P-Chirogenic phosphine/sulfide hybrid ligands

Article abstract of DOI:10.1055/s-2001-18433

P-Chirogenic phosphine/sulfide hybrid ligands 1 were prepared by the use of optically active phosphine-boranes as the intermediates. The palladium complexes of the ligands exhibited high catalytic activity and enantioselectivity in allylic alkylation of 1-acetoxy-1,3-diphenylprop-2-ene with malonate esters.

Full text of DOI:10.1055/s-2001-18433

2
348
SPECIAL TOPIC
P-Chirogenic Phosphine/Sulfide Hybrid Ligands
P
H
-Chirogenic Phos
i
phine/S
r
ulfide
H
o
ybrid Ligan
s
Department of Chemistry, Faculty of Science, Chiba University, Inage-ku, Chiba 263-8522, Japan
Fax +81(43)2902791; E-mail: imamoto@scichem.s.chiba-u.ac.jp
Received 31 July 2001
acid derivatives. This fact intrigued us to develop the bi-
dentate ligands with two different donor atoms in order to
construct highly regulated chiral environment. We report
here the preparation of novel optically active phosphine/
sulfide hybrid bidentate ligands 1 containing a chirogenic
center at a phosphorus atom and their stereoinduction
ability in Pd-catalyzed asymmetric allylic substitution re-
action.9
Abstract: P-Chirogenic phosphine/sulfide hybrid ligands 1 were
prepared by the use of optically active phosphine-boranes as the in-
termediates. The palladium complexes of the ligands exhibited high
catalytic activity and enantioselectivity in allylic alkylation of 1-ac-
etoxy-1,3-diphenylprop-2-ene with malonate esters.
Key words: asymmetric catalysis, allylation, palladium, phospho-
rus, sulfur
P
P
P
SR'
R
Me
Me
R
Me
Introduction
n
R
n
n = 1 : MiniPHOS
n = 2 : BisP*
P-Chirogenic Phosphine/Sulfide
Optically active bidentate phosphine ligands have played
an important role in transition metal-catalyzed asymmet-
ric transformations, and numerous phosphine ligands
Hybrid Ligands (1)
Figure Chemical Structures of C symmetric diphosphine ligands
MiniPHOS and BisP* and the P-chirogenic phosphine/sulfide hybrid
ligands 1
2
have been designed and prepared to develop effective cat-
1
alytic asymmetric processes. The use of C symmetric
2
diphosphine ligands is one of the most powerful strategies
for this purpose owing to their high stereodifferentiation
ability and synthetic accessibility, and a great number of
publications dealing with this type of ligands have ap-
peared so far. On the other hand, an increased attention
has also been paid to the development of the bidentate
Preparation of P-Chirogenic Phosphine/Sulfide
Hybrid Ligands
2
Synthetic routes to P-chirogenic P/S-hybrid ligands are
shown in Schemes 1 and 2. Previously reported phos-
phine-borane procedure was employed to obtain these hy-
brid ligands. (R)-tert-Butylmethyl(p-toluenesulfonyloxy-
methyl)phosphine–borane (2a) and (R)-tert-butylmethyl-
ligands without C symmetry in which two donor atoms
2
3
play different roles from each other. The hybrid type bi-
dentate ligand, in which different heteroatoms are em-
ployed as two donor sites, is one of the representatives and
has already been used in many transition metal-catalyzed
[
2-(p-toluenesulfonyloxy)ethyl]phosphine–borane (2b)
8a,10
were prepared according to the reported procedure.
4
,5
asymmetric reactions with high efficiency. One of the
advantages of the hybrid ligands lies in high accessibility
for structural tuning in both steric and electronic means.
The structural diversity will realize various reactivity and
stereoinduction ability.
(
R)-Methylphenyl(p-toluenesulfonyloxymethyl)phosphi-
ne-borane (2c) was prepared from dimethylphenylphos-
phine–borane via enantioselective hydroxylation and sub-
10,11
sequent tosylation.
The tosylates 2a–c were treated
with sodium thiolate in DMF at ambient temperature. The
Previously, we have designed and prepared C symmetric reactions were completed within 4 hours to give phos-
2
diphosphine ligands with the chirogenic centers at the phine–boranes 3a–j bearing sulfide functionality in excel-
phosphorus atoms (abbreviated as BisP*6 and lent yield. Compounds 3c and 3k could be prepared also
7
MiniPHOS ). These ligands were proven to be quite ef- by a convenient procedure using disulfide (Scheme 2).
fective in some transition metal-catalyzed asymmetric re- Thus, alkyldimethylphosphine–boranes 4a,b were direct-
actions. The non-C symmetric version of BisP*, which ly converted into 3c,k in one pot by successive reactions
2
possesses different substituent patterns on two phospho- with s-BuLi/(–)-sparteine and phenyl disulfide.10
rus atoms, has also been prepared and employed in Rh-
Trialkylphosphine–boranes 3a,c–k were deboranated to
give free phosphine/sulfides 1a,c–k by treatment with tri-
catalyzed asymmetric hydrogenation of dehydroamino
8
acids. The careful choice of substituent combination on
fluoromethanesulfonic acid in toluene, followed by KOH
two phosphorus atoms has provided high enantioselectiv-
ity even in the case of , -disubstituted dehydroamino
12
in ethanol–water (Scheme 3). Compound 3b that bears a
phenyl group on the phosphorus atom was subjected to
deboranation by treatment with 1-methylpyrrolidine to
1
3
1
b. The phosphine/sulfides 1a–k were purified by pass-
Synthesis 2001, No. 15, 12 11 2001. Article Identifier:
ing through a short alumina or silica gel column and used
in the catalytic reactions without further purification.
1
©
437-210X,E;2001,0,15,2348,2353,ftx,en;C04201SS.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

SPECIAL TOPIC
P-Chirogenic Phosphine/Sulfide Hybrid Ligands
2349
BH3
BH3
P
Table Asymmetric Allylic Substitution of 1-Acetoxy-1,3-diphenyl-
prop-2-ene with Malonate Esters Catalyzed by Pd Complexes of 1a
2
R SH, NaH, DMF, rt
SR2
R1
P
OTs
R1
Me
Me
n
n
3
Ph
Ph 1, [(η -allyl)PdCl]2
Ph
(ROCO) HC
Ph
1
3
2
2
2
a : R = t-Bu, n = 1
*
1
b : R = t-Bu, n = 2
CH2(CO2R)2, BSA
1
OAc
c : R = Ph, n = 1
KOAc, CH2Cl2
2
R1
R2
n
time / h yield / %
Entry Ligand
R
Time (h) Yield (%)b ee (%) (config)c
3
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
g
h
i
t-Bu
Ph
t-Bu
t-Bu
Ph
Ph
o-tolyl
p-tolyl
2-naphthyl
p-NO2-C6H4
Cy
1
1
1
1.5
3
3
98
85
97
96
96
89
98
26
92
93
1
2
1a
1b
1c
1c
1c
1d
1d
1d
1e
1f
Me
Me
Me
Me
t-Bu
Me
Me
45
1.5
73
95
99
94
99
99
85
50
61
81
33
39
39
58
90
99
24
19
15 (R)
2 (R)
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
2
3
3
3
4
14
1.5
3
1
1
1
1
1
1
3
2
36
60
1
70 (R)
85 (R)
90 (R)
53 (S)
71 (S)
74 (S)
30 (R)
59 (R)
80 (R)
22 (R)
40 (R)
44 (R)
48 (R)
65 (R)
76 (R)
84 (R)
4d
5d
6
j
Bn
Scheme 1
7d
8d
9
68
BH3
1) s-BuLi/(–)-sparteine
BH3
Et2O, –78 °C, 3 h
t-Bu 117
P
R1
Me
P
SPh
R1
Me
Me
2) PhSSPh, 0 °C to rt
Me
Me
Me
Me
Me
Me
Me
Me
Me
t-Bu
27
43
85
24
22
22
13
1
1
1
3c (R1 = t-Bu) : 92 % yield
3k (R1 = 1-Ad) : 69 % yield
4
a : R = t-Bu
:
R = 1-Ad
4b
10
Scheme 2
1d
1
1
1f
2
1g
1h
1i
BH3
SR2
a or b
R1
Me
P
SR2
13
R1
Me
P
n
n
1
4
3
a-k
1a-k
a) (i) TfOH, toluene, 0 °C to rt, 1 h; (ii) KOH, EtOH/H2O (10/
), 40 °C, 1 h; b) pyrrolidine, 50 °C, 2 h
15
1j
1
1
1
1
6
1k
1k
1k
Scheme 3
7d
84
84
Pd-Catalyzed Asymmetric Allylic Alkylation
8d
The phosphine/sulfide ligands 1 were employed in Pd-cat-
alyzed asymmetric allylic alkylation of allylic acetate
with carbon nucleophiles. The palladium complexes of
phosphine/sulfides were generated in situ from di( -chlo-
ro)bis( -allyl)dipalladium(II) and ligands 1. The allylic
alkylation was performed by mixing 1-acetoxy-1,3-diphe-
a
All reactions were carried out in CH Cl with 3 equiv of malonate es-
2
2
ter, 3 equiv of BSA and 0.1 equiv of KOAc in the presence of 1.5
mol% of [( -allyl)PdCl] and 4 mol% of ligand 1 at r.t., unless other-
3
2
wise noted.
3
b
Isolated yield.
c
Determined by chiral HPLC analysis (DAICEL CHIRALPAK AD,
nylprop-2-ene with dimethyl or di(tert-butyl) malonate, hexane/propan-2-ol, 95:5).
d
The reaction was carried out at –40 °C.
N,O-bis(trimethylsilyl)acetamide (BSA) and potassium
acetate in the presence of Pd complex of 1. The results are
summarized in the Table.
The allylation of dimethyl malonate with Pd complex of
oselectivity is probably due to the formation of a 5-mem-
bered chelate ring structure.
1
a, which has tert-butyl groups on both donor atoms, was
sluggish and gave only 15% ee of allylation product in
3% yield (entry 1). Although ligand 1b, that possesses
Several types of substituent on sulfur atom were also ex-
amined (entries 9–15). Among them, phenyl group was
found to be the best as a substituent on sulfur atom. Intro-
duction of 1-adamantyl group on phosphorus atom result-
ed in high reactivity but rather slightly lower
enantioselectivity than that of 1c (entries 16 and 17). In
each case, the reaction with di(tert-butyl) malonate
showed relatively higher enantioselectivity (entries 5, 8
and 18).
7
phenyl group on phosphorus, provided higher reactivity,
no enantioinduction was observed (entry 2). The use of Pd
complex of 1c, in which phenyl group is introduced on
sulfur atom, showed high catalytic activity and enantiose-
lectivity (entries 3 and 4). The reaction proceeded even at
–
40 °C to afford the allylation product in 94% yield. It is
noteworthy that ligand 1d, in which two donor atoms are
bound to each other by ethylene chain, provided the (S)-
configured products (entries 6–8). This opposite enanti-
Synthesis 2001, No. 15, 2348–2353 ISSN 0039-7881 © Thieme Stuttgart · New York

2
350
H. Sugama et al.
SPECIAL TOPIC
Conclusion
(R)-tert-Butylmethyl(tert-butylthiomethyl)phosphine–borane
(
3a)
Yield: 98%; colorless needles; mp 55–56 °C (hexane); [ ]D -36.9
c = 0.52, CHCl3).
3
0
In summary, novel P-chirogenic phosphine/sulfide hybrid
ligands were prepared according to the phosphine-borane
procedure. The Pd complexs of these P/S-hybrid ligands
exhibited high catalytic activity and enantioselectivity in
asymmetric allylic alkylation of 1-acetoxy-1,3-diphenyl-
prop-2-ene with malonate esters.
(
–
1
IR (KBr): 2970, 2390, 1370, 1070, 910 cm .
1
H NMR (500 MHz, CDCl ): = 0.48 (br q, JHB = 91.9 Hz, 3 H,
3
3
2
BH ), 1.21 [d, J = 13.7 Hz, 9 H, PC(CH ) ], 1.32 (d, J = 9.4
3
HP
3
3
HP
Hz, 3 H, CH ), 1.33 [s, 9 H, SC(CH ) ], 2.67 (dd, J = 13.2 Hz,
3
3 3
2
2
JHP = 8.0 Hz, 1 H, PCH S), 2.78 (dd, J = 13.2 Hz, J = 8.9 Hz, 1
2
HP
H, PCH S).
2
All manipulations were carried out under Argon. NMR spectra were
recorded on a Jeol JMN-LA400 spectrometer (396 MHz for H and
13
C NMR (126 MHz, CDCl ): = 4.6 (d, JCP = 35.1 Hz), 20.3 (d,
3
1
2
JCP = 27.9 Hz), 25.6 (d, J = 3.1 Hz), 28.3 (d, JCP = 32.0 Hz), 30.2,
CP
1
00 MHz for 13C), or Jeol JMN-LA500 spectrometer (500 MHz for
3
4
4.3 (d, J = 3.1 Hz).
CP
1
13
31
H, 126 MHz for C and 202 MHz for P). Chemical shifts are re-
ported in (ppm) referenced to an internal tetramethylsilane stan-
dard for H NMR and to an external 85% H PO standard for
31P NMR (202 Hz, CDCl3): = 28.6 (JPB = 52.0 Hz).
1
31
P
HRMS: m/z Calcd for C H BPS: 219.1508. Found 219.1510.
3
4
10 25
1
3
NMR. Residual CHCl ( = 77.0 for C) was used as internal refer-
3
Anal. Calcd for C H BPS: C 54.55, H 11.90; Found: C 54.58, H
ence for 13C NMR. H, C and P NMR spectra were recorded in
1
13
31
10 26
1
1.89.
CDCl at 25 °C unless otherwise noted. HPLC analysis was per-
3
formed on a Shimadzu LC10AD liquid chromatograph system with
chiral stationary phase column DAICEL CHIRALPAK AD. Com-
pounds 2a and 2b were prepared according to the reported proce-
(
R)-Methylphenyl(tert-butylthiomethyl)phosphine–borane (3b)
3
0
Yield: 85%; colorless needles; mp 112–114 °C (hexane); [ ]D
2
6.7 (c = 0.56, CHCl3).
7
,9
dure described in the literature.
–
1
IR (KBr): 2395, 1435, 1365, 1060, 910 cm .
(
R)-Methylphenyl(p-toluenesulfonyloxymethyl)phosphine–
1H NMR (396 MHz, CDCl3): = 0.57 (br q, J = 92.8 Hz, 3 H,
HB
borane (2c)
2
BH ), 1.25 [s, 9 H, C(CH ) ], 1.68 (d, J = 9.9 Hz, 3 H, CH ), 2.86
3
3
3
HP
3
To a stirred, cooled (0 °C) solution of (R)-methylphenyl(hydroxym-
ethyl)phosphine–borane (2.52 g, 15 mmol, 81% ee) in diisopropyl-
ethylamine (25 mL) was added p-toluenesulfonyl chloride (5.72 g,
2
(
dd, J = 13.4 Hz, J = 7.6 Hz, 1 H, PCH S), 2.90 (dd, J = 13.4 Hz,
HP 2
2
JHP = 8.1 Hz, 1 H, PCH S), 7.44–7.54 (m, 3 H, C H -H ), 7.74–
2
6
5
o,p
7
.79 (m, 2 H, C H -H ).
6 5 m
3
0 mmol) and the mixture was vigorously stirred at r.t. After 1 h, the
1
3
C NMR (126 MHz, CDCl3): = 8.8 (d, JCP = 40.4 Hz), 25.9 (d,
mixture was diluted with EtOAc and treated with 1 M HCl. The or-
ganic layer was separated and the aqueous layer was extracted with
EtOAc (3 30 mL). The combined organic layers were washed with
aq sat. NaHCO solution and brine and dried (Na SO ). The solvent
was removed under reduced pressure and the residue was purified
by flash chromatography on silica gel (hexane–EtOAc, 5:1) to give
3
JCP = 31.0 Hz), 30.2, 43.3 (d, J = 4.2 Hz), 128.6 (d, J = 54.8
CP
CP
2
4
Hz), 128.6 (d, J = 10.3 Hz), 131.5 (d, J = 3.1 Hz), 131.7 (d,
CP
CP
3
JCP = 9.3 Hz).
3
2
4
31P NMR (202 Hz, CDCl3): = 11.0 (JPB = 53.4 Hz).
+
MS-FAB: m/z = 239 (M – H, 100%).
2
8
2
+
c as a white solid; yield: 3.62 g (75%); mp 58.5–61.0 °C; [ ]D
6.8 (c = 0.51, CHCl3).
HRMS: m/z Calcd for C H BNaPS: 263.1171. Found 263.1192.
12 22
–
1
Anal. Calcd for C H BPS: C 60.02, H 9.23. Found C 59.83, H
IR (KBr): 2380, 1360, 1160, 1060, 985 cm .
12 22
9
.20.
1
H NMR (500 MHz, CDCl ): = 0.65 (br q, JHB = 96.0 Hz, 3 H,
3
2
BH ), 1.69 (d, J = 10.4 Hz, 3 H, CH ), 2.44 (s, 3 H, ArCH ), 4.26
(
1
3
HP
2
3
3
(
R)-tert-Butylmethyl(phenylthiomethyl)phosphine–borane (3c)
dd, J = 12.8 Hz, J = 2.5 Hz, 1 H, PCH O), 4.36 (d, J = 12.8 Hz,
HP
2
Yield: 97%; colorless cubes; mp 55.5–56.5 °C (hexane–EtOAc);
[
2
H, PCH O), 7.29 (d, J = 8.5 Hz, 2 Harom), 7.44–7.48 (m, 2 H,
2
26
]D –43.1 (c = 1.38, CHCl3).
C H ), 7.53–7.57 (m, 1 H, C H ), 7.64–7.66 (m, 2 Harom), 7.69–7.73
6
5
6
5
–
1
(
m, 2 H, C H ).
IR (KBr): 2970, 2370, 1580, 1070, 740 cm .
6
5
13C NMR (126 MHz, CDCl3): = 7.1 (d, JCP = 39.3 Hz), 21.7, 65.8
1
H NMR (396 MHz, CDCl ): = 0.51 (br q, JHB = 92.1 Hz, 3 H,
3
3
2
BH ), 1.23 [d, J = 14.0 Hz, 9 H, C(CH ) ], 1.35 (d, J = 9.7 Hz,
3 H, CH
C H -H ), 7.29–7.33 (m, 2H, C H -H ), 7.37–7.40 (m, 2 H, C H -
Ho).
(
d, JCP = 33.1 Hz), 125.6 (d, JCP = 54.8 Hz), 128.1, 129.0 (d,
3
HP
3 3
HP
2
2
3
JCP = 10.3 Hz), 130.1, 131.5, 132.1, 132.2 (d, J = 2.1 Hz), 145.6.
3
), 3.18 (d, JHP = 7.0 Hz, 2 H, PCH
2
S), 7.21–7.25 (m, 1 H,
CP
31P NMR (202 Hz, CDCl3): = 11.3–11.7 (m).
6
5
p
6
5
m
6
5
+
+
MS-FAB: m/z (%) = 321 (M – H, 30), 137 (M – CH OTs, 100).
2
13
C NMR (126 MHz, CDCl3): = 4.7 (d, JCP = 35.2 Hz), 25.4 (d,
2J = 3.1 Hz), 26.6 (d, JCP = 24.8 Hz), 28.3 (d, J = 31.0 Hz),
HRMS: m/z Calcd for C H BO PS: 321.0886. Found 321.0889.
1
5
19
3
CP
CP
3
1
26.8, 129.2, 129.3, 136.4 (d, J = 4.1 Hz).
Anal. Calcd for C H BO PS: C 55.92, H 6.26. Found C 55.90, H
CP
15
20
3
31P NMR (202 Hz, CDCl3): = 30.2 (JPB = 55.5 Hz).
6
.31.
+
MS-FAB: m/z = 239 (M – H, 100%).
Phosphine–Borane/Sulfides 3a–j; General Procedure
HRMS: m/z Calcd for C H BNaPS: 263.1171. Found 263.1173.
To a stirred suspension of NaH (60% oil suspension; 96 mg, 2.4
mmol) in DMF (5 mL) was added the appropriate thiol (2.4 mmol)
at r.t. and the mixture was stirred for 0.5 h. The mixture was added
to a solution of 2a–c (2.0 mmol) in DMF (5 mL) at r.t. After 3 h, the
12 22
Anal. Calcd for C H BPS: C 60.02, H 9.23. Found C 60.11, H
1
2
22
8
.85.
mixture was quenched by 1 M HCl (30 mL) and extracted with Et O
2
(S)-tert-Butylmethyl(2-phenylthioethyl)phosphine–borane (3d)
Yield: 96%; colorless needles; mp 77–78 °C (hexane); [ ]D +13.3
(c = 0.49, CHCl3).
(
3
30 mL). The organic layer was washed with aq sat. NaHCO3
28
solution (20 mL) and brine (20 mL) and dried (Na SO ). After evap-
2
4
oration of the solvent, the residue was chromatographed on silica
gel (hexane–EtOAc, 10:1).
–
1
IR (KBr): 2970, 2370, 1580, 1060, 740 cm .
Synthesis 2001, No. 15, 2348–2353 ISSN 0039-7881 © Thieme Stuttgart · New York

SPECIAL TOPIC
P-Chirogenic Phosphine/Sulfide Hybrid Ligands
2351
1
1
H NMR (396 MHz, CDCl ): = 0.43 (br q, JHB = 92.1 Hz, 3 H,
H NMR (396 MHz, CDCl ): = 0.56 (br q, JHB = 89.8 Hz, 3 H,
3
3
3
2
3
2
BH ), 1.12 [d, J = 13.7 Hz, 9 H, C(CH ) ], 1.22 (d, J = 9.7 Hz,
BH ), 1.26 [d, J = 13.7 Hz, 9 H, C(CH ) ], 1.38 (d, J = 9.7 Hz,
3 HP 3 3 HP
3 H, CH ), 3.28 (d, J = 7.3 Hz, 2 H, PCH S), 7.43–7.52 (m, 3
Harom), 7.76–7.81 (m, 4 Harom).
13
3
HP
3 3
HP
2
3
2
1
H, CH ), 1.76–1.87 (m, 1 H, SCH ), 1.91–2.01 (m, 1 H, SCH ),
3
2
2
3 HP 2
.94–3.03 (m, 1 H, PCH ), 3.21–3.31 (m, 1 H, PCH ), 7.19–7.23 (m,
2
2
H, C H -H ), 7.29–7.35 (m, 4 H, C H -Ho,m).
6
5
p
6
5
C NMR (126 MHz, CDCl3): = 4.8 (d, JCP = 35.1 Hz), 25.5 (d,
13C NMR (100 MHz, CDCl3): = 5.5 (d, JCP = 33.6 Hz), 21.6 (d,
JCP = 27.9 Hz), 25.0, 27.5 (d, JCP = 33.6 Hz), 27.9, 126.5, 129.1,
1
2J = 2.1 Hz), 26.4 (d, JCP = 23.8 Hz), 28.4 (d, JCP = 32.1 Hz),
126.1, 126.8, 127.0, 127.2, 127.3, 127.7, 128.8, 132.0, 133.7, 133.8
(d, J = 4.1 Hz).
CP
3
29.4, 135.0.
CP
31P NMR (202 Hz, CDCl3): = 26.2 (JPB = 58.3 Hz).
31P NMR (202 Hz, CDCl3): = 30.4 (JPB = 54.7 Hz).
+
+
+
MS-FAB: m/z = 253 (M – H, 100%).
MS-FAB: m/z (%) = 289 (M – H, 46), 161 (M – Np – 2 H, 100),
+
5
7 (t-Bu , 56).
HRMS: m/z Calcd for C H BPS: 253.1351. Found 253.1354.
1
3
23
HRMS: m/z Calcd for C H BPS: 289.1351. Found 289.1354.
1
6
23
Anal. Calcd for C H BPS: C 61.43, H 9.52. Found: C 61.17, H
1
3
24
9
.34.
Anal. Calcd for C H BPS: C 66.22, H 8.34. Found C 65.94, H
16 24
7
.96.
(
R)-tert-Butylmethyl[(2-methylphenylthio)methyl]phosphine–
borane (3e):
Yield: 96%; colorless cubes; mp 48–50 °C (hexane); [ ]D 40.5 (c
0.51, CHCl3).
(R)-tert-Butylmethyl[(4-nitrophenylthio)methyl]phosphine–
borane (3h)
3
0
=
Yield: 26%; pale yellow needles; mp 128.5–129.5 °C (hexane–
2
8
–
1
EtOAc); [ ]
D
–55.2 (c = 0.53, CHCl ).
3
IR (KBr): 2360, 1590, 1470, 1060, 750 cm .
–
1
1
IR (KBr): 2380, 1580, 1510, 1340, 1070 cm .
H NMR (500 MHz, CDCl ): = 0.53 (br q, JHB = 91.9 Hz, 3 H,
3
3
2
1
BH ), 1.24 [d, J = 14.0 Hz, 9 H, C(CH ) ], 1.37 (d, J = 9.8 Hz,
H NMR (500 MHz, CDCl ): = 0.55 (br q, JHB = 93.0 Hz, 3 H,
3
HP
3 3
HP
3
2
3
2
3
H, CH ), 2.42 (s, 3 H, ArCH ), 3.10 (dd, J = 13.4 Hz, J = 6.7
BH ), 1.27 [d, J = 14.3 Hz, 9H, C(CH ) ], 1.39 (d, J = 9.8 Hz,
3
3
HP
3 HP 3 3 HP
2
2
Hz, 1 H, PCH S), 3.13 (dd, J = 13.4 Hz, J = 8.4 Hz, 1 H, PCH S),
3 H, CH ), 3.21 (dd, J = 13.1 Hz, J = 9.5 Hz, 1 H, PCH S), 3.27
3 HP 2
2
HP
2
2
7
.13–7.20 (m, 3 Harom), 7.33–7.35 (m, 1 Harom).
(dd, J = 13.1 Hz, J = 5.8 Hz, 1 H, PCH S), 7.40–7.43 (m, 2
HP 2
1
3
H
arom), 8.14–8.18 (m, 2 Harom).
C NMR (126 MHz, CDCl ): = 4.7 (d, JCP = 35.2 Hz), 20.4, 25.5
3
2
13
(
1
d, J = 2.1 Hz), 25.9 (d, JCP = 24.8 Hz), 28.4 (d, J = 32.1 Hz),
26.8, 126.9, 128.9, 130.4, 135.6 (d, J = 5.2 Hz), 138.1.
C NMR (126 MHz, CDCl ): = 5.0 (d, JCP = 34.1 Hz), 24.6 (d,
CP
CP
3
3
2
JCP = 23.8 Hz), 25.4 (d, J = 2.1 Hz), 28.5 (d, JCP = 31.1 Hz),
124.2, 126.7, 145.8, 146.3 (d, JCP = 4.1 Hz).
31P NMR (202 Hz, CDCl
CP
CP
3
31P NMR (202 Hz, CDCl3): = 29.9 (JPB = 54.3 Hz).
+
+
3
): = 31.1 (JPB = 50.6 Hz).
MS-FAB: m/z (%) = 277 (M + Na , 12), 251 (M – 3 H, 84), 57 (t-
Bu , 100).
+
+
+
MS-FAB: m/z (%) = 284 (M – H, 35), 154 (NO C H S , 100), 136
2
6
4
(
74).
HRMS: m/z Calcd for C H BNaPS: 277.1327. Found 277.1330.
1
3
24
HRMS: m/z Calcd for C H BNO PS: 284.1045. Found 284.1048.
1
2
20
2
Anal. Calcd for C H BPS: C 61.43, H 9.52. Found: C 61.30, H
1
3
24
9
.49.
Anal. Calcd for C H BNO PS: C 50.54, H 7.42, N 4.91. Found: C
12 21 2
5
0.41, H 7.39, N 4.90.
(
R)-tert-Butylmethyl[(4-methylphenylthio)methyl]phosphine–
borane (3f)
(R)-tert-Butylmethyl(cyclohexylthiomethyl)phosphine–borane
Yield: 89%; colorless needles; mp 49.5–50.5 °C (hexane–EtOAc);
(3i, Cy = cyclohexyl)
30
28
[
]D –43.9 (c = 0.50, CHCl3).
Yield: 92%; colorless needles; mp 40–41 °C (hexane); [ ]D
(c = 0.53, CHCl ).
67.8
–
1
3
IR (KBr): 2390, 1490, 1070, 910, 810 cm .
–
1
1
IR (KBr): 2930, 2380, 1450, 1060, 915 cm .
H NMR (500 MHz, CDCl ): = 0.50 (br q, JHB = 92.6 Hz, 3 H,
3
3
2
1
BH ), 1.22 [d, J = 13.7 Hz, 9 H, C(CH ) ], 1.34 (d, J = 9.5 Hz,
3
Hz, 1 H, PCH S), 3.16 (dd, J = 13.7 Hz, J = 8.1 Hz, 1 H, PCH S),
7
H NMR (500 MHz, CDCl ): = 0.46 (br q, JHB = 88.2 Hz, 3 H,
3
HP
3 3
HP
3
2
3
2
H, CH ), 2.33 (s, 3 H, ArCH ), 3.13 (dd, J = 13.7 Hz, J = 6.0
BH ), 1.20 [d, J = 13.7 Hz, 9 H, C(CH ) ], 1.32 (d, J = 9.7 Hz,
3
3
HP
3 HP 3 3 HP
2
3 H, CH ), 1.27–1.36 (m, 5 H, CyH), 1.59–1.65 (m, 1 H, CyH),
2
HP
2
3
2
.12 (d, J = 8.0 Hz, 2 Harom), 7.29–7.32 (m, 2 Harom).
1.73–1.82 (m, 2 H, CyH), 1.94–2.04 (m, 2 H, CyH), 2.71 (dd,
2
1
3
J = 13.7 Hz, JHP = 5.8 Hz, 1 H, PCH
2
S), 2.77 (dd, J = 13.7 Hz,
C NMR (126 MHz, CDCl ): = 4.7 (d, JCP = 35.2 Hz), 21.0, 25.5
3
2
2
J
HP = 8.8 Hz, 1 H, PCH
2
S), 2.73–2.79 (m, 1 H, CyH).
(
1
d, J = 3.1 Hz), 27.4 (d, J = 24.8 Hz), 28.3 (d, JCP = 31.0 Hz),
30.0, 130.2, 132.8 (d, JCP = 4.1 Hz), 137.2.
CP
CP
3
13
C NMR (126 MHz, CDCl ): = 4.6 (d, JCP = 36.2 Hz), 21.8 (d,
3
2
31P NMR (202 Hz, CDCl3): = 30.1 (JPB = 54.7 Hz).
JCP = 26.9 Hz), 25.5 (d, JCP = 2.1 Hz), 25.7, 25.9, 26.0, 28.2 (d,
3
JCP = 31.0 Hz), 33.0, 33.1, 46.1 (d, J = 3.1 Hz).
31P NMR (202 MHz, CDCl
CP
+
+
MS-FAB: m/z (%) = 253 (M – H, 100), 251 (M – 3 H, 93), 57 (t-
Bu , 93).
+
3
): = 29.1 (JPB = 57.0 Hz).
+
MS-FAB: m/z = 245 (M – H, 100%).
HRMS: m/z Calcd for C H BNaPS: 277.1327. Found 277.1354.
1
3
24
HRMS: m/z Calcd for C H BPS: 245.1664. Found 245.1667.
1
2
27
Anal. Calcd for C H BPS: C 61.43, H 9.52. Found C 61.19, H
13
24
9
.38.
Anal. Calcd for C H BPS: C 58.54, H 11.46. Found C 58.15, H
12 28
1
1.45.
(
R)-tert-Butylmethyl[(2-naphthylthio)methyl]phosphine–
borane (3g)
Yield: 98%; colorless needles; mp 66–67 °C (hexane); [ ]D –51.8
c = 0.49, CHCl3).
(R)-tert-Butylmethyl[(phenylmethylthio)methyl]phosphine–
2
8
borane (3j)
2
6
(
Yield:93%; colorless needles; mp 48–50 °C (hexane); [ ]D –155.2
(c = 0.50, CHCl ).
–
1
3
IR (KBr): 2390, 1460, 1070, 920, 815 cm .
–
1
IR (KBr): 2970, 2370, 1070, 910, 700 cm .
Synthesis 2001, No. 15, 2348–2353 ISSN 0039-7881 © Thieme Stuttgart · New York

2
352
H. Sugama et al.
SPECIAL TOPIC
1
H NMR (500 MHz, CDCl ): = 0.52 (br q, JHB = 91.7 Hz, 3 H,
Anal. Calcd for C H BPS: C 67.93, H 8.87. Found: C 67.84, H
9.01.
3
18 28
3
2
BH ), 1.13 [d, J = 13.4 Hz, 9 H, C(CH ) ], 1.24 (d, J = 9.4 Hz,
3
(
1
3
HP
3 3
HP
2
H, CH ), 2.53 (dd, J = 14.0 Hz, J = 9.1 Hz, 1 H, PCH S), 2.57
dd, J = 14.0 Hz, J = 4.6 Hz, 1 H, PCH S), 3.82 (d, J = 13.2 Hz,
3 HP 2
2
P-Chirogenic Phosphine/Sulfide Hybrid Ligands 1a,c–k;
General Procedure
HP
2
H, CCH S), 3.89 (d, J = 13.2 Hz, 1 H, CCH S), 7.25–7.28 (m, 1
2
2
H, C H -H ), 7.31–7.35 (m, 4 H, C H -Ho,m).
To a stirred, cooled (0 °C) solution of 3a,c–k (0.5 mmol) in de-
gassed toluene (4 mL) was slowly added trifluoromethanesulfonic
acid (130 L, 1.5 mmol) and the mixture was stirred for 30 min in
an ice-bath. The mixture was further stirred at r.t. for 1 h and con-
centrated under reduced pressure. A solution of KOH (140 mg, 2.5
6
5
p
6
5
1
3
C NMR (126 MHz, CDCl ): = 4.7 (d, JCP = 36.2 Hz), 22.1 (d,
3
2
JCP = 27.9 Hz), 25.3 (d, J = 2.0 Hz), 28.1 (d, JCP = 31.1 Hz), 38.4
(
CP
3
d, J = 3.1 Hz), 127.4, 128.6, 129.2, 137.2.
CP
31P NMR (202 Hz, CDCl3): = 29.8 (JPB = 56.0 Hz).
mmol) in degassed EtOH–H O (1.5 mL, 10:1) was slowly added to
2
+
the resulting pasty oil and the mixture was stirred at 50 °C for 1-2 h
MS-FAB: m/z = 253 (M – H, 100%).
and cooled to r.t. The mixture was diluted with Et O (3 mL) and al-
2
HRMS: m/z Calcd for C H BPS: 253.1351. Found 253.1354.
1
3
23
lowed to stand. The supernatant was separated and the suspended
Anal. calcd for C H BPS: C 61.43, H 9.52. Found C 61.20, H 9.47.
aqueous layer was extracted with freshly distilled Et O (2 3 mL)
13
24
2
and the combined Et O phases were dried (Na SO ) under argon.
2
2
4
(
R)-tert-Butylmethyl(phenylthiomethyl)phosphine–borane (3c)
The solution was filtered through basic alumina column under ar-
gon and concentrated under reduced pressure to give practically
pure 1a,c–k as colorless oil.
from 4a
To a stirred, cooled (–78 °C) solution of (–)-sparteine (1.41 g, 6
mmol) in Et O (10 mL) was added s-BuLi (5.5 mL of a 1.0 M cy-
2
clohexane–hexane solution, 5.5 mmol). After 15 min, a solution of
(R)-tert-Methylphenyl(tert-butylthiomethyl)phosphine (1b)
The phosphine–borane 3b (24.0 mg, 0.1 mmol) was dissolved in 1-
methylpyrrolidine (2 mL) and the solution was stirred for 3 h at
4
a (660 mg, 5 mmol) in Et O (10 mL) was added dropwise and the
2
mixture was stirred at –78 °C. After 3 h, the solution was added to
a Et O solution (20 mL) of diphenyl disulfide (1.64 g, 7.5 mmol) via
50 °C. The volatile was removed as the toluene azeotrope (3
1
2
cannula at 0 °C and the mixture was allowed to warm to r.t. After 2
h, the reaction was quenched by the addition of 1 M HCl and the or-
ganic layer was separated. The aqueous phase was extracted with
EtOAc (3 30 mL) and the combined organic layers were washed
with aq sat. NaHCO solution and brine and dried (Na SO ). The
mL) under reduced pressure (ca. 0.1 Torr) and the residue was fil-
tered through silica gel column with toluene elution under argon.
The filtrate was evaporated in vacuo to give 1b as colorless oil.
3
2
4
Allylic Alkylation of 1-Acetoxy-1,3-diphenylprop-2-ene with
Malonate Esters Catalyzed by Pd Complexes of 1; General
Procedure
solvent was removed under reduced pressure and the residue was
purified by flash chromatography on silica gel (hexane–EtOAc
1
0:1) to give 3c in 92% yield.
To a CH Cl (5 mL) solution of 1a–k (0.04 mmol) was added di( -
2
2
3
chloro)bis( -allyl)dipalladium(II) (5.5 mg, 0.015 mmol) at r.t. and
the solution was stirred for 1 h at this temperature. To the solution
were added a solution of 1-acetoxy-1,3-diphenylprop-2-ene (252
mg, 1.0 mmol) in CH Cl (0.5 mL), N,O-bis(trimethylsilyl)aceta-
(
(
R)-1-Adamantylmethyl(phenylthiomethyl)phosphine–borane
3k)
To a stirred, cooled (–78 °C) solution of (–)-sparteine (914 mg, 3.9
2
2
mmol) in Et O (60 mL) was added s-BuLi (3.6 mL of a 1.0 M cy-
clohexane–hexane solution, 3.6 mmol). After 15 min, a solution of
mide (743 L, 3.0 mmol), KOAc (9.8 mg, 0.1 mmol) and malonate
ester (3 mmol) at –78 °C and the mixture was stirred at r.t. or
2
4
b (630 mg, 3.0 mmol) in toluene (20 mL) was added dropwise and
–40 °C. The reaction was quenched by aq sat. NH Cl solution and
4
the mixture was stirred at –78 °C. After 3 h, the solution was added
diluted with Et O and the organic layer was separated from the
2
to a Et O solution (30 mL) of diphenyl disulfide (982 mg, 4.5 mmol)
aqueous layer. The Et O phase was washed with aq sat. NH Cl and
2
2
4
via cannula at 0 °C and the mixture was allowed to warm to r.t. Af-
ter 2 h, the reaction was quenched by the addition of 1 M HCl and
the organic layer was separated. The aqueous phase was extracted
with EtOAc (3 20 mL) and the combined organic layer was
washed with aq sat. NaHCO solution and brine and dried (Na SO ).
aq sat. NaHCO solutions followed by brine and dried (Na SO ).
3
2
4
The solution was concentrated under reduced pressure and the resi-
due was chromatographed on silica gel (hexane–EtOAc, 5:1). The
enantiomeric excess of the allylation products was determined by
HPLC analysis using a chiral stationary column (DAICEL
CHIRALPAK AD; hexane–propan-2-ol, 95:5).
3
2
4
The solvent was removed under reduced pressure and the residue
was purified by flash chromatography on silica gel (hexane–EtOAc,
1
0:1) to give 3k; yield: 69%; colorless needles; mp 96.5–98.0 °C
28
(hexane–Et O); [ ] –53.5 (c = 0.50, CHCl3).
Acknowledgement
2
D
–
1
IR (KBr): 2910, 2850, 2370, 1060, 745 cm .
This work was supported by a Grant-in Aid for Scientific Research
on Priority Area “Exploitation of Multi-element Cyclic Molecules”
No. 12139299 from the Ministry of Education, Science, Sports and
Culture, Japan.
1
H NMR (400 MHz, CDCl ): = 0.47 (br q, JHB = 91.1 Hz, 3 H,
BH ), 1.31 (d, J = 9.4 Hz, 3 H), 1.71–1.80 (m, 6 H), 1.87–1.89
m, 6 H), 2.05 (br, 3 H), 3.12 (dd, J = 13.5 Hz, J = 5.7 Hz, 1 H,
PCH S), 3.20 (dd, J = 13.5 Hz, J = 8.7 Hz, 1 H, PCH S), 7.20–
3
2
3
HP
2
(
HP
2
2
HP
2
7
.24 (m, 1 H, C H -H ), 7.29–7.33 (m, 2 H, C H -H ), 7.36–7.39
6 5 p 6 5 m
References
(
m, 2 H, C H -H ).
6 5 o
1
3
(1) For reviews, see: (a) Kagan, H. B. In Asymmetric Synthesis,
Vol. 5; Morrison, J. D., Ed.; Academic Press: Orland, 1985,
Chap. 1. (b) Noyori, R. In Asymmetric Catalysis in Organic
Synthesis; Wiley: New York, 1994. (c) Jacobsen, E. N.;
Pfaltz, A.; Yamamoto, H. In Comprehensive Asymmetric
Catalysis; Springer: Berlin, 1999. (d) Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; VCH: Wheinheim, 2000, 2nd ed;.
C NMR (126 MHz, CDCl ): = 3.2 (d, JCP = 36.2 Hz), 25.4 (d,
3
2
JCP = 24.8 Hz), 27.6 (d, J = 8.2 Hz), 31.2 (d, J = 32.1 Hz), 36.2,
3
31P NMR (202 Hz, CDCl3): = 25.5–26.2 (m).
CP
CP
3
6.4, 126.7, 129.1, 129.2, 136.6 (d, J = 4.1 Hz).
CP
+
+
MS-FAB: m/z (%) = 315 (M – H, 76), 135 (adamantyl – H, 100).
HRMS: m/z Calcd for C H BPS: 317.1664. Found 317.1668.
1
8
27
Synthesis 2001, No. 15, 2348–2353 ISSN 0039-7881 © Thieme Stuttgart · New York

SPECIAL TOPIC
P-Chirogenic Phosphine/Sulfide Hybrid Ligands
2353
(
2) For examples, see: (a) Kagan, H. B.; Dang, T.-P. J. Am.
Chem. Soc. 1972, 94, 6429. (b) Vineyard, B. D.; Knowles,
W. S.; Sabacky, S. J.; Bachman, G. L.; Weinkauff, D. J. J.
Am. Chem. Soc. 1977, 99, 5946. (c) Miyashita, A.; Yasuda,
A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R.
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Int. Ed. 1998, 37, 1931. (f) Robin F., Mercier F., Richard L.,
Mathey F., Spagnol M.; Chem. Eur. J.; 1997, 3: 1365.
(5) For recent examples of P/N hybrid ligands, see: (a)Allen, J.
V.; Coote, S. J.; Dawson, G. J.; Frost, C. G.; Martin, C. J.;
Williams, J. M. J. J. Chem. Soc., Perkin Trans. 1 1994,
2065. (b) Lightfoot, A.; Schnider, P.; Pfaltz, A. Angew.
Chem., Int. Ed. 1998, 37, 2897. (c) Flubacher, D.;
Helmchen, G. Tetrahedron Lett. 1999, 40, 3867.
(d) Gilbertson, S. R.; Fu, Z.; Xie, D. Tetrahedron Lett. 2001,
42, 365. (e) Uozumi, Y.; Shibatomi, K. J. Am. Chem. Soc.
2001, 123, 2919.
(
g) Jiang, Q.; Jiang, Y.; Xiao, D.; Cao, P.; Zhang, X. Angew.
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H.; Tsuruta, H.; Matsukawa, S.; Yamaguchi, K. J. Am.
Chem. Soc. 1998, 120, 1635.
Chem.,Int. Ed. 1998, 37, 1100.
(
3) For recent examples, see: (a) Hayashi, T.; Yamamoto, A.;
Hojo, M.; Ito, Y. Chem. Commun. 1989, 495.
(7) Yamanoi, Y.; Imamoto, T. J. Org. Chem. 1999, 64, 2988.
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(9) For general reviews, see: (a) Trost, B. M.; Van Vranken, D.
L. Chem. Rev. 1996, 96, 395; and references cited therein.
(b) Hayashi, T. In Catalytic Asymmetric Synthesis; Ojima, I.,
Ed.; VCH: New York, 1993, 325. (c) Consiglio, G.;
Waymouth, R. M. Chem. Rev. 1989, 89, 257.
(
b) Yoshikawa, K.; Yamamoto, N.; Murata, M.; Awano, K.;
Morimoto, T.; Achiwa, K. Tetrahedron: Asymmetry 1992, 3,
3. (c) Togni, A.; Breutel, C.; Schnyder, A.; Spindler, F.;
Landert, H.; Tijani, A. J. Am. Chem. Soc. 1994, 116, 4062.
d) Nozaki, K.; Sato, N.; Takaya, H. J. Am. Chem. Soc. 1995,
17, 9911. (e) Carmichael, D.; Doucet, H.; Brown, M. J.
1
(
1
Chem. Commun. 1999, 261.
(
4) For recent examples of P/S hybrid ligands, see: (a) Togni,
A.; Häusel, R. Synlett 1990, 633. (b) Hiraoka, M.;
Nishikawa, A.; Morimoto, T.; Achiwa, K. Chem. Pharm.
Bull. 1998, 46, 704. (c) Enders, D.; Peters, R.; Runsink, J.;
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66, 620.
Synthesis 2001, No. 15, 2348–2353 ISSN 0039-7881 © Thieme Stuttgart · New York