Chiral diphenylselenophosphoramides: A new class of chiral ligands for the titanium(IV) alkoxide-promoted addition of diethylzinc to aldehydes

Article abstract of DOI:10.1016/S0957-4166(00)00016-1

Chiral C₂-symmetric diphenylselenophosphoramides 1 and 2 were prepared from the reaction of diphenylselenophosphinic chloride with (1R,2R)-(-)-1,2-diaminocyclohexane and (1R,2R)-(+)-1,2-diphenylethylenediamine, respectively, in high yields. Ano

Full text of DOI:10.1016/S0957-4166(00)00016-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 835–841
Chiral diphenylselenophosphoramides: a new class of chiral
ligands for the titanium(IV) alkoxide-promoted addition of
diethylzinc to aldehydes
Min Shi and Wen-Sheng Sui b
a,∗
a
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
3
54 Fenglin Lu, Shanghai 200032, China
b
East China University of Science and Technology, 130 Mei Long Lu, Shanghai 200237, China
Received 17 December 1999; accepted 4 January 2000
Abstract
Chiral C2-symmetric diphenylselenophosphoramides 1 and 2 were prepared from the reaction of diphenylseleno-
phosphinic chloride with (1R,2R)-(−)-1,2-diaminocyclohexane and (1R,2R)-(+)-1,2-diphenylethylenediamine, res-
pectively, in high yields. Another novel chiral ligand 3 was prepared from the reaction of diphenylselenophosphinic
0
0
chloride with (R)-(+)-1,1 -binaphthyl-2,2 -diamine using butyllithium as the base. The ligands were used as
catalytic chiral ligands in the titanium(IV) alkoxide-promoted enantioselective addition reaction of diethylzinc
to aldehydes. © 2000 Elsevier Science Ltd. All rights reserved.
1
. Introduction
Previously we reported that chiral C -symmetric diphenylphosphoramide and diphenylthiophosphor-
2
amide of (1R,2R)-(−)-1,2-diaminocyclohexane were used as chiral ligands in the catalytic asymmetric
addition reaction of diethylzinc to aldehydes in the presence of titanium(IV) isopropoxide to give the
1
corresponding sec-alcohols with high ee. This result prompted us to synthesize other such novel chiral
ligands for catalytic asymmetric reactions. This time we decided to synthesize diphenylselenophosphor-
amides 1, 2 and 3 as novel chiral ligands for the same titanium(IV) alkoxide-promoted addition reaction
of diethylzinc to aldehydes. We selected selenophosphoramide as a novel chiral ligand because it is well
2
known that the sulfur-containing compounds such as substituted β-aminothiols and β-hydroxysulfides
3
derived from D-camphor are very effective chiral ligands for the enantioselective addition reaction of
aldehydes and reduction of imides. This is largely due to the high coordination ability of sulfur atom to
metal center and the bigger Van der Waals radius of the sulfur atom (N: 1.55; O: 1.52; P: 1.80; S: 1.80
∗
Corresponding author.
0
957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00016-1
tetasy 3239

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M. Shi, W.-S. Sui / Tetrahedron: Asymmetry 11 (2000) 835–841
Å). The selenium atom has a similar coordination ability to various metals as sulfur and a slightly bigger
Van der Waals radius (Se: 1.90 Å). However, we seldom see reports related to chiral ligands containing
4
selenium. Based on this concept and background, we expect that selenium bound to phosphorus could
also have a good coordinative ability to metal centers, and a derived chiral metal complex could achieve
chiral induction similar to thiophosphoramide ligands.1
2. Results and discussion
Diphenylselenophosphoramides 1 and 2 were synthesized from the reaction of diphenylseleno-
phosphinic chloride with (1R,2R)-(−)-1,2-diaminocyclohexane and (1R,2R)-(+)-1,2-diphenylethylene-
diamine in the presence of diisopropylethylamine or triethylamine in dichloromethane, respectively
(Scheme 1). After the usual workup and purification by silica gel column chromatography or recrystalli-
zation, compounds 1 and 2 were obtained as colorless solids in over 90% yields. In addition, by utilizing
0
0
the C -symmetric (R)-(+)-1,1 -binaphthyl-2,2 -diamine as a chiral scaffold, we prepared another novel
2
chiral ligand 3 (Scheme 2).
Scheme 1.
Scheme 2.
5
The corresponding thiophosphoramide ligands have been synthesized using the same methods. Their
structures were confirmed by spectral data and microanalysis. Moreover, the crystal structure of 3 was
6
disclosed by X-ray analysis (Fig. 1).
Fig. 1. The crystal structure of 3
Interestingly, one dichloromethane molecule was included into the crystal lattice of 3 during the re-
crystallization from dichloromethane. These chiral ligands were used for the titanium(IV) isopropoxide-

M. Shi, W.-S. Sui / Tetrahedron: Asymmetry 11 (2000) 835–841
837
promoted enantioselective addition reaction of diethylzinc to p-chlorophenylaldehyde in the presence
i
of titanium(IV) isopropoxide [RCHO:Ti(OPr ) :Et Zn=1:1.4:1.8] under various reaction conditions. The
4
2
ees of the products were determined by HPLC analysis using chiral stationary-phase column (Chiralcel
OD and OJ), and the absolute configuration of the major enantiomer was assigned according to the sign
of the specific rotation. The results are shown in Table 1.
Table 1
Asymmetric addition reaction of diethylzinc to p-chlorobenzaldehyde in the presence of chiral ligands
1
, 2 and 3 under different reaction conditions
For the novel chiral ligand 1, we found that the solvent drastically affected the enantiomeric excess (ee)
1
of this asymmetric addition reaction as found for the analogous thiophosphoramide. Toluene is a good
solvent for achieving higher ee (60%) and the lowest ee of sec-alcohol was obtained in tetrahydrofuran
(THF) and dichloromethane, although the yields of the reaction products are very similar to toluene.
The best reaction conditions were found in toluene at −50°C with 60% ee (Table 1, entry 2). For chiral
selenophosphoramides 2 and 3, we found that the best results were obtained in toluene at −50°C with
3
and 40% ee, respectively (Table 1, entries 6 and 9). Among these three chiral selenophosphoramide
ligands, 2 gave the lowest enantioselectivity. This may be due to chiral ligand 2 not having a rigid
structure; namely, the two diphenylselenophosphoryl groups can rotate around the C and C bond. Thus
1
2
it would be difficult to form a rigid chiral titanium(IV) complex to achieve asymmetric induction. By
means of this optimized reaction conditions, various aldehydes were used as substrates for this addition
reaction and the corresponding sec-alcohols could be obtained in 80–95% yield and 53–73, 3–5 and
4
0–46% ee with R-configuration, respectively. Their results are summarized in Table 2. For various
aldehydes, 2 also gave the lowest ee. For aliphatic aldehyde using 1 as a chiral ligand, the ee decreased to
3%. It should be emphasized that the chiral selenophosphoramide ligands 1, 2 and 3 could be recovered
5
from the reaction mixture in 90% after the usual workup and can be used again in the asymmetric reaction
without loss of enantioselectivity. Thus, the chiral diphenylselenophosphoramides 1, 2 and 3 are quite
stable chiral ligands in this asymmetric addition reaction. However, these selenophosphoramides are
slightly photosensitive and gradually decompose upon sunlight irradiation. For chiral ligands 1 and 2,

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M. Shi, W.-S. Sui / Tetrahedron: Asymmetry 11 (2000) 835–841
as expected, phosphoryl selenium atoms can coordinate to the titanium(IV) metal center to some extent
giving a chiral environment, although the achieved ee is not perfect for 1 and very low for 2. Meanwhile,
for chiral ligand 3, we believe that it is a bidentate chiral ligand; namely, the nitrogen and phosphoryl
selenium atoms can coordinate to the titanium(IV) metal affording the chiral titanium(IV) complex. In
order to verify this speculation, we are trying to get a single crystal of the catalyst to confirm their
structures.
Table 2
Asymmetric addition reaction of diethylzinc to arylaldehydes in the presence of catalytic amounts of
i
chiral ligands [L:RCHO:Ti(OPr )
4
:Et
2
Zn=0.2:1:1.4:1.8]
In conclusion, the chiral C -symmetric bidentate selenophosphoramides 1 and 2 prepared from
2
C -symmetric (1R,2R)-(−)-1,2-diaminocyclohexane and (1R,2R)-(+)-1,2-diphenylethylenediamine and
2
0
0
monodiphenylselenophosphoramide 3 derived from (R)-(+)-1,1 -binaphthyl-2,2 -diamine were found
to be a new class of relatively effective chiral ligands for the titanium(IV) isopropoxide-promoted
enantioselective addition reaction of diethylzinc to aldehydes although they are not as effective as
6
ditriflamide. This paper discloses, for the first time, that chiral selenophosphoramides can catalyze the
enantioselective ethylation reaction using titanium(IV) alkoxide. Hopefully, these results will open a
new way to design and synthesize new chiral ligands for asymmetric reactions. Efforts are underway to

M. Shi, W.-S. Sui / Tetrahedron: Asymmetry 11 (2000) 835–841
839
elucidate the mechanistic details of this addition reaction and to disclose the exact structure of the active
species. Moreover, we are planning to synthesize other such bidentate chiral phosphoramides embedded
into C -symmetric chiral scaffolds in order to seek out more effective and stereoselective chiral ligands
2
and to utilize those novel chiral ligands to the other catalytic asymmetric reactions.
3. Experimental
3.1. General
Melting points (mps) were obtained with a Yanagimoto micro melting point apparatus and are
uncorrected. Optical rotations were determined in a solution of CHCl at 20°C by using a Perkin–Elmer
3
−1
2
−1
1
2
41 MC polarimeter; [α] values are given in units of 10 deg cm g . H NMR spectra were
D
recorded on a Bruker AM-300 spectrometer for solution in CDCl with tetramethylsilane (TMS) as
3
internal standard; J values are in hertz. Mass spectra were recorded with a HP-5989 instrument and
HRMS was measured by a Finnigan MA+ mass spectrometer. Organic solvents used were dried by
standard methods when necessary. All solid compounds reported in this paper gave satisfactory CHN
microanalyses with an Italian Carlo Erba 1106 analyzer. Commercially obtained reagents were used
without further purification. All reactions were monitored by TLC with Huanghai 60F254 silica gel
coated plates. Flash column chromatography was carried out using 300–400 mesh silica gel at increased
pressure. All ethylation experiments were performed under argon using standard Schlenk techniques.
The optical purities of sec-alcohols were determined by HPLC analysis using a chiral stationary phase
column (column, Daicel Co. Chiralcel OD and OJ; eluent, 100:0.5–2 hexane:2-propanol mixture; flow
−
1
rate, 1.0 ml min ; detection, 254 nm light) and the absolute configuration of the major enantiomer was
assigned according to the sign of the specific rotation. Diphenylselenophosphinic chloride was prepared
upon heating chlorodiphenylphosphine with selenium at 100°C for 6 h.
3.2. Preparation of chiral selenophosphoramide 1
To a solution of (1R,2R)-(−)-1,2-diaminocyclohexane (325 mg, 2.85 mmol) and diisopropylethyl-
amine (1.10 g, 8.55 mmol, 1.5 ml) in dichloromethane (20 ml) was added diphenylselenophosphinic
chloride (1.71 g, 5.70 mmol) at −30°C. After stirring the mixture for 6 h, the reaction mixture was
washed with 3% aq. HCl, water, 10% Na CO and brine, and the product was extracted with ether. The
2
3
extract was dried over MgSO , and then evaporated under reduced pressure. The residue was purified
4
by silica gel column chromatography to give the compound 1 (1.74 g, 95%) as a colorless solid. Mp
5
1
3–54°C; [α] +7.8 (c 3.6, CHCl ); δ (CDCl ) 1.0–1.20 (2H, m, CH ), 1.22–1.42 (4H, m, CH ),
D
3
H
3
2
2
.43–1.60 (2H, m, CH ), 1.70–1.90 (2H, m), 3.30–3.51 (2H, m), 3.90–4.02 (2H, m), 7.30–7.40 (4H, m,
2
+
Ar), 7.40–7.60 (8H, m, Ar), 7.70–7.90 (4H, m, Ar), 7.95–8.12 (4H, m, Ar); MS (FAB) m/z (%): 640 (M ,
4
6
0), 561 (30), 297 (40), 265 (100), 183 (80) [found: C, 55.89; H, 4.91; N, 4.07%. HRMS (FAB) m/z:
+
42.0368 (M ); C H N Se P requires: C, 56.26; H, 5.04; N, 4.37%; M, 642.0371].
3
0
32
2
2 2
3.3. Preparation of chiral selenophosphoramide 2
To a solution of (1R,2R)-(+)-1,2-diphenylethylenediamine (214 mg, 1.0 mmol) and triethylamine (300
mg, 3.0 mmol, 0.42 ml) in dichloromethane (20 ml) was added diphenylselenophosphinic chloride (598
mg, 2.0 mmol) at 0°C. After stirring the reaction mixture for 10 h, the solvent was removed under reduced

8
40
M. Shi, W.-S. Sui / Tetrahedron: Asymmetry 11 (2000) 835–841
pressure. The crude product was extracted with ether and washed with water (3×50 ml), 10% Na CO (50
2
3
ml) and brine. The organic layer was dried over anhydrous Na SO and then evaporated under reduced
2
4
pressure. The residue was recrystallized from dichloromethane and hexane (4:1) to give 2 as a colorless
crystal (673 mg, 91%). Mp 170–172°C (dec.); [α] −56.2 (c 1.9, CHCl ); δ (CDCl ) 4.50–4.65 (2H,
D
3
H
3
m, CH), 5.56–5.78 (2H, m, NH), 6.80–6.95 (4H, dd, J=7.4, 1.3 Hz, Ar), 7.0–7.20 (8H, m, Ar), 7.24–7.50
+
(
2
10H, m, Ar), 7.55–7.75 (4H, m, Ar), 7.75–8.0 (4H, m, Ar); MS (EI) m/z (%): 738 (M , 10), 370 (70),
+
90 (30), 265 (100), 183 (90) [found: C, 61.77; H, 4.70; N, 3.80%. HRMS (EI) m/z: 740.0517 (M );
C H N Se P requires: C, 61.80; H, 4.64; N, 3.79%; M, 740.0528].
3
8
34
2
2 2
3.4. Preparation of chiral selenophosphoramide 3
0
0
To a solution of (R)-(+)-1,1 -binaphthyl-2,2 -diamine (244 mg, 0.84 mmol) in THF (20 ml) was added
dropwise 2.0 M n-butyllithium in cyclohexane (1.20 ml, 2.4 mmol) at −40°C over 40 min and the reaction
mixture was stirred for 1 h. Then diphenylselenophosphinic chloride (720 mg, 2.4 mmol) was added
dropwise and the reaction solution was stirred for a further 10 h at −40°C to room temperature. The
mixture was filtered to remove the solid and the THF was removed under reduced pressure. The organic
product was extracted with ether and the organic layer was washed with water, 10% Na CO and brine.
2
3
The extract was dried over MgSO and then evaporated under reduced pressure. The residue was purified
4
by alumina (Al O ) column chromatography to give the compound 3 as colorless solid (428 mg, 92%).
2
3
Mp 110–115°C (dec.); [α]D −9.0 (c 1.10, CHCl ); δ (CDCl ) 3.40 (2H, s, br, NH ), 5.02 (1H, d,
3
H
3
2
J=6.4 Hz), 7.0–7.50 (10H, m, Ar), 7.50–7.70 (4H, m, Ar), 7.70–8.0 (8H, m, Ar); MS (EI) m/z (%): 548
+
(
M , 70), 467 (20), 391 (20), 283 (16), 267 (100) [found: C, 62.60; H, 4.22; N, 4.32%. HRMS (EI) m/z:
+
5
48.0918 (M ); C H N PSe·CH Cl requires: C, 62.67; H, 4.30; N, 4.43%; M, 548.0921].
3
2
25
2
2
2
3.5. Typical reaction procedure
To a solution of selenophosphoramide 1 (104 mg, 0.16 mmol) in dichloromethane (5 ml) was added
titanium(IV) isopropoxide (320 mg, 1.12 mmol, 0.33 ml) at room temperature. After stirring the mixture
for 0.5 h, p-chlorobenzaldehyde (112 mg, 0.8 mmol) was added to the reaction solution and the reaction
mixture was cooled to −50°C. Then diethylzinc (1.44 ml, 1.44 mmol, 1 M solution in hexane) was added
to the solution and the reaction mixture was stirred for 48 h at −50°C. The reaction was quenched by
5% aq. HCl and the product was extracted with ether. The organic layer was washed with brine and dried
over MgSO , and then evaporated under reduced pressure. The residue was purified by silica gel TLC to
4
give the optically active 1-(p-chlorophenyl)propan-1-ol (125 mg, 92%).
Acknowledgements
We thank Prof. Albert S. C. Chan and the National Natural Sciences Foundation of China for financial
support. We also thank the Inoue Photochirogenesis Project (ERATO, JST) for chemical reagents.
References
1
. (a) Shi, M.; Sui, W.-S. Tetrahedron: Asymmetry 1999, 10, 3319, and references cited therein. For reviews and other references
on catalytic enantioselective alkylation using dialkylzincs, see: (b) Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. Engl.
1
991, 30, 49. (c) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833. (d) Schmidt, B.; Seebach, D. Angew. Chem., Int. Ed. Engl.

M. Shi, W.-S. Sui / Tetrahedron: Asymmetry 11 (2000) 835–841
841
1
2
991, 30, 99. (e) Seebach, D.; Plattner, D. A.; Beck, A. K.; Wang, Y. M.; Hunziker, D.; Petter, W. Helv. Chim. Acta 1992, 75,
171. (f) Zhang, F.-Y.; Yip, C.-W.; Cao, R.; Chan, S. C. Tetrahedron: Asymmetry 1997, 8, 585.
2
. (a) Kang, J.; Lee, J. W.; Kim, J. I. J. Chem. Soc., Chem. Commun. 1994, 2009; (b) Hof, R. P.; Poelert, M. A.; Peper, N. C. M.
W.; Kellog, R. M. Tetrahedron: Asymmetry 1994, 5, 31; (c) Kang, J.; Lee, J. W.; Kim, J. I.; Pyum, C. Tetrahedron Lett. 1995,
3
6, 4265. (d) Rijnberg, E.; Jastrzebski, J. T. B. H.; Janssen, M. D.; Boersma, J.; Koten, G. v. Tetrahedron Lett. 1994, 35, 6521;
(e) Carreno, M. C.; Ruano, J. L.; Maestro, M. C.; Cabrejas, L. M. M. Tetrahedron: Asymmetry 1993, 4, 727; (f) Masaki, Y.;
Satoh, Y.; Makihara, T.; Shi, M. Chem. Pharm. Bull. 1996, 44, 454.
3
4
. Arai, Y.; Nagata, N.; Masaki, Y. Chem. Pharm. Bull. 1995, 43, 2243.
. For a few papers related to selenium ligands, see: (a) Kataoka, T.; Iwama, T.; Tsujiyama, S.-I.; Kanematsu, K.; Iwamura, T.;
Watanabe, S.-I., Chem. Lett. 1999, 257. (b) Kataoka, T.; Iwama, T.; Tsujiyama, S.-I. J. Chem. Soc., Chem. Commun. 1998,
1
97. (c) Wirth, T. Tetrahedron Lett. 1995, 36, 7849.
. Shi, M.; Sui, W.-S. Tetrahedron: Asymmetry 2000, 11, 773–779.
. The crystal data of 3. Empirical formula: C33 SePCl ; formula weight: 632.43; crystal color, habit: colorless, prismatic;
crystal dimensions: 0.20×0.20×0.30 mm; crystal system: monoclinic; lattice type: primitive; lattice parameters: a=11.950(3)
Å, b=8.164(3) Å, c=16.127(3) Å, β=107.56(2) Å, V=1500.1(7) Å ; space group: P2 (#4); Z value=2; Dcalc=1.400 g/cm ;
000=644.00; µ(MoKα)=15.08 cm ; diffractometer: Rigaku AFC7R; temperature: 20°C; scan type: ω-2θ.
5
6
H
27
N
2
2
3
3
1
−
1
F