Straightforward Diastereoselective Synthesis of P-Chirogenic (1R)-1,8,8-Trimethyl-2,4-diaza-3-phosphabicyclo[3.2.1]octane 3-Oxides: Application as Chiral NMR Solvating Agents

Article abstract of DOI:10.1002/hc.21309

A direct route to enantio- and diastereopure nitrogen-substituted phosphine oxides has been developed. The desired P-stereogenic compounds were obtained in good yields and high purity. The starting point of the synthesis was (+)-camphor, which is a readil

Full text of DOI:10.1002/hc.21309

Heteroatom Chemistry
Volume 27, Number 2, 2016
S
traightforward Diastereoselective Synthesis
of P-Chirogenic (1R )-1,8,8-Trimethyl-2,4-
diaza-3-phosphabicyclo[3.2.1]octane
3
-Oxides: Application as Chiral NMR
Solvating Agents
Magdalena Uzarewicz-Baig and Ren e´ Wilhelm
Department of Chemistry, University of Paderborn, Paderborn, 33098, Germany
Received 29 September 2015; revised 2 December 2015; accepted 15 December 2015
compounds is especially interesting for the synthe-
ABSTRACT: A direct route to enantio- and diastere-
opure nitrogen-substituted phosphine oxides has been
developed. The desired P-stereogenic compounds were
obtained in good yields and high purity. The start-
ing point of the synthesis was (+)-camphor, which
is a readily available compound from the chiral pool.
The new nitrogen-substituted phosphine oxides could
be transformed from their pentavalent state to their
trivalent form with N,O-bis(trimethylsilyl)acetamide,
which makes them potential chiral ligands. It was pos-
sible to apply these compounds as chiral-solvating
agents in chiral recognition experiments with a
racemic alcohol and acid. ꢀC 2016 Wiley Periodi-
sis of biologically active compounds and for the
preparation of reagents [2]. Furthermore, enantiop-
ure phosphorus compounds have been applied as
organocatalysts [3] and largely as ligands in metal-
catalyzed asymmetric reactions [4].
A special challenge is the synthesis of chiral
phosphorus compounds incorporating a chirogenic
phosphorus atom. Examples of different compounds
1–6 are shown in Fig. 1. For the synthesis of these
compounds, different strategies are possible. Next
to a standard resolution [5], kinetic and dynamic
resolution [6] can be applied. Furthermore, asym-
metric catalytic reactions can directly form a new
P-stereogenic center [7]. Another alternative is to
start the synthesis of these compounds with a start-
ing material from the chiral pool. In the latter case,
an asymmetric phosphorus center will lead to the
construction of enantiopure diastereomers [8]. An
example is the menthyl hydrogen phosphinate 6,
which can also be further transformed to other chi-
ral phosphorus compounds [9].
Especially structures containing phosphorus-
heteroatom bonds [10], which can be abbreviated as
SPO (secondary phosphine oxides) or according to
the suggestion of Ackermann HASPO (heteroatom-
substituted secondary phosphine oxides) like 4, have
recently received much attention [11]. The first het-
erocyclic compounds having both phosphorus and
nitrogen atoms were prepared by Liebig and W o¨ hler
cals, Inc. Heteroatom Chem. 27:121–134, 2016; View
this article online at wileyonlinelibrary.com. DOI
10.1002/hc.21309
INTRODUCTION
Organophosphorus compounds are an important
part of many research areas such as agrochem-
istry, medicinal chemistry, biochemistry, and or-
ganic synthesis [1]. The application of enantiopure
Correspondence to: Ren e´ Wilhelm; e-mail: rene.wilhelm@
uni-paderborn.de.
Supporting Information is available in the online issue at
www.wileyonlinelibrary.com.
ꢀC
2016 Wiley Periodicals, Inc.
121

122 Uzarewicz-Baig and Wilhelm
FIGURE 1 Examples of chiral organophosphorus com-
pounds.
[12]. Enantiopure or enantioenriched heterocycles
containing a trivalent or pentavalent P-stereogenic
phosphorus atom can be easily generated by cycliza-
tion of diamines, amino alcohols, or diols around
phosphorus moieties. Phosphorus-heteroatom het-
erocycles are extremely attractive compounds be-
cause in contrast to the classic phosphines they pre-
sented marked stability toward moisture and air and
can be used as organocatalysts or as ligands in tran-
sition metal transformations [13].
One relevant class of P-stereogenic di-
aminophosphine oxides was discovered by Hamada
and co-workers. They synthesized a new class
of P-chirogenic phosphine oxides based on a
chiral asymmetric diamine framework, called P-
stereogenic diaminophosphine oxides: DIAPHOXs 5
SCHEME 1 Synthesis of enantiopure camphor-based HAS-
POs 16–24.
from (+)-camphoric acid, which was purchased
from commercial sources. The symmetrical substi-
tuted diamines 7 and 8 were prepared according to
a literature procedure [21]. Thereafter, a series of
enantiopure secondary diamines 26 with two differ-
ently substituted nitrogen atoms were synthesized
via an alkylation of monoarylated diamines [22] with
mesitylmethylene chloride in the presence of tri-
ethylamine in acetonitrile under reflux (Scheme 1).
The corresponding diamines 9–15 were obtained in
yields between 50% and 70% as shown in Table 1.
The use of the less sterically demanding benzyl bro-
mide and chloride as electrophile with 9–15 in the
reaction resulted in a mixture of products that could
not be separated.
[14]. These chiral ligands with a stereogenic center
on a phosphorus atom [15] have been prepared
from (S)-aspartic acid [16].
Diaminophosphine oxides have been applied
as preligands in cross-coupling reactions [17] and
Ni-catalyzed asymmetric hydrocarbamoylations of
alkenes [18]. In addition, diaminophosphine oxides
and aminophosphonic acids analogues have a high
potential as biological active compounds [19].
Here, we present the straightforward synthe-
sis of new enantiopure C1 symmetric nitrogen-
substituted SPOs with a P-stereogenic center via a di-
astereoselective route from camphor. The chirogenic
phosphorus atom is embedded in a rigid bicyclic sys-
tem being part of a six- and seven-membered ring.
HASPOs are accessible from diamines [2a,13c,
23]. The new desired nitrogen-substituted SPOs were
prepared in two steps from the diamines 7–15, by
treating these secondary diamines with PCl3 and
Et3N at −60°C (Scheme 1). The temperature was
slowly raised to room temperature in toluene. After
filtration through MgSO4, the heterocyclic chloride
derivative was obtained. In the second step, H2O and
Et3N were added to the chloride derivative at −60°C.
The temperature was slowly raised to room temper-
ature in toluene. After filtration through MgSO4, the
desired product was isolated. The presence of Et3N
as a base was required due to the formation of HCl,
which can decompose the desired product [13h].
The products 16–24 were characterized by mass
spectrometry and multinuclear NMR spectroscopy.
RESULTS AND DISCUSSION
To synthesize the desired chiral nitrogen-substituted
phosphine oxides, the starting diamines 7–
1
5
were prepared from (+)-cis-(1R,3S)-1,2,2-
trimethylcyclopentane-1,3-diamine (25). The latter
3
1
can be synthesized according to the literature [20]
P NMR chemical shifts were, respectively, in the
Heteroatom Chemistry DOI 10.1002/hc

Diastereoselective Synthesis of P-Chirogenic (1R)-1,8,8-trimethyl-2,4-diaza-3-phosphabicyclo[3.2.1]octane 3-oxides 123
TABLE 1 Synthesis of Diamines and SPOs
TABLE 1 Continued
Entry
1
Diamine
Producta
31P, δ (ppm)
9
5.4
5.4
10.1
1
0
2
9.6
aAbsolute configuration assigned by NOESY.
3
4
3.9
3.9
same range as those reported for related compounds
3
1
[13c,13d]. The results with selected P NMR data
are shown in Table 1.
From Table 1, it is possible to conclude that ex-
cellent yields can be obtained for the synthesis of the
secondary phosphine oxides. The products were ob-
tained as one diastereomer. It is remarkable that the
reactions carried out on a larger scale gave cleaner
desired products, which did not need any purifica-
tion. Only one product obtained from diamine 12
was achieved as two diastereomers 21a (Table 1, en-
try 6) and 21b (Table 1, entry 7), which were sep-
arated by column chromatography. Figure 2 shows
5
3.9
3
1
a
P NMR of the diastereomers prior to separation
3
1
and of 21b after isolation. In general, P NMR res-
onances for the compounds were in the range of δ =
1
.9–10 ppm. 21b appeared at δ = −4.2 ppm. The rea-
son of the formation of two diastereomers from 12
can be due to the sterically demanding mesityl sub-
stituent present in the diamine. In all other deriva-
tives, one ortho-position incorporates a small hydro-
gen atom. When a rotation around the N-arly bond
is possible, the sterical hindrance induced by these
aryl substituents can be smaller than that of a mesityl
substituent.
6
7
8
1.9
−4.2
4.9
The absolute configuration of the new P-
stereogenic centers in the obtained products was es-
tablished by NOESY. It can be assumed from the
spectra that substrates containing the same sub-
stituent on the nitrogen atoms have S configuration
on the phosphorus atom whereas ligands with two
different substituents on the nitrogen atoms have
R configuration on the phosphorus atom.
1
The H NMR spectra showed that the proton at-
tached to the phosphorus appeared as a character-
istic doublet with a coupling JP-H = 617.0–649.9 Hz.
Additionally, NOESY studies revealed that the P–H
(
Continued)
Heteroatom Chemistry DOI 10.1002/hc

124 Uzarewicz-Baig and Wilhelm
FIGURE 2 31P NMR of 21a and 21b before separation and of 21b after separation.
bond in the ligands is on the same side as the Me2C
bridge. An example is given in Fig. 3 for compound
toluene-D8. The experiment was controlled at dif-
ferent times; however, the best result was obtained
after 24 h. The reaction was much slower compared
to five-membered ring diaminophosphine oxides like
16.
The exception is diastereomer 21b, where the P–
H bond is on the other side as the Me2C bridge. The
spectra are shown in Fig. 4.
3
1
DIAPHOX 5 [14]. The P NMR showed that pen-
tavalent ligand 16 (chemical shift: 8.1 ppm, toluene-
D8) reacted with BSA to provide the formation of a
trivalent phosphorus species (chemical shift: 117.4
ppm, toluene-D8) (Fig. 5).
Since just very few six- and seven-membered
ring diaminophosphine oxides are known and
for instance even seven-membered enantiopure
binaphthyl-derived analogues are unknown, it was
decided to study the behavior of the newly pre-
pared compounds 16–24 in more detail. The pen-
tavalent phosphorus species were activated in situ
by N,O-bis(trimethylsilyl)acetamide (BSA) to in-
duce P(V)–P(III) tautomerization to afford trivalent
phosphorus compounds, trapped as TMS adducts
Further investigation revealed that when asym-
metric compound 20 with a chemical shift of
2.4 ppm reacted with BSA in toluene-D8, the gen-
eration of the trivalent phosphorus species, with a
chemical shifted 104.9 ppm, could be performed
faster than with compound 16 (Fig. 6).
A current research field is to develop efficient
methods for the easy and fast measurement of the
enantiomeric excess of chiral compounds [24]. The
application of chiral-solvating reagents for NMR
spectroscopy is a very useful method to achieve de-
termination of the enantiomeric excesses of chiral
organic molecules. The advantage of this convenient
(Scheme 2), which can be used as ligands in
metal-catalyzed reactions. The generation of triva-
3
1
lent phosphorus compounds was monitored by
P
NMR spectroscopy. The principal investigation was
performed with symmetric secondary substituted
compound 16 and the addition of 4 equiv BSA to
Heteroatom Chemistry DOI 10.1002/hc

Diastereoselective Synthesis of P-Chirogenic (1R)-1,8,8-trimethyl-2,4-diaza-3-phosphabicyclo[3.2.1]octane 3-oxides 125
SCHEME 2 BSA-induced P(V)-P(III) transformation.
Organophosphorus compounds derived from
chiral C2-symmetric diamines have been used as
chiral-derivatizating reagents for NMR studies [27].
However, the potential of chiral HASPOs as chiral-
solvating agents has not been investigated so far.
Hence, the synthesized new compounds 16 and
18 were evaluated as chiral-solvating agents in dry
toluene. The chiral shift experiments were car-
1
19
ried out by measuring the H NMR and F NMR
spectra of a mixture of α-(trifluoromethyl)benzyl al-
cohol and 16 or 18, respectively, in a ratio of 1:1
in toluene at room temperature. While the symmet-
ric substituted compound 16 showed no shift differ-
1
9
FIGURE 3 1H NMR and NOESY of compound 16.
3
ence of the CF group in the F NMR, compound
18 resulted in a shift difference of 7 Hz (Fig. 7). The
interaction of the two compounds is caused by the
formation of a hydrogen bond of the alcohol with
the oxygen atom of the phosphine oxide.
1
The H NMR spectra were also recorded for the
mixtures mentioned above. Compound 18 interacted
with the methine proton of α-trifluoromethyl ben-
zyl alcohol and showed a shift difference of 7 Hz,
whereas no shift difference was observed with 16
(
Fig. 8).
Furthermore, mandelic acid was investigated
with 16 and 18 and the signal of the proton at the
asymmetric center showed a shift difference of 1 Hz
with 16 and 6 Hz with 18 (Fig. 9).
CONCLUSION
A new class of chiral HASPOs was prepared from
inexpensive camphoric acid, by treating the sec-
ondary diamine with different substituents with PCl3
and Et3N, followed by H2O which provided the de-
sired compounds in pure diastereomeric and enan-
tiomeric form. Preliminary experiments indicated
that trivalent phosphorus compounds are formed in
the presence of BSA. This is beneficial for their ap-
plication as ligands in metal-catalyzed asymmetric
transformations. Furthermore, the new compounds
could also be of interest as chiral-starting mate-
rial for further transformations like a hydrophos-
phorylation to prepare new P,C-stereogenic tertiary
FIGURE 4 1H NMR and NOESY of diastereomer 21b.
method is an easy performance without using any
chiral derivatization of the analyte [25]. Many dif-
ferent kinds of chiral shift reagents, such as crown
ethers, cyclodextrins, porphyrins, macrocycles, and
others have been investigated [26].
Heteroatom Chemistry DOI 10.1002/hc

126 Uzarewicz-Baig and Wilhelm
FIGURE 5 31P NMR of 16 with BSA after 24 h.
FIGURE 6 31P NMR of 20 with BSA after 24 h.
α-hydroxyl phosphinates [28]. Finally, it was pos-
sible to show that the new compounds 16 and 18
can be applied as chiral-solvating agents. The phos-
phorus compounds proved to be versatile chiral-
discriminating agents for different types of racemic
compounds such as alcohols and acids.
EXPERIMENTAL
General
FIGURE 7 19F NMR of α-(trifluoromethyl)benzyl alcohol in
the presence of 16 and 18.
All reactions were carried out using Schlenk line
techniques. All reagents which are not described
below were purchased from commercial sources. Re-
actions were monitored by TLC. Flash column chro-
matography was performed on Silica gel 60 (230–
HSQC, and HMBC. Melting points were taken on a
Dr. Tottoli apparatus and are uncorrected. Infrared
IR data were recorded on a FT-IR spectrometer Ver-
tex from Bruker. Mass spectra were recorded with a
Hewlett Packard 5989B at 70 eV. Analytical data are
given as relative mass (m/z), and the brackets indi-
cate the intensity in percent (%) related to the basic
peak. High-resolution mass spectra were recorded
on a Waters Quadrupole-ToF Synapt 2G. Optical
rotations were measured using a 1-dm path length
4
00 mesh). Nuclear magnetic resonance data were
1
recorded on a Bruker Advance 500 ( H NMR: 500
MHz, C NMR: 126 MHz, N NMR: 51 MHz) and
1
3
15
3
1
19
Bruker Advance 300 ( P NMR: 202 MHz, F NMR:
25 MHz) spectrometers. NMR chemical shifts δ are
1
reported in parts per million (ppm) and are refer-
enced to the residual solvent signal as the inter-
nal standard. The coupling constants J are given in
hertz (Hz). NMR signals were assigned via COSY,
Heteroatom Chemistry DOI 10.1002/hc

Diastereoselective Synthesis of P-Chirogenic (1R)-1,8,8-trimethyl-2,4-diaza-3-phosphabicyclo[3.2.1]octane 3-oxides 127
FIGURE 8 1H NMR of α-(trifluoromethyl)benzyl alcohol in
the presence of 16 and 18.
FIGURE 9 1H NMR of mandelic acid with 16 and 18.
The crude residue was purified by flash column
chromatography.
(
c is given as g/100 mL) on a Perkin-Elmer 241 MC
polarimeter in the reported solvent. (+)-cis-(1R,3S)-
,2,2-Trimethylcyclopentane-1,3-diamine (25) was
synthesized according to the literature [20] from
1
1
(
1R,3S)-1,2,2-Trimethyl-N -(2,4,6-trimethylben-
3
zyl)-N -(o-tolyl)-1,3-cyclopentanediamine (9). Pre-
pared from monoarylated diamine (0.30 g, 1.29
mmol), triethylamine (0.22 mL, 1.58 mmol), and
(
+)-camphoric acid, which was purchased from
commercial sources. Diamines 7 and 8 [21] and
monoarylated diamines [22] were prepared accord-
ing to the literature.
2,4,6-trimethylbenzyl chloride (0.24 g, 1.42 mmol)
in acetonitrile (10 mL). The crude product was pu-
rified via column chromatography (CH2Cl2/MeOH,
9
5:5), and the secondary diamine 9 was obtained
General Procedure for the Alkylation of
Monoarylated Diamines 26 by Mesitylmethyl
Chloride
1
as colorless oil (0.30 g, 0.82 mmol, 64%). H NMR
ꢁ
(
500 MHz, CDCl3) δ = 7.18 – 7.14 (m, 1H, H-5 ,
ꢁ
o-tolyl), 7.06 (dd, J = 7.2, 0.6 Hz, 1H, H-6 ), 6.96
ꢁꢁ
ꢁꢁ
To the stirred mixture of monoarylated diamine
(s, 2H, H-3 , H-5 , mesityl), 6.69 (d, J = 7.9 Hz, 1H,
ꢁ
ꢁ
26 (1 equiv) and triethylamine (1.2 equiv) in
H-3 ), 6.65 (td, J = 7.3, 1.0 Hz, 1H, H-4 ), 4.97 (s, 1H,
H-N1), 3.86 and 3.74 (two d, J = 10.7 Hz, 2H, NCH2,
acetonitrile at room temperature, mesitylmethyl
chloride (1.1 equiv) was added. The resulting so-
lution was refluxed overnight. After refluxing, the
reaction mixture was cooled down and filtered and
the filtrate was evaporated under reduced pressure.
ꢁ
ꢁꢁ
ꢁꢁ
H-1 ), 3.82–3.77 (m, 1H, H-3), 2.46 (s, 6H, 2 -CH3,
ꢁ
ꢁ
ꢁꢁ
6 -CH3), 2.39 (s, 3H, 4 -CH3), 2.28–2.18 (m, 2H,
ꢁ
H-4), 1.90 (s, 3H, 2 -CH3), 1.80–1.71 (m, 2H, H-5),
1.36 (s, 3H, H-8), 1.14 and 1.02 (two s, 6H, H-6, H-7)
Heteroatom Chemistry DOI 10.1002/hc

128 Uzarewicz-Baig and Wilhelm
ppm. 13C NMR (126 MHz, CDCl3) δ = 146.6 (C-1 in
ꢁ
in acetonitrile (10 mL). The crude product was
purified via column chromatography
(CH2Cl2/MeOH, 95:5) and the secondary diamine 11
ꢁꢁ
ꢁꢁ
ꢁꢁ
o-tolyl), 136.8 (C-2 , C-6 in mesityl), 136.4 (C-4 ),
34.1 (C-1 ), 130.2 (C-6 ), 129.2 (C-3 , C-5 ), 126.9
C-5 ), 122.2 (C-2 ), 115.6 (C- 4 ), 109.5 (C-3 ), 65.5
C-1), 62.1 (C-3), 48.8 (C-2), 40.2 (C-1 in NHCH2),
2.5 (C-4), 30.6 (C-5), 25.9 (C-6), 21.0 (4 -CH3), 19.6
2 -CH3, 6 -CH3), 19.0 (C-8), 17.5 (C-2 ), 17.0 (C-7)
ꢁ
ꢁ
ꢁ
ꢁꢁ
ꢁꢁ
1
(
(
3
ꢁ
ꢁ
ꢁ
ꢁ
was obtained as yellow oil (0.30 g, 0.85 mmol, 62%).
ꢁ
ꢁꢁ
1
H NMR (500 MHz, CDCl3) δ = 7.27 – 7.23 (m, 2H,
ꢁꢁ
ꢁ ꢁ ꢁꢁ ꢁꢁ
H-3 , H-5 ), 7.03 (s, 2H, H-3 , H- 5 ), 6.75 – 6.71 (m,
ꢁꢁ
ꢁꢁ
ꢁ
ꢁ
ꢁ
ꢁ
(
1H, H-4 ), 6.64 (dd, J = 8.6, 0.9 Hz, 2H, H-2 , H-6 ),
1
5
3
ꢁꢁꢁ
ppm. N NMR (51 MHz, CDCl3) δ = 83.8 (1N, N ),
3.88 (d, J = 10.6 Hz, 1H, H-1 ), 3.78 – 3.74 (m, 2H,
1
ꢁꢁꢁ ꢁꢁ ꢁꢁ
5
1
1
3.5 (1N, N ). IR (ATR) ν = 3360, 2958, 2914, 2865,
H-1 , H-3), 2.52 (s, 6H, 2 -CH3, 6 -CH3), 2.43 (s, 3H,
ꢁꢁ
601, 1576, 1507, 1477, 1448, 1384, 1370, 1316,
4 -CH3), 2.30 – 2.21 (m, 2H, H-4), 1.81 – 1.72 (m,
2H, H-5), 1.38 (s, 3H, H-8), 1.14 (s, 3H, H-6), 1.05
−
1
257, 1217, 1158, 1070, 1051, 850, 742, 713 cm
.
+
13
MS (ESI, + 3 kV): m/z (%) = 365 ([M + H] , 100%).
(s, 3H, H-7) ppm. C NMR (126 MHz, CDCl3) δ =
ꢁ ꢁ ꢁꢁ ꢁ ꢁꢁ
148.7 (C-1 ), 137.1 (2 -CH3, 6 -CH3 ), 136.6 (C- 1 ),
HRMS (ESI): Calcd. for C25H37N2: 365.2956, found:
2
0
ꢁꢁ ꢁꢁ ꢁꢁ ꢁ ꢁ
3
65.2957. [α] D = +24 (c = 0.5, CH2Cl2).
134.1 (C-4 ), 129.3 (C-3 , C-5 ), 129.2 (C-3 , C-5 ),
1
4
(C- 6), 21.1 (4 -CH3), 19.6 (2 -CH3, 6 -CH3), 19.4
(C-8), 17.1 (C-7) ppm. N NMR (51 MHz, CDCl3) δ
ꢁ ꢁ ꢁ
16.2 (C-4 ), 113.0 (C-2 , C-6 ), 65.5 (C-1), 62.7 (C-3),
ꢁ
ꢁꢁ
8.7 (C-2), 40.6 (C-1 ), 32.3 (C-4), 30.1 (C-5), 26.1
3
ꢁꢁ
ꢁꢁ
ꢁꢁ
(
1R,3S)-N -(2-Methoxyphenyl)-1,2,2-trimethyl-
1
15
N -(2,4,6-trimethylbenzyl)-1,3-cyclopentanediamine
10). Prepared from monoarylated diamine (0.30
mg, 1.21 mmol), triethylamine (0.20 mL, 1.45 mmol,
.2 equiv) and 2,4,6-trimethylbenzyl chloride (0.22
g, 1.33 mmol) in acetonitrile (10 mL). The crude
product was purified via column chromatography
3
(
= 53.46 (s, 1N, N ) ppm. MS (ESI, +3 kV): m/z (%)
+
= 351 ([M+H] , 100%). HRMS (ESI): Calcd. for
2
0
1
C24H35N2: 351.2808, found: 351.2800. [α] D = +71
(c = 0.5, CH2Cl2).
(
1
7
CH2Cl2/MeOH, 95:5), and the secondary diamine
0 was obtained as yellow oil (0.32 g, 0.85 mmol,
3
1
(1R,3S)-N -Mesityl-1,2,2-trimethyl-N -(2,4,6-tri-
methylbenzyl)-1,3-cyclopentanediamine (12). Prep-
ared from monoarylated diamine (0.30 g, 1.15
mmol), triethylamine (0.19 mL, 1.38 mmol) and
2,4,6-trimethylbenzyl chloride (0.21 g, 1.27 mmol)
in acetonitrile (10 mL). The crude product was pu-
rified via column chromatography (CH2Cl2/MeOH,
95:5), and the secondary diamine 12 was obtained
1
1%). H NMR (500 MHz, CDCl3) δ = 6.95 (s, 2H,
ꢁꢁ
ꢁꢁ
ꢁ
H-3 , H-5 ), 6.91 – 6.87 (m, 1H, H-5 ), 6.77 (dd,
ꢁ
J = 7.9, 1.3 Hz, 1H, H-6 ), 6.69 (dd, J = 8.0, 1.2
ꢁ
ꢁ
Hz, 1H, H-3 ), 6.63 (td, J = 7.7, 1.5 Hz, 1H, H-4 ),
ꢁ
ꢁꢁ
3
4
1
4
2
(
1
(
.84 (d, J = 10.6 Hz, 1H, H-1 ), 3.76 (dd, J = 8.4,
ꢁꢁ
.5 Hz, 1H, H-3), 3.72 (s, 3H, 2 -OCH3), 3.70 (s,
ꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁ
H, H-1 ) 2.46 (s, 6H, 2 -CH3, 6 -CH3), 2.36 (s, 3H,
-CH3), 2.20 – 2.11 (m, 2H, H-4), 1.76 – 1.64 (m,
H, H-5), 1.33 (s, 3H, H-8), 1.09 (s, 3H, H-6), 0.97
ꢁ
ꢁ
1
as colorless oil (0.28 g, 0.11 mmol, 61%). H NMR
ꢁ
ꢁ
ꢁꢁ
(500 MHz, CDCl3) δ = 6.94 (s, 2H, H-3 , H-5 ), 6.84
1
3
ꢁ
ꢁ
ꢁꢁꢁ
s, 3H, H-7) ppm. C NMR (126 MHz, CDCl3) δ =
(s, 2H, H-3 , H-5 ), 3.89 (d, J = 10.9 Hz, 1H, H-1 ),
ꢁ
ꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁꢁ
46.9 (C-2 ), 138.8 (C-1 ), 137.2 (C-2 , C-6 ), 136.3
3.75 (d, J = 10.9 Hz, 1H, H-1 ), 3.58 (dd, J = 8.1,
ꢁꢁ
ꢁꢁ
ꢁꢁ
ꢁ
ꢁꢁ ꢁꢁ
C-4 ), 134.3 (C-1 ), 129.0 (C-3 , C-5 ), 121.2 (C-5 ),
15.1 (C-4 ), 109.5 (C- 6 , C-3 ), 65.0 (C-1), 61.9 (C-3),
5.2 (2 -OCH3), 48.6 (C-2), 40.5 (C-1 ), 32.8 (C-4),
0.3 (C-5), 25.5 (C-6), 21.0 (4 -CH3), 20.2 (C-8), 19.5
6.3 Hz, 1H, H-3), 2.48 (s, 6H, 2 -CH3, 6 -CH3), 2.36
ꢁ
ꢁ
ꢁ
ꢁꢁ ꢁ
(s, 3H, 4 -CH3), 2.29 (s, 3H, 4 -CH3), 2.28 (s, 6H,
1
5
3
ꢁ
ꢁꢁꢁ
ꢁ
ꢁ
2 -CH3, 6 -CH3), 2.18–2.01 (m, 2H, H-4, H-5), 1.67
(dqd, J = 12.0, 10.1, 5.8 Hz, 2H, H-4, H-5), 1.32 (s,
3H, H-8), 1.12 (s, 3H, H-6), 1.10 (s, 3H, H-7) ppm.
ꢁꢁ
ꢁ
ꢁ
ꢁꢁ
15
(
(
2 -CH3), 19.4 (6 -CH3), 17.0 (C-7) ppm. N NMR
1
13
ꢁ
51 MHz, CDCl3) δ = 74.1 (bs, 1N, N ), 53.5 (bs, 1N,
C NMR (126 MHz, CDCl3) δ = 143.8 (C-1 ), 136.9
3
ꢁꢁ ꢁꢁ ꢁꢁ ꢁꢁ ꢁ
N ) ppm. IR (ATR) ν = 3424, 2958, 2865, 1596, 1517,
(C-1 ), 136.3 (C-2 , C-6 ), 134.5 (C-4 ), 129.8 (C-3 ,
ꢁ ꢁ ꢁꢁ ꢁꢁ ꢁ
C-5 ), 129.3 (C-4 ), 129.1 (C-3 , C-5 ), 127.7 (C-2 ,
1
453, 1370, 1336, 1252, 1223, 1174, 1110, 1027, 850,
−1
ꢁ
ꢁꢁꢁ
7
32 cm . MS (ESI, +3 kV): m/z (%) = 381 ([M +
C-6 ), 65.8 (C-3), 64.4 (C-1), 48.1 (C-2), 40.9 (C-1 ),
+
ꢁ
H] , 100%). HRMS (ESI): Calcd. for C25H37N2O:
3
CH2Cl2).
34.0 (C-5), 30.0 (C-4), 23.8 (C-7), 21.0 (4 -CH3), 20.6
81.2913, found: 381.2906. [α]20D = +12 (c = 0.49,
ꢁ
ꢁ
ꢁ
ꢁ
(4 -CH3), 20.5 (C-8), 19.6 (2 -CH3, 6 -CH3), 19.5
ꢁꢁ ꢁꢁ
15
(2 -CH3, 6 -CH3), 16.9 (C-6) ppm. N NMR (51
3
1
MHz, CDCl3) δ = 67.46 (1N, N ), 54.62 (1N, N )
ppm. IR (ATR) ν = 3379, 2962, 2864, 1610, 1583,
1477, 1368, 1297, 1226, 1156, 1121, 1085, 1023,
1
(
1R,3S)-1,2,2-Trimethyl-N -(2,4,6-
3
−1
trimethylbenzyl)-N -phenyl-1,3-cyclopentanediamine
11). Prepared from monoarylated diamine (0.30 g,
1004, 846, 737, 717, 686, 564 cm . MS (ESI, +3
+
(
1
2
kV): m/z (%) = 393 ([M + H] , 100%). HRMS (ESI):
.37 mmol), triethylamine (0.23 mL, 1.65 mmol) and
,4,6-trimethylbenzyl chloride (0.26 g, 1.51 mmol)
Calcd. for C27H41N2: 393.3268, found: 393.3270.
2
0
[α] D = −1 (c = 0.48, CH2Cl2).
Heteroatom Chemistry DOI 10.1002/hc

Diastereoselective Synthesis of P-Chirogenic (1R)-1,8,8-trimethyl-2,4-diaza-3-phosphabicyclo[3.2.1]octane 3-oxides 129
1
ꢁꢁ ꢁꢁ ꢁ ꢁꢁ ꢁꢁ
(C-3 , C-5 ), 130.5 (C-4 ), 129.3 (C-2 , C-6 ), 129.1
(
1R,3S)-1,2,2-Trimethyl-N -(2,4,6-
3
ꢁꢁ ꢁꢁ ꢁꢁ ꢁ ꢁ
(C-4 ), 128.7 (C-3 , C-5 ), 127.8 (C-6 ), 127.0 (C-5 ),
trimethylbenzyl)-N -(naphthalen-1-yl)-1,3-
ꢁ ꢁ
116.2 (C-1 ), 110.7 (C-3 ), 64.4 (C- 1), 62.0 (C-3),
cyclopentanediamine
(13). Prepared
from
ꢁꢁ
48.2 (C-2), 40.7 (C-1 ), 33.4 (C-5), 30.1 (C-4), 24.8
monoarylated diamine (0.30 g, 1.12 mmol),
triethylamine (0.19 mL, 1.34 mmol), and 2,4,6-
trimethylbenzyl chloride (0.21 g, 1.23 mmol) in
acetonitrile (10 mL). The crude product was purified
via column chromatography (CH2Cl2/MeOH, 95:5),
and the secondary diamine 13 was obtained as
ꢁ
ꢁ
ꢁꢁ
ꢁꢁ
(4 -CH3), 21.0 (C-8), 19.9 (2 -CH3, 6 -CH3), 19.5
(C-7), 16.9 (C-6) ppm. IR (ATR) ν = 3424, 2958,
2860, 1600, 1578, 1508, 1435, 1317, 849, 768, 739,
−1
702 cm . MS (ESI, +3 kV): m/z (%) = 427 ([M
+
+ H] , 100%). HRMS (ESI): Calcd. for C30H39N2:
1
20
brown oil (0.24 g, 0.61 mmol, 54%). H NMR (500
427.3116, found: 427.3113. [α] D = −50 (c = 0.48,
ꢁ
MHz, CDCl3) δ = 7.80 (d, J = 8.0 Hz, 1H, H-8 ),
CH2Cl2).
ꢁ
7
1
.48–7.43 (m, 1H, H-5 ), 7.39 (dd, J = 9.9, 5.9 Hz,
ꢁ
ꢁ
3
H, H-4 ), 7.29 (d, J = 8.4 Hz, 1H, H-7 ), 7.18 (d, J
(1R,3S)-N -(2-Isopropylphenyl)-1,2,2-trimethyl-
N -(2,4,6-trimethylbenzyl)-1,3-cyclopentanediamine
ꢁ
ꢁ
1
=
8.1 Hz, 1H, H-6 ), 7.11 (t, J = 7.5 Hz, 1H, H-3 ),
ꢁꢁ
ꢁꢁ
7
.01 (s, 2H, H-3 , H-5 ), 6.64 (d, J = 7.6 Hz, 1H,
(15). Prepared from monoarylated diamine (0.30
g, 1.15 mmol), triethylamine (0.19 mL, 1.40 mmol),
and 2,4,6-trimethylbenzyl chloride (0.21 g, 1.27
mmol) in acetonitrile (10 mL). The crude prod-
uct was purified via column chromatography
(CH2Cl2/MeOH, 95:5), and the secondary diamine
15 was obtained as yellow oil (0.23 g, 0.59 mmol,
ꢁ
ꢁꢁꢁ
H-2 ), 3.91 (d, J = 10.6 Hz, 2H, H-1 ), 3.79 (d, J =
ꢁꢁ
1
6
1
0.8 Hz, 1H, H-3), 2.48 (s, 3H, 4 -CH3), 2.41 (d, J =
ꢁꢁ
ꢁꢁ
.4 Hz, 6H, 2 -CH3, 6 -CH3), 2.23-2.09 (m, 2H, H-4),
.91–1.75 (m, 2H, H-5), 1.40 (s, 3H, H-8), 1.18 (s, 3H,
1
3
H-7), 1.09 (s, 3H, H-6) ppm. C NMR (126 MHz,
ꢁ
ꢁꢁ
ꢁ
ꢁꢁ
ꢁ
CDCl3) δ = 143.9 (C-1 ), 137.6 (C-4 ), 136.8 (C-1 ),
ꢁꢁ
ꢁꢁ
1
1
1
(
(
3
2
36.5 (C-2 ), 134.8 (C-6 ), 134.0 (C-4 a), 129.5 (C-5 ),
51%). H NMR (500 MHz, CDCl3) δ = 7.15–7.09 (m,
ꢁꢁ
ꢁꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ ꢁ ꢁꢁ ꢁꢁ
2H, H-3 , H-5 ), 6.95 (s, 2H, H-3 , H- 5 ), 6.69 (dd,
28.8 (C-3 , C-5 ), 128.3 (C-3 ), 126.9 (C-6 ), 125.5
ꢁ
ꢁ
ꢁ
ꢁ
3
C-7 ), 123.9 (C-8 ), 121.1 (C-8 a), 115.4 (C-4 ), 103.0
J = 7.8, 5.1 Hz, 2H, H-4 , H-6 ), 5.20 (br s, 1H, N H),
ꢁꢁ
ꢁꢁ ꢁ
C-2 ), 66.0 (C-1), 62.9 (C-3), 49.2 (C-2), 40.0 (C-1 ),
1.9 (C-5), 30.2 (C-4), 26.5 (4 -CH3), 21.1 (C-11),
0.0 (2 -CH3), 19.7 (6 -CH3), 18.8 (C-7), 17.0 (C-6)
ppm. IR (ATR) ν = 3326, 2958, 2867, 1579, 1524,
482, 1405, 1385, 1371, 1230, 1074, 849, 764, 720
3.92–3.63 (m, 4H, H-1 , H-3, 2 -CH), 2.44 (s, 6H,
ꢁꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁ
2 -CH3, 6 -CH3), 2.38 (s, 3H, 4 -CH3), 2.23 (ddd, J =
ꢁꢁ
ꢁꢁ
18.2, 13.7, 10.5 Hz, 2H, H-5), 1.78–1.68 (m, 2H, H-4),
ꢁ
1.35 (s, 3H, H-8), 1.16 (d, J = 6.7 Hz, 3H, 2 -C-CH3),
ꢁ
1
1.13 (s, J = 5.9 Hz, 3H, 2 -C-CH3), 1.01 (s, 3H, H-7),
−1
+
13
cm . MS (ESI, +3 kV): m/z (%) = 400 ([M + H] ,
0.93 (s, 3H, H-6) ppm. C NMR (126 MHz, CDCl3) δ
ꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁ
1
0%). HRMS (ESI): Calcd. for C28H37N2: 400.2878,
= 146.3 (C-1 ), 136.6 (C-4 ), 136.3 (C-2 ), 134.1 (C- ),
2
0
ꢁꢁ ꢁꢁ ꢁꢁ ꢁ
found: 400.3000. [α] D = −12 (c = 0.47, CH2Cl2).
132.1 (C-2 ), 129.2 (C-3 ), 126.6 (C-5 ), 125.5 (C-3 ),
ꢁ ꢁ ꢁ
24.9 (C-5 ), 115.7 (C-4 ), 109.7 (C-6 ), 65.5 (C-1),
1
6
ꢁꢁ
2.2 (C-3), 49.0 (C-2), 40.2 (C-1 ), 32.5 (C-5), 30.6
(2 - CH), 27.3 (2 -CH-CH3), 26.0 (2 -CH-CH3), 22.1
(4 -CH3), 21.9 (C-8), 21.0 (2 -CH3), 19.5 (6 -CH3),
18.8 (C-6), 17.1 (C-7) ppm. IR (ATR) ν = 3370, 2963,
2870, 1601, 1579, 1508, 1453, 1386, 1369, 1312,
3
ꢁ
ꢁ
ꢁ
ꢁ
(
1R,3S)-N -([1,1 -Biphenyl]-2-yl)-1,2,2-trimethyl-
N -(2,4,6-trimethylbenzyl)-1,3-cyclopentanediamine
14). Prepared from monoarylated diamine (0.30 g,
.02 mmol), triethylamine (0.17 mL, 1.22 mmol) and
,4,6-trimethylbenzyl chloride (0.19 g, 1.12 mmol)
in acetonitrile (10 mL). The crude product was pu-
rified via column chromatography (CH2Cl2/MeOH,
5:5), and the secondary diamine 14 was obtained
1
ꢁꢁ
ꢁꢁ
ꢁꢁ
(
1
2
−1
1258, 1219, 1160, 1084, 1037, 850, 739 cm . MS
+
(ESI, +3 kV): m/z (%) = 393 ([M + H] , 100%).
HRMS (ESI): Calcd. for C27H41N2: 393.3280, found:
2
0
9
393.3270. [α] D = −16 (c = 0.48, CH2Cl2).
1
as yellow oil (0.25 g, 0.58 mmol, 57%). H NMR
ꢁ
ꢁꢁ
(
7
500 MHz, CDCl3) δ = 7.46–7.43 (m, 2H, H-6 , H-4 ),
General Procedure for the Preparation of Pentava-
lent Nitrogen-Substituted SPOs 16–24. A solution of
the suitable diamine (1 equiv) in toluene was added
to the mixture of phosphorus trichloride (1.1 equiv)
and triethylamine (2.5 equiv) in toluene at −60°C
over 30 min. The solution was warmed to room tem-
perature. After 2 h, the mixture was filtered through
MgSO4 and the filtrate was again cooled to −60°C.
Triethylamine (1.1 equiv) and water (1 equiv) were
added, and the cooling bath was removed. After
1 h, the reaction mixture was filtered again through
MgSO4 and the filtrate was concentrated under
ꢁꢁ ꢁꢁ ꢁ ꢁ
.36–7.28 (m, 4H, H-3 , H-5 , H-3 , H-4 ), 7.17 (dd,
ꢁ
ꢁꢁ
ꢁꢁ
J = 7.4, 1.6 Hz, 1H, H-5 ), 6.91 (s, 2H, H-3 , H-5 ),
ꢁꢁ
ꢁꢁ
6
(
3
2
.81 (ddd, J = 8.4, 6.2, 2.6 Hz, 2H, H-2 , H-6 ), 4.49
ꢁ
ꢁꢁꢁ
br s, 1H, H-N3), 3.79 (d, J = 10.7 Hz, 2H, H-1 ),
ꢁꢁ
.62 (d, J = 10.7 Hz, 1H, H-3), 2.39 (s, 3H, 4 -CH3),
ꢁꢁ
ꢁꢁ
.35 (s, 6H, 2 -CH3, 6 -CH3), 2.18–2.11 (m, 1H,
H-4), 2.07–1.99 (m, 1H, H-5), 1.73 (ddd, J = 13.4,
.7, 7.4 Hz, 1H, H-5), 1.56–1.47 (m, 1H, H-4), 1.33
s, 3H, H-8), 1.08 (s, 3H, H-7), 0.85 (s, 3H, H-6)
9
(
1
3
ꢁ
ppm. C NMR (126 MHz, CDCl3) δ = 145.5 (C-2 ),
ꢁꢁ ꢁꢁ ꢁꢁ ꢁꢁ
1
39.8 (C-1 ), 137.1 (C-4 ), 136.2 (C- 2 , C-6 ), 134.2
Heteroatom Chemistry DOI 10.1002/hc

130 Uzarewicz-Baig and Wilhelm
ꢁ
ꢁ
ꢁ
ꢁꢁ
ꢁ
ꢁ
reduced pressure. The method of filtration for each
compounds are given below.
(C- 1 ), 130.1 (C-2 ), 130.0 (C-2 ), 129.1 (C-3 , C-5
ꢁꢁ
ꢁꢁ
ꢁ
ꢁꢁ
C-3 , C-5 ), 128.6 (C-6 ), 128.5 (C-6 ), 69.7 (C-1), 65.2
ꢁꢁ ꢁꢁ
(
C-5), 47.1 (C-8), 43.1 (C-1 ), 42.3 (C-1 ), 35.4 (C-7),
ꢁ ꢁꢁ
28.0 (C-6), 24.9 (C-10), 21.0 (4 -CH3), 20.9 (4 -CH3),
(1R,3S,5S)-2,4-Dibenzyl-1,8,8-trimethyl-2,4-
ꢁ ꢁꢁ ꢁ ꢁꢁ
20.4 (2 -CH3), 20.0 (2 -CH3), 18.9 (6 -CH3, 6 -CH3),
diaza-3-phosphabicyclo[3.2.1]octane 3-oxide (16).
Prepared from diamine 7 (0.60 g, 1.86 mmol),
phosphorus trichloride (0.18 mL, 2.05 mmol), and
triethylamine (0.66 mL, 4.65 mmol) in toluene
3
1
18.0 (C-9), 17.9 (C-11) ppm. P NMR (202 MHz,
CDCl3) δ = 9.6 ppm. IR (ATR) ν = 2949, 2379, 1610,
1468, 1370, 1305, 1257, 1194, 1164, 1115, 1017,
−1
(10 mL), and water (34.00 μL, 1.86 mmol) and
894, 841, 747, 531 cm . MS (ESI, +3 kV): m/z (%)
+
+
triethylamine (0.28 mL, 2.05 mmol) after filtration.
After evaporation, product 16 was obtained as a
yellow solid (0.68 g, 1.75 mmol, 94%). mp: 118.3°C.
= 453 ([M + H] , 100%); 475 ([M + Na] , 100%).
HRMS (ESI): Calcd. for C28H42N2OP: 453.3032,
found: 453.3035; C28H41N2ONaP: 475.2853, found:
1
20
H NMR (500 MHz, CDCl3) δ = 7.44–7.13 (m, 10H,
475.2854. [α] D = −12 (c = 0.50, EtOH).
ArH), 7.30 (d, J = 619.9 Hz, 1H, H-3, P-H), 4.69 (dd,
ꢁꢁ
J = 12.4, 4.9 Hz, 1H, H-1 ), 4.47 (dd, J = 15.4, 10.3
(1R,3R,5S)-1,8,8-Trimethyl-4-(o-tolyl)-
2-(2,4,6-trimethylbenzyl)-2,4-diaza-3-
ꢁꢁ
ꢁꢁ
Hz, 1H, H-1 ), 4.23 (dd, J = 17.3, 10.5 Hz, 1H, H-1 ,
ꢁꢁ
NCH2), and 4.08 (dd, J = 15.4, 7.3 Hz, 1H, H-1 ,
NCH2), 2.86 (dd, J = 15.6, 6.7 Hz, 1H, H- 5), 2.22
phosphabicyclo[3.2.1]octane 3-oxide (18). Prepared
from diamine 9 (0.26 g, 0.72 mmol), phosphorus
trichloride (0.07 mL, 0.79 mmol), triethylamine
(0.25 mL, 1.80 mmol) in toluene (10 mL), and water
(13.00 μL, 0.72 mmol) and triethylamine (0.11
mL, 0.79 mmol) after filtration. After evaporation,
product 18 was obtained as a white solid (0.26 g,
(
2
ddd, J = 13.9, 10.1, 5.8 Hz, 1H, H-6,), 1.99–1.86 (m,
H, H-6, H-7), 1.68 (ddd, J = 13.8, 11.0, 5.5 Hz, 1H,
H-7), 1.04 (s, 6H, H-11, H-9, 2×CH3), 0.78 (s, 3H,
1
3
H-10, CH3) ppm. C NMR (126 MHz, CDCl3) δ =
ꢁ ꢁꢁ ꢁ ꢁ
41.2 (C-1 ), 138.1 (C-1 ), 128.6 (C-3 , C-5 ), 128.5
1
ꢁ
ꢁ
ꢁꢁ
ꢁ
ꢁ
ꢁꢁ
ꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁ
1
(
C-3 , C-5 ), 128.4 (C-2 , C-6 ), 127.4 (C-2 , C-6 ),
0.64 mmol, 89%). mp: 170.5 °C. HNMR (500 MHz,
ꢁꢁ
ꢁ
ꢁ
ꢁ
1
5
27.0 (C-4 ), 126.7 (C-4 ), 71.4 (C-1 ), 67.7 (C-1 ),
0.1 (C-1), 47.3 (C-5), 45.6 (C-8), 36.6 (C-7), 29.2
CDCl3) δ = 7.15–7.04 (m, 3H, H-4 , H-5 , H-6 ), 6.31
ꢁ
(d, J 637.2 Hz, P-H), 6.91 (s, 1H, H-3 ), 6.79 (s, 2H,
3
1
ꢁꢁ
ꢁꢁ
ꢁꢁ
(
C-6), 24.4 (C-9), 19.5 (C-11), 18.4 (C-10) ppm.
P
H-3 , H-5 ), 4.33 (dd, J = 11.7, 3.3 Hz, 1H, H-1 ),
ꢁꢁ
NMR (202 MHz, CDCl3) δ = 10.1 ppm. IR (ATR)
4.21–4.10 (m, 1H, H-1 ), 3.08 (dd, J = 20.4, 5.5
Hz, 1H, H-5), 2.72 (ddd, J = 14.2, 9.7, 4.9 Hz, 1H,
H-6), 2.59 (ddd, J = 14.0, 9.7, 4.1 Hz, 1H, H-7), 2.48
ν = 3429, 3056, 3022, 2949, 2336, 1604, 1493, 1453,
1
373, 1201, 1113, 1092, 1066, 1027, 908, 876, 739,
−1
ꢁꢁ ꢁꢁ ꢁ
(s, 6H, 2 -CH3, 6 -CH3), 2.31 (s, 3H, 2 -CH3), 2.20
6
=
98, 520, 481, 454 cm . MS (ESI, +3 kV): m/z (%)
ꢁꢁ
391 [M + Na]+, 100%). HRMS (ESI): Calcd. for
(s, 3H, 4 -CH3), 2.15–1.91 (m, 2H, H-6, H-7), 1.42 (s,
3H, H-9), 1.37 (s, 3H, H-11), 0.97 (s, 3H, H-10) ppm.
2
0
C22H29N2ONaP: 391.1930, found: 391.1915. [α]
D
1
3
ꢁ
=
+19 (c = 0.60, EtOH).
C NMR (126 MHz, CDCl3) δ = 141.8 (C-1 ), 139.0
ꢁ ꢁꢁ ꢁ ꢁꢁ ꢁꢁ
(
C-2 ), 137.4 (C-4 ), 131.1 (C-3 ), 129.1 (C-3 , C-5 ),
ꢁꢁ
ꢁꢁ
ꢁꢁ
ꢁ
ꢁ
(1R,3S,5S)-1,8,8-Trimethyl-2,4-
128.7 (C-1 ), 128.6 (C-2 , C-6 ), 126.9 (C-4 , C-5 ),
ꢁ
bis(2,4,6-trimethylbenzyl)-2,4-diaza-3-
126.7 (C-6 ), 73.4 (C-11), 70.2 (C-5), 47.4 (C-8), 42.2
ꢁ
ꢁ
ꢁ
ꢁ
phosphabicyclo[3.2.1]octane 3-oxide (17). Prepared
from diamine 8 (0.20 g, 0.49 mmol), phosphorus
trichloride (0.05 mL, 0.54 mmol), and triethylamine
(C-1 ), 35.4 (C-7), 30.0 (C-6), 24.9 (4 -CH3), 20.9
ꢁꢁ
ꢁꢁ
ꢁ
(6 -CH3), 20.5 (4 -CH3), 20.2 (C-11), 19.4 (2 -CH3),
3
1
18.2 (C-9), 18.1 (C-10) ppm. P NMR (202 MHz,
CDCl3) δ = 3.9 ppm. IR (ATR) ν = 3414, 2953,
2409, 1610, 1488, 1458, 1389, 1345, 1207, 1192,
1154, 1110, 1080, 1018, 976, 890, 852, 759, 724, 544,
(0.17 mL, 1.23 mmol) in toluene (10 mL), and
water (8.90 μL, 0.49 mmol) and triethylamine (0.08
mL, 0.54 mmol) after filtration. After evaporation,
product 17 was obtained as a yellow solid (0.16 g,
−1
454 cm . MS (ESI, +3 kV): m/z (%) = 411 ([M +
1
+
+
0
.35 mmol, 73%). mp: 99.7°C. H NMR (500 MHz,
H] , 58%); 433 ([M + Na] , 100%). HRMS (ESI):
ꢁ
ꢁ
ꢁꢁ
CDCl3) δ = 6.83 (d, J = 7.4 Hz, 4H, H-3 , H-5 , H-3 ,
Calcd. for C25H36N2OP: 411.2565, found: 411.2563;
ꢁꢁ
20
H-5 ), 6.32 (d, J = 629.4 Hz, 1H, P-H), 4.28 (dd,
C25H35N2ONaP: 433.2385, found: 433.2391. [α]
= +73 (c = 0.52, EtOH).
D
ꢁꢁ
J = 11.5, 3.0 Hz, 1H, H-1 ), 4.11 (dt, J = 21.3, 9.4
ꢁꢁ
ꢁꢁ
Hz, 2H, H-1 , H-1 ), 3.96 (dd, J = 14.2, 7.4 Hz, 1H,
ꢁꢁ
ꢁ
H-1 ), 2.59–2.50 (m, 1H, H-5), 2.46 (s, 6H, 4 -CH3,
(1R,3R,5S)-4-(2-Methoxyphenyl)-1,8,8-
trimethyl-2-(2,4,6-trimethylbenzyl)-2,4-diaza-3-
phosphabicyclo[3.2.1]octane 3-oxide (19). Prepared
from diamine 10 (0.15 g, 0.39 mmol), phosphorus
trichloride (0.04 mL, 0.43 mmol), triethylamine
(0.14 mL, 0.98 mmol) in toluene (10 mL), and
ꢁ
ꢁ
4
2
-CH3), 2.34 (m, 1H, H-7), 2.25 (d, J = 3.1 Hz, 12H,
ꢁ
ꢁ
ꢁꢁ
ꢁꢁ
-CH3, 6 -CH3, 2 -CH3, 6 -CH3), 2.00–1.81 (m, 3H,
H-6, H-7, H-6), 1.32 (s, 3H, H-9), 0.92 (s, 3H, H-11),
1
3
0
.80 (s, 3H, H-10) ppm. C NMR (126 MHz, CDCl3)
ꢁ
ꢁꢁ
ꢁ
δ = 139.1 (C-4 ), 138.2 (C-4 ), 137.5 (C-1 ), 136.9
Heteroatom Chemistry DOI 10.1002/hc

Diastereoselective Synthesis of P-Chirogenic (1R)-1,8,8-trimethyl-2,4-diaza-3-phosphabicyclo[3.2.1]octane 3-oxides 131
−
1
water (7.00 μL, 0.39 mmol) and triethylamine (0.06
mL, 0.43 mmol) after filtration. After evaporation,
product 19 was obtained as yellow oil (0.16 g, 0.38
mmol, 97%). H NMR (500 MHz, CDCl3) δ = 6.86 (s,
464 cm . MS (ESI, +3 kV): m/z (%) = 397 ([M +
+
+
H] , 50%); 419 ([M + Na] , 100%). HRMS (ESI):
Calcd. for C H N OP: 397.2409, found: 397.2408;
2
4
34
2
1
20
24 33 2 D
C H N ONaP: 419.2228, found: 419.2232. [α]
= +39 (c = 0.46, EtOH).
ꢁ
ꢁ
ꢁꢁ
ꢁ
2
7
6
H, 2 -CH3, 6 -CH3), 6.80 (m, 1H, H-3 ), 6.69 (d, J =
ꢁ
ꢁ
.7 Hz, 1H, H-6 ), 6.60 (dd, J = 7.9, 1.2 Hz, 1H, H-4 ),
ꢁ
.55 (d, J = 7.1 Hz, 1H, H-5 ), 6.36 (d, J = 645.2
ꢁꢁ
ꢁ
Hz, 1H, PH), 3.81–3.58 (m, 5H, H-1 , 2 -O-CH3),
4-Mesityl-1,8,8-trimethyl-2-
(2,4,6-trimethylbenzyl)-2,4-diaza-3-
ꢁꢁ
ꢁꢁ
2
2
.52–2.44 (m, 1H, H-5), 2.38 (s, 6H, 2 -CH3, 6 -CH3),
ꢁ
ꢁ
.28 (s, 3H, 4 -CH3), 2.09 (dd, J = 25.7, 12.1 Hz, 2H,
phosphabicyclo[3.2.1]octane 3-oxide (21a/21b).
Prepared from diamine 12 (0.35 g, 0.89 mmol),
phosphorus trichloride (0.09 mL, 0.98 mmol),
triethylamine (0.31 mL, 2.22 mmol) in toluene (10
mL), and water (16.00 μL, 0.89 mmol) and triethy-
lamine (0.14 mL, 1.00 mmol) after filtration. After
evaporation, product 21 was obtained as a yellow
solid of two diastereoisomers, which were separated
by column chromatography (n-hexane/EtOAc, 7:3).
(1R,3R,5S)-4-Mesityl-1,8,8-trimethyl-
H-7, H-6), 1.62 (dd, J = 19.9, 10.9 Hz, 2H, H-7, H-6),
1
.25 (s, 3H, H-9), 1.01 (s, 3H, H-11), 0.89 (s, 3H,
1
3
H-10) ppm. C NMR (126 MHz, CDCl3) δ = 146.8
ꢁ ꢁꢁ ꢁꢁ ꢁꢁ ꢁꢁ
C-2 ), 138.9 (C-4 ), 137.2 (C-1 ), 136.1 (C-2 , C-6 ),
(
ꢁ ꢁꢁ ꢁꢁ ꢁ
34.3(C-1 ), 128.9 (C-3 ), 128.1 (C-5 ), 125.3 (C-5 ),
1
1
6
3
6
ꢁ
ꢁ
ꢁ
21.3 (C-4 ), 115 (C-6 ), 109.4 (C-2 ), 64.9, (C-1),
1.8 (C-5), 55.1 (2 -OCH3), 48.6 (C-8), 40.5 (C-1 ),
2.8 (C-7), 30.2 (C-6), 25.4 (4 -CH3), 20.9 (2 -CH3,
ꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁ
ꢁ
1
ꢁ
-CH3), 19.5 (C-9), 19.3 (C-10), 16.9 (C-11) ppm.
P NMR (202 MHz, CDCl3) δ = 3.9 ppm. IR (ATR)
3
2-(2,4,6-trimethylbenzyl)-2,4-diaza-3-
phosphabicyclo[3.2.1]octane 3-oxide (21a). The
product was obtained as a yellow solid (0.14 g,
ν = 3424, 2958, 1599, 1515, 1455, 1371, 1224, 1113,
−1
1
=
029, 909, 850, 730 cm . MS (ESI, +3 kV): m/z (%)
+
+
1
427 ([M + H] , 62%); 449 ([M + Na] , 100%).
0.32 mmol, 36%). mp: 144.7°C. H NMR (500 MHz,
ꢁ
ꢁ
ꢁꢁ
HRMS (ESI): Calcd. for C25H36N2O2P: 427.2514,
found: 427.2525; C25H35N2O2NaP: 449.2334, found:
CDCl ) δ = 6.79 (t, J = 20.3 Hz, 4H, H-3 , H-5 , H-3 ,
3
ꢁꢁ
H-5 ), 6.62 (d, J = 627.9 Hz, 1H, P-H), 4.49 (dd,
2
0
ꢁꢁ
ꢁꢁ
4
49.2343. [α] D = +11 (c = 0.45, EtOH).
J = 12.8, 5.9 Hz, 1H, H-1 ), 4.29–4.12 (m, 1H, H-1 ),
3
.09 (dd, J = 17.9, 5.0 Hz, 1H, H-5), 2.67–2.60 (m,
ꢁ
(1R,3R,5S)-1,8,8-Trimethyl-2-(2,4,6-
2H, H-6, H-7), 2.54 (s, 3H, 4 -CH3), 2.47 (s, 6H,
ꢁ
ꢁ
ꢁꢁ
trimethylbenzyl)-4-phenyl-2,4-diaza-3-
2 -CH3, 6 -CH3), 2.26 (s, 3H, 4 -CH3), 2.20 (d, J = 9.3
ꢁꢁ
ꢁꢁ
phosphabicyclo[3.2.1]octane 3-oxide (20). Prepared
from diamine 11 (0.27 g, 0.77 mmol), phosphorus
trichloride (0.07 mL, 0.80 mmol), triethylamine
Hz, 6H, 2 -CH3, 6 -CH3), 2.09–2.01 (m, 1H, H-6),
1.91–1.85 (m, 1H, H-7), 1.37 (s, 3H, H-9), 1.29 (m,
1
3
3H, H-11), 0.94 (s, 3H, H-10) ppm. C NMR (126
ꢁ
ꢁꢁ
(0.27 mL, 1.94 mmol) in toluene (10 mL), and water
MHz, CDCl3) δ = 139.7 (C-1 ), 138.3 (C-4 ), 137.6
ꢁꢁ ꢁꢁ ꢁꢁ ꢁ
(14.00 μL, 0.78 mmol) and triethylamine (0.12
(C-1 ), 137.1 (C-6 ), 136.9 (C-1 ), 136.6 (C-6 ), 130.8
ꢁ ꢁ ꢁ ꢁꢁ ꢁꢁ
(C-3 , C-5 ), 130.5 (C-4 ), 129.9 (C-3 ), 129.2 (C-5 ),
mL, 0.86 mmol) after filtration. After evaporation,
ꢁꢁ
73.4 (C-5), 70.6 (C-1), 48.5 (C-8), 42.3 (C-1 ), 35.8
product 20 was obtained as a white solid (0.27
1
ꢁ ꢁꢁ
(C-6), 30.6 (C-7), 25.9 (4 -CH3), 22.1 (4 -CH3), 21.5
g, 0.68 mmol, 88%). mp: 154.3°C. H NMR (500
ꢁ
ꢁ
ꢁꢁ
ꢁꢁ ꢁꢁ ꢁ
(C-9), 20.9 (2 -CH3), 20.7 (6 -CH3), 20.7 (6 -CH3),
MHz, CDCl3) δ = 7.28–7.18 (m, 4H, H-2 , H-6 , H-3 ,
ꢁꢁ
ꢁ
ꢁ
ꢁ
31
H-5 ), 6.84 (s, 2H, H-3 , H-5 ), 6.37 (d, J = 649.9,
20.6 (2 -CH3), 18.9 (C-11), 18.8 (C-10) ppm.
P
ꢁ
ꢁ
1
4
H, P-H), 4.34 (dd, J = 11.7, 2.9 Hz, 1H, H-1 ),
NMR (202 MHz, CDCl3) δ = 1.9 ppm. IR (ATR) ν
ꢁꢁ
.23–4.11 (m, 1H, H-1 ), 3.63 (dd, J = 18.6, 6.0
= 3424, 2924, 2345, 2212, 1605, 1468, 1341, 1212,
−1
Hz, 1H, H-5), 2.73–2.64 (m, 1H, H-6), 2.49 (s, 6H,
1144, 1081, 1031, 968, 850, 728, 565 cm . MS (ESI,
ꢁꢁ
ꢁꢁ
+
2
3
-CH3, 6 -CH3), 2.45–2.36 (m, 2H, H-7), 2.25 (s,
H, 4 -CH3), 1.95–1.87 (m, 1H, H-6), 1.44 (s, 3H,
+3 kV): m/z (%) = 439 ([M + H] , 100%). HRMS
ꢁꢁ
(ESI): Calcd. for C27H40N2OP: 439.2878, found:
2
0
H-9), 1.24 (s, 3H, H-11), 1.06 (s, 3H, H-10) ppm.
439.2874. [α] D = +54 (c = 0.56, EtOH).
1
3
ꢁ
ꢁ
ꢁ
C NMR (126 MHz, CDCl3) δ = 146.1 (C-1 ), 139.1
(1R,3S,5S)-4-Mesityl-1,8,8-trimethyl-
ꢁꢁ
ꢁꢁ
ꢁ
(
(
(
(
(
C-4 ), 137.5 (C-1 ), 129.3 (C- 3 ), 129.1 (C-5 ), 128.3
C-3 , C-5 ), 125.4 (C-2 , C-6 ), 123.4 (C-4 ), 122.2
C-2 , C-6 ), 71.5 (C-5), 70.7 (C-1), 46.9 (C-8), 42.4
C-1 ), 35.4 (C-7), 30.5 (C-6), 24.7 (4 -CH3), 21.0
2-(2,4,6-trimethylbenzyl)-2,4-diaza-3-
phosphabicyclo[3.2.1]octane 3-oxide (21b). The
product was obtained as a white solid (0.06 g, 0.14
ꢁ
ꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁ
1
mmol, 16%). mp: 139.5°C. H NMR (500 MHz,
ꢁꢁ
ꢁꢁ
ꢁꢁ
ꢁꢁ
2 -CH3), 20.5 (6 -CH3), 19.4 (C-11), 18.0 (C-9, C-10)
CDCl3) δ = 6.79 (m, 4H, H-3, H-5, H-3 , H-5 ), 6.69
(d, J = 617.0 Hz, 1H, P-H), 4.28 (t, J = 10.7 Hz,
3
1
ppm. P NMR (202 MHz, CDCl3) δ = 3.9 ppm.
IR (ATR) ν = 3424, 2943, 2375, 1595, 1493, 1464,
ꢁꢁ
ꢁꢁ
1H, H-1 ), 4.14 (dd, J = 11.1, 7.1 Hz, 1H, H- 1 ),
3.19 (ddd, J = 11.2, 3.5, 1.9 Hz, 1H, H-5), 2.58–2.45
1
1
391, 1360, 1278, 1249, 1224, 1205, 1154, 1114,
087, 1058, 1016, 963, 889, 850, 747, 693, 524,
ꢁ
ꢁ
(m, 1H, H-6), 2.44 (s, 6H, 2 -CH3, 6 -CH3), 2.39
Heteroatom Chemistry DOI 10.1002/hc

132 Uzarewicz-Baig and Wilhelm
ꢁ
ꢁꢁ
(
2
s, 3H, 4 -CH3), 2.31 (s, 3H, 4 -CH3), 2.19 (s, 3H,
(1R,3R,5S)-1,8,8-Trimethyl-2-(2,4,6-
trimethylbenzyl)-4-([1,1 -biphenyl]-2-yl)-2,4-diaza-3-
ꢁꢁ
ꢁꢁ
ꢁ
-CH3), 2.18 (s, 3H, 6 -CH3), 2.13–2.08 (m, 1H,
H-7), 1.98–1.85 (m, 2H, H-6, H-7), 1.83 (s, 1H, H-10),
phosphabicyclo[3.2.1]octane 3-oxide (23). Prepared
from diamine 14 (0.15 g, 0.35 mmol), phosphorus
trichloride (0.03 mL, 0.34 mmol), triethylamine
(0.12 mL, 0.86 mmol) in toluene (10 mL), and
water (6.00 μL, 0.33 mmol) and triethylamine (0.05
mL, 0.36 mmol) after filtration. After evaporation,
product 23 was obtained as a yellow solid (0.16
1
3
1
.45 (s, 1H, H-9), 1.01 (s, 1H, H-11) ppm. C NMR
ꢁ
ꢁꢁ
(
1
1
126 MHz, CDCl3) δ = 139.9 (C-1 ), 139.1 (C-4 ),
ꢁꢁ ꢁꢁ ꢁꢁ ꢁ
37.9 (C-1 ), 136.9 (C- 2 ), 136.7 (C-6 ), 136.4 (C-4 ),
ꢁ
ꢁ
ꢁꢁ
ꢁꢁ
30.3 (C-3 ), 129.7 (C-5 ), 129.0 (C-3 , C-5 ), 127.8
ꢁ
ꢁ
(
4
C-2 ), 127.7 (C-6 ), 73.2 (C-5), 70.0 (C-1), 48.5 (C-8),
ꢁꢁ ꢁ
3.3 (C-1 ), 36.9 (C-6), 30.3 (C-7), 26.9 (4 -CH3), 21.0
ꢁꢁ
ꢁꢁ
ꢁꢁ
1
(
4 -CH3), 20.7 (C-11), 20.4 (2 -CH3), 20.0 (6 -CH3),
g, 0.34 mmol, 97%). mp: 139.1°C. H NMR (500
ꢁ
ꢁ
ꢁ
19.9 (6 -CH3), 19.6 (2 -CH3), 18.6 (C-9), 18.5 (C-10)
MHz, CDCl ) δ = 7.64 (d, J = 8.0 Hz, 1H, H-6 ),
3
3
1
ꢁꢁ
ꢁꢁ
ppm. P NMR (202 MHz, CDCl3) δ = −4.2 ppm.
IR (ATR) ν = 3424, 2924, 2345, 2212, 1605, 1468,
7.39–7.33 (m, 2H, H- 3 , H-5 ), 7.29–7.24 (m, 3H,
H-2 , H-4 , H-3 ), 7.21–7.16 (m, 3H, H-3 , H-4 , H-
ꢁꢁ
ꢁꢁ
ꢁꢁ
ꢁ
ꢁ
ꢁ
ꢁꢁ
ꢁꢁ
1341, 1212, 1144, 1081, 1031, 968, 850, 728, 565
5 ), 6.81 (s, 2H, H-3 , H-5 ), 6.23 (d, J = 642.7 Hz,
−1
ꢁꢁ
cm . MS (ESI, +3 kV): m/z (%) = 439 ([M +
1H, P-H), 4.26 (dd, J = 11.7, 3.7 Hz, 1H, H-1 ),
+
ꢁꢁ
H] , 100%). HRMS (ESI): Calcd. for C27H40N2OP:
4.06 (dd, J = 20.8, 11.7 Hz, 1H, H-1 ), 3.03–2.95
4
39.2878, found: 439.2872. [α]20D = +40 (c = 0.57,
(m, 1H, H-5), 2.59 (ddd, J = 14.0, 9.7, 4.4 Hz, 1H,
ꢁꢁ ꢁꢁ
3 3
H-6), 2.40 (s, 6H, 2 -CH , 6 -CH ), 2.26 (s, 3H,
EtOH).
ꢁꢁ
4
-CH3), 2.21 – 2.13 (m, 1H, H-7), 1.85 (dddd, J =
(
1R,3R,5S)-1,8,8-Trimethyl-2-(2,4,6-
15.9, 13.5, 11.9, 4.5 Hz, 2H, H-6, H-7), 1.28 (s, 3H,
H-9), 0.77 (s, 3H, H-11), 0.61 (s, 3H, H-10) ppm.
trimethylbenzyl)-4-(naphthalen-1-yl)-2,4-diaza-3-
phosphabicyclo[3.2.1]octane 3-oxide (22). Prepared
from diamine 13 (0.17 g, 0.42 mmol), phosphorus
trichloride (0.04 mL, 0.46 mmol), triethylamine
1
3
ꢁ
ꢁꢁ
C NMR (126 MHz, CDCl ) δ = 141.5 (C-2 ), 141.3
3
ꢁꢁ
ꢁꢁ
ꢁꢁ
(C-1 ), 140.8 (C-4 ), 139.0 (C- 1 ), 137.9 (C-2 ), 137.4
ꢁ
ꢁ
ꢁꢁ
ꢁꢁ
ꢁ
(C-6 ), 131.6 (C-3 ), 130.4 (C-5 ), 129.8 (C-4 ), 129.1
ꢁ ꢁ ꢁꢁ ꢁꢁ
(0.15 mL, 1.07 mmol) in toluene (10 mL), and
(C-2 ), 129.1 (C-6 ), 128.5 (C-3 ), 128.3 (C-5 ), 128.2
ꢁꢁ ꢁ ꢁ ꢁ
(C-4 ), 127.9 (C-6 ), 127.1 (C-5 ), 126.0 (C-1 ), 125.3
water (7.60 μL, 0.42 mmol) and triethylamine (0.06
mL, 0.43 mmol) after filtration. After evaporation,
product 22 was obtained as brown oil (0.16 g, 0.36
ꢁ
ꢁꢁ
(C-3 ), 74.0 (C-1), 70.0 (C-1 ), 47.3 (C-5), 42.5 (C-8),
35.7 (C-7), 29.3 (4 -CH ), 24.7 (C-6), 21.5 (C-11),
21.0 (2 -CH ), 20.5 (6 -CH ), 18.5 (C-9), 18.0 (C-10)
ꢁ
ꢁ
3
1
ꢁꢁ ꢁꢁ
mmol, 86 %). H NMR (500 MHz, CDCl3) δ = 8.29
3 3
ꢁ
ꢁ
31
(
1
1
s, 1H, H-8 ), 8.01 (s, 1H, H-5 ), 7.83 (d, J = 8.1 Hz,
ppm. P NMR (202 MHz, CDCl ) δ = 5.4 ppm. IR
3
ꢁ
ꢁ
H, H-6 ), 7.73 (d, J = 6.6 Hz, 1H, H-7 ), 7.48 (m,
(ATR) ν = 3444, 2933, 2399, 1473, 1345, 1193, 1153,
ꢁ
ꢁ
H, H-4 ), 7.31–7.26 (m, 1H, H-3 ), 7.22–7.19 (m, 1H,
1108, 1077, 1018, 976, 894, 850, 762, 749, 703, 559,
ꢁ
ꢁꢁ
ꢁꢁ
−1
H-2 ), 6.81 (s, 2H, H- 3 , H-5 ), 6.38 (d, J = 644.7 Hz,
528 cm . MS (ESI, +3 kV): m/z (%) = 473 ([M +
ꢁꢁ
+
+
1
(
2
2
H, P-H), 4.41 (d, J = 10.4 Hz, 1H, H-1 ), 4.29–4.20
H] , 24%); 495 ([M + Na] , 52%). HRMS (ESI):
ꢁꢁ
m, 1H, H-1 ), 3.27 (d, J = 19.6 Hz, 1H, H-5),
Calcd. for C H N OP: 473.2722, found: 473.2737;
3
0
38
2
ꢁ
ꢁ
ꢁ
20
.55 (s, 6H, 2 -CH3, 6 -CH3), 2.20 (s, 3H, 4 -CH3),
.01 (m, 4H, H-6, H-7), 1.66 (s, 3H, H-9), 1.50
30 37 2 D
C H N ONaP: 495.2541, found: 495.2559. [α]
= +41 (c = 0.45, EtOH).
1
3
(
s, 3H, H-11), 1.01 (s, 3H, H-10) ppm. C NMR (126
ꢁ
ꢁꢁ
MHz, CDCl3) δ = 139.1 (C-1 ), 138.8 (C-4 ), 137.2
(1R,3R,5S)-4-(2-Isopropylphenyl)-1,8,8-
ꢁꢁ
ꢁꢁ
ꢁꢁ
ꢁ
ꢁ
(
(
1
7
(
(
C-1 ), 135.0 (C-2 , C-6 ), 131.9 (C-4 a, C-8 a), 129.1
trimethyl-2-(2,4,6-trimethylbenzyl)-2,4-diaza-3-phos-
phabicyclo[3.2.1]octane 3-oxide (24). Prepared
from diamine 15 (0.15 g, 0.38 mmol), phosphorus
trichloride (0.04 mL, 0.46 mmol), triethylamine
(0.13 mL, 0.93 mmol) in toluene (10 mL), and
water (6.70 μL, 0.37 mmol) and triethylamine (0.06
mL, 0.43 mmol) after filtration. After evaporation,
product 24 was obtained as a brown solid (0.14
ꢁ ꢁꢁ ꢁꢁ ꢁ ꢁ
C-5 ), 128.8 (C-3 , C-5 ), 128.5 (C-3 ), 127.2 (C-6 ),
ꢁ ꢁ ꢁ ꢁ
26.1 (C-7 ), 125.0 (C-8 ), 125.7 (C-4 ), 122.9 (C-2 ),
ꢁꢁ
3.9 (C-5), 70.2 (C-1), 53.4 (C-8), 42.7 (C-1 ), 36.0
C-7), 29.7 (C-6), 24.9 (4 -CH3), 20.9 (C-11), 20.5
2 -CH3, 6 -CH3), 18.3 (C-9), 18.1 (C-10) ppm.
ꢁ
ꢁ
ꢁ
31
P
NMR (202 MHz, CDCl3) δ = 4.9 ppm. IR (ATR)
ν = 3429, 2949, 2390, 2218, 1725, 1610, 1592,
1
1
1
5
573, 1464, 1392, 1267, 1197, 1150, 1113, 1079,
g, 0.32 mmol, 84%). mp: 157.2°C. H NMR (500
ꢁ
ꢁ
ꢁ
052, 1014, 950, 885, 848, 796, 775, 726, 641, 571,
MHz, CDCl3) δ = 7.23–7.04 (m, 3H, H-3 , H-4 , H-5 ),
−
+
1
ꢁ
ꢁꢁ
ꢁꢁ
46, 519, 461, 429 cm . MS (ESI, +3 kV): m/z
6.81 (d, J = 33.2 Hz, 3H, H-6 , H-3 , H-5 ), 6.23 (d,
+
ꢁꢁ
(
%) = 447 ([M + H] , 81%); 469 ([M + Na] ,
J = 638.8 Hz, 1H, PH), 4.40–4.06 (m, 2H, H-1 ),
ꢁ
1
4
4
00%). HRMS (ESI): Calcd. for C28H36N2OP:
47.2565, found: 447.2574; C28H35N2ONaP:
69.2385, found: 469.2388. [α] D = +48 (c = 0.45,
3.45 (s, 1H, 2 -CH), 3.07 (dd, J = 20.7, 5.3 Hz, 1H,
ꢁꢁ
H-5), 2.81–2.53 (m, 2H, H-7), 2.47 (s, 6H, 2 -CH3,
2
0
ꢁꢁ
ꢁꢁ
6 -CH3), 2.19 (s, 3H, 4 -CH3), 1.96 (dd, J = 43.6,
32.4 Hz, 2H, H-6), 1.47–1.32 (m, 6H, H-9, H-11),
EtOH).
Heteroatom Chemistry DOI 10.1002/hc

Diastereoselective Synthesis of P-Chirogenic (1R)-1,8,8-trimethyl-2,4-diaza-3-phosphabicyclo[3.2.1]octane 3-oxides 133
ꢁ
1
.31–1.13 (m, 6H, 2× 2 -CH-CH3), 0.97 (s, 3H, H-10)
[12] Gudat, D. Recent Developments in the Chemistry of
N-Heterocyclic Phosphines; Springer-Verlag: Berlin,
2010.
1
3
ꢁ
ppm. C NMR (126 MHz, CDCl3) δ = 147.6 (C-1 ),
ꢁꢁ ꢁꢁ ꢁꢁ ꢁꢁ
1
(
1
(
2
(
1
5
1
1
5
=
39.9 (C-4 ), 138.9 (C-1 ), 137.5 (C-2 , C-6 ), 132.2
[
13] (a) Grabulosa, A. P-Stereogenic Ligands in Enan-
tioselective Catalysis; RSC: Cambridge, UK, 2010;
(b) Gavrilov, K. N.; Shiryaev, A. A.; Zheglov, S. V.;
Potapova, O. V.; Chuchelkin, I. V.; Novikov, I. M.;
Rastorguev, E. A.; Davankov, V. A. Tetrahedron:
Asymmetry 2013, 24, 409–417; (c) Brunel, J. M.; Con-
stantieux, T.; Buono, G. J Org Chem 1999, 64, 8940–
ꢁꢁ ꢁꢁ ꢁ ꢁ ꢁ
C-3 , C-5 ), 129.1 (C-6 ), 128.5 (C-2 ), 127.4 (C-4 ),
ꢁ ꢁ
26.5 (C-3 ), 126.3 (C-5 ), 74.5 (C-5), 70.0 (C-1), 53.4
ꢁ
ꢁꢁ
2 -C), 47.8 (C-8), 42.6 (C-1 ), 35.7 (C-6), 29.9 (C-7),
ꢁ ꢁ ꢁꢁ
6.6 (2 -C-CH3), 25.0 (2 -C-CH3), 24.5 (4 -CH3), 23.9
ꢁꢁ
ꢁꢁ
C-9), 20.9 (2 -CH3), 20.5 (6[ -CH3), 19.7 (C-10),
8.2 (C-11) ppm. 31P NMR (202 MHz, CDCl3) δ =
.4 ppm. IR (ATR) ν = 3438, 2958, 2384, 1612, 1582,
483, 1443, 1387, 1349, 1308, 1217, 1151, 1112,
079, 1055, 1016, 973, 890, 848, 754, 688, 548, 526,
8
942; (d) Gavrilov, K. N.; Bondarev, O. G.; Tsarev, V.
N.; Shiryaev, A. A.; Lyubimov, S. E.; Kucherenko, A.
S.; Davankov, V. A. Russ Chem Bull 2003, 52, 122–
1
25; (e) Barta, K.; H o¨ lscher, M.; Franci o` , G.; Leitner,
−
1
W. Eur J Org Chem 2009, 4102–4116; (f) Gavrilov,
K. N.; Tsarev, V. N.; Shiryaev, A. A.; Bondarev, O.
G.; Lyubimov, S. E.; Benetsky, E. B.; Korlyukov, A.
A.; Antipin, M. Y.; Davankov, V. A.; Gais, H.-J. Eur J
Inorg Chem 2004, 629–634; (g) Gavrilov, K. N.; Benet-
sky, E. B.; Grishina, T. B.; Zheglov, S. V.; Rastorguev,
E. A.; Petrovskii, P. V.; Macaev, F. Z.; Davankov, V.
A. Tetrahedron: Asymmetry 2007, 18, 2557–2564; (h)
Gavrilov, K. N.; Benetskiy, E. B.; Grishina, T. B.; Ras-
torguev, E. A.; Maksimova, M. G.; Zheglov, S. V.; Da-
vankov, V. A.; Sch a¨ ffner, B.; B o¨ rner, A.; Rosset, S.;
Bailat, G.; Alexakis, A. Eur J Org Chem 2009, 3923–
06, 473, 446, 407 cm . MS (ESI, +3 kV): m/z (%)
+
+
439 ([M + H] , 63%); 461 ([M + Na] , 100%).
HRMS (ESI): Calcd. for C27H40N2OP: 439.2878,
found: 439.2880; C27H39N2ONaP: 461.2698, found:
2
0
4
61.2700. [α] D = + 51 (c = 0.46, EtOH).
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