Novel chiral sulfinamide phosphines: Valuable precursors to chiral β-aminophosphines

Article abstract of DOI:10.1016/j.tet.2015.12.002

Starting from commercially available aldehyde and chiral tert-butanesulfinamide, a series of chiral sulfinamide phosphines (Xiao-Phos) were synthesized via a two-step condensation-nucleophilic addition procedure. In most cases, nucleophilic addition of th

Full text of DOI:10.1016/j.tet.2015.12.002

Tetrahedron 72 (2016) 2700e2706
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Novel chiral sulfinamide phosphines: valuable precursors to chiral
b-aminophosphines
,
a,b,
*
Peng Chen a, Xiao Su a, Wei Zhou a, Yuanjing Xiao a , Junliang Zhang
*
a Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University,
Shanghai, 200062, PR China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, CAS. 345 Lingling Road, Shanghai, 200032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 October 2015
Received in revised form 23 November 2015
Accepted 1 December 2015
Available online 18 December 2015
Starting from commercially available aldehyde and chiral tert-butanesulfinamide, a series of chiral sul-
finamide phosphines (Xiao-Phos) were synthesized via a two-step condensation-nucleophilic addition
procedure. In most cases, nucleophilic addition of the N-tert-butanesulfinyl imine with diphenyl methyl
phosphonic lithium showed high diastereoselectivity (d.r>20:1) with BF3 as additives. Following re-
moval of the chiral auxilliary, an important class of ligands i.e chiral
b
-aminophosphines and its de-
rivatives were obtained in high yields using this approach.
Keywords:
Ó 2015 Published by Elsevier Ltd.
Nucleophilic catalysis
Diastereoselectivity
Imines
Xiao-Phos
Chiral b-aminophosphine
1. Introduction
commercially available chiral tert-butylsulfinamide via a two-step
condensation-nucleophilic addition procedure.3 It was well
In the past two decades, the asymmetric nucleophilic catalysis
has been developed into one of the most powerful and efficient tool
for the preparation of chiral organic molecules. Compared with
similarly substituted amine catalysts, phosphines displayed unique
catalytic activities because of their weaker basicity and stronger
nucleophilicity.1 Phosphine-promoted catalytic processes, particu-
larly asymmetric reactions that are catalyzed by chiral phosphines
have emerged as a powerful approach to structurally diverse and
synthetically valuable optically active organic building blocks,2
which has attracted enormous attention in recent years.
known that chiral b-aminophosphines represent one of the most
attractive chiral phosphines, which have been widely utilized as
nucleophilic catalysts4 or chiral ligands5 in a broad spectrum of
useful organic transformations. However, only a few methods for
the efficient synthesis of b-aminophosphines have been developed
and the one from natural amino acids is the most commonly used
one method (Scheme 1a).6 Very recently, we designed a novel type
of chiral b-sulfinamide phosphines, structured as Xiao-Phos, which
could be obtained by using commercially available aldehyde and
diphenyl methyl phosphonic lithium.7 We envisaged that an im-
The development of novel chiral phosphine catalysts is one of
the most attractive and practical aspects in organocatalysis. Very
recently, our group has developed a new type of chiral sulfinamide
monophosphine ligands (Ming-Phos), which performed well in the
enantioselective gold-catalyzed cycloaddition reaction of 2-(1-
alkynyl)-alk-2-en-1-ones with nitrones. Both enantiomers of the
products could be obtained in good yields and with excellent dia-
stereo- and enantioselectivity by the use of gold complexes derived
from two diastereomers of Ming-Phos. The Ming-Phos ligands
could be easily prepared in good yields from inexpensive,
portant class of ligands i.e. chiral b-aminophosphines could be
Scheme 1. Synthesis of chiral b-aminophosphines.
* Corresponding authors. Tel.: þ86 21 62233213; e-mail addresses: yjxiao@chem.
ecnu.edu.cn (Y. Xiao), jlzhang@chem.ecnu.edu.cn (J. Zhang).
http://dx.doi.org/10.1016/j.tet.2015.12.002
0040-4020/Ó 2015 Published by Elsevier Ltd.

P. Chen et al. / Tetrahedron 72 (2016) 2700e2706
2701
obtained via the removal of the chiral auxilliary (Scheme 1b).
Herein, we report our efforts for the synthesis of Xiao-Phos and the
success of removal of the BuSO auxilliary group.
reported procedure,9 which would undergo nucleophilic addition
to chiral (RS)-sulfinimine N1 at ꢁ78 ꢀC, furnishing the desired
product X1 in 71% yield with 5:1 dr (Table 1, entry 1). The absolute
configurations of (S, RS)-X1 was established by single-crystal X-ray
diffraction analysis.10 Solvent screening was subsequently per-
formed and THF was found to be the best solvent. Other solvents
such as Et2O, toluene, DME and dioxane didn’t bring significant
improvement in diastereoselectivity. When the reaction was car-
ried out at room temperature, the corresponding product could be
obtained in 70% yields with 10:1 dr (Table 1 entry 6). Notably, the
addition of BF3$Et2O (2.0 equiv) to the reaction system could re-
markably improve the diastereoselectivity to >20:1 dr (Table 1
entry 7).
t
2. Results and discussion
Our initial attempts for the preparation of Xiao-Phos started
from readily available benzaldehyde and chiral tert-butanesulfina-
mide (Scheme 2). The corresponding imine N1 was obtained in
excellent yield when the reaction was performed at 60 ꢀC in the
presence of titanium tetraisopropanolate as Lewis acid.8 Treatment
of Ph2PMe with n-BuLi in the presence of TMEDA at room tem-
perature would produce a solution of Ph2PCH2Li in THF according to
Having established the optimal reaction conditions for the
synthesis of chiral sulfinamide phosphines (S, RS)-X1, we next fo-
cused on the substrate scope of this transformation. Chiral sulfinyl
imines N2eN18 were easily prepared by the condensation of tert-
butanesulfinamide with the corresponding aldehydes according to
the reported procedure. With these imines in hand, the scope of
nucleophilic addition of Ph2PCH2Li to these substrates was sub-
sequently investigated under identified reaction conditions and the
results are outlined in Scheme 2. As demonstrated in Scheme 2, the
nucleophilic addition of Ph2PCH2Li with chiral sulfinyl imines
N1eN18 is pretty general and practically useful method for the
preparation of a range of functionalized chiral sulfonamide phos-
phine X1eX18. Chiral sulfinyl imines derived from aromatic alde-
hydes with various substituents at different position of phenyl ring
generally exhibited high diastereoselectivities (d.r>20) with mod-
erate isolated yields (S, Rs)-X1eX9 except the sulfinyl imines
N10eN11, which give the corresponding X10eX11 with a 1: 1 ratio
of two diastereoisomers. The additions to chiral sulfinyl imines
derived from aliphatic aldehydes as well as heteroaromatic alde-
hyde such as furan-2-carbaldehyde and thiophene-2-carbaldehyde
showed acceptable diastereoselectivities (d.r¼5: 1e10:1), delivered
the corresponding (S, Rs)-X12eX18 in good yields, albeit that in
some cases two diastereomers are not easily separated by the flash
column chromatography.
Synthetic applications of our novel designed chiral
mide phosphines (Xiao-Phos) for synthesis of various types of
chiral -aminophosphines and its derivatives have been showcased
b-sulfina-
b
by the selective transformations of the representative Xiao-Phoses
X1, X14, X15 and X16 (Scheme 3). The attempts to direct removal of
t
the BuSO auxilliary group under acid conditions (4M HCl/MeOH)
failed, which led to the oxidation of the phosphine. Thus, we then
decided to protect the phosphine with the use of borane in THF. The
structure of BH3-protected intermediate was confirmed after iso-
lating representative (S, RS)-X1-BH3 through column chromatog-
raphy on silica gel (hexane/ethyl acetate¼3:1, quantitative yield). H
Table 1
Solvent and additive effect on the yield and diastereomeric ratios
Entrya
T (ꢀC)
Additive (2.0 equiv)
Solvent
Yieldb
d.r.c
5:1
5:1
4.2:1
4.4:1
3:1
1
2
3
4
5
6
7
ꢁ78
ꢁ78
ꢁ78
ꢁ78
ꢁ78
RT
d
THF
Et2O
Toluene
DME
Dioxane
THF
71%
65%
67%
46%
58%
72%
71%
d
d
d
d
d
10:1
20:1
RT
BF3$Et2O
THF
a
The reaction was conducted using N1(1.5 mmol), Ph2PCH2Li(3.0 mmol).
Isolated yield.
b
c
Scheme 2. Synthesis of chiral b-sulfinamide phosphines X1eX18.
The d.r was determined by the 1H NMR analysis.

2702
P. Chen et al. / Tetrahedron 72 (2016) 2700e2706
suppliers were used directly without further purification. The [a]
D
was recorded using PolAAr 3005 High Accuracy Polarimeter. 1H
NMR spectra, 13C NMR spectra, and 31P NMR spectra were recorded
on a Bruker 400 MHz spectrometer in chloroform-d3. Chemical
shifts (in ppm) were referenced to tetramethylsilane (
d
¼0 ppm) in
CDCl3 as an internal standard. 13C NMR spectra were obtained by
using the same NMR spectrometers and were calibrated with CDCl3
(
d
¼77.00 ppm). The data is being reported as (s¼singlet, d¼doublet,
t¼triplet, m¼multiplet or unresolved, br¼broad signal, coupling
constant(s) in Hz, integration). Infrared (IR) spectra were obtained
using a Bruker tensor 27 infrared spectrometer.
Tetrahydrofuran (THF) was dried with sodium benzophenone
and distilled before use; Ph2PCH3 was purchased from Acros
Company.
Reactions were monitored by thin layer chromatography (TLC)
using silicycle pre-coated silica gel plates. Flash column chroma-
tography was performed on silica gel 60 (particle size
200e400 mesh ASTM, purchased from Yantai, China) and eluted
with petroleum ether/ethyl acetate.
4.2. General procedure for the preparation of imines N1-187,8
A round bottom flask was charged with a solution of chiral tert-
butanesulfinamide (11 mmol) and aldehyde (10 mmol) in THF
(20 mL) followed by the addition of isopropyl titanate (15 mmol).
The reaction mixture was stirred until completion of aldehyde as
indicated by TLC. The reaction was then quenched with water, di-
luted with EtOAc and dried over MgSO4. The solvent was removed
in vacuo and the crude product was purified by silica gel column
chromatography using Petroleum Ether/AcOEt as an eluent to give
the desired product in 58e95% yields.
Scheme 3. Synthesis of chiral b-aminophosphines and derivatives.
NMR, 31P NMR and HRMS-ESI spectra of (S, RS)-X1-BH3 revealed
that only P-adduct was formed in the presence of 2.0 equiv of BH3.
In some case, after borane protection, the two diastereoisomers
could be more easily separated by the column chromatography. The
chiral auxiliary the tert-butyl sulfinyl group in chiral sulfinamide
phosphines (Xiao-Phos) could be readily removed under acid
4.3. General procedure for the synthesis of Xiao-Phos
conditions (4M HCl) and the corresponding chiral
b-amino-
phosphines (S)-23e26 could be obtained in high yields after
deprotection of borane by treatment with the diethylamine with-
Boron trifluoride diethyl etherate (3.0 mmol) was added to the
solution of the imine N (1.5 mmol) in dry THF (10 mL), a solution of
diphenyl methyl phosphonic lithium (3.0 mmol) that containing
TMEDA (3.0 mmol) in THF was slowly added at room temperature.
The mixture was stirred until completion of imine as indicated by
TLC, followed by hydrolysis with 10 mL of water and diluted with
EtOAc. The organic layer was separated, the aqueous phase was
extracted three times with EtOAc (3ꢂ10 mL). The combined organic
phases were dried over MgSO4 and the solvents were removed in
vacuo. The product was purified by a flash chromatography to af-
ford product.
out loss of the chirality information. These chiral
b-amino-
phosphines are valuable platform precursors for synthesis of other
types of valuable functionalized chiral phosphine catalysts. For
examples,
obtained from the corresponding chiral
reacting with acids or chiral amino acid. The useful
b
-amidephosphines (S)-27, (S, R)-28, and (S)-29 could be
-aminophosphines by
-thiour-
b
b
eaphosphine (S)-30 could be also produced in 93% yield by treat-
ment with isothiocyanate under mild conditions.
3. Conclusions
20
4.3.1. Compound (S, RS)-X1. [
n
a
]
D
¼ ꢁ28.4 (c¼0.50, CHCl3). IR (neat)
In summary, we developed a novel method for the synthesis of
(cmꢁ1) 2863, 1494, 1264, 1047, 915, 735; 1H NMR (400 MHz,
useful chiral
mercially available aldehyde and chiral tert-butane-sulfinamide
and diphenyl methyl phosphine. A series of chiral -sulfinamide
phosphines (Xiao-Phos) were synthesized in good yields with
moderate to high diastereoselectivity via a two-step condensation-
nucleophilic addition procedure. These chiral sulfinamide phos-
phines (Xiao-Phos) were valuable precursors for the synthesis of
b-aminophosphines and its derivatives from com-
CDCl3)
d 7.45e7.41 (m, 2H), 7.36e7.28 (m, 7H), 7.27e7.25 (m, 6H),
4.48e4.41 (m, 1H), 3.63 (d, J¼4.4 Hz, 1H), 2.89 (dd, J¼13.8, 6.8 Hz,
b
1H), 2.50 (dd, J¼13.8, 8.0 Hz, 1H), 1.19 (s, 9H). 13C NMR (100 MHz,
CDCl3)
d
142.08 (d, JC,P¼44 Hz), 138.10 (d, JC,P¼12.9 Hz), 137.51 (d,
JC,P¼13 Hz), 132.78 (d, JC,P¼5.8 Hz), 132.59 (d, JC,P¼5.8 Hz), 128.79,
128.62, 128.60, 128.54 (d, JC,P¼2.3 Hz), 128.35 (d, JC,P¼6.7 Hz),
128.04, 127.12 (d, JC,P¼1 Hz), 57.56 (d, JC,P¼19 Hz), 56.02, 37.47 (d,
chiral
Xiao-Phos as well as
b
-aminophosphines and its derivatives. Other applications of
-aminophosphines and its derivatives in
JC,P¼14 Hz), 22.52; 31P NMR (162 MHz, CDCl3)
¼ ꢁ24.00 ppm. ESI-
d
b
MS calcd for C24H29NOPS: m/z (%): 410.1702 (MþHþ), found:
asymmetric reactions are underway in our laboratory and will be
reported in due course.
410.1687.
20
4.3.2. Compound (S, RS)-X2. [
n
a]
¼ ꢁ26.6 (c¼0.50, CHCl3). IR (neat)
D
4. Experimental section
(cmꢁ1) 2958, 1433, 1035, 892, 801, 739; 1H NMR (400 MHz, CDCl3)
7.79e7.75 (m, 3H), 7.70 (s, 1H), 7.46e7.39 (m, 5H), 7.36e7.27 (m,
d
4.1. General
5H), 7.21e7.18 (m, 3H), 4.66e4.59 (m, 1H), 3.71 (d, J¼4.3 Hz, 1H),
2.98 (dd, J¼13.8, 6.8 Hz, 1H), 2.62 (dd, J¼13.8, 8.0 Hz, 1H), 1.20 (s,
Unless otherwise noted, all reactions were carried out under
9H). 13C NMR (100 MHz, CDCl3)
d
139.25 (d, JC,P¼4.4 Hz), 138.02 (d,
a
nitrogen atmosphere; materials obtained from commercial
JC,P¼12.7 Hz), 137.52 (d, JC,P¼12.9 Hz), 133.13 (d, JC,P¼5.8 Hz), 132.83

P. Chen et al. / Tetrahedron 72 (2016) 2700e2706
2703
(d, JC,P¼3.1 Hz), 132.64(d, JC,P¼3.5 Hz), 128.81, 128.62, 128.55, 128.32
(d, JC,P¼6.7 Hz),128.02,126.40 (d, JC,P¼1.1 Hz),126.11(d, JC,P¼9.9 Hz),
124.77, 57.73 (d, JC,P¼19.6 Hz), 56.08, 37.16 (d, JC,P¼14.4 Hz), 22.56;
9H); 13C NMR (100 MHz, CDCl3)
d
150.91, 114.14 (d, JCP¼3.7 Hz),
138.36 (d, JCP¼13.2 Hz), 138.08 (d, JCP¼12.9 Hz), 132.83, 132.64,
128.62, 128.50, 128.43, 128.26 (d, JCP¼6.9 Hz), 121.95, 121.34, 57.77
(d, JCP¼20.7 Hz), 55.97, 37.35 (d, JCP¼14.3 Hz), 34.81, 22.68; 31P NMR
31P NMR (162 MHz, CDCl3)
d¼ ꢁ23.88 ppm. ESI-MS calcd for
C
28H31NOPS: m/z (%): 460.1858 (MþHþ), found: 460.1827.
(162 MHz, CDCl3)
d
¼ ꢁ23.40 ppm. ESI-MS calcd for C32H45NOPS: m/
z (%): 522.2954 (MþHþ), found: 522.2949.
20
4.3.3. Compound (S, RS)-X3. [
n
a
]
¼ ꢁ11.6 (c¼0.50, CHCl3). IR (neat)
D
20
(cmꢁ1) 3053, 1433, 1067, 925, 885, 132; 1H NMR (400 MHz, CDCl3)
4.3.8. Compound (S, RS)-X8. [
n
a
]
D
¼ ꢁ11.6 (c¼0.50, CHCl3). IR (neat)
d
8.74 (d, J¼8.6 Hz,1H), 8.29 (s,1H), 8.00 (d, J¼8.8 Hz,1H), 7.94e7.90
(cmꢁ1) 1592, 1508, 1460, 1327, 1236, 1121, 1044, 740; 1H NMR
(m, 2H), 7.45e7.30 (m, 9H), 7.04e7.01 (m, 1H), 6.92e6.90 (m, 4H),
6.19e6.14 (m, 1H), 3.96 (s, 1H), 3.31e3.23 (m, 2H),1.27 (s, 9H); 13C
(400 MHz, CDCl3) d 7.43e7.39 (m, 2H), 7.35e7.26 (m, 8H), 6.47 (s,
2H), 4.48e4.42 (m, 1H), 3.80 (s, 3H), 3.79 (s, 6H), 3.64 (d, J¼3.8, 1H),
NMR (100 MHz, CDCl3)
d
137.94 (d, JCP¼12.6 Hz), 136.71 (d,
2.85 (dd, J¼13.8, 6.4 Hz, 1H), 2.53 (dd, J¼13.8, 8.1 Hz, 1H), 1.22 (s,
JCP¼13.2 Hz),132.70 (d, JCP¼23.8 Hz),132.47 (d, JCP¼22.2 Hz),131.91,
131.25, 129.87, 128.99 (d, JCP¼4.0 Hz), 128.52, 128.51 (d,
JCP¼10.6 Hz), 128.35, 127.77 (d, JCP¼7.2 Hz), 126.44, 125.84, 125.21,
124.89, 124.42, 123.55, 56.03, 51.09 (d, JCP¼23.3 Hz), 35.57 (d,
9H). 13C NMR (100 MHz, CDCl3)
d 153.14, 137.96, 137.83, 137.75 (d,
JC,P¼12.3 Hz), 137.44, 137.40, 132.88 (d, JC,P¼19.6 Hz), 132.54 (d,
JC,P¼19.0 Hz), 128.72, 128.53 (d, JC,P¼6.7 Hz), 128.30, 104.08, 60.72,
57.94 (d, JC,P¼21.0 Hz), 56.06, 56.00, 37.14 (d, JC,P¼4.4 Hz), 22.56; 31
P
JCP¼10.4 Hz), 22.78; 31P NMR (162 MHz, CDCl3)
d¼ ꢁ22.62 ppm.
NMR (162 MHz, CDCl3)
C
d
¼ ꢁ23.71 ppm. ESI-MS calcd for
ESI-MS calcd for C32H32NNaOPS: m/z (%): 532.1834 (MþNaþ),
27H34NNaO4PS: m/z (%): 522.1838 (MþNaþ), found: 522.1819.
found: 532.1789.
20
4.3.9. Compound (S, RS)-X9. [
a]
¼ ꢁ25.6 (c¼0.50, CHCl3). 1H NMR
D
20
4.3.4. Compound (S, RS)-X4. [
n
a
]
¼ ꢁ26.9 (c¼0.50, CHCl3). IR (neat)
(400 MHz, CDCl3) d7.48e7.44 (m, 2H), 7.38e7.33 (m, 3H), 7.28e7.22
D
(cmꢁ1) 2954, 1610, 1512, 1434, 1247, 1178, 1050, 830, 738, 694; 1H
(m, 5H), 6.73 (s, 2H), 4.96e4.90 (m,1H), 3.51e3.46 (m,1H), 2.98 (dd,
J¼13.8, 7.2 Hz, 1H), 2.65 (dd, J¼13.8, 8.6 Hz, 1H), 2.45 (s, 3H), 2.22 (s,
NMR (400 MHz, CDCl3) d 7.45e7.42 (m, 2H), 7.35e7.26 (m, 8H), 7.19
(d, J¼2.1 Hz, 2H), 4.44e4.38 (m, 1H), 3.78 (s, 3H), 3.56 (m, 1H),
3H), 1.98 (s, 3H), 1.21 (s, 9H); 13C NMR (100 MHz, CDCl3)
d 159.28,
2.92e2.87 (m, 1H), 2.50e2.44 (m, 1H), 2.45 (s, 3H),1.19 (s, 9H); 13C
138.28 (d, JCP¼12.9 Hz), 137.53 (d, JCP¼12.9 Hz), 134.09 (d,
JCP¼4.3 Hz), 132.85 (d, JCP¼11.9 Hz), 132.66 (d, JCP¼11.9 Hz), 128.83,
128.64, 128.54 (d, JCP¼4.8 Hz), 128.39, 128.32, 113.98, 57.04, 56.85,
55.94, 55.20, 37.32 (d, JCP¼13.9 Hz), 55.57; 31P NMR (162 MHz,
NMR (100 MHz, CDCl3)
d
159.28, 138.28 (d, JCP¼12.9 Hz), 137.53 (d,
JCP¼12.9 Hz), 134.09 (d, JCP¼4.3 Hz), 132.85 (d, JCP¼11.9 Hz), 132.66
(d, JCP¼11.9 Hz), 128.83, 128.64, 128.54 (d, JCP¼4.8 Hz), 128.39,
128.32, 113.98, 56.94 (d, JCP¼19.8 Hz), 55.94, 55.20, 37.32 (d,
CDCl3)
d
¼ ꢁ23.33 ppm. ESI-MS calcd for C27H35NOPS: m/z (%):
JCP¼13.9 Hz), 22.57; 31P NMR (162 MHz, CDCl3)
d¼ ꢁ23.94 ppm.
452.2171 (MþHþ), found: 452.2147.
ESI-MS calcd for C25H31NO2PS: m/z (%): 440.1768 (MþHþ), found:
20
440.1804.
4.3.10. Compound (S, RS)-X10. [
(neat)
(cmꢁ1) 2955, 1592, 1455, 1433, 1204, 11,476, 1113, 1062, 949,
731, 696; 1H NMR (400 MHz, CDCl3)
7.49e7.45 (m, 2H), 7.37e7.30
a
]
¼ þ8.2 (c¼0.50, CHCl3). IR
D
n
20
4.3.5. Compound (S, RS)-X5. [
n
a]
¼ ꢁ24.8 (c¼0.50, CHCl3). IR (neat)
d
D
(cmꢁ1) 2955, 1433, 1047, 903, 828, 792, 741; 1H NMR (400 MHz,
(m, 5H), 7.29e7.24 (m, 3H), 6.05 (s, 2H), 5.03e4.94 (m, 1H), 4.61 (d,
J¼10.9 Hz, 1H), 3.76 (s, 9H), 2.85 (dd, J¼13.8, 9.4 Hz, 1H), 2.49e2.43
CDCl3)
d 7.43e7.39 (m, 2H), 7.33e7.24 (m, 8H), 7.21e7.12 (m, 4H),
4.48e4.42 (m, 1H), 3.60 (d, J¼4.4 Hz, 2H), 2.89e2.83 (m, 2H), 2.51
(m, 1H), 1.10 (s, 9H); 13C NMR (100 MHz, CDCl3)
d 160.37, 139.25 (d,
(d, J¼13.8, 7.8 Hz, 1H), 1.22 (d, J¼6.9 Hz, 6H), 1.19 (s, 9H); 13C NMR
JCP¼13.3 Hz), 138.95 (d, JCP¼13.9 Hz), 132.98 (d, JCP¼19.2 Hz), 132.50
(d, JCP¼18.5 Hz), 128.30, 128.22 (d, JCP¼2.7 Hz), 128.16 (d,
JCP¼2.2 Hz), 128.08, 112.13 (d, JCP¼5.4 Hz), 91.10, 55.79, 55.52, 55.19,
51.01 (d, JCP¼18.5 Hz), 35.93 (d, JCP¼13.7 Hz), 22.46; 31P NMR
(100 MHz, CDCl3)
d
148.54, 139.44 (d, JCP¼4.3 Hz), 138.13 (d,
JCP¼13.0 Hz), 137.82(d, JCP¼12.7 Hz), 132.81 (d, JCP¼10.1 Hz), 132.62
(d, JCP¼9.7 Hz), 128.61 (d, JCP¼15.6 Hz), 128.52 (d, JCP¼6.6 Hz),
127.03, 126.66, 57.41 (d, JCP¼23.6 Hz), 56.01, 37.43 (d, JCP¼14.1 Hz),
33.70, 23.87 (d, JCP¼1.0 Hz), 22.57; 31P NMR (162 MHz, CDCl3)
(162 MHz, CDCl3)
d
¼ ꢁ22.02 ppm. ESI-MS calcd for C27H35NO4PS:
m/z (%): 500.2019 (MþHþ), found: 500.2021.
d
¼ ꢁ23.77 ppm. ESI-MS calcd for C27H35NOPS: m/z (%): 452.2171
20
(MþHþ), found: 452.2134.
4.3.11. Compound (R, RS)-X10. [
(neat)
738, 696, 588; 1H NMR (400 MHz, CDCl3)
d
a
]
¼ ꢁ15.8 (c¼0.50, CHCl3). IR
D
n
(cmꢁ1) 2950, 1591, 1454, 1203, 1147, 1110, 1060, 949, 812,
7.51e7.47 (m, 2H),
20
4.3.6. Compound (S, RS)-X6. [
a]
¼ ꢁ7.5 (c¼0.50, CHCl3). IR (neat)
n
D
(cmꢁ1) 2974, 1591, 1465, 1384, 1239, 1111, 1052, 906; 1H NMR
7.35e7.29 (m, 5H), 7.25e7.16 (m, 5H), 6.86 (dd, J¼6.9, 2.2 Hz, 1H),
6.68e6.60 (m, 2H), 6.07 (dd, J¼7.6, 1.6 Hz, 1H), 5.99 (s, 2H),
5.07e5.02 (m, 1H), 4.60 (d, J¼10.3 Hz, 1H), 3.77 (s, 3H), 3.66 (s, 6H),
3.07e3.02 (m, 1H), 2.91 (dd, J¼13.2, 11.0 Hz, 1H), 1.09 (s, 9H); 13C
(400 MHz, CDCl3) d 7.56e7.52 (m, 2H), 7.37e7.30 (m, 3H), 7.24e7.22
(m, 2H), 7.18e7.16 (m, 3H), 7.10e7.06 (m, 1H), 6.43 (dd, J¼13.0,
8.3 Hz, 2H), 5.24e5.16 (m, 1H), 4.79 (d, J¼10.6 Hz, 1H), 4.62e4.56
(m, 1H), 4.39e4.33 (m, 1H), 3.13e3.08 (m, 1H), 2.90e2.83 (m, 1H),
NMR (100 MHz, CDCl3)
d
160.42, 139.15 (d, JCP¼12.9 Hz), 138.30 (d,
1.37 (d, J¼6.0 Hz, 3H), 1.31 (d, J¼6.0 Hz, 3H), 1.10e1.03 (m, 15H); 13
C
JCP¼13.2 Hz), 132.86 (d, JCP¼14.7 Hz), 132.67 (d, JCP¼14.8 Hz),
128.30, 128.19 (d, JCP¼6.6 Hz), 127.91, 127.90 (d, JCP¼9.9 Hz), 126.49,
110.54 (d, JCP¼2.5 Hz), 91.14, 55.80, 55.69, 55.15, 50.92 (d,
JCP¼22.8 Hz), 36.72 (d, JCP¼13.3 Hz), 22.40; 31P NMR (162 MHz,
NMR (100 MHz, CDCl3)
d
156.20, 154.90, 139.42 (d, JCP¼13.3 Hz),
139.02 (d, JCP¼14.4 Hz), 133.06 (d, JCP¼19.2 Hz), 132.36 (d,
JCP¼18.3 Hz), 128.39, 128.24 (d, JCP¼12.3 Hz), 128.25, 128.08, 121.12
(d, JCP¼6.2 Hz), 106.64, 105.03, 70.96, 69.20, 56.02, 51.46 (d,
JCP¼17.6 Hz), 36.06 (d, JCP¼13.7 Hz), 22.73, 22.51, 22.22; 31P NMR
CDCl3)
d
¼ ꢁ22.39 ppm. ESI-MS calcd for C27H35NO4PS: m/z (%):
500.2019 (MþHþ), found: 500.2017.
(162 MHz, CDCl3)
d
¼ ꢁ21.87 ppm. ESI-MS calcd for C30H41NO3PS:
m/z (%): 526.2539 (MþHþ), found: 526.2530.
4.3.12. Compound (S, RS)-X12. [
(neat)
(cmꢁ1) 2923,1433,1055, 907, 733; 1H NMR (400 MHz, C6D6)
a
]
¼ þ30.7 (c¼0.50, CHCl3). IR
20
D
n
20
4.3.7. Compound (S, RS)-X7. [
n
a
]
D
¼ ꢁ17.4 (c¼0.50, CHCl3). IR (neat)
d
7.49e7.44 (m, 4H), 7.14e7.04 (m, 6H), 3.44(d, J¼8.6 Hz, 1H),
(cmꢁ1) 2951, 1599, 1475, 1361, 1248, 1059, 876, 737, 605; 1H NMR
3.31e3.24 (m, 1H), 2.31e2.18 (m, 2H), 1.90e1.83 (m, 1H), 1.66e1.50
(m, 5H),1.25e1.17 (m,1H),1.10 (s, 9H),1.06e0.99 (m, 3H), 0.96e0.86
(400 MHz, CDCl3)
d 7.38e7.27 (m, 7H), 7.23e7.20 (m, 4H), 7.10 (d,
J¼1.7 Hz, 2H), 4.55e4.49 (m, 1H), 3.66 (d, J¼3.0 Hz, 1H), 2.87 (dd,
(m, 1H); 13C NMR (100 MHz, C6D6)
d
139.97 (d, JC,P¼14.2 Hz), 139.09
J¼14.4, 6.0 Hz,1H), 2.54 (dd, J¼13.8, 8.2 Hz,1H), 1.27 (s,18H), 1.23 (s,
(d, JC,P¼15.4 Hz), 133.68 (d, JC,P¼19.9 Hz), 129.09, 128.81

2704
P. Chen et al. / Tetrahedron 72 (2016) 2700e2706
(d, JC,P¼6.8 Hz), 128.72 (d, JC,P¼6.1 Hz), 128.51, 60.14 (d,
JC,P¼13.3 Hz), 56.05, 43.81 (d, JC,P¼6.7 Hz), 33.11 (d, JC,P¼13.7 Hz),
22.41; 31P NMR (162 MHz, CDCl3)
C
d
¼ ꢁ23.44 ppm. ESI-MS calcd for
22H27NO2PS: m/z (%): 400.1495 (MþHþ), found: 400.1483.
29.22, 28.17, 26.74, 26.52 (d, JC,P¼7.9 Hz), 22.78 (d, JC,P¼0.9 Hz); 31
P
20
NMR (162 MHz, C6D6)
d
¼ ꢁ9.10 ppm. ESI-MS calcd for C24H35NOPS:
4.3.18. Compound (S, RS)-X18. [
a
]
¼ ꢁ26.8 (c¼0.50, CHCl3). IR
D
m/z (%): 416.2171 (MþHþ), found: 416.2173.
(neat)
(400 MHz, CDCl3)
n
(cmꢁ1) 2957, 2865, 1433, 1382, 1067, 817, 739, 695; 1H NMR
d
7.46e7.42 (m, 2H), 7.35e7.29 (m, 5H), 7.22 (d,
20
4.3.13. Compound (S, RS)-X13. [
(neat)
7.48e7.44 (m, 2H), 7.36e7.27 (m, 8H), 3.42 (d, J¼7.9 Hz, 1H),
2.82e2.74 (m, 1H), 2.55e2.50 (m, 1H), 1.98e1.91 (m, 4H), 1.76e1.44
(m, 12H), 1.27 (s, 9H); 13C NMR (100 MHz, CDCl3)
140.00 (d,
a
]
¼ þ67.6 (c¼0.50, CHCl3). IR
J¼4.8 Hz, 2H), 7.02 (d, J¼3.2 Hz, 1H), 6.93e6.91 (m, 1H), 4.77e4.71
D
n
(cmꢁ1) 2899, 1433, 1044, 737; 1H NMR (400 MHz, CDCl3)
(m,1H), 3.66 (d, J¼4.7 Hz,1H), 2.94 (dd, J¼13.8, 6.8 Hz,1H), 2.59 (dd,
d
J¼13.8, 7.8 Hz, 1H), 1.19 (s, 9H); 13C NMR (100 MHz, CDCl3)
d 145.94
(d, JCP¼18.7 Hz), 137.91 (d, JCP¼12.6 Hz), 137.40 (d, JCP¼12.9 Hz),
132.82 (d, JCP¼3.2 Hz), 132.63 (d, JCP¼3.5 Hz), 128.86, 128.64, 128.62
(d, JCP¼9.6 Hz), 128.45 (d, JCP¼6.7 Hz), 126.71, 125.75 (d, JCP¼1.7 Hz),
125.26, 56.18, 53.51 (d, JCP¼20.4 Hz), 38.30 (d, JCP¼14.1 Hz), 22.53;
d
JCP¼13.9 Hz), 137.65 (d, JCP¼15.7 Hz), 133.94 (d, JCP¼20.2 Hz), 131.91
(d, JC,P¼17.9 Hz), 129.14, 128.50 (d, JCP¼7.2 Hz), 128.33 (d,
JC,P¼5.7 Hz), 127.98, 63.46 (d, JC,P¼11.6 Hz), 57.10, 38.81, 36.86 (d,
JC,P¼5.8 Hz), 36.77, 32.11 (d, JC,P¼13.1 Hz), 28.28, 23.27 (d,
31P NMR (162 MHz, CDCl3)
C
d
¼ ꢁ23.78 ppm; ESI-MS calcd for
22H26NNaOPS2: m/z (%): 438.1086 (MþHþ), found: 438.1075.
JC,P¼3.2 Hz); 31P NMR (162 MHz, CDCl3)
¼ ꢁ22.65 ppm. ESI-MS
d
calcd for C28H39NOPS: m/z (%): 468.2428 (MþHþ), found: 468.2487.
4.4. General procedure for the synthesis of Xiao-Phos vari-
ants (S, RS)-X11 and (R, RS)-X11
20
4.3.14. Compound (S, RS)-X14. [
(neat)
(500 MHz, CDCl3)
a
]
¼ þ25.7 (c¼0.33, CHCl3). IR
D
n
(cmꢁ1) 2956, 1495, 1237, 1042, 903, 828, 756; 1H NMR
7.41 (m, 4H), 7.35e7.27 (m, 6H), 3.46e3.36
A solution of diphenyl methyl phosphonic lithium (4.5 mmol)
that containing TMEDA (4.5 mmol) in THF was added very slowly to
the solution of the imine N11 (337.5 mg, 1.5 mmol) in dry THF
(10 mL) at room temperature. The mixture was stirred until com-
pletion of the imine as indicated by TLC, followed by hydrolysis
with 10 mL of water and diluted with EtOAc. The organic layer was
separated, the aqueous phase was extracted three times with EtOAc
(3ꢂ10 mL). The combined organic phases were dried over MgSO4
and the solvents were removed in vacuo to afford two di-
astereoisomers mixture, which should not be isolated by column
chromatography.
d
(m, 1H), 3.26 (d, J¼8.0 Hz, 1H), 2.24e2.21 (m, 1H), 1.69e1.59 (m,
2H), 1.54e1.40 (m, 1H), 1.36e1.20 (m, 1H), 1.16 (s, 9H), 0.88 (t,
J¼7.5 Hz, 3H), 0.78 (t, J¼7.5 Hz, 3H). 31P NMR (200 MHz, CDCl3)
d
¼
ꢁ22.27 ppm 13C NMR (125 MHz, CDCl3)
d 138.54 (d,
JC,P¼62.5 Hz), 138.19 (d, JC,P¼15 Hz), 133.06 (d, JC,P¼20 Hz), 132.18
(d, JC,P¼18.75 Hz), 128.77, 128.4 (d, JC,P¼3.75 Hz), 128.35 (d,
JC,P¼3.75 Hz), 56.11, 56.08, 56.00, 46.78 (d, JC,P¼6.25 Hz), 31.98
(d, JC,P¼13.75 Hz), 22.51, 22.50, 22.31, 21.57, 12.01, 11.82. ESI-MS
calcd for C23H34NNaOPS: m/z (%): 426.1997 (MþHþ), found:
426.1991.
Et3N (15.0 mmol) was added to the above mixture solution in
dry CH2Cl2 (10 mL) containing (R, RS)-X11 and (S, RS)-X11 and the
mixture was stirred at room temperature for 5 min, and then the
corresponding iPr3SiCl reagent was slowly added. The reaction
mixture was then stirred until completion of X11 as indicated by
TLC, followed by quenching with 10 mL of water. The aqueous
phase was separated and extracted three times with 20 mL of
CH2Cl2. The combined organic phases were dried over MgSO4 and
the solvents were removed in vacuo. The product was purified by
chromatography to afford two diastereomers in 90% yield.
TBAF (1.2 equiv) was added slowly to the solution of (S, RS)-
isomer or in dry THF (10 mL) and the mixture was stirred at room
temperature until completion of material as indicated by TLC, fol-
lowed by washing with 10 mL of water. The aqueous phase was
separated and extracted three times with 20 mL of CH2Cl2. The
combined organic phases were dried over MgSO4 and the solvents
were removed in vacuo. Pure (S, RS)-X11 could be obtained in 91%
isolated yield. The corresponding (R, RS)-X11 could be also ob-
tained in 93% yield using the same procedure.
20
4.3.15. Compound (S, RS)-X15. [
(neat)
(400 MHz, C6D6)
a
]
¼ þ32.3 (c¼0.50, CHCl3). IR
D
n
(cmꢁ1) 2956, 1491, 1251, 1048, 913, 838, 782; 1H NMR
7.47e7.43 (m, 4H), 7.16e7.03 (m, 6H), 3.34e3.24
d
(m, 2H), 2.25e2.16 (m, 3H), 1.09 (s, 9H), 0.87 (d, J¼6.8 Hz, 3H), 0.72
(d, J¼6.9 Hz, 3H). 13C NMR (100 MHz, C6D6)
d 139.79 (d,
JC,P¼13.9 Hz), 139.10 (d, JC,P¼15.3 Hz), 133.62 (d, JC,P¼19.8 Hz),
132.66 (d, JC,P¼18.3 Hz), 129.08, 128.81(d, JC,P¼6.9 Hz), 128.74 (d,
JC,P¼6.2 Hz), 128.55, 60.41,56.02, 33.44(d, JC,P¼6.9 Hz), 32.24(d,
JC,P¼13.85 Hz), 22.69, 18.27, 17.32; 31P NMR (162 MHz, C6D6)
d
¼ ꢁ9.05 ppm. ESI-MS calcd for C21H31NOPS: m/z (%): 376.1858
(MþHþ), found: 376.1859.
20
4.3.16. Compound (S, RS)-X16. [
a
]
¼ þ29.3 (c¼0.33, CHCl3). IR
D
(neat)
(500 MHz, CDCl3)
n
(cmꢁ1) 2968, 1481, 1271, 1028, 903, 848, 762; 1H NMR
d
7.47 (ddd, J¼7.3, 4.8, 1.9 Hz, 2H), 7.38e7.25
(m, 8H), 3.33 (d, J¼7.5 Hz, 1H), 3.09e2.75 (m, 1H), 2.46 (ddd,
J¼13.8, 4.9, 1.9 Hz, 1H), 2.00 (ddd, J¼14.0, 10.6, 4.8 Hz, 1H), 1.26 (s,
9H), 0.91 (s, 9H). 13C NMR (125 MHz, CDCl3)
d 139.79 (d,
20
JC,P¼13.5 Hz), 137.69 (d, JC,P¼15 Hz), 134.96 (d, JC,P¼20 Hz), 131.84
(d, JC,P¼17.5 Hz), 129.16, 128.49 (d, JC,P¼7.5 Hz), 128.32 (d,
JC,P¼5 Hz), 127.98, 63.06, 62.97, 56.96, 35.32 (d, JC,P¼6.25 Hz),
33.8 (d, JC,P¼13.75 Hz), 26.80, 23.13 (d, JC,P¼5 Hz). 31P NMR
4.4.1. Compound (S, RS)-X11. [
(neat)
(400 MHz, CDCl3)
a
]
¼ þ30.6 (c¼0.50, CHCl3). IR
D
n
(cmꢁ1) 2955, 1457, 1258, 1034, 917, 870, 740; 1H NMR
9.34 (s, 1H), 7.51e7.46 (m, 2H), 7.35e7.30 (m,
d
5H), 7.27e7.26 (m, 3H), 6.86 (dd, J¼6.9, 2.2 Hz, 1H), 6.68e6.60 (m,
2H), 6.07 (dd, J¼7.6, 1.6 Hz, 1H), 5.34 (d, 5.34 Hz, 1H), 4.31e4.23 (m,
1H), 3.08 (m, 1H), 2.37e2.32 (m, 1H), 1.22 (s, 9H); 13C NMR
(200 MHz, CDCl3)
d
¼ ꢁ22.24 ppm. ESI-MS calcd for C22H33NOPS:
m/z (%): 390.1942 (MþHþ), found: 390.1949.
(100 MHz, CDCl3)
d
154.66, 138.66, 138.65 (d, JC,P¼27 Hz), 132.97 (d,
20
4.3.17. Compound (S, RS)-X17. [
(neat)
(400 MHz, CDCl3)
(m, 2H), 4.53e4.45 (m, 1H), 3.56 (d, J¼7.5 Hz, 1H), 2.78 (dd, J¼13.9,
7.6 Hz, 1H), 1.15 (s, 9H); 13C NMR (100 MHz, CDCl3)
154.28 (d,
a
]
D
¼ ꢁ7.2 (c¼0.50, CHCl3). IR
JC,P¼19.5 Hz), 132.44 (d, JC,P¼18.4 Hz), 129.01, 128.65, 128.43, 128.37
(d, JC,P¼3.0 Hz), 128.32, 7.87 (d, JC,P¼6.6 Hz), 127.14, 118.86, 116.77,
61.85 (d, JC,P¼17.4 Hz), 56.76, 36.12 (d, JC,P¼14.1 Hz), 22.71; 31PNMR
n
(cmꢁ1) 2956, 1482, 1176, 1039, 895, 743, 696; 1H NMR
7.45e7.36 (m, 4H), 7.34e7.30 (m, 7H), 6.30e6.27
d
(162 MHz, CDCl3)
d
¼ ꢁ21.40 ppm. ESI-MS calcd for C24H29NO2PS:
d
m/z (%): 426.1651 (MþHþ), found: 426.1717.
JCP¼5.4 Hz), 142.21, 137.80 (d, JCP¼2.2 Hz), 137.67 (d, JCP¼2.0 Hz),
132.77 (d, JCP¼17.0 Hz), 132.57 (d, JCP¼16.8 Hz), 128.74, 128.71,
128.52 (d, JCP¼6.5 Hz), 128.46 (d, JCP¼6.6 Hz), 110.24, 107.52 (d,
JCP¼1.6 Hz), 56.23, 52.43 (d, JCP¼19.8 Hz), 35.11 (d, JCP¼14.4 Hz),
20
4.4.2. Compound (R, RS)-X11. [
(neat)
(400 MHz, CDCl3)
a]
¼ ꢁ77.8 (c¼0.50, CHCl3). IR
D
n
(cmꢁ1) 2957,1598,1456,1367,1282,1044, 857, 750; 1H NMR
8.88 (s, 1H), 7.45e7.40 (m, 2H), 7.31e7.17 (m,
d

P. Chen et al. / Tetrahedron 72 (2016) 2700e2706
2705
8H), 7.03e6.98 (m, 2H), 6.76e6.73 (m, 2H), 4.90 (t, J¼4.4 Hz, 1H),
4.61e4.55 (m, 1H), 2.86e2.80 (s, 1H), 2.75e2.69 (s, 1H), 1.19 (s, 9H);
7.30e7.22 (m, 1H), 4.06 (ddd, J¼9.1, 7.6, 4.9 Hz, 1H), 2.65e2.56 (m,
1H), 2.54e2.40 (m, 1H), 1.87 (s, 2H); 31P NMR (200 MHz, CDCl3)
13C NMR (100 MHz, CDCl3)
d
155.11, 137.44 (d, JC,P¼11.0 Hz), 137.06
d
¼ ꢁ21.75 ppm; 13C NMR (125 MHz, CDCl3)
d 146.60, 146.55, 138.82
(d, JC,P¼11.4 Hz), 132.91 (d, JC,P¼18.9 Hz), 132.74 (d, JC,P¼18.8 Hz),
129.03, 128.77, 128.57, 128.50, 128.35 (d, JC,P¼6.9 Hz), 126.00 (d,
JC,P¼5.0 Hz), 119.43, 116.52, 56.06, 55.85(d, JC,P¼18.2 Hz), 36.21 (d,
(d, JC,P¼12.5 Hz), 138.12 (d, JC,P¼12.5 Hz), 133.13 (d, JC,P¼20 Hz),
132.69 (d, JC,P¼18.75 Hz), 128.91, 128.63, 128.59, 128.58, 128.56,
128.50, 127.27, 126.23, 53.83, 53.76 (d, JC,P¼16.25 Hz), 40.12 (d,
JC,P¼15 Hz); ESI-MS calcd for C19H27NP: m/z (%): 305.1333 (MþHþ),
found: 305.1127.
JC,P¼15.1 Hz), 22.53; 31P NMR (162 MHz, CDCl3)
¼ ꢁ24.21 ppm.
d
ESI-MS calcd for C24H29NO2PS: m/z (%): 426.1651 (MþHþ), found:
426.1712.
20
4.5.3. Compound (S)-26. [
a
]
D
¼ þ24.1 (c¼0.33, CHCl3). IR (neat)
n
4.5. General procedure for the synthesis of chiral
phosphines from Xiao-Phos
b
-amino-
(cmꢁ1) 3180, 2980, 1372, 1272, 1084, 897, 790; 1H NMR (500 MHz,
CDCl3) 7.43e7.38 (m, 2H), 7.31e7.27 (m, 2H), 7.26e7.22 (m, 3H),
d
7.21e7.13 (m, 3H), 2.41e2.32 (m, 2H), 1.68 (ddd, J¼13.8, 11.4, 4.7 Hz,
BH3-THF(2.0 equiv) was added slowly to the solution of corre-
sponding Xiao-Phos in dry THF at ꢁ30 ꢀC and the mixture was
stirred for 2 h at ꢁ30 ꢀC until completion of material as indicated by
TLC followed by washing with 10 mL of water. The aqueous phase
was separated and extracted three times with 20 mL of EtOAc. The
combined organic phases were dried over MgSO4 and the solvents
were removed in vacuo. 4M HCl (2.0 equiv) was added slowly to the
solution of the above residue in MeOH and the reaction mixture
was stirred at room temperature for 3 h until completion of ma-
terial as indicated by TLC followed by washing with aq NaHCO3 and
10 mL aq brine water. The organic layers was separated and
extracted three times with 20 mL EtOAc. The combined organic
phases were dried over MgSO4 and the solvents were removed in
vacuo. Et2NH (2.0 mL) was added slowly to the above residue and
the mixture was stirred at 55 ꢀC for 6 h under the protection of N2
until completion of material as indicated by TLC. The reaction
mixture was dried in vacuo and residue was directly purified by
1H), 1.29 (s, 2H), 0.77 (s, 9H); 31P NMR (200 MHz, CDCl3)
d
¼
ꢁ19.46 ppm; 13C NMR (125 MHz, CDCl3)
d 139.68 (d,
JC,P¼12.5 Hz), 137.60 (d, JC,P¼15 Hz), 133.34 (d, JC,P¼20 Hz), 132.03
(d, JC,P¼6.25 Hz), 128.83, 128.32 (d, JC,P¼6.25 Hz), 128.19 (d,
JC,P¼7.5 Hz), 127.97, 57.47 (d, JC,P¼12.5 Hz), 34.74 (d, JC,P¼6.25 Hz),
32.47 (d, JC,P¼10 Hz), 25.75; ESI-MS calcd for C18H25NP: m/z (%):
286.3708 (MþHþ), found: 286.3711.
20
4.5.4. Compound (S)-27. [
a
]
¼ þ15 (c¼0.33, CHCl3). IR (neat)
n
D
(cmꢁ1) 3108, 2951, 1680, 1059, 917, 824, 769; 1H NMR (500 MHz,
CDCl3)
d
7.99 (d, J¼19.6 Hz, 3H), 7.59e7.49 (m, 2H), 7.48e7.39 (m,
2H), 7.40e7.32 (m, 10H), 7.31e7.25 (m, 1H), 7.16 (dt, J¼27.0, 7.2 Hz,
1H), 6.73 (d, J¼7.4 Hz, 1H), 5.46e5.34 (m, 1H), 2.88 (dd, J¼14.1,
9.5 Hz, 1H), 2.71 (dd, J¼14.1, 5.5 Hz, 1H); 19F NMR (282 MHz, CDCl3)
d
¼ ꢁ62.79 ppm; 31P NMR (200 MHz, CDCl3)
d
¼ ꢁ22.81 ppm; 13C
NMR (125 MHz, CDCl3)
d
163.63, 141.94 (d, JC,P¼6.25 Hz), 137.78 (d,
JC,P¼12.5 Hz), 137.48 (d, JC,P¼12.5 Hz), 136.16, 133.06, 132.90, 132.71,
132.56, 131.95 (d, JC,F¼33.75 Hz), 130.59, 130.51, 130.47, 130.39,
129.26, 128.99, 128.88, 128.78 (d, JC,P¼7.5 Hz), 128.70 (d,
JC,P¼7.5 Hz), 127.90, 127.28 (d, JC,P¼2.5 Hz), 126.40, 125.86, 124.99,
124.96, 124.93, 122.88 (q, JC,F¼271.25 Hz), 53.01 (d, JC,P¼16.5 Hz),
35.91(d, JC,P¼16.5 Hz); ESI-MS calcd for C29H22F6NNaOP: m/z (%):
568.1258 (MþNaþ), found: 568.1235.
chromatography to afford chiral
b-aminophosphines. The yield of
(S)-23 is 80%, (S)-24 is 82%, (S)-25 is 80%, (S)-26 is 84%.
20
For synthesis of (S, RS)-X1-BH3. [
(neat)
(cmꢁ1) 2893, 1484, 1194, 1087, 905, 715;1H NMR (500 MHz,
CDCl3) 7.73e7.64 (m, 2H), 7.55e7.49 (m, 2H), 7.49e7.36 (m, 4H),
a
]
¼ ꢁ19.4 (c¼0.33, CHCl3). IR
D
n
d
7.31 (td, J¼7.4, 1.7 Hz, 2H), 7.28 (d, J¼1.6 Hz, 1H), 7.24e7.14 (m, 3H),
4.82 (ddt, J¼10.9, 7.4, 5.6 Hz, 1H), 3.91 (d, J¼5.1 Hz, 1H), 3.10 (ddd,
J¼14.7,10.3, 7.6 Hz,1H), 2.77 (ddd, J¼14.7,11.8, 5.7 Hz,1H),1.36e1.11
20
4.5.5. Compound (S, R)-28. [
n
a
]
¼ þ22.6 (c¼0.33, CHCl3). IR (neat)
D
(m, 3H), 1.06 (s, 9H); 31P NMR (200 MHz, CDCl3)
d
12.37(d, JB,
(cmꢁ1) 2959, 1680, 1582, 1382, 1275, 1046, 808, 723, 699; 1H NMR
¼44.0 Hz); 13C NMR (125 MHz, CDCl3)
d
140.79(d, JC,P¼8.75 Hz),
(500 MHz, CDCl3)
d
7.51e7.46 (m, 2H), 7.43 (ddd, J¼7.4, 4.9, 1.5 Hz,
P
132.18, 132.13, 132.11, 132.06, 131.38(d, JC,P¼2.5 Hz), 131.20(d,
JC,P¼2.5 Hz), 129.56, 129.11, 129.04, 128.96, 128.92, 128.81, 128.73,
128.64, 128.48, 128.25, 127.55, 56.36(d, JC,P¼2.5 Hz), 56.12, 34.41(d,
JC,P¼33.75 Hz), 22.49; ESI-MS calcd for C24H31BNNaOPS: m/z (%):
446.1862 (MþNaþ), found: 446.1849.
2H), 7.40e7.31 (m, 6H), 5.85 (d, J¼7.4 Hz, 1H), 4.93 (d, J¼6.5 Hz, 1H),
4.30e4.06 (m, 1H), 3.96e3.62 (m, 1H), 2.29e2.23 (m, 2H),
2.20e2.09 (m, 1H), 1.47 (s, 9H), 1.39 (ddd, J¼9.7, 7.4, 3.8 Hz, 1H), 1.31
(dt, J¼21.1, 6.8 Hz,1H),1.26e1.15 (m, 2H), 0.94 (d, J¼6.8 Hz, 3H), 0.87
(d, J¼6.8 Hz, 3H), 0.83 (dt, J¼10.8, 7.4 Hz, 6H); 31P NMR (200 MHz,
Chiral
b
-aminophosphines (S)-27e(S)-30 were prepared from
CDCl3)
d
¼ ꢁ23.30 ppm; 13C NMR (125 MHz, CDCl3)
d 170.60,155.83,
the methods reported in the literature,11 while (S)-25 were char-
acterized by comparison of their physical and spectroscopic data
with the reported in the literature.12
138.61 (d, JC,P¼15 Hz), 138.26 (d, JC,P¼12.5 Hz), 133.01 (d,
JC,P¼20 Hz), 132.73 (d, JC,P¼18.75 Hz), 130.65, 128.76 (d,
JC,P¼8.75 Hz), 128.60, 128.55, 128.48, 79.77, 60.19, 48.45 (d,
JC,P¼15 Hz), 45.18 (d, JC,P¼6.25 Hz), 42.81, 31.68 (d, JC,P¼13.75 Hz),
30.47, 28.33, 22.48, 21.80, 19.40, 17.70, 11.71, 11.66; ESI-MS calcd for
20
4.5.1. Compound (S)-23. [
a
]
¼ þ33.9 (c¼0.33, CHCl3). IR (neat)
n
D
(cmꢁ1) 2951, 1475, 1298, 1059, 917, 824, 769; 1H NMR (500 MHz,
CDCl3)
C
28H43N2NaO3P: m/z (%): 521.2904 (MþHþ), found: 521.2915.
d
7.47 (ddd, J¼7.4, 4.8, 1.5 Hz, 2H), 7.41 (ddd, J¼8.7, 7.3,1.6 Hz,
20
2H), 7.36e7.28 (m, 6H), 2.87 (tt, J¼9.6, 3.7 Hz, 1H), 2.28 (dt, J¼13.6,
3.5 Hz, 1H), 2.01e1.91 (m, 1H), 1.43e1.31 (m, 3H), 1.31e1.22 (m, 3H),
1.22e1.15 (m, 1H), 0.83 (t, J¼7.4 Hz, 3H), 0.79 (t, J¼7.4 Hz, 3H);
4.5.6. Compound (S)-29. [
a
]
¼ þ13.4 (c¼0.33, CHCl3). IR (neat)
n
D
(cmꢁ1) 2957, 2865, 1433, 1382, 1067, 817, 739, 695; 1H NMR
(500 MHz, CDCl3)
d
7.93 (d, J¼8.5 Hz, 3H), 7.48e7.44 (m, 2H),
31PNMR (200 MHz, CDCl3)
CDCl3)
d
¼ ꢁ21.13 ppm; 13C NMR (125 MHz,
7.43e7.39 (m, 2H), 7.33e7.17 (m, 6H), 5.88 (d, J¼9.0 Hz, 1H),
4.64e4.29 (m, 1H), 2.52e2.29 (m, 2H), 1.64 (m, 1H), 1.51e1.37 (m,
3H), 1.36e1.26 (m, 1H), 0.90 (td, J¼7.3, 0.8 Hz, 6H); 31P NMR
d 139.35, 139.26, 138.22, 138.12, 133.29, 133.13, 132.52,
132.37, 128.85, 128.49, 128.42 (d, JC,P¼3.8 Hz), 128.34 (d,
JC,P¼3.8 Hz), 49.78, 49.67, 48.18, 48.12, 34.96, 34.87, 22.18, 21.45,
12.04, 12.02; ESI-MS calcd for C19H27NP: m/z (%): 300.1876 (MþHþ),
found: 300.1871.
(200 MHz, CDCl3)
d
¼ ꢁ22.98 ppm; 19F NMR (282 MHz, CDCl3)
d
¼ ꢁ62.77 ppm; 13C NMR (125 MHz, CDCl3)
d 163.69, 138.21 (d,
JC,P¼13.75 Hz), 138.05 (d, JC,P¼12.5 Hz), 136.61, 132.84 (d,
JC,P¼8.75 Hz),132.69 (d, JC,P¼7.5 Hz),131.93 (q, JC,F¼32.5 Hz),128.98,
128.90, 128.67(d, JC,P¼3.75 Hz), 128.62(d, JC,P¼3.75 Hz), 127.05 (d,
JC,F¼3.75 Hz), 124.76 (dd, JC,F¼7.5, 3.8 Hz), 122.91 (q, JC,F¼273 Hz),
50.28 (d, JC,P¼13.75 Hz), 45.67 (d, JC,P¼7.5 Hz), 31.21 (d, JC,P¼15 Hz),
20
4.5.2. Compound (S)-24. [
a]
¼ þ46.8 (c¼0.33, CHCl3). IR (neat)
n
D
(cmꢁ1) 3200, 2957, 1456, 1372, 1282, 1044, 857, 750; 1H NMR
(500 MHz, CDCl3) 7.57e7.42 (m, 4H), 7.42e7.32 (m, 10H),
d

2706
P. Chen et al. / Tetrahedron 72 (2016) 2700e2706
ChemCatChem 2013, 5, 2775; (h) Wei, Y.; Shi, M. Chem. Rev. 2013, 113, 6659; (i)
Fan, Y. C.; Kwon, O. Chem. Commun. 2013, 11588; (j) Wang, Z.; Xu, X.; Kwon, O.
Chem. Sos. Rev. 2014, 43, 2927; (k) Wei, Y.; Shi, M. Chem.dAsian J. 2014, 9, 2720.
3. Zhang, Z.-M.; Chen, P.; Li, W.; Niu, Y.; Zhao, X.-L.; Zhang, J. Angew. Chem., Int. Ed.
2014, 53, 4350.
22.20, 22.02, 11.55, 11.40; ESI-MS calcd for C28H28F6NNaOP: m/z (%):
562.1705 (MþNaþ), found: 562.1703.
20
4.5.7. Compound (S)-30. [
a
]
¼ ꢁ6.9 (c¼0.33, CHCl3). IR (neat)
n
D
(cmꢁ1) 2959, 1582, 1453, 1382, 1262, 1046, 817, 739, 695;1H NMR
(500 MHz, CDCl3)
4. For selected leading examples of chiral b-aminephosphines utilized as nucle-
ophilic catalysts, please see: (a) Han, X.; Wang, Y.; Zhong, F.; Lu, Y. J. Am. Chem.
Soc. 2011, 133, 1726; (b) Zhong, F.; Han, X.; Wang, Y.; Lu, Y. Angew. Chem., Int. Ed.
2011, 50, 7837; (c) Han, X.; Zhong, F.; Wang, Y.; Lu, Y. Angew. Chem., Int. Ed. 2012,
51, 767; (d) Zhong, F.; Luo, J.; Chen, G.-Y.; Dou, X.; Lu, Y. J. Am. Chem. Soc. 2012,
134, 10222; (e) Zhong, F.; Dou, X.; Han, X.; Yao, W.; Zhu, Q.; Meng, Y.; Lu, Y.
Angew. Chem., Int. Ed. 2013, 52, 943; (f) Wang, T.; Yao, W.; Zhong, F.; Pang, G. H.;
Lu, Y. Angew. Chem., Int. Ed. 2014, 53, 2964; (g) Han, X.; Yao, W.; Wang, T.; Tan,
Y. R.; Yan, Z.; Kwiatkowski, J.; Lu, Y. Angew. Chem., Int. Ed. 2014, 53, 5643; (h)
Henry, C. E.; Xu, Q.; Fan, Y. C.; Martin, T. J.; Belding, L.; Dudding, T.; Kwon, O. J.
Am. Chem. Soc. 2014, 136, 11890; (i) Fang, Y.-Q.; Tadross, P. M.; Jacobsen, E. N. J.
Am. Chem. Soc. 2014, 136, 17966; (j) Yao, W.; Dou, X.; Lu, Y. J. Am. Chem. Soc.
2015, 137, 54; (k) Wang, H.-Y.; Zhang, K.; Zheng, C.-W.; Chai, Z.; Cao, D.-D.;
Zhang, J.-X.; Zhao, G. Angew. Chem., Int. Ed. 2015, 54, 1775.
d
8.67 (s, 1H), 7.68 (d, J¼9.1 Hz, 3H), 7.54e7.41 (m,
4H), 7.38e7.30 (m, 6H), 6.32 (s, 1H), 4.84 (s, 1H), 2.47 (dd, J¼14.1,
3.9 Hz, 1H), 2.37 (dd, J¼14.0, 8.8 Hz, 1H), 1.74 (d, J¼36.9 Hz, 2H),
1.44e1.19 (m, 4H), 0.88 (dt, J¼14.3, 7.3 Hz, 6H); 31P NMR (200 MHz,
CDCl3)
d
d
¼
ꢁ24.09 ppm; 19F NMR (282 MHz, CDCl3)
¼ ꢁ63.02 ppm; 13C NMR (125 MHz, CDCl3)
d 179.61, 138.77, 137.67
(d, JC,P¼10 Hz), 132.96 (d, JC,P¼18.75 Hz), 132.66(d, JC,P¼18.75 Hz),
129.02 (d, JC,P¼18.75 Hz), 128.64 (d, JC,P¼6.25 Hz), 123.21, 122.78 (d,
JC,P¼271.25 Hz), 118.95, 118.92, 118.89, 55.02 (d, JC,P¼15 Hz), 44.94,
30.68, 22.45, 11.70, 11.51; ESI-MS calcd for C28H30F6N2SP: m/z (%):
571.1766 (MþHþ), found: 571.1761.
5. For selected examples of chiral b-aminephosphines utilized as ligand of tran-
sition metal complexes, please see: (a) Zuo, W.; Lough, A. J.; Li, Y. F.; Morris, R.
H. Science 2013, 342, 1080; (b) Werkmeister, S.; Junge, K.; Wendt, B.; Alberico,
E.; Jiao, H.; Baumann, W.; Junge, H.; Gallou, F.; Beller, M. Angew. Chem., Int. Ed.
2014, 53, 8722; (c) Lagaditis, P. O.; Sues, P. E.; Sonnenberg, J. F.; Wan, K. Y.;
Lough, A. J.; Morris, R. H. J. Am. Chem. Soc. 2014, 136, 1367.
Acknowledgements
6. For selected strategies for the synthesis of chiral aminephosphines please see:
(a) Saitoh, A.; Morimoto, T.; Achiwa, K. Tetrahedron: Asymmetry 1997, 8, 3567;
(b) Porte, A. M.; van der Donk, W. A.; Burgess, K. J. Org. Chem. 1998, 63, 5262; (c)
Saitoh, A.; Uda, T.; Morimoto, T. Tetrahedron: Asymmetry 1999, 10, 4501; (d)
Krauss, I. J.; Leighton, J. L. Org. Lett. 2003, 5, 3201; (e) Ito, M.; Osaku, A.; Ko-
bayashi, C.; Shiibashi, A.; Ikariya, T. Organometallics 2009, 28, 390; (f) Guo, R.;
Lu, S.; Chen, X.; Tsang, C.-W.; Jia, W.; Sui-Seng, C.; Amoroso, D.; Abdur-Rashid,
K. J. Org. Chem. 2010, 75, 937.
We are grateful to the National Natural Science Foundation of
China (21372084, 21425205), and Changjiang Scholars and In-
novative Research Team in University (PCSIRT) for financial
supports.
Supplementary data
7. Su, X.; Zhou, W.; Li, Y.; Zhang, J. Angew. Chem., Int. Ed. 2015, 54, 6874.
8. (a) Pei, D.; Wang, Z.; Wei, S.; Zhang, Y.; Sun, J. Org. Lett. 2006, 8, 5913; (b)
Bolshan, Y.; Batey, R. A. Org. Lett. 2005, 7, 1481; (c) Mita, T.; Sugawara, M.; Saito,
K.; Sato, Y. Org. Lett. 2014, 16, 3028; (d) Liu, G.; Cogan, D. A.; Ellman, J. A. J. Am.
Chem. Soc. 1997, 119, 9913; (e) Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. D.;
Ellman, J. A. J. Org. Chem. 1999, 64, 1278; (f) Tanuwidjaja, J.; Peltier, H. M.; Lewis,
J. C.; Schenkel, L. B.; Ellman, J. A. Synthesis 2007, 3385.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2015.12.002.
References and notes
9. Camus, J.-M.; Andrieu, J.; Richard, P.; Poli, R. Eur. J. Inorg. Chem. 2004, 1081.
10. See the Supporting Information for X-ray structures. CCDC 1045425 ((S, Rs)-X1)
and 1045426 ((R, Rs)-X11) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
11. Zhong, F.; Han, X.; Wang, Y.; Lu, Y. Chem. Sci. 2012, 3, 1231.
1. For selected reviews, see: (a) Valentine, D. H.; Hillhouse, J. H. Synthesis 2003,
317; (b) Spivey, A. C.; Arseniyadis, S. Top. Curr. Chem. 2010, 291, 233.
2. For selected reviews related to nucleophilic catalysis with chiral phosphines,
please see: (a) Methot, J. L.; Roush, W. R. Adv. Syn. Catal. 2004, 346, 1035; (b) Ye,
L.-W.; Zhou, J.; Tang, Y. Chem. Sos. Rev. 2008, 37, 1140; (c) Wei, Y.; Shi, M. Acc.
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