Enantioselective addition of terminal alkynes to N-(diphenylphosphinoyl) imines catalyzed by Zn-BINOL complexes

Article abstract of DOI:10.1016/j.tet.2012.01.037

Chiral nonracemic N-(diphenylphosphinoyl)-protected propargylic amines have been prepared by addition of terminal alkynes to N-(diphenylphosphinoyl) aldimines in the presence of dimethylzinc and 3,3′-dibromo-BINOL as catalyst. The reaction works with a va

Full text of DOI:10.1016/j.tet.2012.01.037

Tetrahedron 68 (2012) 2128e2134
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journal homepage: www.elsevier.com/locate/tet
Enantioselective addition of terminal alkynes to N-(diphenylphosphinoyl)imines
catalyzed by ZneBINOL complexes
*
ꢀ
ꢀ
Gonzalo Blay, Eric Ceballos, Alicia Monleon, Jose R. Pedro
ꢁ
ꢁ
ꢁ
Departament de Química Organica, Facultat de Química, Universitat de Valencia, Dr. Moliner 50, E-46100 Burjassot, Valencia, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Chiral nonracemic N-(diphenylphosphinoyl)-protected propargylic amines have been prepared by ad-
dition of terminal alkynes to N-(diphenylphosphinoyl)aldimines in the presence of dimethylzinc and
3,30-dibromo-BINOL as catalyst. The reaction works with a variety of aromatic and heteroaromatic al-
dimines and with different alkynes, providing the expected products in generally good yields and en-
antiomeric excesses (up to 96%).
Received 27 October 2011
Received in revised form 12 January 2012
Accepted 13 January 2012
Available online 21 January 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Alkynylation
CeC bond formation
Propargylic amines
Asymmetric catalysis
Nucleophilic addition
1. Introduction
addition of aryl alkynes to a-imino esters by dual catalysis
€
(Bronsted acid and metal salt) with good results.
The catalytic enantioselective addition of terminal alkynes to
C]N bonds is currently one of the most important objectives in
organic synthesis as the resulting chiral propargylamines are im-
portant synthetic intermediates for the construction of biologically
active nitrogen-containing compounds and natural products.1
However, in contrast to the extensive studies on the asymmetric
alkynylation of carbonyl compounds,2 the number of studies on the
enantioselective alkynylation of imines and imine derivatives are
much more reduced. Most of these studies have focused on the use
of Cu(I) salts in combination with nitrogen-containing ligands to
catalyze the enantioselective alkynylation of N-aryl imines.3 Lead-
ing studies of this reaction have been developed by Wei,4 Chan,5
Bisai,6 Benaglia,7 Knochel,8 Carreira,9 and Zhao.10
Other methods that do not make use of copper complexes as the
catalyst have been also described. Hoveyda11 has used peptide-
based ligands in combination with Zr(OiPr)4$HOiPr to catalyze the
alkynylation of N-aryl aromatic imines. Jiang12 has reported the
addition of terminal alkynes to a trifluoromethyl activated cyclic
imine by using a stoichiometric amount of a chiral amino alcohol
ligand and Zn(OTf)2 as promoter. Bolm13 has described the use of
amino alcohol ligands and dimethylzinc to promote the addition of
terminal alkynes to N-aryl imines. Rueping14 has reported the
Other methods are based in the enhancement of the electro-
philicity of the imine by introducing an electron-withdrawing
group attached to the nitrogen atom. The alkynylation of these
substrates lead to protected propargylic amines. Chong15 and
Soderquist16 accomplished the alkynylation of N-acylimines by
using chiral alkynylboronates and alkynylboranes based on the
BINOL and the borabicyclo[3.3.2]decane scaffolds, respectively, as
nucleophilic reagents. Recently we have reported17 the direct ad-
dition of terminal alkynes to N-sulfonylimines by using dime-
thylzinc and BINOL as catalyst. Finally, Wang has described the
alkynylation of N-(diphenylphosphinoyl)imines promoted by
proline-derived b-amino alcohol ligands and diethylzinc, requiring
high (60 mol %) or stoichiometric amounts of ligand,18 which could
be reduced (35 mol %) when a tridentate amino alcohol was
used.19
N-Phosphinoylimines are very attractive activated imines since
the phosphinoyl group can be easily removed from the addition
products under mild reaction conditions leading to the free
amines.20 For this reason, they have been widely used in catalytic
asymmetric nitro-Mannich,21 Mannich,22 Strecker,23 and organo-
metallic addition24 processes. Herein we report our results on the
enantioselective addition of terminal alkynes to N-(diphenylphos-
phinoyl)imines catalyzed by a BINOL-type ligand and dimethylzinc
(Scheme 1). Commercially available BINOL-type ligands were cho-
sen in our study because they are known to give highly enantio-
selective reactions with a variety of metals, including zinc.25
* Corresponding author. Tel.: þ34 963544329; fax: þ34 963544328; e-mail
address: jose.r.pedro@uv.es (J.R. Pedro).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.01.037

G. Blay et al. / Tetrahedron 68 (2012) 2128e2134
2129
effect on achieving good enantioselectivity and yield in the re-
action, the enantioselectivity increasing in the order L1<L3 and
L7<L6<L3.
O
O
P(Ph)2
P(Ph)2
HN
R1
N
L, R2Zn
Ligand L1, bearing the smallest substituent (R¼H), gave the
lowest enantioselectivity and a moderate yield (entry 1), while 3,30-
dibromobinol (L3) gave the best result consisting of 84% ee and 81%
yield (entry 3). However, further increases of the bulkiness of the
substituents at the 3,30-positions led to decreased enantiose-
lectivities (entries 5e7). The optimization was continued using L3
with the screening of different temperatures, solvents and dia-
lkylzinc reagents. Lowering the temperature to ꢁ20 ꢀC or in-
creasing it to room temperature had a negative effect on the
enantioselectivity in both cases (entries 8 and 9). The use of other
solvents (hexane, dichloromethane, tetrahydrofuran) resulted also
in a lower yield and enantioselectivity (entries 10e12). Finally, the
use of diethylzinc as reported by Wang,18a instead of dimethylzinc
resulted also in a detriment of enantioselectivity (entry 13).
Therefore, the best results in terms of yields and enantioselectivity
were obtained by performing the reaction with ligand L3, dime-
thylzinc and toluene at 0 ꢀC (entry 3).
+
R2
H
R1
H
R2
solvent
1
3
2
X1
X2
X1
OH
OH
OH
OH
X1
X2
X1
(R)-L4 X1 = H
(R)-L5 X1 = Br
(R)-L1 X1 = X2 = H
(R)-L2 X1 = H, X2 = Br
(R)-L3 X1 = Br, X2 = H
(R)-L6 X1 = Ar1, X2 = H
(R)-L7 X1 = Ar2, X2 = H
Under these optimized conditions we examined the reaction of
phenylacetylene 2a with various substituted N-(diphenylphosphi-
noyl)aldimines 1 (Table 2).
CF3
i-Pr
i-Pr
Table 2
Enantioselective addition of phenylacetylene (2a) to N-(diphenylphosphinoyl)im-
CF3
i-Pr
Ar2
ines 1a
Ar1
O
O
Br
P(Ph)2
Scheme 1. Alkynylation of N-phosphinoyl imines and BINOL-type ligands used in this
P(Ph)2
HN
R1
N
OH
OH
L3, Me2Zn
L3
study.
+
Ph
H
R1
H
toluene, 0 o
C
Ph
Br
1
3
2a
2. Results and discussion
Entry
1
R1
t (h)
3
Yieldb (%)
ee (%)c
To optimize the reaction conditions we used the asymmetric
reaction of phenylacetylene (2a, R2¼Ph) with N-(diphenylphos-
phinoyl)benzaldimine (1a, R1¼Ph). A 2 M dimethylzinc solution in
toluene (6 equiv) was added dropwise to a mixture of ligand
(0.2 equiv) and alkyne (7.2 equiv) in toluene at room temperature.
After stirring for 1 h the reaction mixture was cooled to 0 ꢀC and
then a solution of the imine 1a (1 equiv) in toluene was added.
Under these conditions a series of BINOL-type ligands L1eL7 were
tested (Table 1). The results revealed that the size of the sub-
stituents at the 3,30-positions on the BINOL ligand had an essential
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
Ph
30
24
30
42
24
48
30
42
48
24
30
30
30
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
81
60
54
67
61
59
71
56
62
68
68
46
37
84
85
96
76
65
68
86
77
76
91
78
83
16
4-MeC6H4
4-MeOC6H4
4-FC6H4
4-ClC6H4
3-MeC6H4
2-MeC6H4
2-MeOC6H4
2-Naphthyl
2-Furanyl
2-Thienyl
3-Furanyl
PhCH2CH2
9
10
11
12
13d
1j
1k
1l
3ja
3ka
3la
1m
3ma
Table 1
a
Compound 1 (0.125 mmol), 2a (0.90 mmol), 2 M Me2Zn in toluene (0.75 mmol),
L3 (0.025 mmol).
Enantioselective addition of phenylacetylene (2a, R2¼Ph) to N-(diphenylphosphi-
noyl)imine 1a (R1¼Ph). Screening of ligands and conditionsa
b
Yield after column chromatography.
Determined by HPLC using chiral stationary phases.
This alkylimine was prepared in situ from the corresponding a-amido sulfone
c
Entry
L
Solvent
T (ꢀC)
t (h)
Yieldb (%)
ee (%)c
d
1
2
3
4
5
6
7
8
L1
L2
L3
L4
L5
L6
L7
L3
L3
L3
L3
L3
L3
L3
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Hexane
CH2Cl2
0
0
0
0
0
0
0
ꢁ20
rt
0
0
0
20
48
30
24
30
24
35
48
20
20
30
48
30
48
68
66
81
57
75
63
68
63
84
70
61
73
75
66
3
37
84
12
72
36
22
65
24
5
(Ref. 26).
Benzaldimines gave the alkynylation products with good
enantioselectivities, regardless of the steric or electronic nature of
the substituents (65e96% ee, entries 1e8). Both electron-donating
(Me, OMe) or electron-withdrawing (F, Cl) substituents, as well as
ortho, meta or para substitution were well tolerated. It is interesting
to note that arylaldimines with a substituent in the ortho position of
the aromatic ring gave a moderate yield and good enantioselectivity
(entries 7 and 8). Particularly interesting is the result of the reaction
of phenylacetylene (2a) with N-(diphenylphosphinoyl)-2-methyl
benzaldimine (1g), which gave product 3ga in 71% yield and 86%
ee with our catalytic system against a 72% yield and 33% ee with the
catalytic system described by Wang.18a Bulky N-(diphenylphos-
phinoyl)imine 1i derived from 2-naphthylcarbaldehyde (entry 9)
gave the corresponding product 3ia with a good ee value (76%).
9
10
11
12
13d
14e
57
20
73
73
THF
Toluene
Toluene
0
0
a
According to Scheme 1: 1a (0.125 mmol), 2a (0.90 mmol), 2 M Me2Zn in toluene
(0.75 mmol), L (0.025 mmol).
b
Yield after column chromatography.
Determined by HPLC using chiral stationary phases.
Et2Zn (1 M) in toluene was used instead of Me2Zn.
Me2Zn (0.5 mmol).
c
d
e

2130
G. Blay et al. / Tetrahedron 68 (2012) 2128e2134
A number of N-(diphenylphosphinoyl)arylaldimines derived
O
from heteroaromatic aldehydes (entries 10e12) were also suit-
able substrates providing the corresponding propargylic phos-
phonylamides with good enantioselectivities (ee values
between 78 and 91%). However, the alkyl-substituted imine 1m,
P(Ph)2
NH2
HN
Ph
HCl
Ph
MeOH, rt
92%
Ph
a
-amido sulfone,26
Ph
generated in situ from the corresponding
4
3aa
84% ee
reacted to give product 3ma with low yield and enantiose-
lectivity (entry 13).
84% ee
Finally, we also studied the applicability of the reaction with
other alkynes. The results are summarized in Table 3.
Scheme 2. Deprotection of the amino group.
The
reactions
of
4-methoxyphenylacetylene
(2b),
4-
In conclusion, we have developed a procedure for the catalytic
enantioselective addition of terminal alkynes to N-(diphenylphos-
phinoyl)aldimines to give N-(diphenylphosphinoyl)-protected
propargylic amines by using dimethylzinc and BINOL-type ligands.
Substitution on the BINOL ligand at the 3,30-positions seems to be
essential for obtaining good enantioselectivities. The reaction
works with a variety of aromatic and heteroaromatic aldimines and
with different alkynes, providing the expected products in gener-
ally good yields and enantiomeric excesses. The products can be
conveniently converted into the corresponding propargylic amines
by treatment with HCl/MeOH.
fluorophenylacetylene (2c), 4-chlorophenylacetylene (2d), and
3,5-dimethoxyphenylacetylene (2e), with N-(diphenylphosphi-
noyl)benzaldimine (1a) afforded the corresponding products with
good enantioselectivities (89e92%) (entries 1e4). The reaction of
heteroaromatic alkynes, such as 3-ethynylthiophene (2f) gave
moderate enantioselectivity (76% ee) (entry 5). However, the alkyl
substituted terminal alkynes, 1-hexine (2g) and cyclo-
propylacetylene (2h) reacted with N-(diphenylphosphinoyl)ben-
zaldimine (1a) to give products 3ag and 3ah with low yields
(entries 6e7) although the alkynylation product 3ah was obtained
with moderate enantioselectivity (72% ee). Interestingly, when the
sterically hindered ortho-substituted imine 1g was used with the
aromatic terminal alkynes 2bef the alkynylation products were
still obtained with moderate to good enantioselectivity (73e93%
ee) (entries 8e12).
3. Experimental section
3.1. General procedures
Reactions were carried out under nitrogen in round bottom
flasks oven-dried overnight at 120 ꢀC. N-(diphenylphosphinoyl)
imines 1 were prepared according to reported procedures.27
Commercial reagents were used as purchased. Toluene was dis-
tilled from CaH2. Reactions were monitored by TLC analysis using
Silica el 60 F254 thin layer plates. Flash column chromatography was
performed on silica gel 60, 0.040e0.063 mm. Melting points were
determined in capillary tubes. NMR spectra were run at 300 MHz
for 1H and at 75 MHz for 13C NMR and internally referenced to the
Table 3
Enantioselective addition of alkynes 2 to N-(diphenylphosphinoyl)imines 1a and 1ga
O
O
Br
P(Ph)2
P(Ph)2
HN
R1
N
OH
OH
L3, Me2Zn
L3
+
R2
H
R1
H
Toluene, 0 o
C
R2
Br
1
3
2
CHCl3 signal (d¼7.26 and 77.0 ppm, respectively). Chemical shifts
are reported in parts per million. The carbon type was determined
by DEPT experiments. Electrospray ionization mass spectra (ESI)
were recorded on a Q-TOF premier mass spectrometer with an
electrospray source. The drying gas as well as the nebulizing gas
was nitrogen. Specific optical rotations were measured using so-
dium light (D line 589 nm). Chiral HPLC analyses were performed in
a chromatograph equipped with a UV diode-array detector using
chiral stationary phase columns.
Entry
1
R1
2
R2
t (h)
3
Yieldb (%) ee (%)c
1
2
3
4
5
6
7
8
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
2b 4-MeOC6H4
2c 4-FC6H4
2d 4-ClC6H4
2e 3,5-(MeO)2C6H3 20
2f 3-Thienyl
2g n-Butyl
20
30
24
3ab 69
3ac 69
3ad 79
3ae 64
3af 70
3ag 22
3ah 38
3gb 93
3gc 77
3gd 81
3ge 67
3gf 90
85
91
92
90
76
14
72
90
93
73
85
83
50
72
48
48
24
48
2h Cyclopropyl
1g 2-MeC6H4 2b 4-MeOC6H4
1g 2-MeC6H4 2c 4-FC6H4
1g 2-MeC6H4 2d 4-ClC6H4
1g 2-MeC6H4 2e 3,5-(MeO)2C6H3 48
1g 2-MeC6H4 2f 3-Thienyl 48
9
10
11
12
3.2. General procedure for the enantioselective alkynylation
of compounds 1
a
Compound 1 (0.125 mmol), 2 (0.90 mmol), 2 M Me2Zn in toluene (0.75 mmol),
L3 (0.025 mmol).
A 2 M solution of Me2Zn in toluene (0.375 mL, 0.75 mmol) was
added dropwise to a solution of ligand L3 (11.2 mg, 0.025 mmol)
and alkyne 2 (0.9 mmol) in toluene (0.2 mL) at rt under nitrogen.
After stirring for 1 h, the reaction mixture was cooled to 0 ꢀC. After
15 min, a solution of imine 1 (0.125 mmol) in toluene (0.4 mL) was
added via syringe. The solution was stirred until the reaction was
complete (TLC). The reaction mixture was quenched with 1 M HCl
(15 mL), extracted with CH2Cl2 (3ꢂ15 mL), dried over MgSO4 and
concentrated under reduced pressure. Purification by flash chro-
matography on silica gel eluting with hexane/EtOAc mixtures
afforded compound 3.
b
Yield after column chromatography.
Determined by HPLC using chiral stationary phases.
c
Deprotection of the amino group in N-(diphenylphosphinoyl)
propargylamines can be easily carried out by treatment with
HCl/MeOH. After this treatment compound 3aa gave the free
amine 4 in 92% yield (Scheme 2).18a Compound 3aa obtained
with our catalyst showed identical optical rotation sign as (S)-
(ꢁ)-3aa, whose absolute stereochemistry had been determined
by chemical correlation with (S)-(ꢁ)-N-(1,3-diphenylprop-2-
ynyl)-4-toluenesulfonamide, which had been previously pre-
pared by our group.17 The stereochemistry of the rest of
the propargylic diphenylphosphinoylamides was assigned by
analogy.
3.3. N-(1,3-Diphenylprop-2-ynyl)-P,P-diphenylphosphinamide
(3aa)
Mp 173e175 ꢀC; ½a D20
ꢃ
ꢁ63.1 (c 0.9, CHCl3, 84% ee); 1H NMR
d
8.13e8.06 (m, 2H), 7.90e7.83 (m, 2H), 7.71e7.69 (m, 2H),

G. Blay et al. / Tetrahedron 68 (2012) 2128e2134
2131
7.54e7.46 (m, 4H), 7.44e7.37 (m, 5H), 7.35e7.30 (m, 5H), 5.40 (t,
7.59e7.44 (m, 4H), 7.44e7.36 (m, 4H), 7.36e7.28 (m, 5H), 5.36 (d,
J¼9.6 Hz, 1H), 3.55 (t, J¼9.3 Hz, 1H); 13C NMR
d
140.4 (d,
J¼9.3 Hz, 1H), 3.93e3.55 (br s, 1H); 13C NMR
138.8 (d, JCeP¼4.0 Hz,
d
JCeP¼4.5 Hz, C), 133.4, 132.8 (d, JCeP¼9.8 Hz), 132.1 (d, JCeP¼6.8 Hz,
CH), 131.7, 131.5, 129.0, 128.7 (d, JCeP¼6 Hz), 128.4 (d, JCeP¼12 Hz),
128.0, 127.4, 122.8 (C), 89.0 (d, JCeP¼6 Hz, C), 85.6 (C), 47.2 (CH);
HRMS (ESI) m/z: 430.1336 (MþþNa), C27H22NNaOP requires
430.1337. Enantiomeric excess (84%) was determined by chiral
HPLC (Chiralpak AD-H), hexane/iPrOH 85:15, 1 mL/min, major en-
antiomer tR¼13.9 min, minor enantiomer tR¼12.5 min.
C), 133.8 (C), 132.8 (CH), 132.7 (CH), 122.4 (C), 132.2 (d, J¼2.7 Hz,
CH), 132.1 (d, J¼2.7 Hz, CH), 131.8 (CH), 131.7 (CH), 131.6 (CH), 128.8
(CH), 128.7 (CH), 128.7 (CH), 128.6 (d, JCeP¼3.1 Hz, CH), 128.5 (d,
J¼2.7 Hz, CH), 128.3 (CH), 88.2 (d, JCeP¼6.7 Hz, C), 85.9 (C), 46.6
(CH); HRMS (ESI) m/z: 464.0945 (MþþNa), C27H21ClNNaOP requires
464.0947. Enantiomeric excess (65%) was determined by chiral
HPLC (Chiralpak AD-H), hexane/iPrOH 85:15, 1 mL/min, major en-
antiomer tR¼17.5 min, minor enantiomer tR¼12.7 min.
3.4. N-(3-Phenyl-1-p-toluylprop-2-ynyl)-P,P-diphenyl
phosphinamide (3ba)
3.8. N-(3-Phenyl-1-m-toluylprop-2-ynyl)-P,P-diphenyl
phosphinamide (3fa)
Mp 183e185 ꢀC; ½a D20
ꢃ
ꢁ60.4 (c 0.79, CHCl3, 85% ee); 1H NMR
d
8.12e8.01 (m, 2H), 7.91e7.89 (m, 2H), 7.58e7.53 (m, 2H),
Mp 129e131 ꢀC; ½a D20
ꢃ
ꢁ42.1 (c 1.45, CHCl3, 68% ee); 1H NMR
7.52e7.42 (m, 4H), 7.42e7.34 (m, 4H), 7.32e7.26 (m, 3H), 7.15 (d,
d
8.09e8.02 (m, 2H), 7.87e7.80 (m, 2H), 7.24 (t, J¼7.6 Hz, 1H), 7.09
J¼7.9 Hz, 2H), 5.34 (d, J¼9.31 Hz,1H), 3.64 (br s,1H), 2.32 (s, 3H); 13C
(d, J¼7.6 Hz, 1H), 5.34 (t, J¼9.3 Hz, 1H), 3.59 (t, J¼8.2 Hz, 1H), 2.34 (s,
NMR
d
137.7 (C), 137.4 (d, JCeP¼4.6 Hz, C), 132.9 (d, JCeP¼47.0 Hz, C),
3H); 13C NMR
d
140.3 (d, JCeP¼4.7 Hz, C), 138.3 (C), 132.7 (d,
132.8 (CH), 132.7 (CH), 132.1 (CH), 132.00 (CH), 131.96 (CH), 131.8
(CH) (d, JCeP¼9.9 Hz, C), 131.6 (CH), 131.2 (d, J¼49.0 Hz, C), 129.3
(CH), 128.5 (CH), 128.4 (CH), 128.2 (CH), 127.2 (CH), 122.7 (C), 89.0
(d, J¼6.5 Hz, C), 85.4 (C), 46.9 (CH), 21.1 (CH3); HRMS (ESI) m/z:
444.1483 (MþþNa), C28H24NNaOP requires 444.1493. Enantiomeric
excess (85%) was determined by chiral HPLC (Chiralpak AD-H),
hexane/iPrOH 85:15, 1 mL/min, major enantiomer tR¼16.7 min,
minor enantiomer tR¼15.0 min.
JCeP¼9.9 Hz, CH), 131.8 (d, JCeP¼9.9 Hz, CH), 131.6 (CH), 128.7 (CH),
128.6 (CH), 128.54 (CH), 128.51 (CH), 128.4 (CH), 128.3 (CH), 128.3
(CH), 128.2 (CH), 128.0 (CH), 124.3 (CH), 122.7 (C), 89.0 (d,
JCeP¼6.0 Hz, C), 85.4 (C), 47.1 (CH), 21.4 (CH3); HRMS (ESI) m/z:
430.1536 (MþþNa), C27H22NNaOP requires 430.1337. Enantiomeric
excess (68%) was determined by chiral HPLC (Chiralpak AD-H),
hexane/iPrOH 90:10, 1 mL/min, major enantiomer tR¼14.5 min,
minor enantiomer tR¼13.7 min.
3.5. N-(1-(4-Methoxyphenyl)-3-phenylprop-2-ynyl)-P,P-
3.9. N-(3-Phenyl-1-o-toluylprop-2-ynyl)-P,P-diphenyl
diphenylphosphinamide (3ca)
phosphinamide (3ga)
Mp 187e189 ꢀC; ½a D20
ꢃ
ꢁ62.6 (c 1.06, CHCl3, 96% ee); 1H NMR
Mp 184e186 ꢀC; ½a D20
ꢃ
ꢁ57 (c 0.99, CHCl3, 86% ee); 1H NMR
d
8.12e8.02 (m, 2H), 7.89e7.79 (m, 2H), 7.59 (d, J¼8.6 Hz, 2H),
d 8.10e7.99 (m, 2H), 7.84e7.74 (m, 2H), 7.70e7.64 (m,1H), 7.55e7.12
7.52e7.42 (m, 4H), 7.41e7.34 (m, 4H), 7.33e7.26 (m, 3H), 6.86 (d,
J¼8.8 Hz, 2H), 5.34 (t, J¼9.7 Hz, 1H), 3.78 (s, 3H), 3.54 (t, J¼9.1 Hz,
(m, 14H), 5.52 (t, J¼8.8 Hz, 1H), 3.52 (br t, J¼7.0 Hz, 1H), 2.41 (s, 3H);
3C NMR1
d
138.7 (d, JCeP¼5.6 Hz, C), 135.6 (C), 132.5 (d, JCeP¼9.9 Hz,
1H); 13C NMR
d
159.2 (C), 133.4 (C), 132.8 (CH), 132.7 (CH), 132.5 (d,
CH), 131.9 (d, JCeP¼4.6 Hz, CH), 131.9 (CH), 131.8 (CH), 131.6 (CH),
130.9 (CH), 128.5 (d, JCeP¼2.5 Hz, CH), 128.3 (d, JCeP¼2.4 Hz, CH),
128.2 (CH), 128.1 (CH), 127.0 (CH), 126.4 (CH), 122.7 (C), 89.1 (d,
JCeP¼4.6 Hz, C), 85.0 (C), 44.4 (CH), 19.1 (CH3); HRMS (ESI) m/z:
422.1683 (MþþH), C28H25NOP requires 422.1668. Enantiomeric
excess (86%) was determined by chiral HPLC (Chiralpak AD-H),
hexane/iPrOH 85:15, 1 mL/min, major enantiomer tR¼15.4 min,
minor enantiomer tR¼18.1 min.
JCeP¼4.3 Hz, C), 132.0 (d, J¼2.9 Hz, CH), 131.9 (d, J¼2.8 Hz, CH), 131.8
(d, JCeP¼9.8 Hz, CH), 131.6 (CH), 128.6 (CH), 128.39 (CH), 128.37
(CH), 128.34 (CH), 128.2 (CH), 122.7 (C), 113.9 (CH), 89.0 (d,
JCeP¼6.2 Hz, C), 85.3 (C), 55.3 (CH3), 46.6 (CH); HRMS (ESI) m/z:
438.1621 (MþþH), C28H25NO2P requires 438.1617. Enantiomeric
excess (96%) was determined by chiral HPLC (Chiralpak AD-H),
hexane/iPrOH 85:15, 1 mL/min, major enantiomer tR¼19.9 min,
minor enantiomer tR¼15.7 min.
3.10. N-(1-(2-Methoxyphenyl)-3-phenylprop-2-ynyl)-P,P-
3.6. N-(1-(4-Fluorophenyl)-3-phenylprop-2-ynyl)-P,P-
diphenylphosphinamide (3ha)
diphenylphosphinamide (3da)
Mp 178e180 ꢀC; ½a D20
ꢃ
ꢁ68.3 (c 0.65, CHCl3, 77% ee); 1H NMR
Mp 174e175 ꢀC; ½a D20
ꢃ
ꢁ55.5 (c 1.035, CHCl3, 76% ee); 1H NMR
d 7.99e7.91 (m, 2H), 7.85e7.78 (m, 2H), 7.48e7.23 (m, 13H), 6.92 (td,
d
8.12e8.02 (m, 2H), 7.88e7.79 (m, 2H), 7.71e7.63 (m, 2H),
J¼7.5, 1.1 Hz, 1H), 6.86 (dd, J¼8.3, 0.9 Hz, 1H), 5.47 (br t, J¼9.4 Hz,
7.55e7.28 (m, 11H), 7.02 (t, J¼8.7 Hz, 2H), 5.37 (t, J¼8.6 Hz, 1H), 3.73
1H), 4.03 (br t, J¼8.8 Hz, 1H), 3.78 (s, 3H); 13C NMR
d 156.6 (C), 133.4
(br t, J¼8.1 Hz, 1H); 13C NMR
d
162.3 (d, JCeF¼246.5 Hz, C), 136.1 (dd,
(C), 132.3 (d, JCeP¼9.8 Hz, CH), 132.2 (d, JCeP¼9.9 Hz, CH), 131.8 (d,
JCeP¼2.7 Hz, CH), 131.7 (d, J¼2.9 Hz, CH), 131.6 (CH), 129.3 (CH),
129.1 (d, JCeP¼5.0 Hz, C), 128.5 (CH), 128.3 (d, JCeP¼3.1 Hz, CH),
128.2 (d, JCeP¼4.4 Hz, CH), 128.0 (CH), 123.0 (C), 120.8 (CH), 111.3
(CH), 89.4 (d, JCeP¼6.1 Hz, C), 83.8 (C), 55.5 (CH3), 43.7 (CH); HRMS
(ESI) m/z: 438.1624 (MþþH), C28H25NO2P requires 438.1617. Enan-
tiomeric excess (77%) was determined by chiral HPLC (Chiralpak
JCeP¼JCeF¼3.6 Hz, C), 133.1 (C), 132.8 (CH), 132.7 (CH), 132.1 (d,
JCeP¼2.8 Hz, CH), 132.0 (d, JCeP¼2.7 Hz, CH), 131.8 (CH), 131.7 (CH),
131.6 (CH), 131.4 (C), 130.7 (C), 129.2 (CH), 129.1 (CH), 128.6 (d,
J¼3.3 Hz, CH), 128.5 (CH), 128.4 (d, J¼3.2 Hz, CH), 128.3 (CH), 122.4
(C), 115.36 (d, JCeF¼21.6 Hz, C), 88.5 (d, JCeP¼6.7 Hz, C), 85.7 (C), 46.5
(CH); HRMS (ESI) m/z: 426.1420 (MþþH), C27H21FNOP requires
426.1418. Enantiomeric excess (76%) was determined by chiral
HPLC (Chiralpak AD-H), hexane/iPrOH 85:15, 1 mL/min, major en-
antiomer tR¼14.5 min, minor enantiomer tR¼11.3 min.
AD-H), hexane/iPrOH 85:15,
tR¼20.9 min, minor enantiomer tR¼26.5 min.
1 mL/min, major enantiomer
3.11. N-(1-(Naftalen-2-il)-3-phenylprop-2-ynyl)-P,P-
3.7. N-(1-(4-Chlorophenyl)-3-phenylprop-2-ynyl)-P,P-
diphenylphosphinamide (3ia)
diphenylphosphinamide (3ea)
Mp 190e192 ꢀC; ½a D20
ꢃ
ꢁ33.9 (c 1.33, CHCl3, 76% ee); 1H NMR
Mp 193e195 ꢀC; ½a D20
ꢃ
ꢁ46.4 (c 0.595, CHCl3, 65% ee); 1H NMR
d 8.12e8.05 (m, 2H), 8.04 (br s, 1H), 7.88e7.79 (m, 6H), 7.51e7.30
d
8.12e8.02 (m, 2H), 7.88e7.79 (m, 2H), 7.64 (d, J¼8.4 Hz, 2H),
(m, 13H), 5.54 (br t, J¼9.5 Hz, 1H), 3.72 (br t, J¼8.8 Hz, 1H); 13C NMR

2132
G. Blay et al. / Tetrahedron 68 (2012) 2128e2134
d
137.6 (d, JCeP¼4.5 Hz, C), 133.1 (C), 133.0 (C), 132.8 (d, JCeP¼9.9 Hz,
128.5 (CH), 128.42 (CH), 128.39 (CH), 128.3 (CH), 128.4 (CH), 125.9
(CH), 122.8 (C), 89.7 (d, JCeP¼7.4 Hz, C), 84.2 (C), 43.8 (CH), 40.3 (d,
JCeP¼3.7 Hz, CH2), 32.0 (CH2). HRMS (ESI) m/z: 458.1651 (MþþNa),
C29H26NOPNa requires 458.1650. Enantiomeric excess (16%) was
determined by chiral HPLC (Chiralpak AD-H), hexane/iPrOH 85:15,
1 mL/min, major enantiomer tR¼13.3 min, minor enantiomer
tR¼10.0 min.
CH), 132.1 (d, JCeP¼2.8 Hz, CH), 132.0 (d, JCeP¼2.7 Hz, CH), 131.9
(CH), 131.8 (CH), 131.7 (CH), 128.7 (CH), 128.6 (d, JCeP¼4.1 Hz, CH),
128.4 (CH), 128.3 (CH), 128.2 (CH), 127.6 (CH), 126.2 (CH), 125.9
(CH), 125.5 (CH), 122.7 (C), 88.8 (d, JCeP¼6.0 Hz, C), 85.8 (C), 47.3
(CH); HRMS (ESI) m/z: 480.1489 (MþþNa), C31H24NNaOP requires
480.1493. Enantiomeric excess (76%) was determined by chiral
HPLC (Chiralpak AD-H), hexane/iPrOH 85:15, 1 mL/min, major en-
antiomer tR¼15.6 min, minor enantiomer tR¼14.6 min.
3.16. N-(3-(4-Methoxyphenyl)-1-phenylprop-2-ynyl)-P,P-
diphenylphosphinamide (3ab)
3.12. N-(1-(Furan-2-il)-3-phenylprop-2-ynyl)-P,P-diphenyl
phosphinamide (3ja)
Mp 173e175 ꢀC; ½a D20
ꢃ
ꢁ67.9 (c 1.02, CHCl3, 85% ee); 1H NMR
d
8.10e8.03 (m, 2H), 7.87e7.80 (m, 2H), 7.68e7.65 (m, 2H),
Mp 133e136 ꢀC; ½a D20
ꢃ
ꢁ44.7 (c 1.027, CHCl3, 91% ee); 1H NMR
7.37e7.27 (m, 11H), 6.82 (d, J¼8.9 Hz, 2H), 5.36 (t, J¼9.6 Hz, 1H),
d
8.01e7.85 (m, 4H), 7.50e7.36 (m, 9H), 7.30e7.26 (m, 3H), 6.37 (dt,
3.79 (s, 3H), 3.57 (t, J¼9.0 Hz, 1H); 13C NMR
d 159.7 (C), 140.5 (d,
J¼3.2, 0.8 Hz, 1H), 6.29 (dd, J¼3.3, 1.9 Hz, 1H), 5.38 (br t, J¼9.2 Hz,
JCeP¼4.5 Hz, C), 133.1 (CH), 132.8 (d, JCeP¼9.8 Hz, CH), 132.0 (CH),
131.97 (CH), 131.93 (CH), 131.89 (CH), 131.8 (CH), 128.6 (CH), 128.5
(d, JCeP¼12.6 Hz, CH), 127.9 (CH), 126.5 (CH), 126.3 (CH), 114.8 (C),
113.8 (CH), 87.4 (d, JCeP¼6.1 Hz, C), 85.5 (C), 55.3 (CH3), 47.2 (CH);
HRMS (ESI) m/z: 460.1448 (MþþNa), C28H24NNaO2P requires
460.1442. Enantiomeric excess (85%) was determined by chiral
HPLC (Chiralpak AD-H), hexane/iPrOH 85:15, 1 mL/min, major en-
antiomer tR¼20.7 min, minor enantiomer tR¼16.9 min.
1H), 3.69 (br t, J¼8.4 Hz, 1H); 13C NMR
d
152.1 (d, JCeP¼5.8 Hz, C),
142.7 (CH), 132.7 (C), 132.5 (CH), 132.3 (CH), 132.2 (CH), 132.1 (d,
JCeP¼6.5 Hz, CH), 131.8 (CH), 131.0 (C), 128.6 (d, JCeP¼3.0 Hz, CH),
128.5 (CH), 128.4 (d, JCeP¼2.9 Hz, CH), 128.2 (CH), 122.3 (C), 110.4
(CH), 107.5 (CH), 86.5 (d, JCeP¼5.6 Hz, C), 84.4 (C), 41.4 (CH); HRMS
(ESI) m/z: 398.1307 (MþH)þ, C25H21NO2P requires 398.1304. En-
antiomeric excess (91%) was determined by chiral HPLC (Chiralpak
AD-H), hexane/iPrOH 85:15,
1 mL/min, major enantiomer
tR¼13.6 min, minor enantiomer tR¼11.8 min.
3.17. N-(3-(4-Fluorophenyl)-1-phenylprop-2-ynyl)-P,P-
diphenylphosphinamide (3ac)
3.13. N-(3-Phenyl-1-(tien-2-il)prop-2-ynyl)-P,P-diphenyl
phosphinamide (3ka)
Oil; ½a 2D0
ꢃ
ꢁ47.3 (c 1.42, CHCl3, 91% ee); 1H NMR
d 8.08e8.01 (m,
2H), 7.87e7.80 (m, 2H), 7.65e7.62 (m, 2H), 7.51e7.28 (m, 11H), 6.97
Mp 131e133 ꢀC; ½a D20
ꢃ
ꢁ58.4 (c 0.91, CHCl3, 78% ee); 1H NMR
(t, J¼8.8 Hz, 2H), 5.30 (t, J¼9.0 Hz, 1H), 3.55 (t, J¼7.8 Hz, 1H); 13C
d
8.07e8.00 (m, 2H), 7.93e7.85 (m, 2H), 7.52e7.38 (m, 8H),
d
NMR 162.5 (d, JCeF¼249.6 Hz, C),140.2 (d, JCeP¼4.9 Hz, C),133.5 (d,
7.30e7.23 (m, 5H), 6.93 (dd, J¼5.0, 3.7 Hz, 1H), 5.55 (br t, J¼9.5 Hz,
JCeP¼8.3 Hz, CH), 132.7 (d, JCeP¼9.7 Hz, CH), 132.0 (d, JCeP¼2.2 Hz,
CH), 131.9 (d, JCeP¼9.9 Hz, CH), 128.7 (CH), 128.5 (d, JCeP¼12.7 Hz,
CH), 128.0 (CH), 127.2 (CH), 118.7 (d, JCeF¼3.6 Hz, C), 115.5 (d,
JCeF¼22.0 Hz, CH), 88.5 (d, JCeP¼4.5 Hz, CH), 84.5 (C), 47.1 (CH);
HRMS (ESI) m/z: 448.1247 (MþNa)þ, C27H21FNNaOP requires
448.1242. Enantiomeric excess (91%) was determined by chiral
HPLC (Chiralpak AD-H), hexane/iPrOH 85:15, 1 mL/min, major en-
antiomer tR¼16.6 min, minor enantiomer tR¼14.7 min.
1H), 3.78 (dd, J¼9.9, 8.1 Hz, 1H); 13C NMR
144.8 (d, JCeP¼6.1 Hz, C),
d
132.8 (C), 132.5 (d, JCeP¼10.0 Hz, CH), 132.1 (d, JCeP¼2.3 Hz, CH),
131.9 (d, JCeP¼10.0 Hz, CH), 131.7 (CH), 131.0 (d, JCeP¼16.2 Hz, C),
128.6 (d, JCeP¼1.1 Hz, CH), 128.5 (CH), 128.4 (d, JCeP¼0.8 Hz, CH),
128.2 (CH), 126.9 (CH), 125.9 (CH), 125.5 (CH), 122.3 (C), 88.3 (d,
JCeP¼5.4 Hz, C), 84.7 (C), 43.1 (CH); HRMS (ESI) m/z: 414.1074
(MþþH), C25H21NOPS requires 414.1076. Enantiomeric excess (78%)
was determined by chiral HPLC (Chiralpak AD-H), hexane/iPrOH
85:15,1 mL/min, major enantiomer tR¼14.3 min, minor enantiomer
tR¼13.1 min.
3.18. N-(3-(4-Chlorophenyl)-1-phenylprop-2-ynyl)-P,P-
diphenylphosphinamide (3ad)
3.14. N-(1-(Furan-3-il)-3-phenylprop-2-ynyl)-P,P-diphenyl
phosphinamide (3la)
Mp 165e167; ½a 2D0
ꢃ
ꢁ72.5 (c 0.32, CHCl3, 92% ee); 1H NMR
d 8.09e8.02 (m, 2H), 7.88e7.81 (m, 2H), 7.67e7.63 (m, 2H),
7.53e7.25 (m, 4H), 5.39 (t, J¼9.3 Hz, 1H), 3.61 (br t, J¼9.0 Hz, 1H),
Oil; ½a 2D0
ꢃ
ꢁ49.0 (c 1.21, CHCl3, 83% ee); 1H NMR
d
8.10e8.04 (m,
2.41 (s, 3H); 13C NMR
d
140.1 (d, JCeP¼5.2 Hz, C), 134.4 (C), 132.9
2H), 7.92e7.85 (m, 2H), 7.58e7.32 (m, 13H), 6.70 (d, J¼0.9 Hz, 1H),
(CH), 132.7 (d, JCeP¼9.8 Hz, CH), 132.0 (d, JCeP¼2.3 Hz, 2CH), 131.8
(d, JCeP¼9.8 Hz, CH), 128.7 (CH), 128.6 (CH), 128.5 (CH), 128.4 (CH),
128.1 (CH), 127.2 (CH), 121.0 (C), 89.8 (d, JCeP¼6.0 Hz, C), 84.5 (C),
47.1 (CH); HRMS (ESI) m/z: 464.0943 (MþþNa), C27H21ClNNaOP
requires 464.0947. Enantiomeric excess (92%) was determined by
chiral HPLC (Chiralpak AD-H), hexane/iPrOH 85:15, 1 mL/min,
major enantiomer tR¼18.5 min, minor enantiomer tR¼16.7 min.
5.26 (br t, J¼9.6 Hz, 1H), 3.51 (br t, J¼9.3 Hz, 1H); 13C NMR
d 143.6
(C), 140.4 (CH), 132.8 (d, JCeP¼9.8 Hz, CH), 132.1 (C), 131.8 (CH), 131.7
(CH), 128.7 (d, JCeP¼4.5 Hz, CH), 128.5 (d, JCeP¼3.8 Hz, CH), 128.3
(CH), 126.5 (CH), 122.5 (C), 110.1 (CH), 88.3 (C), 83.6 (C), 39.8 (CH);
HRMS (ESI) m/z: 398.1305 (MþþH), C25H21NO2P requires 398.1304.
Enantiomeric excess (83%) was determined by chiral HPLC (Chir-
alpak AD-H), hexane/iPrOH 85:15, 1 mL/min, major enantiomer
tR¼11.5 min, minor enantiomer tR¼10.1 min.
3.19. N-(3-(3,5-Dimethoxyphenyl)-1-phenylprop-2-ynyl)-P,P-
diphenylphosphinamide (3ae)
3.15. N-(1,5-Diphenylpent-1-yn-3-yl)-P,P-diphenylphos
phinamide (3ma)
Mp 169e171 ꢀC; ½a D20
ꢃ
ꢁ63.4 (c 0.69, CHCl3, 90% ee); 1H NMR
d
8.09e8.02 (m, 2H), 7.86e7.79 (m, 2H), 7.67e7.64 (m, 2H),
Mp 127e129 ꢀC; ½a D20
ꢃ
ꢁ9.7 (c 1.2, CHCl3, 16 ee); 1H NMR
7.51e7.27 (m,10H), 6.54 (d, J¼2.3 Hz, 2H), 6.43 (t, J¼2.3 Hz,1H), 5.37
d
8.01e7.93 (m, 2H), 7.87e7.80 (m, 2H), 7.50e7.36 (m, 8H),
(t, J¼9.3 Hz, 1H), 3.76 (s, 6H); 13C NMR
d 160.4 (C), 140.3 (d,
7.32e7.27 (m, 3H), 7.25e7.11 (m, 5H), 4.21e4.09 (m, 1H), 3.27 (dd,
J¼10.2, 8.1 Hz, 1H), 2.94e2.75 (m, 2H), 2.27e2.07 (m, 2H); 13C NMR
JCeP¼4.6 Hz, C), 132.8 (d, JCeP¼9.9 Hz, CH), 132.1 (CH), 132.02 (CH),
131.99 (CH), 131.8 (d, JCeP¼9.8 Hz, CH), 128.5 (d, JCeP¼12.6 Hz, CH),
128.0 (CH), 127.3 (CH), 123.9 (C), 109.5 (CH), 101.7 (CH), 88.4 (d,
JCeP¼5.9 Hz, C), 85.5 (C), 55.4 (CH3), 47.1 (CH); HRMS (ESI) m/z:
d
141.0 (C), 133.5 (C), 132.6 (d, JCeP¼9.9 Hz), 132.0 (d, JCeP¼2.7 Hz,
CH), 131.7 (d, JCeP¼9.9 Hz, CH), 131.7 (CH), 130.8 (C), 128.6 (CH),

G. Blay et al. / Tetrahedron 68 (2012) 2128e2134
2133
490.1557 (MþþNa), C29H26NO3PNa requires 490.1548. Enantio-
(ESI) m/z: 474.1598 (MþþNa), C29H26NO2PNa requires 474.1599.
Enantiomeric excess (90%) was determined by chiral HPLC (Chir-
alpak IC), hexane/iPrOH 85:15, 1 mL/min, major enantiomer
tR¼9.1 min, minor enantiomer tR¼11.9 min.
meric excess (90%) was determined by chiral HPLC (Chiralpak AD-
H), hexane/iPrOH 85:15,
1
mL/min, major enantiomer
tR¼20.7 min, minor enantiomer tR¼16.9 min.
3.20. N-(1-Phenyl-3-(thien-3-yl)prop-2-ynyl)-P,P-diphenyl
3.24. N-(3-(4-Fluorophenyl)-1-o-toluylprop-2-ynyl)-P,P-
phosphinamide (3af)
diphenylphosphinamide (3gc)
Mp 163e165 ꢀC; ½a D20
ꢃ
ꢁ51.3 (c 0.85, CHCl3, 76% ee); 1H NMR
Mp 196e198 ꢀC; ½a D20
ꢃ
ꢁ57.5 (c 1.595, CHCl3, 93% ee); 1H NMR
d
8.10e8.03 (m, 2H), 7.88e7.81 (m, 2H), 7.67e7.63 (m, 2H),
d 8.08e8.00 (m, 2H), 7.83e7.76 (m, 2H), 7.69e7.66 (m, 1H),
7.53e7.24 (m, 11H), 7.07 (dd, J¼5.1, 1.2 Hz), 5.37 (t, J¼9.9 Hz, 1H),
7.53e7.43 (m, 4H), 7.40e7.34 (m, 2H), 7.29e7.22 (m, 4H), 7.20e14
(m, 1H), 6.96 (t, J¼8.8 Hz, 2H), 5.53 (t, J¼8.9 Hz, 1H), 3.53 (t,
3.61 (br t, J¼9.3 Hz, 1H); 13C NMR
140.2 (d, JCeP¼5.2 Hz, C), 132.7
d
(d, JCeP¼9.8 Hz, CH), 132.05 (d, JCeP¼2.3 Hz, CH), 132.02 (d,
JCeP¼2.3 Hz, CH), 131.8 (d, JCeP¼9.8 Hz, CH), 129.8 (CH), 128.7 (CH),
128.6 (CH), 128.4 (CH), 128.0 (CH), 127.3 (CH), 125.2 (CH), 121.6 (C),
88.3 (d, JCeP¼6.0 Hz, C), 80.7 (C), 47.1 (CH); HRMS (ESI) m/z:
414.1075 (MþþH), C25H21NOPS requires 414.1076. Enantiomeric
excess (76%) was determined by chiral HPLC (Chiralpak AD-H),
hexane/iPrOH 85:15, 1 mL/min, major enantiomer tR¼18.5 min,
minor enantiomer tR¼17.0 min.
J¼8.1 Hz, 1H), 2.41 (s, 3H); 13C NMR
d
162.4 (d, JCeF¼249.4 Hz, C),
138.6 (d, JCeP¼6.0 Hz, C), 135.5 (C), 133.5 (d, JCeP¼8.3 Hz, CH), 133.0
(d, JCeP¼11.2 Hz, CH), 132.5 (d, JCeP¼9.9 Hz, CH), 132.0 (CH), 131.94
(CH), 131.91 (CH), 131.8 (d, JCeP¼10.0 Hz, CH), 131.3 (d, JCeP¼11.6 Hz,
CH), 130.9 (CH), 128.5 (CH), 128.3 (CH), 128.1 (CH), 127.0 (CH), 126.4
(CH), 118.7 (d, JCeF¼3.6 Hz, C), 115.3 (d, JCeF¼22.0 Hz, CH), 88.8 (d,
JCeP¼5.5 Hz, C), 84.0 (C), 44.3 (CH), 19.1 (CH3); HRMS (ESI) m/z:
462.1401 (MþþNa), C28H23FNOPNa requires 462.1399. Enantio-
meric excess (93%) was determined by chiral HPLC (Chiralpak AD-
3.21. N-(1-Phenylhept-2-ynyl)-P,P-diphenylphosphin
H), hexane/iPrOH 85:15,
1
mL/min, major enantiomer
amide (3ag)
tR¼21.4 min, minor enantiomer tR¼23.0 min.
Mp 114e116 ꢀC; ½a D20
ꢃ
ꢁ5.2 (c 0.70, CHCl3, 14% ee); 1H NMR
3.25. N-(3-(4-Chlorophenyl)-1-o-toluylprop-2-ynyl)-P,P-
diphenylphosphinamide (3gd)
d
8.05e7.98 (m, 2H), 7.84e7.78 (m, 2H), 7.60e7.57 (m, 2H),
7.52e7.26 (m, 9H), 5.12 (t, J¼9.8 Hz, 1H), 3.38 (t, J¼9.0 Hz, 1H), 2.20
(td, J¼6.9, 2.1 Hz, 2H), 1.53e1.33 (m, 4H), 0.90 (t, J¼7.1 Hz, 3H); 13C
Mp 203e205 ꢀC; ½a D20
ꢃ
ꢁ49.7 (c 0.5, CHCl3, 73% ee); 1H NMR
NMR
d
141.0 (d, JCeP¼4.6 Hz, C), 132.7 (d, JCeP¼9.8 Hz, CH), 132.0
d 8.06e7.98 (m, 2H), 7.81e7.44 (m, 2H), 7.64 (m, 1H), 7.54e7.33 (m,
(CH), 131.93 (CH), 131.89 (CH), 131.8 (CH), 128.5 (CH), 128.3 (CH),
127.7 (CH), 127.2 (CH), 86.3 (C), 79.7 (d, JCeP¼6.2 Hz, C), 46.8 (CH),
30.7 (CH2), 22.0 (CH2), 18.4 (CH2), 13.6 (CH3); HRMS (ESI) m/z:
410.1646 (MþþNa), C25H26NNaOP requires 410.1650. Enantiomeric
excess (14%) was determined by chiral HPLC (Chiralpak AD-H),
hexane/iPrOH 85:15, 1 mL/min, major enantiomer tR¼11.1 min,
minor enantiomer tR¼10.4 min.
6H), 7.26e7.13 (m, 7H), 5.52 (t, J¼8.7 Hz, 1H), 3.48 (br t, J¼8.0 Hz,
1H), 2.40 (s, 3H); 13C NMR
d
138.4 (d, JCeP¼5.9 Hz, C),135.6 (C),134.2
(C), 132.8 (CH), 132.5 (d, JCeP¼9.8 Hz, CH), 132.03 (d, JCeP¼2.3 Hz,
CH), 132.00 (d, JCeP¼2.3 Hz, CH), 131.8 (d, JCeP¼9.8 Hz, CH), 130.9
(CH),128.5 (CH),128.4 (CH),128.3 (CH),128.2 (CH),127.0 (CH),126.5
(CH), 121.1 (C), 90.0 (d, JCeP¼4.4 Hz, C), 84.0 (C), 44.3 (CH), 19.1
(CH3). HRMS (ESI) m/z: 478.1102 (MþþNa), C28H23ClNNaOP re-
quires 478.1104. Enantiomeric excess (73%) was determined by
chiral HPLC (Chiralpak IC), hexane/iPrOH 85:15, 1 mL/min, major
enantiomer tR¼10.7 min, minor enantiomer tR¼17.8 min.
3.22. N-(3-Cyclopropyl-1-phenylprop-2-ynyl)-P,P-
diphenylphosphinamide (3ah)
Mp 148e150 ꢀC; ½a D20
ꢃ
ꢁ19.5 (c 2.15, CHCl3, 72% ee); 1H NMR
3.26. N-(3-(3,5-Dimethoxyphenyl)-1-o-toluylprop-2-ynyl)-
P,P-diphenylphosphinamide (3ge)
d
7.98e7.91 (m, 2H), 7.86e7.80 (m, 1H), 7.77e7.71 (m, 2H), 7.51e7.17
(m, 10H), 5.03 (t, J¼8.2 Hz, 1H), 3.38 (br s, 1H), 1.22e1.13 (m, 1H),
0.71e0.61 (m, 2H), 0.60e0.51 (m, 2H); 13C NMR
d140.9 (d,
Mp 165e167 ꢀC; ½a D20
ꢃ
ꢁ50.1 (c 1.67, CHCl3, 85% ee); 1H NMR
JCeP¼4.8 Hz, C), 133.1 (d, JCeP¼37.2 Hz, C),132.7 (d, JCeP¼8.9 Hz, CH),
131.9 (d, JCeP¼2.9 Hz, CH), 131.8 (CH), 131.7 (CH), 131.4 (d,
JCeP¼39.1 Hz, C), 128.4 (CH), 128.5 (d, JCeP¼12.8 Hz, CH), 128.3 (CH),
127.7 (CH), 127.2 (CH), 89.2 (C), 74.8 (d, JCeP¼6.1 Hz, C), 46.8 (CH),
8.1 (CH2), ꢁ0.47 (CH); HRMS (ESI) m/z: 394.1328 (MþþNa),
C24H22NNaOP requires 394.1337. Enantiomeric excess (72%) was
determined by chiral HPLC (Chiralpak AD-H), hexane/iPrOH 85:15,
1 mL/min, major enantiomer tR¼21.4 min, minor enantiomer
tR¼20.3 min.
d 7.99e7.91 (m, 2H), 7.72e7.65 (m, 2H), 7.59e7.56 (m, 1H),
7.43e7.33 (m, 4H), 7.29e7.23 (m, 2H), 7.17e7.10 (m, 2H), 7.07e7.03
(s,1H), 6.36 (d, J¼2.3 Hz, 2H), 6.32 (t, J¼2.3 Hz,1H), 5.44 (t, J¼9.1 Hz,
1H) 3.65 (s, 6H), 3.46 (t, J¼8.3 Hz, 1H), 2.32 (s, 3H); 13C NMR
d 160.3
(C), 138.6 (d, JCeP¼5.5 Hz, C), 135.5 (CH), 133.0 (d, JCeP¼24.3 Hz, C),
132.5 (d, JCeP¼9.9 Hz, CH), 131.91 (CH), 131.88 (CH), 131.84 (CH),
131.7 (CH), 131.3 (d, JCeP¼24.5 Hz, C), 130.8 (CH), 128.4 (d,
JCeP¼2.6 Hz, CH), 128.3 (d, JCeP¼2.4 Hz, CH), 128.1 (CH), 127.0 (CH),
126.4 (CH), 124.0 (C), 109.3 (CH), 101.7 (CH), 88.7 (d, JCeP¼4.7 Hz, C),
84.8 (C), 55.3 (CH3), 44.3 (CH), 19.1 (CH3); HRMS (ESI) m/z: 504.1705
(MþþNa), C30H28NO3PNa requires 504.1704. Enantiomeric excess
(85%) was determined by chiral HPLC (Chiralpak AD-H), hex-
ane/iPrOH 85:15, 1 mL/min, major enantiomer tR¼24.2 min, minor
enantiomer tR¼27.7 min.
3.23. N-(3-(4-Methoxyphenyl)-1-o-toluylprop-2-ynyl)-P,P-
diphenylphosphinamide (3gb)
Mp 167e169 ꢀC; ½a D20
ꢃ
ꢁ55.5 (c 1.94, CHCl3, 90% ee); 1H NMR
d
8.07e8.00 (m, 2H), 7.81e7.75 (m, 2H), 7.68e7.65 (m, 1H),
7.51e7.42 (m, 4H), 7.37e7.32 (m, 2H), 7.26e7.11 (m, 5H), 6.78 (d,
J¼8.9 Hz, 1H), 5.51 (br t, J¼9.0 Hz, 1H), 3.78 (s, 3H), 3.54 (t, J¼8.0 Hz,
3.27. N-(3-(Thien-3-yl)-1-o-toluylprop-2-ynyl)-P,P-
diphenylphosphinamide (3gf)
1H), 2.40 (s, 3H); 13C NMR
d
159.5 (C),138.9 (d, JCeP¼5.6 Hz, C),135.5
(C), 133.0 (CH), 132.5 (d, JCeP¼9.8 Hz, CH), 131.9 (CH), 131.8 (d,
JCeP¼7.0 Hz, CH), 130.8 (CH), 128.4 (d, JCeP¼2.5 Hz, CH), 128.2 (d,
JCeP¼2.4 Hz, CH), 127.0 (CH), 126.3 (CH), 114.8 (C), 113.7 (CH), 87.7
(d, JCeP¼4.6 Hz, C), 84.8 (C), 55.2 (CH3), 44.4 (CH), 19.1 (CH3); HRMS
Mp 181e183 ꢀC; ½a D20
ꢃ
ꢁ53.8 (c 1.13, CHCl3, 83% ee); 1H NMR
d
8.05e7.98 (m, 2H), 7.81e7.74 (m, 2H), 7.65 (dd, J¼6.3, 2.7 Hz, 2H),
7.54e7.12 (m, 11H), 6.96 (dd, J¼5.1, 1.2 Hz), 5.50 (t, J¼9.0 Hz, 1H),
3.54 (br t, J¼7.8 Hz, 1H), 2.34 (s, 3H); 13C NMR
d138.6 (d,

2134
G. Blay et al. / Tetrahedron 68 (2012) 2128e2134
Lett. 2007, 9, 3477e3479; (o) Ruan, J.; Lu, G.; Xu, L.; Li, Y. M.; Chan, A. S. C. Adv.
Synth. Catal. 2008, 350, 76e84; (p) Yue, Y.; Turlington, M.; Yu, X. Q.; Pu, L. J. Org.
Chem. 2009, 74, 8681e8689; (q) Blay, G.; Cardona, L.; Fernandez, I.; Marco-
JCeP¼5.5 Hz, C), 135.5 (C) 132.5 (d, JCeP¼9.8 Hz, CH), 131.9 (d,
JCeP¼2.7 Hz, 2CH), 131.8 (d, JCeP¼9.8 Hz, CH), 130.8 (CH), 129.8 (CH),
128.8 (CH), 128.5 (2CH), 128.30 (CH), 127.29 (CH), 127.0 (CH), 126.4
(CH), 125.0 (CH), 121.7 (C), 88.6 (d, JCeP¼4.5 Hz, C), 80.2 (C), 44.4
(CH), 19.1 (CH3); HRMS (ESI) m/z: 428.1240 (MþþH), C26H23NOPS
requires 428.1238. Enantiomeric excess (83%) was determined by
chiral HPLC (Chiralpak AD-H), hexane/iPrOH 85:15, 1 mL/min,
major enantiomer tR¼22.05 min, minor enantiomer tR¼23.60 min.
~
Aleixandre, A.; Munoz, M. C.; Pedro, J. R. Org. Biomol. Chem. 2009, 7,
4301e4308; (r) Ito, J.; Asai, R.; Nishiyama, H. Org. Lett. 2010, 12, 3860e3862; (s)
Graham, E. R.; Tykwinski, R. R. J. Org. Chem. 2011, 76, 6574e6583 examples of
alkynylation of ketones; (t) Lu, G.; Li, X.; Li, Y. M.; Kwang, F. Y.; Chan, A. S. C. Adv.
Synth. Catal. 2006, 348, 1926e1933; (u) Chen, C.; Hong, L.; Xu, Z. Q.; Liu, L.;
Wang, R. Org. Lett. 2006, 8, 2277e2280; (v) Chinkov, N.; Warm, A.; Carreira, E.
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H.; Nie, J.; Zhang, W. Q.; Ma, J. A. Angew. Chem., Int. Ed. 2011, 50, 3538e3542; (x)
Tanaka, K.; Kukita, K.; Ichibasake, T.; Kotani, S.; Nakajima, M. Chem. Commun.
2011, 5614e5616.
3.28. 1,3-Diphenylprop-2-yn-1-amine (4)
3. (a) Zani, L.; Bolm, C. Chem. Commun. 2006, 4246e4275; (b) Blay, G.; Monleon,
A.; Pedro, J. R. Curr. Org. Chem. 2009, 13, 1498e1539.
Concentrated aqueous HCl (1 mL) was added to a solution of
compound 3aa (55 mg, 0.12 mmol, 84% ee) in MeOH (15 mL). After
2 h, the reaction mixture was concentrated under reduced pressure,
the residue was dissolved in 1 M HCl (6 mL) and the precipitated
was removed by filtration. The filtrated was basified with 2 M NaOH
(10 mL) and extracted with CH2Cl2 (3ꢂ20 mL). The organic phase
was dried over Na2SO4, filtered, and concentrated under reduced
pressure. Flash chromatography on silica gel eluting with hexane/
EtOAc (1:9) gave compound 4 (24.4 mg, 92%).18a
4. (a) Wei, C.; Li, C. J. J. Am. Chem. Soc. 2002, 124, 5638e5639; (b) Wei, C.; Mague, J.
T.; Li, C. J. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5749e5754.
5. Ji, J. X.; Wu, J.; Chan, A. S. C. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 11196e11200.
6. Bisai, A.; Singh, V. K. Org. Lett. 2006, 8, 2405e2408.
7. (a) Benaglia, M.; Negri, D.; Dell’Anna, G. Tetrahedron Lett. 2004, 45, 8705e8708;
(b) Colombo, F.; Benaglia, M.; Orlandi, S.; Usuelli, F.; Celentano, G. J. Org. Chem.
2006, 71, 2064e2070; (c) Orlandi, S.; Colombo, F.; Benaglia, M. Synthesis 2005,
1689e1692.
8. (a) Gommermann, N.; Koradin, C.; Polborn, K.; Knochel, P. Angew. Chem., Int. Ed.
2003, 42, 5763e5766; (b) Gommermann, N.; Knochel, P. Chem. Commun. 2004,
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Gommermann, N.; Knochel, P. Chem.dEur. J. 2006, 12, 4380e4392.
½
a 2D0
ꢃ
ꢁ21.7 (c 0.9, CHCl3, 84% ee), lit.18a
½
a 2D0
ꢃ
ꢁ27 (c 0.6, CHCl3,
€
9. (a) Knopfel, T. P.; Aschwanden, P.; Ichikawa, T.; Carreira, E. M. Angew. Chem., Int.
99% ee) for the S enantiomer.
Ed. 2004, 43, 5971e5973; (b) Aschwanden, P.; Stephenson, C. R. J.; Carreira, E.
M. Org. Lett. 2006, 8, 2437e2440.
10. (a) Dodda, R.; Zhao, C. G. Org. Lett. 2007, 9, 165e167; (b) Dodda, R.; Zhao, C. G.
Tetrahedron Lett. 2007, 48, 4339e4342.
Acknowledgements
11. Traverse, J. F.; Hoveyda, A. H.; Snapper, M. L. Org. Lett. 2003, 5, 3273e3275.
12. Jiang, B.; Si, Y. G. Angew. Chem., Int. Ed. 2004, 43, 216e218.
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6903e6906; (b) De Armas, P.; Tejedor, D.; García-Tellado, F. Angew. Chem., Int.
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ꢀ
Financial support from the Ministerio de Ciencia e Innovacion
and FEDER (CTQ2009-13083) and from Generalitat Valenciana
(ACOMP/2011/267) is acknowledged. AM thanks the Generalitat
Valenciana for a pre-doctoral grant.
15. Wu, T. R.; Chong, J. M. Org. Lett. 2006, 8, 15e18.
16. Gonzalez, A. Z.; Canales, E.; Soderquist, J. A. Org. Lett. 2006, 8, 3331e3334.
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5593e5596.
Supplementary data
18. (a) Yan, W.; Mao, B.; Zhu, S.; Jiang, X.; Liu, Z.; Wang, R. Eur. J. Org. Chem. 2009,
3790e3794; (b) Zhu, S.; Yan, W.; Mao, B.; Jiang, X.; Wang, R. J. Org. Chem. 2009,
74, 6980e6985.
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Asymmetry 2010, 21, 2037e2042.
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(b) Weinreb, S. M.; Orr, R. K. Synthesis 2005, 1205e1227.
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Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2012.01.037. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
References and notes
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