Stereoselective addition of grignard reagents to new P-chirogenic N-phosphinoylbenzaldimines: Effect of the phosphorus substituents on the stereoselectivity

Article abstract of DOI:10.1002/ejoc.201100380

Several phosphinoylimines have been synthesized in five steps by starting from the appropriate phosphane oxide and were then treated with methylmagnesium bromide to give both diastereoisomers in high yields and with promising diastereomeric ratios. Then N-[(tert-butyl)(phenyl)phosphinoyl]benzaldimine, which displayed the best results, was subjected to the 1,2-addition of various Grignard reagents to evaluate the best chiral induction due to the stereogenic phosphorus atom. The corresponding adducts were obtained in excellent yields and with moderate to excellent diastereoisomeric ratios. Copyright

Full text of DOI:10.1002/ejoc.201100380

FULL PAPER
DOI: 10.1002/ejoc.201100380
Stereoselective Addition of Grignard Reagents to New P-Chirogenic N-
Phosphinoylbenzaldimines: Effect of the Phosphorus Substituents on the
Stereoselectivity
Irene Notar Francesco,[a,b] Coraline Egloff,[c] Alain Wagner,*[c] and Françoise Colobert*[a]
Keywords: Chirality / Imines / Grignard reaction / Stereoselectivity / Phosphorus
Several phosphinoylimines have been synthesized in five
steps by starting from the appropriate phosphane oxide and
were then treated with methylmagnesium bromide to give
both diastereoisomers in high yields and with promising dia-
stereomeric ratios. Then N-[(tert-butyl)(phenyl)phosphinoyl]-
benzaldimine, which displayed the best results, was sub-
jected to the 1,2-addition of various Grignard reagents to
evaluate the best chiral induction due to the stereogenic
phosphorus atom. The corresponding adducts were obtained
in excellent yields and with moderate to excellent diastereo-
isomeric ratios.
philes. Although (diphenylphosphinoyl)imines are by far
the most common electrophiles used in the stereoselective
Introduction
Chiral amines play an important role in biologically addition of nucleophiles with chiral metal-complex cata-
active systems. These motifs form part of the most impor- lysts,[4] rare examples of chiral phosphinoylimines bearing
tant structural frameworks in chiral drugs. It is now well a P-chirogenic center or a chiral auxiliary linked to the P
established that the stereoselective addition of organometal- atom can be found in the literature. Very recently, Li and
lic reagents to imines is one of the most powerful and direct co-workers reported the synthesis of chiral C2-symmetric
methods for the asymmetric construction of amines.[1] In phosphinoylimines derived from secondary enantiopure
particular, imines activated by electron-withdrawing groups trans-cyclohexane-1,2-diamine, which were successfully
on the nitrogen atom, such as sulfonyl-, sulfinyl-, and acyl- used as electrophiles in asymmetric reactions such as aza-
imines, have been extensively used in recent decades because Darzens,[5] aza-Henry,[6] and Mannich reactions,[7] the ad-
of their high electrophilicity. Chiral sulfinylimines are dition of Grignard reagents[8] and various enolates,[9] and
doubtless the most widely used in such transformations be- very recently in the addition of lithium aryl- and alkylacet-
cause of their chiral sulfur atoms, which ensures high ste- ylides[10] and lithium phosphites[11] with excellent results in
reocontrol.[2] Nevertheless, there still exist some limitations terms of yields and diastereomeric excesses of the final
and shortcomings in their use in asymmetric synthesis due products. In 1994, Jennings et al. reported the synthesis of
to the sensitivity of the N-sulfinyl group to the oxidation N-[(mesityl)(phenyl)phosphinoyl]benzaldimine and the oxi-
and action of Brønsted acids or strong Lewis acids dation of the C=N double bond leading to new chiral ox-
(TiCl4),[3] which can cause the racemization of the sulfur aziridines,[12] important reagents in the asymmetric oxi-
center and strongly compromise the recovery of the chiral dation of prochiral sulfides and olefins. Moreover, 2 months
auxiliary at the end of the process. On the other hand, before the publication of our communication, Royer and
phosphinoylimines have begun to attract more attention co-workers described the diastereoselective alkynylation of
from synthetic chemists and have been employed in a wide new N-[(methyl)(phenyl)phosphinoyl]benzaldimine by alu-
range of asymmetric transformations with various nucleo- minium acetylides.[13] To the best of our knowledge, these
are the only examples of asymmetric transformations in-
volving chiral or P-chirogenic phosphinoylimines described
to date. Recently, we reported the synthesis of P-chirogenic
[a] Laboratoire de Stéréochimie, Université de Strasbourg
N-[(tert-butyl)(phenyl)phosphinoyl]benzaldimine,
which
(ECPM),
25 rue Becquerel, 67087 Strasbourg Cedex 2, France
Fax: +33-3-68852742
was successfully applied to the diastereoselective addition
of various Grignard reagents with encouraging levels of
stereoselection.[14] We now report a full account of our re-
sults concerning the synthesis of both P-chirogenic [diaryl-
and (alkyl)(aryl)phosphinoyl]imines as well as their use in
the diastereoselective 1,2-addition of Grignard reagents.
E-mail: francoise.colobert@unistra.fr
[b] Novalix Pharma, Bld Sébastien Brant,
B. P. 30170, 67405 Illkirch cedex, France
[c] Université de Strasbourg, CNRS UMR 7175,
74 Route du Rhin, 67401 Illkirch cedex, France
E-mail: alwag@unistra.fr
Eur. J. Org. Chem. 2011, 4037–4045
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I. Notar Francesco, C. Egloff, A. Wagner, F. Colobert
FULL PAPER
Table 1. Synthesis of P-chirogenic phosphinoylimines 5a–d and pre-
cursors 1–4a–d.
Results and Discussion
A series of racemic N-[(aryl)(phenyl)- and (tert-butyl)-
(phenyl)phosphinoyl]benzaldimines were synthesized in five
steps by starting from commercially available dichlo-
ro(phenyl)phosphane. Indeed, according to the general re-
action sequence described by Yeung and co-workers[15] for
the preparation of (tert-butyl)(phenyl)phosphinamide,
dichloro(phenyl)phosphane was treated with Grignard rea-
gents followed by treatment with HCl to afford the corre-
sponding secondary phosphane oxides 1a–d. The phos-
phane oxides were then deprotonated with LDA and
trapped with 1,2-dibromoethane to afford the bromophos-
phane oxides 2a–d. Then nucleophilic substitution at the
phosphorus center with benzylamine was performed in
Et2O at room temperature. Debenzylation of the corre-
sponding secondary phosphinamides 3a–d carried out in an
autoclave with H2 at 20 bar and 10% Pd/C in EtOH gave
the phosphinamides 4a–d. Benzaldehyde was then con-
densed with 4a–d under TiCl4/triethylamine catalysis in
CH2Cl2 to produce the corresponding N-phosphinoylben-
zaldimines 5a–d (Scheme 1). All the results are summarized
in Table 1. Secondary phosphane oxides (Entries 1, 6, and
11) were synthesized in good to excellent yields from dichlo-
ro(phenyl)phosphane by addition of the desired Grignard
reagent: 3 equiv. of freshly prepared tBuMgCl was neces-
sary to obtain phosphane oxide 1a, whereas only 1.1 equiv.
of organometallic reagent was required for 1b and 1c, which
were isolated in almost quantitative yields.
Entry
R1
R2
Yield [%][a]
1
2
3
4
5
tBu
H[b]
1a
2a
3a
4a
5a
54
69
79
73
89
Br[c]
NHBn[d]
[e]
NH2
imine[f]
6
7
8
9
10
2-biphenylyl
mesityl
H[g]
1b
2b
3b
4b
5b
97
12[h]
73
97
59
Br[c]
NHBn[d]
[e]
NH2
imine[f]
11
12
13
14
15
H[g]
1c
2c
3c
4c
5c
98
47
93
98
67
Br[c]
NHBn[d]
[e]
NH2
imine[f]
16
17
18
19
20
2-naphthyl
H[i]
1d
2d
3d
4d
5d
41
54
71
96
61
Br[c]
NHBn[d]
[e]
NH2
imine[f]
[a] Isolated yield after chromatography. [b] Reagents and condi-
tions: RMgX (3 equiv.), PCl2Ph (1 equiv.), Et2O, reflux, 16 h. [c]
Reagents and conditions: LDA(1.2 equiv.), BrCH2CH2Br
(1 equiv.), THF, –78 °C, 3 h. [d] Reagents and conditions:
PhCH2NH2 (5 equiv.), NEt3 (2.2 equiv.), Et2O, room temp. [e] Rea-
gents and conditions: H2 (20 bar), 10% Pd/C, EtOH, room temp. [f]
Reagents and conditions: PhCHO (1 equiv.), NEt3 (3 equiv.), TiCl4
(0.5 equiv.), CH2Cl2, 0 °C, room temp. [g] Reagents and conditions:
RMgX (1.1 equiv.), PCl2Ph (1 equiv.), Et2O, reflux, 16 h. [h] A by-
product (diphosphane) was isolated in 32% yield. [i] Synthesized
from a diastereoisomeric mixture of menthyl phenylphosphinate
(see Exp. Sect.).
yield due to the formation of a byproduct, the diphosphane
probably originating from a side-reaction of the lithiated
phosphane oxide with the bromophosphane formed. N-
Benzylphosphinamides 3a–d and phosphinamides 4a–d
were recovered in high yields after nucleophilic substitution
at the P atom (Entries 3, 8, 13, and 18) and catalytic de-
benzylation (Entries 4, 9, 14, and 19). Benzaldehyde was
then condensed with 4a–d under TiCl4/triethylamine cataly-
sis in CH2Cl2 to produce the corresponding N-phosphinoyl-
benzaldimines 5a–d in good yields.
These imines were then subjected to methylmagnesium
bromide to compare the different levels of diastereoselec-
tion exerted by the adjacent P-chirogenic center. In our pre-
Scheme 1. Synthesis of P-chirogenic phosphinoylimines 5a–d.
Surprisingly, the addition of 2-naphthylmagnesium bro- vious report, we identified two different reaction conditions
mide to the chlorophosphane failed, and (2-naphthyl)- (dichloromethane at room temp. or toluene at 0 °C) that
(phenyl)phosphane oxide (1d) (Entry 16) was prepared in allowed the adducts from the addition of methylmagnesium
moderate yield by addition of the organolithiated com- bromide to N-[(tert-butyl)(phenyl)phosphinoyl]benzaldim-
pound to a diastereoisomeric mixture of (–)-menthyl hydro- ine to be isolated in high yields and satisfactory dia-
genphenylphosphinate according to the procedure devel- stereomeric ratios (Scheme 2).
oped by Han and co-workers.[16] Note that a high yield of
Indeed, we decided to apply these two different condi-
91% has been reported by Buono and co-workers for the tions to the synthesis of imines 5b–d. The results are sum-
addition of 2-naphthylmagnesium bromide to (–)-menthyl marized in Table 2. The (diarylphosphinoyl)imines (Table 2,
hydrogenphenylphosphinate.[17] Bromophosphane oxides Entries 1–6) displayed good reactivity and chiral induction,
2a–c were obtained in moderate to good yields from phos- affording the corresponding addition products in excellent
phane oxides, except 2b, which was isolated in very low yields and moderate to good diastereoisomeric ratios al-
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4037–4045

Grignard Addition to P-Chirogenic N-Phosphinoylbenzaldimine
gents, and the corresponding adducts were isolated in excel-
lent yields and with moderate to excellent diastereomeric
ratios.
Branched and linear aliphatic Grignard reagents were
first tested with N-[(tert-butyl)(phenyl)phosphinoyl]benz-
aldimine (5a). A diastereomeric ratio of 75:25 and a yield
of 98% were obtained from the addition of isopropylmag-
nesium bromide in CH2Cl2 at room temperature. To be sure
that CH2Cl2 is the best solvent for this diastereoselective
addition irrespective of the Grignard reagent used, we per-
formed in parallel the reaction in toluene and obtained, as
expected, a slightly lower selectivity of 70:30 (Table 3, En-
tries 1 and 2). By using the sterically more hindered tert-
butylmagnesium chloride, we observed only 47% conver-
sion of the phosphinoylbenzaldimine 5a in CH2Cl2 at
25 °C, and the selectivity decreased to 60:40. Heating to
reflux completed the reaction, but no improvement in the
stereoselectivity was noted (Table 3, Entries 3 and 4). With
linear aliphatic Grignard reagents such as n-butyl- and n-
decylmagnesium bromide, we observed modest selectivity
(70:30) and high yields in CH2Cl2 at 25 °C (Table 3, En-
tries 5 and 6). Then we turned our attention to the use of
unsaturated Grignard reagents. The addition of vinylmag-
nesium bromide to the phosphinoylbenzaldimine 5a led to
the corresponding phosphinamide in a 60:40 diastereomeric
ratio (Table 3, Entry 7). The use of the sterically more hin-
dered (2-methylallyl)magnesium chloride allowed us to im-
prove the selectivity to 75:25 in CH2Cl2 in 85% yield
(Table 3, Entry 8). Surprisingly, the addition of mesitylmag-
nesium bromide was completely diastereoselective giving
the corresponding amine in 98% yield in CH2Cl2 in con-
Scheme 2. Methylmagnesium bromide addition to racemic N-[(tert-
butyl)(phenyl)phosphinoyl]benzaldimine (5a).
though to a lesser extent than with imine 5a. Note that the
steric hindrance of the aryl moiety seems to be a key factor
in the diastereoselective process.
Table 2. 1,2-Addition of methylmagnesium bromide to racemic N-
(phenylphosphinoyl)benzaldimines 5b–e.
Entry Imine Solvent, T [°C] Yield [%][a,b]
dr[c]
Products
1
2
3
4
5
6
7
5b
5c
CH2Cl2, 25
toluene, 0
CH2Cl2, 25
toluene, 0
CH2Cl2, 25
toluene, 0
CH2Cl2, 25
89
83
79
95
81
85
91
65:35 (Ϯ)-6b/(Ϯ)-7b
75:25
70:30 (Ϯ)-6c/(Ϯ)-7c
75:25
55:45 (Ϯ)-6d/(Ϯ)-7d
60:40
70:30 (Ϯ)-6e/(Ϯ)-7e
5d
5e[d]
[a] Overall yields of the four stereoisomers. [b] Yield after
chromatography. [c] Determined by 1H or 31P NMR analysis of the
crude mixture. [d] 5e (R = Me) was synthesized according to the
procedure reported by Jennings and co-workers.[18]
Table 3. Grignard 1,2-addition to racemic N-[(tert-butyl)(phenyl)-
phosphinoyl]benzaldimine (5a).[a]
For instance, imine 5c, bearing a mesityl group highly
hindered at the ortho positions, provided the addition prod-
ucts in a 70:30 diastereomeric ratio when the reaction was
carried out in dichloromethane at room temperature and
in a 75:25 diastereomeric ratio in toluene at 0 °C (Table 2,
Entries 3 and 4). With less hindered aryl groups such as 2-
biphenylyl and 2-naphthyl, lower diastereoisomeric ratios in
the addition adducts were observed (Table 2, Entries 2 and
6, respectively) when the reaction was carried out in toluene
at 0 °C. Curiously, in contrast to what we observed in the
case of N-[(tert-butyl)(phenyl)phosphinoyl]benzaldimine
(Scheme 2), we noticed when (diarylphosphinoyl)imines
were employed that toluene seems to be the best solvent
at 0 °C (Table 2, Entries 2, 4, and 6). The 1,2-addition of
MeMgBr to imine 5e was also explored, 5e easily being pre-
pared from the corresponding commercially available
(methyl)(phenyl)phosphinyl chloride as previously reported
by Jennings and co-workers[18] and employed by Royer and
co-workers.[13] The addition reaction was carried out in
dichloromethane at room temperature and provided the ad-
ducts in 91% yield and a diastereomeric ratio of 70:30
(Table 2, Entry 7). These results encouraged us to explore
thescopeoftheGrignardadditionreactionwithN-[(tert-butyl)-
(phenyl)phosphinoyl]benzaldimine (5a). Thus, this imine
Entry
R
dr[b]
Yield [%][c]
Products
1
2[d]
3[e]
4[h]
5
6
7
8
9
10
11
12
13
isopropyl
75:25
70:30
60:40
65:35
70:30
70:30
60:40
75:25
60:40
60:40
55:45
100:0[i]
85:15
98
83
29[g]
90
93
91
67
85
97
97
95
98
99
(Ϯ)-8a/(Ϯ)-8b
tert-butyl[f]
(Ϯ)-9a/(Ϯ)-9b
n-butyl
n-decyl
vinyl
(Ϯ)-10a/(Ϯ)-10b
(Ϯ)-11a/(Ϯ)-11b
(Ϯ)-12a/(Ϯ)-12b
(Ϯ)-13a/(Ϯ)-13
(Ϯ)-14a/(Ϯ)-14b
(Ϯ)-15a/(Ϯ)-15b
(Ϯ)-16a/(Ϯ)-16b
(Ϯ)-17a/(Ϯ)-17b
(Ϯ)-18a/(Ϯ)-18b
2-methylallyl[f]
p-methoxyphenyl
o-methoxyphenyl
o-methylphenyl
mesityl
2,6-dimethylphenyl
[a] Unless otherwise specified, reactions were complete in 3–4 h. [b]
1
Calculated from the H or 31P NMR spectra of the crude mixture.
[c] Isolated yield after chromatography. [d] Carried out in toluene
at 0 °C. [e] 24 h at room temperature. [f] Using tert-butylmagnesium
chloride and (2-methylallyl)magnesium chloride. [g] 47% conver-
sion was observed at room temperature. [h] Carried out in CH2Cl2
at reflux. [i] Calculated from the 31P NMR spectra of the crude
was treated with a large number of organomagnesium rea- mixture..
Eur. J. Org. Chem. 2011, 4037–4045
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I. Notar Francesco, C. Egloff, A. Wagner, F. Colobert
FULL PAPER
trast to (p-methoxy-, o-methoxy-, and o-methylphenyl)mag- of the diastereomeric complex with (+)-(S)-mandelic acid
nesium bromides (60:40, 60:40, and 55:45, respectively; and treatment with aqueous potassium carbonate
Table 3, Entries 9–12). The 31P NMR spectrum of the crude (Scheme 3).[19] Addition of methylmagnesium bromide to
product confirmed the obtention of only one diastereomer the enantiopure phosphinoylimine (+)-(R)-5a led, after
in the case of Entry 12. Furthermore, as expected, the ad- chromatographic separation, to the major diastereoisomer
dition of bulky (2,6-dimethylphenyl)magnesium bromide 6a in 70% yield and a diastereomeric ratio of 85:15
gave the corresponding phosphinoylamine in high yield and (Scheme 4). Crystallization in hexane/CH2Cl2 provided a
selectivity (Table 2, Entry 13).
single crystal, which allowed us to determine the absolute
(Arylphosphinoyl)imines derived from pentafluoro-, 4- configuration (–)-(RP,R)-6a of the two stereocenters by X-
cyano-, and 3,4,5-trimethoxybenzaldehyde were also tested ray crystallography.[14]
in the addition of methylmagnesium bromide (Table 4).
Compared with benzaldimine, the pentafluorophenyl and
m,mЈ,p-trimethoxyphenyl groups showed comparable dr
values (Table 4, Entries 1 and 2), but with 4-cyanophenyl
the diastereomeric ratio dropped to 55:45 (Table 4, En-
try 3), which suggests that both electronic and steric effects
could disturb the correct arrangement of the molecules in a
rigid transition state, essential for reaching high selectivities.
Although aromatic aldehydes are good reagents in the prep-
aration of phosphinoylimines, every attempt to synthesize
[(tert-butyl)(phenyl)phosphinoyl]imines starting from ali-
phatic aldehydes failed by the present method and those
commonly reported.
Scheme 3. Racemate resolution of (tert-butyl)(phenyl)phosphane
oxide (1a) with (+)-(S)-mandelic acid as chiral solvating agent.
Table 4. Grignard 1,2-addition to racemic N-[(tert-butyl)(phenyl)-
phosphinoyl]benzaldimines 5f–h.[a]
Taking into account the absolute configuration (RP,R) of
the major diastereoisomer, we proposed a transition-state
model invoking the coordination of the magnesium atom
with the oxygen atom of the phosphane oxide arranged in a
chair-like conformation in which the hindered group would
occupy the equatorial position (Scheme 4).
Phosphinamides are generally highly reactive towards
cleavage of the phosphinoyl group, providing deprotected
amines in high yields under mild acidic conditions. In our
case, this behavior was confirmed for amides bearing two
aromatic groups at the phosphorus atom; free amines were
obtained in 57 and 68% yields from phosphinamides 6,7b
and 6,7c (as a mixture of enantiomers), respectively, after
Entry
Ar
Imine Yield
[%][b]
dr[c]
Products
1
2
3
C6F5
5f
5g
5h
75
81
88
75:25 (Ϯ)-19a/(Ϯ)-19b
70:30 (Ϯ)-20a/(Ϯ)-20b
55:45 (Ϯ)-21a/(Ϯ)-21b
m,mЈ,p-(MeO)3C6H2
p-NCC6H4
[a] Unless otherwise specified, reactions were complete in 3–4 h. [b]
Isolated yield after chromatography. [c] Calculated from the 1H
NMR spectra of the crude mixture.
For a better understanding of the chiral induction and 18–24 h in 1.5 m HCl in MeOH after a basic workup
to determine the absolute configuration of the major dia- (Table 5, Entries 1 and 2). In contrast, [(tert-butyl)(phenyl)-
stereomer afforded by the addition of methylmagnesium phosphin]amides were completely unreactive under these
bromide, we decided to prepare an enantiopure imine. Thus, conditions, the reason for which we explored systematically.
(+)-(R)-N-[(tert-butyl)(phenyl)phosphinoyl]benzaldimine (5a) We observed in a few cases (severe conditions like high acid
was synthesized by starting from (–)-(S)-(tert-butyl)- concentration and high temperatures) cleavage of the P–N
(phenyl)phosphane oxide according to the reaction se- bond, as confirmed by phosphinic acid recovered after
quence shown in Scheme 1. The optically active phosphane acidic workup, but the free amine was never isolated
oxide 1a was obtained as a single enantiomer by resolution (Table 5, Entries 3 and 4). Note that we observed the depro-
Scheme 4. Determination of the absolute configuration of the major diastereomer (–)-6a.
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Grignard Addition to P-Chirogenic N-Phosphinoylbenzaldimine
Table 5. Cleavage of phosphinamides 6,7a–e.
Entry
1
R
(Ϯ)-6a–e/(Ϯ)-7a–e
(Ϯ)-6b/(Ϯ)-7b
Conditions
Yield [%]
57
2-biphenylyl
1. 1.5 m HCl in MeOH, 18 h, room temp.;
2. NaOH aq.
2
3
4
5
mesityl
tert-butyl
tert-butyl
methyl
(Ϯ)-6c/(Ϯ)-7c
(Ϯ)-6a/(Ϯ)-7a
(Ϯ)-6a/(Ϯ)-7a
(Ϯ)-6e/(Ϯ)-7e
1. 1.5 m HCl in MeOH, 18 h, room temp.;
2. NaOH aq.
1. 2 n HCl in 35% dioxane/H2O, 110 °C, 24 h;
2. NaOH aq.
1. concd. HCl, 90 °C, 5 h;
2. NaOH aq.
1. 3 m HCl in MeOH (1:5), 2 h, room temp.;
2. NaOH aq
68
0
0
85
umns were prepared with Merck silica gel Si 60 (40–63 μm). All
hydrogenation reactions were carried out in a 75 mL standard
stainless-steel autoclave. Melting points were determined with a
Büchi apparatus according to Dr. Tottoli. 1H, 13C, and large-band-
decoupled 31P NMR spectra were recorded at 300, 75, and
162 MHz, respectively, with Bruker Avance 300 and 400 instru-
ments. Chemical shifts are reported in δ units (ppm) downfield
from tetramethylsilane as reference and were measured relative to
the signals of residual chloroform (1H: δ =7.26 ppm; 13C: δ
=77.00 ppm). Coupling constants J are given in Hz. Coupling pat-
terns are abbreviated as: br. (broad) s (singlet), d (doublet), t (trip-
let), and m (multiplet). Mass spectra were recorded by HRMS
using the electrospray ionization method with a microTOF LC
Bruker Daltonics microTOF LC spectrometer from Bruker Dalton-
ics. Melting point ranges (m.p.) were found to be reproducible after
resolidification. N-[(tert-Butyl)(phenyl)phosphinoyl]benzaldimine
(5a), its precursors 1–4a and derivatives 6,7a were prepared accord-
ing to known literature procedures and fully characterized.[16]
tection of phosphinamides 6,7e derived from the [(meth-
yl)(phenyl)phosphinoyl]imine (5e). The cleavage was com-
plete in 2 h at room temperature in a slightly acidic water/
methanol solution and provided (α-methylbenzyl)amine in
high yield (Table 5, Entry 5).
Conclusions
We have reported herein an efficient stereoselective ad-
dition of various Grignard reagents to new P-chirogenic N-
[diaryl- and (alkyl)(phenyl)phosphinoyl]benzaldimines, af-
fording the corresponding phosphinoylamines in excellent
yields and with good stereoselectivities. The initial results
of the stereoselective addition of Grignard reagents towards
the synthesized activated imines were quite encouraging,
suggesting that this new class of compounds deserves to be
further explored. This original class of chiral inducers could
offer interesting alternatives in the field of asymmetric ca-
talysis and also new alternatives to the widely used sulfin-
ylimines. Further investigations concerning the design of
other interesting synthetic routes involving these P-chiro-
genic compounds are currently underway in our laboratory.
General Experimental Procedure for the Preparation of (؎)-1b and
(؎)-1c:[16] A solution of the desired Grignard reagent (1.1 equiv.)
was added dropwise to dichloro(phenyl)phosphane (1 equiv.) in dry
diethyl ether at 0 °C under argon. After the addition, the resulting
suspension was heated under reflux overnight. The mixture was
cooled to 0 °C, poured into ice, and treated with HCl (5 m). The
organic phase was separated, and the acidic water layer was ex-
tracted with dichloromethane (3ϫ15 mL) to afford the crude phos-
phane oxide, which was purified by chromatography (cyclohexane/
EtOAc, 7:3).
Experimental Section
(؎)-1b: Yield: 97%. White solid; m.p. 154.4–155.8 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.13–7.28 (m, 11 H, CH arom.), 7.30–7.36
General: All the solvents used were dried and freshly distilled under
argon. Toluene was distilled from sodium, and dichloromethane
was dried with calcium hydride and fractionally distilled. Benzalde-
hyde, triethylamine, and benzylamine were distilled prior to use.
Palladium on carbon (10%, 50% wet with water for safety) was
purchased from Acros and stored in a drying device. Titanium tet-
rachloride was used as a 1 m solution in dichloromethane. Alkyl-
and arylmagnesium halide solutions were purchased from Aldrich
and Acros or prepared by adding a solution of corresponding or-
ganohalide in dry diethyl ether to activated magnesium and heating
the resulting solution at reflux for 2 h. All the reactions were per-
formed under argon in flame-dried high-vacuum flasks. Thin-layer
chromatography (TLC) was carried out on aluminium plates coated
with silica gel 60 F254 purchased from Merck. Chromatography col-
1
(m, 1 H, CH arom.), 7.41–7.54 (m, 1 H, CH arom.), 7.80 (d, JPH
= 492.6 Hz, 1 H, PH), 7.88 (dd, 2JPH = 13.7, 3J = 7.5 Hz, 1 H, CH
2
arom.) ppm. 13C NMR (75 MHz, CDCl3): δ = 127.5 (d, JP,C
=
2
11.8 Hz, CH), 128.0 (CH), 128.2 (CH), 128.4 (d, JP,C = 12.9 Hz,
CH), 129.4 (CH), 130.1 (d, 1JP,C = 108 Hz, C quat.), 130.4 (d, 3JP,C
3
1
= 11.5 Hz, CH), 130.6 (d, JP,C = 9 Hz, CH), 131.6 (d, JP,C
=
=
=
4
4
97.5 Hz, C quat.), 131.9 (d, JP,C = 1.9 Hz, CH), 132.3 (d, JP,C
3
3
1.4 Hz, CH), 132.7 (d, JP,C = 10.7 Hz, CH), 139.2 (d, JP,C
5.2 Hz, C quat.), 145.9 (d, 2JP,C = 10.4 Hz, C quat.) ppm. 31P NMR
(162 MHz, CDCl3): δ = 18.44 ppm.
(؎)-1c: Yield: 98%. White crystalline solid. 1H NMR (300 MHz,
CDCl3): δ = 2.24 (s, 3 H, p-CH3 Mes), 2.38 (s, 6 H, o,oЈ-CH3 Mes),
Eur. J. Org. Chem. 2011, 4037–4045
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4041

I. Notar Francesco, C. Egloff, A. Wagner, F. Colobert
FULL PAPER
4
6.80 (d, JPH = 3.8 Hz, 2 H, CH arom. Mes), 7.41–7.51 (m, 3 H, 28.34 ppm. C15H16BrOP·CH3CO2C2H5 (C19H24BrO3P) (410.06):
1
CH arom.), 7.58–7.65 (m, 2 H, CH arom.), 8.55 (d, JPH
=
calcd. C 55.49, H 5.88; found C 55.12, H 6.01.
483.2 Hz, 1 H, PH) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.0
(؎)-2d: Yield: 54%. White solid; m.p. 167.3–169.2 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.29–7.47 (m, 6 H, CH), 7.63–7.99 (m, 5 H,
CH), 8.37 (d, 3JPH = 15.6 Hz, 1 H, CH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 125.03, 125.26, 127.29, 127.74, 127.86, 128.35, 128.83,
128.85, 128.87, 128.99, 129.11, 129.15, 130.69, 130.89, 130.92,
132.31, 132.52, 132.60, 132.64, 132.71, 132.81, 132. 92, 135.26,
2
1
(p-CH3), 21.5 (d, JP,C = 8.2 Hz, o,oЈ-CH3), 125.0 (d, JP,C
=
2
3
102.9 Hz, C quat.), 128.0 (d, JP,C = 12.6 Hz, CH), 130.3 (d, JP,C
3
4
= 10.4 Hz, CH), 130.4 (d, JP,C = 11.3 Hz, CH), 131.9 (d, JP,C
=
=
1
2
2.5 Hz, CH), 132.2 (d, JP,C = 99.1 Hz, C quat.), 142.1 (d, JP,C
9.9 Hz, C quat.), 142.8 (d, 4JP,C = 1.6 Hz, C quat.) ppm. 31P NMR
(162 MHz, CDCl3): δ = 9.87 ppm.
135.28 ppm. 31P NMR (162 MHz, CDCl3):
δ = 38.57 ppm.
C16H12BrOP (329.98): calcd. C 58.03, H 3.65; found C 58.35, H
3.98.
Synthesis of (؎)-1d: Menthyl phosphinate (3 g, 10.7 mmol, 1 equiv.)
as a 1 m solution in THF was slowly added to a Schlenk tube con-
taining 2-naphthyllithium (12.8 mmol, 1.2 equiv.) in THF at –78 °C
under argon for 5 h and then quenched with a saturated NH4Cl
solution (1 mL) and slowly warmed to room temperature. The re-
sulting solution was poured into a separation funnel and diluted
with water. A first extraction with hexane allowed removal of the
menthol, and then the aqueous phase was extracted twice (10 mL)
with chloroform. The combined organic phases were dried with
MgSO4, filtered, and concentrated under vacuum to give the crude
(naphthyl)(phenyl)phosphane oxide as a colorless oil. Column
chromatography with cyclohexane/AcOEt (1:1) gave the pure prod-
uct in 41% as a white crystalline solid (1.31 g). 1H NMR
(300 MHz, CDCl3): δ = 7.47–7.62 (m, 5 H, CH), 7.69–7.76 (m, 3
General Experimental Procedure for the Preparation of (؎)-3b–d:
Benzylamine (0.69 mL, 6.25 mmol) was added to a solution of tri-
ethylamine (0.39 mL, 2.8 mmol) and phosphinoyl bromide 2b–d
(1.25 mmol) in Et2O (10 mL) at room temperature. The mixture
was stirred for 16 h, and the white precipitate of ammonium bro-
mide was filtered off. The filtrate was then poured into a saturated
NH4Cl solution (15 mL). The aqueous layer was extracted with
Et2O (3ϫ15 mL), and the combined organic phases were dried
with magnesium sulfate and concentrated in vacuo. Silica gel col-
umn chromatography (EtOAc/cyclohexane, 4:1) of the crude mix-
ture afforded pure 3b–d as white solid.
(؎)-3b: Yield: 73%. White solid; m.p. 189.3–193.2 °C. 1H NMR
(300 MHz, CDCl3): δ = 4.37 [AB part of ABX (X = P), JAB = 10.8,
3JPHa = 4.5, 3JPHb = 5.4 Hz, 2 H, CH2], 2.99 (br. s, 1 H, NH), 7.15–
7.29 (m, 11 H, CH), 7.32–7.64 (m, 7 H, CH), 7.88 (dd, 2JPH = 13.9,
3J = 7.5 Hz, 1 H, CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 45.8
(d, 2JP,C = 2.6 Hz, CH2), 127.3 (CH), 127.5 (d, 2JP,C = 11.8 Hz, CH
arom.), 128.0 (CH arom.), 128.1 (CH arom.), 128.2 (CH arom.),
128.4 (d, 2JP,C = 12.9 Hz, CH arom.), 129.4 (CH arom.), 128.7 (CH
1
H, CH), 7.84–7.92 (m, 3 H, CH), 8.19 (d, JPH = 480.9 Hz, 1 H,
PH), 8.34 (d, 3JPH = 15.6 Hz, 1 H, CH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 125.02, 125.18, 127.2, 127.74, 127.99, 128.46, 128.81,
128.84, 128.86, 128.98, 129.03, 129.03, 129.09, 130.72, 130.87,
132.26, 132.47, 132.59, 132.63, 132.78, 132. 92, 135.09, 135.12 ppm.
31P NMR (162 MHz, CDCl3): δ = 12.37 ppm.
General Experimental Procedure for the Preparation of (؎)-2b–d:
LDA (1.2 equiv. in 8 mL/mmol of THF) was added by cannula to
a solution of phosphane oxide 1b–d in THF (10 mL/mmol) at
–78 °C . The resulting yellow to dark brown solution was stirred at
the same temperature for 1 h. 1,2-Dibromoethane was then added
dropwise, and the mixture was stirred at –78 °C for a further 1 h.
The reaction was quenched by addition of saturated aq. NH4Cl.
The organic layer was separated, and the aqueous phase was
washed with diethyl ether (3ϫ30 mL). The combined organic
phases were dried with MgSO4, filtered, and concentrated under
vacuum to give the crude bromophosphane oxide as an orange oil,
which was purified by chromatography (cyclohexane/EtOAc, 1:1).
1
3
arom.), 129.6 (d, JP,C = 108 Hz, C quat. arom.), 130.4 (d, JP,C
=
3
11.5 Hz, CH arom.), 130.6 (d, JP,C = 9 Hz, CH arom.), 130.9 (d,
1JP,C = 101 Hz, C quat. arom.), 131.9 (d, 4JP,C = 1.9 Hz, CH arom.),
4
3
132.3 (d, JP,C = 1.4 Hz, CH arom.), 132.7 (d, JP,C = 10.7 Hz, CH
3
3
arom.), 139.2 (d, JP,C = 5.2 Hz, C quat. arom.), 139.7 (d, JP,C
=
2
7.8 Hz, C quat. arom.), 145.9 (d, JP,C = 10.4 Hz, C quat. arom.)
ppm. 31P NMR (162 MHz, CDCl3): δ = 35.12 ppm.
(؎)-3c: Yield: 93%. White solid; m.p. 178.0–180.3 °C. 1H NMR
(300 MHz, CDCl3): δ = 2.34 (s, 3 H, p-CH3 Mes), 2.47 (s, 6 H,
o,oЈ-CH3 Mes), 3.03 (br. s, 1 H, NH), 4.52 [AB part of ABX (X =
3
3
P), JAB = 10.5, JPHa = 4.1, JPHb = 4.9 Hz, 2 H, CH2], 6.80 (d,
4JPH = 4.1 Hz, 2 H, CH arom Mes), 7.40–7.52 (m, 3 H, CH arom.),
7.56–7.79 (m, 7 H, CH arom.) ppm. 13C NMR (75 MHz, CDCl3):
(؎)-2b: Yield: 12%. White solid; m.p. 146.8–149.2 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.15–7.29 (m, 11 H, CH), 7.33–7.39 (m, 1
H, CH), 7.44–7.52 (m, 1 H, CH), 7.88 (dd, 2JPH = 13.9, 3J = 7.5 Hz,
3
δ = 21.1 (p-CH3 Mes), 21.8 (d, JP,C = 7.9 Hz, o,oЈ-CH3 Mes),
2
1 H, CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 127.5 (d, JP,C
=
44.376 (d, 2JP,C = 2.7 Hz, CH2), 125.0 (d, 1JP,C = 102.9 Hz, C quat.
2
2
11.8 Hz, CH), 128.0 (CH), 128.2 (CH), 128.4 (d, JP,C = 12.7 Hz,
arom.), 127.3 (CH arom.), 127.6 (CH arom.), 128.0 (d, JP,C
=
1
3
CH), 129.4 (CH), 129.6 (d, JP,C = 106.4 Hz, C quat.), 130.4 (d,
12.3 Hz, CH), 128.4 (CH arom.), 130.3 (d, JP,C = 10.4 Hz, CH),
3JP,C = 11.5 Hz, CH), 130.6 (d, JP,C = 9 Hz, CH), 131.9 (d, JP,C
3
4
131.6 (d, 3JP,C = 10.9 Hz, CH), 131.9 (d, 4JP,C = 2.2 Hz, CH), 132.2
1
4
1
3
= 1.9 Hz, CH), 132.0 (d, JP,C = 101 Hz, C quat.), 132.3 (d, JP,C
(d, JP,C = 99.1 Hz, C quat. arom.), 139.9 (d, JP,C = 7.5 Hz, C
3
3
2
= 1.4 Hz, CH), 132.7 (d, JP,C = 10.7 Hz, CH), 139.2 (d, JP,C
=
quat. arom.), 142.1 (d, JP,C = 9.9 Hz, C quat. arom.), 143.0 (C
5.2 Hz, C quat.), 145.9 (d, 2JP,C = 10.4 Hz, C quat.) ppm. 31P NMR
(162 MHz, CDCl3): δ = 46.34 ppm.
quat. arom.) ppm. 31P NMR (162 MHz, CDCl3): δ = 21.15 ppm.
C22H24NOP (349.16): calcd. C 75.62, H 6.92, N 4.01; found C
75.25, H 7.01, N 3.89.
(؎)-2c: Yield: 47%. White solid; m.p. 124.6–125.3 °C. 1H NMR
(300 MHz, CDCl3): δ = 2.29 (s, 3 H, p-CH3 Mes), 2.40 (s, 6 H,
o,oЈ-CH3 Mes), 6.80 (d, 4JPH = 3.8 Hz, 2 H, CH arom. Mes), 7.41–
(؎)-3d: Yield: 71%. White solid; m.p. 193.5–196.2 °C. 1H NMR
(300 MHz, CDCl3): δ = 3.02 (br. s, 1 H, NH), 4.22 [AB part of
3
7.51 (m, 3 H, CH arom.), 7.58–7.65 (m, 2 H, CH arom.) ppm. 13C ABX (X = P), JAB = 11.2, JPHa = 4.8, 3JPHb = 5.6 Hz, 2 H, CH2],
3
NMR (75 MHz, CDCl3): δ = 21.2 (p-CH3), 21.8 (d, 3JP,C = 8.3 Hz, 7.29–7.57 (m, 11 H, CH), 7.69–8.01 (m, 5 H, CH), 8.45 (d, JPH
=
15.6 Hz, 1 H, CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 45.14,
125.21, 125.35, 127.32, 127.66, 127.77, 127.92, 128.04, 128.61,
128.70, 129.03, 129.11, 130.12, 130.21, 131.88, 132.39, 132.43,
132.65, 132.69 132.78, 132.92, 135.87, 132.89, 140.41, 140.52 ppm.
1
2
o,oЈ-CH3), 125.3 (d, JP,C = 104 Hz, C quat.), 128.1 (d, JP,C
=
=
=
3
3
12.5 Hz, CH), 130.3 (d, JP,C = 10.7 Hz, CH), 130.4 (d, JP,C
10.9 Hz, CH), 132.5 (d, JP,C = 2.4 Hz, CH), 132.9 (d, JP,C
4
1
2
4
101 Hz, C quat.), 142.1 (d, JP,C = 9.9 Hz, C quat.), 142.8 (d, JP,C
= 2 Hz, C quat.) ppm. 31P NMR (162 MHz, CDCl3): δ =
31P NMR (162 MHz, CDCl3):
δ = 29.81 ppm. C23H20NOP
4042
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4037–4045

Grignard Addition to P-Chirogenic N-Phosphinoylbenzaldimine
(357.13): calcd. C 77.30, H 5.64, N 3.92; found C 77.15, H 5.41, N
3.97.
C25H20NOP (381.13): calcd. C 78.73, H 5.29, N 3.67; found C
79.01, H 5.18, N 3.73.
(؎)-5c: Yield: 67%. White solid; m.p. 189.7–193.1 °C. 1H NMR
(300 MHz, CDCl3): δ = 2.00 (s, 3 H, p-CH3 Mes), 2.77 (s, 6 H,
o,oЈ-CH3 Mes), 6.99 (d, 4JPH = 3.8 Hz, 2 H, CH arom. Mes), 7.33–
7.48 (m, 3 H, CH arom.), 7.51–7.66 (m, 3 H, CH arom.), 7.73–7.77
General Experimental Procedure for the Preparation of (؎)-4b–d:
Phosphinamide 3b–d (0.7 mmol), Pd/C (10 mg/100 mg phosphina-
mide), and EtOH (5 mL) were placed in an autoclave and flushed
three times with hydrogen before raising the pressure up to 20 bar.
The mixture was stirred at room temperature for 24 h and then
depressurized. The solution was filtered through a pad of Celite,
which was washed thoroughly with ethanol. The solvent was re-
moved in vacuo to afford pure phosphinamide 4b–d.
3
(m, 2 H, CH arom.), 7.96–8.03 (m, 2 H, CH arom.), 9.65 (d, JP,C
= 32.6 Hz, 1 H, CH imine) ppm. 13C NMR (75 MHz, CDCl3): δ
3
= 21.2 (p-CH3), 23.8 (d, JP,C = 3 Hz, o,oЈ-CH3), 125.78, 127.26,
127.38, 127.69, 128.01, 128.33, 128.44, 128.61, 128.84, 130.63,
130.62, 130.72, 130.90, 130.97, 131.01, 131.12, 132.29, 140.66,
143.91, 173.88, 173.99 ppm. 31P NMR (162 MHz, CDCl3): δ =
25.92 ppm.
(؎)-5d: Yield: 61%. White solid; m.p. 206.6–209.1 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.40–7.61 (m, 11 H, CH), 7.69–8.01 (m, 5
H, CH), 8.37 (d, 3JPH = 15.6 Hz, 1 H, CH), 9.02 (d, 3JP,C = 32.1 Hz,
1 H, CH imine) ppm. 13C NMR (75 MHz, CDCl3): δ = 125.21,
125.90, 127.35, 127.71, 127.86, 128.02, 128.41, 128.63, 128.71,
128.98, 129.13, 130.24, 131.93, 132.45, 132.66, 132.81, 132.96,
136.20, 140.51, 140.57, 172.12, 172.23 ppm. 31P NMR (162 MHz,
(؎)-4b: Yield: 97%. White solid; m.p. 179.0–180.5 °C. 1H NMR
(300 MHz, CDCl3): δ = 2.73 (br. s, 2 H, NH2), 7.21–7.60 (m, 14
3
3
4
H, CH), 7.84 (ddd, JPH = 14.2, J = 7.8, J = 1.3 Hz, 1 H, CH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 126.8 (d, JP,C = 12.9 Hz,
2
CH), 127.8 (CH), 127.8 (CH), 128.1 (d, 2JP,C = 12.9 Hz, CH), 129.6
(CH), 130.9 (d, 3JP,C = 10.7 Hz, CH), 131.1 (d, 4JP,C = 1.9 Hz, CH),
131.5 (d, 4JP,C = 2.5 Hz, CH), 131.7 (d, 3JP,C = 10.2 Hz, CH), 132.4
1
3
(d, JP,C = 104 Hz, C quat.), 132.6 (d, JP,C = 11 Hz, CH), 134.2
1
4
(d, JP,C = 107 Hz, C quat.), 141.0 (d, JP,C = 3.6 Hz, C quat.),
144.9 (d, JP,C = 9.3 Hz, C quat.) ppm. 31P NMR (162 MHz,
2
CDCl3):
δ
=
29.15 ppm. C23H18NOP·0.25CH3CO2C2H5
CDCl3):
δ
=
35.92 ppm. C18H16NOP·0.25CH3CO2C2H5
(C24H20NO1.5P) (377.13): calcd. C 76.38, H 5.34, N 3.71; found C
76.13, H 5.99, N 4.02.
(C19H18NO1.5P) (315.11): calcd. C 72.37, H 5.75, N 4.44; found C
72.56, H 5.21, N 4.36.
(؎)-5e:[13] Yield: 36%. Colorless oil. 1H NMR (400 MHz, CDCl3):
(؎)-4c: Yield: 98%. White solid; m.p. 143.8–145.2 °C. 1H NMR
(300 MHz, CDCl3): δ = 2.28 (s, 3 H, p-CH3 Mes), 2.48 (s, 6 H,
o,oЈ-CH3 Mes), 3.07 (br. s, 2 H, NH2), 6.89 (d, 4JPH = 3.6 Hz, 2 H,
CH arom. Mes), 7.37–7.49 (m, 3 H, CH arom.), 7.67–7.75 (m, 2
H, CH arom.) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.0 (p-
2
δ = 1.86 (d, JP,H = 14.4 Hz, 3 H, CH3), 7.52 (m, 6 H, CH arom.),
3
7.94 (m, 4 H, CH arom.), 9.19 (d, JP,H = 33.1 Hz, 1 H, N=CH)
1
ppm. 13C NMR (100 MHz, CDCl3): δ = 17.3 (d, JP,C = 93.2 Hz,
3
CH3), 128.7 (d, JP,C = 12.1 Hz, 2 CH arom.), 129.0 (CH arom.),
2
130.2 (CH arom.), 131.1 (d, JP,C = 9.2 Hz, CH arom.), 132.0 (d,
3
1
CH3), 23.7 (d, JP,C = 3 Hz, o,oЈ-CH3), 126.0 (d, JP,C = 123.2 Hz,
1
4JP,C = 2.6 Hz, CH arom.), 133.1 (d, JP,C = 122.1 Hz, C quat.
2
3
C quat.), 128.4 (d, JP,C = 12.9 Hz, CH), 130.2 (d, JP,C = 11 Hz,
3
arom.), 133.6 (s, 2 CH arom.), 135.9 (d, JP,C = 25.3 Hz, C quat.
CH), 130.9 (d, 3JP,C = 12.3 Hz, CH), 131.2 (d, 4JP,C = 2.2 Hz, CH),
2
arom.), 173.4 (d, JP,C = 8.4 Hz, CH imine) ppm. 31P NMR
1
4
136.9 (d, JP,C = 125.4 Hz, C quat.), 141.5 (d, JP,C = 2.5 Hz, C
(162 MHz, CDCl3): δ = 34.34 ppm.
quat.), 142.9 (d, JP,C = 11.3 Hz, C quat.) ppm. 31P NMR
3
(؎)-5f: Yield: 75%. White solid; m.p. 189.3–190.8 °C. 1H NMR
(162 MHz, CDCl3): δ = 25.92 ppm. C15H18NOP (259.11): calcd. C
69.48, H 7.00, N 5.40; found C 69.89, H 7.16, N 5.23.
3
(300 MHz, CDCl3): δ = 1.42 (d, JPH = 15.3 Hz, 9 H, 3 CH3 tBu),
7.38–7.51 (m, 3 H, CH arom.), 7.99–8.12 (m, 2 H, CH arom.), 9.50
(؎)-4d: Yield: 96%. White solid; m.p. 177.8–179.0 °C. 1H NMR
(300 MHz, CDCl3): δ = 3.05 (br. s, 2 H, NH2), 7.27–7.93 (m, 11 H,
CH), 8.37 (d, 3JPH = 15.6 Hz, 1 H, CH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 125.11, 125.34, 127.37, 127.71, 127.84, 128.43, 128.89,
128.91, 128.95, 128.99, 129.13, 129.16, 130.75, 130.92, 130.97,
132.31, 132.52, 132.62, 132.66, 132.71, 133.12, 133.25, 135.89,
3
(d, JPH = 29.7 Hz, 1 H, CH imine) ppm. 13C NMR (75 MHz,
1
CDCl3): δ = 24.3 (CH3 tBu), 32.9 (d, JP,C = 87.8 Hz, quat. tBu),
2
111.1–111.7 (m, CF C6F5), 128.3 (d, JP,C = 11.3 Hz, CH arom.),
130.2 (d, 1JP,C = 112.5 Hz, C quat. arom.), 132.1 (d, 4JP,C = 2.2 Hz,
3
CH arom.), 133.6 (d, JP,C = 7.7 Hz, CH arom.), 135.7–139.5 (m,
2
CF C6F5), 145.0–148.5 (m, CF C6F5), 162.6 (d, JP,C = 4.1 Hz,
135.92 ppm. 31P NMR (162 MHz, CDCl3):
δ = 21.89 ppm.
CH imine) ppm. 31P NMR (162 MHz, CDCl3): δ = 42.44 ppm.
C17H15F5NOP (375.08): calcd. C 54.41, H 5.03, N 3.73; found C
54.36, H 5.58, N 3.72.
C16H14NOP (267.08): calcd. C 71.90, H 5.28, N 5.24; found C
72.05, H 4.89, N 4.99.
(؎)-5g: Yield: 81%. White solid; m.p. 199.6–201.8 °C. 1H NMR
(300 MHz, CDCl3): δ = 1.52 (d, JPH = 14.7 Hz, 9 H, 3 CH3 tBu),
General Experimental Procedure for the Preparation of (؎)-5b–h:
TiCl4 (0.5 equiv.) was added dropwise to a solution of benzalde-
hyde (1 equiv.), the desired phosphinamide (1 equiv.), and triethyl-
amine (3 equiv.) in dichloromethane at 0 °C. The reaction mixture
was stirred for 2 h before the solvent was removed in vacuo. The
yellow oily solid was diluted with ethyl acetate and the precipitate
filtered through Celite. The filtrate was concentrated in vacuo. The
crude imine was purified by flash chromatography (EtOAc, 100%)
to afford the pure N-phosphinoylbenzaldimine.
3
3.58 (s, 6 H, m,mЈ-OCH3), 4.04 (s, 3 H, p-OCH3), 6.85 (s, 2 H, CH
arom.), 7.29–7.48 (m, 3 H, CH arom.), 7.54–8.06 (m, 2 H, CH
3
arom.), 9.60 (d, JPH = 29.3 Hz, 1 H, CH imine) ppm. 13C NMR
1
(75 MHz, CDCl3): δ = 24.7 (CH3 tBu), 33.1 (d, JP,C = 89.2 Hz,
quat. tBu), 55.8 (m,mЈ-OCH3), 60.5 (p-OCH3), 107.6 (CH arom.),
2
1
128.1 (d, JP,C = 11.5 Hz, CH arom.), 130.0 (d, JP,C = 117.3 Hz,
C quat. arom.), 132.1 (d, 4JP,C = 2.2 Hz, CH arom.), 132.2 (C quat.
arom.), 133.6 (d, JP,C = 7.7 Hz, CH arom.), 136.8 (d, JP,C
3
3
=
=
(؎)-5b: Yield: 59%. White solid; m.p. 201.5–202.7 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.04–7.06 (m, 4 H, CH), 7.24–7.44 (m, 7
H, CH), 7.48–7.53 (m, 3 H, CH), 7.66–7.76 (m, 5 H, CH), 8.74 (d,
3JPH = 32.5 Hz, 1 H, CH imine) ppm. 13C NMR (75 MHz, CDCl3):
δ = 126.75, 126.92, 127.09, 127.52, 127.69, 127.86, 128.01, 128.33,
128.50, 130.14, 130.72, 131.25, 131.69, 131.84, 132.62, 132.73,
132.84, 133.16, 133.30, 134.75, 136.41, 136.75, 141.41, 147.04,
173.80, 173.90 ppm. 31P NMR (162 MHz, CDCl3): δ = 25.52 ppm.
2
7.3 Hz, C quat. arom.), 151.7 (C quat. arom.), 174.6 (d, JP,C
7.4 Hz, CH imine) ppm. 31P NMR (162 MHz, CDCl3): δ =
41.14 ppm.
C20H26NO4P·0.5CH3CO2C2H5
(C22H30NO5P)
(419.19): calcd. C 63.00, H 7.21, N 3.34; found C 63.02, H 7.066,
N 3.52.
(؎)-5h: Yield: 88%. White solid; m.p. 197.7–199.3 °C. 1H NMR
3
(300 MHz, CDCl3): δ = 1.20 (d, JPH = 15.4 Hz, 9 H, 3 CH3 tBu),
Eur. J. Org. Chem. 2011, 4037–4045
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4043

I. Notar Francesco, C. Egloff, A. Wagner, F. Colobert
FULL PAPER
7.47–7.55 (m, 3 H, CH arom.), 7.80 (d, 3J = 8.3 Hz, 2 H, CH 6.8 Hz, 3 H, HCCH3 minor),1.29 (d, 3J = 6.8 Hz, 3 H, HCCH3
3
2
arom.), 7.93–8.00 (m, 2 H, CH arom.), 8.08 (d, J = 8.3 Hz, 2 H,
major), 2.78 (br. t, JPH =
3JHCNH = 8.3 Hz, 1 H, NH minor +
CH arom.), 9.24 (d, JPH = 28.8 Hz, 1 H, CH imine) ppm. 13C
major), 4.01–4.19 (m, 1 H, CHNH min), 4.21–4.29 (m, 1 H, CHNH
major), 7.12–7.72 (m, 16 H, CH arom. minor + major), 8.34 (d,
3
1
NMR (75 MHz, CDCl3): δ = 24.4 (CH3 tBu), 33.5 (d, JP,C
=
87 Hz, quat. tBu), 116.4 (C quat., CϵN), 128.1 (CH arom.), 118.1 3JPH = 15.6 Hz, 1 H, CH minor), 8.37 (d, 3JPH = 15.6 Hz, 1 H, CH
2
3
(C quat. arom.), 128.2 (d, JP,C = 9 Hz, CH arom.), 129.7 (CH
major) ppm. 13C NMR (75 MHz, CDCl3): δ = 24.3 (d, JP,C
=
1
arom.), 131.5 (d, JP,C = 111 Hz, C quat. arom.), 131.9 (d,
4 Hz, HCCH3 major), 25.8 (d, 3JP,C = 3.7 Hz, HCCH3 minor), 49.7
(HNCH minor), 50.7 (HNCH major), 125.04, 125.16, 125.44,
127.22, 127.45, 127.78, 127.96, 128.03, 128.27, 128.53, 128.54,
128.78, 128.89, 129.01, 129.23, 129.72, 129.85, 129.93, 130.04,
4JP,C = 2.3 Hz, CH arom.), 132.3 (d, JP,C = 7.7 Hz, CH arom.),
3
2
139.0 (C quat. arom.), 172.4 (d, JP,C = 7.5 Hz, CH imine) ppm.
31P
NMR
(162 MHz,
CDCl3):
δ
=
43.49 ppm.
C18H19N2OP·0.25CH3CO2C2H5 (C19H21N2O1.5P) (332.14): calcd. 130.23, 130.38, 130.72, 130.94, 131.76, 131.88, 132.23, 132.40,
C 68.66, H 6.37, N 8.43; found C 68.28, H 6.21, N 8.72.
132.71, 132.76, 132.93, 135.13, 135.22, 135.35 ppm. 31P NMR
(162 MHz, CDCl3): δ = 25.13 (major), 26.86 (minor) ppm.
C24H22NOP (371.14): calcd. C 77.61, H 5.97, N 3.77; found C
78.33, H 5.04, N 4.06.
General Experimental Procedure for the Grignard 1,2-Addition to
N-Phosphinoylaldimines 5b–e: Methylmagnesium bromide (3 m
solution in diethyl ether, 3 equiv., 0.6 mmol, 200 μL) was added
dropwise at 0 °C to a solution of the desired phosphinamide
(1 equiv., 0.2 mmol) in dichloromethane (1.5 mL). The mixture was
stirred at room temperature for 3 h, then cooled to 0 °C, quenched
with aqueous KHSO4 (0.5 m, 10 mL), and extracted with ethyl acet-
ate (3 ϫ 10 mL). The combined organic phases were washed once
with brine (20 mL), dried with MgSO4, and concentrated in vacuo.
The solid residue was purified by flash chromatography.
1
(؎)-6e/(؎)-7e: Major/minor = 70:30. Yield: 91%. White solid. H
3
NMR (300 MHz, CDCl3): δ = 1.45 (d, J = 6.8 Hz, 3 H, HCCH3
2
3
minor), 1.54 (d, JP,C = 15 Hz, 3 H, P-CH3 minor), 1.55 (d, J =
2
6.8 Hz, 3 H, HCCH3 major), 1.63 (d, JP,C = 15 Hz, 3 H, P-CH3
major), 2.30 (br. s, 1 H, NH major), 2.99 (br. s, 1 H, NH minor),
4.19–4.26 (m, 1 H, CHNH major), 4.50–4.57 (m, 1 H, CHNH
minor), 7.17–7.28 (m, 3 H, CH arom. minor + major), 7.33–7.41
(m, 3 H, CH arom. minor + major), 7.46–7.56 (m, 2 H, CH arom.
(؎)-6b/(؎)-7b: Major/minor = 65:35. Yield: 89%. White solid; m.p.
211.0–213.1 °C. 1H NMR (300 MHz, CDCl3): δ = 1.14 (d, 3J = minor + major), 7.69–7.75 (m, 2 H, CH arom. major), 7.83–7.88
6.8 Hz, 3 H, HCCH3 minor), 1.30 (d, 3J = 6.8 Hz, 3 H, HCCH3
(m, 2 H, CH arom. minor) ppm. 13C NMR (CDCl3, 400 MHz): δ
2
2
2
major), 2.64 (br. t, JPH
=
3JHCNH = 8.3 Hz, 1 H, NH minor +
= 145.4 [d, JP,C = 4.0 Hz, CH(CH3)], 145.0 [d, JP,C = 6.6 Hz,
1
major), 3.99–4.07 (m, 1 H, CHNH minor), 4.26–4.39 (m, 1 H,
CHNH major), 6.97–7.72 (m, 19 H, CH arom. minor + major)
CH(CH3)], 133.7 (d, JP,C = 124.3 Hz, C quat. arom.), 132.0 (d,
4JP,C = 2.6 Hz, CH arom.), 131.8 (d, JP,C = 9.5 Hz, CH arom.),
2
ppm. 13C NMR (75 MHz, CDCl3): δ = 25.1 (d, 3JP,C = 4.7 Hz, HC- 131.5 (d, 2JP,C = 9.9 Hz, CH arom.), 128.8 (s, C quat. arom.), 128.6
CH3 major), 26.4 (d, 3JP,C = 4.5 Hz, HC-CH3 minor), 49.7 (HNCH (d, JP,C = 26.4 Hz, C quat. arom.), 128.6 (s, CH arom.), 128.5 (s,
3
3
minor), 50.7 (HNCH major), 126.11, 126.67, 126.93, 127.5, 127.78,
128.04, 128.21, 128.43, 129.67, 131.08, 131.42, 131.5, 132.28,
132.34, 133.09, 133.21, 140.89, 131.37, 131.43, 131.51, 132.24,
132.33, 133.18, 133.34, 135.07, 137.01, 138.25, 140.89, 144.9,
CH arom.), 127.3 (d, JP,C = 12.8 Hz, CH arom.), 126.2 (CH
arom.), 126.1 (s, CH arom.), 51.1 (s, CH3), 50.6 (s, CH3), 17.2 (d,
1JP,C = 49.9 Hz, P-CH3), 16.3 (d, 1JP,C = 51.4 Hz, P-CH3) ppm. 31
P
NMR (162 MHz, CDCl3): δ = 29.69 (major), 30.32 (minor) ppm.
144.86, 145.03, 145.27, 145.41 ppm. 31P NMR (162 MHz, CDCl3): C15H18NOP (259.11): calcd. C 69.48, H 6.99, N 5.40; found C
δ = 25.13 (major), 26.86 (minor) ppm. C26H24NOP (397.16): calcd. 69.77, H 7.08, N 5.07.
C 78.57, H 6.09, N 3.52; found C 78.46, H 6.13, N 3.73.
(؎)-19a/(؎)-19b: Major/minor = 75:25. Yield: 75%. Major: Yield:
59%. Pale-yellow solid; m.p. 205.4–207.8 °C. H NMR (300 MHz,
(؎)-6c/(؎)-7c: Major/minor = 70:30. Yield: 79%. White solid; m.p.
1
207.4–209.7 °C. 1H NMR (300 MHz, CDCl3): δ = 1.44 (d, J =
3
3
CDCl3): δ = 1.13 (d, JPH = 15.1 Hz, 9 H, 3 CH3 tBu), 1.62 (d, J
6.8 Hz, 3 H, HCCH3 minor),1.57 (d, J = 6.8 Hz, 3 H, HCCH3
major), 2.19 (s, 3 H, p-CH3 Mes major), 2.21 (s, 3 H, p-CH3 Mes
minor), 2.28 (s, 6 H, o,oЈ-CH3 Mes major), 2.39 (s, 6 H, o,oЈ-CH3
2
3
= 7 Hz, 3 H, HCCH3), 3.01 (br. t, JPH = JHCNH = 10.2 Hz, 1 H,
NH), 4.64–4.68 (m, 1 H, CHNH), 7.29–7.35 (m, 2 H, CH arom.),
7.43–7.46 (m, 1 H, CH arom.), 7.57–7.61 (m, 2 H, CH arom.) ppm.
13C NMR (75 MHz, CDCl3): δ = 24.2 (HCCH3), 24.8 (CH3 tBu,
2
3
Mes minor), 2.99 (br. t, JPH = JHCNH = 8.3 Hz, 1 H, NH minor
+ major), 4.39–4.51 (m, 1 H, CHNH major), 4.53–4.67 (m, 1 H,
1
minor), 32.1 (d, JP,C = 89.5 Hz, C quat. tBu), 42.1 (CHNH),
4
CHNH minor), 6.74 (d, JPH = 3.8 Hz, 2 H, CH arom. Mes,
2
118.1–118.3 (m, CF C6F5), 127.9 (d, JP,C = 11.5 Hz, CH arom.),
4
major), 6.82 (d, JPH = 3.8 Hz, 2 H, CH arom. Mes, minor), 7.11–
128.8 (d, 1JP,C = 117.5 Hz, C quat. arom.), 131.8 (CH arom.), 133.3
7.38 (m, 8 H, CH arom. major + minor), 7.46–7.54 (m, 2 H, CH
arom. minor), 7.46–7.54 (m, 2 H, CH arom. minor), 7.57–7.65 (m,
3
(d, JP,C = 8.5 Hz, CH arom.), 135.6–136.0 (m, CF C6F5), 138.3–
139.2 (m, CF C6F5), 145.8–146.2 (m, CF C6F5) ppm. 31P NMR
(162 MHz, CDCl3): δ = 42.07 ppm. C18H19F5NOP (391.11): calcd.
C 55.25, H 4.89; F, 24.28, N 3.58; found C 55.34, H 4.87, N 3.52.
Minor: Yield: 16%. Pale-yellow solid; m.p. 208.3–209.1 °C. 1H
NMR (300 MHz, CDCl3): δ = 1.08 (d, 3JPH = 15.1 Hz, 9 H, 3 CH3
2 H, CH arom. major) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.0
3
(p-CH3 Mes, major), 21.1 (p-CH3 Mes, minor), 23.7 (d, JP,C
=
3
3.3 Hz, o,oЈ-CH3 Mes, major), 23.9 (d, JP,C = 3.3 Hz, o,oЈ-CH3
Mes, minor), 25.7 (d, JP,C = 3.6 Hz, HCCH3 major), 25.9 (d, 3JP,C
3
= 2.9 Hz, HCCH3 minor), 50.7 (HNCH minor), 51.2 (HNCH
major), 124.45, 125.89, 126.11, 126.23, 127.04, 127.12, 127.91,
128.18, 128.26, 128.41, 128.53, 128.57, 130.45, 130.62, 130.81,
131.05, 131.06, 131.23, 131.54, 131.56, 135.63, 135.66, 135.88,
137.56, 141.28, 141.45, 143.03, 143.22, 143.40, 143.61, 145.13,
145.22, 145.52, 145.65 ppm. 31P NMR (162 MHz, CDCl3): δ =
26.95 (major), 27.45 (minor) ppm. C23H26NOP (363.18): calcd. C
76.01, H 7.21, N 3.85; found C 76.75, H 7.08, N 4.07.
3
2
tBu), 1.54 (d, J = 7 Hz, 3 H, HCCH3), 3.40 (br. t, JPH = 3JHCNH
= 10.2 Hz, 1 H, NH), 4.55–4.68 (m, 1 H, CHNH), 7.24–7.57 (m, 3
H, CH arom.), 7.43–7.46 (m, 1 H, CH arom.), 7.78–7.85 (m, 2 H,
3
CH arom.) ppm. 13C NMR (75 MHz, CDCl3): δ = 23.6 (d, JP,C
=
1
8.2 Hz, HCCH3), 24.6 (CH3 tBu, minor), 32.1 (d, JP,C = 88.9 Hz,
C quat. tBu), 42.2 (CHNH), 118.1–119.2 (m, CF C6F5), 128.3 (d,
2JP,C = 11.5 Hz, CH arom.), 129.3 (d, JP,C = 118.6 Hz, C quat.
1
3
arom.), 131.9 (CH arom.), 133.5 (d, JP,C = 8.5 Hz, CH arom.),
(؎)-6d/(؎)-7d: Major/minor = 55:45. Yield: 81%. White solid; m.p.
135.7–136.0 (m, CF C6F5), 131.3–139.6 (m, CF C6F5), 142.6–146.2
204.6–205.9 °C. 1H NMR (300 MHz, CDCl3): δ = 1.18 (d, 3J = (m, CF C6F5) ppm. 31P NMR (162 MHz, CDCl3): δ = 42.07 ppm.
4044
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4037–4045

Grignard Addition to P-Chirogenic N-Phosphinoylbenzaldimine
C18H19F5NOP (391.11): calcd. C 55.25, H 4.89; F, 24.28, N 3.58;
found C 55.19, H 4.73, N 3.63.
(326.15): calcd. C 69.92, H 7.10, N 8.58; found C 69.76, H 7.01, N
8.96.
(؎)-20a/(؎)-20b: Major/minor = 70:30. Yield: 81%. Major: Yield:
[1] a) G. K. Friestad, A. K. Mathies, Tetrahedron 2007, 63, 2541–
2569; b) S. Kobayashi, H. Ishitani, Chem. Rev. 1999, 99, 1069–
1094; c) R. Bloch, Chem. Rev. 1998, 98, 1407–1438; d) D. En-
ders, U. Reinhold, Tetrahedron: Asymmetry 1997, 8, 1895–
1946.
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35, 984–995; b) P. Zhou, B.-C. Chen, F. A. Davis, Tetrahedron
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A. Pérez-Luna, Chem. Soc. Rev. 2009, 38, 1162–1186; e) M. T.
Robak, M. A. Herbage, J. A. Ellman, Chem. Rev. 2010, 99,
3600–3740.
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1999, 64, 1061–1064; b) H.-X. Wei, J. D. Hook, K. A. Fitzger-
ald, G. Li, Tetrahedron: Asymmetry 1999, 10, 661–665.
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2005, 1205–1227.
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2008, 71, 216–223.
[7] a) J. Han, T. Ai, G. Li, Synthesis 2008, 2519–2526; b) J. Han,
T. Ai, T. Nguyen, G. Li, Chem. Biol. Drug Des. 2008, 72, 120–
126; c) T. Ai, J. Han, Z.-X. Chen, G. Li, Chem. Biol. Drug Des.
2009, 73, 203–208.
[8] A. Kattuboina, P. Kaur, T. Nguyen, G. Li, Tetrahedron Lett.
2008, 49, 3772–3724.
[9] a) Z.-X. Chen, T. Ai, P. Kaur, G. Li, Tetrahedron Lett. 2009,
50, 1079–1081; b) P. Kaur, T. Nguyen, G. Li, Eur. J. Org. Chem.
2009, 912–916; c) T. Ai, G. Li, Bioorg. Med. Chem. Lett. 2009,
19, 3967–3969.
[10] P. Kaur, G. Shakya, H. Sun, Y. Pan, G. Li, Org. Biomol. Chem.
2010, 8, 1091–1096.
62%. White solid; m.p. 199.6–201.1 °C. 1H NMR (300 MHz,
3
3
CDCl3): δ = 1.11 (d, JPH = 14.7 Hz, 9 H, 3 CH3 tBu), 1.42 (d, J
= 6.8 Hz, 3 H, HCCH3), 2.85 (br. s, 1 H, NH), 3.83 (s, 3 H, p-
OCH3), 3.87 (s, 6 H, m,mЈ-OCH3), 4.41 (br. s, 1 H, CHNH), 6.74
(s, 2 H, CH arom.), 7.48–7.52 (m, 3 H, CH arom.), 7. 78–7.89 (m,
2 H, CH arom.) ppm. 13C NMR (75 MHz, CDCl3): δ = 24.3 (d, J
= 4.1 Hz, HCCH3), 24.8 (CH3 tBu, minor), 32.2 (d, 1JP,C = 89.7 Hz,
C quat. tBu), 49.7 (CHNH), 56.2 (m,mЈ-OCH3), 60.8 (p-OCH3),
2
103.7 (CH arom.), 128.1 (d, JP,C = 11.5 Hz, CH arom.), 130.6 (d,
1JP,C = 117.5 Hz, C quat. arom.), 131.6 (CH arom.), 133.6 (d, 3JP,C
= 8.5 Hz, CH arom.), 137.0 (C quat.), 141.1 (3JP,C = 6.3 Hz, C
quat. arom.), 153.2 (C quat.) ppm. 31P NMR (162 MHz, CDCl3):
δ = 41.75 ppm. C21H30NO4P (391.19): calcd. C 64.43, H 7.72, N
3.58; found C 63.66, H 7.71, N 3.38. Minor: Yield: 19%. White
1
solid; m.p. 198.2–200.0 °C. H NMR (300 MHz, CDCl3): δ = 1.12
3
(d, JPH = 14.7 Hz, 9 H, 3 CH3 tBu), 1.57 (d, 3J = 6.8 Hz, 3 H,
2
3
HCCH3), 2.77 (br. t, JPH = JHCNH = 8.9 Hz, 1 H, NH), 3.77 (s,
6 H, m,mЈ-OCH3), 3.81 (s, 3 H, p-OCH3), 4.64–4.68 (m, 1 H,
CHNH), 6.41 (s, 2 H, CH arom.), 7.29–7.35 (m, 2 H, CH arom.),
7.41–7.46 (m, 1 H, CH arom.), 7.62–7.68 (m, 2 H, CH arom.) ppm.
13C NMR (75 MHz, CDCl3): δ = 24.9 (CH3 tBu, minor), 25.7
1
(HCCH3), 32.1 (d, JP,C = 89.2 Hz, C quat. tBu), 50.7 (CHNH),
56.1 (m,mЈ-OCH3), 60.8 (p-OCH3), 103.2 (CH arom.), 127.7 (d,
1
2JP,C = 11.5 Hz, CH arom.), 129.6 (d, JP,C = 117.5 Hz, C quat.
3
arom.), 131.4 (CH arom.), 133.9 (d, JP,C = 8.5 Hz, CH arom.),
136.9 (C quat.), 141.0 (3JP,C = 6.3 Hz, C quat. arom.), 153.2 (C
quat.) ppm. 31P NMR (162 MHz, CDCl3): δ = 40.90 ppm.
C21H30NO4P (391.19): calcd. C 64.43, H 7.72, N 3.58; found C
63.90, H 7.73, N 3.41.
[11] P. Kaur, W. Wever, T. Rajale, G. Li, Chem. Biol. Drug Des.
2010, 76, 314–319.
[12] W. B. Jennings, M. J. Kochanewycz, C. J. Lovely, D. R. Boyd,
J. Chem. Soc., Chem. Commun. 1994, 2569–2570.
[13] M. Benamer, S. Turcaud, J. Royer, Tetrahedron Lett. 2010, 51,
645–648.
[14] I. Notar Francesco, A. Wagner, F. Colobert, Chem. Commun.
2010, 46, 2139–2141.
(؎)-21a/(؎)-21b: Major/minor = 55:45. Yield: 88%. M.p. 201.7–
3
204.3 °C. 1H NMR (300 MHz, CDCl3): δ = 1.08 (d, JPH
=
3
13.4 Hz, 9 H, 3 CH3 tBu minor), 1.14 (d, JPH = 13 Hz, 9 H, 3
CH3 tBu major), 1.44 (d, J = 6.9 Hz, 3 H, HCCH3 minor), 1.56
3
3
(d, J = 6.9 Hz, 3 H, HCCH3 major), 2.93 (br. m, 1 H, NH major
[15] W.-L. Lam, R. K. Haynes, L.-L. Yeung, W.-K. Chan, Tetrahe-
dron Lett. 1996, 37, 4733–4736.
+ minor), 4.30–4.51 (m, 1 H, CHNH, major + minor), 7.30–7.87
(m, 9 H, CH arom. major + minor) ppm. 13C NMR (75 MHz,
CDCl3): δ = 24.7 (HCCH3 major), 24.8 (CH3 tBu minor), 24.9
[16] Q. Xu, C.-Q. Zhao, L.-B. Han, J. Am. Chem. Soc. 2008, 130,
12648–12655.
3
(CH3 tBu major), 26.2 (d, JP,C = 3.7 Hz, HCCH3 minor), 32.3 (d,
[17] A. Leyris, J. Bigeault, D. Nuel, L. Giordano, G. Buono, Tetra-
hedron 2007, 63, 5247–5250.
[18] T. A. Harmor, W. B. Jennings, C. J. Lovely, K. A. Reever, J.
Chem. Soc. Perkin Trans. 2 1992, 843–849.
[19] J. Drabowicz, P. Lyzwa, J. Omelanczuk, K. M. Pietrusiewicz,
M. Mikolajczyk, Tetrahedron: Asymmetry 1999, 10, 2757–2763.
Received: March 18, 2011
1
1JP,C = 89.2 Hz, C quat. tBu, major), 32.4 (d, JP,C = 89.5 Hz, C
quat. tBu. major), 49.7 (HNCH minor), 50.3 (HNCH major), 110.8
(C quat. CϵN major + minor), 118.8, 118.9, 126.1, 126.9, 127.1,
128.1, 128.3, 131.6, 131.7, 131.8, 131.7, 131.8, 132.3, 133.4, 133.5,
133.6, 133.7, 150.7, 150.8, 150.9 ppm. 31P NMR (162 MHz,
CDCl3): δ = 41.15 (major), 42.54 (minor) ppm. C19H23N2OP
Published Online: June 8, 2011
Eur. J. Org. Chem. 2011, 4037–4045
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4045