Synthesis of new sulfonium ylides bearing the chiral diazaphospholidine group as reagents for asymmetric cyclopropanation

Article abstract of DOI:10.1002/hc.21183

Sulfonium ylides derived from chiral N,N′-substituted (benzyl, isopropyl, neopentyl) phosphonamides were prepared by reacting appropriate chiral diamidophosphites with potassium hydride and chloromethyl methyl sulfide, and then with methyl iodide in the presence AgBF4 to give the corresponding sulfonium salts in high yields. One of them was analyzed by X-ray crystallography. The salts upon treatment with different bases (LithiumDiisopropylAmine, BuLi, K₂CO₃) were converted in situ into ylides, which were reacted with activated olefins to produce phosphonocyclopropanes as a mixture of two diastereoisomers with moderate-to-high diastereoselectivities.

Full text of DOI:10.1002/hc.21183

Heteroatom Chemistry
Volume 25, Number 6, 2014
Synthesis of New Sulfonium Ylides Bearing
the Chiral Diazaphospholidine Group as
Reagents for Asymmetric Cyclopropanation
Krzysztof Owsianik,1 Wanda Wieczorek,2 Agnieszka Balin´ska,3
and Marian Mikołajczyk1
1Department of Heteroorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish
Academy of Sciences, 90-363 Ło´dz´, Poland
2Institute of General and Ecological Chemistry, Technical University of Ło´dz´, 90-924 Ło´dz´, Poland
3Institute of Chemistry and Environmental Protection, Jan Długosz Academy, 42-200
Cze˛stochowa, Poland
Received 21 February 2014; revised 25 April 2014
great interest of scientific community due to very
ABSTRACT: Sulfonium ylides derived from chiral
wide spectrum of biological activities [1]. Since
N,N’-substituted (benzyl, isopropyl, neopentyl) phos-
the planar carboxylic group in aminoacids is re-
phonamides were prepared by reacting appropriate
placed by a tetrahedral phosphonic acids moiety,
chiral diamidophosphites with potassium hydride and
APs mimic the unstable tetrahedral transition state
chloromethyl methyl sulfide, and then with methyl io-
formed in enzymatic peptide bond cleavage and act
dide in the presence AgBF4 to give the correspond-
as inhibitors of proteolytic enzymes. Moreover, they
ing sulfonium salts in high yields. One of them was
show antibacterial, anticancer, and antiviral prop-
analyzed by X-ray crystallography. The salts upon
erties as well as exhibit pesticidal, insecticidal, and
treatment with different bases (LithiumDiisopropy-
herbicidal activities. The selected APs have found
lAmine, BuLi, K2CO3) were converted in situ into
practical applications in medicine and agriculture.
ylides, which were reacted with activated olefins to pro-
As part of our program on the asymmetric
duce phosphonocyclopropanes as a mixture of two di-
synthesis of APs [2], we have also been engaged
astereoisomers with moderate-to-high diastereoselec-
in the invention and development of methods for
ꢀC
tivities.
2014 Wiley Periodicals, Inc. Heteroatom
the synthesis of aminocyclopropanephosphonic
acids, which are the so-called conformationally
constrained APs [3]. It should be pointed out
that the design and synthesis of conformation-
ally constrained peptidomimetics has been an
important strategy in modern drug discovery
processes. Our endeavors resulted in the elaboration
of new asymmetric synthesis of β-amino-γ -
phenylcyclopropanephosphonic acid [4], cyclo-
propylphosphonate analogues of purine nucleotides
[5], and 2-amino-6-phosphonobicyclo[3.0.1]hexane-
2-carboxylic acid [6]. These constrained analogues
of APs were obtained by a tandem Michael ad-
dition/ring closure reaction of achiral, properly
Chem. 25:690–697, 2014; View this article online at
wileyonlinelibrary.com. DOI 10.1002/hc.21183
INTRODUCTION
Aminophosphonic acids (APs) are analogues of pro-
tein and nonprotein amino acids. They attracted a
Correspondence to: Marian Mikolajczyk; e-mail: marmikol@
cbmm.lodz.pl.
Dedicated to Professor Renji Okazaki on the occasion of his
77th birthday.
ꢀC
2014 Wiley Periodicals, Inc.
690

Synthesis of New Sulfonium Ylides Bearing the Chiral Diazaphospholidine Group 691
FIGURE 1 Chiral sulfinyl reagents used in cyclopropanation.
substituted sulfur ylides to chiral electron-deficient
alkenes such as 1-(diethoxyphosphoryl)vinyl p-tolyl
sulfoxide and 2-(p-tolylsulfinyl)cyclopent-2-enone
(see Fig. 1).
Recently, Midura and colleagues have designed
and synthesized a new type of a chiral sulfur ylide
containing the sulfinyl group bonded to the ylidic
carbon atom [7]. Using this ylide, she prepared
in three steps (R)-[2,2–2H2]-1-aminocyclopropane-
1-phosphonic acid in which the α-carbon atom is
chiral due to isotopic substitution (CH2 vs. CD2) [8].
In this paper, we wish to describe the synthe-
sis of new chiral sulfur ylides in which the ylidic
carbon atom is bonded to the chiral diamidophos-
phonic group derived from trans-N,N’-disubstituted
1,2-diaminocyclohexane. This stereodirecting group
with a cyclic diamino C2-symmetric system at phos-
phorus was introduced to asymmetric synthesis by
Hanessian et al. [9] and also used in the asymmetric
synthesis of β-aminocyclopropanephosphonic acid
[10]. Our initial results on asymmetric cyclopropa-
nation of activated alkenes with these new sulfonium
ylides are also reported herein.
SCHEME
1 Synthesis of N,N’-disubstituted trans-1,2-
cyclohexanediamines 1a–c.
cally active (methylsulfanyl)methylphosphonamides
3. After chromatographic purification to remove
unreacted chloromethyl methyl sulfide, phospho-
namides 3a–c were obtained as viscous oils in 64–
76% overall yields. These new compounds were fully
characterized by NMR, IR, MS, and elemental anal-
ysis or HRMS. The methylsulfanyl protons in the
1H NMR spectra of 3 appeared as singlets at 2.12
and 2.13 ppm for 3a and 3b, respectively, and as a
RESULTS
4
doublet with a small coupling constant J
= 1.5
P-H
The enantiomerically pure trans-1,2-cyclohexane-
diamine [11] was converted into its N,N’-dibenzyl
analogue 1a through reductive amination with ben-
zaldehyde [12]. The N,N’-diizopropyl-(1R,2R)-1,2-
cyclohexanediamine 1b was obtained by a reac-
tion with acetone, followed by H2/PtO2 reduction
in ethanol [13]. The N,N’-dineopentyl-trans-(1R,2R)-
1,2-cyclohexanediamine 1c was prepared from the
corresponding N,N’-diacyl compound by reduction
with BH3·SMe2 in THF [14] (Scheme 1).
Hz for 3c. The 31P NMR spectra show singlets at
32.4–39.8 ppm in CDCl3. The 13C NMR spectra ex-
hibit characteristic doublets at 31.2–33.0 ppm with
a large coupling constant: 88.7 Hz for 3c, 113.3 Hz
for 3b, and 131.2 Hz for 3a, which are typical for the
P–C–S methylene bridge.
The phosphonamides 3a–c formed the corre-
sponding sulfonium salts 4a–c upon treatment with
methyl iodide in the presence of AgBF4 (Scheme 2).
They were purified by column chromatography and
1
Condensation of the diamines 1a–c with PCl3
and Et3N in a toluene solution followed by filtration
of the resulting Et3N·HCl gave the crude diamido
chlorophosphites. The addition of 1 equiv of water
and 1 equiv of NEt3 to a toluene solution of the lat-
ter gave the corresponding diamido phosphites 2a–c
(Scheme 2) [15].
We have found that phosphonamides 2 react
with potassium hydride and chloromethyl methyl
sulfide at low temperature in THF to give opti-
characterized by NMR spectroscopy. The H NMR
spectra showed strong signals of the two methyl
groups, which appear as singlets in the region of
2.78–3.18 ppm. In the 31P NMR (CDCl3) spectra, the
salts 4 resonate at 24.2–31.1 ppm.
Single crystals of the salt 4a, which were suit-
able for X-ray diffraction study, were obtained by
slow diffusion of hexane into a saturated solu-
tion of 4a in chloroform. The molecular structure
of this compound is depicted in Fig. 2. Absolute
Heteroatom Chemistry DOI 10.1002/hc

692 Owsianik et al.
SCHEME 2 Synthesis of sulfonium salts 4a–c.
of ࢣN = 360o for planar groups, which proves the
nonplanar configuration of nitrogen. Both nitrogen
atoms are tilted out of the plane formed by the three
˚
neighboring atoms, about 0.181(3) and –0.259(3) A.
The phosphorus center adopts a slightly deformed
tetrahedral geometry. The average value of the six va-
lence angles around the phosphorus atom is 109.3o.
Torsion angles are in the range of 94.9 (1)°–121.6
(1)°. The N2–P1–N1 torsion angle is the smallest,
and the O–P–N angle is the largest. The same re-
lationships exist in other phosphonamides [16–24].
The angle between the phenyl rings, C8–C13 and
C15–C20, is 35.7(2)°. The cyclohexane ring C1–C6
adopts a chair conformation [16, 17, 19, 20, 24], C3
and C6 atoms are tilted with respect to the plane C1,
˚
C2, C4, C5 of –0.725(6) and 0.717(5) A, respectively.
The five-membered ring has an envelope conforma-
tion [17, 20]. The C2 atom is tilted from the plane 1
(P1, N1, N2, C1) of 0.593 A, and the angle between
FIGURE 2 Molecular structure of solid 4a. The thermal
ellipsoids were drawn at the 50% probability level. Se-
˚
o
˚
lected bond distances (A) and angles ( ): P(1) N(1),
1.641(3); P(1) N(2), 1.634(3); P(1) C(21), 1.822(3);
S(1) C(21), 1.787(3); S(1) C(22), 1.793(4); S(1) C(23),
1.762(4); N(1) C(1), 1.464(4); N(1) C(7), 1.471(4);
N(2) C(2), 1.481(4); N(2) C(14), 1.462(4); C(1) C(2),
1.514(4); P(1) O(1), 1.459(2); O(1) P(1) N(1), 121.6(1);
O(1) P(1) N(2), 117.4(1); O(1) P(1) C(21), 107.4(1);
N(2) P(1) N(1), 94.9(1); N(2) P(1) C(21), 109.8(2);
O(1) P(1) N(1), 121.6(1).
the planes 1 and 2 (N2, C2, C1) is 39.5 (2)° [16].
The angle between the cyclohexane ring and five-
membered ring is –5.07(9)o [23].
The C22 and C23 atoms of the methyl groups
adopt a conformation –ap (φ = –176.9(3)°) and +sc
(φ = 76.9(3)°) relative to the phosphorus atom P1.
The atoms O1, N1, and N2 adopt a conformation
–sc (φ = –31.1(3)°), –ap (φ = –161.6(2)°), and +ac
(φ = 97.6(2)°), respectively, relative to the phospho-
rus atom P1 (Fig. 3).
The crystal structure of the compound 4a
is stabilized by weak hydrogen bonds (Fig. 4,
Table 1).
The generation of sulfonium ylides was achieved
by treatment of the sulfonium salts 4a–c with butyl-
litium, lithium diisopropylamide in THF or K2CO3
in dichloromethane. Owing to their instability, the
configuration of the two carbon atoms was con-
firmed as RC1 and RC2. The P–N distances are
1.641(3) and 1.634(3) and are slightly shorter than in
the other phosphonamides [16–20, 22]. The valence
angles of the sulfur atom are in the range of 101.3(2)–
103.8(2) and are characteristic for the tetrahedral ge-
ometry. The sum of valence angles of nitrogen atoms
are ࢣN1 = 355.8(6)o and ࢣN2 = 351.4(6)o instead
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of New Sulfonium Ylides Bearing the Chiral Diazaphospholidine Group 693
˚
TABLE 1 Hydrogen-Bond Parameters (A, °) for 4a
D
H
H···A
2.46
2.56
2.39
D···A
3.116(5)
2.889(4)
3.251(5)
D
H···A
125.7
101.5
148.5
C23 H23A···O1
C20 H20···N2
C22 H22A···F3i
0.96
0.93
0.96
Symmetry codes: (i) 2 – x, –1/2 + y, 1/2 – z.
FIGURE 3 Newman projection along the C21 S1 bond (a)
and C21 P1 bond (b) for compound 4a.
electron and steric factors having an influence on
the reaction course. Moreover, an inspection of the
results in Table 2 revealed that a little better stere-
oselection was obtained with smaller substituents
such as Bn (entry 1, 7) and iPr (Entry 2, 5), whereas
slightly worse for larger substituents like neopentyl
(entry 3, 6). Other aspects of the asymmetric cyclo-
propanation reaction briefly reported herein such as
the effect of solvent and base on yield and diastere-
oselectivity, separation of diastereoisomers, and de-
termination of their absolute configuration and hy-
drolysis of the chiral phosphonamido auxiliary are
under current investigation.
resulting ylides 5a–c are characterized only by the
31P NMR. A significant downfield shift has been ob-
served in the 31P NMR spectra of the compounds
5a–c (5a δ = 45.8 ppm; 5b δ = 43.4 ppm; 5c δ =
50.4 ppm) in comparison with the sulfonium salts
4a–c (4a δ = 28.1 ppm; 4b δ = 24.2 ppm; 4c δ =
31.1 ppm).
The ylides 5a–c were found to react with
different activated symmetrical 1,1-disubstituted
ethylenes [R1 = P(O)(OEt)2, SO2Ph, COOtBu], yield-
ing a mixture of the two diastereoisomeric cyclo-
propanes 6, 7, and 8 in moderate-to-good yields
and with diastereoselectivity in the range from
60:40 to 90:10 (Scheme 3, Table 2). The presence
of two electron-withdrawing groups in ethylenes
makes them much more reactive than those with
one activating group such as, e.g., vinylphospho-
nate. We found that the reaction of ylides 5a–c with
vinylphosphonate does not lead to the correspond-
ing cyclopropanes. A similar lack of reactivity of
the ylides was observed with diethyl 2-(propan-2-
ylidene)malonate. In this case, the decisive factor is
probably the steric hindrance. Therefore, as shown
in Table 2, preliminary results of the cyclopropana-
tion reaction represent a compromise between the
CONCLUSIONS
In conclusion, we have presented the synthesis of
a new type of sulfonium ylides containing a chi-
ral stereodirecting phosphonoamido group derived
from N,N’-disubstituted trans-diaminocyclohexane.
The reaction of the sulfonium ylides prepared with
activated olefins afforded cyclopropylamidophos-
phonates with moderate-to-high diastereoselectivi-
ties. Further studies on asymmetric cyclopropana-
tion are continued.
FIGURE 4 Unit-cell packing diagram for 4a. Dashed line represents a hydrogen bond.
Heteroatom Chemistry DOI 10.1002/hc

694 Owsianik et al.
SCHEME 3 Synthesis of cyclopropanes 6–8.
TABLE 2 Formation of Cyclopropanes 6–8 from Ylides 5
Ratio of
Entry
Compound
R
R1
Diastereoisomersa
Yieldb(%)
1
2
3
4
5
6
7
8
9
6a
6b
6c
7a
7b
7c
8a
8b
8c
Bn
iPr
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
SO2Ph
85:15
90:10
67:33d
60:40c
90:10
64:36d
80:20c
60:40
75:25d
63
70
66
60c
52
60
62c
35
38
tBuCH2
Bn
iPr
SO2Ph
tBuCH2
Bn
SO2Ph
COOtBu
COOtBu
COOtBu
iPr
tBuCH2
aDetermined from the 31P NMR spectra of the crude product mixture.
bYield of isolated product after chromatographic work-up.
cK2CO3 in CH2Cl2 was used as a base.
d BuLi in THF was used as a base.
EXPERIMENTAL
General
stirred for 1 h. The temperature was decreased to
–78°C, and 0.483 g (5 mmol) of chloromethyl methyl
sulfide in 5 mL of THF was added dropwise and
stirred for 12 h at room temperature. The mixture
was washed at 0°C with 5 mL of a saturated solu-
tion of NH4Cl and extracted with CH2Cl2 (2×10 mL).
After aqueous work-up, the organic layer was sepa-
rated, dried (MgSO4), and concentrated in vacuo.
The crude product was purified by column chro-
matography on silica gel using toluene/ethyl acetate
(2/1 v/v) for elution to give viscous oil of sulfide 3.
1H, 13C, and 31P NMR spectra were recorded on a
Bruker AC 200 spectrometer at 200.13, 50.32, and
81.02 MHz, respectively (using CDCl3 as a solvent)
unless otherwise noted. IR spectra were measured
on an Ati Mattson Infinity FTIR 60 spectrometer.
MS spectra (FAB and HRMS) were recorded on a
Finnigan MAT 95 spectrometer. Optical rotation val-
ues were measured in a 100-mm cell on Perkin–
Elmer 241 MC under Na lamp radiation. Column
chromatography was conducted on a Merck silica
gel (70–230 mesh). All solvents were dried by con-
ventional methods and distilled before use. All com-
mercially available products were purified by either
distillation or crystallization and were bought from
Aldrich. Tetraethyl ethenylidenebis(phosphonate)
[25] and di-tert-butyl methylenemalonate [26] were
obtained according to a known procedure.
1,3-Bis(phenylmethyl)-2-[(methylthio)methyl]
octahydro-2-oxide-(3aR,7aR)-1H, 1,3,2-benzodiazap-
25
hosphole 3a. Yellowish oil; 83% yield; [α]D = –69
(CHCl3, 1.1). IR (film): ν = 2935, 2862, 1453, 1209,
1
1171, 1028, 738 cm−1. H NMR (200 MHz, CDCl3):
δ = 7.70–7.05 (m, 10H), 4.62–4.25 (m, 2H), 4.20–
3.82 (m, 2H), 3.14 (ddd, J = 2.8, 2.9, 11.8 Hz, 1H),
3.00–2.62 (m, 3H), 2.13 (s, 3H), 1.90–1.45 (m, 4H),
1.35–0.72 (m, 4H) ppm. 31P NMR (81 MHz, CDCl3):
δ = 37.3 (s) ppm. 13C NMR (50 MHz, CDCl3): δ =
139.8, 138.5, 128.4, 128.2, 127.4, 127.1, 126.9 (s),
65.2, 63.8 (d, J = 6.8 Hz), 47.6, 46.5 (s), 31.2 (d, J =
131.2 Hz), 29.5 (d, J = 6.1 Hz), 24.2 (s), 13.5 (d, J =
6.7 Hz) ppm. MS(FAB) 401 (M + H). HRMS (FAB)
calcd. for C22H30OPSN2 [M + H]+ 401.1816; found
401.1820.
General Procedure for Synthesis of Sulfides 3a–c
To a suspension of 0.735 g (5.5 mmol) of KH (30%
dispersion in mineral oil) in 10 mL of THF, a solu-
tion of 5 mmol of phosphorus acid diamide 2 was
added in 20 mL of THF at –78°C. The resulting mix-
ture was allowed to warm to room temperature and
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of New Sulfonium Ylides Bearing the Chiral Diazaphospholidine Group 695
TABLE 3 Crystallographic Data for 4a
Crystal data
C23H32N2OPS·BF4
Dx = 1.308 g·cm−3
Mr = 502.36
Mo Kα radiation
Orthorhombic, P212121
Cell parameters from 18,034 reflections
˚
˚
a = 8.6160 (2) A
θ = 1.9–27.8°
μ = 0.24 mm−1
T = 296 (2) K
b = 9.2538 (2) A
˚
c = 31.9945 (8) A
3
˚
V = 2550.95 (10) A
Needle, colorless
Z = 4
0.35 × 0.15 × 0.10 mm
Data collection
Kuma KM4 CCD area-detector diffractometr
ω scan
Absorption correction: none
Tmin = 0.922, Tmax = 0.977
45,044 measured reflections
5,376 independent reflections
3,707 reflections with I > 2σ(I)
Rint = 0.029
θmax = 27.0°
h = –11 → 10
k = –11 → 11
l = –39 → 39
Refinement
Refinement on F2
Calculated weights w = 1/[σ2(Fo2) +
2
(0.0817P)2], where P = (Fo + 2Fc2)/3
R [F2 > 2σ(F2)] = 0.043
wR (F2) = 0.144
(ꢀ/σ)max <0.0001−3
˚
ꢀρmax = 0.32 e A
−3
˚
S = 1.12
ꢀρmin = – 0.29 e A
5,376 reflections
Extinction correction: none
300 parameters
H atoms constrained to parent site
Absolute structure/ Flack [23] parameter
Flack parameter: – 0.10 (10)
0.99 (s, 9H) ppm. 31P NMR (81 MHz, C6D6): δ =
39.8 (s) ppm. 13C NMR (50 MHz, C6D6): δ = 67.1 (d,
J = 5.7 Hz), 66.2 (d, J = 7.6 Hz), 58.2 (s), 56.7 (d, J =
2.5 Hz), 32.3 (d, J = 20.5 Hz), 32.0 (d, J = 21.6 Hz),
31.2 (d, J = 88.7 Hz), 29.3 (d, J = 6.7 Hz), 25.4 (s),
18.1 (d, J = 9.0 Hz) ppm. MS(FAB) 361 (M + H).
Anal. Calcd. for C18H37N2POS (360.58): C, 59.95; H,
10.36. Found: C, 59.81; H, 10.34.
1,3-Bis(1-methylethyl)-2-[(methylthio)methyl]
octahydro-2-oxide-(3aR,7aR)-1H, 1,3,2-benzodiaza-
25
phosphole 3b. Yellowish oil; 87% yield; [α]D
=
–75 (CHCl3, 1). IR (film): ν = 2930, 2871, 1440, 1209,
1015, 693 cm−1.1H NMR (200 MHz, CDCl3): δ =
3.65–3.27 (m, 2H), 3.08–2.84 (m, 3H), 2.80–2.58 (m,
1H), 2.12 (s, 3H), 2.10–1.83 (m, 2H), 1.80–1.52 (m,
2H), 1.30 (d, J = 6.8 Hz, 6H), 1.28–1.17 (m, 4H), 1.15
(d, J = 6.8 Hz, 6H) ppm. 31P NMR (81 MHz, CDCl3):
δ = 32.4 (s) ppm. 13C NMR (50 MHz, CDCl3): δ =
60.6 (d, J = 7.5 Hz), 59.6 (d, J = 6.2 Hz), 44.6 (d, J =
2.5 Hz), 43.8 (d, J = 5.5 Hz), 33.0 (d, J = 113.3 Hz),
30.1 (d, J = 7.5 Hz), 29.7 (d, J = 10.1 Hz), 24.0 (s),
23.0 (d, J = 3.0 Hz), 21.8 (d, J = 4.5 Hz), 20.4, 20.0
(s), 17.6 (d, J = 7.5 Hz) ppm. MS(FAB) 305 (M + H).
Anal. Calcd. for C14H29N2POS (304.46): C, 55.22; H,
9.62. Found: C, 55.18; H, 9.66.
General Procedure for Synthesis of Sulfonium
Salts 4a–c
To a solution of sulfide 3 in methyl iodide, AgBF4
at 0°C was added and the suspension was stirred
at room temperature overnight. Volatiles were re-
moved in vacuo, and acetone was added. The yellow
precipitate that formed was collected by filtration on
Celite, and a solution was concentrated to give a sul-
fonium salt 4 as a glassy white or yellowish solid.
Colorless needle-shaped crystals suitable for X-ray
crystallography were obtained by slow diffusion of
hexane into a saturated solution of 4a in chloroform.
1,3-Bis(2,2-dimethylpropyl)-2-[(methylthio)
methyl]octahydro-2-oxide-(3aR,7aR)-1H, 1,3,2-benz-
odiazaphosphole 3c. Yellowish oil; 85% yield;
25
[α]D = –77 (CHCl3, 1). IR (film): ν = 2973, 2870,
1458, 1220, 1106, 1043, 731, 705 cm−1 1H NMR
.
(200 MHz, C6D6): δ = 3.65 (dd, J = 16.7, 16.7 Hz,
1H), 3.04 (d, J = 13.7 Hz, 2H), 2.92–2.80 (m, 2H),
2.65–2.30 (m, 2H), 2.12 (dd, J = 14.6, 14.6 Hz,
1H), 1.78 (d, J = 1.5 Hz, 3H), 1.75–1.58 (m, 2H),
1.55–1.28 (m, 2H), 1.07 (s, 9H), 1.02–0.83 (m, 4H),
{[1,3-Bis(phenylmethyl)octahydro-2-oxide-(3aR,
7aR)-1H-1,3,2-benzodiazaphosphol-2-yl]methyl}(di-
methyl)sulfonium Tetrafluoroborate 4a. Colorless
crystals; 87% yield; [α]D = –35 (CHCl3, 1.2). IR
25
Heteroatom Chemistry DOI 10.1002/hc

696 Owsianik et al.
(film): ν = 3030, 2938, 2866, 1454, 1211, 1106, 1053,
1067, 739, 700 cm−1.1H NMR (200 MHz, CDCl3):
δ = 7.70–7.05 (m, 10H), 4.50–3.95 (m, 3H), 3.80
(dd, J = 10.8, 10.9 Hz, 1H), 3.40 (dd, J = 12.1, 12.4
Hz, 1H), 3.06 (dd, J = 11.5, 11.5 Hz, 1H), 2.82 (s,
3H), 2.78 (s, 3H), 2.05–1.85 (m, 2H), 1.82–1.45 (m,
3H), 1.43–1.05 (m, 3H), 1.04–0.65 (m, 2H) ppm. 31P
NMR (81 MHz, CDCl3): δ = 28.1 (s) ppm. 13C NMR
(50 MHz, CDCl3): δ = 138.8 (d, J = 5.0 Hz), 136.5,
128.9, 128.7, 128.3, 127.7, 127.5, 127.2 (s), 63.4 (d,
J = 9.5 Hz), 62.5 (d, J = 7.0 Hz), 46.1 (s), 45.5 (d, J =
4.5 Hz), 38.8 (d, J = 104.8 Hz), 29.0 (d, J = 8.4 Hz),
28.5 (d, J = 9.0 Hz), 26.9, 24.7 (s) ppm. MS(FAB)
415 (M-BF4). HRMS (FAB) calcd. for C23H32OPSN2
[M – BF4]+ 415.1973; found 415.1989.
X-Ray Crystallography
Crystal Data for {[1,3-bis(phenylmethyl)octa-
hydro-2-oxide-(3aR,7aR)-1H-1,3,2-benzodiazaphos-
phol-2-yl]methyl}(dimethyl)sulfonium Tetrafluorobo-
rate 4a. C23H32N2OPS·BF4, colorless, needle 0.35
× 0.15 × 0.10 mm, orthorhombic, space group
P212121, a = 8.6160 (2), b = 9.2538 (2), c = 31.9945
3
˚
˚
(8) A, V = 2550.95 (10) A , Mr = 502.36, Z = 4,
dcalcd = 1.308 g cm−3, μ = 0.24 mm−1, T = 296 (2) K,
F(000) = 1056 (see Table 3). Data collection: Kuma
KM4 CCD area-detector diffractomer with graphite
monochromatized Mo Kα radiation. Measured
reflections 45,044 (θmax 27.0°), 5376 independent
(Rint 0.029). Structure solution: direct method,
anisotropic refinement on F2 for all non-H atoms,
hydrogen atoms attached to C atoms were included
using a riding model. The structure was refined
over 3707 reflections with I >2 σ (I) (300 refined
parameters with 12.4 reflections on parameter). The
correct absolute structure was proved by the Flack
parameter [27] x = –0.10 (10). For all data, the final
wR2 was 0.144, R1 = 0.043, S = 1.12, max. ꢀρ =
{[1,3-Bis(1-methylethyl)octahydro-2-oxide-(3aR,
7aR)-1H-1,3,2-benzodiazaphosphol-2-yl]methyl}
(dimethyl)sulfonium Tetrafluoroborate 4b. Glassy
25
white solid; 90% yield; [α]D = –24 (CHCl3, 1). IR
(film): ν = 3028, 2944, 2870, 1208, 1064, 1071, 736
cm−1.1H NMR (200 MHz, CDCl3): δ = 4.10–3.65 (m,
2H), 3.65–3.40 (m, 2H), 3.18 (s br, 6H), 3.08–2.75
(m, 2H), 2.34–1.97 (m, 2H), 1.97–1.65 (m, 2H),
1.60–1.08 (m, 4H), 1.35 (d, J = 5.9 Hz, 6H), 1.25 (d,
J = 5.9 Hz, 6H) ppm. 31P NMR (81 MHz, CDCl3):
δ = 24.2 (s) ppm. 13C NMR (50 MHz, CDCl3): δ =
62.8 (d, J = 7.8 Hz), 58.9 (d, J = 6.0 Hz), 45.4 (d, J =
3.0 Hz), 43.0 (d, J = 4.0 Hz), 37.5 (d, J = 108.0 Hz),
30.6 (d, J = 7.0 Hz), 28.9 (d, J = 9.2 Hz), 24.8, 24.0,
22.6 (s), 22.0 (d, J = 4.0 Hz), 21.1, 20.9 (s), 20.5 (d,
J = 6.5 Hz) ppm. MS (FAB) 319 (M – BF4). Anal.
Calcd. for C15H32N2POSBF4 (406.27): C, 44.34; H,
7.95. Found: C, 44.28; H, 7.92.
0.32 e A−3. Data processing was carried out with
˚
the Oxford Diffraction [28, 29]; structure solution
SHELXS [30]; structure refinement SHELXL [31].
SUPPLEMENTARY MATERIAL
Full details (excluding the structure factors) for the
structure reported in this paper have been deposited
at the Cambridge Crystallographic Data Center, as
supplementary publication no. CCDC 976694 and
can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(e-mail: deposit@ccdc.cam.ac.uk).
{[1,3-Bis(2,2-dimethylpropyl)octahydro-2-oxide-
(3aR,7aR)-1H-1,3,2-benzodiazaphosphol-2-yl]meth-
yl}(dimethyl)sulfonium Tetrafluoroborate 4c. Glassy
yellowish solid; 95% yield; [α] = –22 (CHCl3, 1).
IR (film): ν = 3032, 2941, 2851, 1452, 1207, 1050,
1073, 732 cm−1.1H NMR (200 MHz, CDCl3): δ =
4.15–3.95 (m, 1H), 3.80–3.56 (m, 1H), 3.15 (s, 6H),
3.05–2.23 (m, 4H), 1.92–1.71 (m, 2H), 1.58–1.10
(m, 4H), 1.10–0.90 (m, 4H), 0.96 (s, 9H), 0.93 (s,
9H) ppm. 31P NMR (81 MHz, CDCl3): δ = 31.1 (s)
ppm. 13C NMR (50 MHz, CDCl3): δ = 64.6 (d, J
= 8.6 Hz), 64.0 (d, J = 11.0 Hz), 57.7 (s), 55.5 (d,
J = 28.1 Hz), 54.4 (d, J = 33.6 Hz), 38.2 (d, J = 98.5
Hz), 32.9, 31.7, 30.9, 28.6, 28.3, 27.3, 27.1, 24.3,
22.9 (s) ppm. MS(FAB) 375 (M – BF4). Anal. Calcd.
for C19H40N2POSBF4 (462.46): C, 49.34; H, 8.74.
Found: C, 49.29; H, 8.72.
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