Synthesis of novel bidentate P-chiral diaminophosphine oxide preligands: Application to Pd-catalyzed asymmetric allylic substitution reactions

Article abstract of DOI:10.1248/cpb.59.412

We developed a novel (S)-L-phenylalanine derived-bidentate chiral diaminophosphine oxide (DIAPHOX) preligand (S,S_P)-9b, which was successfully applied to Pd-catalyzed asymmetric allylic alkylation and amination. Using the Pd-(S,S_P)-9

Full text of DOI:10.1248/cpb.59.412

4
12
Note
Chem. Pharm. Bull. 59(3) 412—415 (2011)
Vol. 59, No. 3
Synthesis of Novel Bidentate P-Chiral Diaminophosphine Oxide
Preligands: Application to Pd-Catalyzed Asymmetric Allylic
Substitution Reactions
Teisuke HARADA, Tetsuhiro NEMOTO, Long JIN, and Yasumasa HAMADA*
Graduate School of Pharmaceutical Sciences, Chiba University; 1–33 Yayoi-cho, Inage-ku, Chiba 263–8522, Japan.
Received November 27, 2010; accepted December 15, 2010; published online December 15, 2010
We developed a novel (S)-L-phenylalanine derived-bidentate chiral diaminophosphine oxide (DIAPHOX)
preligand (S,S )-9b, which was successfully applied to Pd-catalyzed asymmetric allylic alkylation and amination.
P
Using the Pd-(S,S )-9b catalyst system, asymmetric allylic alkylation and amination proceeded very smoothly, af-
P
fording the corresponding products in excellent yield with high enantiomeric excess. It is noteworthy that both
enantiomers were accessible with high enantiomeric purity using the structurally related DIAPHOX preligands
(
S,S )-9b and a monodentate chiral diaminophosphine oxide preligand (S,R )-10a, both of which can be prepared
P
P
from a single chiral source, (S)-L-phenylalanine.
Key word chiral diaminophosphine oxide; asymmetric allylic substitution; palladium; asymmetric catalysis; preligand
Pd-catalyzed asymmetric allylic substitutions have re- ene-tethered P-chiral diaminophosphine oxide–triphenyl-
ceived considerable attention as useful asymmetric carbon– phosphine hybrids as our target ligands. (S)-Phenylalanine
carbon bond or carbon–heteroatom bond-forming reactions, was selected as the starting material to prepare both diastere-
where racemic or achiral allylic substrates can be converted omers of chiral ligands originating from the chirality of the
23)
into optically active products in the presence of a palla- phosphorus atom.
dium–chiral ligand complex. Extensive efforts have been di- Our ligand synthesis started with commercially available
rected towards the development of effective chiral ligands for N-Z-(S)-phenylalanine 4 (Chart 2). First, 4 was reacted
1—3)
this transformation.
Over the past two decades, we have with aniline using 1-ethyl-3-(3-diethylaminopropyl)-carbodi-
focused on the development of chiral phosphorus ligands imide·hydrochloride (EDC) as a coupling reagent to give the
for transition metal-catalyzed asymmetric allylic substitu- corresponding anilide, which was converted into the known
4—7)
tions.
In 2004, we developed a new class of chiral phos- primary amine derivative 5 through reductive removal of the
phorus ligands: aspartic acid-derived P-chiral diaminophos- Z group (94% yield, 2 steps). Subsequent condensation of 5
phine oxide 1 and its derivatives (DIAPHOXs). These pen- with 2-diphenylphosphinobenzoic acid using 1 eq of dicyclo-
tavalent phosphorus compounds, preligands, are activated in
situ by N,O-bis(trimethysilyl)acetamide (BSA) induced
P(V)—P(III) tautomerization to afford trivalent phosphorus
species such as 2, which function as actual ligands (Chart 1).
These preligands have been successfully applied to Pd- and
8—22)
Ir-catalyzed asymmetric allylic substitution reactions.
Detailed investigations into the reaction mechanism using a
Pd-catalyzed asymmetric allylic alkylation of 1,3-diphenylal-
lyl acetate with dimethyl malonate revealed that complex 3
9)
[
Pd-2 (1 : 2) complex] was the active catalyst. With this re-
sult in hand, we became interested in the development of
bidentate P-chiral diaminophosphine oxide preligands with
an achiral diphenylphosphine moiety as the second coordi-
nating group. Herein, we report the design and synthesis of
novel phenylalanine derived-bidentate P-chiral diaminophos- Chart 1. BSA-Induced P(V)—P(III) Tautomerization of DIAPHOXs and
phine oxide preligands that can be applied to Pd-catalyzed the Active Catalyst Structure of the Asymmetric Allylic Substitution Using
the Pd-DIAPHOX Catalyst System
asymmetric allylic alkylation and amination.
Results and Discussion
Our ligand design is outlined in Fig. 1. The original DI-
APHOX preligands involve an arylmethylene unit on a nitro-
gen atom adjacent to the phosphorus atom, which is intro-
duced by reduction of the corresponding benzamide. The
commercial availability of 2-diphenylphosphinobenzoic acid
led us to introduce a diphenylphosphine moiety into the DI-
APHOX framework by reducing the corresponding benza-
mide prepared from this reagent. Thus, we set up the methyl- Fig. 1. Design of Bidentate P-Chiral Diaminophosphine Oxide Preligands
∗
To whom correspondence should be addressed. e-mail: hamada@p.chiba-u.ac.jp
© 2011 Pharmaceutical Society of Japan

March 2011
413
Table 1. Pd-Catalyzed Asymmetric Allylic Alkylation
Entry
DIAPHOX
Time
Yield
ee
1
2
3
4
5
(S,R )-10a (4 mol%)
4 h
96 h
0.5 h
0.5 h
4 h
99%
35%
99%
99%
99%
95% ee (S)
89% ee (R)
69% ee (S)
93% ee (R)
95% ee (R)
P
(S,S )-10b (4 mol%)
P
Reagents and conditions: (a) aniline, EDC, DMF, rt. (b) Pd-C, H , DMF–2-
2
(S,R )-9a (2 mol%)
P
propanol, rt. (c) DCC, DMAP, CH Cl , rt. (d) NaBH , I , THF, reflux. (e) PCl ,
2
2
4
2
3
(S,S )-9b (2 mol%)
P
NEt , toluene, ꢁ78 °C to rt, then H O.
3
2
(R,S )-10a (4 mol%)
P
Chart 2. Ligand Synthesis
hexylcarbodiimide (DCC) and 10 mol% of N,N-dimethyl-
24)
aminopyridine (DMAP) provided 6 in 98% yield. Reduc-
tion of the amide groups of 6 using in situ-generated BH af-
3
forded a mixture of the desired diamine 8 (63% yield) and
the monoamine 7 (25% yield). Recovered 7 was successfully
transformed into 8 in 76% yield by treating with BH again
3
(total yield of 8: 82%). Finally, the obtained diamine 8 was
reacted with phosphorous trichloride in the presence of NEt3.
After work-up by the addition of water, the obtained residue
was purified by flash column chromatography to give the tar-
get compounds (S,R )-9a and (S,S )-9b in 27% yield and
Chart 3. Pd-Catalyzed Asymmetric Allylic Amination
P
P
25)
55% yield, respectively.
corresponding products (S)-13 and (S)-14 were obtained in
We next used the bidentate P-chiral diaminophosphine ox- 96% yield with 85% ee and in 98% yield with 80% ee, re-
ides (S,R )-9a and (S,S )-9b as chiral phosphorus ligands for spectively (Chart 3).
P
P
a Pd-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-
In conclusion, we developed a novel phenylalanine de-
allyl acetate 11 with dimethyl malonate (Table 1). We first rived-bidentate chiral diaminophosphine oxide preligand
examined the reaction using the corresponding monodentate- (S,S )-9b, which was successfully applied to Pd-catalyzed
P
1
6)
16)
type DIAPHOX (S,R )-10a and (S,S )-10b as the control asymmetric allylic alkylation and amination. Both enan-
P
P
3
experiments. Using 1 mol% of [h -C H PdCl] and 4 mol% tiomers were accessible in a highly enantioselective manner
3
5
2
2
6)
of (S,R )-10a (Pd/ligandꢀ1/2),
the reaction proceeded using (S,S )-9b and (S,R )-10a, both of which can be pre-
P
P P
smoothly at 4 °C to provide (S)-12 in 99% yield with 95% ee pared from a single chiral source. Detailed mechanistic
entry 1). Using (S,S )-10b, however, the same reaction pro- investigations into the present catalyst system, as well as
(
P
ceeded very sluggishly, affording the product with an oppo- studies on the application of bidentate-type DIAPHOX
site stereochemistry in only 35% yield, even after 96 h (entry preligands to other catalytic asymmetric reactions, are in
2). In striking contrast, chiral Pd catalysts prepared using progress.
(
S,R )-9a or (S,S )-9b effectively promoted the reaction. In
P P
Experimental
particular, when the reaction was performed using 1 mol% of
General Infrared (IR) spectra were recorded on a JASCO Fourier trans-
form (FT)/IR 230 Fourier transform infrared spectrophotometer, equipped
3
[
4
h -C H PdCl] and 2 mol% of (S,S )-9b (Pd/ligandꢀ1/1) at
3
5
2
P
°C, (R)-12 was obtained in 99% yield with 93% ee (entry with ATR (Smiths Detection, DuraSample IR II, Canada). NMR spectra
). Conventionally, unnatural (R)-D-amino acid-derived DI- were recorded on a JEOL ecp 400 spectrometer, operating at 400 MHz for
4
1
13
31
H-NMR, 100 MHz for C-NMR, and 160 MHz for P-NMR. Optical rota-
APHOX preligands, such as (R,S )-10a, were essential to ob-
tain products with an opposite stereochemistry to that ob-
tained with DIAPHOXs bearing (S,R ) configurations (entry
P
tions were measured on a JASCO P-1020 polarimeter. Electrospray ioniza-
tion (ESI) mass spectra were measured on JEOL AccuTOF LC-plus JMS-
T100LP. The enantiomeric excess was determined by HPLC analysis. HPLC
P
5
). It is noteworthy that both enantiomers were accessible was performed on JASCO HPLC systems consisting of the following: pump,
with high enantiomeric purity using the structurally related PU-980; detector, UV-970, measured at 254 nm. Reactions were carried out
in dry solvent. Other reagents were purified by the usual methods.
DIAPHOX preligands derived from a single chiral source,
Preparation of Bidentate P-Chiral Diaminophosphine Oxide (S,R )-
P
(
S)-L-phenylalanine. The Pd-(S,S )-9b catalyst system was
P
9
a and (S,S )-9b. Compound 6 To a stirred solution of 5 (200 mg,
P
also applicable to asymmetric allylic amination. When ben-
zylamine and morpholine were utilized as nucleophiles, the steps from 4), 2-diphenylphosphinobenzoic acid (280.4 mg, 0.915 mmol)
0
.832 mmol), which was prepared using the reported method (94% yield, 2
16)

4
14
Vol. 59, No. 3
and DMAP (111.8 mg, 0.915 mmol) in CH Cl (4.1 ml) at room temperature (CDCl ) d: 38.4, 45.6 (dd, Jꢀ7.0, 20.5 Hz), 47.8 (d, Jꢀ9.2 Hz), 56.1 (d,
2
2
3
was added DCC (206.3 mg, 1.00 mmol). The resulting mixture was kept stir-
ring at the same temperature. After 24 h, the mixture was filtered through a
short pad of celite, and the filtrate was evaporated under reduced pressure.
Jꢀ6.5 Hz), 115.7 (d, Jꢀ5.3 Hz) (2C), 121.6, 126.6, 128.4—129.3 (m, 9C),
129.2 (d, Jꢀ5.4 Hz) (2C), 129.2 (d, Jꢀ5.4 Hz) (2C), 130.1 (d, Jꢀ5.4 Hz),
133.5 (d, Jꢀ19.5 Hz) (2C), 133.5 (d, Jꢀ19.5 Hz) (2C), 135.1, 136.0 (d,
The crude residue was purified by flash column chromatography (SiO2, Jꢀ8.8 Hz), 136.5 (d, Jꢀ3.1 Hz), 136.6 (d, Jꢀ9.1 Hz), 137.9, 141.2 (dd,
3
1
hexane/AcOEtꢀ10/1) to give 6 (430.9 mg, 98% yield) as white solids. IR
Jꢀ6.1, 25.2 Hz), 141.9 (d, Jꢀ8.1 Hz); P-NMR (CDCl ) d: ꢁ16.3 (d,
3
(
1
ATR) n 3264, 3058, 1678, 1618, 1584, 1530, 1496, 1444, 1434, 1389,
Jꢀ10.2 Hz), 12.4 (d, Jꢀ10.2 Hz); ESI-HR-MS. Calcd for C H N NaOP
3
4
32
2
2
ꢁ1
1
ꢂ
23
299, 1251, 738, 692 cm ; H-NMR (CDCl ) d: 2.91 (dd, Jꢀ7.6, 14.4 Hz, (MꢂNa ): 569.1888. Found: 569.1892; [a]D ꢂ38.4 (cꢀ0.58, CHCl3).
3
1
H), 3.20 (dd, Jꢀ6.8, 14.4 Hz, 1H), 4.84 (ddd, Jꢀ6.8, 7.2, 7.6 Hz, 1H), 6.33
General Procedure for the Pd-Catalyzed Asymmetric Allylic Alkyla-
3
(
1
d, Jꢀ7.2 Hz, 1H), 6.97—7.01 (m, 1H), 7.06—7.11 (m, 2H), 7.21—7.38 (m, tion Using (S,S )-9b To a stirred solution of [h -C H PdCl] (1.1 mg,
P
3
5
2
1
3
8H), 7.40—7.44 (m, 1H), 7.48—7.50 (m, 2H), 8.44 (s, 1H); C-NMR
0.003 mmol), (S,S )-9b (3.3 mg, 0.006 mmol) in CH Cl (1 ml) at room tem-
P
2
2
(
(
(
CDCl ) d: 37.5, 55.9, 120.2 (2C), 124.3, 127.0, 127.8 (d, Jꢀ5.8 Hz), 128.7 perature was added BSA (222 ml, 0.90 mmol). After being stirred for 10 min
3
d, Jꢀ7.2 Hz) (2C), 128.7 (2C), 128.8 (2C), 128.9 (d, Jꢀ7.3 Hz) (2C), 129.2
2C), 128.8—129.2 (m, 3C), 130.6, 133.6 (d, Jꢀ13.0 Hz) (2C), 133,8 (d,
at the same temperature, a CH Cl solution of 11 (76.0 mg, 0.30 mmol in
2 2
0.5 ml of CH Cl ) and dimethyl malonate (103 ml, 0.90 mmol) were added
2
2
Jꢀ13.4 Hz) (2C), 134.3, 135.5—138.4 (m, 3C), 136.5, 137.6, 140.5, 168.6, successively to the reaction at 4 °C. After 30 min, the reaction was concen-
3
1
1
69.4; P-NMR (CDCl ) d: ꢁ10.7; ESI-high resolution (HR)-MS. Calcd trated under reduced pressure. The obtained residue was purified by flash
3
ꢂ
23
9)
for C H N NaO P (MꢂNa ): 551.1864. Found: 551.1858; [a] ꢁ48.0 column chromatography (SiO2, hexane/AcOEt, 30/1) to give (R)-12
3
4
29
2
2
D
(
cꢀ2.41, CHCl ).
(96.3 mg, 99% yield, 93% ee) as colorless oil. The enantiomeric excess was
3
Compound 8 To a stirred suspension of 6 (427.3 mg, 0.81 mmol) and determined by HPLC analysis (DAICEL CHIRALPAK AD-H, 2-
NaBH (184.7 mg, 4.86 mmol) in tetrahydrofuran (THF) (4.1 ml) was added
a THF solution of I2 (308.4 mg, 2.43 mmol in 4 ml of THF) at 0 °C over
propanol/hexane 8/92, flow rate 0.5 ml/min, tR 22.9 min [(R)-isomer] and
31.8 min [(S)-isomer], detection at 254 nm).
4
11)
3
1
min. The reaction mixture was refluxed for 48 h, cooled to 0 °C, and then
N HCl was added to the reaction mixture. After refluxing for 2 h, the reac-
Compound (S)-13
The enantiomeric excess was determined by
HPLC analysis (DAICEL CHIRALCEL OJ-H, 2-propanol/hexane 15/85,
flow rate 0.4 ml/min, tR 27.1 min [(S)-isomer] and 35.3 min [(R)-isomer], de-
tection at 254 nm).
tion mixture was neutralized using 1 N NaOH. The organic layer was sepa-
rated and aqueous layer was extracted with AcOEt. The combined organic
layers were washed with water, brine, and dried over Na SO . After concen-
11)
Compound (S)-14
The enantiomeric excess was determined by
2
4
tration under reduced pressure, the residue was purified by flash column
HPLC analysis (DAICEL CHIRALCEL OJ-H, 2-propanol/hexane 5/95, flow
rate 0.5 ml/min, tR 20.5 min [(S)-isomer] and 29.1 min [(R)-isomer], detec-
tion at 254 nm).
chromatography (SiO , hexane/AcOEtꢀ10/1 to 2/1) to give diamine 8
2
(
7
255.0 mg, 63% yield) and monoamine 7 (102.9 mg, 25% yield). Compound
could be transformed into 8 in 76% yield by treating with the same reac-
tion conditions again (total yield of 8: 82%). IR (ATR) n 3368, 3324, 3052,
Acknowledgments This work was supported in part by a Grant-in-Aid
for Encouragement of Young Scientists (B) from the Ministry of Education,
ꢁ
1 1
3
2
3
024, 2921, 2851, 1602, 1505, 1477, 744, 694 cm ; H-NMR (CDCl ) d:
3
.64—2.74 (m, 2H), 2.90 (dd, Jꢀ5.6, 11.6 Hz, 1H), 3.03—3.08 (m, 1H), Culture, Sports, Science and Technology of Japan.
.10 (dd, Jꢀ7.6, 11.6 Hz, 1H), 3.93 (dd, Jꢀ1.6, 12.8 Hz, 1H), 4.00 (d,
Jꢀ12.8 Hz, 1H), 4.30—4.70 (broad peak (NH), 2H), 6.54—6.56 (m, 2H), References and Notes
1
3
6
(
1
.64—6.68 (m, 1H), 6.88—6.91 (m, 1H), 7.06—7.38 (m, 20H); C-NMR
1) For a review of transition metal-catalyzed asymmetric allylic substitu-
tions, see: Trost B. M., Van Vranken D. L., Chem. Rev., 96, 395—422
(1996).
CDCl ) d: 39.2, 45.2, 49.8 (d, Jꢀ19.8 Hz), 57.9, 113.0 (2C), 116.9, 126.2,
27.4, 128.4—129.3 (m, 14C), 133.7 (d, Jꢀ9.8 Hz) (2C), 133.9 (d,
3
Jꢀ9.8 Hz) (2C), 134.0, 135.9 (d, Jꢀ14.0 Hz), 136.8 (d, Jꢀ9.9 Hz), 136.9 (d,
2) For a review of transition metal-catalyzed asymmetric allylic substitu-
tions, see: Trost B. M., Crawley M. L., Chem. Rev., 103, 2921—2943
(2003).
3) For a review of transition metal-catalyzed asymmetric allylic substitu-
tions, see: Lu Z., Ma S., Angew. Chem. Int. Ed., 47, 258—297 (2008).
4) Hamada Y., Seto N., Ohmori H., Hatano K., Tetrahedron Lett., 37,
7565—7568 (1996).
3
1
Jꢀ9.9 Hz), 138.8, 144.3 (d, Jꢀ23.8 Hz), 148.8; P-NMR (CDCl ) d:
3
ꢂ
ꢁ
15.4; ESI-HR-MS. Calcd for C H N P (MꢂH ): 501.2460. Found:
34 34 2
2
4
5
01.2453; [a] ꢂ3.55 (cꢀ0.81, CHCl3).
D
Compound (S,R )-9a and (S,S )-9b To
a stirred solution of 8
P
P
(721.1 mg, 1.44 mmol) and triethylamine (0.783 ml, 5.62 mmol) in toluene
(14.4 ml) at ꢁ78 °C was added phosphorous trichloride (0.138 ml,
1
.58 mmol) over 3 min. The reaction temperature was gradually warmed up
5) Hamada Y., Seto N., Takayanagi Y., Nakano T., Hara O., Tetrahedron
Lett., 40, 7791—7794 (1999).
6) Hamada Y., Sakaguchi K., Hatano K., Hara O., Tetrahedron Lett., 42,
1297—1299 (2001).
7) Hara O., Koshizawa T., Makino K., Kunimune I., Namiki A., Hamada
Y., Tetrahedron, 63, 6170—6181 (2007).
to room temperature, and then the mixture was kept stirring for 12 h. After
diluting with AcOEt, the reaction was quenched with the addition of water.
The obtained mixture was washed with water, brine, and then dried over
Na SO . After concentration in vacuo, the obtained residue was purified by
2
4
flash column chromatography (SiO , hexane/AcOEtꢀ4/1 to 1/1) to give
2
(
S,R )-9a (213.1 mg, 27% yield) and (S,S )-9b (431.8 mg, 55% yield) as
8) Nemoto T., Matsumoto T., Masuda T., Hitomi T., Hatano K., Hamada
Y., J. Am. Chem. Soc., 126, 3690—3691 (2004).
9) Nemoto T., Masuda T., Matsumoto T., Hamada Y., J. Org. Chem., 70,
7172—7178 (2005).
P
P
white solids. (S,R )-9a: IR (ATR) n 3068, 2926, 1600, 1500, 1434, 1302,
1
2
P
ꢁ
1
1
232, 1204, 1166, 1109, 1029, 963, 744, 695 cm
;
H-NMR (CDCl ) d:
3
.44 (dd, Jꢀ10.0, 13.2 Hz, 1H), 3.13 (dd, Jꢀ3.6, 13.2 Hz, 1H), 3.24 (ddd,
Jꢀ4.4 Hz (CH –NPh–P(ꢀO)H), 9.6, 9.6 Hz, 1H), 3.44 (ddd, Jꢀ6.0 Hz 10) Nemoto T., Fukuda T., Matsumoto T., Hitomi T., Hamada Y., Adv.
2
(
CH –NPh–P(ꢀO)H), 6.0, 9.6 Hz, 1H), 3.68—3.78 (m, 1H), 4.38 (dd,
Synth. Catal., 347, 1504—1506 (2005).
Jꢀ9.6 Hz (H(Oꢀ)P–NCH Ar), 15.6 Hz, 1H), 4.90 (ddd, Jꢀ5.2 Hz 11) Nemoto T., Masuda T., Akimoto Y., Fukuyama T., Hamada Y., Org.
2
2
(
(
7
Ph P–C–C–CH N), 10.8 Hz (H(Oꢀ)P–NCH Ar), 15.6 Hz, 1H), 6.87—7.08
Lett., 7, 4447—4450 (2005).
m, 7H), 7.20—7.52 (m, 16H), 7.58 (d, Jꢀ629.2 Hz (P(ꢀO)H), 1H), 7.82— 12) Nemoto T., Jin L., Nakamura H., Hamada Y., Tetrahedron Lett., 47,
2
2
2
13
.85 (m, 1H); C-NMR (CDCl ) d: 39.4, 43.8 (dd, Jꢀ6.5, 27.5 Hz), 47.8 (d,
6577—6581 (2006).
3
Jꢀ9.5 Hz), 56.1 (d, Jꢀ6.9 Hz), 115.8 (d, Jꢀ5.3 Hz) (2C), 121.6, 126.8, 13) Nemoto T., Sakamoto T., Matsumoto T., Hamada Y., Tetrahedron Lett.,
28.4—132.1 (m, 15C), 133.3, 133.7 (d, Jꢀ19.5 Hz) (2C), 134.1 (d,
47, 8737—8740 (2006).
Jꢀ19.5 Hz) (2C), 135.8 (d, Jꢀ14.1 Hz), 136.0 (d, Jꢀ9.2 Hz), 136.8, 141.2 14) Nemoto T., Fukuyama T., Yamamoto E., Tamura S., Fukuda T., Mat-
1
3
1
(
dd, Jꢀ3.4, 23.6 Hz), 141.6 (d, Jꢀ7.3 Hz); P-NMR (CDCl ) d: ꢁ16.3 (d,
sumoto T., Akimoto Y., Hamada Y., Org. Lett., 9, 927—930 (2007).
Jꢀ10.2 Hz), 12.4 (d, Jꢀ10.2 Hz); P-NMR (CDCl ) d: ꢁ15.3, 11.3; ESI- 15) Nemoto T., Sakamoto T., Fukuyama T., Hamada Y., Tetrahedron Lett.,
3
3
1
3
ꢂ
HR-MS. Calcd for C H N NaOP (MꢂNa ): 569.1888. Found: 569.1900;
48, 4977—4981 (2007).
a] ꢁ68.0 (cꢀ0.41, CHCl ). (S,S )-9b: IR (ATR) n 3051, 2926, 1600, 16) Nemoto T., Harada T., Matsumoto T., Hamada Y., Tetrahedron Lett.,
34
32
2
2
2
4
[
1
D
3
P
ꢁ
1 1
497, 1473, 1434, 1301, 1228, 1166, 965, 742, 697 cm ; H-NMR (CDCl )
48, 6304—6307 (2007).
3
d: 2.72—2.42 (m, 1H), 2.73 (dd, Jꢀ10.8, 13.2 Hz, 1H), 3.03—3.09 (m, 1H), 17) Jin L., Nemoto T., Nakamura H., Hamada Y., Tetrahedron: Asymmetry,
3
.24—3.33 (m, 1H), 3.34 (dd, Jꢀ3.6, 13.2 Hz, 1H), 4.55 (dd, Jꢀ8.8 Hz
19, 1106—1113 (2008).
(
1
1
H(Oꢀ)P–NCH Ar), 14.4 Hz, 1H), 4.79 (dd, Jꢀ6.8 Hz (H(Oꢀ)P–NCH Ar),
18) Nemoto T., Tamura S., Sakamoto T., Hamada Y., Tetrahedron: Asym-
metry, 19, 1751—1759 (2008).
19) Nemoto T., Kanematsu M., Tamura S., Hamada Y., Adv. Synth. Catal.,
2
2
4.4 Hz, 1H), 6.94—7.06 (m, 6H), 7.14—7.33 (m, 16H), 7.40—7.44 (m,
1
3
H), 7.46 (d, Jꢀ628.8 Hz (P(ꢀO)H), 1H), 7.54—7.57 (m, 1H); C-NMR

March 2011
415
3
51, 1773—1778 (2009).
pathway in the stage of introduction of the phosphine oxide moiety.
See ref. 9 for details.
24) Breit B., Laungani A. C., Tetrahedron: Asymmetry, 14, 3823—3826
(2003).
2
2
2
2
0) Nemoto T., Yamamoto E., Franzén R., Fukuyama T., Wu R., Fuka-
machi T., Kobayashi H., Hamada Y., Org. Lett., 12, 872—875 (2010).
1) For a review, see: Nemoto T., Hamada Y., Chem. Rec., 7, 150—158
(
2007).
2) For a review, see: Nemoto T., Chem. Pharm. Bull., 56, 1213—1228
2008).
25) The absolute configuration of the phosphorus atom of 9a and 9b was
predicted by comparing the measured optical rotation with that of
(S,R )-(ꢁ)-10a and (S,S )-(ꢂ)-10b.
(
P
P
3) Aspartic acid-derived P-chiral DIAPHOX preligands with (S,S ) con- 26) The Pd-ligand ratio (Pd/10a or Pd/10bꢀ1/2) was set based on the pre-
P
figurations are not accessible because of the characteristic reaction
vious examinations using DIAPHOX 1. See ref. 9 for details.