts with hemilabile
à Corresponding author

784
A. Jansen and S. Pitter
ligands may decrease the enthalpy of activation for fundamental reactions of the
catalytic cycle.
Similar P,N ligands with one phosphino and one pyridyl moiety have attracted
considerable interest in the remaining decade [4]. They offer unique properties in
some catalytic reactions like the alkoxycarbonylation of alkynes [5]. Other recent
®
elds of interest are the synthesis of heterobimetallic complexes [6] or studies on
novel organic reactions [7]. Phosphinopyridines are often ®xed in sterically rigid
systems: As ligands, they tend to form stable cis chelate complexes [4].
Phosphinopyridines with (CH ) chains (n > 3) as spacers are rare [8]. Increasing
2
n
the number of spacer atoms should decrease the tendency to form chelate
complexes and therefore might have a signi®cant in¯uence on catalytic processes.
In order to study the behaviour of phosphinopyridines with variable spacer
lengths in catalytic systems as well as in the formation of mononuclear complexes,
our aim was to establish their synthetic approach. In this report, we describe the
preparation and properties of a variety of !-2-pyridyl-n-alkylphosphines and of
some related P,P,N ligands.
Results and Discussion
ꢀ
-Metalation of 2-picoline (1) provides an easy access to further substitution with
alkyl halides [9]. Two routes for the syntheses of !-2-pyridyl-n-alkylphosphines
were examined (Scheme 1).
After metalation of 1, the reaction with ꢀ-bromo-!-chloro-n-alkanes affords
3a±d in up to 94% yield. Interestingly, 3a and 3b undergo intramolecular SN
reactions to chlorides 5a and 5b (Scheme 2). Similar cyclic pyridinium salts have
been synthesized by other methods [10±12]. The C,N stretching frequencies of the
�
1
� 1
pyridine moiety shift from 1561 and 1591 cm to 1635 and 1583 cm , indicating
a positive charge at the nitrogen. In particular, all attempts to purify 3a result in low
yield.
3c and 3d do not yield cyclic pyridinium salts as consecutive products.
Obviously, the reaction is controlled by the formation of thermodynamically
favoured ring sizes in the case of 3a and 3b. Molecular mass determination of 5a
Scheme 1. Synthesis of 4a±d (R: i-Pr, n ˆ 4±7) and 4e±g (R: Ph, n ˆ 5±7)

!
-2-Pyridyl-n-alkylphosphines
785
Scheme 2. Intramolecular reactions of 3a and 3b
via measuring the osmotic pressure in chloroform solution indicates the existence of
a dimer species. Dimers are also indicated by the FAB mass spectrum of 5a and the
EI mass spectrum of 5b, whereas the EI mass spectrum of 5a and the FAB mass
spectrum of 5b indicate monomeric structures. The NMR spectra of 5a and 5b are
in good agreement with the analogous iodide derivatives reported by Murphy et al.
[12, 13].
Attempts to quantify the reaction enthalpy of the ring closure reaction by
differential scanning calorimetry were not successful because of interference of the
exothermic reaction with rapid crystallization of nascent 5a and 5b, respectively.
The reaction of 3a in CDCl solution is slow enough to be followed by NMR
3
spectroscopy (Fig. 1). The rate constant of this ®rst order reaction is calculated to
be 1.38 Á 10�
5
� 1
s
with a half time of 14 h at 298 K, corresponding to an
1
Fig. 1. Relative integral values of selected H NMR resonances for the reaction of 3a to 5a at 298 K
(
Scheme 2, Experimental); Æ Int(H) {(Et Si) O} ˆ 100
3
2

786
A. Jansen and S. Pitter
Table 1. Selected spectroscopic data of P,N and P,P,N ligands
31
( P)/ppm
� 1
/cm
ꢁ
ꢂ
Ref.
C ˆ N
a
a
a
a
a
a
a
a
4
4
4
4
4
4
4
6
6
7
7
9
1
a
b
c
4.4
3.2
4.5
4.4
1590, 1569
1590, 1569
1590, 1569
1590, 1569
1589, 1566
1598, 1586, 1567
1587, 1568
1591, 1567
1589, 1580, 1567
1584, 1565
1580
d
e
� 15.6
� 15.5
� 15.5
13.3
f
g
a
b
a
b
b
b
b
� 10.1
12.6
[14]
a
� 4.5
12.7
[15]
a
1587, 1573
1589, 1579, 1568
0
� 9.1
This work; previously not reported, P NMR spectra in CDCl3
[17]
a
b
31
intramolecular pathway (Scheme 2). In THF solution, the ring closure of 3a is very
slow, and 3b is fairly stable in most common solvents.
3
a is less suitable than 3b±d for further reaction with lithium phosphides (cf.
Scheme 1). The desired products 4b±g are obtained in 67±89% yield after
puri®cation. The yield of 4a (9%) is low over both steps due to the low yield of 3a.
The analogous reaction of 3a with Ph PLi yields a product mixture: Attempts to
2
purify the desired product by distillation or column chromatography have not been
successful. 4a may be alternatively synthesized (Scheme 1, lower part). As a side
product, (i-Pr) P-(CH ) -P(i-Pr) is formed resulting from a metal halogen
2
2 6
2
exchange in Cl-(CH ) -P(i-Pr) followed by reaction with a second molecule
2
3
2
Cl(CH ) -P(i-Pr) .
3
2
2
Spectroscopic data of 4a±g (Table1; Experimental) are in agreement with their
constitution. The AX spin systems of the diastereotopic methyl groups in 4a±d
3
(also in 6a, 7a, and 9) are not resolved in CDCl solution. To verify the J
the JH,P coupling constants, H NMR spectra were also acquired in C D solution.
and
3
H,H
1
6
6
As expected, the phenyl substituted phosphines 4e±g are moderately stable
after puri®cation. The diisopropylphosphino derivatives 4a±d undergo fast
decomposition when exposed to air.
1
is also suitable to allow elegant access to potential terdentate ligands. In
analogy to Pignolet and coworkers [15], stepwise metalation of 1 and reaction with
i-Pr) P-Cl or Ph P-Cl yield P,N ligands 6a and 6b [14] and then the symmetrical
(
2
2
P,P,N ligands 7a and 7b (Scheme 3) [15]. When metalation of 1 is performed with
LDA instead of n-BuLi, secondary reaction with Ph PCl affords Ph P-N(i-Pr)
2
2
2
[16]. In 7a, there are two diastereotopic P(i-Pr) groups, resulting in a magnetic
inequivalence of the CH groups bound to each phosphorus and a duplication of the
2
1
CH signals in the H and C NMR spectra.
13
3
Analogous to the synthesis of 2,6-bis-(diphenylphosphino-methyl)-pyridine 10,
17, 18], the diisopropylphosphino derivative 9 is accessible via reaction of 2,6-
[

!
-2-Pyridyl-n-alkylphosphines
787
Scheme 3. Synthesis of P,P,N ligands (R: i-Pr for 6a, 7a; Ph for 6b, 7b)
bis(chloromethyl)-pyridine 8 with (i-Pr) PLi. 9 is expected to form highly stable
2
chelate complexes.
Investigations on the coordination behaviour of these new hemilabile ligands
and, in particular, details on their application to catalysis will be reported
separately.
Experimental
All manipulations were carried out under an atmosphere of dry argon by standard Schlenk
techniques. Solvents were distilled prior to use after puri®cation with standard methods.
Commercially available reagents were used as received or freshly degassed. 6b [14], 7b [15], 10
[
17], and Cl-(CH ) -(i-Pr) [2] were prepared according to literature methods.
2 3 2
Physical measurements
NMR spectra were acquired on a Bruker AC 200 spectrometer ( H: 200.13 MHz, C: 50.32 MHz,
1
13
3
1
1
P: 81.02 MHz) at 298 K. Chemical shifts are referenced to internal or external TMS ( H, C) or to
13
3
external 85% H PO ( P). In experiments using non-deuterated solvents, a coaxial tube with D O
1
3
4
2
1
1
1
13
serving as lock substance was inserted. Assignments were con®rmed by H, H-COSY, H, C-
1
HETCOR, C-DEPT, and selective P decoupling of H and C{ H} NMR spectra. Coupling
3
31
1
13
1
constants are given in Hz.
�
3
The kinetic measurement for the reaction of 3a to 5a was performed with a 0.1745 mol Á dm
�
3
1
CDCl solution of 3a and hexaethyldisiloxane (0.1712 mol Á dm ) as an internal standard; H NMR
3
spectra were acquired at 298 K every 15 min until nearly complete conversion of 2a.
Mass spectra (EI: 70 eV, CI: H O, FAB: glycerine) were recorded on a Finigan SSQ 710
2
instrument. For GC-MS analysis, a Hewlett Packard 5890/5972 (He, 30 m HP5-MS capillary
column) system was used. IR measurements were performed on a Perkin Elmer PC-16 spectrometer.
The results of the elemental analyses agreed satisfactorily with the theoretical values.
General procedure for the synthesis of 2-(!-chloroalkyl)pyridines
ꢀ
2
-Picoline is added dropwise to a freshly prepared solution of one equivalent LDA in THF at � 50 C.
After stirring for 3 h at room temperature, the dark red solution of lithiated picoline is transferred via
3
a canula to a well-stirred solution of ꢀ-bromo-!-chloro-n-alkane in thf (2cm per 1 mmol) at

788
A. Jansen and S. Pitter
ꢀ
a
50 C . The mixture is stirred for 36 h at room temperature to complete reaction. After distillation
�
3
of the solvent the residue is hydrolyzed with water (1 cm per 1 mmol). The organic layer is
separated, and the aqueous phase is extracted four times with diethyl ether. The combined organic
phases are dried over Na SO , and the solvent is removed under vacuum. Fractionation on a 20 cm
2
4
Vigreux column affords the products as light yellow viscous liquids.
2-(4-Chlorobutyl)-pyridine, (3a; C H ClN)
9 12
Following the procedure described above, reaction of 4.66 g (50 mmol) 1 and 7.87 g (50 mmol)
1
3
-bromo-3-chloro-propane affords the crude product which is dissolved in 10 cm pentane, ®ltered
ꢀ
over silica, and dried under vacuum to give 1.27 g (7.5 mmol, 15%) of 2a (b.p.: 58 C at
ꢀ
�
1 3
6
4
Á 10 mbar). Pure 3a slowly decomposes at � 78 C.
3
4
H NMR (CDCl ): ꢁ ˆ 8.51 (d, J ˆ 4.6, 1H, H-6), 7.58 (dt, J ˆ 7.6, J ˆ 1.9, 1H, H-4), 7.10 (m,
3
3
3
13
C
2
H, H-3/5), 3.54 (t, J ˆ 6.2, 2H, H-10), 2.80 (t, J ˆ 7.3, 2H, H-7), 1.85 (m, 4H, H-8/9) ppm;
NMR (CDCl ): ꢁ ˆ 161.4 (C-2), 149.2 (C-6), 136.2 (C-4), 122.6 (C-3), 121.0 (C-5), 44.7 (C-10),
3
3
7.3 (C-7), 32.0 (C-9), 26.8 (C-8) ppm.
2
-(5-Chloropentyl)-pyridine (3b; C H ClN)
1
0 14
Reaction of 5.59 g (60 mmol) 1 and 10.29 g (60 mmol) 1-bromo-4-chloro-butane affords 7.97 g
ꢀ
ꢀ
1 3 4 5
(
43 mmol, 72%) of 2b (b.p.: 72 C at 0.01 mbar), which is stable at � 30 C.
3
H NMR (CDCl ): ꢁ ˆ 8.50 (ddd, J ˆ 4.9, J ˆ 1.9, J ˆ 1.0, 1H, H-6), 7.55 (dt, J ˆ 7.7,
3
4
3
3
J ˆ 1.9, 1H, H-4), 7.08 (m, 2H, H-3/5), 3.50 (t, J ˆ 6.6, 2H, H-11), 2.77 (t, J ˆ 7.6, 2H, H-7), 1.76
1
3
(
m, 4H, H-8/10), 1.47 (m, 2H, H-9) ppm; C NMR (CDCl ): ꢁ ˆ 161.9 (C-2), 149.2 (C-6), 136.2
3
(
C-4), 122.7 (C-3), 120.9 (C-5), 44.9 (C-11), 38.1 (C-7), 32.4 (C-10), 29.0 (C-8), 26.6 (C-9) ppm;
MS (EI): m/z (%) ˆ 182 (0.3), 148, 134, 120, 106, 93 (100), 78, 65, 51.
2
-(6-Chlorohexyl)-pyridine (3c; C H ClN)
1
1 16
Reaction of 9.31 g (0.1 mol) 1 and 18.55 g (0.1 mol) 1-bromo-5-chloro-pentane affords 13.41 g
(
ꢀ
1 3 4
� 5
68 mmol, 68%) of 2c (b.p.: 88 C at 1 Á 10 mbar).
5
3
H NMR (CDCl ): ꢁ ˆ 8.47 (ddd, J ˆ 4.9, J ˆ 1.8, J ˆ 1.0, 1H, H-6), 7.52 (dt, J ˆ 7.6,
3
4
3
3
4
5
J ˆ 1.9, 1H, H-4), 7.08 (d, J ˆ 7.7, 1H, H-3), 7.03 (ddd, J ˆ 7.5, J ˆ 4.9, J ˆ 1.2, 1H, H-5), 3.46
3
3
(
t, J ˆ 6.7, 2H, H-12), 2.74 (t, J ˆ 7.7, 2H, H-7), 1.71 (m, 4H, H-8/11), 1.38 (m, 4H, H-9/10) ppm;
1
3
C NMR (CDCl ): ꢁ ˆ 162.1 (C-2), 149.1 (C-6), 136.1 (C-4), 122.6 (C-3), 120.8 (C-5), 44.9 (C-12),
3
3
1
8.1 (C-7), 32.4 and 29.5 (C-8/11), 28.4 and 26.6 (C-9/10) ppm; MS (EI): m/z (%) ˆ 196 (0.3), 162,
48, 134, 120, 106, 93 (100), 78, 65, 51.
2
-(7-Chloroheptyl)-pyridine (3d; C H ClN)
1
2 18
Reaction of 9.31 g (0.1 mol) 1 and 19.95 g (0.1 mol) 1-bromo-6-chloro-hexane affords 16.97 g
(
ꢀ
1 3 4
� 5
80 mmol, 80%) 2d (bp.: 82 C at 1 Á 10 mbar).
5
3
H NMR (CDCl ): ꢁ ˆ 8.48 (ddd, J ˆ 4.8, J ˆ 1.8, J ˆ 0.9, 1H, H-6), 7.53 (dt, J ˆ 7.6,
3
4
3
3
4
5
J ˆ 1.9, 1H, H-4), 7.09 (d, J ˆ 7.7, 1H, H-3), 7.05 (ddd, J ˆ 7.5, J ˆ 5.0, J ˆ 1.2, 1H, H-5), 3.47
3
3
(
t, J ˆ 6.7, 2H, H-13), 2.74 (t, J ˆ 7.7, 2H, H-7), 1.71 (m, 4H, H-8/11), 1.38 (m, 6H, H-9/10/12)
13
ppm; C NMR (CDCl ): ꢁ ˆ 162.3 (C-2), 149.2 (C-6), 136.1 (C-4), 122.6 (C-3), 120.8 (C-5), 45.0
3
(
C-13), 38.3 (C-7), 32.5, 29.7 and 29.1 (C-8/11/12), 28.6 and 26.7 (C-9/10) ppm; MS (EI): m/z
%) ˆ 210 (0.3), 176, 162, 148, 134, 120, 106, 93 (100), 78, 65, 51.
(
a
Lithiation may be also carried out with n-BuLi solution

!
-2-Pyridyl-n-alkylphosphines
789
1
,2,3,4-Tetrahydroquinolizinium chloride (5a; C H ClN)
9
12
ꢀ
Compound 3a, kept at 25 C for several hours, affords crystalline colourless 5a in quantitative yield.
a is washed with hexane, dried under vacuum, and has to be stored in a dry atmosphere due to its
hygroscopic character.
5
1
3
3
4
H NMR (CDCl ): ꢁ ˆ 9.61 (dm, J ˆ 6.3, 1H, H-6), 8.29 (dt, J ˆ 7.8, J ˆ 1.4, 1H, H-4), 7.89
3
3
3
3
3
(
d, J ˆ 7.7, 1H, H-3), 7.76 (t, J ˆ 6.9, 1H, H-5), 4.91 (t, J ˆ 5.9, 2H, H-7), 3.28 (t, J ˆ 6.6, 2H,
13
H-10), 2.07 (m, 2H, H-8), 1.97 (m, 2H, H-9) ppm; C NMR (CDCl ): ꢁ ˆ 155.9 (C-2), 145.7 (C-6),
3
1
44.3 (C-4), 128.6 (C-3), 125.2 (C-5), 55.6 (C-7), 28.4 (C-10), 21.0 (C-8), 17.3 (C-10) ppm; MS
(
FAB): m/z (%) ˆ 303 (27), 226 (37), 185 (25), 134 (100).
7,8,9,10-Tetrahydro-6H-pyrido[1,2-a]azepinium chloride (5b; C H ClN)
10 14
ꢀ
Compound 3b, reacted at 130 C for 2 h, gives crystalline colourless 5b in quantitative yield. 5b is
washed with hexane, dried under vacuum, and has to be stored in a dry atmosphere.
1
3
4
3
4
H NMR (CDCl ): ꢁ ˆ 9.74 (dd, J ˆ 6.1, J ˆ 1.3, 1H, H-6), 8.32 (dt, J ˆ 7.8, J ˆ 1.5, 1H,
3
3
4
3
4
5
H-4), 7.91 (dd, J ˆ 8.0, J ˆ 1.5, 1H, H-3), 7.75 (dd, J ˆ 7.7, J ˆ 6.5, J ˆ 1.5, 1H, H-5), 5.06 (m,
1
3
2
1
H, H-7), 3.30 (m, 2H, H-11), 1.74 (m, 6H, H-8/9/10) ppm; C NMR (CDCl ): ꢁ ˆ 159.5 (C-2),
3
46.7 (C-6), 145.5 (C-4), 129.0 (C-3), 125.9 (C-5), 61.1 (C-7), 34.1 (C-11), 28.1, 26.8, 24.5
(
C-8/9/10)ppm; MS (EI): m/z (%) ˆ 331 (2), 294 (23), 184 (24), 148 (31), 147 (80), 146 (22), 132 (19),
1
1
20 (36), 118 (55), 106 (21), 93 (100), 78 (17); MS (FAB): m/z (%) ˆ 331 (10), 295 (2), 148 (100),
32 (6), 118 (7), 106 (7).
General procedure for the synthesis of !-2-pyridyl-n-alkylphosphines
3
To a vigorously stirred solution of (i-Pr) PH in THF (3 cm per mmol), one equivalent MeLi (1.6 N
2
ꢀ
solution in diethyl ether) or n-BuLi (1.6 N solution in hexane) is added at � 30 C. The mixture is
ꢀ
allowed to warm up slowly to 25 C and is stirred for another 3 h. The light yellow phosphide solution
is now transferred dropwise to a stirred solution of the 2-(!-chloroalkyl)pyridine in THF
3
ꢀ
ꢀ
(
2 cm per mmol) at � 50 C. The mixture is reacted for 12 h at 25 C. Volatile components are
removed carefully at reduced pressure. The raw product is obtained from the residue by high vacuum
condensation into a cold trap or by crystallization. Further puri®cation is performed by vacuum
distillation or recrystallization.
2-(4-Diisopropylphosphino-butyl)-pyridine (4a; C H NP)
15 26
3
Method 1: Analogous to the general procedure, 15.8 cm (25 mmol) MeLi, 2.99 g (25 mmol)
ꢀ
(
i-Pr) PH and 4.30 g (25 mmol) 3a yield 3.69 g (15 mmol, 58%) 4a after distillation (b.p.: 98 C at
2
�
6
4
Á 10 mbar) as a light yellow liquid.
3
Method 2: A solution of 20 mmol 2 in 30 cm THF is prepared as described above. This solution
3
ꢀ
is added dropwise to a solution of 3.89 g (20 mmol) Cl-(CH ) -P(i-Pr) in 30 cm THF at � 60 C.
2
3
2
ꢀ
After 90 min the reaction mixture is allowed to warm up to 25 C under stirring. The remaining red
3
solution is re¯uxed for 4 h, hydrolyzed with 20 cm water, and extracted with diethyl ether. The
organic phase is dried over Na SO and ®ltered. The solvent is removed under vacuum, and the
2
4
residue is condensed into a cold trap to yield 1.63 g (6.5 mmol, 32%) 4a.
5
1
3
4
3
H NMR (CDCl ): ꢁ ˆ 8.45 (ddd, J ˆ 4.9, J ˆ 1.8, J ˆ 1.0, 1H, H-6), 7.51 (dt, J ˆ 7.7,
3
4
3
4
3
4
5
J ˆ 1.9, 1H, H-4), 7.07 (dt, J ˆ 7.8, J ˆ 1.1, 1H, H-3), 7.01 (ddd, J ˆ 7.5, J ˆ 4.9, J ˆ 1.2, 1H,
3
3
2
H-5), 2.74 (t, J ˆ 7.7, 2H, H-7), 1.77 (m, 2H, H-8), 1.63 (dsp, J ˆ 7.1, J ˆ 2.8, 2H, H-12), 1.48
HP
3
3
3
(m, 2H, H-9), 1.32 (m, 2H, H-10), 1.00 (dd, J ˆ 7.2, J =13.8, 6H, H-13a), 0.97 (dd, J ˆ 6.9,
HP
3
13
ˆ 11.3, 6H, H-13b) ppm; C NMR (CDCl ): ꢁ ˆ 162.1 (C-2), 149.1 (C-6), 136.1 (C-4), 122.5
J
HP
3
3
2
(
C-3), 120.7 (C-5), 38.0 (C-7), 31.6 (d, | J | ˆ 11.8, C-8), 27.9 (d, | J | ˆ 18.7, C-9), 23.1 (d,
CP
CP

790
A. Jansen and S. Pitter

!
-2-Pyridyl-n-alkylphosphines
791
1
1
2
2
|
JCP| ˆ 12.2, C-12), 21.4 (d, | J | ˆ 16.8, C-10), 20.0 (d, | J | ˆ 15.6, C-13a), 18.7 (d, | J | ˆ 9.2,
CP
CP
CP
3
1
C-13b) ppm; P NMR (CDCl ): ꢁ ˆ 4.4 ppm; MS (EI): m/z (%) ˆ 251 (2), 236, 222, 208 (100), 166,
3
145, 132, 118, 106, 90, 76, 65, 51.
2
-(5-Diisopropylphosphino-pentyl)-pyridine (4b; C H NP)
1
6 28
3
Analogous to the procedure described above, 21.9 cm (35 mmol) MeLi, 4.14 g (35 mmol) (i-Pr) PH,
2
ꢀ
and 6.43 g (35 mmol) 3b yield 7.76 g (29 mmol, 84%) 4b after distillation (b.p.: 90 C at
�
6
4
Á 10 mbar) as a colourless liquid.
1
3
4
5
3
H NMR (CDCl ): ꢁ ˆ 8.50 (ddd, J ˆ 4.8, J ˆ 1.8, J ˆ 1.0, 1H, H-6), 7.55 (dt, J ˆ 7.7,
3
4
3
J ˆ 1.9, 1H, H-4), 7.08 (m, 2H, H-3/5), 2.76 (t, J ˆ 7.8, 2H, H-7), 1.71 (m, 2H, H-8), 1.67 (dsp,
3
3
2
J ˆ 7.0, J ˆ 2.9, 2H, H-13), 1.39±1.52 (m, 4H, H-9/10), 1.24±1.38 (m, 2H, H-11), 1.04 (dd,
HP
3
J
3
3
J
13
ˆ 11.1, 6H, H-14b) ppm; C NMR
J ˆ 7.2,
ˆ 13.8, 6H, H-14a), 1.02 (dd, J ˆ 7.0,
HP
HP
(
CDCl ): ꢁ ˆ 162.2 (C-2), 149.0 (C-6), 136.0 (C-4), 122.5 (C-3), 120.7 (C-5), 38.2 (C-7), 31.2 (d,
3
3
2 1
| ˆ 11.8, C-9), 29.5 (C-8), 27.9 (d, | J | ˆ 18.3, C-10), 23.1 (d, | J | ˆ 12.2, C-13), 21.4 (d,
|
|
J
CP
CP CP
2 2 31
1
JCP| ˆ 16.4, C-11), 20.0 (d, | J | ˆ 15.3, C-14a), 18.7 (d, | J | ˆ 9.2, C-14b) ppm; P NMR
CP
CP
(
CDCl ): ꢁ ˆ 4.4 ppm; MS (EI): m/z (%) ˆ 265 (13), 250, 222, 180, 173 (100), 160, 148, 132, 118,
3
1
06, 90, 76, 65, 43.
2
-(6-Diisopropylphosphino-hexyl)-pyridine (4c; C H NP)
1
7 30
3
1.9 cm (35 mmol) MeLi, 4.14 g (35 mmol) (i-Pr) PH, and 6.92 g (35 mmol) 3c yield 8.75 g
2
2
�
1 3 4 5 3
6
(
31 mmol, 89%) 4c after condensation at 4 Á 10 mbar into a cold trap as a colourless liquid.
H NMR (CDCl ): ꢁ ˆ 8.49 (ddd, J ˆ 4.9, J ˆ 1.8, J ˆ 0.9, 1H, H-6), 7.55 (dt, J ˆ 7.6,
3
4
3
3
4
5
J ˆ 1.9, 1H, H-4), 7.10 (d, J ˆ 7.5, 1H, H-3), 7.05 (ddd, J ˆ 7.4, J ˆ 4.8, J ˆ 1.2, 1H, H-5), 2.76
3
3
2
(
t, J ˆ 7.7, 2H, H-7), 1.71 (m, 2H, H-8), 1.67 (dsp, J ˆ 7.1, J ˆ 2.8, 2H, H-14), 1.20±1.50
HP
3 3 3 3
m, 8H, H-9/10/11/12), 1.04 (dd, J ˆ 7.2, J ˆ 13.9, 6H, H-15a), 1.01 (dd, J ˆ 6.9, J ˆ 11.1,
(
HP
HP
1
3
6
H, H-15b) ppm; C NMR (CDCl ): ꢁ ˆ 162.4 (C-2), 149.2 (C-6), 136.1 (C-4), 122.6 (C-3), 120.8
3
3 2
(
C-5), 38.4 (C-7), 31.4 (d, | J | ˆ 11.4, C-10), 29.8 and 29.1 (C-8/9), 28.1 (d, | J | ˆ 18.3, C-11),
CP
CP
1
1
2
2
3.2 (d, | J | ˆ 12.2, C-14), 21.6 (d, | J | ˆ 16.4, C-12), 20.1 (d, | J | ˆ 15.6, C-15a), 18.8 (d,
CP
CP
CP
2
31
JCP| ˆ 9.5, C-15b) ppm; P NMR (CDCl ): ꢁ ˆ 4.5 ppm; MS (EI): m/z (%) ˆ 279 (22), 264, 236,
|
3
1
94, 187 (100), 173, 162, 145, 132, 118, 106, 93, 90, 76, 65, 43.
2
-(7-Diisopropylphosphino-heptyl)-pyridine (4d; C H NP)
8 32
1
3
1.9 cm (35 mmol) MeLi, 4.14 g (35 mmol) (i-Pr) PH, and 7.41 g (35 mmol) 3d yield 6.93 g
2
2
ꢀ
1 3 4 5 3
� 4
(
24 mmol, 67%) 4d after distillation (b.p.: 124 C at 2 Á 10 mbar) as a colourless liquid.
H NMR (CDCl ): ꢁ ˆ 8.48 (ddd, J ˆ 4.9, J ˆ 1.8, J ˆ 1.0, 1H, H-6), 7.53 (dt, J ˆ 7.7,
3
4
3
3
4
5
J ˆ 1.9, 1H, H-4), 7.09 (d, J ˆ 7.7, 1H, H-3), 7.04 (ddd, J ˆ 7.5, J ˆ 5.0, J ˆ 1.2, 1H, H-5), 2.74
3
3
2
(
t, J ˆ 7.8, 2H, H-7), 1.69 (m, 2H, H-8), 1.66 (dsp, J ˆ 7.1, J ˆ 2.8, 2H, H-15), 1.24±1.45 (m,
HP
3
3
3
3
1
6
0H, H-9/10/11/12/13), 1.03 (dd, J ˆ 7.2, J ˆ 13.8, 6H, H-16a), 1.00 (dd, J ˆ 7.0, J ˆ 11.6,
HP
HP
1
3
H, H-16b) ppm; C NMR (CDCl ): ꢁ ˆ 162.4 (C-2), 149.1 (C-6), 136.1 (C-4), 122.6 (C-3), 120.8
3
3
(
C-5), 38.4 (C-7), 31.4 (d, | J | ˆ 11.4, C-11), 29.8 (C-8), 29.24 and 29.15 (C-9/10), 28.1 (d,
CP
2
1
1
2
|
JCP| ˆ 17.9, C-12), 23.2 (d, | J | ˆ 11.8, C-15), 21.5 (d, | J | ˆ 16.8, C-13), 20.1 (d, | J | ˆ 15.6,
CP
2 31
CP
CP
C-16a), 18.8 (d, | J | ˆ 9.1, C-16b) ppm; P NMR (CDCl ): ꢁ ˆ 4.4 ppm; MS (EI): m/z (%) ˆ 293
CP
3
(
14), 278, 250, 201, 187, 176, 162, 145, 132, 118, 106, 93, 90 (100), 76, 65, 61, 43.
2-(5-Diphenylphosphino-pentyl)-pyridine (4e; C H NP)
22 24
3
2.8 cm (20 mmol) n-BuLi, 3.80 g (20 mmol) Ph PH, and 3.75 g (20 mmol) 3b yield 4.92 g
1
2
ꢀ
ꢀ
(
15 mmol, 72%) 4e after crystallization from hexane at � 35 C as colourless crystals (m.p.: 44 C).

792
A. Jansen and S. Pitter
1
3
4
5
3
H NMR (CDCl ): ꢁ ˆ 8.50 (ddd, J ˆ 4.6, J ˆ 1.9, J ˆ 1.1, 1H, H-6), 7.54 (dt, J ˆ 7.6,
3
4
3
J ˆ 1.9, 1H, H-4), 7.40 (m, 4H, H-14), 7.31 (m, 6H, H-15/16), 7.08 (d, J ˆ 7.7, 1H, H-3), 7.05 (dd,
3
5
3
J ˆ 7.5, J ˆ 1.3, 1H, H-5), 2.74 (t, J ˆ 7.6, 2H, H-7), 2.04 (m, 2H, H-11), 1.73 (m, 2H, H-8), 1.49
1
3
1
(
m, 4H, H-9/10)ppm; C NMR (CDCl ): ꢁ ˆ 162.2 (C-2), 149.2 (C-6), 138.9 (d, J | ˆ 13.0, C-13),
3
CP
2
3
1
36.1 (C-4), 132.6 (d, | J | ˆ 18.3, C-14), 128.4 (C-16), 128.3 (d, | J | ˆ 6.9, C-15), 122.6 (C-3),
CP
CP
3 1
1
20.8 (C-5), 38.2 (C-7), 30.9 (d, | J | ˆ 12.6, C-9), 29.4 (C-8), 27.9 (d, | J | ˆ 11.5, C-11), 25.8 (d,
CP
CP
2
31
JCP| ˆ 16.0, C-10) ppm; P NMR (CDCl ): ꢁ ˆ � 15.6 ppm; MS (CI): m/z (%) ˆ 334 (100), 255,
|
3
2
41, 199, 183, 148, 134, 108, 93.
2
-(6-Diphenylphosphino-hexyl)-pyridine (4f; C H NP)
3 26
2
3
Analogous to the synthesis of 4c, 18.4 cm (29 mmol) n-BuLi, 5.47 g (29 mmol) Ph PH, and 5.81 g
2
ꢀ
(
29 mmol) 3c yield 7.92 g (23 mmol, 78%) 4f after crystallization from hexane at � 35 C as
ꢀ
colourless crystalline needles (m.p.: 48 C).
1
3
4
5
3
H NMR (CDCl ): ꢁ ˆ 8.51 (ddd, J ˆ 4.9, J ˆ 1.8, J ˆ 0.9, 1H, H-6), 7.55 (dt, J ˆ 7.6,
3
4
3
J ˆ 1.8, 1H, H-4), 7.28±7.44 (m, 10H, H-15/16/17), 7.07 (m, 2H, H-3/5), 2.75 (t, J ˆ 7.7, 2H, H-7),
1
.03 (m, 2H, H-12), 1.70 (m, 2H, H-8), 1.27±1.54 (m, 6H, H-9/10/11) ppm; C NMR (CDCl ):
3
2
3
1
2
ꢁ
ˆ 162.3 (C-2), 149.2 (C-6), 139.0 (d, | J | ˆ 13.4, C-14), 136.1 (C-4), 132.6 (d, | J | ˆ 18.3,
CP
CP
3
C-15), 128.4 (C-17), 128.3 (d, | J | ˆ 6.5, C-16), 122.6 (C-3), 120.8 (C-5), 38.3 (C-7), 31.0 (d,
CP
3
1
2
|
JCP| ˆ 12.6, C-10), 29.7 (C-8), 28.9 (C-9), 28.0 (d, | J | ˆ 11.4, C-12), 25.8 (d, | J | ˆ 16.0,
CP
CP
31
C-11) ppm. P NMR (CDCl ): ꢁ ˆ � 15.5 ppm; MS (CI): m/z (%) ˆ 348 (100), 255, 241, 199, 187,
3
1
62, 148, 134, 109, 93.
2
-(7-Diphenylphosphino-heptyl)-pyridine (4g; C H NP)
2
4 28
3
Analogous to the synthesis of 4e, 18.8 cm (30 mmol) n-BuLi, 5.59 g (30 mmol) Ph PH, and 6.35 g
2
ꢀ
(
30 mmol) 3d yield 8.60 g (24 mmol, 79%) 4g after crystallization from hexane at � 35 C as
ꢀ
colourless crystalline needles (m.p:. 30 C).
1
3
4
5
3
H NMR (CDCl ): ꢁ ˆ 8.51 (ddd, J ˆ 4.9, J ˆ 1.5, J ˆ 0.9, 1H, H-6), 7.54 (dt, J ˆ 7.6,
3
4
3
J ˆ 1.9, 1H, H-4), 7.28±7.46 (m, 10H, H-16/17/18), 7.07 (m, 2H, H-3/5), 2.76 (t, J ˆ 7.8, 2H, H-7),
1
.03 (m, 2H, H-13), 1.71 (m, 2H, H-8), 1.38 (m, 8H, H-9/10/11/12) ppm; C NMR (CDCl ):
3
2
3
1
2
ꢁ
ˆ 162.4 (C-2), 149.1 (C-6), 139.0 (d, | J | ˆ 13.0, C-15), 136.1 (C-4), 132.6 (d, | J | ˆ 18.3,
CP
CP
3
C-16), 128.33 (C-18), 128.27 (d, | J | ˆ 6.9, C-17), 122.5 (C-3), 120.7 (C-5), 38.3 (C-7), 31.0
CP
3
1
(
d, | J | ˆ 13.0, C-11), 29.7 (C-8), 29.1 and 29.0 (C-9/10), 27.9 (d, | J | ˆ 11.1, C-13), 25.8
CP
2 31
CP
(
d, | J | ˆ 16.0, C-12) ppm; P NMR (CDCl ): ꢁ ˆ � 15.5 ppm; MS (CI): m/z (%) ˆ 362 (100), 284,
CP
3
2
69, 255, 176, 109, 93.
2-(Diisopropylphosphino-methyl)-pyridine (6a; C H NP)
12 20
3
ꢀ
A solution of 2.33 g (25 mmol) 1 in 50 cm THF is treated with one equivalent n-BuLi at � 50 C. The
ꢀ
mixture is stirred for one hour at 25 C to give a clear red solution of 2 which is slowly transferred to
3
ꢀ
a well stirred solution of 3.82 g (25 mmol) (i-Pr) PCl in 50 cm THF at � 50 C. After the reaction
2
mixture has been stirred for 12 h, the volatile components are removed carefully at reduced pressure.
ꢀ
4
.05 g (19 mmol, 77%) 6a are obtained as a yellow liquid from the residue by distillation (b.p.: 68 C
6
�
at 4 Á 10 mbar).
1
3
4
5
3
H NMR (CDCl ): ꢁ ˆ 8.41 (ddd, J ˆ 4.9, J ˆ 1.8, J ˆ 0.9, 1H, H-6), 7.49 (dt, J ˆ 7.6,
3
4
5
3
3
5
4
3
4
J ˆ 1.9, 1H, H-4), 7.24 (ddt, J ˆ 7.9, J ˆ 0.9, J ˆ 0.8, 1H, H-3), 6.99 (ddd, J ˆ 7.4, J ˆ 5.0,
HP
2
3
2
J ˆ 1.2, 1H, H-5), 2.94 (d, J ˆ 2.2, 2H, H-7), 1.75 (dsp, J ˆ 7.1, J ˆ 1.9, 2H, H-8), 1.00 (dd,
HP
HP
3
3
3
13
J ˆ 7.0, J ˆ 11.5, 6H, H-9a), 0.99 (dd, J ˆ 7.2, J ˆ 13.6, 6H, H-9b) ppm; C NMR (CDCl ):
HP
HP
3
4
3
ꢁ
ˆ 160.6 (d, | J | ˆ 8.4, C-2), 149.0 (C-6), 135.9 (C-4), 123.5 (d, | JCP| ˆ 6.9, C-3), 120.5
CP

!
-2-Pyridyl-n-alkylphosphines
793
5
1
1
2
(
d, | J | ˆ 1.5, C-5), 32.3 (d, | J | ˆ 22.1, C-7), 23.4 (d, | J | ˆ 13.7, C-8), 19.6 (d, | J | ˆ 14.5,
CP
CP
CP
CP
2
C-9a), 18.8 (d, | J | ˆ 10.7, C-9b), MS (EI): m/z (%) ˆ 209 (2.4), 194, 166, 150, 135, 124 (100), 93,
CP
7
8, 65.
2
-(bis-Diisopropylphosphino-methyl)-pyridine (7a; C H NP )
2
1
8
33
3
Analogous to the synthesis of 6a, 6.2 cm (10 mmol) n-BuLi, 2.09 g (10 mmol) 6a and 1.53 g
ꢀ
(
10 mmol) (i-Pr) PCl yield 1.68 g (5 mmol, 52%) 7a as a light brown viscous liquid (b.p.: 108 C at
2
�
6
3
Á 10 mbar).
1
3
4
5
3
H NMR (CDCl ): ꢁ ˆ 8.42 (ddd, J ˆ 4.8, J ˆ 1.9, J ˆ 0.9, 1H, H-6), 7.47 (dt, J ˆ 7.7,
3
4
3
5
4
3
4
J ˆ 1.9, 1H, H-4), 7.13 (ddt, J ˆ 7.9, J ˆ 1.0, J ˆ 0.3, 1H, H-3), 6.97 (ddd, J ˆ 7.4, J ˆ 4.8,
HP
5
3
2
3
J ˆ 1.2, 1H, H-5), 3.51 (s, 1H, H-7), 2.00 (tsp, J ˆ 7.1, J ˆ 1.8, 2H, H-9a), 1.87 (tsp, J ˆ 7.2,
HP
2
3
3
3
3
J
ˆ 1.5, 2H, H-9b), 1.17 (dt, J ˆ 7.2, J ˆ 13.2, 6H, H-10a), 1.08 (dt, J ˆ 7.0, J ˆ 12.4, 6H,
HP
HP
3 3 3 3
HP
0
0
H-10a ), 0.97 (dt, J ˆ 7.4, J ˆ 15.1, 6H, H-10b), 0.63 (dt, J ˆ 7.2, J ˆ 10.3, 6H, H-10b ) ppm;
HP
2
HP
1
3
3
C NMR (CDCl ): 160.2 (t, | J | ˆ 2.7, C-2), 148.9 (C-6), 135.3 (C-4), 123.6 (t, | J | ˆ 3.8, C-3),
3
CP
CP
1
2
1
1
20.3 (C-5), 38.4 (t, | J | ˆ 33.9, C-7), 22.2 (t, | J | ˆ 10.7, C-10b), 22.0 (t, | J | ˆ 5.0, C-9a), 21.8
CP
1 2 2 2
CP
CP
0
(
t, | J | ˆ 6.9, C-9b), 20.5 (t, | J | ˆ 8.4, C-10a), 20.0 (t, | J | ˆ 8.0, C-10a ), 19.3 (t, | J | ˆ 3.8,
CP
0
CP
CP
CP
31
C-10b ) ppm; P NMR (CDCl ): ꢁ ˆ 12.6 ppm; MS (CI): m/z (%) ˆ 326 (100), 282, 251, 226, 210,
3
1
96, 166, 135, 124, 93.
2
,6-bis-(Diisopropylphosphino-methyl)-pyridine (9; C H NP)
9 35
1
3
A solution of 2.62 g (22 mmol) (i-Pr) PH in 20 cm THF is treated with one equivalent n-BuLi at
2
ꢀ
�
50 C. The mixture is stirred for 3 h without further cooling to yield a yellow phosphide solution.
This solution is slowly transferred to a stirred solution of 1.96 g (11 mmol) 2,6-bis(chloromethyl)-
ꢀ
pyridine (8) in 30 ml THF at � 50 C. After the reaction mixture has been stirred for 12 h, the volatile
components are removed carefully at reduced pressure. 2.29 g (6.5 mmol, 59%) 6a are obtained as a
�
6
light yellow liquid from the residue by condensation into a cold trap at 4 Á 10 mbar.
1
3
3
H NMR (CDCl ): ꢁ ˆ 7.40 (dd, J ˆ 7.6, 1H, H-4), 7.06 (d, J ˆ 7.5, 2H, H-3), 2.91 (d,
3
2
3
2
3
3
JHP ˆ 2.2, 2H, H-5), 1.76 (dsp, J ˆ 7.1, J ˆ 2.1, 4H, H-7), 1.02 (dd, J ˆ 7.2, J ˆ 11.5, 12H,
HP
HP
3
3
13
ˆ 13.5, 12H, H-8b) ppm; C NMR (CDCl ): ꢁ ˆ 159.7 (d,
H-8a), 1.01 (dd, J ˆ 7.2,
J
HP
3
3 5 1
2
|
JCP| ˆ 8.4, C-2), 136.0 (C-4), 120.3 (dd, | J | ˆ 8.0, | J | ˆ 1.9, C-3), 32.4 (d, | J | ˆ 21.4,
CP
CP
1 2 2
CP
C-5), 23.4 (d, | J | ˆ 13.7, C-7), 19.6 (d, | J | ˆ 14.5, C-8b), 19.0 (d, | J | ˆ 10.7, C-8a) ppm;
CP
CP
CP
3
1
P NMR (CDCl ): ꢁ ˆ 12.7 ppm; MS (CI): m/z (%) ˆ 340 (100), 296, 254, 240, 223, 135, 119.
3
Acknowledgements
We are grateful to the Institute of Organic Chemistry, Jena, and to the Microanalytical Laboratory
Kolbe, M uÈ lheim a. d. Ruhr, for performing the elemental analyses. We also thank Dr. M. Poppitz for
mass spectrometric analyses and Dr. H. Schreer for molecular mass determinations. This work was
®nancially supported by the Max-Planck-Gesellschaft.
References
[
[
[
[
[
[
1] Jeffrey JC, Rauchfuss TB (1979) Inorg Chem 18: 2658
2] Pitter S, Dinjus E, Jung B, G oÈ rls H (1996) Z Naturforsch B 51b: 934
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4] Newkome R (1993) Chem Rev 93: 2067
5] Drent E, Arnoldy P, Budzelaar PHM (1993) J Organomet Chem 455: 247
6] Chan WH, Zhang ZZ, Mak TCW, Che CM (1998) J Chem Soc Dalton Trans 797

794
A. Jansen and S. Pitter: !-2-Pyridyl-n-alkylphosphines
[7] Budzelaar PHM (1998) J Org Chem 63: 1131
[8] Chelucci G, Cabras MA, Botteghi C, Marchetti M (1994) Tetrahedron: Asymmetry 5: 299
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[
[
[
[
[
[
[
[
[
10] Moyhenan TM, Scho®eld K, Jones RAY, Katritzky AR (1962) J Chem Soc 2637
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15] Anderson MP, Mattson BM, Pignolet LH (1983) Inorg Chem 22: 2644
16] Cristau H-J, Chene A, Christol H (1980) Synthesis 7: 551
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Received November 9, 1998. Accepted (revised) January 19, 1999