3-Amino- and 3-acylamido-2-phosphonopyridines: synthesis by Pd-catalyzed P-C coupling, structure and conversion to pyrido[b]-anellated P{double bond, long}C-N heterocycles

Article abstract of DOI:10.1016/j.tet.2008.06.010

Palladium catalyzed cross-coupling of 3-amino- and 3-acylamido-2-bromopyridines 1a-f with triethyl phosphite allowed the synthesis of 3-amino- and 3-acylamido pyridine-2-phosphonic acid diethyl esters 2a-f, whereas nickel catalysts, although providing acc

Full text of DOI:10.1016/j.tet.2008.06.010

Tetrahedron 64 (2008) 7960–7967
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3-Amino- and 3-acylamido-2-phosphonopyridines: synthesis by Pd-catalyzed P–C
coupling, structure and conversion to pyrido[b]-anellated P]C–N heterocycles
,
b
Mohamed Shaker S. Adam a, Olaf Ku¨hl a, Markus K. Kindermann a, Joachim W. Heinicke a , Peter G. Jones
*
a Institut fu¨r Biochemie, Ernst-Moritz-Arndt-Universita¨t Greifswald, Felix-Hausdorff-Strasse 4, 17489 Greifswald, Germany
b Institut fu¨r Anorganische und Analytische Chemie, Technische Universita¨t Braunschweig, Hagenring 30, 38106 Braunschweig, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Palladium catalyzed cross-coupling of 3-amino- and 3-acylamido-2-bromopyridines 1a–f with triethyl
phosphite allowed the synthesis of 3-amino- and 3-acylamido pyridine-2-phosphonic acid diethyl esters
2a–f, whereas nickel catalysts, although providing access to related anilido-2-phosphonates, proved
inactive. Reduction of the aminophosphonate 2a with LiAlH4 afforded 3-amino-2-phosphinopyridine
(3a), which was cyclocondensed with dimethylformamide dimethyl acetal (DMFA) via phosphaalkene
intermediates 4a to the novel pyrido[b]-anellated 1,3-azaphosphole 5a. Reaction of amidophosphonates
2b–f with LiAlH4 did not result in the expected reductive cyclization, as shown by closely related anilido-
2-phosphonates, but led to product mixtures containing N-secondary 3-amino-2-phosphinopyridines
3b–f as the main or major component. The conversion of 3b,d,e with DMFA to 5b,d,e provides first
examples of N-substituted pyrido[b]-anellated azaphospholes. Structures were confirmed by multinu-
clear NMR and X-ray crystallography (for 2c, 3b).
Received 12 May 2008
Accepted 4 June 2008
Available online 7 June 2008
Keywords:
Pyridine phosphonates
Phosphines
Heterophospholes
Palladium catalysis
Hydrogen bonds
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
knowledge were so far unknown, and their behaviour towards re-
duction with LiAlH4. We also report the first representatives of
Amino-substituted phosphonic acid derivatives are of interest
with respect to their biological properties1 but are also useful
building blocks for the synthesis of amino-functional phosphines,
P,N-heterocycles orhybrid ligands. This was shown by investigations
of phosphonoanilines and their conversion to 2-phosphinoanilines
and P,N-heterocycles, which in turn were found useful as ligands in
Pd-catalyzed arylamination or Ni-catalyzed ethylene oligomeriza-
tion.2 Introduction of nitrogen into the arene ring would change the
influence of anellation3 on the azaphosphole ring, thus allowing li-
gand tuning and access to further coordination modes. 2-Pyridyl
phosphines are known to form four-membered hemilabile PXN
chelate complexes, which are of importance in transition metal co-
ordination chemistry and catalysis.4 Pyrido-anellated azaphos-
pholes with the same structural motif, pyridine nitrogen and
phosphorus bound at the same carbon atom, have so far not been
studied, whereas pyrido[a]-anellated azaphospholes with bridging
nitrogen atom are known.5 Thispromptedus toextendour studies of
anellated azaphospholes2,5–7 to related novel pyrido[b]-anellated
1,3-azaphospholes.
azaphospholo[4,5-b]pyridines.
2. Results and discussion
2.1. Synthesis of 3-amino- and 3-amido-pyridine-
2-phosphonates
The most convenient syntheses of pyridylphosphines are P–C
coupling reactions of chloro- or alkoxyphosphines with metallated
pyridines. Alternatively, 2-bromopyridines are also sufficiently re-
active for conversion with alkali metal phosphides.4 However, the
presence of NH-groups has severely restricted the use of these
methods. Attempts at triple lithiation of 3-amino-2-bromopyr-
idine, applicable to P–C coupling of 2-bromoaniline,6b or double
lithiation of 3-pivalamido-2-bromopyridine and subsequent cou-
pling with excess ClP(NMe2)2 or ClP(O)(OEt)2, did not lead to
defined products. Therefore, couplings of 3-amino- and 3-amido-
2-halopyridines with diethyl phosphite in the presence of a strong
base and with triethyl phosphite were tested. Despite the consid-
erably increased reactivity of 2-bromopyridines towards nucleo-
philes compared to bromobenzenes, the usual Michaelis–Becker
or Michaelis–Arbuzov-reactions8 could not be achieved with
3-amino-2-bromopyridine up to 220 ꢀC in the absence of a catalyst.
Palladium and in some cases nickel or copper catalysts are known
to allow efficient coupling of diethyl or triethyl phosphite with
We report here the synthesis and structure of 3-amino- and
3-amido pyridine-2-phosphonates, which to the best of our
* Corresponding author. Tel.: þ49 3834 864337.
E-mail address: heinicke@uni-greifswald.de (J.W. Heinicke).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.06.010

M.S.S. Adam et al. / Tetrahedron 64 (2008) 7960–7967
7961
Table 1
a variety of halobenzenes and even nitrogen-containing heterocy-
Yields of 2a–f for various molar ratios of 1a–f to P(OEt)3 and catalyst loada
cles9,10 and were used by us in couplings of 2-amino- and 2-ami-
dobromobenzenes.2a,6 While fair to good yields were achieved
in the palladium catalyzed coupling of 2-bromo-N-methylaniline
with diethyl phosphite,2a attempts to couple 3-amino-2-bromo-
pyridine with diethyl phosphite in the presence of Pd(OAc)2 or
Pd2(dba)3 (5 mol %) and triisopropylphosphine or triphenylphos-
phine (10 mol %) failed (in THF or toluene at 65–120 ꢀC and reaction
times up to 48 h). Attempts to couple 3-amino- or 3-amido-2-
bromopyridines with triethyl phosphite in the presence of anhy-
drous nickel bromide were also unsuccessful, although acylamido
bromobenzene couples in the presence of electron-withdrawing
CF3 groups under the same conditions (20 min, 200 ꢀC).6 It is
therefore assumed that the catalysts are deactivated by the amino
group or the combination of amino group and pyridine nitrogen.
Use of palladium catalysts, which are more tolerant of functional
groups, finally allowed coupling of 3-amino- and 3-amido-2-bro-
mopyridines 1a–f with triethyl phosphite (Scheme 1). The yields
are rather low to moderate (very low for the chloro analogues of
1a,b) and could not significantly be improved by addition of a more
basic auxiliary phosphine such as tricyclohexylphosphine.
2
R
Yielda
%
b
1.0 P(OEt)3
1.2 P(OEt)3
1.2 P(OEt)3
1.4 P(OEt)3
a
b
c
d
e
f
H
15
26
20
18
21
16
26
38
29
26
33
22
20
33
25
20
25
17
22
36
25
25
28
20
tert-Butyl
Phenyl
Furyl
Thienyl
Naphthyl
a
Unless indicated otherwise 10 mol % PdCl2 or Pd(OAc)2 was used; yields are
identical within experimental error; work-up is more convenient in case of PdCl2.
b
5 mol % catalyst.
Conditions for the synthesis of 2a were varied with regard to
temperature (120–180 ꢀC) and catalyst loading (2.5–10 mol %)
showing that neat triethyl phosphite (1.2 equiv), heating at 160 ꢀC
and 10 mol % catalyst was the optimum in the low-yield couplings
of 1a and P(OEt)3. Further optimization was not carried out. In
a series of related bromoanilines, the yields of coupling products
increased strongly in the case of N-secondary precursors,2a and the
above conditions were therefore chosen also in the coupling
reactions with N-acyl-substituted 2-bromopyridines 1b–f. The rise
in yield was rather low and limited to few examples, but the
comparison of the yields of 2a–f (tert-butyl>thienyl>phe-
nyl>furylzhydrogen>naphthyl) (Table 1) shows still a clear in-
fluence of the substituent R and that this is mainly electronic in
nature. Thus, a tert-butyl group with the greatest þI-effect within
the series results in the highest yield. Likewise yields are higher
with the electron-rich five-membered thienyl ring than with phe-
nyl or naphthyl groups.
The amount of phosphite is crucial because it is not only re-
quired (consumed) as coupling component, but is also involved in
the catalyst stabilization. Use of 1.2 equiv of phosphite, represent-
ing exactly the stoichiometric amount for a 10% catalyst load and
coordination of two ligands at palladium, increased the yield
by about one third compared to exactly equimolar amounts. As the
P(OEt)3 is added at the beginning, there is at first a factual excess,
which diminishes with the progress of the reaction and may cause
early catalyst decomposition in using a 1:1 molar ratio. If 1.4 equiv
of phosphite were used, the yields decreased slightly, probably
by favouring formation of [Pd{P(OEt)3}3] at the expense of
[Pd{P(OEt)3}2], which is required for the oxidative addition step.
H
NH2
Br
N
P
P(OEt)3
H
O
10 mol% Pd(OAc)2
N
N
OC2H5
C2H5O
1a
2a
RCOCl/Base
NHC(O)R
O
3
R
4
N
P(OEt)3
5
6
H
O
2
10 mol% Pd(OAc)2
N
1b-f
Br
N
P
OC2H5
C2H5O
2b-f
b
c
d
e
f
R
tBu Ph 2-furyl 2-thienyl 1-naphthyl
Scheme 1. Synthesis of 3-amino- and 3-amido-pyridine-2-phosphonates 2a–f.
The reaction is likely to proceed via formation of the active
catalyst involving phosphite coordination to palladium, oxidative
addition of the bromopyridine at the palladium centre, nucleophilic
substitution of bromide at an ethyl group of the coordinated
phosphite with elimination of ethylbromide and subsequent re-
ductive elimination of the product 2 and concomitant coordination
of another phosphite ligand to palladium to reform the catalytic
species. We assume that the catalytic cycle contains intermediate
Pd(0)[P(OEt)3]2, which is stabilised in the presence of unconsumed
or excess P(OEt)3 as Pd(0)[P(OEt)3]3.11 A tentative reaction mecha-
nism is depicted in Scheme 2.
2.2. Reduction of 3-amino- and 3-amido-pyridine-2-
phosphonates and synthesis of PCN heterocycles
Reduction of 3-aminopyridine-2-phosphonic acid ester 2a with
LiAlH4 provided 3-amino-2-phosphinopyridine (3a) in moderate
yield, only slightly contaminated by two other phosphines. Because
of the high air sensitivity, no attempts were made at purification by
chromatography. The crude product was used directly in the re-
action with dimethylformamide dimethyl acetal (DMFA). Reaction
control by 1H and 31P NMR indicated primary formation of a major
amount of the trans-phosphaalkene E-4a and minor amount of the
cis-isomer Z-4a and slow condensation to the pyridoazaphosphole
5a (after 3 days at 50 ꢀC, 3.5:1:1.5 molar ratio by CH-2 integration).
The signals of the latter increase with the reaction time, the others
decrease. Although the intermediates 4 are not fully characterized,
unambiguous structure information is gained by characteristic
P]CH phosphorus and proton signals. The phosphorus resonances
OEt
(EtO)3P
OEt
O
N
Br
P
Pd
N
Br Et
NHR
NHR
1a-f
_P(OEt)3
Pd[P(OEt)3]3 Pd[P(OEt)3]2
+P(OEt)3
_EtBr
EtO OEt
N
P
O
H
(EtO)3P
OEt
OEt
of both intermediates, Z- and E-4a (d
31P 46.3, 57.1), appear strongly
Pd
N
N
R
P
P(OEt)3
upfield from those of other types of phosphaalkenes, which typi-
O
2a-f
¼200–350 ppm.12 This feature indicates the con-
N
R
cally absorb at
d
H
jugation of the nitrogen lone pair to the P]C
p-bond. In the
Scheme 2. Tentative P–C coupling mechanism.
heterocycle 5a (d
31P 75.6) the effect is rendered somewhat smaller

7962
M.S.S. Adam et al. / Tetrahedron 64 (2008) 7960–7967
by more effective delocalization of
p
-density into the electron-
with pivaloyl-2-pyridylamide (R¼pyridyl), which displays phenyl-
phosphine and N-neopentyl-2-aminopyridine in a molar ratio of
1:3. The faster reduction of pivaloyl pyridylamide compared to
pivaloylanilide is attributed to the ꢁM effect of the pyridyl group
and will also lead to preferred reduction of the amido groups of 2b–
f. This prevents the reductive cyclization, which requires primary
formation of 2-phosphino- or 2-phosphido imidates. The resulting
N-secondary lithium pyridylamides are then reduced at the phos-
phono group to give 3b–f after aqueous work-up (Scheme 4). The
identity of the by-products was not studied in detail, but phos-
withdrawing pyridine ring. Even more indicative are the P]CH
proton signals, which are strongly downfield shifted and display
large and characteristic two-bond 31P–1H coupling constants. 2JPH is
particularly large if the proton is in cis-position to the phosphorus
2
lone pair (Z-4a,
d
1H 10.05, JPH¼58.7 Hz; 5a,
d
1H 7.87,
2JPH¼36.9 Hz). In the opposite configuration it is considerably
smaller but the value is still twice that of the other aryl protons (in
2
CDCl3 E-4a
d
1H 10.68, JPH¼14.0 Hz). The intermediates 4a are
slowly converted to the heterocycle 5a. Small amounts of acid
catalyze the cyclocondensation (Scheme 3). Compound 5a was
separated from the mixture in good yield after prolonged heating
by high-vacuum distillation as an air-sensitive white solid.
phorus resonances of the reaction mixtures in the region of
d
ꢁ71 to
ꢁ50 and ꢁ25 to ꢁ4 ppm hint at secondary and tertiary phos-
phines.12 These might be formed by lithiation of the amidomethyl
group and nucleophilic attack of CLi at the phosphono group,
known from intramolecular carbanionic rearrangements of aryl-
phosphates,13 and subsequent reduction of P(V) to P(III) species.
The potential of the N-secondary 2-phosphino pyridylamines
as starting materials for the synthesis of N-substituted pyr-
idoazaphospholes 5b,d,e was demonstrated by reaction of crude
3b,d,e with DMFA (Scheme 4). The use of crude 3b,d,e did not lead
to optimal results and pure products, but provides initial in-
formation on the new type 5 of pyrido[b]-anellated P]C–N
heterocycles.
NH
2 Me2NCH(OMe)2
1. 3 LiAlH4
2a
2. H2O
(6-7 d, 50 °C)
NH2
N
PH2
3a
4
5
NH2
P
3
+
NMe2
6
2
N
N
NMe2
P
E-4a
Z-4a
(H+)
H
7
7a
N
2.3. Structure elucidation and conformation control by
hydrogen bonds
6
5
2
3a
P
N
4
3
The structure elucidation is based on characteristic 31P and fully
assigned, conclusive proton and 13C NMR data, elemental analysis
or molecular ions in HRMS, and crystal structure analyses of 2c and
3b. The solution NMR spectra of the 3-amidopyridine derivatives
display strongly downfield shifted resonances (Dd 2.0–2.4 ppm) for
the protons H-4 in o-position to the amido group (1H NMR 1b–f
5a
Scheme 3. Reduction of 2a with LiAlH4 and cyclization of 3a to pyridoazaphos-
phole 5a.
The reduction of the 3-amido-pyridine-2-phosphonates 2b–f
with LiAlH4 (and subsequent hydrolysis) was expected to furnish
pyridoazaphospholes 6 with the substituent R in 2-position by
reductive cyclization, the main reaction of the closely related 2-
acylamidophenyl phosphonic acid diethyl esters.6 The experiments
led, however, to mixtures, containing primary 2-phosphino-3-
organomethylamino-pyridines 3 as the main (3b,d,e) or a major
constituent (3c) while pyridoazaphospholes could not even be
detected as trace signals in the crude mixtures, indicating that re-
ductive cyclization is completely suppressed (Scheme 4). To un-
derstand this particular reactivity, mixtures of PhP(O)(OEt)2 and
RNHC(O)tBu with R¼phenyl and R¼2-pyridyl were reduced in
diethyl ether with LiAlH4 in a 1:1:1 molar ratio (15 h, room tem-
perature), which is insufficient for complete reduction. Thus, the
preferred reduction site becomes evident. Whereas phenyl phos-
phonic acid ester is reduced faster than pivaloylanilide (R¼Ph), as
shown by the higher amount of phenylphosphine compared to N-
neopentylaniline (molar ratio 2:1–2.4:1 by 1H NMR integration of
PH2 and NCH2 signals), the opposite is true for the mixture obtained
d
8.70–8.97, 2b–f
d
9.04–9.39 ppm) compared to the corresponding
7.02 ppm) while the impact on the p-protons
pyridylamines (2a
d
H-6, similarly influenced by the þM-effect of the acylamido group,
is much lower (Dd ca. 0.4 ppm). The major contribution is thus due
to the magnetic anisotropy influence of the C]O double bond in
the Z-configuration, where oxygen is directed towards the pyridine
ring. The large downfield NH proton shifts of the o-phosphono
amides 2b–f (
amides 1b–f (
d
11.0–11.9 ppm in CDCl3) compared to the o-bromo
8.0–8.7 ppm in CDCl3) give evidence that the
d
o-amidopyridine phosphonates form significantly stronger P]O/
H–N than C]O/H–N hydrogen bonds; the former are also fav-
oured by the possibility of intramolecular hydrogen bonds. The
preferred solution structures are thus similar to the structure
determined for 2c in the crystal.
The X-ray crystal structure analysis of 2c (Fig. 1) reveals four
molecules in the monoclinic unit cell, space group P21/c. The bond
Li
N
H
N
N=C(OLi)R
R
R
CR
N
P
N
PHLi
P
N
6
1. 3 LiAlH4
2. H2O
2b-f
R
H2C
H2C
R
NLi
NH
N
P
Me2NCH(OMe)2
(6-7 d, 50 °C)
N
N
PO(OEt)2
N
PH2
3b-f
N
5b,d,e
R
CHLi
Li
N
unidentified secondary
and tertiary phosphanes
PO(OEt)2
Scheme 4. Reduction of 2b–f with LiAlH4 and cyclization of 3b–f to pyridoazaphosphole 5b,d,e.

M.S.S. Adam et al. / Tetrahedron 64 (2008) 7960–7967
7963
Figure 1. Molecular structure of 2c in the crystal (ellipsoids with 50% probability).
Figure 3. Packing of 3b in the crystal.
Selected bond lengths (Å) and angles (ꢀ): P–O1 1.4759(9), P–O2 1.5595(9), P–C11
1.8086(13), C12–N2 1.4031(15), N2–C5 1.3664(16), C5–O4 1.2170(15); O1–P–O2
111.01(6), O(2)–P–O(3) 102.25(5), C5–N2–C12 127.74(11), O4–C5–N2 123.86(12), O4–
C5–C21 121.17(11), N2–C5–C21 114.97(11), N1–C11–P 113.23(9), C12–C11–P 123.99(9),
C13–C12–C11 117.68(11). 3.1762(18) Å, N2–H/N1 146.5(16)ꢀ.
Neighbouring strands, not shown in Figure 3, are connected by
C5–H5/Cent interactions (Cent¼centroid of pyridyl ring) with
H5/Cent 2.64 Å, angle 138ꢀ. The phosphorus is slightly angled
towards N1 (N1–C2–P 113.09(10)ꢀ) and nitrogen N2 slightly
towards phosphorus. The torsion angle C2–C3–N2–C7 (2.0(2)ꢀ)
indicates a nearly planar structure and sp2-hybridization of nitro-
gen (cf. C3–N2–C7 126.27(12)ꢀ), allowing mesomeric interactions
lengths and angles lie in the normal ranges. The O and C atoms at
phosphorus form a distorted tetrahedron with the O2–P–O3 angle
smaller than the O–P]O angles. The pyridine ring is somewhat
distorted with a rather small angle C13–C12–C11. The phosphono
group forms a six-membered ring with an intramolecular P]O/
H–N hydrogen bond (H02/O1 1.926(16), N2/O1 2.7217(14) Å,
angle 151.3(14)ꢀ). The geometry at C11 and, to a lesser extent, C12, is
irregular; the phosphorus is angled towards the pyridine-N atom
(N1–C11–P 113.23(9)ꢀ, cf. C12–C11–P 123.99(9)ꢀ), while N2 is
slightly bent towards O1 (C13–C12–N2 123.22(11), C11–C12–N2
between the nitrogen lone electron pair and the pyridine p-system.
3. Conclusions
A route to novel 3-amino- and 3-acylamidopyridine-2-phos-
phonates by palladium-catalyzed cross-coupling of 3-amino- and
3-acylamido-functional 2-bromopyridines was demonstrated.
Optimization is still necessary to improve yields. Reduction of
3-aminopyridine-2-phosphonic acid esters with LiAlH4 leads to
3-amino-2-phosphinopyridine, which allows cyclocondensation
with N,N-dimethylformamide dimethyl acetal to novel pyrido[b]-
anellated 1H-1,3-azaphospholes. Reductive cyclization of 3-
acylamidopyridine-2-phosphonates with LiAlH4, in analogy to the
synthesis of benzazaphospholes from acylanilido-2-phosphonates,
is, however, not possible. The crucial step is the relative reduction
rate of phosphono and amido groups. Reductive cyclization re-
quires primary reduction of the phosphono group, but the electron-
withdrawing pyridyl group activates the C]O bond of the amide
and thus causes preferred reduction at this site. Subsequent re-
duction of the phosphono group leads to N-secondary 3-amino-2-
phosphinopyridines, in some cases the main product, but more or
less abundant side reactions prevent this being a suitable route to
these compounds. By use of enriched samples, it could be, however,
shown that these compounds are suitable starting materials for the
synthesis of N-substituted pyrido[b]-anellated 1,3-azaphospholes.
119.09(11)ꢀ). The distance of H13 to O4 is 2.22 Å. The
p-systems of
the amido group and pyridine ring are nearly coplanar (interplanar
angle 3.1ꢀ) allowing stabilization by extended delocalization while
the benzene
p-plane is somewhat rotated with respect to the
amide plane (interplanar angle 22.6ꢀ). The packing is rather fea-
tureless, with just two weak C–H/O interactions from ethyl
hydrogens.
3-Neopentylamino-2-phosphinopyridine (3b) also formed sin-
gle crystals with four molecules (Fig. 2) in the tetragonal unit cell,
space group P41. In the packing (Fig. 3) the molecules interact via
the 41 screw axis by N2–H/N1 hydrogen bonds (H01/N1 2.42(2),
N2/N1 3.176 Å).
4. Experimental
4.1. General
All manipulations were performed under dry argon, using
Schlenk techniques and freshly distilled ketyl-dried solvents.
3-Amido-2-bromopyridines were prepared in analogy to 2-amido-
3-bromopyridines.14 3-Amino-2-bromopyridine (1a) and other
chemicals were used as purchased. NMR spectra were recorded at
25 ꢀC on multinuclear FT-NMR spectrometers ARX 300 (Bruker) or
Avance II 300 (Bruker) at 300.1 (1H), 75.5 (13C), and 121.5 (31P) MHz.
Figure 2. Molecular structure of 3b in the crystal (ellipsoids with 50% probability).
Selected bond lengths (Å) and angles (ꢀ): P–C(2) 1.8299(15), C(2)–C(3) 1.4199(19),
N(1)–C(2) 1.3429(19), N(2)–C(3) 1.3673(18), N(2)–C(7) 1.4512(18); C(3)–C(2)–P
123.84(10), N(2)–C(3)–C(4) 123.44(13); C(3)–N(2)–C(7)–C(8) ꢁ104.08(17).
Chemical shifts
d are given in parts per million, shift references are
tetramethylsilane for 1H and 13C and H3PO4 (85%) for 31P. Coupling

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M.S.S. Adam et al. / Tetrahedron 64 (2008) 7960–7967
constants, unless indicated otherwise, refer to JHH in 1H and JPC
4.1.4. N-(2-Bromopyrid-3-yl)thiophene-2-carboxamide (1e)
Thiophene-2-carbonyl chloride (1.86 mL, 17.4 mmol) was con-
verted with 1a (3.00 g, 17.34 mmol) in pyridine (18 mL) and worked
up as described for 1c. Purification on silica gel using ethyl acetate/
in 13C NMR data. Assignment numbers follow the nomenclature
and/or use position abbreviations (i, o, m, p for aryl and a, b, etc. for
alkyl groups); examples for numbering pyridine derivatives and
heterocycles are given in schemes. IR spectra were measured on
a FTIR-spectrometer System 2000 (Perkin–Elmer) and EI mass
spectra on a single-focusing mass spectrometer AMD40 (Intectra).
HRMS data were recorded on MAT95 (Finnigan) with EI (70 eV, PFK
as reference substances) or on a 7T Fourier transform ion cyclotron
resonance mass spectrometer APEX IV (Bruker Daltonics) with ESI
([MþH]þ in MeOH/NH4OAc or Me/H2O/formic acid) at the Univer-
sity of Go¨ttingen. Elemental analyses were carried out with a CHNS-
932 analyzer from LECO using standard conditions. Melting points
were determined in a capillary and are uncorrected.
n-hexane (10:90%) gave 3.35 g (68%) of 1e, mp 126 ꢀC. 1H NMR
3
(CDCl3, ppm):
d
7.19 (dd, J¼5.0, 3.8 Hz, 1H, 40-H), 7.32 (dd, 3J¼8.2,
4.6 Hz, 1H, 5-H), 7.63 (dd, 3J¼5.0 Hz, J¼1.1 Hz, 1H, 30-H), 7.71 (dd,
3J¼3.8 Hz, 4J¼1.1 Hz, 1H, 50-H), 8.13 (dd, 3J¼4.6 Hz, 4J¼1.8 Hz, 1H, 6-
H), 8.35 (br s, 1H, NH), 8.79 (dd, 3J¼8.2 Hz, 4J¼1.8 Hz, 1H, 4-H).
4
13C{1H} NMR (CDCl3, ppm):
d 123.73, 128.14, 128.50, 129.09, 131.96
(CH-5, CH-4, CH-40, CH-50, CH-30), 133.14, 133.49 (Cq-2, Cq-3), 138.32
(Cq-20), 144.57 (CH-6), 159.88 (s, CO). IR (KBr pellet):
nCO¼1671 cmꢁ1
. C10H7BrN2OS (283.15), HRMS (ESI) calcd for
[Mþ1]þ: 282.95352, found: 282.95368.
4.1.1. N-(2-Bromopyrid-3-yl)trimethylacetamide (1b)
4.1.5. N-(2-Bromopyrid-3-yl)-1-naphthalene-carboxamide (1f)
1-Naphthoylchloride (3.33 mL, 22.1 mmol) was converted with
1a (3.82 g, 22.1 mmol) in pyridine (23 mL) and worked up as de-
scribed for 1c. Purification on silica gel using ethyl acetate/n-hex-
ane (10:90%) gave 4.50 g (62%) 1f, mp 142 ꢀC. 1H NMR (CDCl3, ppm):
Pivaloylchloride (2.55 mL, 20.8 mmol) was added dropwise to
a solution of 1a (3.0 g, 17.34 mmol) and triethylamine (2.90 mL,
20.8 mmol) in THF (20 mL) and Et2O (20 mL) at 0 ꢀC. The mixture
was stirred at room temperature overnight and digested with water
and concd aqueous NaHCO3 solution. The ether extracts were dried
over MgSO4. Removal of solvent in vacuum gave 3.72 g (83%) of
NMR spectroscopically pure 1b, mp 47 ꢀC. 1H NMR (CDCl3, ppm):
d
7.39 (dd, 3J¼8.1, 4.6 Hz, 1H, 5-H), 7.53–7.67 (m, 3H, naph-H), 7.85
(dd, 3J¼7.1 Hz, 4J¼1.2 Hz, 1H, naph-H), 7.94 (dd, 3J¼7.5 Hz, 4J¼2 Hz,
1H, naph-H), 8.04 (br d, 3J¼8.3 Hz, 1H, naph-H), 8.18 (dd, 3J¼4.6 Hz,
4J¼1.8 Hz, 1H, 6-H), 8.30 (br s, 1H, NH), 8.46 (dm, 3Jz7 Hz, 4J¼
1.3 Hz, 1H, naph-H), 8.97 (dd, 3J¼8.2 Hz, 4J¼1.7 Hz, 1H, 4-H). 13C{1H}
d
1.36 (s, 9H, CMe3), 7.27 (dd, 3J¼8.2, 4.6 Hz, 1H, 5-H), 8.04 (br s, 1H,
NH), 8.08 (dd, 3J¼4.6 Hz, 4J¼1.8 Hz, 1H, 6-H), 8.70 (dd, 3J¼8.1 Hz,
4J¼1.8 Hz, 1H, 4-H). MS (EI 70 eV, 210 ꢀC): m/z (%)¼259 (0.9), 258
NMR (CDCl3, ppm):
d 123.68, 124.77, 125.08, 125.59, 126.84,
(5) [Mþ
(
81Br)], 257 (0.9), 256 (5) [Mþ
(
79Br)], 177 (31), 174 (12), 172
127.72, 128.58, 128.89 (8CH), 130.06 (Cq-10), 132.03 (CH-40), 133.18,
133.42, 133.86, 133.89 (Cq-8a0, Cq-4a0, Cq-2, Cq-3), 144.82 (CH-6),
(12), 93 (10), 57 (100), 41 (20). Anal. Calcd for C10H13BrN2O (257.13):
C, 46.71; H, 5.10; N, 10.89. Found: C, 46.92; H, 4.82; N, 10.90.
167.60 (CO). IR (KBr pellet): nCO¼1660 (s), 1675 (m) cmꢁ1
.
C
16H11BrN2O (327.18), HRMS (ESI) calcd for [Mþ1]þ: 327.01275,
4.1.2. N-(2-Bromopyrid-3-yl)benzamide (1c)
found: 327.01276.
Benzoylchloride (2.15 mL, 18.5 mmol) was added dropwise to
a solution of 1a (3.20 g, 18.5 mmol) in pyridine (20 mL) at ꢁ10 ꢀC.
The reaction mixture was stirred at room temperature overnight,
washed with water several times and the product was extracted by
ethylacetate. Afterdryingwithanhydrous MgSO4 andremovalof the
solvent in vacuum the residue was purified by column chromatog-
raphy on silica gel using ethyl acetate/n-hexane (5:95%). The yield
4.1.6. 3-Amino-2-pyridine phosphonic acid diethylester (2a)
Triethyl phosphite (4.8 mL, 27.7 mmol) was added dropwise to
a mixture of solid 1a (4.0 g, 23.1 mmol) and palladium acetate
(0.52 g, 2.3 mmol, 10 mol %) heated at 160 ꢀC in a distillation
apparatus while a slow stream of nitrogen or argon removed the
ethylbromide formed in the reaction. Heating was continued for
15 min at 160 ꢀC. The resulting yellow oil was purified by distilla-
tion at 10ꢁ5 mbar/100 ꢀC (bath temperature) in repeated experi-
ments by column chromatography using silica gel and ethyl
acetate/n-hexane (25:75%) yielding 1.4 g (26%) of yellow oil. 1H
was 3.82 g (74%), mp 95 ꢀC. 1H NMR (CDCl3, ppm):
d
7.34 (dd, 3J¼8.1,
4.6 Hz,1H, 5-H), 7.55 (tm, 3Jz7 Hz, 2H, m0-H), 7.63 (tm, 3Jz7 Hz,1H,
4
p0-H), 7.94 (dm, 3Jz7 Hz, Jz2 Hz, 2H, o0-H), 8.14 (dd, 3J¼4.6 Hz,
4J¼1.8 Hz,1H, 6-H), 8.50 (br s,1H, NH), 8.88 (dd, 3J¼8.1 Hz, 4J¼1.8 Hz,
1H, 4-H). 13C{1H} NMR (CDCl3, ppm):
d
123.72 (CH-4 or CH-5),127.11
NMR (CDCl3, ppm):
d
1.34 (t, 3J¼7.1 Hz, 6H, CH3), 4.14, 4.21 (m,
(2CH-o0), 128.60 (CH-5 or CH-4), 129.10 (2CH-m0), 132.65 (CH-p0),
133.40,133.74,133.83 (Cq-i0, Cq-2, Cq-3),144.59(CH-6),165.56(s, CO).
IR (KBr pellet): nCO¼1653 cmꢁ1. MS (EI 70 eV, 260 ꢀC): m/z (%)¼279
2JAB¼10.1 Hz, 3J¼7.1 Hz, 3JPH¼7.9 Hz, 4H, OCH2), 5.54 (br s, 2H, NH),
7.02 (dt, 3J¼8.5 Hz, JPH¼7.6 Hz, 4J¼1.3 Hz, 1H, 4-H), 7.15 (ddd,
4
3J¼8.5, 4.3 Hz, 5JPH¼2.1 Hz, 1H, 5-H), 8.09 (dd, 3J¼4.3 Hz, 4J¼1.2 Hz,
(0.3), 278 (3) [Mþ
(
81Br)], 277 (0.3), 276 (3) [Mþ
(
79Br)],197 (40),105
1H, 6-H). 13C{1H} NMR (CDCl3, ppm):
d
16.01 (d, 3J¼6.4 Hz, CH3),
(100), 77 (58), 51 (14). Anal. Calcd for C12H9BrN2O (277.12): C, 52.01;
H, 3.27; N, 10.11. Found: C, 51.88; H, 3.34; N, 9.88.
62.56 (d, 2J¼5.7 Hz, OCH2), 123.23 (d, 3J¼11.0 Hz, CH-4), 126.81 (d,
4J¼3.5 Hz, CH-5), 129.94 (d, 1J¼225.9 Hz, Cq-2), 139.10 (d,
3J¼21.5 Hz, CH-6),148.95 (d, 2J¼25.8 Hz, Cq-3). 31P{1H} NMR (CDCl3,
4.1.3. N-(2-Bromopyrid-3-yl)furan-2-carboxamide (1d)
ppm):
d
14.44. MS (EI 70 eV, 130 ꢀC): m/z (%)¼231 (9), 230 (62)
2-Furoylchloride (2.00 mL, 20.3 mmol) was converted with 1a
(3.50 g, 20.2 mmol) in pyridine (20 mL) and worked up as described
for 1c. Purification on silica gel using ethyl acetate/n-hexane
[Mþ], 201 (28), 186 (48), 127 (62), 99 (100). Anal. Calcd for
C9H15N2O3P (230.20): C, 46.96; H, 6.57. Found: C, 46.75; H, 7.02.
(10:90%) yielded 3.75 g (69%) 1d, mp 108 ꢀC. 1H NMR (CDCl3, ppm):
4.1.7. 3-Pivaloylamido-pyridine-2-phosphonic acid
diethylester (2b)
4
d
6.61 (dd, 3J¼3.5 Hz, J¼1.7 Hz, 1H, 40-H), 7.30 (superimposed dd,
3J¼3.5 Hz, J¼0.7 Hz, 1H, 30-H), 7.32 (superimposed dd, 3J¼8.2,
Triethyl phosphite(4.3 mL, 24.8 mmol),1b (5.4 g, 21.0 mmol) and
palladium acetate (0.47 g, 2.1 mmol) were heated for 15 min at
160 ꢀC in a slowstream of argon (see 2a), and the resulting yellow oil
was purified by distillation at 10ꢁ6 mbar/110 ꢀC (bath temperature)
and subsequently by column chromatography using silica gel and
ethyl acetate/n-hexane (10:90%), yield 2.5 g (38%). 1H NMR (CDCl3,
4
4.8 Hz, 1H, 5-H), 7.60 (dd, 3J¼1.7 Hz, J¼0.7 Hz, 1H, 50-H), 8.13 (dd,
4
3J¼4.7 Hz, 4J¼1.8 Hz, 1H, 6-H), 8.82 (dd, 3J¼8.2 Hz, 4J¼1.8 Hz, 1H, 4-
H), 8.73 (br s, 1H, NH). 13C{1H} NMR (CDCl3, ppm): 112.89 (CH-40),
d
116.34 (CH-30), 123.65,128.45 (CH-5, CH-4), 133.18,133.41 (Cq-2, Cq-
3), 144.59, 145.10 (CH-6, CH-50), 147.07 (Cq-20), 156.17 (s, CO). IR (KBr
pellet): nCO¼1680 cmꢁ1. MS (EI 70 eV, 270 ꢀC): m/z (%)¼268 (5) [Mþ
ppm):
d
1.35 (s, 9H, CMe3), 1.35 (t, 3J¼7.2 Hz, 6H, CH3), 4.18, 4.26 (m,
3
(
81Br)], 266 (5) [Mþ
(
79Br)], 187 (100), 95 (97). Anal. Calcd for
2JAB¼10.0 Hz, 3J¼7.1 Hz, JPH¼8.0 Hz, 4H, OCH2), 7.41 (ddd, 3J¼8.8,
C
10H7BrN2O2 (267.08): C, 44.97; H, 2.64; N, 10.49. Found: C, 45.43;
4.5 Hz, 4JPH¼2.0 Hz,1H, 5-H), 8.44 (br d, 3J¼4.5 Hz,1H, 6-H), 9.04 (td,
4
H, 2.83; N, 10.30.
3J¼8.7 Hz, JPH¼7.6 Hz, 4J¼1.4 Hz, 1H, 4-H), 11.01 (br s, 1H, NH).

M.S.S. Adam et al. / Tetrahedron 64 (2008) 7960–7967
7965
13C{1H} NMR (CDCl3, ppm):
d
16.10 (d, 3J¼6.1 Hz, CH3), 27.28 (s,
165.93 (s, CO). 31P{1H} NMR (CDCl3, ppm):
d
12.1. C16H19N2O4P,
CMe3), 40.24 (s, CMe3), 63.55 (d, 2J¼5.9 Hz, OCH2), 126.73 (d,
4J¼3.9 Hz, CH-5),127.55 (d, 3J¼9.5 Hz, CH-4),136.08 (d, 1J¼220.1 Hz,
Cq-2), 141.68 (d, 2J¼24.1 Hz, Cq-3), 144.15 (d, 3J¼21.3 Hz, CH-6),
HRMS (ESI in MeOHþNH4OAc) calcd for [MþH]þ: 335.11552, found:
335.11557.
178.51 (s, CO). 31P{1H} NMR (CDCl3, ppm):
d
12.05. Anal. Calcd for
4.1.9. 3-(2-Furoyl)amido-pyridine-2-phosphonic acid
C
14H23N2O4P (314.32): C, 53.50; H, 7.38; N, 8.91. Found: C, 53.73; H,
diethylester (2d)
6.90; N, 8.83. MS (EI 70 eV, 25 ꢀC): m/z (%)¼315 (0.2), 314 (4) [Mþ],
Triethyl phosphite (3.48 mL, 20.1 mmol), 1d (4.5 g, 16.8 mmol)
and palladium acetate (0.38 g, 1.7 mmol, 10 mol %) were heated for
15 min at 160 ꢀC in a slow stream of argon (see 2a), and the
resulting brown oil was purified by column chromatography using
silica gel and ethyl acetate/n-hexane (20:80%) yielding 1.4 g (26%)
258 (11), 257 (100), 229 (22), 201 (39), 57 (10).
4.1.8. 3-Benzoylamido-2-pyridine phosphonic acid diethylester (2c)
Triethyl phosphite (4.1 mL, 23.6 mmol), 1c (5.5 g, 19.9 mmol)
and palladium acetate (0.45 g, 2.0 mmol, 10 mol %) were heated for
15 min in a slow stream of argon (see 2a). The resulting brown oil
was purified by column chromatography using silica gel and ethyl
acetate/n-hexane (15:85%) to yield 1.9 g (29%) of white crystalline
solid, mp 65 ꢀC. Single crystals were grown by slow evaporation of
of pale yellow solid, mp 48 ꢀC. 1H NMR (CDCl3, ppm):
d 1.36 (td,
4
2
3J¼7.1 Hz, JPH¼0.5 Hz, 6H, CH3), 4.20, 4.28 (m, JAB¼10.1 Hz,
3
3J¼7.1 Hz, JPH¼7.7 Hz, 4H, OCH2), 6.55 (dd, 3J¼3.6 Hz, 4J¼1.7 Hz,
1H, 40-H), 7.30 (dd, 3J¼3.6 Hz, J¼0.7 Hz, 1H, 30-H), 7.46 (ddd,
4
3J¼8.8, 4.5 Hz, 4JPH¼2.0 Hz, 1H, 5-H), 7.63 (dd, 3J¼1.7 Hz, 4J¼0.7 Hz,
1H, 50-H), 8.49 (dm, 3J¼4.5 Hz, 4J¼1.4 Hz, 4JPHz0.7 Hz, 1H, 6-H),
9.16 (td, 3J¼8.8 Hz, 4JPH¼7.6 Hz, 4J¼1.4 Hz, 1H, 4-H), 11.77 (br s, 1H,
an ethereal solution, for crystal data see Table 2. 1H NMR (CDCl3,
4
ppm):
d
1.36 (td, 3J¼7.1 Hz, JPH¼0.5 Hz, 6H, CH3), 4.20, 4.29 (m,
2JAB¼10.0 Hz, 3J¼7.1 Hz, JPH¼7.8 Hz, 4H, OCH2), 7.48 (ddd, 3J¼8.7,
NH). 13C{1H} NMR (CDCl3, ppm):
d
16.23 (d, 3J¼6.2 Hz, CH3), 63.82
3
5
4.5 Hz, JPH¼1.9 Hz, 1H, 5-H), 7.50–7.60 (m, 3H, m0-H, p0-H), 8.13
(d, 2J¼5.5 Hz, OCH2), 112.22 (CH-40), 115.76 (CH-30), 127.02
(d, 4J¼3.8 Hz, CH-5), 127.69 (d, 2J¼10.1 Hz, CH-4), 136.45 (d,
1J¼226 Hz, Cq-2), 141.11 (d, 2J ca. 24 Hz, Cq-3), 144.70 (d,
3J¼21.2 Hz, CH-6), 145.56 (CH-50), 147.63 (Cq-20), 157.21 (s, CO).
(dm, 3Jz8 Hz, Jz2 Hz, 2H, o0-H), 8.50 (dm, 3J¼4.4 Hz, 4J¼1.4 Hz,
4
4JPHz0.8 Hz, 1H, 6-H), 9.26 (td, 3J¼8.7 Hz, JPH¼7.5 Hz, 4J¼1.4 Hz,
4
1H, 4-H), 11.92 (br s, 1H, NH). 13C{1H} NMR (CDCl3, ppm):
d 16.07 (d,
3J¼6.4 Hz, CH3), 63.72 (d, 2J¼6.0 Hz, OCH2), 126.91 (d, 4J¼3.7 Hz,
CH-5), 127.43 (s, 2CH-o0), 127.49 (d, 2J¼8.5 Hz, CH-4), 128.68 (s,
2CH-m0), 132.09 (s, CH-p0), 133.80 (s, Cq-i0), 136.17 (d, 1J¼219.1 Hz,
Cq-2), 141.67 (d, 2J¼24.0 Hz, Cq-3), 144.43 (d, 3J¼21.2 Hz, CH-6),
31P{1H} NMR (CDCl3, ppm):
d
12.0. IR (KBr pellet):
n
¼1684 (CO),
1308 (PO), 1028 (vs) cmꢁ1. Anal. Calcd for C14H17N2O5P (324.27): C,
51.86; H, 5.28; N, 8.64. Found: C, 49.46 (incomplete combustion);
H, 5.05; N, 8.47.
4.1.10. 3-(2-Thenoyl)amido-pyridine-2-phosphonic acid
diethylester (2e)
Table 2
Crystal data and structure refinement
Triethyl phosphite (3.6 mL, 20.8 mmol), 1e (5.0 g, 17.7 mmol)
and palladium acetate (0.39 g, 1.74 mmol, 10 mol %) were heated for
about 15 min at 160 ꢀC in a slow stream of argon (see 2a), and the
resulting yellow oil was purified by column chromatography using
silica gel and ethyl acetate/n-hexane (20:80%) yielding 2.0 g (33%)
Identification code
2c
3b
Empirical formula
Formula weight
Temperature
Wavelength
Crystal system
Space group
Unit cell
C
16H19N2O4P
C10H17N2P
196.23
133(2) K
0.71073 Å
Tetragonal
P41
334.30
133(2) K
0.71073 Å
Monoclinic
P21/c
of white solid, mp 64 ꢀC. 1H NMR (CDCl3, ppm):
d
1.36 (td, 3J¼7.1 Hz,
2
4JPH¼0.5 Hz, 6H, CH3), 4.20, 4.28 (m, JAB¼10.1 Hz, 3J¼7.1 Hz,
3JPH¼7.7 Hz, 4H, OCH2), 7.14 (dd, 3J¼5.0, 3.8 Hz, 1H, 40-H), 7.46 (ddd,
3J¼8.8, 4.5 Hz, 5JPH¼2.0 Hz, 1H, 5-H), 7.58 (dd, 3J¼5.1 Hz, 4J¼1.1 Hz,
a¼10.6093(18) Å
a
¼90ꢀ
a¼9.6108(11)
dimensions
Å
a
¼90ꢀ
b¼12.119(2) Å
c¼13.328(2) Å
b
¼110.531(5)ꢀ b¼9.6108(11)
4
1H, 30-H), 7.91 (dd, 3J¼3.8 Hz, J¼1.1 Hz, 1H, 50-H), 8.48 (ddd,
Å
b
¼90ꢀ
4
3J¼4.5 Hz, 4J¼1.4 Hz, JPH¼0.7 Hz, 1H, 6-H), 9.14 (td, 3J¼8.7 Hz,
g
¼90ꢀ
c¼12.229(2)
Å
g
¼90ꢀ
4JPH¼7.5 Hz, 4J¼1.4 Hz, 1H, 4-H), 11.86 (br s, 1H, NH). 13C{1H} NMR
Volume
Z
1604.7(5) Å3
4
1129.5(3) Å3
4
(CDCl3, ppm):
d
16.20 (d, 3J¼6.0 Hz, CH3), 63.87 (d, 2J¼6.4 Hz,
OCH2), 127.09 (d, 4J¼3.2 Hz, CH-5), 127.31 (d, 3J¼9.4 Hz, CH-4),
128.16, 129.27, 131.75 (CH-40, CH-50, CH-30), 135.94 (d, 1J¼218.8 Hz,
Cq-2), 139.68 (Cq-20), 141.60 (d, 2J¼24.1 Hz, Cq-3), 144.53 (d,
3J¼21.1 Hz, CH-6), 160.86 (s, CO). 31P{1H} NMR (CDCl3, ppm):
Density (calcd)
Absorption coefficient
F(000)
Crystal size
Theta range
for data collection
Index ranges
1.384 Mg/m3
0.193 mmꢁ1
704
1.154 Mg/m3
0.204 mmꢁ1
424
0.35ꢂ0.20ꢂ0.10 mm3
0.4ꢂ0.3ꢂ0.1 mm3
2.05–30.50ꢀ
2.12–30.51ꢀ
d
12.28. MS (EI 70 eV, 280 ꢀC): m/z (%)¼341 (8), 340 (41) [Mþ], 325
(3), 232 (18), 231 (13), 204 (19), 203 (100), 143 (12), 110 (82). Anal.
Calcd for C14H17N2O4PS (340.33): C, 49.41; H, 5.03; N, 8.23. Found:
C, 49.46; H, 5.05; N, 8.17.
ꢁ15ꢃhꢃ15, ꢁ17ꢃkꢃ17,
ꢁ19ꢃlꢃ19
22,163
ꢁ13ꢃhꢃ13, ꢁ13ꢃkꢃ13,
ꢁ17ꢃlꢃ17
Reflections collected
Independent reflections
15,938
4887
3456 [R(int)¼0.0287]
[R(int)¼0.0617]
4.1.11. 3-(1-Naphthoyl)amido-pyridine-2-phosphonic acid
diethylester (2f)
Completeness to
theta¼30.00ꢀ
99.9%
100.0%
Absorption correction
None
Semi-empirical from
equivalents
0.9799 and 0.8546
Triethyl phosphite (0.32 mL, 1.84 mmol), 1f (0.5 g, 1.53 mmol)
and palladium acetate (0.15 g, 0.67 mmol, 44 mol %) were heated
for 15 min at 160 ꢀC in a slow stream of argon (see 2a). The resulting
brown oil was purified by column chromatography using silica gel
and ethyl acetate/n-hexane (20:80%) yielding 0.13 g (22%) of white
Max. and min.
transmission
Refinement method
Full-matrix least-squares
Full-matrix least-squares
on F2
3456/3/130
on F2
crystalline solid, mp 81 ꢀC. 1H NMR (CDCl3, ppm):
d 1.34 (td,
Data/restraints/parameters 4887/0/214
Goodness-of-fit on F2
1.027
1.058
3J¼7.1 Hz, JPH¼0.6 Hz, 6H, CH3), 4.18, 4.26 (m, JAB¼10.0 Hz,
3J¼7.1 Hz, 3JPH¼7.8 Hz, 4H, OCH2), 7.57 (m, 4H, 5-H, 3naph-H), 7.90
(dd, 3J¼7.1 Hz, 4J¼1.9 Hz, 1H, naph-H), 7.95 (dd, 3J¼7.2 Hz,
4J¼1.1 Hz, 1H, naph-H), 7.99 (br d, 3J¼8.3 Hz, 1H, naph-H), 8.55
(partly superimposed dm, 3Jz4.5 Hz, 4J¼1.4 Hz, 4JPHz1 Hz, 1H, 6-
H), 8.57 (partly superimposed dd, 3Jz8 Hz, 4J¼1.3 Hz, 1H, naph-H),
4
2
Final R indices [I>2
R indices (all data)
Absolute structure
parameter
Largest diff.
peak and hole
s(I)]
R1¼0.0407, wR2¼0.0963
R1¼0.0372, wR2¼0.0898
R1¼0.0452, wR2¼0.0947
0.00(8)
R1¼0.0616, wR2¼0.1043
0.390 and ꢁ0.316 e Åꢁ3
0.333 and ꢁ0.125 e Åꢁ3

7966
M.S.S. Adam et al. / Tetrahedron 64 (2008) 7960–7967
9.39 (td, 3J¼8.7 Hz, 4JPH¼7.6 Hz, 4J¼1.4 Hz, 1H, 4-H), 11.58 (br s, 1H,
4.1.15. 3-(1-Furyl)methylamino-2-phosphino-pyridine (3d)
NH). 13C{1H} NMR (CDCl3, ppm):
d
16.20 (d, 3J¼6.0 Hz, CH3), 63.95
Reduction of 2d (1.08 g, 3.33 mmol) in diethyl ether (30 mL) by
LiAlH4 pellets (0.38 g, 9.99 mmol) in diethyl ether (20 mL) and
work-up as described for 3a gave 0.53 g yellow oil. NMR control of
the crude product showed the most intense phosphorus signal at
2
(d, J¼6.0 Hz, OCH2), 124.92, 125.50. 125.92, 126.48 (CH-30, CH-80,
4
CH-60, CH70), 127.22 (d, J¼3.7 Hz, CH-5), 127.31 (CH-50), 128.16 (d,
3J¼9.3 Hz, CH-4), 128.45 (CH-20), 130.51 (Cq-10), 131.86 (CH-40),
133.13 (Cq-8a0), 133.99 (Cq-4a0), 136.10 (d, 1J¼202 Hz, Cq-2), 141.89
(d, 2J¼22.7 Hz, Cq-3), 144.50 (d, 3J¼20.8 Hz, CH-6), 168.38 (CO).
d
ꢁ144.26, minor signals at
d
ꢁ71.0, ꢁ62.6 (br), ꢁ49.6, ꢁ22.5 and
trace signals at ꢁ86.7, ꢁ15.0. The proton signals of the main com-
31P{1H} NMR (CDCl3, ppm):
d 11.3. C20H21N2O4P (384.37), MS (EI
ponent and HRMS confirm its identity as 3d. 1H NMR (CDCl3, ppm):
70 eV, 185 ꢀC): m/z (%)¼384 (7) [Mþ], 248 (15), 247 (71), 156 (11),
155 (100), 127 (60). HRMS (ESI in MeOHþNH4OAc) calcd for
[MþH]þ: 385.13117, found: 385.13125.
d
3.89 (d, 1J¼202.2 Hz, PH2), 4.34 (s, NCH2), 4.38 (br s, NH), 6.25 (dd,
3J¼3.2 Hz, J¼0.6 Hz, 30-H), 6.33 (dd, 3J¼3.2 Hz, J¼1.8 Hz, 40-H),
6.96 (ddd, 3J¼8.3 Hz, 4JPH¼2.9 Hz, 4J¼1.4 Hz, 4-H), 7.10 (ddd, 3J¼8.3,
4.7 Hz, 4JPH¼0.6 Hz, 5-H), 7.99 (dd, 3J¼4.5 Hz, 4J¼1.4 Hz, 6-H); 50-H
uncertain. MS (EI 70 eV, 100 ꢀC): m/z (%)¼206 (5), 203 (11), 202
(26), 174 (20), 173 (9) [MþꢁPH2], 95 (17), 81 (100). HRMS (EI) calcd
for 3d, C10H11N2OP: 206.0609, found: 206.0606.
4
4
4.1.12. 3-Amino-2-phosphinopyridine (3a)
A solution of 2a (0.90 g, 3.91 mmol) in diethyl ether (20 mL) was
added dropwise with stirring at 0 ꢀC to LiAlH4 pellets (0.45 g,
11.9 mmol) in diethyl ether (10 mL). After 2 days at room temper-
ature degassed water was added dropwise until the evolution of
hydrogen ceased. Solids were filtered off and washed with ether,
the filtrate was dried with Na2SO4, and the solvent was removed in
vacuum (ca. 1 Torr) affording 0.25 g (50%) colourless oily liquid 3a.
4.1.16. 3-(2-Thienyl)methylamino-2-phosphino-pyridine (3e)
Reduction of 2e (1.20 g, 3.53 mmol) in diethyl ether (30 mL) by
LiAlH4 pellets (0.40 g, 10.54 mmol) in diethyl ether (20 mL) and
work-up as described for 3a furnished 0.50 g of pale yellow viscous
liquid containing 3e as main component. 1H NMR (CDCl3, ppm):
1H NMR (CDCl3, ppm):
d
2.69 (br s, 2H, NH2), 3.45 (d, 1JPH¼200.2 Hz,
2H, PH2), 5.86 (ddd, 3J¼8.1 Hz, 4JPH¼3.3 Hz, 4J¼1.4 Hz,1H, 4-H), 6.25
d
3.84 (d, 1JPH¼202.3 Hz, 2H, PH2), 4.47 (br s, NH), 4.51 (d, 3J¼5.4 Hz,
(dd, 3J¼8.1 Hz, 3J¼4.6 Hz, 1H, 5-H), 7.77 (dd, 3J¼4.6 Hz, 4J¼1.3 Hz,
2H, NCH2), 6.83 (superimposed m, 3Jz8 Hz, 4-H), 6.92 (dd, 3J¼5,
4 Hz, 40-H), 7.03 (dd, 3J¼8.4, 4.4 Hz, 5-H), 7.17 (dd, 3J¼4 Hz, 4J¼1 Hz,
30-H), 7.98 (dd, 3J¼4.6 Hz, 4J¼1.2 Hz, 1H, 6-H), 8.02 (dd, 3J¼5 Hz,
1H, 6-H). 13C{1H} NMR (CDCl3, ppm):
d 121.07 (s, CH-4), 124.12 (s,
CH-5), 140.84 (d, 3J¼11.7 Hz, CH-6), 145.82 (d, 2J¼10.8 Hz, Cq-3),
139.87 (d, 1J¼9.2 Hz, Cq-2). 31P{1H} NMR (CDCl3, ppm):
d
ꢁ144.29.
4J¼1 Hz, 50-H). 31P NMR (CDCl3, ppm):
d
ꢁ146.22. MS (EI 70 eV,
MS (EI, 25 ꢀC): m/z (%)¼127 (4), 126 (100) [Mþ], 125 (9), 124 (6), 94
(19), 79 (12). HRMS (EI) calcd for C5H7N2P: 126.03469, found:
126.0347. (The 31P NMR spectrum indicated small impurities at
150 ꢀC): m/z (%)¼280 (7) [C12H13N2O2PSþ], 248 (9), 222 (5) [Mþ 3e],
221 (7), 220 (5) [C10H9N2PSþ], 219 (22), 97 (100). Further evidence
for 3e is provided by formation of 5e from the crude product and
DMFA. (Hints as to the nature of the side products: C12H13N2O2PS is
consistent with 2-thienyl-3-ethoxy-3-oxo-2,3-dihydro-1,3-aza-
phospholo[4,5-b]pyridine that might have formed after amide re-
duction by intramolecular attack of NCHLi at the PO(OEt)2 group;
d
ꢁ123.2, ꢁ63.3 ppm.)
4.1.13. 3-Neopentylamino-2-phosphino-pyridine (3b)
Reduction of 2b (0.80 g, 2.55 mmol) in diethyl ether (10 mL) by
LiAlH4 pellets (0.29 g, 7.64 mmol) in diethyl ether (10 mL) and
work-up as described for 3a furnished 0.21 g pale yellow viscous
oil. NMR control showed strongly impure 3b, content slightly less
than 50 mol %. Single crystals of pure 3b were grown from diethyl
ether by slow concentration (diffusion of ether through a rubber
septum). For crystal data of 3b see Table 2. 1H NMR (CDCl3, ppm):
C10H9N2PS might be its reduction product, P-secondary 2-thienyl-
2,3-dihydro-1,3-azaphospholo[4,5-b]pyridine, occurring as a dia-
stereoisomeric mixture.)
4.1.17. 1H-1,3-Azaphospholo[4,5-b]pyridine (5a)
A mixture of 3a (0.19 g, 1.51 mmol) and dimethylformamide
dimethyl acetal (DMFA) (0.22 mL, 1.66 mmol) was heated for 5 days
at 50 ꢀC. Volatiles were removed in vacuum and the product was
separated by distillation at 10ꢁ5 mbar/45–50 ꢀC bath temperature
using a microdistillation device to yield 0.13 g (63%) of highly air-
d
1.04 (s, 9H, CMe3), 2.93 (s, 3J¼5.7 Hz, 2H, NCH2), 3.86 (d,
1JPH¼200.6 Hz, 2H, PH2), 3.98 (br s, NH), 6.86 (dd, 3J¼8.5 Hz,
4JPH¼2.8 Hz, 4J¼1.3 Hz, 1H, 4-H), 7.09 (dd, 3J¼8.4, 4.6 Hz, 1H, 5-H),
7.97 (dd, 3J¼4.6 Hz, 4J¼1.0 Hz, 1H, 6-H). 13C{1H} (DEPT) NMR (CDCl3,
ppm):
d
27.64 (s, CMe3), 31.91 (s, CMe3), 55.30 (s, 7-C, NCH2), 115.61
sensitive white solid. 1H NMR (CDCl3, ppm):
d
7.28 (solvent super-
(s, CH-4), 124.31 (s, CH-5), 138.46 (d, 3J¼13.0 Hz, CH-6), 139.87 (d,
imposed ddd, 3J¼4.5 Hz, JPH¼1.5 Hz, 1H, 6-H), 7.93 (d, 3J¼8.6 Hz,
5
1J¼9.2 Hz, Cq-1, low intensity, uncertain), 147.99 (d, 2J¼9.4 Hz, Cq-
1H, 7-H), 8.66 (dd, 3J¼4.5 Hz, JPH¼1.4 Hz, 1H, 5-H), 8.83 (dd,
4
3). 31P{1H} NMR (CDCl3, ppm):
d
ꢁ146.2. C10H17N2P (196.11), MS (EI
3JPH¼36.8 Hz, 3JHCNH¼4.7 Hz, 1H, 2-H), 9.57 (br s, NH). 13C{1H} NMR
70 eV, 25 ꢀC): m/z (%)¼197 (2), 196 (35) [Mþ], 195 (8), 167 (26), 139
(100) [Mþꢁ57], 106 (37), 57 (22). HRMS (ESI in MeOHþNH4OAc)
calcd for [MþH]þ C10H17N2P: 197.12021, found: 197.12033. 31P NMR
(CDCl3, ppm): d 117.45, 118.58 (2s, CH-6, CH-7), 143.1 (d, low in-
tensity, CH-5), 163.53 (d, 1J¼55.1 Hz, CH-2), Cq-7a and Cq-3a in
noise. 31P{1H} NMR (CDCl3, ppm):
d
81.68. MS (EI 70 eV, 100 ꢀC):
impurity signals:
d
ꢁ62.7 (medium), ꢁ25.4 (small).
m/z (%)¼137 (9), 136 (100) [Mþ], 135 (4), 109 (46), 108 (11), 82 (48),
81 (20), 68 (16). HRMS (ESI in MeOH/H2O/HCOOH) calcd for
C6H5N2P 136.0911: [MþH]þ 137.02631, found: 137.02636.
4.1.14. Detection of 3-benzylamino-2-phosphino-pyridine (3c) in
a mixture of products
Reduction of 2c (1.42 g, 2.25 mmol) in diethyl ether (30 mL) by
LiAlH4 pellets (0.48 g, 12.74 mmol) in diethyl ether (20 mL) and
work-up as described for 3a afforded 0.57 g of pale yellow oil. NMR
control of the crude product showed intense phosphorus signals at
4.1.18. 1-Neopentyl-1,3-azaphospholo[4,5-b]pyridine (5b)
A mixture of crude 3b (0.20 g, content of 3b ca. 0.5 mmol) and
DMFA (0.15 mL, 1.1 mmol) was heated for 7 days at 50 ꢀC and sep-
arated at 10ꢁ5 Torr using a microdistillation device. Compound 5b
(0.10 g) was collected at 79–81 ꢀC bath temperature as colourless
oil, contaminated by small amounts of phosphorus compounds
d
ꢁ144.7, ꢁ62.9 (br), ꢁ60.7 (br), ꢁ55.5, ꢁ21.1, ꢁ4.8 (br) and proton
signals among others for NCH2, PH and multiplets in the NCH region.
This indicates formation of a mixture containing primary 3-benzyl-
aminopyridylphosphine 3c (detected also by HRMS), secondary
and tertiary phosphines. No attempts were made to separate the
multi-component mixture. MS (EI 70 eV,120 ꢀC): m/z (%)¼244 (2.4),
242 (1.4), 216 (7.6), 215 (7.1), 213 (8.1),184 (34) [3cþꢁPH]. HRMS (EI)
calcd for 3c, C12H13N2P: 216.08163, found: 216.0808.
with
d
31P ꢁ51.1, ꢁ25.3, 42.6, 43.4, content of 5b 63 mol % (by 1H
NMR integration of aryl protons), yield of 5b relative to 3b was
about 60%. 1H NMR (CDCl3, ppm):
d 1.02 (s, 9H, CMe3), 4.10 (s, 2H,
NCH2), 7.26 (ddd, 3J¼8.7, 4.4 Hz, JPH¼1.5 Hz, 1H, 6-H), 7.88 (br d,
5
3J¼8.7 Hz, 1H, 7-H), 8.61 (d, JPH¼37.2 Hz, 1H, 2-H), 8.63 (d,
2
3J¼4.4 Hz, 4JPH¼1.4 Hz, 1H, 5-H). 13C{1H} (DEPT) NMR (CDCl3, ppm):

M.S.S. Adam et al. / Tetrahedron 64 (2008) 7960–7967
7967
d
28.26 (s, CMe3), 61.39 (d, 3J¼2.7 Hz, NCH2), 67.99 (s, CqMe3), 118.14
crystallographic data for 2c and 3b have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publi-
cation no. CCDC 687134 and CCDC 687135. Copies of the data can be
obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: (int. code) þ44 1223 336 033, e-mail:
deposit@ccdc.cam.ac.uk].
(d, 4J¼1.8 Hz, CH-6), 120.24 (s, CH-7), 136.58 (low intensity d,
1J¼71 Hz, Cq-3a, uncertain), 144.26 (d, 3J¼15.1 Hz, CH-5), 165.08 (d,
1J¼53.8 Hz, CH-2), 165.78 (d, J¼26.5 Hz, Cq-7a or 3a). 31P{1H} NMR
(CDCl3, ppm):
d
71.79. MS (EI 70 eV, 120 ꢀC): m/z (%)¼207 (10), 206
(92) [Mþ], 165 (30), 148 (100) [MþꢁC4H8], 57 (30). HRMS (EI): calcd
for C11H15N2P: 206.0973, found: 206.0974.
Acknowledgements
4.1.19. 1-(20-Furyl)methyl-1,3-azaphospholo[4,5-b]-pyridine (5d)
A mixture of crude 3d (0.45 g) and DMFA (0.35 mL, 2.63 mmol)
was heated for 7 days at 50 ꢀC and separated using a micro-
distillation device. At 10ꢁ5 Torr/79–84 ꢀC bath temperature 0.31 g
of pale yellow oil was collected, consisting of 5d, 3-(20-fur-
yl)methylamino-pyridine and 3-(20-furoyl)amido-pyridine, molar
ratio 10:25:5 (by 1H NMR integration of selected aryl protons).
Financial support from the Deutsche Forschungsgemeinschaft and
a
fellowship (M.S.S.A.) from the Deutsche Akademische Aus-
landsdienst is gratefully acknowledged. We thank B. Witt for NMR
and W. Heiden for mass spectra, Dr. H. Frauendorf and G. Sommer-
Udvarnoki (Georg-August-Universita¨t Go¨ttingen, Institut fu¨r
Organische und Biomolekulare Chemie) for HRMS measurements.
Compound 5d: 1H NMR (CDCl3, ppm):
d
5.42 (s, 2H, NCH2), 6.35 (dd,
3
3J¼3.3 Hz, J¼1.8 Hz, 1H, 40-H), 7.28 (superimposed m, 2H, 3J¼8.6,
Supplementary data
4.5 Hz, J¼1.5 Hz, 6-H, 50-H), 7.96 (br d, 3J¼8.6 Hz, 1H, 7-H), 8.1
4
(superimposed, 30-H, uncertain), 8.66 (dd, 3J¼4.5 Hz, 4J¼1.5 Hz, 1H,
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2008.06.010.
5-H), 8.69 (d, JPH¼36.7 Hz, 1H, 2-H); 31P{1H} NMR (CDCl3, ppm):
2
d
76.56. HRMS: calcd for C11H9N2OP 216.0453: [MþH] 217.05264;
found (ESI in MeOH, NH4Oac): 217.05253. Side products: 3-(20-
furyl)methylamino-pyridine, 1H NMR (CDCl34, ppm):
d 3.49 (br s,
References and notes
NH), 4.34 (s, 2H, NCH2), 6.25 (dd, 3J¼3.2 Hz, J¼0.6 Hz, 30-H), 6.33
1. Aminophosphonic and Aminophosphinic Acids; Kuhkar, V. P., Hudson, H. R., Eds.;
Wiley: Chichester, UK, 2000.
2. (a) Aluri, B. R.; Kindermann, M. K.; Jones, P. G.; Dix, I.; Heinicke, J. W. Inorg.
Chem., in press; (b) Aluri, B. R.; Kindermann, M. K.; Jones, P. G.; Heinicke, J. W.
Chem.dEur. J. 2008, 14, 4328.
3. Ku¨hl, O.; Lifson, K.; Langel, W. Eur. J. Org. Chem. 2006, 2336.
4. (a) Newkome, G. R. Chem. Rev. 1993, 93, 2067; (b) Espinet, P.; Soulantica, K.
Coord. Chem. Rev. 1999, 193–194, 499; (c) Speiser, F.; Braunstein, P.; Saussine, L.
Acc. Chem. Res. 2005, 38, 784.
5. (a) Bansal, R. K.; Heinicke, J. Chem. Rev. 2001, 101, 3549; (b) Bansal, R. K.; Kar-
aghiosoff, K.; Schmidpeter, A. Tetrahedron 1994, 50, 7675; (c) Gupta, N.; Jain, C.
B.; Heinicke, J.; Bansal, R. K.; Jones, P. G. Eur. J. Inorg. Chem. 1998, 1079; (d)
Bansal, R. K.; Karaghiosoff, K.; Gupta, N.; Schmidpeter, A.; Spindler, C. Chem. Ber.
1991, 124, 475.
6. (a) Heinicke, J.; Gupta, N.; Surana, A.; Peulecke, N.; Witt, B.; Steinhauser, K.;
Bansal, R. K.; Jones, P. G. Tetrahedron 2001, 57, 9963; (b) Bansal, R. K.; Gupta, N.;
Heinicke, J.; Nikonov, G. N.; Saguitova, F.; Sharma, D. C. Synthesis 1999, 264.
7. (a) Heinicke, J.; Surana, A.; Peulecke, N.; Bansal, R. K.; Murso, A.; Stalke, D. Eur. J.
Inorg. Chem. 2001, 2563; (b) Surana, A.; Singh, S.; Bansal, R. K.; Peulecke, N.;
Spannenberg, A.; Heinicke, J. J. Organomet. Chem. 2002, 646, 113; (c) Heinicke, J.;
Gupta, N.; Singh, S.; Surana, A.; Ku¨hl, O.; Bansal, R. K.; Karaghiosoff, K.; Vogt,
M. Z. Anorg. Allg. Chem. 2002, 628, 2869; (d) Heinicke, J.; Steinhauser, K.;
Peulecke, N.; Spannenberg, A.; Mayer, P.; Karaghiosoff, K. Organometallics 2002,
21, 912.
8. Corbridge, D. E. C. Phosphorus 2000: Chemistry, Biochemistry and Technology;
Elsevier: Amsterdam, 2000; Chapter 6, pp 297–454.
9. (a) Kohler, M. C.; Stockland, R. A.; Rath, N. P. Organometallics 2006, 25, 5746 and
references cited therein; (b) Gelman, D.; Jiang, L.; Buchwald, S. L. Org. Lett. 2003,
5, 2315; (c) Park, J.; Ho Lee, P. Bull. Korean Chem. Soc. 1997, 18, 1130; (d) Hirao, T.;
Masunaga, T.; Ohshiro, Y.; Agawa, T. Synthesis 1981, 56.
(dd, J¼3.2, 1.9 Hz, 40-H), 6.95 (ddd, 3J¼8.3 Hz, 4J¼2.9, 1.4 Hz, 4-H),
3
7.10 (ddd, 3J¼8.3, 4.7 Hz, 5J¼0.5 Hz, 5-H), 7.37 (dd, 3J¼1.8 Hz,
4J¼0.7 Hz, 50-H), 8.00 (dd, 3J¼4.7 Hz, 4J¼1.3 Hz, 6-H), 8.10 (br d,
4J¼2.8 Hz, 2-H). 3-(20-Furoyl)amido-pyridine, 1H NMR (CDCl3,
3
ppm):
d
6.59 (dd, J¼3.5, 1.8 Hz, 40-H), 7.34 (superimposed br dd,
3J¼8.6, 4.9 Hz, 5-H), 7.38 (superimposed dd, 3Jz2.7 Hz, 4Jz0.7 Hz,
30-H), 7.55 (dd, 3J¼1.7 Hz, J¼0.8 Hz, 50-H), 8.30 (ddd, 3J¼8.3 Hz,
4
4J¼2.6, 1.5 Hz, 4-H), 8.40 (dd, 3J¼4.7 Hz, 4J¼1.5 Hz, 6-H), 8.70 (br d,
4J¼2.5 Hz, 2-H).
4.1.20. 1-(20-Thienyl)methyl-1,3-azaphospholo[4,5-b]pyridine (5e)
A mixture of crude 3e (0.42 g) and DMFA (0.21 mL, 1.89 mmol)
was heated for 7 days at 50 ꢀC, and 0.19 g of a pale yellow oil was
separated by distillation at 10ꢁ5 mbar/79–84 ꢀC bath temperature.
NMR spectra indicated strongly contaminated 5e, content 45 mol %
by 1H NMR integration of aryl protons. 1H NMR (CDCl3, ppm):
d 5.64
(s, 2H, NCH2), 6.90–7.25 (m, 20-H, 30-H, 50-H), 7.29 (solvent super-
imposed ddd, 3J¼8.6, 4.5 Hz, 4J¼1.4 Hz, 1H, 6-H), 7.95 (d, 3J¼8.6 Hz,
1H, 7-H), 8.66 (superimposed dd, 3Jz4.0 Hz, 4J¼1.2 Hz, 1H, 5-H),
8.74 (d, 2JPH¼36.5 Hz, 1H, 2-H). 31P{1H} NMR (CDCl3, ppm):
d 76.97.
HRMS calcd for C11H9N2PS 232.25: [MþH] 233.02968, found (ESI in
MeOH, NH4OAc): 233.02980.
10. Allen, D. W.; Coles, S. J.; Hursthouse, M. B. Heteroat. Chem. 2005, 16, 242; (b)
Tavs, P. Chem. Ber. 1970, 103, 2428.
5. Crystal structure analysis
11. Yang, H.; Li, H.; Wittenberg, R.; Egi, M.; Huang, W.; Liebeskind, L. S. J. Am. Chem.
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1978, 43, 4538; (c) Balthazor, T. M.; Grabiak, R. C. J. Org. Chem. 1980, 45, 5425.
12. Ku¨hl, O. Concise Introduction to 31P-NMR SpectroscopydA Guide for the Synthetic
Organic and Organometallic Chemist; Springer: Heidelberg, 2008; (b) Berger, S.;
Braun, S.; Kalinowski, H. O. NMR-Spektroskopie von Nichtmetallen, Band 3, 31P-
NMR-Spektroskopie; Thieme: Stuttgart, 1993; p 173.
13. Heinicke, J.; Musina, E.; Peulecke, N.; Karasik, A. A.; Kindermann, M. K.; Do-
brynin, A.; Litvinov, I. Z. Anorg. Allg. Chem. 2007, 633, 1995; (b) Dee, A.; Peri, S. P.
Synthesis 1991, 691; (c) Heinicke, J.; Boehle, I.; Tzschach, A. J. Organomet. Chem.
1986, 317, 11; (d) Dhawan, B.; Redmore, D. J. Org. Chem. 1984, 49, 4018; (e)
Melvin, L. S. Tetrahedron Lett. 1981, 22, 3375.
14. Garnier, E.; Blanchard, S.; Rodriguez, I.; Jarry, C.; Leger, J.; Caubere, P.; Guil-
laumet, G. Synthesis 2003, 13, 2033.
15. SHELXS-97 and SHELXL-97. Programs for the Solution and Refinement of Crystal
Structures; Sheldrick, G. M., Ed.; University of Go¨ttingen: Go¨ttingen, Germany,
1997.
Data collection. Crystals were mounted on glass fibers in inert oil
and transferred to the cold gas stream of the diffractometer (Bruker
SMART 1000 CCD). Data were collected with monochromated Mo
Ka
radiation.
Structure refinement. The structures were refined anisotropically
on F2 using the program SHELXL-97 (Prof. G.M. Sheldrick, Univer-
sity of Go¨ttingen, Germany).15 Hydrogen atom treatment. NH free,
PH free but with distance restraints, methyls as idealised rigid
groups, others riding. For compound 3b, the Flack parameter re-
fined to 0.00(8).
For selected bond lengths and angles of 2c and 3b see Figures 1
and 2. The crystallographic data are listed in Table 2. Complete