Synthesis of chiral α-(N-sulfoximido) phosphines, phosphine oxides, and phosphonates through hydrophosphination and hydrophosphorylation of N-vinyl sulfoximines

Article abstract of DOI:10.1055/s-2008-1066992

The reaction of N-vinyl sulfoximines with HPPh₂, HP(O)Ph ₂, and HP(O)(OMe)₂ gave the corresponding α-(N-sulfoximido) phosphines, phosphine oxides, and phosphonates, respectively, with high regioselectivity in high yield. The N-vinyl sulfoximines showed an enamine-like regioselectivity in hydrophosphination and hydrophosphorylation (Pudovik reaction). While the acid-catalyzed hydrolysis of a cyclic N-vinyl sulfoximine gave the corresponding NH-sulfoximine and cyclohexanone, its hydroboration/oxidation afforded the corresponding N-(β-hydroxycyclohexenyl) sulfoximine. The structure of an α-(N-sulfoximido) phosphine was determined by X-ray crystal structure analysis. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1066992

1126
PAPER
Synthesis of Chiral a-(N-Sulfoximido) Phosphines, Phosphine Oxides, and
Phosphonates through Hydrophosphination and Hydrophosphorylation of
N-Vinyl Sulfoximines
C
hira
l
a
-
(
N
-Sulfo
a
ximido) Ph
l
osphin
f
es, Phosphine
Oxides, and
Phospehinates lmut Hetzer, Hans-Joachim Gais,* Gerhard Raabe
Institut für Organische Chemie, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Landoltweg 1, 52074 Aachen, Germany
Fax +49(241)8092665; E-mail: gais@rwth-aachen.de
Received 8 November 2007; revised 8 January 2008
Dedicated to Professor Klaus Hafner on the occasion of his 80th birthday
imines I with phosphines II. The resulting a- or b-(N-
Abstract: The reaction of N-vinyl sulfoximines with HPPh2,
sulfoximido) phosphines, phosphine oxides, and phos-
HP(O)Ph2, and HP(O)(OMe)2 gave the corresponding a-(N-sulfox-
phonates III and IV, respectively, should both be of inter-
est as new potential N,P-ligands for transition metals and
imido) phosphines, phosphine oxides, and phosphonates, respec-
tively, with high regioselectivity in high yield. The N-vinyl
sulfoximines showed an enamine-like regioselectivity in hydro- analogues of a- and b-amino phosphonic acids. N,P-
phosphination and hydrophosphorylation (Pudovik reaction). While
Ligands have found much application, for example, in
transition-metal-catalyzed asymmetric synthesis.11 Both
the acid-catalyzed hydrolysis of a cyclic N-vinyl sulfoximine gave
the corresponding NH-sulfoximine and cyclohexanone, its hydro-
a- and b-amino phosphonic acids are of significant inter-
boration/oxidation afforded the corresponding N-(b-hydroxycyclo-
hexenyl) sulfoximine. The structure of an a-(N-sulfoximido)
phosphine was determined by X-ray crystal structure analysis.
est as analogues of a- and b-amino acids.12
The N-vinyl sulfoximines 39 and 5 of 95% purity were ob-
tained through a copper-mediated coupling of the enan-
tiopure S-configured sulfoximine 113 with the
corresponding bromides 2 and 4 in practically quantitative
yields (Scheme 2). Despite their ready availability almost
nothing was known about the reactivity of N-vinyl sulfox-
imines of type I. Specifically, the question whether they
behave like enamines as hinted by the polar structure,
which is according to ab initio calculations an appropriate
representation of the electronic structure of the sulfox-
imine group,14 or react as electron-withdrawing group
activated alkenes, awaited experimental verification.
Therefore, the reactivity of sulfoximine 5 towards water
and acid was first investigated. The N-vinyl sulfoximine
proved to be stable towards water in CDCl3 at room tem-
perature for at least 24 hours as shown by NMR spectros-
copy and GC analysis. However, the addition of acetic
acid to a mixture of 5 and water in CDCl3 at room temper-
ature resulted within one hour in a complete hydrolysis of
the N-vinyl sulfoximine and gave sulfoximine 1 and ke-
tone 6 (Scheme 3). Furthermore, an attempted chromatog-
raphy of 3 and 5 on silica gel also led to a hydrolysis of the
N-vinyl sulfoximines and the isolation of sulfoximine 1.
Key words: Pudovik reaction, N-vinyl sulfoximines, hydrophos-
phination, hydrophosphorylation, phosphines, a-(N-sulfoximido)
phosphines, a-(N-sulfoximido) phosphine oxides, a-(N-sulfoximi-
do) phosphonates, hydroboration
Sulfoximines have emerged as valuable chiral auxiliaries1–4
and chiral ligands5,6 for asymmetric synthesis. In addition
sulfoximines have found important application as enzyme
inhibitors7 and peptidomimetics.8 Recently, the N-vinyl
sulfoximines I have been described, which are readily
available through a palladium-catalyzed or copper-medi-
ated coupling reaction of NH-sulfoximines with the corre-
sponding vinyl halides or triflates (Scheme 1).9
O
O
R5
R4
S
N
R5
R4
S
N
R2
R1
R2
R1
R3
R3
I
HP(O)n(R6)2
O
II
O
P(O)n(R6)2
R5
P(O)n(R6)2
R5
S
N
S
N
R2
R1
R2
R1
Me
R3
R3
O
2
R4
IV
O
Br
Me
Me
Me
S
N
R4
Ph
III
S
NH
Ph
Me
CuI, K2CO3, toluene
Me
Scheme 1
NHMe
MeHN
Br
3
1
We decided to study the hydrophosphination and hydro-
phosphorylation (Pudovik reaction10) of N-vinyl sulfox-
O
4
O
S
N
Ph
Me
S
NH
Ph
Me
CuI, K2CO3, toluene
NHMe
SYNTHESIS 2008, No. 7, pp 1126–1132
Advanced online publication: 13.03.2008
DOI: 10.1055/s-2008-1066992; Art ID: T17307SS
x
x
.
x
x
.2
0
0
8
MeHN
5
1
© Georg Thieme Verlag Stuttgart · New York
Scheme 2

PAPER
Chiral a-(N-Sulfoximido) Phosphines, Phosphine Oxides, and Phosphonates
1127
O
A similar reaction of 3 with 1 equivalent of neat 7b at
100 °C was complete after only 3 hours and gave a mix-
ture of the diastereomeric a-(N-sulfoximido) phosphine
oxides 8ba and 8bb in a ratio of 3:2 in 87% yield. Separa-
tion by HPLC furnished the pure diastereomers 8ba and
8bb. Finally, the treatment of 3 with 1.5 equivalents of
neat 7c at 100 °C for 23 hours gave a mixture of the dia-
stereomeric a-(N-sulfoximido) phosphonates 8ca and 8cb
in a ratio of 3:2 in 99% yield. Separation by HPLC afford-
ed the pure diastereomers 8ca and 8cb. The addition of
7a–c to 3 had occurred with high regioselectivity. The
NMR spectra of the crude reaction mixtures gave no indi-
cation for the formation of regioisomers of type IV. Thus,
the N-vinyl sulfoximine 3 showed in the Pudovik reaction
with 7a–c an enamine like reactivity16 and gave the a-ad-
ducts of type III with high regioselectivity. The reactivity
of 3 decreased in the order HP(O)Ph2 > HP(O)(OMe)2 >
HPPh2, which roughly parallels their acidity.17
O
O
S
N
H+/H2O
Ph
Me
S
NH
+
Ph
Me
5
1
6
Scheme 3
Having established an enamine like reactivity of 5 to-
wards H2O/H+, the reactions of the acyclic N-vinyl sulfox-
imine
3 with HPPh2 (7a), HP(O)Ph2 (7b) and
HP(O)(OMe)2 (7c) were studied. The treatment of 3 with
1.3 equivalents of neat 7a at 100 °C for 48 hours resulted
in complete conversion of the starting sulfoximine and
gave, after the addition of BH3·THF, a mixture of the
diastereomeric a-(N-sulfoximido) phosphine–borane ad-
ducts (S)-8aa·BH3 and (R)-8ab·BH3 in a ratio of 1:1 in
87% yield (Scheme 4, Table 1). Crystallization and
HPLC afforded the pure diastereomers (S)-8aa·BH3 and
(R)-8ab·BH3. The configuration of (S)-8aa·BH3 was de-
termined by X-ray crystal structure analysis (Figure 1).15
Next the reaction of the cyclic N-vinyl sulfoximine 5 with
7a–c was studied. Surprisingly, the synthesis of phos-
phine 9a from 5 and 7a could not be achieved. The treat-
ment of 5 with 7a at 100 °C for a prolonged period of time
resulted only in a low conversion of the vinyl sulfoximine
to 9a (10%) (Scheme 5). Attempts to achieve an addition
of HPPh2·BH3 to the N-vinyl sulfoximine 5 also failed. In-
stead, the saturated sulfoximine 10 was directly isolated in
84% yield after chromatography of the crude reaction
product on silica gel (Scheme 6). Treatment of 5 with
BH3·THF followed by an oxidation with H2O2 in the pres-
ence of NaOH gave the b-hydroxy sulfoximine 11 as a
mixture of two diastereomers in a ratio of 2:1 in 71%
O
O
HP(O)n(R)2
S
N
P(O)n(R)2
i-Pr
S
N
Ph
Me
Me
Me
7a–c
Ph
Me
∆T
H
8a–c
3
a: n = 0, R = Ph, b: n = 1, R = Ph, c: n = 1, R = OMe
Scheme 4
1
yield. According to H NMR spectroscopy, both diaste-
reomers have the trans-configuration. These results show
that BH3 caused a highly regioselective hydroboration of
the N-vinyl sulfoximine 5. In contrast to 7a, the reaction
of 7b with 5 at 100 °C proceeded cleanly and gave after a
reaction time of 3 hours the a-(N-sulfoximido) phosphine
oxide 9b in 86% yield (Table 2). Similarly, the treatment
of 5 with 7c at 100 °C for 18 hours afforded the a-(N-
sulfoximido) phosphonate 9c in 96% yield. The addition
of 7b and 7c to 5 proceeded with high regioselectivity ac-
cording to NMR spectroscopy of the crude reaction mix-
tures.
Figure 1 Structure of (S)-8aa·BH3 in the crystal. Selected bonding
parameters: S–O 1.447(2), S–N 1.517(1), C–P 1.851(2), P–B
1.929(2), S–N–C 120.9(1), P–C–N–S 130.1(1).
O
O
HP(O)n(R)2
S
N
P(O)n(R)2
S
N
7a–c
Ph
Me
Ph
Me
Table 1 Hydrophosphination and Hydrophosphorylation of the
Acyclic N-Vinyl Sulfoximine 3
∆T
Reagent
Products
Yield (%)dr
Yield (%)
5
9a–c
Major Minor
a: n = 0, R = Ph, b: n = 1, R = Ph, c: n = 1, R = OMe
HPPh2
8aa, 8aba
8ba, 8bb
8ca, 8cb
87
87
99
1:1
40
49
56
38
32
40
Scheme 5
HP(O)Ph2
HP(O)(OMe)2
3:2
3:2
Because of the ready synthesis of the functionalized S-
methyl sulfoximines 8 and 9, we became interested to see
whether they can be derivatized at the methyl group
through lithiation and to study the reaction of the lithiated
derivatives with electrophiles.1–3 Thus, treatment of sul-
a Isolated as the borane adduct.
Synthesis 2008, No. 7, 1126–1132 © Thieme Stuttgart · New York

1128
R. H. Hetzer et al.
PAPER
O
were heated without solvent at elevated temperatures. The
asymmetric induction in the addition to the acyclic N-vi-
nyl sulfoximine 3 was only low. It is not known, however,
whether the addition of 7a–c to 3 and 5 is kinetically or
thermodynamically controlled since it might be reversible
under the reaction conditions employed. The reaction of
sulfoximines 3 and 5 with 7a–c show the same regioselec-
tivity as that of enamines. However, the Pudovik reaction
of enamines has been studied only in a few cases and noth-
ing is known about its mechanism.16 It has been suggested
that the addition of 7a–c to imines, for example, takes
place via a four-membered cyclic transition state.10c
Therefore the addition of 7a–c to 3 and 5 may occur by a
similar mechanism. We found that the reaction of 3 and 5
with 7a–c in the presence or in the absence of oxygen oc-
curred with a similar high regioselectivity. Thus a radical
mechanism for the reaction of 3 and 5 with 7a–c seems
unlikely. Because of the successful derivatization of
sulfoximine 9b at the S-methyl group via lithiation, the
synthesis of interesting functionalized derivatives of III
can be envisioned. Finally, it should be noted that hydro-
boration of 5 occurred readily and showed the same regio-
selectivity as that of enamines.18 This suggests a perhaps
facile route to cyclic N-(b-hydroxyalkyl) sulfoximines
which are not easily accessible otherwise.3a
O
1. Ph2PH⋅BH3
S
N
S
N
Ph
Me
Ph
Me
∆T
2. silica gel
10
5
1. BH3⋅THF
2. H2O2, OH–
O
O
S
N
S
N
OH
OH
Ph
Ph
Me
Me
+
11b
11a
Scheme 6
Table 2 Hydrophosphorylation of the Cyclic N-Vinyl Sulfoximine
5
Reagent
Product
9a
Yield (%)
a
HPPh2 (7a)
–
HP(O)Ph2 (7b)
HP(O)OMe2 (7c)
9b
86
96
9c
a Only a 10% conversion of 5 to 9a was observed.
foximine 9b with n-BuLi furnished the lithiomethyl deriv-
ative 12 which upon reaction with 3-methylbutanal All reactions were carried out under argon with flame-dried glass-
ware and dried solvents. Reactions involving oxygen sensitive
phosphorus compounds were performed with degassed solvents (ar-
gon). Solvents were dried and purified by conventional methods be-
fore use. THF and toluene were freshly distilled from Na under N2.
afforded a mixture of the diastereomeric alcohols 13a and
13b in 83% yield (Scheme 7). The ratio of the diastereo-
mers of 13, the configuration of which was not deter-
mined, was 85:15. HPLC furnished the major
diastereomer of 13 in 68% yield and the minor diaste-
reomer of 13 in 4% yield.
Sulfoximine 1,13 the N-vinyl sulfoximine 39 and bromide 419 were
synthesized according to the literature. All other chemicals were ob-
tained from commercial sources. TLC was performed on silica gel
60 F254 aluminum sheets (Merck) with UV and iodine detection.
Flash chromatography was performed on silica gel 60, 0.040–0.063
mm (Merck). Analytical HPLC was carried out on Waters 600 E
UV 481 and Hewlett Packard HP 1050 instruments. Optical rota-
tions were measured on a PerkinElmer P241 polarimeter. NMR
spectra were recorded on Varian Mercury 300 and Varian Inova 400
instruments. Chemical shifts are reported relative to TMS. MS spec-
tra were measured on a Finnigan SSQ 7000 (EI, 70 eV or CI, meth-
ane or isobutane) instrument and HRMS spectra on a Varian MAT
95 (EI, 70 eV) instrument. IR spectra were run on a Perkin Elmer
FTIR 1760 S instrument. Microanalyses were obtained with a Vario
EL element analyzer. Melting points were determined on a Leica
melting point apparatus and are uncorrected.
O
O
O
O
Li
S
N
PPh2
S
N
PPh2
Me
n-BuLi
THF
Ph
Ph
9b
12
R
O
O
R = CH2CHMe2
OH
O
OH
O
O
S
N
PPh2
S
N
PPh2
R
R
Ph
Ph
(S)-N-Cyclohex-1-enyl-S-methyl-S-phenylsulfoximine (5)
A Schlenk flask was charged with CuI (1.03 g, 5.4 mmol), K2CO3
(1.49 g, 10.8 mmol), and (S)-S-methyl-S-phenylsulfoximine (1; 840
mg, 5.4 mmol). Subsequently, the flask was purged with argon and
then toluene (50 mL), N,N¢-dimethylethylenediamine (1.16 mL,
10.8 mmol), and bromide 4 (1.30 g, 8.1 mmol) were added. The
mixture was heated under stirring for 20 h at 110 °C. Then, the mix-
ture was cooled to r.t., Et2O (50 mL) was added, and the mixture
was filtered through a layer of Celite (1 cm) by washing with Et2O
(50 mL). Removal of the solvents under reduced pressure gave the
N-vinyl sulfoximine 5 (1.25 g, 98%) as a yellow oil; [a]D20 +137.6
(c 1.00, CH2Cl2).
+
13a
13b
Scheme 7
In conclusion, we have shown that the N-vinyl sulfox-
imines 3 and 5 readily undergo with high regioselectivity
a noncatalyzed hydrophosphination and hydrophosphory-
lation with 7a–c to give a-(N-sulfoximido) phosphines,
phosphine oxides and phosphonates of type III in high
yields. A complete conversion of 3 and 5 was only ob-
served when the N-vinyl sulfoximines and the phosphines
IR (capillary): 2925 (s), 2839 (m), 1640 (m), 1444 (m), 1366 (w),
1243 (s), 1184 (s), 1093 (m), 1015 (m), 970 (m), 843 (w), 789 (m),
744 (s), 689 cm–1 (m).
Synthesis 2008, No. 7, 1126–1132 © Thieme Stuttgart · New York

PAPER
Chiral a-(N-Sulfoximido) Phosphines, Phosphine Oxides, and Phosphonates
1129
1H NMR (300 MHz, C6D6): d = 1.24–1.47 (m, 2 H, CH2), 1.50–1.60
(m, 2 H, CH2), 1.76–2.05 (m, 2 H, CH2), 2.28–2.35 (m, 2 H, CH2),
2.65 (s, 3 H, SCH3), 5.39–5.44 (m, 1 H, CH), 7.09–7.16 (m, 3 H,
ArH), 7.88–7.97 (m, 2 H, ArH).
13C NMR (75 MHz, C6D6): d = 22.7 (CH2), 23.7 (CH2), 25.1 (CH2),
32.1 (CH2), 45.1 (SCH3), 109.9 (CH), 128.6 (CHAr), 129.2 (CHAr),
132.5 (CHAr), 141.0 (C or CAr), 141.4 (C or CAr).
MS (EI, 70 eV): m/z (%) = 235 (M+, 58), 234 (12), 173 (14), 172
(100), 157 (13), 145 (16), 144 (10), 141 (10), 140 (15), 130 (11),
125 (54), 124 (16).
(S)-8ab·BH3
Mp 143 °C; [a]D20 +58.0 (c 1.00, CHCl3); Rf = 0.14 (cyclohexane–
EtOH, 4:1).
IR (CHCl3): 3061 (w), 2969 (w), 2926 (m), 2880 (w), 2388 (s),
2350 (m), 2285 (w), 1477 (m), 1436 (m), 1343 (w), 1249 (s), 1143
(s), 1106 (m), 1064 (m), 970 (w), 949 (m), 876 (w), 822 (w), 729
(s), 687 (s), 687 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 0.60–1.80 (m, br, 3 H, BH3), 0.72–
0.91 (m, 6 H, CH3), 2.42–2.44 (m, 4 H, CH and SCH3), 4.22–4.27
(m, 1 H, CH), 7.43–7.61 (m, 9 H, ArH), 7.67–7.81 (m, 4 H, ArH),
8.14–8.26 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 18.0 (d, JC,P = 1.8 Hz, CH3), 23.2
(d, JC,P = 12.6 Hz, CH3), 30.6 (d, JC,P = 7.8 Hz, CH), 43.7 (SCH3),
61.0 (d, JC,P = 41.3 Hz, CHNP), 127.3 (CHAr), 127.5 (CAr), 128.2,
128.3, 128.4 and 128.6 (4 CHAr), 129.0 (CHAr), 130.7 (d, JC,P = 1.8
Hz, CHAr), 131.4 (d, JC,P = 1.7 Hz, CHAr), 132.7 (CHAr), 132.8
(CHAr), 134.9 (JC,P = 12.4 Hz, CHAr), 141.57 (CAr).
Anal. Calcd for C13H17NOS (235.10): C, 66.34; H, 7,28; N, 5.95.
Found: C, 66.33; H, 7.37; N, 6.08.
(S)-1-N-[(S)-S-Methyl-S-phenylsulfonimidoyl]-P-diphenyl-P-
(2-methylpropyl)-1-phosphine–Borane Adduct [(S)-8aa·BH3]
and (R)-1-N-[(S)-S-Methyl-S-phenylsulfonimidoyl]-P-diphenyl-
P-(2-methylpropyl)-1-phosphine–Borane Adduct
[(R)-8ab·BH3]
31P NMR (121 MHz, CDCl3): d = 25.7.
A Schlenk tube (5 mL) with a screw cap was charged with the N-
vinyl sulfoximine 3 (500 mg, 2.4 mmol) and HPPh2 (7a; 578 mg,
3.1 mmol). The tube was purged with argon and the mixture was
heated for 48 h at 100 °C. After the mixture had cooled to r.t., de-
gassed CH2Cl2 (20 mL) was added and the solution was transferred
to a Schlenk flask. Then borane (6 mL of 1 M in THF, 6.0 mmol)
was added dropwise. After the mixture had stirred for 3 h at r.t., it
was quenched by the dropwise addition of aq 2 M HCl (3 mL) under
ice-bath cooling (formation of H2 gas!). The mixture was diluted
with CH2Cl2 (100 mL) and washed successively with aq NaHCO3
(50 mL) and H2O (50 mL). The organic layer was dried (MgSO4)
and concentrated under reduced pressure. Purification by flash
chromatography (cyclohexane–EtOH, 80:20) gave the phosphine–
borane adduct 8a·BH3 (859 mg, 87%) as a mixture of diastereomers
in a ratio of 1:1 as a viscous colorless oil. Crystallization from cy-
clohexane–EtOH (92:8) furnished (S)-8aa·BH3 (230 mg, 23%) as
colorless crystals. The mother liquor was concentrated under re-
duced pressure. Separation by HPLC (Kromasil Si 100; 30 mm ×
250 mm; cyclohexane–EtOH, 92:8; 20 mL/min) afforded (R)-
8ab·BH3 (378 mg, 38%) and (S)-8aa·BH3 (168 mg, 17%) as color-
less crystals.
MS (EI, 70 eV): m/z (%) = 408 (M+ – 1, 3), 211 (14), 210 (100), 141
(25).
Anal. Calcd for C23H29BNOPS (409.18): C, 67.49; H, 7.14; N, 3.42.
Found: C, 67.63; H, 6.90; N, 3.39.
(1R)-1-N-[(S)-S-Methyl-S-phenylsulfonimidoyl]-P-diphenyl-P-
(2-methylpropyl)-1-phosphine Oxide [(1R)-8b] and (1S)-1-N-
[(S)-S-Methyl-S-phenylsulfonimidoyl]-P-diphenyl-P-(2-meth-
ylpropyl)-1-phosphine Oxide [(1S)-8b]
A Schlenk tube (5 mL) with a screw cap was charged with the N-
vinyl sulfoximine 3 (435 mg, 2.1 mmol) and HP(O)Ph2 (7b; 420
mg, 2.1 mmol). The tube was carefully purged with argon and the
mixture was heated for 3 h at 100 °C. Then the mixture was cooled
to r.t. Purification by flash chromatography (EtOAc) gave the phos-
phine oxide 8b (740 mg, 87%) as mixture of diastereomers in a ratio
of 3:2. Separation by HPLC (cyclohexane–EtOH, 95:5); Kromasil
Si 100-column, 30 mm × 250 mm; 20 mL/min) afforded the major
diastereomer (423 mg, 49%) and the minor diastereomer (270 mg,
32%) as colorless crystals.
(R)-8aa·BH3
Major Diastereomer
Mp 143 °C; [a]D20 –28.0 (c 1.00, CH2Cl2); Rf = 0.11 (EtOAc).
20
Mp 95 °C; [a]D –39.3 (c 1.00, CHCl3); Rf = 0.14 (cyclohexane–
EtOH, 4:1).
IR (KBr): 3058 (w), 2965 (m), 2869 (w), 2802 (w), 2344 (w), 1730
(w), 1583 (w), 1476 (w), 1441 (m), 1314 (w), 1247 (s), 1172 (s),
1097 (s), 950 (m), 874 (w), 837 (w), 747 (s), 695 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 0.90–0.97 (m, 6 H, CH3), 2.30–
2.44 (m, 1 H, CH), 3.08 (s, 3 H, SCH3), 3.41–3.48 (m, 1 H, CHNP),
6.95–6.99 (m, 2 H, ArH), 7.20–7.29 (m, 2 H, ArH), 7.40–7.56 (m,
7 H, ArH), 7.77–7.86 (m, 2 H, ArH), 8.16–8.25 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 18.3 (CH3), 22.4 (d, JC,P = 13.1
Hz, CH3), 29.1 (CH), 45.7 (SCH3), 63.5 (d, JC,P = 90.9 Hz, CHNP),
128.0, 128.0, 128.1 and 128.2 (CHAr), 128.2 (CHAr), 129.1 (CHAr),
131.3 (CHAr), 131.5 (CHAr), 132.0 (d, JC,P = 8.4 Hz, CHAr), 132.6
(CHAr), 132.7 (CHAr), 133.2 and 134.4 (2 CAr), 136.8 (CAr).
IR (CHCl3): 3017 (m), 2974 (w), 2853 (s), 2395 (w), 1459 (w),
1218 (s), 1151 (w), 1103 (w), 1049 (m), 879 (w), 823 (w), 787 (s),
734 (s), 670 cm–1 (s).
1H NMR (400 MHz, CDCl3): d = 0.60–1.60 (m, br, 3 H, BH3), 0.85–
0.94 (m, 6 H, CH3), 2.29–2.41 (m, 1 H, CH), 3.05 (s, 3 H, SCH3),
3.56–3.60 (m, 1 H, CH), 6.96–6.98 (m, 2 H, ArH), 7.24–7.31 (m, 2
H, ArH), 7.37–7.53 (m, 7 H, Ar), 7.65–7.72 (m, 2 H, ArH), 8.15–
8.21 (m, 2 H, ArH).
13C NMR (101 MHz, CDCl3): d = 17.8 (CH3), 22.9 (d, JC,P = 13.7
Hz, CH3), 30.0 (d, JC,P = 7.6 Hz, CH), 45.6 (SCH3), 62.6 (d,
JC,P = 44.2 Hz, CHNP), 127.8, 127.91, 127.96, 128.05 and 128.15
31P NMR (121 MHz, CDCl3): d = 29.9.
MS (EI, 70 eV): m/z (%) = 412 (M+ + 1, 1), 211 (13), 210 (100), 201
(5 CHAr), 128.4 (CAr), 128.9 (CHAr), 130.1 (d, JC,P = 54.2 Hz, CAr),
130.6 (d, JC,P = 2.3 Hz, CHAr), 131.0 (d, JC,P = 3.2 Hz, CHAr), 132.4
(CHAr), 133.2 (d, JC,P = 8.4 Hz, CHAr), 134.5 (d, JC,P = 8.3 Hz,
CHAr), 136.9 (CAr).
(13), 141 (34).
Anal. Calcd for C23H26NO2PS (411.14): C, 67.13; H, 6.37; N, 3.40.
Found: C, 66.81; H, 6.53; N, 3.27.
31P NMR (162 MHz, CDCl3): d = 22.3.
MS (EI, 70 eV): m/z (%) = 408 (M+ – 1, 3), 211 (13), 210 (100), 141
(27).
Minor Diastereomer
Mp 184 °C; [a]D20 +45.2 (c 1.00, CH2Cl2); Rf = 0.11 (EtOAc).
Anal. Calcd for C23H29BNOPS (409.18): C, 67.49; H, 7.14; N, 3.42.
Found: C, 67.85; H, 6.84; N, 3.44.
Synthesis 2008, No. 7, 1126–1132 © Thieme Stuttgart · New York

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R. H. Hetzer et al.
PAPER
IR (KBr): 3058 (w), 2985 (w), 2965 (w), 2906 (m), 2876 (w), 1477
(m), 1439 (m), 1340 (w), 1248 (s), 1180 (s), 1142 (s), 1109 (s), 971
(m), 879 (m), 727 (s), 699 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 0.80–0.92 (m, 6 H, CH3), 2.25–
2.38 (m, 1 H, CH), 2.46 (s, 3 H, SCH3), 4.15–4.20 (m, 1 H, CHNP),
7.42–7.60 (m, 9 H, ArH), 7.78–7.92 (m, 4 H, ArH), 8.10–8.22 (m,
2 H, ArH).
1H NMR (300 MHz, CDCl3): d = 1.04–1.07 (m, 3 H, CH3), 1.10 (d,
J
H,P = 6.9 Hz, 3 H, CH3), 2.20 (sept d, JH,P = 6.9 Hz, J = 3.3 Hz 1
H, H-2), 3.15 (s, 3 H, SCH3), 3.32 (dd, J = 3.3 Hz, JH,P = 12.4 Hz,
1 H, H-1), 3.60–3.67 (m, 6 H, OCH3), 7.52–7.64 (m, 3 H, ArH),
8.00–8.10 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 18.0 (CH3), 20.1 (d, JC,P = 14.5
Hz, CH3), 30.4 (CH), 45.8 (SCH3), 52.5 (d, JC,P = 7.8 Hz, OCH3),
52.71 (d, JC,P = 7.6 Hz, OCH3), 57.1 (d, JC,P = 162.5 Hz), 128.5
(CHAr), 128.9 (CHAr), 132.6 (CHAr), 139.4 (CAr).
13C NMR (75 MHz, CDCl3): d = 18.5 (CH3), 22.5 (d, JC,P = 12.0
Hz, CH3), 29.7 (d, JC,P = 3.0 Hz, CH), 44.3 (SCH3), 60.5 (d,
JC,P = 88.6 Hz, CHPN), 127.1 (CHAr), 128.0, 128.2, 128.3 and
31P NMR (162 MHz, CDCl3): d = 29.1.
128.5 (4 CHAr), 129.03 (CHAr), 131.3 (CAr), 131.5 and 131.6 (2
CHAr), 132.6 and 132.7 (2 CHAr), 134.0 (d, JC,P = 93.4 Hz, CAr),
142.6 (CAr).
31P NMR (121 MHz, CDCl3): d = 32.8.
MS (EI, 70 eV): m/z (%) = 320 (M+ + 1, 1.5), 211 (14), 210 (100),
141 (49), 109 (10).
Anal. Calcd for C13H22NO4PS (319.10): C, 48.89; H, 6.94; N, 4.39.
Found: C, 48.49; H, 7.27; N, 4.56.
MS (EI, 70 eV): m/z (%) = 412 (M+ + 1, 1), 211 (13), 210 (100), 201
(14), 141 (35).
(S)-1-N-(S-Methyl-S-phenylsulfonimidoyl)-P-diphenyl-P-cyclo-
hexyl-1-phosphine Oxide (9b)
Anal. Calcd for C23H26NO2PS (411.14): C, 67.13; H, 6.37; N, 3.40.
Found: C, 66.83; H, 6.14; N, 3.36.
A Schlenk tube (5 mL) with a screw cap was charged with the N-
vinyl sulfoximine 5 (600 mg, 2.55 mmol) and HP(O)Ph2 (7b; 516
mg, 2.55 mmol). After the tube was carefully purged with argon, the
mixture was heated for 3 h at 100 °C. Then the mixture was cooled
to r.t. Purification by flash chromatography (EtOAc) furnished the
phosphine oxide 9b (959 mg, 86%) as colorless crystals; mp 61 °C;
[a]D20 –27.7 (c 1.00, CH2Cl2); Rf = 0.29 (EtOH).
(1R)-P-Dimethyl-1-N-[(S)-S-methyl-S-phenylsulfonimidoyl]-P-
(2-methylpropyl)-1-phosphonate [(1R)-8c] and (1S)-P-Dimeth-
yl-1-N-[(S)-S-methyl-S-phenylsulfonimidoyl]-P-(2-methylpro-
pyl)-1-phosphonate [(1S)-8c]
A Schlenk tube (5 mL) with a screw cap was charged with the N-
vinyl sulfoximine 3 (300 mg, 1.43 mmol) and HP(O)(OMe)2 (7c;
236 mg, 2.15 mmol). The tube was carefully purged with argon and
the mixture was heated for 23 h at 100 °C. Then the mixture was
cooled to r.t. Purification by flash chromatography (cyclohexane–
EtOH, 80:20) gave the phosphonate 8c (450 mg, 99%) as a mixture
of diastereomers in a ratio of 3:2. Separation by HPLC (cyclohex-
ane–EtOH, 90:10; Kromasil Si 100-column, 30 mm × 250 mm; 15
mL/min) afforded the major diastereomer (254 mg, 56%) and the
minor diastereomer (181 mg, 40%) as viscous oils.
IR (CHCl3): 3063 (w), 2938 (s), 2861 (m), 1441 (m), 1257 (s), 1163
(s), 1115 (m), 968 (w), 751 (s), 698 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 1.22–2.12 (m, 10 H, CH2), 3.02 (s,
3 H, SCH3), 7.14–7.30 (m, 4 H, ArH), 7.40–7.62 (m, 7 H, ArH),
7.96–8.03 (m, 2 H, ArH), 8.27–8.38 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.4 (d, JC,P = 17.3 Hz, CH2), 21.4
(CH2), 25.0 (CH2), 31.9 (CH2), 34.0 (CH2), 48.8 (SCH3), 63.3 (d,
JC,P = 92.2 Hz, C), 127.4 (CHAr), 127.9, 127.9, 128.0 and 128.1 (4
CHAr), 128.8 (CHAr), 130.8 (CAr), 131.1 (d, JC,P = 3.0 Hz, CHAr),
131.4 (d, JC,P = 2.4 Hz, CHAr), 132.0 (d, JC,P = 1.8 Hz, CAr), 132.2
(CHAr), 133.1, 133.2, 133.2 and 133.3 (4 CHAr), 144.2 (CAr).
Major Diastereomer
20
[a]D +64.1 (c 1.00, CH2Cl2); Rf = 0.11 (cyclohexane–EtOH,
31P NMR (162 MHz, CDCl3): d = 36.7.
80:20).
IR (CHCl3): 3446 (w), 2959 (s), 2853 (s), 1453 (m), 1246 (s), 1144
(m), 1038 (s), 973 (w), 884 (w), 823 (w), 749 (s), 691 cm–1 (w).
MS (EI, 70 eV): m/z (%) = 237 (15), 236 (100), 202 (10), 201 (27),
172 (10), 96 (12), 91 (10).
1H NMR (400 MHz, CDCl3): d = 0.93–0.99 (m, 3 H, CH3), 1.04 (d,
J3 = 6.6 Hz, 3 H, CH3), 2.00–2.12 (m, 1 H, CH), 3.19 (s, 3 H,
SCH3), 3.50 (dd, J3 = 4.1 Hz, JH,P = 14.3 Hz, 1 H, CHNP), 3.80 (d,
MS (CI, Isobutane): m/z (%) = 439 (M+ + 1, 30), 237 (15), 236
(100), 203 (63).
Anal. Calcd for C25H28NO2PS (437.16): C, 68.63; H, 6.45; N, 3.20.
Found: C, 68.49; H, 6.41; N, 3.02.
JH,P = 14.1 Hz, 3 H, OCH3), 3.85 (d, JH,P = 14.1 Hz, 3 H, OCH3),
7.52–7.64 (m, 3 H, ArH), 8.00–8.05 (m, 2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 18.4 (d, JC,P = 3.9 Hz, CH3), 21.0
(d, JC,P = 13.7 Hz, CH3), 30.3 (CH), 44.02 (SCH3), 52.8 (d,
JC,P = 7.2 Hz, OCH3), 53.2 (d, JC,P = 7.2 Hz, OCH3), 56.8 (d,
P-Dimethyl-1-N-[(S)-S-methyl-S-phenylsulfonimidoyl]-P-cy-
clohexyl-1-phosphonate (9c)
A Schlenk tube (5 mL) with a screw cap was charged with the N-
vinyl sulfoximine 5 (100 mg, 0.42 mmol) and HP(O)(OMe)2 (7c; 92
mg, 0.84 mmol). The tube was carefully purged with argon and the
mixture was heated for 18 h at 100 °C. Then the mixture was cooled
to r.t. Purification by flash chromatography (hexane–EtOH, 77:33)
gave the phosphonate 9c (137 mg, 96%) as a colorless viscous oil;
[a]D20 –21.0 (c 0.25, CH2Cl2); Rf = 0.20 (hexane–EtOH, 77:33).
JC,P = 161.0 Hz), 127.5 (CHAr), 128.9 (CHAr), 132.6 (CHAr), 140.5
(CAr).
31P NMR (162 MHz, CDCl3): d = 28.8.
MS (EI, 70 eV): m/z (%) = 320 (M+ + 1, 1), 211 (14), 210 (100),
141 (52), 109 (10).
Anal. Calcd for C13H22NO4PS (319.10): C, 48.89; H, 6.94; N, 4.39.
Found: C, 49.24; H, 7.05; N, 4.25.
IR (CHCl3): 3002 (w), 2935 (s), 2853 (m), 1447 (m), 1285 (s), 1236
(s), 1166 (s), 1128 (m), 1067 (s), 1031 (s), 965 (w), 819 (s), 745 (s),
691 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.18–2.18 (m, 10 H, CH2), 3.16 (s,
3 H, SCH3), 3.65 (d, JH,P = 10.1 Hz, 3 H, OCH3), 3.72 (d, JH,P = 10.1
Hz, 3 H, OCH3), 7.48–7.58 (m, 3 H, ArH), 8.06–8.10 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 20.8 (CH2), 20.9 (CH2), 25.5
(CH2), 33.2 (CH2), 33.8 (CH2), 48.9 (SCH3), 52.7 (d, JC,P = 7.8 Hz,
OCH3), 53.3 (d, JC,P = 7.8 Hz, OCH3), 60.1 (d, JC,P = 158.6 Hz,
CPN), 127.5 (CHAr), 128.8 (CHAr), 132.1 (CHAr), 144.4 (CAr).
Minor Diastereomer
20
[a]D –65.5 (c 1.00, CH2Cl2); Rf = 0.11 (cyclohexane–EtOH,
80:20).
IR (CHCl3): 3455 (w), 3062 (w), 2958 (s), 2875 (w), 1450 (m),
1244 (s), 1146 (m), 1038 (s), 978 (w), 881 (m), 823 (m), 789 (m),
749 (s), 691 cm–1 (m).
Synthesis 2008, No. 7, 1126–1132 © Thieme Stuttgart · New York

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Chiral a-(N-Sulfoximido) Phosphines, Phosphine Oxides, and Phosphonates
1131
31P NMR (121 MHz, CDCl3): d = 30.3.
HRMS-EI: m/z calcd for C13H19NO2S: 253.113651; found:
253.113733.
MS (EI, 70 eV): m/z (%) = 237 (14), 236 (100), 96 (16).
MS (CI, Isobutane): m/z (%) = 346 (M + 1, 100), 236 (29).
Minor Diastereomer
[a]D20 +42.2 (c 1.50, CH2Cl2); Rf = 0.13 (EtOH–cyclohexane, 1:4).
HRMS-EI: m/z calcd for C13H18NOS (C15H24NO4PS – C2H6O3P):
236.110912; found: 236.110975 and for C2H6O3P (C15H24NO4PS –
C13H18NOS): 109.005458; found: 109.005483.
IR (KBr): 3504 (s), 3064 (w), 3013 (w), 2931 (s), 2859 (s), 1447
(m), 1406 (w), 1231 (s), 1137 (s), 1081 (s), 990 (s), 963 (m), 900
(w), 844 (m), 787 (m), 747 (s), 691 cm–1 (s).
(S)-N-Cyclohexyl-S-methyl-S-phenylsulfoximine (10)
A Schlenk tube (5 mL) with a screw cap was charged with the N-
vinyl sulfoximine 5 (70 mg, 0.30 mmol) and HPPh2·BH3 (80 mg,
0.40 mmol) was added. After the tube was carefully purged with ar-
gon, the mixture was heated for 19 h at 80 °C. Then the mixture was
cooled to r.t. and applied to a silica gel column. Purification by flash
chromatography (EtOAc) gave the sulfoximine 10 (59 mg, 84%) as
a colorless viscous liquid; [a]D20 –45.7 (c 1.00, CH2Cl2); Rf = 0.14
(EtOAc).
1H NMR (300 MHz, CDCl3): d = 1.01–1.80 (m, 7 H, CH2), 1.97–
2.05 (m, 1 H, CH2), 2.52–2.64 (m, 1 H, CHN), 3.16 (s, 3 H, SCH3),
3.26–3.34 (m, 1 H, CHO), 3.40–3.80 (br s, 1 H, OH), 7.54–7.68 (m,
3 H, ArH), 7.90–7.96 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 24.3 (CH2), 25.0 (CH2), 32.5
(CH2), 34.6 (CH2), 45.7 (SCH3), 61.5 (CHN), 74.5 (CHO), 127.7
(Ar), 128.7 (Ar), 129.5 (Ar), 139.4 (Ar).
MS (EI, 70 eV): m/z (%) = 253 (M+, 17), 194 (50), 142 (10), 141
IR (CHCl3): 3389 (w), 3017 (w), 2930 (s), 2854 (m), 1146 (m),
1232 (s), 1132 (m), 1082 (w), 971 (w), 885 (w), 754 (s), 669 cm–1
(m).
1H NMR (400 MHz, CDCl3): d = 1.00–1.55 (m, 6 H, CH2), 1.60–
1.75 (m, 3 H, CH2), 1.85–1.95 (m, 1 H, CH2), 2.82–2.90 (m, 1 H,
CH), 3.06 (s, 1 H, SCH3), 7.51–7.64 (m, 3 H, ArH), 7.93–7.97 (m,
2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 25.3 (CH2), 25.5 (CH2), 25.6
(CH2), 36.4 (CH2), 37.6 (CH2), 45.7 (SCH3), 54.1 (CH), 128.7
(CHAr), 129.1 (CHAr), 132.5 (CHAr), 140.7 (CAr).
(100), 140 (37), 125 (29), 124 (10).
HRMS-EI: m/z calcd for C13H19NO2S: 253.113651; found:
253.113691.
1-N-(S)-[(2S,S)-2-Hydroxy-4-methylpentyl-S-phenylsulfonimi-
doyl]-P-diphenyl-P-cyclohexyl-1-phosphine Oxide (13a) and
1-N-(S)-[(2R,S)-2-Hydroxy-4-methylpentyl-S-phenylsulfonimi-
doyl]-P-diphenyl-P-cyclohexyl-1-phosphine Oxide (13b)
A Schlenk flask was charged with sulfoximine 9b (100 mg, 0.23
mmol) and THF (5 mL) was added. After the solution was cooled to
–78 °C, n-BuLi (1.6 M in hexane, 0.17 mL, 0.27 mmol) was added
dropwise. The mixture was kept for 15 min at –78 °C and then 3-
methylbutanal (50 mL, 0.46 mmol) was added. After stirring the
mixture for 1 h at –78 °C, it was warmed to r.t. and stirred for 1 h.
Then aq NH4Cl (0.5 mL) and EtOAc (10 mL) were added and the
organic phase was washed with H2O (1 mL). The organic phase was
dried (MgSO4) and concentrated under reduced pressure. Purifica-
tion by flash chromatography (EtOAc–cyclohexane, 1:1) gave the
alcohol 13 (99 mg, 83%) as a mixture of two diastereomers in a ratio
of 85:15. Separation by HPLC (EtOAc–cyclohexane, 1:1; Kromasil
Si 100-column, 30 mm × 250 mm; 20 mL/min) afforded the major
diastereomer of 13 (81 mg, 68%) and the minor diastereomer of 13
(5 mg, 4%) as colorless crystals.
MS (EI, 70 eV): m/z (%) = 237 (M+, 49), 195 (12), 194 (100).
HRMS-EI: m/z calcd for C13H19NOS [M]: 237.118737; found:
237.118643.
(S)-N-[(1R,2R)-2-Hydroxycyclohexyl]-S-methyl-S-phenylsulf-
oximine (11a) and (S)-N-[(1S,2S)-2-Hydroxycyclohexyl]-S-
methyl-S-phenylsulfoximine (11b)
A Schlenk flask (50 mL) was charged with the N-vinyl sulfoximine
5 (100 mg, 0.42 mmol) and THF (10 mL) was added. Then the mix-
ture was cooled to 0 °C and borane–THF complex (1.0 M in THF,
0.84 mL, 0.84 mmol) was added dropwise. The mixture was stirred
first for 15 min at 0 °C and then for 2 h at r.t. After cooling the mix-
ture to 0 °C, it was successively treated with aq NaOH (5 mL, 20%)
and H2O2 (1 mL, 35%). Then the mixture was stirred for 2 h at r.t. It
was then diluted with CH2Cl2 (20 mL), the organic layer was sepa-
rated and the aqueous phase was extracted with CH2Cl2 (20 mL).
The combined organic phases were washed with brine (10 mL),
dried (MgSO4), and concentrated under reduced pressure. Purifica-
tion and separation by flash chromatography (EtOH–cyclohexane,
1:4) gave the major diastereomer of 11 (44 mg, 41%) and the minor
diastereomer of 11 (22 mg, 20%) as colorless oils.
Major Diastereomer
Mp 73 °C; [a]D20 –8.2 (c 1.00, CHCl3); Rf = 0.31 (EtOAc–cyclohex-
ane, 1:1).
IR (KBr): 3505 (m), 3308 (s), 3058 (m), 2930 (s), 2864 (s), 1439 (s),
1288 (s), 1254 (s), 1156 (s), 1115 (s), 1018 (m), 895 (m), 747 (s),
723 (s), 697 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 0.80–0.91 (m, 6 H, CH3), 1.00–
1.11 (m, 1 H, CH), 1.18–1.32 (m, 1 H, CH2), 1.35–2.15 (m, 11 H,
CH2), 2.98–3.22 (m, 2 H, CH2), 4.38–4.30 (m, 2 H, OH and CH),
7.25–7.35 (m, 3 H, ArH), 7.44–7.65 (m, 8 H, ArH), 7.87–7.99 (m,
2 H, ArH), 8.20–8.33 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.2, 21.3 and 21.47 (3 CH2), 21.8
(CH3), 23.3 (CH3), 24.1 (CH), 25.0 (CH2), 32.7 (CH2), 34.0 (CH2),
45.8 (CH2), 63.5 (d, JC,P = 90.3 Hz, CPN), 64.5 (CHO), 67.0 (CH2),
127.8 (CHAr), 128.0, 128.1, 128.2 and 128.2 (4 CHAr), 128.9 (CHAr),
130.7 (CAr), 131.3 (CHAr), 131.6 (CHAr), 131.8 (d, JC,P = 38.7 Hz,
CAr), 132.4 (CHAr), 133.0, 133.1, 133.2 (3 CHAr), 143.6 (CAr).
Major Diastereomer
[a]D20 +116.6 (c 1.00, CH2Cl2); Rf = 0.20 (EtOH–cyclohexane, 1:4).
IR (KBr): 3485 (m), 2930 (s), 2859 (s), 1447 (m), 1407 (w), 1234
(s), 1139 (s), 1079 (s), 988 (m), 961 (m), 899 (w), 842 (w), 788 (m),
747 (s), 690 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.08–1.72 (m, 6 H, CH2), 1.94–
2.05 (m, 2 H, CH2), 2.70–2.81 (m, 1 H, CHN), 3.04–3.15 (m, 4 H,
SCH3 and OH), 3.32–3.42 (m, 1 H, CHO), 7.49–7.66 (m, 3 H, ArH),
7.94–8.00 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 24.4 (CH2), 24.9 (CH2), 32.4
(CH2), 34.9 (CH2), 45.1 (SCH3), 62.1 (CHN), 75.4 (CHO), 128.6
(Ar), 129.5 (Ar), 133.0 (Ar), 139.5 (Ar).
31P NMR (121 MHz, CDCl3): d = 37.2.
MS (EI, 70 eV): m/z (%) = 323 (33), 322 (100), 321 (15), 278 (42),
202 (19), 201 (43).
MS (CI, Isobutane): m/z (%) = 524 (M+ + 1, 17), 323 (21), 322
(100), 203 (65).
MS (EI, 70 eV): m/z (%) = 253 (M+, 17), 194 (49), 142 (10), 141
(100), 140 (37), 125 (29), 114 (10).
Synthesis 2008, No. 7, 1126–1132 © Thieme Stuttgart · New York

1132
R. H. Hetzer et al.
PAPER
HRMS-EI: m/z calcd for C30H38NO3PS (C18H28NO2S – C12H10OP):
322.184077; found: 322.184045.
(8) Hackenberger, C. P. R.; Raabe, G.; Bolm, C. Chem. Eur. J.
2004, 10, 2942.
(9) (a) Dehli, J. R.; Bolm, C. J. Org. Chem. 2004, 69, 8518.
(b) Dehli, J. R.; Bolm, C. Adv. Synth. Catal. 2005, 347, 239.
(10) (10 (a) Pudovik, A. N.; Konovalova, I. V. Synthesis 1979,
81. (b) Cherkasov, R. A.; Galkin, V. I.; Khabibullina, A. B.;
Al Kurdi, K. Phosphorus, Sulfur Silicon Relat. Elem. 1990,
49-50, 61. (c) Semenzin, D.; Etemad-Moghadam, G.;
Albouy, D.; Diallo, O.; Koenig, M. J. Org. Chem. 1997, 62,
2414. (d) Galkin, V. I.; Cherkasov, A. R.; Cherkasov, R. A.
Phosphorus, Sulfur Silicon Relat. Elem. 1999, 144-146,
329. (e) Lewkowski, J. Focus Organomet. Chem. Res. 2005,
167. (f) Delacroix, O.; Gaumont, A. C. Curr. Org. Chem.
2005, 9, 1851. (g) Enders, D.; Saint-Dizier, A.; Lannou, M.-
I.; Lenzen, A. Eur. J. Org. Chem. 2006, 29. (h) Hirai, T.;
Han, L.-B. Org. Lett. 2007, 9, 53. (i) Yoa, Q. Tetrahedron
Lett. 2007, 48, 2749.
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Chem. Rev. 2000, 100, 2159. (b) Ansell, J.; Wills, M. Chem.
Soc. Rev. 2002, 31, 259. (c) Guiry, P. J.; Saunders, C. P.
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(12) (a) Huang, J.; Chen, R. Heteroat. Chem. 2000, 11, 480.
(b) Savignac, P.; Iorga, B. Modern Phosphonate Chemistry;
CRC Press: Boca Raton, 2003. (c) Ma, J.-A. Chem. Soc.
Rev. 2006, 35, 630.
Minor Diastereomer
1H NMR (400 MHz, CDCl3): d = 0.72 (d, J3 = 6.9 Hz, 3 H, CH3),
0.76 (d, J3 = 6.6 Hz, 3 H, CH3), 1.00–1.11 (m, 1 H, CH), 1.25–2.01
(m, 12 H, CH2), 2.95–3.04 (d, J3 = 4.0 Hz, 1 H, CH2), 3.30–3.60 (m,
1 H, CH2), 3.74–3.80 (m, 1 H, CH), 7.20–7.32 (m, 5 H, ArH), 7.48–
7.65 (m, 6 H, ArH), 7.90–8.10 (m, 2 H, ArH), 8.22–8.34 (m, 2 H,
ArH).
MS (EI, 70 eV): m/z (%) = 323 (23), 322 (100), 321 (27), 279 (16),
278 (78), 202 (31), 201 (65), 172 (12).
MS (CI, Isobutane): m/z (%) = 524 (M+ + 1, 21), 405 (27), 323 (22),
322 (100), 203 (43).
Acknowledgment
Financial support of this work by the Deutsche Forschungsgemein-
schaft (SFB 380 and GK 440) is gratefully acknowledged. We thank
Prof. Dr. G. Roth for the determination of the data set of (S)-
8aa·BH3 and C. Vermeeren for HPLC separation.
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Synthesis 2008, No. 7, 1126–1132 © Thieme Stuttgart · New York