Distinct chemoselectivity in the reaction of N-(thio)phosphoryl imines with diethylzinc

Article abstract of DOI:10.1016/j.jorganchem.2007.05.001

This report describes the reaction of N-(thio)phosphoryl imines with diethylzinc under different conditions. An interesting and distinct chemoselectivity between hydrogen-addition and ethyl-addition to imine double bond is disclosed: in weakly polar solve

Full text of DOI:10.1016/j.jorganchem.2007.05.001

Journal of Organometallic Chemistry 692 (2007) 3685–3690
www.elsevier.com/locate/jorganchem
Distinct chemoselectivity in the reaction of N-(thio)phosphoryl
imines with diethylzinc
*
*
Xinpeng Ma, Xinyuan Xu, Chungui Wang, Guofeng Zhao , Zhenghong Zhou ,
Chuchi Tang
State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China
Received 12 February 2007; received in revised form 23 March 2007; accepted 1 May 2007
Available online 6 May 2007
Abstract
This report describes the reaction of N-(thio)phosphoryl imines with diethylzinc under different conditions. An interesting and distinct
chemoselectivity between hydrogen-addition and ethyl-addition to imine double bond is disclosed: in weakly polar solvent, e.g. toluene,
N-(thio)phosphoryl imines were exclusively reduced in excellent yields via a b-H transfer from diethylzinc to imine double bond; in polar
solvents like THF, the reduction product was competitively formed as a major product together with the minor product resulting from
ethyl-addition to imine double bond; in sharp contrast, in the presence of strong coordinative additive N,N,N0,N0-tetramethylethylenedi-
amine (TMEDA), the ethylation product was formed exclusively from the reaction of N-(thio)phosphoryl imine with diethylzinc. These
results are discussed and explained in terms of the coordination interactions between the imine, solvent, and additive with diethylzinc.
ꢀ 2007 Elsevier B.V. All rights reserved.
Keywords: (Thio)phosphorylimine; (Thio)phosphinoylimine; Phosphonylimine; Diethylzinc; Reduction; Alkylation
Ph
Ph
O
N
1. Introduction
Ph
Ph
O
P
H
Cat.
P
R
+
R Zn
2
NH
*
Asymmetric addition of imines is a convenient and prac-
tical method for the preparation of synthetic valuable
nitrogen-containing compounds, such as chiral amines,
1,2-diamines, and a- or b-amino acids. Recently, significant
progress has been witnessed in this area [1]. Imines with
electron-withdrawing groups, e.g. acyl, sulfonyl, aryl and
phosphoryl group, on the nitrogen have been intensively
investigated due to their enhanced reactivity. For example,
diphenylphosphinoylimines 1 have been successfully emp-
loyed as the substrates in many asymmetric reactions [2],
such as hydrogenation, alkylation, Mannich reaction,
aza-Henry reaction and Strecker reaction. The asymmetric
alkylation of 1 with diethylzinc could also be run smoothly
in the presence of chiral copper catalysts [3] or chiral 1,2-
aminoalcohols [4].
Ar
Ar
1
We have noted that the N-phosphoryl group in phos-
phorylimines is an excellent imine auxiliary, because of its
activation of the C@N bond for nucleophilic addition
and its ease of deprotection from the final product under
mild acidic conditions. Also, introducing different substitu-
ents to phosphorus center could easily modulate its elec-
tronic properties. Therefore, we followed this successful
strategy to extend diphenylphosphinoylimines 1 to cheaper
and readily available O,O-diethyl phosphorylimine 2 and
its thio analogues 3. Herein, we report an interesting and
distinct chemoselectivity between hydrogen-addition and
ethyl-addition to imine double bond in the reaction of
N-(thio)phosphoryl imines and diethylzinc.
*
Corresponding authors.
E-mail address: z.h.zhou@nankai.edu.cn (Z. Zhou).
0022-328X/$ - see front matter ꢀ 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2007.05.001

3686
X. Ma et al. / Journal of Organometallic Chemistry 692 (2007) 3685–3690
2. Results and discussion
lar solvent toluene (entries 3–8, Table 1). The aryl group at
the carbon atom of imine double bond in 3 did not show
much influence on the reaction.
It was surprising that the reaction of 2 or 3 with dieth-
ylzinc in toluene exclusively afforded the corresponding
reduction product rather than the ethylation product. At
the same time, the by-product ethylene was detected and
confirmed in the reaction. This result revealed that modu-
lating of the substituents on the phosphorus atom in
N-phosphoryl imine might cause the total reversion of
the chemoselectivity in this reaction. Thus, different types
of N-(thio)phosphoryl imines were further synthesized,
and their reactions with diethylzinc in toluene were exten-
sively investigated with the results listed in Table 1.
The influence of solvents on the reaction was also inves-
tigated employing imine 3a as the substrate. The results
(Table 2) showed that the polarity of solvent had a moder-
ate influence on the reaction, although the conversion of
the reaction was nearly 100% in all tested solvents. In
non-polar solvent toluene, the reduction product 9a exclu-
sively formed. However, in polar solvent like THF, chloro-
form, and ether, the reduction reaction took place
competitively with the ethylation reaction, although the
reduction product 9a was still obtained as the major with
the minor ethylation product 12a.
As shown in Table 1, the reduction products were read-
ily obtained in high yields for those substrates containing
alkoxy or aryloxy group on phosphorus atom (imines 2,
3, 4, and 6). However, no reaction occurred when diphenyl-
(thio)phosphinoylimine 1(7) and bis(diethylamino)phos-
phorylimine 5 were employed as the substrate, respectively.
The variation of P@O double bond to P@S double bond
did not exhibit any considerable influence on the reaction
direction, except that better yield was observed for thio-
phosphorylimine 3a versus its oxygen analogue 2. The
starting material, O,O-diethyl phosphorochloridothioate,
for the preparation of thiophosphorylimine 3a is available
from the industrial source. Also, the existence of P@S dou-
ble bond made the thiophosphorylimine or its related inter-
mediate more stable against hydrolysis and heating. This
property of P@S double bond resulted in the ease of puri-
fication and high yields in the preparation of thiophospho-
rylimine. Thus, we chose N-thiophosphorylimine 3 as the
substrate to explore its reaction with diethylzinc. For all
selected substrates 3, the reduction products were obtained
in high yields from the reactions with diethylzinc in nonpo-
With these findings in hand, we supposed that the che-
moselectivity might be adjusted between the hydrogen-
reduction and ethylation of the imine double bond in the
reaction of imine 3 with diethylzinc by introducing appro-
priate additives to the reaction system. Thus, the reaction
of imine 3 and diethylzinc was surveyed in the presence
of different types of additives. The results were listed in
Table 3.
Introduction of coordinative additives proved to be a
successful strategy to promote the selectivity (stereo- or
chemo-) for the reaction of diphenylphosphinoylimine 1
with diethylzinc. For example, many chiral 1,2-aminoalco-
hols can catalyze or promote the ethylation reaction
between diphenylphosphinoylimine 1 and diethylzinc [4].
Thus, the reaction was first carried out in the presence of
chiral aminoalcohols 13 or 14. Almost quantitative reduc-
tion product 9a was isolated in cases of all specified molar
ratios of diethylzinc to chiral aminoalcohol used (entries
1–3, Table 3). Beresford has reported that cincho-
nidine could promote the addition of diethylzinc to diph-
Table 1
Reactions of different phosphoryl imines with diethylzinc in toluenea
1
1
R
2
X
N
R
2
X
P
H
P
Toluene
+
+
NH
Et Zn
R
R
o
2
20 C
Ar
Ar
Entry
Imine
R1
Ph
R2
X
Ar
Time (h)
Yield (%) of productsb
1
2
3
4
5
6
7
8
9
1
Ph
O
O
S
S
S
S
S
S
S
O
S
S
Ph
Ph
Ph
48
1
1
0.5
2
24
12
12
12
48
6
NRc
2
EtO
EtO
EtO
EtO
EtO
EtO
EtO
PhO
Et2N
EtO
Ph
EtO
EtO
EtO
EtO
EtO
EtO
EtO
PhO
Et2N
Ph
83 (8)
90 (9a)
>99 (9b)
90 (9c)
77 (9d)
86 (9e)
79 (9f)
83 (10)
NRb
3a
3b
3c
3d
3e
3f
4
4-MeOC6H4
2-ClC6H4
4-BrC6H4
3-FC6H4
3-F3CC6H4
Ph
Ph
Ph
Ph
10
11
12
a
5
6
83 (11)
NRb
7
Ph
48
All the reactions were carried out with a 1:4 molar ratio of imine substrate to diethylzinc.
Isolated yield.
NR means no reaction.
b
c

X. Ma et al. / Journal of Organometallic Chemistry 692 (2007) 3685–3690
3687
Table 2
obtained as the dominant products (entries 6–11). The aryl
group in the substrate imine 3 has a margin influence on
this addition reaction. Imines substituted with electron-
withdrawing group (entries 8 and 9) exhibited higher reac-
tivity than those containing electron-donating group
(entries 10 and 11). Based on this result, chiral analogue
of TMEDA, cyclohexanediamine 15, was synthesized and
employed as the additive in this reaction. The ethylation
product was attained exclusively with the enantioselectivity
of 28% ee (entry 12). However, under the otherwise same
conditions the non-vicinal aromatic diamine 16 could not
promote the alkylation reaction. The reduction product
was still preferentially formed (entry 13).
Reaction of imine 3a with diethylzinc in different solventsa
EtO
EtO
S
EtO
EtO
S
EtO
EtO
S
N
P
P
P
H
Solvent
20oC
+
NH
NH
+
Et2Zn
Ph
Et
Ph
12a
Ph
3a
9a
Solvent
Toluene THF CH2Cl2 CHCl3
Et2O 1,4-
Dioxane
Conversion
(%)b
9a:12a
>99
>99
>99
>99
>99
>99
100:0
93:7 88:12
72:28
(70:30)c
88:12 83:17
a
All the reactions were carried out in 1 mmol scale with a 1:4 molar
ratio of imine substrate to diethylzinc.
OH
b
Ratio determined by the 31P NMR spectra of the reaction mixture.
Data in the parenthesis determined by GC–MS analysis.
Ph
Ph
NMe2
NMe2
c
HO
N
NMe2
Me2N
NMe2
OH
Me
NO2
13
14
15
16
enylphosphinoylimine 1. The corresponding ethylated
products were obtained in good yields (56–77%) with mod-
erate to excellent enantioselectivity (56–93%) [4a,4d]. How-
ever, under the similar conditions, the reaction of imine 3a
with diethylzinc exclusively gave the reduction product
rather than the ethylation product 12 (entry 4). Further
increase of the molar ratio of cinchonidine to diethylzinc
to 3:3 made the reaction sluggish, and resulted in the for-
mation of a mixture of ethylation and reduction product
(entry 5). Contrarily, it was quite surprising that the use
of N,N,N0,N0-tetramethylethylenediamine (TMEDA) as
the additive led to the total reversion of the reaction orien-
tation. The corresponding ethylation products were
Thus far, the exact mechanism of the reaction between
N-(thio)phosphoryl imine and diethylzinc remains unclear.
In terms of the coordination interactions among the imine,
diethylzinc, and additive, we herein try to propose a ratio-
nal mechanism to interpret above results. Since imine 3 has
both imine and ethoxy groups, and both N and O atoms
are r-electron donors, it could first coordinate with dieth-
ylzinc as a N,O-bidentate ligand. In non-polar solvent like
toluene, this coordination binding firmly holds the imine
and zinc species together, so that the b-hydrogen of ethyl
Table 3
Reaction of imine 3 with diethylzinc in the presence of different additivesa
EtO
EtO
S
EtO
EtO
S
EtO
EtO
S
N
P
P
P
H
Additive
Solvent, 20oC
+
NH
NH
+
Et2Zn
Ar
Et
Ar
Ar
3
9
12
Entry
Additive
Ar
3:Et2Zn:additive
Time (h)
Conversion/%b (Yield/%c)
9:12c
1
2
3
4
5
6
7
8
9
10
11
12d
13
a
13
13
Ph
Ph
Ph
Ph
Ph
Ph
Ph
1:4:1
1:3:3
1:3:3
1:4:1
24
36
48
24
36
48
48
36
36
72
72
48
48
>99
>99
>99
>99 (90)
49
>99 (82)
>99 (86)
>99 (80)
>99 (81)
92 (75)
90 (72)
>99 (93)
>99
100:0
98:2
100:0
100:0
14
Cinchonidine
Cinchonidine
TMEDA
TMEDA
TMEDA
TMEDA
TMEDA
TMEDA
15
1:3:3
38:62
1:1.6:1.6
1:1.6:1.6
1:1.6:1.6
1:1.6:1.6
1:1.6:1.6
1:1.6:1.6
1:3:3
4:96 (12a)
7:93 (12a)
0:100 (12b)
0:100 (12c)
2:98 (12d)
4:96 (12e)
0:100 (12a)
91:9
2-ClC6H4
3-FC6H4
4-MeC6H4
3-MeOC6H4
Ph
16
Ph
1:3:3
All the reactions were conducted in toluene except for entry 7 which was carried out in THF.
b
c
Determined by 31P NMR spectra.
Isolated yield.
d
The addition product was obtained with 28% ee. Determined by HPLC analysis on an OD-H column, hexane: 2-propanol = 90:10, flow rate 1.0 mL/
min, retention time t1 = 6.97 min (major), t2 = 33.10 min (minor).

3688
X. Ma et al. / Journal of Organometallic Chemistry 692 (2007) 3685–3690
X
P
N
points were determined on a T-4 melting point apparatus.
1
O
R
All temperatures and pressures were uncorrected. All of
the solvent was dried according to the standard method
and used after fresh distillation. N-(Thio)phosphoryl imi-
nes were prepared according to the literature method [6].
R
Zn
Ar
H
3.2. Reaction of N-(thio)phosphoryl imines with diethylzinc
(general procedure)
Fig. 1. Transition state for the b-hydrogen transfer process.
group could be easily transferred onto the imine carbon
through a chair-like six-membered ring transition state,
affording the exclusive hydrogen-reduction product
together with the release of ethylene (Fig. 1). When the
reaction is carried out in polar solvent, the coordination
or solvation of the solvent with diethylzinc weakens the
coordination interaction between diethylzinc and imine.
Thus the ethylated product could be competitively formed
(see Table 2). When TMEDA, which has proven to be a
strong coordinating ligand to Zn2+ ion [5], is employed,
then diethylzinc would preferentially coordinate with such
an additive, and its interaction with the imine would be
replaced or destroyed. The separation of the imine with
diethylzinc would hinder the b-hydrogen transfer through
a chair-like six-membered ring transition state (Fig. 1),
but favors the nucleophilic attack of diethylzinc as an ethy-
lating agent at the imine double bond. As the result, the
ethylated product was formed dominantly in the presence
of TMEDA (see Table 3). The fact that the ethylated prod-
uct was obtained exclusively with an enantioselectivity of
28% ee in the presence of chiral TMEDA analogue 15 does
provide a solid support for the coordination interaction
between the additive and diethylzinc.
In conclusion, we demonstrate a quite distinct chemose-
lectivity in the reaction of O,O-diethyl thiophosphorylimine
with diethylzinc. Under different conditions, the hydrogen
reduction product or ethylation product could be selectively
and exclusively obtained. The determining factor for this
chemoselectivity presumably originates from the coordina-
tion interactions between the imine, solvent, and additive
with diethylzinc. These findings provide some helpful
insights for the reactions of imines with diethylzinc. Further
investigation on the asymmetric ethylation of O,O-diethyl
thiophosphorylimines with diethylzinc under the promotion
of strongly coordinative chiral additives is ongoing in our
laboratory.
To a solution of N-(thio)phosphoryl imine (1 mmol) in
toluene (3 mL) was added diethylzinc (4 mL, 1 M solution
in n-hexane) under an argon atmosphere. The resulting
mixture was then stirred at 20 ꢁC until the disappearance
of N-(thio)phosphoryl imine (monitored by 31P NMR).
The reaction was quenched with the addition of saturated
aqueous ammonium chloride and stirred for 0.5 h. After
phase separation, the aqueous layer was extracted with
ethyl acetate (3 · 5 mL). The combined organic phase
was dried over anhydrous sodium sulfate. After removal
of solvent the crude product was purified by column chro-
matography on silica gel (200–300 meshes, gradient eluted
with petroleum ether and ethyl acetate).
For 8: Colourless oil, 83% yield, 31P NMR (d, CDCl3):
9.58; 1H NMR (d, CDCl3): 1.31 (t, 6H, JH–H = 7.2 Hz,
2CH3), 2.98 (br., 1H, NH), 3.99–4.11 (m, 6H, 3CH2),
7.24–7.36 (m, 5H arom). Anal. Calc. for C11H18NO3P: C,
54.31; H, 7.46; N, 5.76. Found: C, 54.19; H, 7.38; N, 5.62%.
For 9a: Pale yellow oil, 90% yield, 31P NMR (d, CDCl3):
1
72.20; H NMR (d, CDCl3): 1.30 (t, 6H, JH–H = 7.2 Hz,
2CH3), 3.31 (br., 1H, NH), 3.96–4.14 (m, 6H, 3CH2),
7.25–7.35 (m, 5H arom). Anal. Calc. for C11H18NO2PS:
C, 50.95; H, 7.00; N, 5.40. Found: C, 50.93; H, 6.89; N,
5.34%.
For 9b: Pale yellow oil, >99% yield, 31P NMR
(d, CDCl3): 72.35; 1H NMR (d, CDCl3): 1.19 (t, 6H,
JH–H = 7.2 Hz, 2CH3), 3.63 (br., 1H, NH), 3.75 (s, 3H,
OCH3), 3.79–3.85 (m, 2H, CH2), 3.93–4.02 (m, 4H, CH2),
6.77–6.84 (m, 2H arom), 7.15–7.20 (m, 2H arom). Anal.
Calc. for C12H20NO3PS: C, 49.81; H, 6.97; N, 4.84. Found:
C, 49.67; H, 6.86; N, 4.79%.
For 9c: Pale yellow oil, 90% yield, 31P NMR (d, CDCl3):
1
72.39; H NMR (d, CDCl3): 1.24 (t, 3H, JH–H = 7.2 Hz,
CH3), 1.25 (t, 3H, JH–H = 7.2 Hz, CH3), 3.53 (br., 1H,
NH), 3.90–3.95 (m, 2H, CH2), 4.01–4.07 (m, 2H, CH2),
4.18–4.22 (m, 2H, CH2), 7.20–7.25 (m, 2H arom),
7.32–7.34 (m, 1H arom), 7.40–7.42 (m, 1H arom). Anal.
Calc. for C11H17ClNO2PS: C, 44.97; H, 5.83; N, 4.77.
Found: C, 44.85; H, 5.66; N, 4.38%.
3. Experimental
3.1. General methods
For 9d: Pale yellow oil, 77% yield, 31P NMR (d, CDCl3):
1
72.40; H NMR (d, CDCl3): 1.28 (t, 6H, JH–H = 7.2 Hz,
1H and 31P NMR spectra were recorded in CDCl3 on a
Varian 400 instrumental using TMS as an internal stan-
dard for 1H NMR and 85% H3PO4 as an external standard
for 31P NMR. Enantiomeric excesses were determined on a
HP-1100 instrument (OD-H column; mobile phase: hex-
ane/i-PrOH). Elemental analyses were conducted on a
Yanaco CHN Corder MT-3 automatic analyzer. Melting
2CH3), 3.33 (br., 1H, NH), 3.94–4.12 (m, 6H, 3CH2),
7.17–7.19 (d, 2H arom, JH–H = 8.0 Hz), 7.42–7.44 (d, 2H
arom, JH–H = 8.0 Hz). Anal. Calc. for C11H17BrNO2PS:
C, 39.06; H, 5.07; N, 4.14. Found: C, 38.96; H, 5.05; N,
4.14%.
For 9e: Pale yellow oil, 86% yield, 31P NMR (d, CDCl3):
1
72.42; H NMR (d, CDCl3): 1.30 (t, 6H, JH–H = 7.2 Hz,

X. Ma et al. / Journal of Organometallic Chemistry 692 (2007) 3685–3690
3689
2CH3), 3.29 (br., 1H, NH), 3.99–4.16 (m, 6H, 3CH2), 6.93–
7.09 (m, 3H arom), 7.26–7.32 (m, 1H arom). Anal. Calc.
for C11H17FNO2PS: C, 47.64; H, 6.18; N, 5.05. Found:
C, 47.53; H, 6.24; N, 4.96%.
CH3), 1.31 (t, 3H, JH–H = 6.8 Hz, CH3), 1.69–1.79 (m,
2H, CH2), 3.47–3.54 (m, 1H, one proton of CH2), 3.59
(br. 1H, NH), 3.84–4.09 (m, 3H, CH2 and one proton of
CH2), 4.61–4.63 (m, 1H, CH), 7.17–7.33 (m, 4H arom).
Anal. Calc. for C13H21ClNO2PS: C, 48.52; H, 6.58; N,
4.35. Found: C, 48.69; H, 6.45; N, 4.73%.
For 9f: Pale yellow oil, 79% yield, 31P NMR (d, CDCl3):
1
72.42; H NMR (d, CDCl3): 1.26 (t, 6H, JH–H = 7.2 Hz,
2CH3), 3.52 (t, 1H, JH–H = 6.8 Hz, NH), 3.93–4.09 (m,
4H, 2CH2) 4.19 (dd, 2H, JH–H = 7.2 Hz, JP–H = 12.0 Hz,
CH2), 7.42–7.44 (t, 1H arom, JH–H = 7.6 Hz), 7.49–7.51
(d, 2H arom, JH–H = 7.6 Hz), 7.58 (s, 1H arom). Anal.
Calc. for C12H17F3NO2PS: C, 44.03; H, 5.24; N, 4.28.
Found: C, 44.06; H, 4.81; N, 4.31%.
For 12c: Pale yellow oil, 81% yield, 31P NMR
(d, CDCl3): 70.43; 1H NMR (d, CDCl3): 0.87 (t, 3H,
JH–H = 7.2 Hz, CH3), 1.03 (t, 3H, JH–H = 7.2 Hz, CH3),
1.30 (t, 3H, JH–H = 6.8 Hz, CH3), 1.68–1.80 (m, 2H,
CH2), 3.38 (br., 1H, NH), 3.53–3.63 (m, 1H, CH),
3.89–4.18 (m, 4H, 2CH2), 6.92–7.31 (m, 4H arom). Anal.
Calc. for C13H21FNO2PS: C, 51.13; H, 6.93; N, 4.59.
Found: C, 51.32; H, 6.74; N, 4. 68%.
For 10: Pale yellow oil, 80% yield, 31P NMR (d, CDCl3):
1
63.96; H NMR (d, CDCl3): 3.68 (br., 1H, NH), 4.11 (d,
2H, JH–H = 9.2 Hz, CH2), 7.16–7.36 (m, 15H arom). Anal.
Calc. for C19H18NO2PS: C, 64.21; H, 5.11; N, 3.94. Found:
C, 64.03; H, 5.14; N, 3.74%.
For 12d: Pale yellow oil, 75% yield, 31P NMR (d,
CDCl3): 71.08; 1H NMR (d, CDCl3): 0.85 (t, 3H,
JH–H = 7.2 Hz, CH3), 1.01 (t, 3H, JH–H = 7.2 Hz, CH3),
1.30 (t, 3H, JH–H = 7.2 Hz, CH3), 1.66–1.78 (m, 2H,
CH2), 2.32 (s, 3H, CH3), 3.48 (br., 1H, NH), 3.43–3.52
(m, 1H, CH), 3.91–4.22 (m, 4H, 2CH2), 7.32 (d, 2H arom,
JH–H = 8.0 Hz), 7.96 (d, 2H arom, JH–H = 8.0 Hz). Anal.
Calc. for C14H24NO2PS: C, 55.79; H, 8.03; N, 4.65. Found:
C, 55.58; H, 7.87; N, 4.81%.
For 11: Pale yellow oil, 83% yield, 31P NMR (d, CDCl3):
1
70.88; H NMR (d, CDCl3): 1.34 (t, 3H, JH–H = 7.2 Hz,
CH3), 3.39 (br., 1H, NH), 3.99–4.07 (m, 3H, CH2, H-
CH), 4.17–4.25 (m, 1H, H-CH–), 7.21–7.31 (m, 5H arom),
7.43–7.51 (m, 3H arom), 7.87–7.92 (m, 2H arom). Anal.
Calc. for C15H18NOPS: C, 61.83; H, 6.23; N, 4.81. Found:
C, 61.81; H, 6.28; N, 4.79%.
For 12e: Pale yellow oil, 72% yield, 31P NMR (d,
CDCl3): 71.11; 1H NMR (d, CDCl3): 0.86 (t, 3H,
JH–H = 7.2 Hz, CH3), 0.99 (t, 3H, JH–H = 7.2 Hz, CH3),
1.29 (t, 3H, JH–H = 6.8 Hz, CH3), 1.69–1.78 (m, 2H,
CH2), 3.41 (br., 1H, NH), 3.45–3.61 (m, 1H, CH), 3.80
(s, 3H, OCH3), 3.89–4.17 (m, 4H, 2CH2), 6.79–7.25 (m,
4H arom). Anal. Calc. for C14H24NO3PS: C, 52.98; H,
7.62; N, 4.41. Found: C, 53.02; H, 7.43; N, 4.36%.
3.3. Reaction of O,O-diethyl thiophosphorylimine 3 with
diethylzinc in the presence of additives (general procedure)
To a solution of additive (3.2–6.0 mmol, as depicted in
Table 3) in solvent (10 mL) was added diethylzinc
(3.2–8.0 mmol, as depicted in Table 3, 1 M solution in
n-hexane) under an argon atmosphere and the resulting
mixture was stirred for 15 min. Then O,O-diethyl thiophos-
phorylimine 3 (2 mmol) was added and the reaction mix-
ture was stirred at 20 ꢁC for 24–72 h. The reaction was
quenched with the addition of saturated ammonium chlo-
ride solution. After phase separation, the aqueous layer
was extracted with ethyl acetate (3 · 5 mL). The combined
organic phase was dried over anhydrous sodium sulfate.
After removal of solvent the crude product was used
directly to determine the conversion and the ratio of the
reducing product to the ethylation product through 31P
NMR analysis. In some cases, the crude product was fur-
ther purified by column chromatography on silica gel
(200–300 meshes, gradient eluted with petroleum ether
and ethyl acetate).
Acknowledgments
We are grateful to the National Natural Science Foun-
dation of China (No. 20472033) and Key Science and
Technology projects of Ministry of Education of China
for generous financial support for our programs. We thank
professor Zhengjie He for helpful discussion.
References
[1] (a) R. Bloch, Chem. Rev. 98 (1998) 1407;
(b) S. Kobayashi, H. Ishitani, Chem. Rev. 99 (1999) 1069;
(c) T. Vilaivan, W. Bhanthumnavi, Y. Sritana-Anant, Curr. Org.
Chem. 9 (2005) 1315.
For 12a: Pale yellow oil, 83% yield, 31P NMR (d,
[2] S.M. Weinreb, R.K. Orr, Synthesis (2005) 1205.
[3] (a) A. Cote, A.B. Charette, J. Org. Chem. 70 (2005) 10864;
(b) J.N. Desrosiers, A. Cote, A.B. Charette, Tetrahedron 61 (2005)
6186;
1
CDCl3): 70.89; H NMR (d, CDCl3): 0.85 (t, 3H, JH–H
=
7.2 Hz, CH3), 0.99 (t, 3H, JH–H = 7.2 Hz, CH3), 1.30
(t, 3H, JH–H = 7.2 Hz, CH3), 1.70–1.80 (m, 2H, CH2),
3.35–3.54 (m, 2H, CH, NH), 3.83–4.16 (m, 4H, 2CH2),
7.23–7.33 (m, 5H arom). Anal. Calc. for C13H22NO2PS:
C, 54.33; H, 7.72; N, 4.87. Found: C, 54.69; H, 7.51; N,
4.86%.
(c) M.C. Wang, L.T. Liu, Y.Z. Hua, J.S. Zhang, Y.Y. Shi, D.K.
Wang, Tetrahedron: Asymmetry 16 (2005) 2531;
(d) A. Cote, A.A. Boezio, A.B. Charette, Angew. Chem., Int. Ed. 43
(2004) 6525;
(e) A.A. Boezio, A.B. Charette, J. Am. Chem. Soc. 125 (2003) 1692;
(f) A.A. Boezio, J. Pytkowicz, A. Cote, A.B. Charette, J. Am. Chem.
Soc. 125 (2003) 14260;
For 12b: White solid, m.p. 43–45 ꢁC, 80% yield, 31P
1
NMR (d, CDCl3): 70.48; H NMR (d, CDCl3): 0.91 (t,
(g) C.J. Wang, M. Shi, J. Org. Chem. 68 (2003) 6229;
(h) M. Shi, C.J. Wang, Adv. Synth. Catal. 345 (2003) 971.
3H, JH–H = 7.2 Hz, CH3), 0.96 (t, 3H, JH–H = 7.2 Hz,

3690
X. Ma et al. / Journal of Organometallic Chemistry 692 (2007) 3685–3690
`
`
[4] (a) K.J.M. Beresford, Tetrahedron Lett. 45 (2004) 6041;
(b) X.M. Zhang, H.L. Zhang, W.Q. Lin, L.Z. Gong, A.Q. Mi, X. Cui,
Y.Z. Jiang, K.B. Yu, J. Org. Chem. 68 (2003) 4322;
(c) H.L. Zhang, X.M. Zhang, L.Z. Gong, A.Q. Mi, X. Cui, Y.Z.
Jiang, M.C.K. Choi, A.S.C. Chan, Org. Lett. 4 (2002) 1399;
(d) K.J.M. Beresford, Tetrahedron Lett. 43 (2002) 7175;
(e) I. Sato, K. Hosoi, R. Kodaka, K. Soai, Eur. J. Org. Chem. (2002)
3115;
(h) C. Jimeno, K.S. Reddy, L. Sola, A. Moyano, M.A. Pericas, A.
Riera, Org. Lett. 2 (2000) 3157;
(i) I. Sato, R. Kodaka, T. Shibata, Y. Hirokawa, N. Shirai, K.
Ohtake, K. Soai, Tetrahedron: Asymmetry 11 (2000) 2271;
(j) D. Guijarro, P. Pinho, P.G. Andersson, J. Org. Chem. 63 (1998)
2530;
(k) P.G. Andersson, D. Guijarro, D. Tanner, J. Org. Chem. 62 (1997)
7364.
(f) I. Sato, R. Kodaka, K. Soai, J. Chem. Soc., Perkin Trans. I (2001)
2912;
(g) P. Pinho, P.G. Andersson, Tetrahedron 57 (2001) 1615;
[5] F.F. Gao, M.Z. Deng, C.T. Qian, Tetrahedron 61 (2005) 12238.
[6] X.Y. Xu, C.G. Wang, Z.H. Zhou, Z.B. Zeng, X.P. Ma, G.F. Zhao,
C.C. Tang, Lett. Org. Chem. 3 (2006) 640.