Synthesis of electron-rich sterically hindered P1 phosphazene bases by the staudinger reaction

Article abstract of DOI:10.1002/ejoc.201201400

The synthesis of electron-rich P₁ phosphazene bases with a sterically protected basic center by a Staudinger reaction is reported. The initial products of the reaction between peralkylated triaminophosphanes and bulky alkyl azides, phosphazides 1a-f, were isolated in all cases in good to quantitative yield. The structures of 1d and 1e were confirmed by single-crystal X-ray diffraction. Acidic hydrolysis of pyrrolidino-substituted phosphazide (pyrr)₃PN₃tBu 1d led to the quantitative formation of aminophosphonium salt (pyrr)₃PNH₂⁺· BF₄^- 8, a direct precursor to a Schwesinger's "building block" synthetic unit. Thermally induced denitrogenation of the phosphazides, which is the second step performed in most cases under solvent-free conditions gave P₁ phosphazene bases 2a-f in moderate to excellent yields. A "one-pot" two-step synthesis of phosphazene bases from commercially available triaminophosphanes was discovered. Most of the syntheses were performed on a large laboratory scale. The basicities of the newly synthesized bases 2e and 2f were determined. X-ray crystal structures were obtained for base 2e and for protonated species 2d·HBF₄, 2e·HBF₄, and 2f·HOTs, which provided the crucial geometrical parameters around the basic center. A rationale for the higher basicity of the pyrrolidino- (pyrr)₃P=NR than the piperidino- (pip)₃P=NR phosphazenes is presented. A Staudinger reaction was successfully used for the synthesis of a number of sterically congested electron-rich P₁ phosphazene bases in moderate to quantitative yield. The intermediate phosphazides were isolated and characterized in all cases; their application in the preparation of higher-order phosphazenes is described. Copyright

Full text of DOI:10.1002/ejoc.201201400

FULL PAPER
DOI: 10.1002/ejoc.201201400
Synthesis of Electron-Rich Sterically Hindered P1 Phosphazene Bases by the
Staudinger Reaction
[a]
[a]
[a]
[b]
ˇ
ˇ
ˇ
Anastasia V. Alexandrova,* Tomás Masek, Svetlana M. Polyakova, Ivana Císarová,
Jaan Saame,[c] Ivo Leito,[c] and Ilya M. Lyapkalo[a][‡]
Keywords: Phosphazenes / Phosphazides / Staudinger reaction / Azides / Basicity / Structure-activity relationships
The synthesis of electron-rich P1 phosphazene bases with a
sterically protected basic center by a Staudinger reaction is
reported. The initial products of the reaction between per-
alkylated triaminophosphanes and bulky alkyl azides,
phosphazides 1a–f, were isolated in all cases in good to quan-
titative yield. The structures of 1d and 1e were confirmed by
single-crystal X-ray diffraction. Acidic hydrolysis of pyrrolid-
ino-substituted phosphazide (pyrr)3PN3tBu 1d led to the
quantitative formation of aminophosphonium salt (pyrr)3-
PNH2+·BF4– 8, a direct precursor to a Schwesinger’s “building
block” synthetic unit. Thermally induced denitrogenation of
the phosphazides, which is the second step performed in
most cases under solvent-free conditions gave P1 phosphaz-
ene bases 2a–f in moderate to excellent yields. A “one-pot”
two-step synthesis of phosphazene bases from commercially
available triaminophosphanes was discovered. Most of the
syntheses were performed on a large laboratory scale. The
basicities of the newly synthesized bases 2e and 2f were de-
termined. X-ray crystal structures were obtained for base 2e
and for protonated species 2d·HBF4, 2e·HBF4, and 2f·HOTs,
which provided the crucial geometrical parameters around
the basic center. A rationale for the higher basicity of the
pyrrolidino- (pyrr)3P=NR than the piperidino- (pip)3P=NR
phosphazenes is presented.
Nowadays, Pn phosphazene bases covering a pKa range
of roughly fifteen orders of magnitude have found a broad
spectrum of applications in organic synthesis as selective
basic catalysts and stoichiometric auxiliary bases.[8] Their
unique properties such as strong basicity and low nucleo-
philicity, non-ionic, metal-free nature, easy handling due to
their intrinsic stability towards hydrolysis and oxidation in
air, appreciable solubility in conventional organic solvents,
possible recovery for re-use, etc. make phosphazene bases
attractive and truly indispensable reagents for organic syn-
thesis. Monophosphazenes (P1 phosphazene bases) are the
most frequently used among numerous Pn phosphazene
bases, and weakly nucleophilic monophosphazenes with
bulky substituents around the basic imine center are most
valuable for the selective deprotonation of complex multi-
functional substrates. Several iminophosphorane bases are
commercially available, but their prices are relatively high.
Many iminophosphoranes described in the literature
originate from the thermally induced denitrogenation of
phosphazides – the first-step products of the Staudinger re-
Introduction
Phosphazene bases are widely used in organic synthesis,
and they occupy a special place among superbasic com-
pounds.[1–2] Since the first representative of a large family
of iminophosphorane bases was synthesized in the 1970s,[3]
a large amount of information about their synthesis, prop-
erties, and applications has appeared in the literature.[4–7]
An intense development of the chemistry of phosphazene
bases is associated with the systematic investigations by
Schwesinger and co-workers.[5–7] Several routes for the
high-yielding preparation of electron-rich sterically hin-
dered P1 phosphazene bases have been developed. These
approaches, which are applicable to multi-molar scale syn-
thesis, are, to date, the only preparative methods for labora-
tory synthesis, despite the fact that they suffer from draw-
backs such as the time-consuming preparation of the reac-
tive intermediates and necessity of their isolation, the use
of and also the formation of irritating gases, application of
low reaction temperatures, etc.[6]
[a] Institute of Organic Chemistry and Biochemistry, Academy of action.[9–10] Phosphazides initially appeared to be unstable
Sciences of the Czech Republic,
entities that liberated nitrogen with ease to give iminophos-
v. v. i., Flemingovo námeˇstí 2, 16610 Prague 6, Czech Republic
phoranes.[9a,11] It was later found that some of them are
Fax: +420-220-183-578
E-mail: anastasia.alexandrova1@gmail.com
[b] Department of Inorganic Chemistry, Charles University,
Hlavova 2030, 12840 Prague 2, Czech Republic
[c] Institute of Chemistry, University of Tartu,
Ravila 14a, 50411 Tartu, Estonia
relatively stable, and that they can be used as Lewis and/
or Brønsted bases to facilitate a variety of base-mediated
transformations.[12,13] The second step in the Staudinger
protocol is the denitrogenation of the phosphazides at an
elevated temperature to give iminophosphoranes. There is
good evidence that the extrusion of dinitrogen proceeds via
[†] Deceased, September 10, 2010
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201400.
Eur. J. Org. Chem. 2013, 1811–1823
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1811

A. V. Alexandrova et al.
FULL PAPER
a four-membered transition state.[9,14] Because of the strain
of the transition state, less bulky substituents in a phos-
phazide structure favor denitrogenation.
Results and Discussion
The synthesis of sterically hindered alkyl azides was
Although the preparation of numerous functionalized achieved following Bottaro’s procedure.[20] The starting ma-
triaminophosphorane imines by the thermal denitro- terial for tert-heptyl azide, 2,3,3-trimethyl-2-butanol, was
genation of the corresponding phosphazides has been de- prepared by alkylation of pinacolone with methylmagne-
scribed,[15] the synthesis of valuable P1 phosphazene bases sium iodide. The synthesis of tert-heptyl azide was achieved
with sterically protected basic center has so far not been for the first time in a very good yield on a multi-gram scale
accomplished by the Staudinger reaction, even though this by a safe and effective procedure. tert-Octyl azide was syn-
process seems to be the most direct. Only two P1 phos- thesized from 2,4,4-trimethyl-1-pentene instead of an
phazene bases have been synthesized in good yield by the alcohol. All three alkyl azides were obtained in high crude
reaction between P(NMe2)3 and methyl and phenyl azides, yields. Further purification was not required, since the pu-
1
without isolation of the intermediately formed phosphaz- rity of the azides was confirmed by H NMR spectroscopy
ides.[16] The preparation of sterically hindered iminophos- after a simple work-up. The work-up of the reaction was
phorane bases by the Staudinger reaction has been assessed performed under conditions to prevent an explosion haz-
to be hazardous because of the unsafe nature of the corre- ard: as well as careful neutralization of the aqueous phase,
sponding azides, which are not readily available.[6] Never- the accumulation of hydrazoic acid in the organic phase
theless, the reaction of hexamethylphosphorous triamide was excluded by using pentane as an extracting solvent.
P(NMe2)3 with tert-butyl azide was examined in dichloro- This crucially reduces the probability of explosion during
methane as a solvent, and the corresponding phosphazide the evaporation of the residual solvent on a rotary evapora-
was isolated in 91% yield.[17] The quantitative formation of tor, and makes the method safe for laboratory practice.
the same phosphazide by a reaction in toluene was demon-
The Staudinger reaction has been reported as being per-
strated more recently in our group.[18] As organic azides are formed both in solution[16,17] and without a solvent (for in
important starting materials for the synthesis of nitrogen- situ generation of the phosphazene motif; no phosphazides
containing compounds, they are usually readily available, nor phosphazenes were isolated).[21] A solvent-free reaction
except for sterically congested alkyl azides; an effective syn- certainly seems to be more environmentally benign and sim-
thetic protocol for the multi-gram preparation of these lat- pler. Indeed, phosphazide 1a was obtained by the neat reac-
ter compounds hardly exists.[19] The only reliable and scal- tion between tris(dimethylamino)phosphane [P(NMe)3] and
able method for their synthesis is Bottaro’s protocol,[20] in tert-butyl azide in excellent yield (Scheme 1, Table 1, en-
which tert-butyl alcohol reacts with in situ generated hydra- try 1). The reaction proceeded quickly and even showed
zoic acid (HN3) to give tert-butyl azide in quantitative yield. exothermic character at the beginning of the addition of the
In this paper, we report the synthesis of a number of azide to the P(NMe)3. The formed phosphazide (i.e., 1a)
electron-rich P1 phosphazene bases with a sterically pro- was a viscous oil. This resulted in a reduction of the efficacy
tected basic center using the Staudinger reaction between of the stirring, and therefore the reaction was conducted
peralkylated triaminophosphanes and bulky alkyl azides. overnight at room temperature to guarantee complete con-
The intermediate phosphazides are sufficiently stable in air version of the starting materials. The NMR spectroscopic
at ambient temperature to be handled easily. Their subse- data proved the high purity of crude 1a. The 1H NMR spec-
quent pyrolysis, performed under solvent-free conditions, trum was completely consistent with the proposed struc-
causes extrusion of molecular nitrogen with formation of ture, and the 31P NMR spectrum of 1a showed a single
P1 phosphazene bases in moderate to excellent yields. Also, signal at δP = 41.77 ppm.[17] The more bulky tert-heptyl and
a facile and efficient one-pot procedure for the synthesis tert-octyl azides reacted similarly with P(NMe)3 to give
of iminophosphoranes starting from commercially available phosphazides 1b and 1c quantitatively (Table 1, entries 2
triaminophosphanes is reported.
and 3). Since 1b crystallized readily under the reaction con-
Scheme 1. Preparation of phosphazides 1a–e and phosphazenes 2a–e.
1812
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 1811–1823

Electron-Rich Sterically Hindered P1 Phosphazene Bases
Table 1. Conditions for the preparation of compounds 1a–e and 2a–e.
Entry Compd.
R
tert-Alk
Time of preparation of 1
Yield[a] of 1
Time of preparation of 2 Yield of 2[a]
[%]
[h]
[%]
1
2
3
4
5
a
b
c
d
e
Me
Me
Me
-(CH2)4-
-(CH2)5-
CMe3
overnight[b]
3 h[c]
99
99
25
210
115
36
83
40
65
CMe2CMe3
CMe2CH2CMe3
CMe3
overnight[b]
overnight[b]
overnight[b]
99
91[d]
96[d]
84
CMe3
180
77[e]
[a] Isolated yields. [b] 0 °C to room temp. [c] 0–40 °C. [d] Yield after two steps. [e] Base 2e was isolated via its tetrafluoroborate salt.
ditions, mild heating at 40 °C was applied in order to Tricyclic triaminophosphane 7[27a] was prepared according
achieve complete conversion.
to the literature by alkylation of bicyclic guanidine 3 with
Two other triaminophosphanes were synthesized by reac- propylene 1,3-ditosylate,[27b] reduction of iminium salt
tion of phosphorus trichloride with secondary amines.[22] 4,[27b–c] hydrolysis of orthoamine 5,[27a,c] and transamid-
Tripyrrolidinophosphane,[23] P(pyrr)3, which is known to be ation of P(NMe2)3 with 6[27a] in 67% overall yield. All of
water- and oxygen-sensitive, required inert conditions for its the phosphazides prepared (i.e., 1a–f) were stable under am-
isolation, and the product was isolated in only 75% yield. bient conditions; however, storing them at low temperature
Its neat small-scale reaction with tert-butyl azide resulted under dry argon is beneficial to avoid acid-mediated decom-
as before in the quantitative formation of the corresponding position.
phosphazide (i.e., 1d). The evident loss of P(pyrr)3 during
The structures of 1d and 1e were proved by single-crystal
the time-consuming and laborious isolation[24] prompted X-ray diffraction (Figure 1 and Figure 2).[28] Both com-
the development of a one-pot approach. Thus, tripyrrolid- pounds have a distorted tetrahedral geometry at the phos-
inophosphane was initially generated by the reaction of phorus atom with averaged tetrahedral angles at the apex
PCl3 with an excess of pyrrolidine, and was subsequently and the base of the tetrahedron with atom N1 on the top
converted into phosphazide 1d in THF solution in 91% of 109.6° and 111.9°, respectively, in 1d and 111.8° and
yield by the addition of tert-butyl azide (Table 1, entry 4). 107.1° in 1e. Despite the precedent for phosphazides with a
The latter reaction in THF was compatible with pyrrolidine cis-geometry in the P=N–N=N unit,[12b,29] the structures of
hydrochloride present in the mixture. An excess of pyrrolid- both 1d and 1e show a planar trans-configured phosphazide
ine was used in order to keep the medium basic and so moiety, which is more often described in the literature.[9,17]
to prevent the possible acid-mediated decomposition of 1d. The interatomic distances and angles of the {PNNNC} unit
Tripiperidinophosphane,[25] P(pip)3 was similarly prepared, in 1d and 1e are remarkably similar. The torsion angle P1–
and, without isolation, was converted into phosphazide 1e N3–N2–N1 is close to 176°. The P1–N3 imine bond dis-
overnight at room temperature (Table 1, entry 5). Subse- tances are short, being 1.612 and 1.606 Å for 1d and 1e
quent aqueous work-up gave phosphazide 1e in 96% yield. respectively, which is at the short end of the range for typi-
Attempts to synthesize the bulky hexakis(diisopropyl- cal P–N double-bond lengths,[30] and shorter than what has
amino)phosphane P(NiPr2)3 by the reaction of PCl3 with been described for a phosphazide structure in the litera-
diisopropylamine under the conditions described above ture.[17] The bond alternation in the {PNNN} unit is
failed, and the product formed was bis(diisopropyl- slightly more pronounced in structure 1d.
amino)chlorophosphane.[26]
Phosphazides 1a–f can serve as starting materials for the
Tricyclic phosphazide 1f was obtained from triamino- synthesis of tetraaminophosphonium salts (phosphazene
phosphane 7 and tert-butyl azide in toluene. It was neces- salts), which are building blocks for the construction of
sary to use a solvent, since 7 was a solid at 0 °C. Complete higher-order phosphazene bases. Phosphazide 1d under-
conversion of 7 into 1f was achieved in 2.5 h (Scheme 2). went elimination of molecular nitrogen and isobutylene on
Scheme 2. Preparation of phosphazide 1f and base 2f.
Eur. J. Org. Chem. 2013, 1811–1823
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1813

A. V. Alexandrova et al.
FULL PAPER
Scheme 3. Acid-promoted decomposition of 1d.
Phosphazenes 2 were prepared from phosphazides 1 by
the thermal extrusion of nitrogen. Phosphazide 1a was
heated neat at 145 °C under an atmosphere of dry argon
(Scheme 1, Table 1, entry 1). In contrast to literature re-
ports where gum formation and even an explosion were ob-
served on heating without a solvent,[9a] the conversion of
1a into base 2a proceeded smoothly; the progress of the
reaction was monitored by 31P NMR spectroscopy, and the
spectrum of the residue after pyrolysis showed a single
strongly upfield-shifted signal due to 2a at δ = 1.25 ppm.[4d]
The other two phosphazides (i.e., 1b and 1c) showed higher
resistance to thermal denitrogenation than did 1a, and their
complete conversion into bases 2b and 2c required 210 and
115 h of heating, respectively (Table 1, entries 2 and 3). The
dark sticky residue obtained after pyrolysis in both cases
was purified by high-vacuum distillation; other purification
methods were found to be ineffective. Base 2b was isolated
in moderate yield as a colorless thick oil, which became an
amorphous solid on standing at room temperature, whereas
2c was an oil. In practice, the synthesis of 2a–c was per-
formed in a Schlenk flask: the residue obtained after the
first step was freed from the excess of tert-alkyl azide under
high vacuum, and the crude but clean phosphazide was de-
nitrogenated under argon at elevated temperature.
Figure 1. X-ray crystal structure of phosphazide 1d. Displacement
ellipsoids are drawn at the 30% probability level. Hydrogen atoms
are omitted for clarity. Selected bond lengths [Å] and angles [°]:
P1–N3 1.612(1), P1–N4 1.647(1), P1–N5 1.634(1), P1–N6 1.640(1),
N2–N3 1.371(2), N1–N2 1.253(2), N1–C1 1.495(2); N3–P1–N4
121.63(6), N3–P1–N5 111.67(7), N3–P1–N6 102.39(7), N4–P1–N5
101.85(6), N4–P1–N6 105.19(6), N5–P1–N6 114.49(7), P1–N3–N2
109.12(9), N1–N2–N3 113.1(1), N2–N1–C1 111.7(1); P1–N3–N2–
N1 175.9(1).
Phosphazide 1d was completely consumed after 36 h of
heating at 145 °C in the absence of solvent. High-vacuum
distillation gave 2d in good yield (Table 1, entry 4). The py-
rolysis of phosphazide 1e required 180 h of heating at
145 °C for complete conversion into base 2e. Purification of
the resulting brown oil was achieved by the formation of
tetrafluoroborate salt 2e·HBF4, which was isolated in 79%
yield as a non-hygroscopic crystalline solid. Free base 2e
was subsequently obtained in 98% yield by treatment of a
methanolic solution of 2e·HBF4 with a mixture of hexane
and aqueous KOH.
Phosphazide 1f provided base 2f with only moderate
selectivity after heating neat at 145 °C. The 31P NMR spec-
trum of the residue showed several signals due to unidenti-
fied by-products, together with the signal due to the desired
base (i.e., 2f). To improve the selectivity of the reaction,
triethylamine was used as a medium, and this gave 2f in
98% yield after 24 h of heating at reflux (Scheme 2). Trieth-
ylamine was beneficial because of its basic character, which
disfavors partial acid-mediated degradation of phoshazide
Figure 2. X-ray crystal structure of phosphazide 1e. Displacement
ellipsoids are drawn at the 30% probability level. Hydrogen atoms
are omitted for clarity. Selected bond lengths [Å] and angles [°]:
P1–N3 1.606(1), P1–N4 1.651(2), P1–N5 1.657(1), P1–N6 1.636(2),
N2–N3 1.377(2), N1–N2 1.254(2), N1–C1 1.492(2); N3–P1–N4
112.19(7), N3–P1–N5 120.36(7), N3–P1–N6 102.95(7), N4–P1–N5
102.96(7), N4–P1–N6 112.23(8), N5–P1–N6 106.22(7), P1–N3–N2
110.8(1), N1–N2–N3 112.2(1), N2–N1–C1 112.1(2); P1–N3–N2–
N1 176.1(1).
treatment with aqueous tetrafluoroboric acid to give 1f. Moreover, in this case, the solvent excluded any possible
aminophosphonium salt in quantitative yield undesired local overheating that could result from irregular
8
(Scheme 3).[18,31] Tetraaminophosphonium salt 8 can be de- stirring affected by viscosity fluctuations.
protonated to give tris(1-pyrrolidinyl)iminophosphorane,[7]
Liquid P1 phosphazene bases 2a,c,d can be stored in a
which is a building block for the synthesis of Pn phosphaz- fridge under argon over solid barium oxide. Crystalline
ene bases.[5c,6]
bases 2b,e,f were kept neat at ca. 0 °C under argon. All
1814
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 1811–1823

Electron-Rich Sterically Hindered P1 Phosphazene Bases
bases 2a–f can be stored as stock solutions in hexane over
solid BaO.
The structure of 2e was confirmed by single-crystal X-
ray diffraction (Figure 3).[28] The tetrahedral symmetry
around the phosphorus atom is strongly distorted. A sig-
nificant difference between the angles at the apex and the
base of the tetrahedron with N1 at an apex of more than
10° was found (114.6 and 104.1° respectively, N1 is the apex
of the tetrahedron). The three P–N(sp3) bonds do not differ
considerably in length from each other and are rather
long,[30] while the length of the P=N double bond is much
shorter.[30]
Figure 4. X-ray crystal structure of salt 2d·HBF4. Displacement el-
lipsoids are drawn at the 30% probability level. Hydrogen atoms
except N1–H are omitted for clarity. Atom C15 is disordered into
two positions; only the position with a larger occupancy factor
(0.86) is shown. Selected bonds lengths [Å] and angles [°]: P1–N1
1.629(1), P1–N2 1.622(1), P1–N3 1.616(1), P1–N4 1.626(1), N1–C1
1.495(2); N1–P1–N2 111.92(7), N1–P1–N3 115.45(7), N1–P1–N4
101.43(7), N2–P1–N3 104.93(7), N2–P1–N4 112.44(7), N3–P1–N4
110.93(7), P1–N1–C1 130.5(1). Hydrogen bond N1–H1···F1 pa-
rameters: N1–H1 0.92 Å, H1···F1 2.46 Å, N1···F1 3.2556(19) Å,
N1–H1···F1 145°.
Figure 3. X-ray crystal structure of base 2e. Displacement ellipsoids
are drawn at the 50% probability level. Hydrogen atoms are omit-
ted for clarity. Selected bonds lengths [Å] and angles [°]: P1–N1
1.539(1), P1–N2 1.682(1), P1–N3 1.680(1), P1–N4 1.671(1), N1–C1
1.457(2); N1–P1–N2 114.44(6), N1–P1–N3 123.47(6), N1–P1–N4
105.87(6), N2–P1–N3 99.75(5), N2–P1–N4 110.93(5), N3–P1–N4
101.55(5), P1–N1–C1 134.42(9).
To reveal the structural features of the stable phos-
phazenium cations, X-ray crystal structures of 2d·HBF4,
2e·HBF4, and 2f·HOTs were obtained (see Figures 4, 5,
6).[28] The most important bond distances, angles, and in-
teratomic distances for all three protonated species and for
base 2e are summarized in Table 2. Since base 2d is a liquid,
the X-ray crystal structure of tris(1-pyrrolidinyl)(1,1,2,2-tet-
(pyrr)3P=NCMe2-
CMe3 obtained by Schwesinger was used for the compara-
tive analysis with base 2e and the salts of 2d–f.
Figure 5. X-ray crystal structure of salt 2e·HBF4. Displacement el-
lipsoids are drawn at the 30% probability level. Hydrogen atoms
except N1–H are omitted for clarity. Selected bonds lengths [Å]
and angles [°]: P1–N1 1.623(1), P1–N2 1.629(1), P1–N3 1.642(1),
P1–N4 1.630(1), N1–C1 1.494(2); N1–P1–N2 116.22(7), N1–P1–
N3 110.09(7), N1–P1–N4 103.37(7), N2–P1–N3 105.03(7), N2–P1–
N4 108.44(7), N3–P1–N4 114.00(7), P1–N1–C1 130.3(1). Hydrogen
ramethylpropylimino)phosphorane,[6]
The protonated forms of 2d, 2e, and 2f have a higher bond N1–H1···F1 parameters: N1–H1 0.842(18) Å, H1···F1
2.076(19) Å, N1···F1 2.9116(18) Å, N1–H1···F1 171.3(16)°.
symmetry at the phosphorus atom than the respective bases.
The structure of 2d·HBF4 is the most symmetrical among
them, because the difference in lengths between P1–N1 and tetrahedral geometry around the phosphorus atoms in-
the other P1–N bonds is minimal (Table 2, entries 1 and 2). creases considerably on protonation of the bases (pyrr)3-
Moreover, the P1–N1 bond in 2d·HBF4 is the longest of all P=NCMe2CMe3 and 2e to form the phosphazenium cat-
P1–N bonds, which is one of the criteria of a good degree ions (Table 2, entries 3 and 4). While the structure of
of delocalization of the positive charge. The symmetry of 2e·HBF4 also has an almost ideal tetrahedral arrangement
Eur. J. Org. Chem. 2013, 1811–1823
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1815

A. V. Alexandrova et al.
FULL PAPER
from planarity of all of the phosphazenium cations
(Table 2, entry 5), despite the fact that the angles C–Ncycl.
C in this structure are the largest (Table 2, entry 6).
–
The extent of the charge delocalization in structures
2d·HBF4, 2e·HBF4 and 2f·HOTs is further supported by
comparison of the length of the hydrogen bonds between
H1 and the electronegative atom of the anion (F or O) in
the salt forms. Thus, only a weak interaction N1–H1···F1
was found in 2d·HBF4, because of the stretched hydrogen
bond (Figure 4), whereas the hydrogen bonds in 2e·HBF4
and 2f·HOTs are shorter, which reflects a stronger interac-
tion between the electronegative atom of the anion and the
hydrogen atom H1 (Figure 5, Figure 6), due to the greater
localization of the positive charge at N1.
The basicity of novel iminophosphoranes 2e and 2f was
determined by titration in acetonitrile according to the es-
tablished procedure.[32] The pKa values were measured rela-
tive to the reference bases PhP2(dma), PhP2(pyrr), and 4-
MeO-C6H4-P2(pyrr).[33] Measured pKa values for bases 2e
and 2f are collected in Table 3 together with the pKa values
of related monophosphazenes, for which pKa-values in
acetonitrile are known.[32a]
Figure 6. X-ray crystal structure of salt 2f·HOTs. Displacement el-
lipsoids are drawn at the 30% probability level. Hydrogen atoms
except N1–H are omitted for clarity. Selected bonds lengths [Å]
and angles [°]: P1–N1 1.610(1), P1–N2 1.639(1), P1–N3 1.639(1),
P1–N4 1.633(1), N1–C1 1.492(2); N1–P1–N2 110.18(6), N1–P1–
N3 108.85(6), N1–P1–N4 112.97(6), N2–P1–N3 107.44(6), N2–P1–
N4 109.01(6), N3–P1–N4 108.23(6), P1–N1–C1 130.12(9). Hydro-
gen bond N1–H1···O1 parameters: N1–H1 0.84(2) Å, H1···O1
2.11(2) Å, N1···O1 2.9457(15) Å, N1–H1···O1 174.2(17)°.
around the phosphorus with nearly equal tetrahedral
angles, the P1–N1 bond is shorter than the three other P1–
N bonds; this fact unequivocally demonstrates that the pos-
itive charge is located more at N1. The same structural ten-
dency is even more pronounced in the structure of 2f·HOTs,
where the P1–N1 bond is considerably shorter than the P1–
N2(3,4) bonds, so giving evidence for back-bonding of N1
with the phosphorus and therefore a poor degree of delocal-
Table 3. pKa Values of triamino iminophosphorane bases in aceto-
nitrile.
Base 2e
2f
2a[32a] 2d[32a] (pyrr)3-
P=NEt[32a]
(Me2N)3-
P=NMe[32a]
pKa 26.69 27.39 26.98 28.42 28.88
27.52
Bases 2e and 2f are both less basic than 2d; base 2e is
ization of the positive charge among the other nitrogen even a weaker base than 2a.[6,32a] More surprisingly, the
atoms. simplest conceivable alkyl P1 phosphazene base, (Me2N)3-
Protonation of phosphazene bases 2dǞ2d·HBF4 or P=NMe is slightly more basic than 2e and 2f, but it is prob-
2eǞ2e·HBF4 causes little change of the already almost ably also more nucleophilic. The nucleophilicity of phos-
planar geometry around nitrogen atoms N2, N3, and N4 phazene bases depends largely on the steric characteristics
(Table 2, entry 5); it seems to be somewhat more pro- of the substituents at the basic imine center.[7] Thus, the
nounced for the piperidine-based pair 2e–2e·HBF4. The ge- most basic monophosphazene known, (pyrr)3P=NEt, is by
ometry of the nitrogen atoms in 2f·HOTs deviated the most three orders of magnitude more prone to methylation by
Table 2. Selected geometrical parameters for structures (pyrr)3P=NCMe2CMe3,[6] 2e, 2d·HBF4, 2e·HBF4, and 2f·HOTs.
Entry Parameter
(pyrr)3P=NCMe2CMe3
2e
2d·HBF4
2e·HBF4
2f·HOTs
1
2
P1–N1 bond length [Å]
1.512[a]
1.658[b]
1.539
1.678
1.629
1.621
1.623
1.634
1.610
1.637
Average length of bonds
P1–N2, P1–N3, and P1–N4 [Å]
Average angles[c]
3
4
5
103.9[b]
114.7[b]
104.1
114.6
109.4
110.3
109.2
109.9
108.2
110.7
N(2,3,4)–P1–N(3,4,2) [°]
Average angles[d]
N(1)–P1–N(2,3,4) [°]
Average angles around the cyclic
nitrogen atoms N2, N3, and N4 [°]
120.0; 116.8; 118.0; av.:[e]
118.3
118.4; 116.6;
117.6; av.:
117.5
118.0; 119.9;
119.1; av.: 119.0
119.6; 119.8;
119.6; av.: 119.7
114.0; 113.6;
117.1; av.:
114.9
6
7
Angles C–N2–C, C–N3–C, and
C–N4–C [°]
110.5; 109.3; 107.8; av.:
109.2
110.7; 111.0;
113.2; av.:
111.6
2.686; 3.281;
av.: 2.957
109.5; 110.5;
110.6; av.: 110.2
112.7; 112.1;
111.8; av.: 112.2
113.2; 115.0;
117.3; av.:
115.2
Minimal and maximal interatomic
distances between the α-hydrogen
atoms of the ring[f] and P1 [Å]
2.757; 3.253; av.: 2.964
2.825; 3.312; av.: 2.656; 3.407; av.: 2.739; 3.501;
3.003 3.033 av.: 3.211
[a] P=N bond is implied. [b] Numbering of the nitrogen atoms in the X-ray structure of the base is in the same order as in 2e. [c] Tetrahe-
dral angles at the base of the tetrahedron with N1 atom at its apex. [d] Tetrahedral angles at the apex of the tetrahedron with N1 atom
at its apex. [e] Average value. [f] A good visual depiction of the considered α-hydrogen atoms is presented in Scheme 4.
1816
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 1811–1823

Electron-Rich Sterically Hindered P1 Phosphazene Bases
MeI than 2d. Base (Me2N)3P=NMe is more nucleophilic compared to the pyrrolidine ring (see Figures 3 and 5,
than 2a by four orders of magnitude.[6] Since low nucleophi- Scheme 4). While the equatorial pair of hydrogen atoms is
licity is one of the main advantages of sterically congested located almost in the same plane as the nitrogen, but rela-
phosphazenes, new bases 2e and 2f may be attractive, since tively close to the phosphorus atom, the axial pair is located
a low nucleophilicity can be predicted for them.
far away from both the nitrogen and phosphorus atoms
During the early investigations by Schwesinger’s group, (Table 2, entry 7). Therefore, the α-hydrogen atoms in the
it was proved that replacement of the dimethylamino sub- piperidine structure with sp3-hybridized nitrogen do not in-
stituents at the phosphorus by pyrrolidino groups causes an teract much with the lone pair of the nitrogen atom. On
increase in the basicity of the phosphazene bases. The effect protonation, the distance between the axial α-hydrogen
of piperidino groups has not been investigated in that con- atoms and the phosphorus atom becomes longer, but the
text.[5c] The pKa data obtained here show that this group equatorial pair of α-hydrogen atoms becomes even closer to
does not give a similar basicity-increasing effect; rather, re- the phosphorus atom, which hampers the contraction of
placement of the dimethylamino by a piperidino group even the Npip–P bond, so disfavoring delocalization.
causes a slight decrease in basicity.
As a result, the pyrrolidine structure is more prone to
The different behaviour of five- and six-membered rings protonation due to a release of steric strain and a signifi-
in a number of reactions involving a change of hybridiza- cant benefit in energy. In contrast, the geometry of the pip-
tion of an atom in a cycle between sp2 and sp3 has been eridine ring accommodates both sp3- and sp2-hybridized
discussed in detail in the literature.[34] Thus, five-membered nitrogen atoms without essential change of strain, and pro-
rings have been found to be more likely to accommodate tonation is therefore less favored.
an sp2-hybridized atom in the ring; but six-membered ring
apparently have a lower energy if all of the ring atoms are ture 2f·HOTs (Table 2, entry 7). Surprisingly, the minimal
sp3-hybridized.[34]
distance between the phosphorus atom and the closest α-
A similar but less pronounced picture is found for struc-
The different effects of the pyrrolidino and piperidino hydrogen in pyrrolidine base (pyrr)3P=NCMe2CMe3 is still
fragments in structures 2d, 2e, 2d·HBF4, and 2e·HBF4 can longer than those in both protonated forms of 2e and 2f,
be rationalized by comparing the geometries of the rings which reveals a reduced ability of the latter species to
with the help of the generalized structures shown in shorten the Ncycl–P bonds, and a lower tendency to delo-
Scheme 4, where G denotes the remaining iminophos- calize the positive charge. The same effect is most probably
phorane unit, P=N–tAlk.
responsible for the slightly lower basicity of base 2e com-
The geometry around the nitrogen atom is very similar pared to 2a.
in both of the basic structures, and it remains almost un-
changed on protonation (Table 2, entry 5). Comparison of
the interatomic distances between the α-hydrogen atoms of
the ring and the phosphorus atom proved to be crucial
Conclusions
(Scheme 4). The geometry of the pyrrolidine ring reveals a
In summary, a one-pot two- or three-step procedure for
destabilizing repulsive interaction between the α-hydrogen the preparation of P1 phosphazene bases with a sterically
atoms and the nitrogen lone pair. On protonation, the dis- protected basic center starting from phosphorus triamides
tance between the α-hydrogen atoms of the pyrrolidine ring or phosphorus trichloride has been developed. The protocol
and the nitrogen lone pair increases, which results in a de- may be used with a variety of starting materials, and there-
crease in the repulsive interaction (Table 2, entry 7). Thus, fore a wide range of phosphazides 1 and phosphazenes 2
the Npyrr–P bonds become shorter on protonation of 2d, may be prepared. Moreover, commercially unavailable tria-
thereby facilitating delocalization of the positive charge. minophosphanes can be prepared directly from phosphorus
Therefore the structure with an sp2-hybridized cyclic nitro- trichloride and secondary amines, and transformed into the
gen atom is energetically more favored.
phosphazides by Staudinger reaction in the same vessel, as
demonstrated by the syntheses of 1d–e in high yields. The
synthesized phosphazides serve as convenient starting mate-
rials for the preparation of tetraaminophosphonium salts,
which are important synthons for the synthesis of higher-
order phosphazene bases.
Despite the fact that the new method gives somewhat
lower overall yields of phosphazene bases 2 compared to
Schwesinger’s protocol,[6] it is more convenient overall,
since the experimental technique is much simpler due to the
use of a one-pot procedure, solvent-free conditions, and an
easy work-up for isolation.
Scheme 4. Comparison of the geometries of pyrrolidine- and piper-
idine-based structures with sp3- and sp2-hybridized nitrogen atoms.
Novel bases 2e and 2f expand the library of the known P1
phosphazene bases. Experimentally determined pKa values
The piperidine ring, in contrast, has a chair-like confor- increase the amount of quantitative information about the
mation, and the α-hydrogens have different spatial locations basicity of monophosphazenes. A rationalization of the ob-
Eur. J. Org. Chem. 2013, 1811–1823
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1817

A. V. Alexandrova et al.
FULL PAPER
Agilent 7890A gas chromatograph coupled with a 5975C quadru-
pole mass-selective electron-impact detector (EI, 70 eV).
served basicities in terms of the geometric features of the
amino substituents of the phosphazenes helps further inves-
tigation of strong organic bases and their synthesis.
All reactions were carried out in heat-gun-dried glassware with
magnetic PTFE-coated stirring bars under an atmosphere of dry
argon. 1H and 31P NMR or GC-MS monitoring of the reaction
mixtures was routinely performed to ensure complete conversions
of the starting materials. Solvents were dried by standard pro-
cedures: THF was distilled from over Na/K alloy with added
benzophenone; acetonitrile was distilled from CaH2; hexane was
distilled from P2O5.
Experimental Section
General Remarks: NMR spectra were recorded with a Bruker Av-
ance 400 spectrometer at ambient temperature. 1H NMR spectra
are reported using the δ scale in parts per million (ppm) referenced
to internal standard Me4Si in CDCl3 and C6D6, and to residual
solvent peaks[35] in CD3CN. 13C NMR spectra are referenced to
[D]-solvent signals.[35] 31P NMR spectra were run with the follow-
ing internal standards: (MeO)3PO[36] for salts 2d–f in CDCl3;
HMPA [δ = 24.41 ppm relative to (MeO)3PO[36] in C6D6] for phos-
phazides and P1 phosphazene bases in C6D6. 1H and 31P NMR
spectra of bases 2d–f and their protonated forms 2d·HBF4,
2e·HBF4, and 2f·HBF4 were additionally recorded in CD3CN in
the presence of the internal standard tetra(methylneopentylamino)-
phosphonium tetrafluoroborate (TMNAPT) [δ = 49.18 ppm rela-
tive to (MeO)3PO[36] in CD3CN]. Multiplicities are indicated as
follows: s (singlet), d (doublet), m (multiplet). IR spectra were re-
corded with a Bruker ALPHA-P spectrometer equipped with a
Platinum ATR module as neat compounds. ESI mass spectra were
recorded using a Thermo Scientific LCQ Fleet mass spectrometer.
High-resolution mass spectra (HRMS) were obtained with a LTQ
Orbitrap XL instrument using electrospray ionization (ESI). Melt-
ing points were measured with a SMP10 melting point apparatus.
Elemental analysis was performed with a Perkin–Elmer PE 2400
Series II CHNS analyzer. GC-MS spectra were obtained on an
Hexamethylphosphorous triamide, tert-butyl alcohol, 2,4,4-tri-
methyl-1-pentene, 1,5,7-triazabicyclo[4.4.0]dec-5-ene, sodium azide,
and LiAlH4 were used as purchased from commercial suppliers.
Et3N was distilled and stored over KOH pellets. Phosphorus tri-
chloride was distilled prior to use. Pyrrolidine and piperidine were
distilled from over Na/K alloy directly prior to use. tert-Butyl
azide,[20] 1,3-propylene ditosylate,[37] and compounds 4,[27b] 5,[27b,c]
6,[27a,c] and 7[27a] were synthesized as described.
CAUTION: Although in the course of our experiments no acci-
dents were encountered, the utmost care should be taken during
all procedures associated with azides; the wearing of protective
gloves and goggles and working behind a safety shield are required.
X-ray Crystallography: X-ray quality crystals of phosphazides 1d
and 1e were grown from hexane and benzene, respectively; base 2e
was crystallized from hexane. Salts 2d·HBF4 and 2e·HBF4 were
crystallized from ethyl acetate, and 2f·HOTs was obtained from a
mixture of EtOAc/CHCl3 by slow cooling of a saturated solution.
Data were collected with a Nonius Kappa CCD diffractometer (for
Table 4. X-ray crystallographic data for structures 1d, 1e, 2e, 2d·HBF4, 2e·HBF4, and 2f·HOTs.
Compound
1d
1e
2e
2d·HBF4
2e·HBF4
2f·HOTs
Formula
Mr
C16H33N6P
340.45
C19H39N6P
382.53
C19H39N4P
354.51
C16H34N4P·BF4 C19H40N4P·BF4 C13H28N4P·C7H7O3S
400.25
442.33
442.55
Crystal appearance
Crystal size [mm]
Crystal system
Space group
a [Å]
b [Å]
c [Å]
α [°]
β [°]
colorless prism
colorless plate
colorless prism
colorless prism
colorless plate
colorless, irregular shape
0.4 ϫ 0.3 ϫ 0.12 0.4 ϫ 0.4 ϫ 0.2 0.55 ϫ 0.48 ϫ 0.30 0.4 ϫ 0.3 ϫ 0.2 0.3 ϫ 0.2 ϫ 0.2 0.4 ϫ 0.4 ϫ 0.4
monoclinic
P21/c
10.2661 (2)
9.1664 (2)
20.3028 (3)
triclinic
triclinic
monoclinic
P21/n
10.2280 (3)
15.7880 (4)
12.7398 (2)
orthorhombic
P212121
9.9140 (2)
13.9490 (3)
16.7222 (3)
orthorhombic
P212121
11.08610 (10)
12.6234 (2)
16.0037 (2)
¯
¯
P1 (No.2)
P1 (No.2)
10.4740 (5)
11.1853 (5)
11.4437 (4)
113.418 (3)
99.005 (3)
106.877(2) (19)
1119.40 (8)
2
9.5315 (4)
10.6071 (3)
11.0259 (4)
67.0900 (10)
85.5310 (10)
84.8330 (10)
1021.51 (6)
2
93.8193 (10)
98.1334 (12)
γ [°]
V [Å3]
1906.31 (6)
4
1.186
0.15
2036.53 (9)
4
1.305
0.18
2312.52 (8)
4
1.270
0.16
2239.63 (5)
4
1.312
0.25
Z
Dx [Mgm–3]
μ (mm–1)
F(000)
1.135
0.14
420
1.153
0.14
392
744
856
952
952
T [K]
θmax [°]
150 (2)
27.5
150 (2)
27.4
150 (2)
27.6
150 (2)
27.5
150 (2)
27
150 (2)
27.5
Reflections
measured
unique
Rint
Refined
41886
4362
0.054
211
19278
4944
0.051
238
12911
4700
0.018
220
33851
4672
0.035
243
43639
5094
0.044
269
45549
5143
0.028
270
[a]
parameters
wR(F2, all refl.)[b]
R[F, Ͼ4σ(F)][c]
GOF[d]
0.101
0.040
1.08
0.137
0.048
1.07
0.090
0.035
1.03
0.112
0.042
1.06
0.077
0.032
1.04
0.069
0.026
1.04
Flack parameter
0.00(7)
0.16/–0.30
0.02(5)
0.18/–0.33
max./min. Δρ [eÅ–3]
0.43/–0.33
0.44/–0.35
0.33/–0.32
0.47/–0.31
[a] Rint = Σ|Fo – Fo,mean2|/ΣFo2. [b] Weighting scheme w = [σ2(Fo2) + (w1P)2 + w2P]–1, where P = [max(Fo2) + 2Fc ]. [c] R(F) = Σ|(|Fo| –
2
2
|Fc|)|/Σ|Fo|, wR(F2) = {Σ[w(Fo – Fc ) ]/[Σw(Fo2)2]} . [d] GOF = {Σ(w[Fo – Fc ) ]/(Ndiffrs – Nparams)} .
2
2 2
½
2
2 2
½
1818
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 1811–1823

Electron-Rich Sterically Hindered P1 Phosphazene Bases
the measurement of the crystal of 2e, the diffractometer was
equipped with a Bruker ApexII detector) at a temperature of
150 K. The structures were solved by direct methods (SIR92)[38]
and refined by the full-matrix least-squares method based on F2
(SHELXL97).[39] The hydrogen atoms on carbon were fixed into
idealized positions (riding model) and assigned temperature factors
either Hiso(H) = 1.2 Ueq (pivot atom) or Hiso(H) = 1.5 Ueq (pivot
atom) for the methyl moiety. The hydrogen atom of the N1–H units
in the salts was found on the difference Fourier maps and refined
isotropically. The compilation of the X-ray data is presented in
Table 4.
room temperature and stirred overnight. The content of the flask
was poured into a mixture of chilled water and hexane/toluene (2:1)
and triethylamine (5 vol.-%). Extraction followed by separation of
the phases was performed immediately, and the aqueous phase was
washed three times with hexane. The combined organic extracts
were washed with chilled water. This aqueous phase was carefully
extracted twice with hexane. The combined organic extracts were
dried with solid KOH with stirring for 2 h and put into a freezer
(–25 °C) for a few hours. The liquid organic phase was carefully
decanted from the frozen alkaline layer. The solvents were evapo-
rated under reduced pressure, and the residue was dried under high
vacuum to give the products as colorless solids.
General Procedure 1 (GP1) for the Preparation of Phosphazides 1a–
c: Aliphatic azide (13 mmol) was added dropwise to P(NMe2)3
(10 mmol) at 0 °C under argon with stirring. After completion of
the addition, the reaction mixture was warmed to room tempera-
ture and stirred overnight. The residual amount of the azide was
evaporated in high vacuum, providing phosphazides 1a–c.
Tris(dimethylamino)(tert-butyl)phosphazide (1a):[17] Compound 1a
(19.36 g, 99%) was prepared according to GP1 from P(NMe2)3
(12.11 g, 74.2 mmol) and tert-butyl azide (9.56 g, 96.4 mmol). Col-
Note: Attention should be paid to the quality of the secondary
amine, since the reaction was found to be extremely sensitive to
traces of water. Thus, pyrrolidine “directly from a bottle” or dis-
tilled and kept over KOH pellets gave rise to the formation of nu-
merous by-products in the reaction with phosphorus trichloride,
according to 31P NMR spectroscopy. Distillation of the amine from
Na/K alloy directly before use was strictly required.
Tris(1-pyrrolidinyl)(tert-butyl)phosphazide (1d): Compound 1d
(62.1 g, 91%) was prepared according to GP2 from pyrrolidine
orless oily liquid. IR (neat): ν = 2964 (w), 2893 (w), 1458 (m), 1294
˜
(m), 1188 (m), 1097 (m), 1051 (m), 975 (s), 883 (m), 739 (m) cm–1. (128.0 g, 1.8 mol), phosphorus trichloride (17.5 mL, 0.2 mol), and
1H NMR (400 MHz, C6D6): δ = 1.45 [s, 9 H, (CH3)3C], 2.38 [d, J tert-butyl azide (25.8 g, 0.26 mol). Colorless solid, m.p. 89–90 °C
= 9.0 Hz, 18 H, (CH3)2N] ppm. 13C NMR (101 MHz, C6D6): δ =
29.2, 37.3 (d, J = 2.2 Hz), 59.7 ppm. 31P NMR (162 MHz, C6D6,
HMPA): δ = 41.77 ppm. HRMS (ESI): calcd. for C10H28N6P [M +
H]+ 263.2108; found 263.2109. LRMS: m/z (%) = 166 (13), 179
(100) [(Me2N)3PNH2+], 263 (70).
(dec.). IR (neat): ν = 2962 (m), 2863 (m), 1456 (m), 1204 (m), 1072
˜
1
(s), 1011 (s), 913 (m), 882 (m), 777 (m) cm–1. H NMR (400 MHz,
C6D6): δ = 1.45 [s, 9 H, (CH3)3C], 1.46–1.49 (m, 12 H, β-CH2 pyrr.),
3.08–3.12 (m, 12 H, α-CH2 pyrr.) ppm. 13C NMR (101 MHz,
C6D6): δ = 26.6 (d, J = 6.7 Hz), 29.3, 47.2 (d, J = 2.6 Hz),
59.5 ppm. 31P NMR (162 MHz, C6D6; HMPA): δ = 30.52 ppm.
HRMS (ESI): calcd. for C16H34N6P [M + H]+ 341.2577; found
341.2579. LRMS: m/z (%) = 257 (100) [(pyrr)3PNH2+], 341 (25).
Tris(dimethylamino)(tert-heptyl)phosphazide (1b): Compound 1b
(6.09 g, 99%) was prepared from P(NMe2)3 (3.26 g, 20 mmol) and
tert-heptyl azide (3.67 g, 26 mmol) according to GP1, but the reac-
tion mixture was warmed to 40 °C after addition of the azide and
Tris(1-piperidinyl)(tert-butyl)phosphazide (1e): Compound 1e
(10.1 g, 96%) was prepared according to GP2 from piperidine
stirred for 3 h. Colorless solid, m.p. 58–60 °C. IR (neat): ν = 2971
˜
(m), 2953 (m), 2904 (m), 2805 (w), 1459 (m), 1292 (m), 1183 (m), (21.0 g, 246.6 mmol), phosphorus trichloride (3.8 g, 2.4 mL,
1085 (s), 1063 (m), 1044 (m), 973 (s), 865 (m), 751 (m), 732 (m) 27.4 mmol), and tert-butyl azide (3.5 g, 35.6 mmol). Colorless crys-
cm–1. 1H NMR (300 MHz, C6D6): δ = 1.23 [s, 9 H, (CH3)3C], 1.34 talline solid, m.p. Ͼ75 °C (dec.). IR (neat): ν = 2926 (m), 2847 (m),
˜
[s, 6 H, (CH3)2C], 2.39 [d, J = 9.0 Hz, 18 H, (CH3)2N] ppm. 13C
NMR (101 MHz, C6D6): δ = 22.6, 26.5, 37.3 (d, J = 2.2 Hz), 37.4,
1451 (m), 1442 (m), 1375 (m), 1337 (m), 1211 (m), 1161 (m), 1110
(m), 1061 (s), 1025 (m), 946 (s), 854 (w), 722 (m) cm–1. H NMR
1
66.7 ppm. 31P NMR (162 MHz, C6D6, HMPA): δ = 42.11 ppm. (400 MHz, C6D6): δ = 1.27–1.33 (m, 18 H, β,γ-CH2 pip.), 1.46 [d,
HRMS (ESI): calcd. for C13H34N6P [M + H]+ 305.2577; found J = 0.3 Hz, 9 H, (CH3)3C], 2.95–2.97 (m, 12 H, α-CH2 pip.) ppm.
305.2576. LRMS: m/z (%) = 179 (100) [(Me2N)3PNH2+], 305 (93).
13C NMR (101 MHz, C6D6): δ = 25.2, 26.7 (d, J = 4.6 Hz), 29.4,
46.5, 59.7 ppm. 31P NMR (162 MHz, C6D6; HMPA):
35.26 ppm. HRMS (ESI): calcd. for C19H40N6P [M
δ
=
Tris(dimethylamino)(tert-octyl)phosphazide (1c): Compound 1c
(10.74 g, 99%) was prepared according to GP1 from P(NMe2)3
(5.56 g, 34.1 mmol) and tert-octyl azide (6.87 g, 44.3 mmol). Color-
less viscous liquid that became a waxy solid on storage. IR (neat):
+
H]+
= 299 (100)
383.3047; found 383.3047. LRMS: m/z (%)
[(pip)3PNH2+], 383 (47).
ν = 2896 (m), 2803 (m), 1462 (m), 1293 (m), 1191 (m), 1085 (m),
Phosphazide 1f: tert-Butyl azide (1.6 g, 16.2 mmol) was added drop-
wise to a solution of 7 (2.5 g, 12.5 mmol) in dry toluene (3 mL) at
˜
1
1045 (m), 974 (s), 734 (m) cm–1. H NMR (300 MHz, C6D6): δ =
1.15 [s, 9 H, (CH3)3C], 1.46 [s, 6 H, (CH3)2C], 1.89 (s, 2 H, CH2), 0 °C under argon with stirring. After completion of the addition,
2.42 [d, J = 9.0 Hz, 18 H, (CH3)2N] ppm. 13C NMR (101 MHz,
C6D6): δ = 29.5, 32.2, 32.5, 37.4 (d, J = 2.2 Hz), 55.7, 63.9 ppm.
31P NMR (162 MHz, C6D6, HMPA): δ = 42.0 ppm. HRMS (ESI):
calcd. for C14H36N6P [M + H]+ 319.2734; found 319.2735. LRMS:
m/z (%) = 179 (40) [(Me2N)3PNH2+], 319 (100).
the reaction mixture was allowed to warm to room temperature
over 2.5 h. The toluene and the excess of tert-butyl azide were evap-
orated under high vacuum to give 1f (3.73 g, 99%) as a colorless
solid, m.p. Ͼ148 °C (dec.). IR (neat): ν = 2943 (m), 2859 (m), 1449
˜
(m), 1304 (m), 1270 (m), 1123 (s), 1080 (s), 1045 (m), 925 (m), 910
1
(m), 883 (m), 722 (s) cm–1. H NMR (400 MHz, C6D6): δ = 1.14–
General Procedure 2 (GP2) for the “One-Pot” Preparation of
Phosphazides 1d–e: Phosphorus trichloride (8.7 mL, 0.1 mol) was
cautiously added to a solution of secondary amine (0.9 mol) in dry
THF (270 mL) cooled to –60 °C under argon with vigorous stir-
ring. The addition was performed at such a rate as would keep the
temperature below –35 °C. After completion, the reaction mixture
was warmed to room temperature and stirred overnight. The flask
was immersed in an ice/water bath, and tert-butyl azide (0.13 mol)
was added dropwise. The reaction mixture was allowed to warm to
1.22 (m, 3 H), 1.49 [s, 9 H, (CH3)3C], 1.52–1.61 (m, 3 H), 2.42–2.52
(m, 6 H), 3.15–3.24 (m, 6 H) ppm. 13C NMR (101 MHz, C6D6): δ
= 23.5 (d, J = 4.4 Hz), 29.3, 48.8 (d, J = 3.2 Hz), 60.4 ppm. 31P
NMR (162 MHz, C6D6; HMPA): δ = 28.20 ppm. HRMS (ESI):
calcd. for C13H28N6P [M + H]+ 299.2108; found 299.2109. LRMS:
m/z (%) = 215 (100), 299 (7).
General Procedure 3 (GP3) for the Preparation of Salts 2d·HBF4,
2e·HBF4, and 2f·HBF4: A solution of the corresponding base 2 in
Eur. J. Org. Chem. 2013, 1811–1823
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1819

A. V. Alexandrova et al.
FULL PAPER
methanol (1 mL per 3 mmol of a base) was added to chilled water.
HCl (35% aq.) was added until the solution reached a pH of 3–4.
Addition of an equimolar amount of NaBF4 (3 m aq.) led to the
immediate formation of a white precipitate. The tetrafluoroborate
salt of the base was extracted with dichloromethane. The organic
phase was washed once with ice/water and dried with MgSO4. The
residue obtained after evaporation of the volatiles in high vacuum
was recrystallized. The salts can alternatively be prepared by direct
addition of HBF4 (1 m aq.) to a solution of the base in methanol
cooled to –15 °C, followed by evaporation of the volatiles in high
vacuum.
give 2d·HBF4 (1.16 g, 89%), m.p. 148–149 °C (from ethyl acetate).
1H NMR (400 MHz, CDCl3): δ = 1.33 [d, J = 0.8 Hz, 9 H,
(CH3)3C], 1.92–1.95 (m, 12 H, β-CH2 pyrr.), 3.23–3.27 (m, 12 H,
α-CH2 pyrr.), 4.09 (d, J = 9.9 Hz, 1 H, NH) ppm. 13C NMR
(101 MHz, CDCl3): δ = 26.1 (d, J = 8.1 Hz), 31.3 (d, J = 4.4 Hz),
47.6 (d, J = 4.9 Hz), 52.5 ppm. 31P NMR [162 MHz, CDCl3;
(MeO)3PO]: δ = 22.32 ppm. 1H NMR (400 MHz, CD3CN): δ =
1.29 [d, J = 0.9 Hz, 9 H, (CH3)3C], 1.87–1.91 (m, 12 H, β-CH2
pyrr.), 3.18–3.22 (m, 12 H, α-CH2 pyrr.), 3.68 (d, J = 9.1 Hz, 1 H,
NH) ppm. 31P NMR (162 MHz, CD3CN; TMNAPT): δ =
22.75 ppm. HRMS (ESI) calcd. for C16H34N4P [M]+ 313.2516;
found 313.2514.
(tert-Butylimino)tris(dimethylamino)phosphorane (2a)[4d,6] and (tert-
Butylamino)tris(dimethylamino)phosphonium
Tetrafluoroborate
Tris(1-piperidinyl)(tert-butylamino)phosphonium Tetrafluoroborate
(2e·HBF4) and Tris(1-piperidinyl)(tert-butylimino)phosphorane (2e):
Phosphazide 1e (10.05 g, 26.3 mmol) was heated under argon with
stirring at 145 °C for 180 h. The residual dark viscous oil was sub-
jected to a treatment according to GP3. The salt 2e·HBF4 (9.15 g,
79%) was purified by recrystallization from ethyl acetate/diethyl
(2a·HBF4): Phosphazide 1a (19.5 g, 74.2 mmol) was heated under
argon with stirring at 145 °C for 25 h. The residue was fractionally
distilled, and the fraction containing 2a (14.5 g, 83%) with b.p. 73–
75 °C/5 mbar was collected. Colorless oily liquid. 1H NMR
(400 MHz, C6D6): δ = 1.45 [d, J = 1.3 Hz, 9 H, (CH3)3C], 2.49 [d,
J = 9.5 Hz, 18 H, (CH3)2N] ppm. 31P NMR [162 MHz, C6D6,
(MeO)3PO]: δ = 1.25 ppm. For further characterization, 2a (1.17 g,
5.0 mmol) was converted into its 2a·HBF4 salt according to GP3.
The crystalline product was recrystallized from ethyl acetate/methyl
tert-butyl ether (4:1) to give 2a·HBF4 (1.48 g, 92%), m.p. 276–
277 °C. 1H NMR (400 MHz, CDCl3): δ = 1.32 [d, J = 1.0 Hz, 9 H,
(CH3)3C], 2.77 [d, J = 9.9 Hz, 18 H, (CH3)2N], 4.24 (d, J = 8.6 Hz,
1 H, NH) ppm. 31P NMR [162 MHz, CDCl3, (MeO)3PO]: δ =
35.68 ppm.
ether. Colorless crystals, m.p. 190–192 °C. IR (neat): ν = 3299 (w),
˜
2931 (m), 2848 (w), 1442 (w), 1369 (m), 1344 (m), 1230 (w), 1200
(m), 1165 (m), 1108 (m), 1065 (s), 1006 (s), 963 (s), 945 (s), 858
1
(m), 723 (m) cm–1. H NMR (400 MHz, CDCl3): δ = 1.31 [d, J =
0.9 Hz, 9 H, (CH3)3C], 1.59–1.64 (m, 18 H, β,γ-CH2 pip.), 3.09–
3.13 (m, 12 H, α-CH2 pip.), 4.18 (d, J = 8.2 Hz, 1 H, NH) ppm.
13C NMR (101 MHz, CDCl3): δ = 24.1, 25.8 (d, J = 5.4 Hz), 31.6
(d, J = 4.4 Hz), 47.1 (d, J = 1.8 Hz), 52.8 (d, J = 1.5 Hz) ppm. 31P
NMR [162 MHz, CDCl3; (MeO)3PO]: δ = 30.28 ppm. 1H NMR
(400 MHz, CD3CN): δ = 1.29 [d, J = 1.0 Hz, 9 H, (CH3)3C], 1.54–
1.66 (m, 18 H, β,γ-CH2 pip.), 3.08–3.12 (m, 12 H, α-CH2 pip.), 3.67
(d, J = 7.8 Hz, 1 H, NH) ppm. 31P NMR (162 MHz, CD3CN;
TMNAPT): δ = 30.16 ppm. HRMS (ESI) calcd. for C19H40N4P
[M]+ 355.2985; found 355.2985. C19H40N4P (355.53): calcd. C 51.5,
H 9.3, N 12.6, P 7.0; found C 51.5, H 9.2, N 12.6, P 7.2.
Tris(dimethylamino)(tert-heptylimino)phosphorane (2b):[6] Phosphaz-
ide 1b (6.1 g, 20 mmol) was heated under argon with stirring at
145 °C for 210 h. The residue was subjected to high-vacuum distil-
lation, and the fraction with b.p. 87–88 °C/0.028 mbar provided 2b
(2.2 g, 40%) as a colorless viscous liquid that became a waxy solid
at room temperature. 1H NMR (400 MHz, C6D6): δ = 1.30 [s, 9 H,
(CH3)3C], 1.33 [s, 6 H, (CH3)2C], 2.48 [d, J = 9.4 Hz, 18 H,
(CH3)2N] ppm. 13C NMR (101 MHz, C6D6): δ = 26.9, 29.0 (d, J
= 3.7 Hz), 38.0 (d, J = 3.2 Hz), 39.8 (d, J = 18.4 Hz), 57.1 ppm.
31P NMR (162 MHz, C6D6, HMPA): δ = 1.67 ppm.
For isolation and characterization of 2e, 2e·HBF4 (1.50 g,
3.4 mmol) was dissolved in MeOH (2 mL), and the solution was
added to a mixture of hexane (10 mL) and KOH (30% aq.; 10 g)
at room temperature. The mixture was shaken vigorously, the layers
were separated, and the aqueous phase was extracted with hexanes
(2ϫ 20 mL). The combined organic extracts were dried with solid
KOH with stirring for 1 h and put into a freezer overnight. The
solution was carefully decanted from the frozen aqueous KOH, so-
lid barium oxide was added and the solution was stirred vigorously
for 1 h. The barium oxide was removed by filtration under argon,
and the solvents were evaporated in high vacuum to give colorless
crystalline 2e (1.17 g, 98%). 1H NMR (400 MHz, C6D6): δ = 1.32–
1.44 (m, 18 H, β,γ-CH2 pip.), 1.48 [d, J = 1.3 Hz, 9 H, (CH3)3C],
3.02–3.06 (m, 12 H, α-CH2 pip.) ppm. 13C NMR (101 MHz, C6D6):
δ = 25.7 (d, J = 0.7 Hz), 27.1 (d, J = 6.4 Hz), 36.5 (d, J = 9.3 Hz),
47.0 (d, J = 0.8 Hz), 49.5 (d, J = 4.5 Hz) ppm. 31P NMR (162 MHz,
C6D6; HMPA): δ = –3.16 ppm. 1H NMR (400 MHz, CD3CN): δ =
1.13 [d, J = 1.2 Hz, 9 H, (CH3)3C], 1.40–1.46 (m, 12 H, β-CH2
pip.), 1.51–1.55 (m, 6 H, γ-CH2 pip.), 3.00–3.03 (m, 12 H, α-CH2
pip.) ppm. 31P NMR (162 MHz, CD3CN; TMNAPT): δ =
1.31 ppm. HRMS (ESI): calcd. for C19H40N4P [M + H]+ 355.2985;
found 355.2985.
Tris(dimethylamino)(tert-octylimino)phosphorane (2c):[6] Phosphaz-
ide 1c (10.8 g, 34.1 mmol) was heated under argon with stirring at
145 °C for 115 h. The residue was fractionally distilled under high
vacuum to give 2c (6.4 g, 65%) as a colorless oil. B.p. 77–79 °C/
0.03 mbar. IR (neat): ν = 2948 (w), 2870 (m), 2794 (w), 1459 (w),
˜
1330 (m), 1307 (m), 1277 (m), 1191 (m), 990 (m), 962 (s), 717 (m)
cm–1. 1H NMR (400 MHz, C6D6): δ = 1.32 [s, 9 H, (CH3)3C], 1.45
[s, 6 H, (CH3)2C], 1.72 (d, J = 3.2 Hz, 2 H, CH2), 2.48 [d, J =
9.4 Hz, 18 H, (CH3)2N] ppm. 13C NMR (101 MHz, C6D6): δ =
32.4, 32.5, 36.2 (d, J = 6.8 Hz), 38.0 (d, J = 3.4 Hz), 53.6 (d, J =
2.8 Hz), 60.5 (d, J = 14.5 Hz) ppm. 31P NMR (162 MHz, C6D6,
HMPA): δ = 1.62 ppm.
Tris(1-pyrrolidinyl)(tert-butylimino)phosphorane (2d)[6] and Tris-
(1-pyrrolidinyl)(tert-butylamino)phosphonium
Tetrafluoroborate
(2d·HBF4):[6] Phosphazide 1d (58.45 g, 171.7 mmol) was heated un-
der argon with stirring at 145 °C for 36 h. High-vacuum distillation
of the residue gave 2d (44.8 g, 84%) as a viscous transparent liquid,
b.p. 124.5 °C/0.019 mbar. 1H NMR (400 MHz, C6D6): δ = 1.54–
1.58 [m, 21 H, (CH3)3C and β-CH2 pyrr.], 3.09–3.13 (m, 12 H, α- Base 2f and its Tetrafluoroborate, 2f·HBF4 and Tosylate, 2f·HOTs:
CH2 pyrr.) ppm. 31P NMR (162 MHz, C6D6, HMPA): δ =
–9.83 ppm. 1H NMR (400 MHz, CD3CN): δ = 1.15 [d, J = 1.1 Hz,
9 H, (CH3)3C], 1.71–1.75 (m, 12 H, β-CH2 pyrr.), 3.05–3.10 (m, 12
Phosphazide 1f (2.30 g, 7.7 mmol) was heated at reflux in triethyl-
amine (7 mL) for 24 h under argon. After cooling to room tempera-
ture, the solution was decanted from a small amount of slightly
H, α-CH2 pyrr.) ppm. 31P NMR (162 MHz, CD3CN; TMNAPT): yellow polymeric residue, which had appeared during the pyrolysis.
δ = –4.67 ppm. For further characterization, a sample of 2d (1.02 g,
3.3 mmol) was converted into its HBF4 salt according to GP3 to
The triethylamine was evaporated to give 2f (2.04 g, 98%) as a col-
orless crystalline solid. IR (neat): ν = 2935 (m), 2929 (m), 2892 (m),
˜
1820
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 1811–1823

Electron-Rich Sterically Hindered P1 Phosphazene Bases
2849 (m), 1283 (s), 1258 (s), 1212 (m), 1125 (s), 1112 (s), 1095 (s),
1048 (s), 1000 (w), 924 (m), 883 (s), 859 (s), 818 (m), 718 (s), 700
(s) cm–1. 1H NMR (400 MHz, C6D6): δ = 1.18–1.23 (m, 3 H, β-
CH2 cycl.), 1.66 [s, 9 H, (CH3)3C], 1.68–1.76 (m, 3 H, β-CH2 cycl.),
2.52–2.61 (m, 6 H, α-CH2 cycl.), 3.31 (ddt, J = 3.1, 10.0, 11.8 Hz,
6 H, α-CH2 cycl.) ppm. 13C NMR (101 MHz, C6D6): δ = 24.0 (d,
liquid (CAUTION: The product is volatile, b.p. 152–153 °C/
760 Torr19b; no heating should be used during the evaporation of
the solvent). IR (neat): ν = 2975 (m), 2878 (w), 2094 (s), 2053 (w),
˜
1467 (w), 1381 (m), 1371 (m), 1267 (m), 1221 (w), 1171 (w), 1131
(m), 852 (w), 719 (w) cm–1. 1H NMR (400 MHz, CDCl3): δ = 0.94
[s, 9 H, (CH3)3C], 1.27 [s, 6 H, (CH3)2C] ppm. 13C NMR
J = 3.5 Hz), 35.0 (d, J = 11.6 Hz), 49.6 (d, J = 4.2 Hz), 50.7 (d, J (101 MHz, CDCl3): δ = 22.0, 25.7, 37.9, 67.4 ppm. GC-MS data:
= 5.0 Hz) ppm. 31P NMR (162 MHz, C6D6; HMPA): δ =
–3.20 ppm. 1H NMR (400 MHz, CD3CN): δ = 1.19 [d, J = 1.0 Hz,
9 H, (CH3)3C], 1.41–1.49 (m, 3 H), 1.97–2.07 (m, 3 H), 2.78–2.87
(m, 6 H), 3.25–3.34 (m, 6 H) ppm. 31P NMR (162 MHz, CD3CN;
TMNAPT): δ = 2.05 ppm. HRMS (ESI): calcd. for C13H28N4P [M
+ H]+ 271.2046; found 271.2045.
tR 5.07; m/z (%) = 41 (50), 57 (100), 99 (15), 112 (1).
tert-Octyl Azide:[19c–f] tert-Octyl azide (13.55 g, 87%) was synthe-
sized from sodium azide (13.0 g, 200 mmol), H2SO4 (96%; 31 mL)
in water (53 mL) and 2,4,4-trimethyl-1-pentene (11.2 g, 100 mmol).
The heterogeneous reaction mixture was vigorously stirred for 10 d
for complete conversion of the alkene. Work-up was the same as for
1
A sample of 2f (1.00 g, 3.7 mmol) was converted into its HBF4 salt
according to GP3, and the solid obtained was recrystallized from
ethyl acetate to give colorless crystalline of 2f·HBF4 (1.22 g, 92%),
tert-heptyl azide. Colorless liquid. H NMR (400 MHz, CDCl3): δ
= 1.03 [s, 9 H, (CH3)3C], 1.32 [s, 6 H, (CH3)2C], 1.52 (s, 2 H,
CH2) ppm. 13C NMR (101 MHz, CDCl3): δ = 28.6, 31.3, 31.7, 53.1,
62.3 ppm. GC-MS data: tR 5.89; m/z (%) = 29 (10), 41 (30), 56
(100), 155 [M]+ (1).
m.p. Ͼ195 °C (dec.). IR (neat): ν = 3304 (w), 2935 (w), 2871 (w),
˜
1394 (w), 1304 (m), 1280 (m), 1173 (m), 1093 (m), 1043 (s), 1032
1
(s), 1006 (s), 936 (m), 874 (m), 755 (m), 748 (m), 715 (m) cm–1. H
Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectra for phosphazides 1a–f and bases
NMR (400 MHz, CDCl3): δ = 1.36 [s, 9 H, (CH3)3C], 1.71–1.75
(m, 3 H, β-CH2 cycl.), 2.07–2.17 (m, 3 H, β-CH2 cycl.), 3.04–3.14
(m, 6 H, α-CH2 cycl.), 3.43–3.52 (m, 6 H, α-CH2 cycl.), 4.72 (d, J
= 16.2 Hz, 1 H, NH) ppm. 13C NMR (101 MHz, CDCl3): δ = 22.9
(d, J = 5.5 Hz), 30.6 (d, J = 4.2 Hz), 48.5 (d, J = 1.2 Hz), 53.8 (d,
J = 5.0 Hz) ppm. 31P NMR [162 MHz, CDCl3; (MeO)3PO]: δ =
21.78 ppm. 1H NMR (400 MHz, CD3CN): δ = 1.34 [d, J = 0.7 Hz,
9 H, (CH3)3C], 1.65–1.73 (m, 3 H), 2.04–2.15 (m, 3 H), 3.06–3.15
(m, 6 H), 3.30–3.39 (m, 6 H), 4.23 (d, J = 16.0 Hz, 1 H, NH) ppm.
31P NMR (162 MHz, CD3CN; TMNAPT): δ = 22.09 ppm. HRMS
(ESI): calcd. for C13H28N4P [M]+ 271.2046; found 271.2047.
C13H28N4P (271.36): calcd. C 43.6, H 7.9, N 15.6, P 8.65; found C
43.6, H 7.9, N 15.5, P 8.55.
1
2a–f together with H NMR spectra for tert-heptyl and tert-octyl
azides.
Acknowledgments
Financial support of this work by the Institute of Organic Chemis-
try and Biochemistry of the Academy of Sciences of the Czech
Republic under grant number Z4 055 0506 and by the Ministry of
Education, Youth and Sports of the Czech Republic (grant number
MSM0021620857, to I. C.) is gratefully acknowledged. The experi-
ments on basicity measurement were supported by the Estonian
Ministry of Education and Research (targeted financing project
number SF0180061s08). The work of Dr. Ivo Leito and Dr. Jaan
Saame was supported by the Estonian Science Foundation (grant
number 9105). The authors thank Dr. Ullrich Jahn (IOCB, Prague)
for helpful discussions and invaluable help in the preparation of
the manuscript.
Salt 2f·HOTs (1.48 g, 99%), was prepared from 2f (902.2 mg,
3.3 mmol) and p-toluenesulfonic acid (574.6 mg, 3.3 mmol), m.p.
1
194–195 °C (from ethyl acetate/chloroform). H NMR (400 MHz,
CDCl3): δ = 1.30 [s, 9 H, (CH3)3C], 1.60–1.64 (m, 3 H), 1.96–2.05
(m, 3 H), 2.27 (s, 3 H), 2.91–3.00 (m, 6 H), 3.46–3.55 (m, 6 H),
6.46 (d, J = 16.7 Hz, 1 H, NH), 7.07 (d, J = 8.4 Hz, 2 H, Harom.),
7.76 (d, J = 8.1 Hz, 2 H, Harom.) ppm. 31P NMR [162 MHz, CDCl3;
(MeO)3PO]: δ = 22.21 ppm.
[1] T. Ishikawa, Y. Kondo, H. Kotsuki, T. Kumamoto, D.
Margetic, K. Nagasawa, W. Nakanishi, Superbases for Organic
Synthesis Wiley, Chichester, UK, 2009.
Tris(1-pyrrolidinyl)(amino)phosphonium Tetrafluoroborate (8):[7]
HBF4 (1 m aq.; 21.6 mL) was added to a solution of 1d (7.36 g,
21.6 mmol) in methanol (20 mL) cooled to –78 °C. The reaction
mixture was allowed to warm to room temperature and stirred for
2 h. The volatiles were evaporated in high vacuum to give 8 (7.43 g,
99%) as a colorless solid, m.p. 101–102 °C. Compound 8 was alter-
natively prepared according to GP3 in quantitative yield. 1H NMR
(400 MHz, CDCl3): δ = 1.83–1.87 (m, 12 H, β-CH2 pyrr.), 3.15–
3.20 (m, 12 H, α-CH2 pyrr.), 4.01 (d, J = 5.9 Hz, 2 H, NH2) ppm.
13C NMR (101 MHz, CDCl3): δ = 26.3 (d, J = 8.1 Hz), 47.1 (d,
J = 4.8 Hz) ppm. 31P NMR [162 MHz, CDCl3; (MeO)3PO]: δ =
29.14 ppm. HRMS (ESI): calcd. for C12H26N4P [M]+ 257.1890;
found 257.1888.
[2] H. R. Allcock, Chemistry and Applications of Polyphosphaz-
enes, Wiley, Hoboken, 2003.
[3] K. Issleib, M. Lischewski, Synth. Inorg. Met. Org. Chem. 1973,
3, 255–264.
[4] a) R. Appel, M. Halstenberg, Angew. Chem. 1977, 89, 268; An-
gew. Chem. Int. Ed. Engl. 1977, 16, 263–264; b) A. P. Mar-
chenko, G. N. Koidan, A. M. Pinchuk, A. V. Kirsanov, Zh.
Obshch. Khim. 1984, 54, 1774–1782 (Russ. J. Gen. Chem. Engl.
1984, 54, 1581–1588); c) I. S. Zal’tsman, G. N. Koidan, A. A.
Kudrjavtsev, A. P. Marchenko, A. M. Pinchuk, Zh. Obshch.
Khim. 1989, 59, 2135–2136; (Russ. J. Gen. Chem. Engl. 1989,
59, 1914–1915); d) V. V. Miroshnichenko, G. N. Koidan, V. A.
Olejnik, A. P. Marchenko, A. M. Pinchuk, Zh. Obshch. Khim.
1989, 59, 2136–2138; (Russ. J. Gen. Chem. Engl. 1989, 59,
1916–1917).
[5] a) R. Schwesinger, Chimia 1985, 39, 269–272; b) R. Schwes-
inger, H. Schlemper, Angew. Chem. 1987, 99, 1212–1214; An-
gew. Chem. Int. Ed. Engl. 1987, 26, 1167–1169; c) R. Schwes-
inger, Ch. Hasenfratz, H. Schlemper, L. Walz, E.-M. Peters, K.
Peters, H. G. von Schnering, Angew. Chem. 1993, 105, 1420–
1422; Angew. Chem. Int. Ed. Engl. 1993, 32, 1361–1363.
[6] R. Schwesinger, J. Willaredt, H. Schlemper, M. Keller, D.
Schmitt, H. Fritz, Chem. Ber. 1994, 127, 2435–2454.
tert-Heptyl Azide:[19b] tert-Heptyl azide (10.2 g, 90%) was synthe-
sized according to a published method[20] from sodium azide
(10.5 g, 161.5 mmol), dilute sulfuric acid [H2SO4 (96%; 28 mL) in
water (48 mL)], and tert-heptyl alcohol (9.3 g, 80.4 mmol). The re-
action mixture was stirred at room temperature for 48 h. The upper
layer was separated, and the aqueous phase was extracted with
pentane (2ϫ 35 mL). The combined organic extracts were washed
twice with NaOH (2 m; 10 mL), and dried with solid KOH. The
pentane was carefully evaporated at 100 mbar to give a colorless
Eur. J. Org. Chem. 2013, 1811–1823
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1821

A. V. Alexandrova et al.
FULL PAPER
[7]
[22]
[23]
R. Schwesinger, H. Schlemper, Ch. Hasenfratz, J. Willaredt, T.
Dambacher, T. Breuer, C. Ottaway, M. Fletschinger, J. Boele,
H. Fritz, D. Putzas, H. W. Rotter, F. G. Bordwell, A. V. Satish,
G.-Z. Ji, E.-M. Peters, K. Peters, H. G. von Schnering, L. Walz,
Liebigs Ann. 1996, 1055–1081.
a) T. E. Waldman, W. D. McGhee, J. Chem. Soc., Chem. Com-
mun. 1994, 957; b) D. Bensa, J. Rodriguez, Synth. Commun.
2004, 34, 1515–1533; c) V. Raab, E. Gauchenova, A. Merkou-
lov, K. Harms, J. Sundermeyer, B. Kovacˇevic´, Z. Maksic´, J.
Am. Chem. Soc. 2005, 127, 15738–15743; d) I. M. Lyapkalo,
M. A. K. Vogel, Angew. Chem. 2006, 118, 4124–4127; Angew.
Chem. Int. Ed. 2006, 45, 4019–4023; e) M. A. K. Vogel,
C. B. W. Stark, I. M. Lyapkalo, Synlett 2007, 2907–2911.
a) Yu. G. Gololobov, I. N. Zhmurova, L. F. Kasukhin, Tetrahe-
dron 1981, 37, 437–472 and references cited therein; b) Yu. G.
Gololobov, Tetrahedron 1992, 48, 1353–1406, and references
cited therein.
C. Stuebe, H. P. Lankelma, J. Am. Chem. Soc. 1956, 78, 976–
977.
a) T. Høeg-Jensen, K. E. Olsen, A. Holm, J. Org. Chem. 1994,
59, 1257–1263; b) D. J. Dellinger, D. M. Sheehan, N. K. Chris-
tensen, J. G. Lindberg, M. H. Caruthers, J. Am. Chem. Soc.
2003, 125, 940–950.
[8]
[24]
The initial procedure for the preparation and isolation of
P(pyrr)3 was as follows: Pyrrolidine (9 equiv., freshly distilled
from Na/K alloy) was dissolved in dry THF, and cooled to
0 °C, and PCl3 (1 equiv.) was added dropwise with stirring un-
der argon. The mixture was stirred at room temp. for 3 h.
Work-up of the reaction mixture was performed as follows. A
portion of dry hexane was added in order to precipitate the
pyrrolidine hydrochloride completely, and the upper trans-
parent layer was carefully decanted from the precipitate under
a stream of argon. The solution was concentrated on a rotary
evaporator connected to an argon supply. The yield of the re-
sidual viscous oil of P(pyrr)3 was 75 %.
[9]
[10]
a) J. G. Verkade, Ph. B. Kisanga, Tetrahedron 2003, 59, 7819–
7858; b) M. W. P. Bebbington, D. Bourissou, Coord. Chem. Rev.
2009, 253, 1248–1261.
[25]
[26]
a) J. L. Bolliger, O. Blacque, C. M. Frech, Angew. Chem. 2007,
119, 6634–6637; Angew. Chem. Int. Ed. 2007, 46, 6514–6517;
b) J. L. Bolliger, C. M. Frech, Chem. Eur. J. 2010, 16, 4075–
4081.
[11]
[12]
H. Staudinger, Helv. Chim. Acta 1919, 2, 635–646.
a) M. Alajarín, P. Molina, A. López-Lázaro, C. Foces-Foces,
Angew. Chem. 1997, 109, 147–150; Angew. Chem. Int. Ed. Engl.
1997, 36, 67–70; b) M. Alajarín, A. López-Lázaro, A. Vidal, J.
Berná, Chem. Eur. J. 1998, 4, 2558–2570; c) M. Alajarín, A.
López-Lázaro, J. Berná, J. W. Steed, Tetrahedron 2007, 63,
2078–2083; d) R. D. Kennedy, Chem. Commun. 2010, 46, 4782–
4784.
a) P. Ilankumaran, J. G. Verkade, J. Org. Chem. 1999, 64, 9063–
9066; b) H. Naka, N. Kanase, M. Ueno, Y. Kondo, Chem. Eur.
J. 2008, 14, 5267–5274; c) C. R. Venkat Reddy, J. G. Verkade, J.
Org. Chem. 2007, 72, 3093–3096; d) C. R. Venkat Reddy, B. M.
Fetterly, J. G. Verkade, Energy Fuels 2007, 21, 2466–2472.
a) H. Goldwhite, P. Gysegem, S. Schow, Ch. Swyke, J. Chem.
Soc., Dalton Trans. 1975, 16–18; b) Ch. Widauer, H.
Grützmacher, I. Shevchenko, V. Gramlich, Eur. J. Inorg. Chem.
1999, 1659–1664; c) W. Quan, Y. A. Wang, J. Org. Chem. 2004,
69, 4299–43.
a) Ch. W. Rees, D. I. Smith, J. Chem. Soc. Perkin Trans. 1 1987,
1159–1164; b) J. Tang, J. Dopke, J. G. Verkade, J. Am. Chem.
Soc. 1993, 115, 5015–5020; c) A. A. Kolomeitsev, I. A. Koppel,
T. Rodima, J. Barten, E. Lork, G.-V. Röschenthaler, I. Kaljur-
and, A. Kütt, I. Koppel, V. Mäemets, I. Leito, J. Am. Chem.
Soc. 2005, 127, 17656–17666; d) M. Alajarín, M. Marin-Luna,
M.-M. Ortin, P. Sanchez-Andrada, A. Vidal, Tetrahedron 2009,
65, 2579–2590.
For the formation of (iPr2N)2PCl as the sole product of the
reaction of PCl3 with diisopropylamine, see: a) E. H. Wong,
M. M. Turnbull, K. D. Hutchinson, C. Valdez, E. J. Gabe, F. L.
Lee, Y. L. Page, J. Am. Chem. Soc. 1988, 110, 8422–8428; b) S.
Hamamoto, H. Takaku, Chem. Lett. 1986, 1401–1404; c) A.
Baceiredo, G. Bertrand, J.-P. Majoral, F. E. Anba, G. Manuel,
J. Am. Chem. Soc. 1985, 107, 3945–3949. For precedent for the
formation of P(NiPr2)3, see: d) E. E. Nifant’ev, S. V. Suvorkin,
E. N. Rasadkina, O. V. Selyutina, A. V. Shishin, Zh. Obshch.
Khim. 2002, 72, 1263–1266; (Russ. J. Gen. Chem. Engl. 2002,
72, 1183–1185). Applications of P(NiPr2)3: e) T.-B. Huang, J.-
L. Zhang, Phosphorus Sulfur Silicon Relat. Elem. 1995, 104,
33–44; f) H. Hund, R.-D. Hund, S. Has, G.-V. Röschenthaler,
Phosphorus Sulfur Silicon Relat. Elem. 1996, 111, 193. For an
explanation of the dichotomy, see: g) A. P. Marchenko, G. N.
Koidan, Y. M. Pustovit, M. I. Povolotskii, A. N. Chernega,
A. M. Pinchuk, Phosphorus Sulfur Silicon Relat. Elem. 2008,
183, 797–798.
a) T. J. Atkins, Tetrahedron Lett. 1978, 45, 4331–4332; b)
R. D. H. Kim, M. Wilson, J. Haseltine, Synth. Commun. 1994,
24, 3109–3114; c) R. W. Alder, R. W. Mowlam, D. J. Vachon,
G. R. Weisan, J. Chem. Soc., Chem. Commun. 1992, 507–508.
CCDC-831687 (for 1d), CCDC-831688 (for 1e), CCDC-831689
(for 2d·HBF4), CCDC-831690 (for 2e·HBF4), CCDC-831691
(for 2f·HOTs) and CCDC-849644 (for 2e) contain the supple-
mentary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[13]
[14]
[15]
[27]
[28]
[16]
[17]
[18]
[19]
H. Goldwhite, P. Gysegem, S. Schow, Ch. Swyke, J. Chem. Soc.,
Dalton Trans. 1975, 12–15.
J. R. Goerlich, M. Farkens, A. Fischer, P. G. Jones, R.
Schmutzler, Z. Anorg. Allg. Chem. 1994, 620, 707–715.
ˇ
R. A. Kunetskiy, I. Císarˇová, D. Saman, I. M. Lyapkalo,
[29]
[30]
G. C. Fortman, B. Captain, C. D. Hoff, Inorg. Chem. 2009, 48,
188–1810.
Chem. Eur. J. 2009, 15, 9477–9485.
a) M. Kitamura, M. Yano, N. Tashiro, S. Miyagawa, M. Sando,
T. Okauchi, Eur. J. Org. Chem. 2011, 548–462; b) E. P. Kyba,
R. A. Abramovich, J. Am. Chem. Soc. 1980, 102, 735–740; c)
P. J. Baldry, A. R. Forrester, M. M. Ogilvy, R. H. Thomson, J.
Chem. Soc. Perkin Trans. 1 1982, 2027–2034; d) S. P. Klump,
H. Shechter, Tetrahedron Lett. 2002, 43, 8421–8423; e) V. V.
Zhdankin, A. P. Krasutsky, Ch. J. Kuehl, A. J. Simonsen, J. K.
Woodward, B. Mismash, J. T. Bolz, J. Am. Chem. Soc. 1996,
118, 5192–5197; f) C. J. Cavender, V. J. Shiner Jr., J. Org. Chem.
1972, 37, 3567–3569.
The average P–N single bond length is 1.663 Å for pentacoor-
dinate phosphorus compounds of type (X2N)3P=O, and the
common length of the P=N double bond is 1.599 Å in com-
pounds of type Ph3P=N–C. These values are taken from: F. H.
Allen, O. Kennard, D. G. Watson, L. Brammer, A. G. Orpen,
R. Taylor, J. Chem. Soc. Perkin Trans. 2 1987, S1–S19.
[31]
[32]
A. A. Grishina, S. M. Polyakova, R. A. Kunetskiy, I. Císarˇová,
I. M. Lyapkalo, Chem. Eur. J. 2011, 17, 96–100.
a) I. Kaljurand, A. Kütt, L. Sooväli, T. Rodima, V. Mäemets,
I. Leito, I. A. Koppel, J. Org. Chem. 2005, 70, 1019–1028; b)
E.-I. Rõõm, A. Kütt, I. Kaljurand, I. Koppel, I. Leito, I. A.
Koppel, M. Mishima, K. Goto, Y. Miyahara, Chem. Eur. J.
2007, 13, 7631–7643; c) L. Sooväli, I. Kaljurand, A. Kütt, I.
Leito, Anal. Chim. Acta 2006, 566, 290–303.
“dma” and “pyrr” in abbreviations for the reference bases (Rb)
denote dimethylamino and 1-pyrrolidinyl groups; for the struc-
tures of the bases see: T. Rodima, I. Kaljurand, A. Pihl, V.
[20]
[21]
J. C. Bottaro, P. E. Penwell, R. J. Schmitt, Synth. Commun.
1997, 27, 1465–1467.
a) M. Sathishkumar, P. Shanmugavelan, S. Nagarajan, M.
Maheswari, M. Dinesh, A. Ponnuswamy, Tetrahedron Lett.
2011, 52, 2830–2833; b) M. Sathishkumar, S. Nagarajan, P. Sh.
Velan, M. Dinesh, A. Ponnuswamy, J. Braz. Chem. Soc. 2011,
22, 2065–2069; c) A. Ponnuswamy, P. Shanmugavelan, S. Naga-
rajan, M. Sathishkumar, Helv. Chim. Acta 2012, 95, 922–928.
[33]
1822
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 1811–1823

Electron-Rich Sterically Hindered P1 Phosphazene Bases
Mäemets, I. Leito, I. A. Koppel, J. Org. Chem. 2002, 67, 1873–
1881.
[34] D. A. Evans discussed the issue in detail in his course of
Advanced Organic Chemistry, see http://isites.harvard.edu/
[36] R. Streck, A. J. Barnes, Spectrochim. Acta Part A 1999, 55,
1049–1058.
[37] T. W. Bell, H.-J. Choi, W. Harte, M. G. B. Drew, J. Am. Chem.
Soc. 2003, 125, 12196–12210.
[38] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi,
M. C. Burla, G. Polidori, M. Camalli, J. Appl. Crystallogr.
1994, 27, 435–443.
icb/icb.do?keyword=k7863&pageid=icb.page52877,
Lecture
Number 6 (visited 15/11/2012). The key references cited therein
are: a) H. C. Brown, K. Ichikawa, Tetrahedron 1957, 1, 221–
230 and b) H. C. Brown, J. H. Brewster, H. Shechter, J. Am.
Chem. Soc. 1954, 76, 467–474.
[39] G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr.
2008, 64, 112–122.
[35] H. E. Gottlieb, V. Kotlyar, A. Nudelman, J. Org. Chem. 1997,
62, 7512–7515.
Received: October 22, 2012
Published Online: February 6, 2013
Eur. J. Org. Chem. 2013, 1811–1823
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1823