Synthesis of aryl anti -vicinal diamines via aza-brook rearrangement-initiated nucleophilic addition of α-silylamines to imines

Article abstract of DOI:10.1021/acs.joc.5b00255

An efficient protocol is described for the synthesis of vicinal diamines via aza-Brook rearrangement-initiated nucleophilic addition of α-silylamines to imines. Various symmetrical and unsymmetrical aryl diamine derivatives were prepared in moderate to hi

Full text of DOI:10.1021/acs.joc.5b00255

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Note
Synthesis of Aryl anti-Vicinal Diamines via Aza-Brook Rearrangement-
Initiated Nucleophilic Addition of alpha-Silylamines to Imines
Chao-Yang Lin, Zhao Sun, Yan-Jun Xu, and Chong-Dao Lu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b00255 • Publication Date (Web): 10 Mar 2015
Downloaded from http://pubs.acs.org on March 16, 2015
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Synthesis
of
Aryl
anti-Vicinal
Diamines
via
Aza-Brook
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Rearrangement-Initiated Nucleophilic Addition of α-Silylamines to Imines
Chao-Yang Lin,† Zhao Sun,‡ Yan-Jun Xu,*,† and Chong-Dao Lu*,†,‡
†The Key Laboratory of Plant Resources and Chemistry of Arid Zones, Xinjiang Technical
Institute of Physics & Chemistry, Chinese Academy of Sciences, Urumqi 830011, China
and University of the Chinese Academy of Sciences
‡Department of Chemistry and Applied Chemistry, Changji University, Changji 831100,
China
*E-mail: xuyj@ms.xjb.ac.cn
*E-mail: clu@ms.xjb.ac.cn
ABSTRACT: An efficient protocol is described for the synthesis of vicinal diamines via
aza-Brook rearrangement-initiated nucleophilic addition of α-silylamines to imines. Various
symmetrical and unsymmetrical aryl diamine derivatives were prepared in moderate to high
yields with high anti/syn diasteroselectivity.
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The structural unit of vicinal diamines is present in a broad range of bioactive molecules
as well as in ligands and organocatalysts useful in asymmetric catalysis.1–8 Tremendous
efforts have been made by synthetic community to prepare this structural motif, in which
the most effective synthetic protocols include diaza-Cope rearrangement,9 direct alkene
diamination,7, 10–12 imine-imine coupling,13 and aza-Henry/nitro-reduction cascades.14–17
Moreover, as a straightforward approach toward the synthesis of non-symmetric
1,2-diamines, direct nucleophilic addition of an α-amino carbanion or its equivalent to
imines is also notable, however, which shows syn selectivity in most cases.18–24
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Here we describe anti-selective synthesis of symmetrical and unsymmetrical
1,2-diaryl-1,2-diamines using aryl α-silylamine as a precursor of the α-amino anion
(Scheme 1). In this process, a base-induced [1,2]-aza-Brook rearrangement25–28 of aryl
α-silylamine 1 afford the α-amino carbanion A2 that is subsequently intercepted by the
imine 2 to give the anti-diamine 3 after desilylation. The stereochemical outcome may be
rationalized by considering that the coupling of A2 and 2 occurs via open transition state A3
to minimize the nonbonding interactions between the N-diphenylphosphinyl group of the
imine and the highly hindered silylamino group of the α-amino carbanion. Notably, the
described synthetic protocol represents one of the few applications of the discovery by
Brook and co-workers29, 30 in 1974 that 1,2-silyl migration of α-silylamines from carbon to
nitrogen can occur in the presence of suitable bases.31–38
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Scheme 1. [1,2]-Aza-Brook Rearrangement-Initiated Nucleophilic Addition of
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α-Silylamines to Imines for the Synthesis of Vicinal Diamines
Ar2
Ar1
Ar2
Ar1
SiR'3
Ar2
Ar1
[1,2]-aza-Brook
rearrangement
NH
SiR'3
N
N
base
SiR'3
1
A1
A2
DPP
N
R = Ar, or tBu
DPP = Ph2P(O)
2
R
N
Ar2
SiR'3
Ar2
SiR'3
R
Ar2
Ar1
N
R
NH
acid workup
desilylation
H
Ar1
O
R
Ar1
H
N
N
HN
P
DPP
DPP
4
Ph
3
Ph
A3
Our preliminary investigations indicated that potassium hexamethyldisilazide (KHMDS)
can efficiently trigger the envisaged [1,2]-aza-Brook rearrangement of N-phenyl α-phenyl
α-silylamines 1a to give N-phenylbenzylamine (5), whereas nBuLi or tBuLi can not.39, 40
Thus, further study of the reactivity of α-silylamines and imines was conducted using
KHMDS as a base. We quickly recognized that the N-protecting groups on both 1 and 2
(Scheme 1) are critical to the success of the desired transformations. The anticipated
coupling reaction occurred when N-aryl α-silylamine and N-diphenylphosphinyl ('N-DPP')
imine were used simultaneously. For example, using 1a and 2a as coupling partners gave
the desired vicinal diamine 3a in 80% yield with 10:1 dr after quenching with 1 N HCl
(Scheme 2, only the major diamine diastereomer is shown in eq 1). The stereochemistry of
the predominant diastereomer 3a was assigned to be anti based on X-ray crystallography.41
o
o
Carrying out the reaction at 0 C or at –78 C led to similar yields and drs. Replacing the
N-DPP imine 2a with other activated imines such as N-Ts and N-Boc imines did not
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generate any coupling products; instead, the benzylamine 5 was detected in the resulting
complex mixtures.42 The formation of the desilylation product 5 may reflect the abstraction
of a proton from the reaction mixture by the α-amino carbanion intermediate (Scheme 1,
A2), given that other suitable electrophiles were absent. Overwhelming desilylation was
also observed when KHMDS and 2a were added stepwise to the THF solution of 1a, which
failed to give any 1,2-diamine 3a (eq 2). Replacing the N-phenyl α-silylamine 1a with N-Bz
or N-tert-butylsulfinyl analogues yielded complex mixtures of unidentified products.43
Attempts to improve yield and diastereoselectivity by introducing Lewis acids44 such as
ZnBr2 and BF3·Et2O proved unsuccessful; these acids completely inhibited the reaction.
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Scheme 2. Initial Results and Control Experiments
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Control experiments were conducted to verify the reaction mechanism. To confirm that
the presumed C→N silyl migration actually occurred, we quenched the reaction with
aqueous NaHCO3 rather than 1 N HCl solution and obtained the N-silyl diamine 4a (eq 1).
To rule out the possibility that the coupling reaction was initiated by deprotonation at the
α-position of the α-silylamine, we labelled N-phenyl α-silylamine with deuterium on the
α-carbon (d-1a) and coupled it to the imine 2a to afford the vicinal diamine d-3a or the
N-silyl diamine d-4a with the deuterium intact (eq 3). Coupling 1a and 2a in the presence of
CsF was examined,40 and predominantly benzylamine 5 formed; the coupling product 3a
was obtained in low yield (24%) with poor diastereocontrol (1.2:1 dr) showing syn
selectivity (eq 4). In this case, the intermediate N-H α-amino carbanion generated from
fluoride-induced desilylation did not show good stereocontrol in the coupling with N-DPP
imine. This indicates that in our protocol, the N-silyl group on the α-amino carbanion
(Scheme 1, A2) is important for achieving high anti diastereoselectivity.
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Next, we examined the scope and limitations for the coupling of N-aryl α-silylamines and
N-DPP imines. We were pleased to observe that the anti-selective protocol for synthesizing
aryl 1,2-diamines was versatile (Table 1). A range of aryl N-DPP imines coupled efficiently
with α-silylamine 1a to generate the desired products in 50–90% yields with high
diastereoselectivities of 8:1 to >20:1 dr (entries 1–11). Bulky tert-butyl N-DPP imine 2l was
also a suitable substrate and efficiently coupled with 1a (90% yield, 14:1 dr, entry 12).
Notably, enolizable N-DPP imine derived from cyclohexanecarboxaldehyde was not
tolerated under these reaction conditions. The α-silylamines 1a–l were prepared by
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nucleophilic addition of PhMe2Si-MgiPr·LiCl or PhMe2Si-Bpin (pin = pinacolato) to the
corresponding aryl adimines45–51 then used in the coupling protocol to afford aryl vicinal
diamines in 63–93% yield with diastereoselectivities ranging from 6:1 to >20:1 (entries
13–23).52 Together, these studies suggest that a variety of symmetrical and unsymmetrical
aryl anti-1,2-diamines can easily be synthesized by selecting the appropriate coupling
partners.
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Table 1. Substrate Scope for the Coupling of α-Silylamines and Imines
entry Ar
R
product yieldc
drd
1
2
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4
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7
8
Ph (1a)
4-MeOC6H4 (2a)
Ph (2b)
80%
10:1
3a
3b
3c
3d
3e
3f
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
80% (70%)b 11:1
4-MeC6H4 (2c)
2-MeC6H4 (2d)
3-MeOC6H4 (2e)
4-BrC6H4 (2f)
4-FC6H4 (2g)
4-ClC6H4 (2h)
87%
59%
83%
66%
90%
77%
>20:1
8:1
14:1
20:1
>20:1
14:1
3g
3h
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Ph (1a)
1-naph (2i)
2-furyl (2j)
2-thienyl (2k)
tBu (2l)
61%
50%
60%
90%
58%e
93%e
64%e
69%
70%
63%
77%e
79%
70%
90%
90%e
9:1
3i
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Ph (1a)
10:1
14:1
14:1
8:1
3j
Ph (1a)
3k
3l
Ph (1a)
4-MeOC6H4 (1b)
4-FC6H4 (1c)
4-BrC6H4 (1d)
4-ClC6H4 (1e)
3-BrC6H4 (1f)
4-tBuC6H4 (1g)
3-MeOC6H4 (1h)
3-MeC6H4 (1i)
2-MeC6H4 (1j)
Ph (2b)
3m
3n
3o
3p
3q
3r
3s
Ph (2b)
11:1
6:1
Ph (2b)
Ph (2b)
10:1
8:1
Ph (2b)
Ph (2b)
10:1
10:1
>20:1
11:1
20:1
10:1
Ph (2b)
Ph (2b)
3t
Ph (2b)
3u
3v
3w
3,5-diMeC6H3 (1k) Ph (2b)
3,4-diMeC6H3 (1l) Ph (2b)
a All reactions were carried out with α-silylamine 1 (0.20 mmol), N-DPP imine 2 (0.30 mmol), KHMDS
b
(0.50 mmol), and dry THF (2.0 mL) under argon. Crude α-silylamine 1a prepared by reacting
c
d
PhMe2Si-MgiPr·LiCl with N-benzylideneaniline was used. Isolated yield of major diastereoisomers.
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1
e
Anti:syn ratios were determined by H NMR analysis of crude reaction mixtures. Isolated yield of an
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inseparable mixture of diastereoisomers. f N-PMP α-silylamine was used instead of N-Ph α-silylamine.
To elucidate the potential synthetic applications of this process, the anti-1,2-diamine 3x
was prepared in 85% yield by combining N-PMP α-silylamine 1m and N-DPP imine 2c in
the presence of KHMDS. The coupling product 3x was converted to the corresponding
imidazolidinone 6 in order to remove the nitrogen-protecting groups.53 Then 6 was treated
with NaOMe to remove the DPP group and with CAN (cerium ammonium nitrate) to
remove the PMP group. Finally, acidic hydrolysis (HBr/HOAc) produced the free diamine
7.
Scheme 3. Deprotection of Nitrogen Substituents of anti-Vicinal Diamines
In summary, we have developed a new method for the synthesis of aryl vicinal diamines
involving the coupling of N-aryl α-silylamines and N-DPP imines. This transformation
relies on base-induced [1,2]-aza-Brook rearrangement to generate N-silyl α-amino
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carbanion in situ, and it provides access to symmetrical and unsymmetrical aryl
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1,2-diamines with high anti/syn diasteroselectivity.
EXPERIMENTAL SECTION
General Methods. All commercially available reagents were used without further
purification unless otherwise stated. THF was freshly distilled from sodium-benzophenone
under argon atmosphere. All reactions were carried out under an argon atmosphere in
flame-dried glassware under positive pressure of argon with magnetic stirring using
standard Schlenk techniques. Column chromatography was performed on silica gel
(200-300 mesh). Visualization on TLC (analytical thin layer chromatography) was achieved
by the use of UV light (254 nm) and treatment with aqueous ceric ammonium molybdate or
1
KMnO4 followed by heating. H NMR spectra were recorded on a 400 MHz NMR
spectrometer and 13C NMR spectra were recorded on a 100 MHz with solvent resonance as
the internal standard (1H NMR: CDCl3 at 7.26 ppm, C6D6 at 7.16 ppm; 13C NMR: CDCl3 at
77.1 ppm, C6D6 at 128.0 ppm). NMR data are reported as follows: chemical shift,
multiplicity (br = broad singlet, s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet), coupling constant (Hz) and integration. High-resolution mass spectra (HRMS)
were recorded using electron spray ionization (ESI) with a time-of-flight mass analyzer.
Diphenylphosphinyl aldimines were synthesized using the procedure of Jennings and
co-workers.54 PhMe2SiLi (appro. 1.0 M solution in THF) was prepared according to the
procedure of Fleming and co-workers.55
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General procedure for the preparation of α-Silylamine 1:
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Method A: A flame-dried Schlenk tube equipped with a magnetic stirring bar was
successively charged with PhMe2SiLi (appro. 1.0 M solution in THF, 0.60 mmol, 1.5 equiv)
and i-PrMgCl (2.0 M solution in THF, 0.60 mmol, 1.5 equiv), the reaction mixture was
maintained at 0 oC for 15 min, then the imine (0.40 mmol, 1.5 equiv) in 2.0 mL of toluene is
added via syringe. The reaction is subsequently maintained at 0 °C until full conversion
(TLC monitoring). The reaction was quenched with saturated aqueous ammonium chloride
and extracted with ethyl acetate (3 times). The organic extracts were washed with brine,
dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The α-silylated amine
(1a–c, 1g–n) was purified by flash column chromatography on silica gel using
hexanes/dichloromethane = 5/1 as eluent.
Method B: To a flame-dried Schlenk flask were added CuCN (0.020 mmol, 5.0 mol%)
and NaOMe (0.040 mmol, 10 mol%). After addition of THF (1.0 mL), the reaction mixture
was maintained at room temperature for 1 h. At 0 °C, Me2PhSiBpin (0.60 mmol, 1.5 equiv)
and imine (0.40 mmol) in THF (1.0 mL) were added via syringe followed by MeOH (1.60
mmol, 4 equiv) and the reaction was subsequently maintained until full conversion (TLC
monitoring). Evaporation of the solvents under reduced pressure afforded α-silylated amine
(1d-f) as the crude product which was purified by flash column chromatography using
hexanes/dichloromethane = 5/1 as eluent.
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N-(Phenyl)-α-(phenyldimethylsilyl)-benzylamine (1a). Pale yellow oil (112 mg, 90%); Rf
= 0.60 (hexanes/ethyl acetate = 20/1); 1H NMR (400 MHz, CDCl3): δ = 7.34–7.15 (m, 5H),
7.10–7.00 (m, 2H), 7.00–6.90 (m, 3H), 6.85 (t, J = 7.7 Hz, 2H), 6.41 (t, J = 7.3 Hz, 1H),
6.29 (d, J = 8.3 Hz, 2H), 3.99 (d, J = 5.8 Hz, 1H), 3.92 (d, J = 5.5 Hz, 1H), 0.17 (s, 3H),
0.10 (s, 3H). 13C NMR (100 MHz, CDCl3): δ = 148.6, 142.2, 135.2, 134.5, 129.9, 129.1,
128.3, 128.2, 126.1, 125.6, 117.3, 113.6, 50.3, –4.2, –5.3. HRMS (ESI-TOF): calculated for
C21H24NSi [M+H]+: m/z = 318.1673, found 318.1667.
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N-(Phenyl)-α-(phenyldimethylsilyl)-4-methoxybenzylamine (1b). Yellow oil (115 mg,
83%); Rf = 0.35 (hexanes/ethyl acetate = 20/1); 1H NMR (400 MHz, CDCl3): δ = 7.37–7.17
(m, 5H), 6.93–6.81 (m, 4H), 6.62 (d, J = 8.7 Hz, 2H), 6.44 (t, J = 7.3 Hz, 1H), 6.33 (d, J =
7.9 Hz, 2H), 3.96 (s, 1H), 3.60 (s, 3H), 0.19 (s, 3H), 0.13 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ = 157.7, 148.5, 135.3, 134.5, 133.7, 129.8, 129.0, 128.1, 127.0, 117.4, 113.8,
113.7, 55.3, 49.6, –4.3, –5.2; HRMS (ESI-TOF): calculated for C22H26NOSi [M+H]+: m/z =
348.1778, found 348.1773.
N-(Phenyl)-α-(phenyldimethylsilyl)-4-fluorobenzylamine (1c). Yellow oil (80.3 mg,
60%); Rf = 0.67 (hexanes/ethyl acetate = 20/1); 1H NMR (400 MHz, CDCl3): δ = 7.50–7.40
(m, 5H), 7.11–7.03 (m, 4H), 6.95 (t, J = 8.7 Hz, 2H), 6.66 (t, J = 7.3 Hz, 1H), 6.50 (d, J =
8.0 Hz, 2H), 4.18 (s, 1H), 0.39 (s, 3H), 0.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ =
161.2 (d, JC-F = 241.5 Hz), 148.3, 137.6, 134.9, 134.4, 130.0, 129.1, 128.3, 127.4 (d, JC-F
=
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7.7 Hz), 117.6, 115.1 (d, JC-F = 24.8 Hz), 113.7, 49.8, –4.5, –5.2; HRMS (ESI-TOF):
calculated for C21H23FNSi [M+H]+: m/z = 336.1578, found 336.1590.
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N-(Phenyl)-α-(phenyldimethylsilyl)-4-bromobenzylamine (1d). Yellow oil (94.4 mg,
60%); Rf = 0.62 (hexanes/ethyl acetate = 20/1); 1H NMR (400 MHz, CDCl3): δ = 7.36–7.18
(m, 5H), 7.06 (d, J = 8.4 Hz, 2H), 6.95–6.85 (m, 4H), 6.49 (t, J = 7.3 Hz, 1H), 6.31 (d, J =
7.9 Hz, 2H), 4.00 (s, 2H), 0.22 (s, 3H), 0.15 (s, 3H); 13C NMR (100 MHz, CDCl3): δ =
148.2, 141.5, 134.7, 134.4, 131.4, 130.1, 129.1, 128.3, 127.7, 119.1, 117.7, 113.6, 50.0, –4.5,
–5.3; HRMS (ESI-TOF): calculated for C21H23BrNSi [M+H]+: m/z = 396.0778, found
396.0770.
N-(Phenyl)-α-(phenyldimethylsilyl)-4-chlorobenzylamine (1e). Yellow oil (111 mg,
79%); Rf = 0.66 (hexanes/ethyl acetate = 20/1); 1H NMR (400 MHz, CDCl3): δ = 7.36–7.18
(m, 5H), 7.06 (d, J = 8.4 Hz, 2H), 6.95–6.80 (m, 4H), 6.49 (t, J = 7.3 Hz, 1H), 6.31 (d, J =
7.9 Hz, 2H), 4.00 (s, 2H), 0.22 (s, 3H), 0.15 (s, 3H); 13C NMR (100 MHz, CDCl3): δ =
148.2, 140.9, 134.7, 134.4, 131.1, 130.1, 129.1, 128.5, 128.2, 127.4, 117.7, 113.6, 50.0, –4.5,
–5.2; HRMS (ESI-TOF): calculated for C21H22ClNNaSi [M+Na]+: m/z = 374.1102, found:
374.1084.
N-(Phenyl)-α-(phenyldimethylsilyl)-3-bromobenzylamine (1f). Yellow oil (130 mg,
82%); Rf = 0.58 (hexanes/ethyl acetate = 20/1); 1H NMR (400 MHz, CDCl3): δ = 7.53–7.40
(m, 5H), 7.32–7.24 (m, 2H), 7.15–7.05 (m, 4H), 6.68 (t, J = 7.3 Hz, 1H), 6.51 (d, J = 7.8 Hz,
2H), 4.16 (s, 1H), 0.42 (s, 3H), 0.35 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 148.2, 145.1,
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134.6, 134.4, 130.2, 129.9, 129.2, 129.0, 128.7, 128.3, 124.7, 122.7, 117.7, 113.6, 50.3, –4.5,
–5.3; HRMS (ESI-TOF): calculated for C21H23BrNSi [M+H]+: m/z = 396.0778, found
396.0792.
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N-(Phenyl)-α-(phenyldimethylsilyl)-4-tert-butylbenzylamine (1g). Yellow oil (132 mg,
88%); Rf = 0.50 (hexanes/ethyl acetate = 40/1); 1H NMR (400 MHz, CDCl3): δ = 7.32–7.17
(m, 5H), 7.08 (d, J = 8.4 Hz, 2H), 6.92–6.82 (m, 4H), 6.45 (t, J = 7.3 Hz, 1H), 6.35 (d, J =
7.7 Hz, 2H), 3.99 (s, 1H), 1.14 (s, 9H), 0.19 (s, 3H), 0.13 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ = 148.6, 148.2, 138.7, 135.6, 134.5, 129.8, 129.1, 128.1, 125.8, 125.1, 117.4,
113.7, 49.9, 34.4, 31.6, –4.1, –5.2; HRMS (ESI-TOF): calculated for C25H32NSi [M+H]+:
m/z = 374.2299, found 374.2289.
N-(Phenyl)-α-(phenyldimethylsilyl)-3-methoxybenzylamine (1h). Yellow oil (121 mg,
87%); Rf = 0.52 (hexanes/ethyl acetate = 20/1); 1H NMR (400 MHz, CDCl3): δ = 7.33–7.29
(m, 2H), 7.25–7.18 (m, 3H), 6.99 (t, J = 7.9 Hz, 1H), 6.88 (t, J = 7.8 Hz, 2H), 6.57 (d, J =
7.6 Hz, 1H), 6.51 (dd, J = 8.1, 2.5 Hz, 1H), 6.49 – 6.41 (m, 2H), 6.34 (d, J = 8.0 Hz, 2H),
3.99 (s, 2H), 3.51 (s, 3H), 0.21 (s, 3H), 0.14 (s, 3H); 13C NMR (100 MHz, CDCl3): δ =
159.7, 148.7, 144.1, 135.3, 134.5, 129.9, 129.3, 129.1, 128.1, 118.6, 117.4, 113.2, 111.6,
111.1, 55.1, 50.5, –4.3, –5.2; HRMS (ESI-TOF): calculated for C22H26NOSi [M+H]+: m/z =
348.1778, found 348.1775.
N-(Phenyl)-α-(phenyldimethylsilyl)-3-methylbenzylamine (1i). Yellow oil (111 mg,
84%); Rf = 0.70 (hexanes/ethyl acetate = 40/1); 1H NMR (400 MHz, CDCl3): δ = 7.55–7.40
(m, 5H), 7.19 (t, J = 7.5 Hz, 1H), 7.15–7.09 (m, 2H), 6.99 (t, J = 8.0 Hz, 2H), 6.94 (s, 1H),
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6.67 (t, J = 7.3 Hz, 1H), 6.56 (d, J = 7.7 Hz, 2H), 4.20 (s, 2H), 2.33 (s, 3H), 0.42 (s, 3H),
0.35 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 148.7, 142.0, 137.7, 135.4, 134.5, 129.9,
129.1, 128.2, 128.1, 126.9, 126.4, 123.3, 117.3, 113.6, 50.3, 21.7, –4.3, –5.3; HRMS
(ESI-TOF): calculated for C22H26NSi [M+H]+: m/z = 332.1829, found 332.1824.
N-(Phenyl)-α-(phenyldimethylsilyl)-2-methylbenzylamine (1j). Yellow oil (109 mg,
82%); Rf = 0.62 (hexanes/ethyl acetate = 40/1); 1H NMR (400 MHz, CDCl3): δ = 7.55–7.35
(m, 5H), 7.15–7.10 (m, 6H), 6.62 (t, J = 7.3 Hz, 1H), 6.45 (d, J = 8.0 Hz, 2H), 4.43 (s, 1H),
4.20 (br, 1H), 2.30 (s, 3H), 0.39 (s, 3H), 0.35 (s, 3H); 13C NMR (100 MHz, CDCl3): δ =
148.5, 140.2, 135.5, 134.6, 134.1, 130.4, 129.9, 129.0, 128.1, 126.3, 125.9, 125.4, 117.4,
113.3, 45.7, 20.0, –4.1, –5.2; HRMS (ESI-TOF): calculated for C22H26NSi [M+H]+: m/z =
332.1829, found 332.1815.
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N-(Phenyl)-α-(phenyldimethylsilyl)-3,5-dimethylbenzylamine (1k). Yellow oil (123 mg,
87%); Rf = 0.55 (hexanes/ethyl acetate = 40/1); 1H NMR (400 MHz, CDCl3): δ = 7.54–7.38
(m, 5H), 7.13–7.06 (m, 2H), 6.81 (s, 1H), 6.74 (s, 2H), 6.66 (t, J = 7.3 Hz, 1H), 6.56 (d, J =
7.7 Hz, 2H), 4.13 (s, 1H), 2.28 (s, 6H), 0.39 (s, 3H), 0.33 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ = 148.9, 141.9, 137.5, 135.5, 134.5, 129.8, 129.0, 128.0, 127.3, 124.1, 117.3,
113.6, 50.3, 21.5, –4.3, –5.3; HRMS (ESI-TOF): calculated for C23H28NSi [M+H]+: m/z =
346.1986, found 346.1982.
N-(Phenyl)-α-(phenyldimethylsilyl)-4,5-dimethylbenzylamine (1l). Yellow oil (117 mg,
82%); Rf = 0.60 (hexanes/ethyl acetate = 40/1); 1H NMR (400 MHz, CDCl3): δ = 7.57–7.37
(m, 5H), 7.12–7.00 (m, 3H), 6.88 (d, J = 6.8 Hz, 2H), 6.64 (t, J = 7.3 Hz, 1H), 6.54 (d, J =
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7.9 Hz, 2H), 4.14 (s, 1H), 2.25 (s, 3H), 2.21 (s, 3H), 0.38 (s, 3H), 0.32 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ = 148.7, 139.2, 136.1, 135.6, 134.5, 133.6, 129.8, 129.6, 129.1, 128.0,
127.6, 123.6, 117.3, 113.7, 50.0, 20.0, 19.5, –4.2, –5.2; HRMS (ESI-TOF): calculated for
C23H27NNaSi [M+Na]+: m/z = 368.1805, found 368.1801.
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N-(4-Methoxyphenyl)-α-(phenyldimethylsilyl)-benzylamine (1m). Yellow oil (98.7 mg,
79%); Rf = 0.45 (hexanes/ethyl acetate = 20/1); 1H NMR (400 MHz, CDCl3): δ = 7.65–7.48
(m, 5H), 7.40–7.34 (m, 2H), 7.30–7.20 (m, 3H), 6.78 (d, J = 8.9 Hz, 2H), 6.58 (d, J = 8.6
Hz, 2H), 4.26 (s, 1H), 3.80 (s, 3H), 0.49 (s, 3H), 0.43 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ = 152.1, 142.2, 135.4, 134.5, 133.2, 129.9, 128.3, 128.1, 126.3, 125.6, 122.3, 114.8, 55.8,
51.3, –4.2, –5.3; HRMS (ESI-TOF): calculated for C22H26NOSi [M+H]+: m/z = 348.1778,
found 348.1773.
N-(Phenyl)-α-(phenyldimethylsilyl)-α-D-benzylamine (d-1a). Yellow oil (114 mg, 89%);
Rf = 0.55 (hexanes/ethyl acetate = 40/1); 1H NMR (400 MHz, CDCl3): δ = 7.30–7.14 (m,
5H), 7.02 (t, J = 7.4 Hz, 2H), 6.95 – 6.85 (m, 3H), 6.83 (t, J = 7.9 Hz, 2H), 6.40 (t, J = 7.3
Hz, 1H), 6.28 (d, J = 8.2 Hz, 2H), 4.04 (br, 1H), 0.15 (s, 3H), 0.08 (s, 3H); 13C NMR (100
MHz, CDCl3): δ = 148.5, 142.1, 135.2, 134.4, 129.9, 129.1, 128.3, 128.1, 126.1, 125.6,
117.4, 113.6, 49.8 (t, JC-D = 31.4 Hz), –4.3, –5.2; HRMS (ESI-TOF): calculated for
C21H22DNNaSi [M+Na]+: m/z = 341.1555, found 341.1562.
N-(2-(N-(Phenyl)-N-(phenyldimethylsilyl))-1-(4-methoxyphenyl)-2-phenylethyl)-P,P-di
phenylphosphinic amide (4a)
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1a (0.20 mmol, 63.5 mg) and 2a (0.30 mmol, 101 mg, 1.5 equiv) were dissolved in 2.0 mL
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of THF in a flame-dried Schlenk flask under argon. At 0 C, KHMDS (0.5 M solution in
toluene, 0.50 mmol) was added dropwise to the solution via syringe and the reaction
mixture was stirred for 1 h, then it was quenched by the addition of 1.0 mL of saturated
aqueous sodium bicarbonate. The reaction mixture was extracted with EtOAc, and the
combined organic layers were washed with brine and dried over anhydrous sodium sulfate,
filtered, and concentrated under vacuum. The residue was purified by flash column
chromatography using (hexanes/ethyl acetate/triethylamine=100/50/1) as eluent to give 4a
(108 mg, 83%) as a pale yellow solid; mp 55−57 °C; Rf = 0.25 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, C6D6): δ = 7.43–7.37 (m, 3H), 7.37–7.32 (m, 3H), 7.32–7.25 (m, 2H),
7.23 7.16 (m, 8H), 6.99–6.79 (m, 9H), 6.72 (dd, J = 12.6, 7.5 Hz, 4H), 5.18–5.06 (m, 1H),
4.92 (d, J = 10.7 Hz, 1H), 3.41 (s, 3H), 2.98 (t, J = 8.0 Hz, 1H), 0.11 (s, 3H), 0.09 (s, 3H);
13C NMR (100 MHz, C6D6): δ = 159.4, 143.4, 141.5, 138.9, 135.8, 135.3, 134.9, 134.7,
134.5, 133.8, 133.4, 132.8 (d, JC-P = 9.6 Hz), 131.8 (d, JC-P = 9.9 Hz), 131.1, 131.0 (d, JC-P
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9.9 Hz), 130.7, 130.6, 129.4, 128.2, 127.7, 127.3, 125.7, 113.8, 68.5, 55.4, 55.0, 0.0, –0.6;
HRMS (ESI-TOF): calculated for C41H42N2O2PSi [M+H]+: m/z = 653.2748, found:
653.2732.
N-(2-(N-(Phenyl)-N-(phenyldimethylsilyl))-1-(4-methoxyphenyl)-2-D-2-phenylethyl)-P,
P-diphenylphosphinic amide (d-4a). Pale yellow solid; mp 58−59 °C; Rf = 0.25
(hexanes/ethyl acetate = 1/1); 1H NMR (400 MHz, C6D6): δ = 7.44–7.32 (m, 6H), 7.22–7.24
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(m, 2H), 7.24–7.16 (m, 8H), 6.99–6.90 (m, 5H), 6.90–6.79 (m, 4H), 6.76–6.67 (m, 4H),
5.11 (t, J = 8.0 Hz, 1H), 3.41 (s, 3H), 2.98 (t, J = 8.0 Hz, 1H), 0.11 (s, 3H), 0.09 (s, 3H); 13C
NMR (100 MHz, C6D6): δ = 159.4, 143.4, 141.4, 138.9, 135.7, 135.2, 134.9, 134.6, 134.5,
133.8, 133.4, 132.8 (d, JC-P = 9.7 Hz), 131.8 (d, JC-P = 9.9 Hz), 131.1, 131.0 (d, JC-P = 12.3
Hz), 130.7, 130.6, 129.4, 128.2, 127.7, 127.3, 125.7, 113.8, 68.0, 55.3, 55.0, 0.0, –0.6;
HRMS (ESI-TOF): calculated for C41H41DN2O2PSi [M+H]+: m/z = 654.2810, found:
654.2812.
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General procedure for the preparation of 3. 1 (0.20 mmol) and 2 (0.30 mmol, 1.5 equiv)
were dissolved in 2.0 mL of THF in a flame-dried Schlenk flask under argon. Then
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KHMDS (0.50 mmol) was added dropwise via syringe at 0 C, the reaction mixture was
stirred for 1h and quenched by the addition of 2.0 mL of 1.0 M solution of HCl, the
resulting heterogeneous mixture was allowed to warm to room temperature and stirred for
an additional 0.5 h. The reaction mixture was extracted with EtOAc (3×15 mL), the
combined organic layers were washed with aqueous sodium bicarbonate and brine, dried
over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was
purified by column chromatography.
anti-N-(2-(N-(Phenyl)-1-(4-methoxyphenyl)-2-phenylethyl)-P,P-diphenylphosphinic
amide (anti-3a). White solid (83.3 mg, 80%) ; mp 242−243 °C; Rf = 0.55 (hexanes/ethyl
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acetate = 1/1); H NMR (400 MHz, CDCl3): δ = 7.95–7.85 (m, 2H), 7.83–7.73 (m, 2H),
7.57–7.41 (m, 4H), 7.35–7.28 (m, 2H), 7.20–7.10 (m, 3H), 7.05 (t, J = 7.9 Hz, 2H),
6.95–6.80 (m, 6H), 6.65 (d, J =7.6 Hz, 1H), 6.63–6.54 (m, 3H), 4.84–4.68 (m, 2H), 3.84 (s,
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3H), 3.33 (dd, J = 12.0, 7.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 158.9, 147.0, 137.4,
133.4, 132.8 (d, JC-P = 9.8 Hz), 132.40 (d, JC-P = 7.8 Hz), 132.3 (d, JC-P = 2.7 Hz), 132.2 (d,
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C-P = 2.7 Hz), 132.1, 131.62 (d, JC-P = 9.7 Hz), 131.55, 130.2, 129.1, 128.9, 128.7 (d, JC-P =
9.7 Hz), 128.6, 128.4, 128.1 (d, JC-P = 9.7 Hz), 127.5, 116.8, 113.6, 113.5, 63.1, 59.1, 55.4;
HRMS (ESI-TOF): calculated for C33H31N2NaO2P [M+Na]+: m/z = 541.2015, found
541.2024.
syn-N-(2-(N-(Phenyl)-1-(4-methoxyphenyl)-2-phenylethyl)-P,P-diphenylphosphinic
amide (syn-3a). White solid (7.6 mg, 7%) ; mp 203−205 °C; Rf = 0.56 (hexanes/ethyl
acetate = 1/1); 1H NMR (400 MHz, CDCl3): δ = 7.83–7.66 (m, 4H), 7.50–7.35 (m, 4H),
7.35–7.28 (m, 2H), 7.15–7.00 (m, 7H), 6.75–6.67 (m, 4H), 6.67–6.57 (m, 3H), 6.40 (d, J =
3.4 Hz, 1H), 4.40 (dd, J = 9.2, 4.0 Hz, 1H), 4.29–4.17 (m, 1H), 3.78 (s, 3H), 3.58 (dd, J =
10.6, 7.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 158.9, 148.0, 140.9, 133.3, 133.1 (d,
J
C-P = 9.9 Hz), 132.8 (d, JC-P = 5.9 Hz), 132.2 (d, JC-P = 7.7 Hz), 132.0, 131.8, 131.5 (d, JC-P
= 9.8 Hz), 130.4, 129.1, 128.8, 128.6 (d, JC-P = 7.0 Hz), 128.5, 128.0 (d, JC-P = 17.7 Hz),
127.1, 116.9, 113.6, 113.4, 65.5, 60.9, 55.3; HRMS (ESI-TOF): calculated for
C33H31N2NaO2P [M+Na]+: m/z = 541.2015, found 541.2017.
N-(2-(N-(Phenyl)-1-(4-methoxyphenyl)-2-D-2-phenylethyl)-P,P-diphenylphosphinic
amide (d-3a). White solid (99.4 mg, 86%); mp 240−241 °C; Rf = 0.45 (hexanes/ethyl
acetate = 1/1); 1H NMR (400 MHz, CDCl3): δ =7.92–7.83 (m, 2H), 7.78 (dd, J = 12.0, 7.2
Hz, 2H), 7.55–7.40 (m, 4H), 7.37–7.32 (m, 2H), 7.20–7.10 (m, 3H), 7.06 (t, J = 7.8 Hz, 2H),
6.93–6.80 (m, 6H), 6.68–6.55 (m, 3H), 4.81 (t, J = 11.8 Hz, 1H), 3.84 (s, 3H), 3.33 (dd, J =
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12.2, 6.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 158.9, 146.6, 137.1, 133.3, 132.8 (d,
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C-P = 9.7 Hz), 132.3 (d, JC-P = 2.5 Hz), 132.2 (d, JC-P = 2.8 Hz), 132.0, 131.6 (d, JC-P = 9.7
Hz), 131.5, 130.1, 129.1, 128.9, 128.8 (d, JC-P = 4.3 Hz), 128.6, 128.5, 128.1 (d, JC-P = 11.5
Hz), 127.5, 117.2, 113.9, 113.7, 62.9 (t, JC-D = 19.9 Hz), 59.0, 55.3; HRMS (ESI-TOF):
calculated for C33H31DN2O2P [M+H]+: m/z = 520.2259, found 520.2244.
N-(2-(N-(Phenyl)-1,2-diphenylethyl)-P,P-diphenylphosphinic amide (3b). White solid
(78.2 mg, 80%) ; mp 175−177 °C; Rf = 0.62 (hexanes/ethyl acetate = 1/1); 1H NMR (400
MHz, CDCl3): δ = 7.93–7.84 (m, 2H), 7.77 (dd, J = 12.1, 8.0 Hz, 2H), 7.56–7.50 (m, 1H),
7.50–7.40 (m, 3H), 7.35–7.27 (m, 5H), 7.20–7.03 (m, 6H), 7.00–6.93 (m, 2H), 6.88 (d, J =
7.3 Hz, 2H), 6.67–6.57 (m, 3H), 4.90–4.75 (m, 2H), 3.41 (dd, J = 11.9, 6.8 Hz, 1H); 13C
NMR (100 MHz, CDCl3): δ = 146.7, 140.2 (d, JC-P = 7.6 Hz), 136.9, 133.2, 132.8 (d, JC-P
=
9.7 Hz), 132.4 (d, JC-P = 2.4 Hz), 132.3 (d, JC-P= 2.4 Hz), 131.9, 131.6 (d, JC-P = 9.7 Hz),
131.3, 130.0, 129.1, 128.9, 128.8 (d, JC-P = 6.3 Hz), 128.6, 128.3 (d, JC-P = 5.0 Hz), 128.1,
127.6, 126.9, 117.1, 113.6, 63.2, 59.6; HRMS (ESI-TOF): calculated for C32H30N2OP
[M+H]+: m/z = 489.2090, found 489.2070.
N-(2-(N-(Phenyl)-1-(4-methylphenyl)-2-phenylethyl)-P,P-diphenylphosphinic
amide
(3c). White solid (91.3 mg, 87%) ; mp 151−153°C; Rf = 0.65 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, C6D6): δ = 8.07–7.96 (m, 4H), 7.91 (d, J = 7.6 Hz, 1H), 7.15–7.09 (m,
2H), 7.05–6.97 (m, 7H), 6.94–6.87 (m, 4H), 6.85–6.78 (m, 3H), 6.67 (t, J = 7.3 Hz, 1H),
6.57 (d, J = 8.0 Hz, 2H), 4.95 (td, J = 12.3, 2.2 Hz, 1H), 4.79 (dd, J = 7.6, 2.5 Hz, 1H), 3.39
13
(dd, J = 12.4, 6.5 Hz, 1H), 2.08 (s, 3H); C NMR (100 MHz, C6D6): δ = 148.0, 138.3 (d,
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4.3 Hz) 132.07, 131.8 (d, JC-P = 9.5 Hz), 131.4, 129.6, 129.1, 129.0, 128.9, 128.7, 127.7,
127.1, 117.1, 113.8, 63.5, 59.7, 21.0; HRMS (ESI-TOF): calculated for C33H31N2NaOP
[M+Na]+: m/z = 525.2066, found 525.2045.
N-(2-(N-(Phenyl)-1-(2-methylphenyl)-2-phenylethyl)-P,P-diphenylphosphinic
amide
(3d). White solid (61.9 mg, 59%); mp 90−91°C; Rf = 0.63 (hexanes/ethyl acetate = 1/1); 1H
NMR (400 MHz, C6D6): δ = 8.03–7.95 (m, 2H), 7.94–7.87 (m, 2H), 7.81 (d, J = 7.8 Hz,
1H), 7.13–7.03 (m, 3H), 7.03–6.91 (m, 10H), 6.91–6.82 (m, 5H), 6.67–6.61 (m, 1H), 6.47
(d, J = 7.7 Hz, 1H), 5.15 (td, J = 12.2, 2.2 Hz, 1H), 4.71 (dd, J = 7.9, 2.2 Hz, 1H), 3.52 (dd,
J = 12.3, 6.7 Hz, 1H), 1.78 (s, 3H); 13C NMR (100 MHz, C6D6): δ = 147.8, 139.4 (d, JC-P
7.6 Hz), 137.7, 135.0, 134.1, 133.1 (d, JC-P = 9.5 Hz), 132.9, 132.7, 132.2, 132.0, 131.9 (d,
C-P = 9.5 Hz), 131.4, 130.7, 129.5, 129.3, 129.0, 128.8 (d, JC-P = 5.2 Hz), 128.6(d, JC-P = 7.9
=
J
Hz), 127.5, 127.0, 125.7, 117.2, 113.9, 61.4, 56.8, 18.8; HRMS (ESI-TOF): calculated for
C33H32N2OP [M+H]+: m/z = 503.2252, found 503.2261.
N-(2-(N-(Phenyl)-1-(3-methoxyphenyl)-2-phenylethyl)-P,P-diphenylphosphinic amide
(3e). White solid (86.1 mg, 83%); mp 172−173°C; Rf = 0.50 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, C6D6): δ = 8.06–7.96 (m, 4H), 7.84 (d, J = 7.5 Hz, 1H), 7.12 (t, J = 7.8
Hz, 2H), 7.04–6.88 (m, 11H), 6.85–6.76 (m, 3H), 6.70–6.60 (m, 2H), 6.48 (s, 1H), 6.32 (d,
J = 7.6 Hz, 1H), 4.98 (td, J = 12.1, 2.2 Hz, 1H), 4.84 (dd, J = 7.5, 2.4 Hz, 1H), 3.44 (dd, J =
12.4, 6.2 Hz, 1H), 3.22 (s, 3H); 13C NMR (100 MHz, C6D6): δ = 160.1, 147.9, 142.9 (d, JC-P
= 8.3 Hz), 137.9, 134.2, 133.2 (d, JC-P = 9.6 Hz), 133.0, 132.7, 132.1 (d, JC-P = 2.6 Hz),
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131.8 (d, JC-P = 9.6 Hz), 131.3, 129.6, 129.4, 129.0, 128.9 (d, JC-P = 2.3 Hz), 128.8, 127.7,
119.5, 117.2, 113.9, 113.3, 112.9, 63.5, 59.9, 54.8; HRMS (ESI-TOF): calculated for
C33H31N2NaO2P [M+Na]+: m/z = 541.2015, found: 541.2018.
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N-(2-(N-(Phenyl)-1-(4-bromophenyl)-2-phenylethyl)-P,P-diphenylphosphinic
amide
(3f). White solid (75.0 mg, 66%); mp 205−206°C; Rf = 0.55 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, CDCl3): δ = 7.93–7.83 (m, 2H), 7.75 (dd, J = 12.2, 7.3 Hz, 2H),
7.59–7.51 (m, 1H), 7.51–7.40 (m, 6H), 7.37–7.30 (m, 2H), 7.20–7.11 (m, 3H), 7.06 (t, J =
7.8 Hz, 2H), 6.89 (d, J = 6.2 Hz, 2H), 6.84 (d, J = 8.3 Hz, 2H), 6.61 (t, J = 8.0 Hz, 3H),
4.88–4.61 (m, 2H), 3.36 (dd, J = 12.1, 6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 146.4,
139.3 (d, JC-P = 7.9 Hz), 136.6, 132.9, 132.7 (d, JC-P = 9.8 Hz), 132.5 (d, JC-P = 2.5 Hz),
132.4 (d, JC-P = 2.5 Hz), 131.6, 131.5 (d, JC-P = 4.8 Hz), 131.1, 130.4, 129.8, 129.2, 129.1,
129.0, 128.8 (d, JC-P = 1.9 Hz), 128.7, 128.3 (d, JC-P = 2.0 Hz), 127.8, 121.5, 117.3, 113.9,
63.1, 59.1; HRMS (ESI-TOF): calculated for C32H28BrN2NaOP [M+Na]+: m/z = 589.1015,
found 589.1018.
N-(2-(N-(Phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-P,P-diphenylphosphinic
amide
(3g). White solid (87.5 mg, 90%); mp 181−182°C; Rf = 0.56 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, CDCl3): δ = 7.95–7.84 (m, 2H), 7.81–7.73 (m, 2H), 7.57–7.50 (m, 1H),
7.50–7.41 (m, 3H), 7.37–7.29 (m, 2H), 7.20–7.11 (m, 3H), 7.06 (t, J = 7.9 Hz, 2H), 7.00 (t,
J = 8.6 Hz, 2H), 6.96–6.87 (m, 4H), 6.69–6.58 (m, 3H), 4.85 (t, J = 11.7 Hz, 1H), 4.75 (d, J
= 2.0 Hz, 1H), 3.38 (dd, J = 12.0, 6.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 162.1 (d,
JC-F = 244.7 Hz), 146.5, 136.8, 136.1 (d, JC-P = 7.6 Hz), 133.0, 132.7 (d, JC-P = 9.7 Hz),
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132.44 (d, JC-P = 2.5 Hz), 132.35 (d, JC-P = 2.6 Hz), 131.8, 131.6 (d, JC-P = 9.7 Hz), 131.3,
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129.9, 129.1, 129.0, 128.8 (d, JC-P = 6.8 Hz), 128.6 (d, JC-F = 4.2 Hz), 128.5, 128.3 (d, JC-P
=
4.8 Hz), 127.7, 117.3, 115.2 (d, JC-F = 21.2 Hz), 113.8, 63.2, 58.9; HRMS (ESI-TOF):
calculated for C32H28FN2NaOP [M+Na]+: m/z = 529.1815, found 529.1818.
N-(2-(N-(Phenyl)-1-(4-Chlorophenyl)-2-phenylethyl)-P,P-diphenylphosphinic
amide
(3h). White solid (80.1 mg, 77%); mp 215−217 °C; Rf = 0.63 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, CDCl3): δ = 7.89–7.80 (m, 2H), 7.79–7.69 (m, 2H), 7.54–7.48 (m, 1H),
7.47–7.39 (m, 3H), 7.34–7.27 (m, 2H), 7.23 (d, J = 4.2 Hz, 2H), 7.16–7.08 (m, 3H),
7.07–7.00 (m, 2H), 6.92–6.82 (m, 4H), 6.65–6.54 (m, 3H), 4.82 (t, J = 11.8 Hz, 1H), 4.73 (d,
J = 2.2 Hz, 1H), 3.33 (dd, J = 12.1, 6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 146.2,
138.8 (d, JC-P = 7.8 Hz), 136.5, 133.4, 132.9, 132.7 (d, JC-P = 9.8 Hz), 132.5 (d, JC-P = 2.7
Hz), 132.4 (d, JC-P = 2.8 Hz), 131.7, 131.6 (d, JC-P = 9.8 Hz), 131.1, 130.4, 129.8, 129.1,
129.0, 128.8 (d, JC-P = 2.8 Hz), 128.7, 128.5, 128.3 (d, JC-P = 2.2 Hz), 127.8, 117.6, 114.0,
63.3, 59.0; HRMS (ESI-TOF): calculated for C32H28ClN2NaOP [M+Na]+: m/z = 545.1520,
found 545.1520.
N-(2-(N-(Phenyl)-1-(naphthalen-1-yl)-2-phenylethyl)-P,P-diphenylphosphinic
amide
(3i). White solid (66.3 mg, 61%); mp 180−182 °C; Rf = 0.64 (hexanes/ethyl acetate = 2/1);
1H NMR (400 MHz, CDCl3): δ = 7.99–7.83 (m, 5H), 7.78 (dd, J = 12.2, 7.6 Hz, 2H),
7.58–7.43 (m, 5H), 7.44–7.31 (m, 2H), 7.25–7.17 (m, 2H), 7.13 (t, J = 7.2 Hz, 1H),
7.10–7.00 (m, 4H), 6.89 (d, J = 7.2 Hz, 1H), 6.68 (d, J = 7.3 Hz, 2H), 6.65–6.55 (m, 3H),
5.60 (t, J = 11.9 Hz, 1H), 4.93 (d, J = 6.6 Hz, 1H), 3.39 (dd, J = 12.1, 6.8 Hz, 1H); 13C
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NMR (100 MHz, CDCl3): δ = 147.0, 137.1, 136.1 (d, JC-P = 9.7 Hz), 133.8, 133.3, 132.6 (d,
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C-P = 9.8 Hz), 132.4 (d, JC-P = 2.7 Hz), 132.2 (d, JC-P = 2.7 Hz), 132.0, 131.6 (d, JC-P = 9.8
Hz), 131.3, 130.2, 130.0, 129.2, 129.0, 128.9, 128.8 (d, JC-P = 2.0 Hz), 128.6 (d, JC-P = 2.4
Hz), 128.4, 127.9, 127.6, 126.9, 126.0, 124.8, 124.3, 122.6, 116.6, 113.5, 61.2, 56.2; HRMS
(ESI-TOF): calculated for C36H31N2NaOP [M+Na]+: m/z = 561.2066, found 561.2075.
N-(2-(N-(Phenyl)-1-(furan-2-yl)-2-phenylethyl)-P,P-diphenylphosphinic amide (3j).
1
White solid (47.5 mg, 50%); mp 91−93 °C; Rf = 0.50 (hexanes/ethyl acetate = 2/1); H
NMR (400 MHz, CDCl3): δ =8.00–7.80 (m, 4H), 7.59–7.34 (m, 7H), 7.21–7.13 (m, 3H),
7.08 (t, J = 7.8 Hz, 2H), 7.04–6.96 (m, 2H), 6.67 (d, J = 7.9 Hz, 3H), 6.61 (t, J = 7.2 Hz,
1H), 6.34 (s, 1H), 6.07 (d, J = 3.0 Hz, 1H), 5.07 (s, 1H), 4.84–4.72 (m, 1H), 3.23 (dd, J =
12.0, 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 153.5 (d, JC-P = 1.0 Hz), 147.0, 142.0,
137.7, 133.0, 132.7 (d, JC-P = 9.7 Hz), 132.41 (d, JC-P = 2.7 Hz), 132.36 (d, JC-P = 2.8 Hz),
131.7, 131.6 (d, JC-P = 9.7 Hz), 131.3, 129.9, 129.1, 128.9 (d, JC-P = 6.4 Hz), 128.7 (d, JC-P
=
6.5 Hz), 128.3, 127.8, 127.5, 117.0, 113.7, 110.7, 107.7, 60.4, 55.4; HRMS (ESI-TOF):
calculated for C30H27N2NaO2P [M+Na]+: m/z = 501.1702, found 501.1711.
N-(2-(N-(Phenyl)-1-(thiophen-2-yl)-2-phenylethyl)-P,P-diphenylphosphinic amide (3k).
1
White solid (59.1mg, 60%); mp 158−160 °C; Rf = 0.55 (hexanes/ethyl acetate = 2/1); H
NMR (400 MHz, CDCl3): δ = 8.01–7.89 (m, 4H), 7.61–7.43 (m, 4H), 7.43–7.32 (m, 2H),
7.24 (d, J = 5.0 Hz, 1H), 7.20–7.12 (m, 3H), 7.12–7.05 (m, 4H), 7.04–6.98 (m, 1H), 6.79 (d,
J = 3.1 Hz, 1H), 6.70 (d, J = 7.9 Hz, 2H), 6.63 (t, J = 7.3 Hz, 1H), 5.10–4.90 (m, 2H), 3.42
(dd, J = 12.0, 6.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 146.4, 145.3 (d, JC-P = 9.8 Hz),
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131.7 (d, JC-P = 9.7 Hz), 131.6, 131.1, 129.8, 129.1, 128.9, 128.8, 128.7, 128.3 (d, JC-P
=
10.1 Hz), 127.7, 127.3, 124.4 (d, JC-P = 14.2 Hz), 117.5, 114.0, 63.3, 56.7; HRMS
(ESI-TOF): calculated for C30H27N2NaOPS [M+Na]+: m/z = 517.1474, found 517.1473.
N-(2-(N-(Phenyl)-1-tert-butyl-2-phenylethyl)-P,P-diphenylphosphinic amide (3l). White
solid (83.8mg, 90%); mp 130−131 °C; Rf = 0.56 (hexanes/ethyl acetate = 1/1); 1H NMR
(400 MHz, C6D6): δ = 8.17–8.09 (m, 2H), 8.09–8.00 (m, 3H), 7.59 (d, J = 7.2 Hz, 2H), 7.14
(s, 1H), 7.12–7.05 (m, 5H), 7.04–6.99 (m, 3H), 6.91 (t, J = 7.3 Hz, 2H), 6.84 (t, J = 7.3 Hz,
1H), 6.66 (t, J = 7.1 Hz, 1H), 6.60 (t, J = 7.2 Hz, 1H), 4.92 (dd, J = 10.0, 1.2 Hz, 1H),
3.44–3.35 (m, 1H), 3.11 (dd, J = 12.4, 5.3 Hz, 1H), 0.66 (s, 9H); 13C NMR (100 MHz,
C6D6): δ = 148.1, 140.9, 134.0, 133.3 (d, JC-P = 9.5 Hz), 132.7, 132.5, 132.4 (d, JC-P = 8.8
Hz), 132.3 (d, JC-P = 2.4 Hz), 131.7 (d, JC-P = 2.7 Hz), 131.2, 129.9, 129.5, 129.0 (d, JC-P
=
12.1 Hz), 128.4, 127.5, 117.1, 114.1, 65.3, 56.6, 35.7, 27.8; HRMS (ESI-TOF): calculated
for C30H34N2OP [M+H]+: m/z = 469.2403, found 469.2400.
N-(2-(N-(Phenyl)-2-(4-methoxyphenyl)-1-phenylethyl)-P,P-diphenylphosphinic amide
(3m). White solid (61.1mg, 58%); mp 160−161 °C; Rf = 0.58 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, CDCl3, major isomer): δ = 7.90 (dd, J = 12.0, 7.1 Hz, 2H), 7.78 (dd, J
= 12.1, 7.6 Hz, 2H), 7.56–7.50 (m, 1H), 7.50–7.40 (m, 3H), 7.35–7.27 (m, 5H), 7.06 (t, J =
7.8 Hz, 2H), 7.02–6.96 (m, 2H), 6.79 (d, J = 8.5 Hz, 2H), 6.68–6.56 (m, 5H), 4.97–4.78 (m,
1H), 4.74 (d, J = 4.3 Hz, 1H), 3.70 (s, 3H), 3.37 (dd, J = 12.1, 6.8 Hz, 1H); 13C NMR (100
MHz, CDCl3, major isomer): δ = 158.9, 147.0, 140.4 (d, JC-P = 3.9 Hz), 133.3, 132.7 (d, JC-P
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= 9.8 Hz), 132.3 (d, JC-P = 2.5 Hz), 132.2 (d, JC-P = 2.8 Hz), 132.0, 131.6 (d, JC-P = 9.5 Hz),
131.5, 130.1, 129.4, 129.0, 128.9, 128.7 (d, JC-P = 8.1 Hz), 128.6, 128.3, 127.5, 126.9, 116.8,
113.5, 62.4, 59.7, 50.9; HRMS (ESI-TOF): calculated for C33H31N2NaO2P [M+Na]+: m/z =
541.2015, found 541.2022.
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N-(2-(N-(Phenyl)-2-(4-fluorophenyl)-1-phenylethyl)-P,P-diphenylphosphinic
amide
(3n). White solid (94.0 mg, 93%); mp 150−151 °C; Rf = 0.55 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, CDCl3, major isomer): δ = 7.94–7.85 (m, 2H), 7.78 (dd, J = 12.2, 7.3
Hz, 2H), 7.58–7.51 (m, 1H), 7.51–7.41 (m, 3H), 7.36–7.28 (m, 5H), 7.07 (t, J = 7.8 Hz, 2H),
7.02–6.94 (m, 2H), 6.86–6.75 (m, 5H), 6.65–6.55 (m, 3H), 4.89–4.72 (m, 2H), 3.29 (dd, J =
12.2, 7.1 Hz, 1H); 13C NMR (100 MHz, CDCl3, major isomer): δ = 162.3 (d, JC-F = 244.4
Hz), 146.7, 140.0 (d, JC-P = 8.1 Hz), 133.2, 132.9 (d, JC-F = 3.0 Hz), 132.7 (d, JC-P = 9.9 Hz),
132.4 (d, JC-P = 2.7 Hz), 132.3 (d, JC-P = 2.6 Hz), 131.9, 131.6 (d, JC-P = 9.5 Hz), 131.3,
130.0, 129.8 (d, JC-F = 7.9 Hz), 129.1, 129.0, 128.8 (d, JC-P = 8.8 Hz), 128.6, 128.4, 127.7,
126.9, 117.0, 115.1 (d, JC-F = 21.1 Hz), 113.5, 62.5, 59.6; HRMS (ESI-TOF): calculated for
C32H29FN2OP [M+H]+: m/z = 507.1996, found 507.1995.
N-(2-(N-(Phenyl)-2-(4-bromophenyl)-1-phenylethyl)-P,P-diphenylphosphinic
amide
(3o). White solid (68.8 mg, 64%); mp 190−193 °C; Rf = 0.55 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, CDCl3, major isomer): δ = 7.87 (dd, J = 11.6, 7.5 Hz, 2H), 7.76 (dd, J
= 11.8, 7.7 Hz, 2H), 7.56–7.49 (m, 1H), 7.49–7.39 (m, 3H), 7.35–7.26 (m, 5H), 7.26–7.19
(m, 3H), 7.05 (t, J = 7.6 Hz, 2H), 6.97 (s, 2H), 6.80 (s, 1H), 6.73 (d, J = 8.2 Hz, 2H),
6.66–6.52 (m, 3H), 4.83 (t, J = 11.7 Hz, 1H), 4.72 (d, J = 2.8 Hz, 1H), 3.30–3.12 (m, 1H);
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13C NMR (100 MHz, CDCl3, major isomer): δ = 146.6, 139.9 (d, JC-P = 7.7 Hz), 136.4,
133.1, 132.7 (d, JC-P = 9.8 Hz), 132.5 (d, JC-P = 2.5 Hz), 132.3 (d, JC-P = 2.7 Hz), 131.8,
131.5 (d, JC-P = 9.7 Hz), 131.4, 131.2, 130.1, 129.1, 129.0, 128.8 (d, JC-P = 9.4 Hz), 128.6,
128.5, 127.7, 126.8, 121.5, 117.0, 113.4, 62.6, 59.4; HRMS (ESI-TOF): calculated for
C32H29BrN2OP [M+H]+: m/z = 567.1195, found 567.1202.
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N-(2-(N-(Phenyl)-2-(4-chlorophenyl)-1-phenylethyl)-P,P-diphenylphosphinic
amide
(3p). White solid (72.5 mg, 69%); mp 113−114 °C; Rf = 0.60 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, CDCl3): δ = 7.89 (dd, J = 12.0, 7.1 Hz, 2H), 7.77 (dd, J = 12.2, 7.3 Hz,
2H), 7.57–7.41 (m, 4H), 7.38–7.28 (m, 5H), 7.13–7.03 (m, 4H), 7.02–6.94 (m, 2H), 6.80 (d,
J = 8.3 Hz, 3H), 6.61 (t, J = 8.3 Hz, 3H), 4.93–4.80 (m, 1H), 4.75 (d, J = 1.9 Hz, 1H), 3.27
(dd, J = 12.2, 7.1 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 146.5, 139.9 (d, JC-P = 7.7 Hz),
135.7, 133.4, 133.1, 132.8 (d, JC-P = 9.8 Hz), 132.5 (d, JC-P = 2.6 Hz), 132.3 (d, JC-P = 2.6
Hz), 131.8, 131.6 (d, JC-P = 9.6 Hz), 131.2, 129.7, 129.1, 129.0, 128.8 (d, JC-P = 8.6 Hz),
128.7, 128.5, 128.3, 127.8, 126.8, 117.3, 113.7, 62.7, 59.4; HRMS (ESI-TOF): calculated
for C32H28ClN2NaOP [M+Na]+: m/z = 545.1520, found 545.1519.
N-(2-(N-(Phenyl)-2-(3-bromophenyl)-1-phenylethyl)-P,P-diphenylphosphinic
amide
(3q). White solid (80.0 mg, 70%); mp 190−192 °C; Rf = 0.60 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, CDCl3): δ = 7.85 (dd, J = 12.2, 7.0 Hz, 2H), 7.77 (dd, J = 12.3, 7.3 Hz,
2H), 7.57–7.51 (m, 1H), 7.50–7.42 (m, 3H), 7.37–7.27 (m, 6H), 7.07 (t, J = 7.9 Hz, 2H),
7.03–6.91 (m, 4H), 6.84 (d, J = 7.6 Hz, 1H), 6.64–6.56 (m, 3H), 4.84 (td, J = 12.3, 2.6 Hz,
1H), 4.70 (d, J = 1.2 Hz, 1H), 3.26 (dd, J = 12.2, 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
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δ = 146.6, 140.0, 139.7 (d, JC-P = 7.3 Hz), 133.1, 132.9 (d, JC-P = 9.8 Hz), 132.5 (d, JC-P
=
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2.5 Hz), 132.4 (d, JC-P = 2.7 Hz), 131.9, 131.5 (d, JC-P = 3.8 Hz), 131.5, 131.2, 130.8, 129.9,
129.7, 129.2, 129.0, 128.9 (d, JC-P = 8.3 Hz), 128.7, 128.5, 127.9, 126.8, 122.3, 117.3, 113.6,
63.0, 59.6; HRMS (ESI-TOF): calculated for C32H29BrN2OP [M+H]+: m/z = 567.1195,
found 567.1199.
N-(2-(N-(Phenyl)-2-(4-tert-butylphenyl)-1-phenylethyl)-P,P-diphenylphosphinic amide
(3r). White solid (68.8 mg, 63%); mp 190−191 °C; Rf = 0.65 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, CDCl3): δ = 7.95–7.84 (m, 2H), 7.81–7.71 (m, 2H), 7.58–7.39 (m, 4H),
7.34–7.27 (m, 5H), 7.11 (d, J = 8.3 Hz, 2H), 7.05 (t, J = 7.9 Hz, 2H), 6.97–6.90 (m, 2H),
6.79 (d, J = 8.0 Hz 2H), 6.68–6.53 (m, 4H), 4.93–4.68 (m, 2H), 3.43 (dd, J = 11.9, 6.8 Hz,
1H), 1.22 (s, 9H); 13C NMR (100 MHz, CDCl3): δ = 150.3, 147.0, 140.4 (d, JC-P = 9.8 Hz),
134.0, 133.5, 132.8 (d, JC-P = 9.7 Hz), 132.3 (d, JC-P = 2.7 Hz), 132.2 (d, JC-P = 7.3 Hz),
131.8 (d, JC-P = 9.6 Hz), 131.6, 130.2, 129.1, 128.9, 128.7 (d, JC-P = 6.5 Hz), 128.6, 128.1 (d,
J
C-P = 33.7 Hz), 127.5, 127.1, 125.1, 116.7, 113.5, 110.2, 62.7, 59.8, 34.5, 31.4; HRMS
(ESI-TOF): calculated for C36H38N2OP [M+H]+: m/z = 545.2716, found 545.2721.
N-(2-(N-(Phenyl)-2-(3-methoxyphenyl)-1-phenylethyl)-P,P-diphenylphosphinic amide
(3s). White solid (79.6 mg, 77%); mp 175−177 °C; Rf = 0.65 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, CDCl3 major isomer): δ = 7.93–7.84 (m, 2H), 7.82–7.73 (m, 2H), 7.53
(t, J = 8.0 Hz, 1H), 7.49–7.39 (m, 3H), 7.35–7.28 (m, 5H), 7.09–6.97 (m, 5H), 6.77 (d, J =
7.6 Hz, 1H), 6.69 (dd, J = 8.2, 2.0 Hz, 1H), 6.63–6.58 (m, 3H), 6.53 (d, J = 7.6 Hz, 1H),
6.29 (s, 1H), 4.85 (td, J = 11.9, 2.6 Hz, 1H), 4.73 (dd, J = 7.6, 2.7 Hz, 1H), 3.49 (s, 3H),
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3.40 (dd, J = 12.2, 6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3 major isomer): δ = 159.2,
147.0, 140.4 (d, JC-P = 7.6 Hz), 138.9, 133.3, 132.8 (d, JC-P = 9.8 Hz), 132.4 (d, JC-P = 2.7
Hz), 132.3 (d, JC-P = 8.2 Hz), 132.0, 131.6 (d, JC-P = 9.7 Hz), 131.4, 130.1, 129.2, 129.1,
128.9, 128.8 (d, JC-P = 5.8 Hz), 128.6, 128.3, 127.5, 127.0, 120.5, 116.9, 114.0, 113.5, 113.1,
63.3, 59.5, 55.0; HRMS (ESI-TOF): calculated for C33H32N2O2P [M+H]+: m/z = 519.2196,
found 519.2196.
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N-(2-(N-(Phenyl)-2-(3-methylphenyl)-1-phenylethyl)-P,P-diphenylphosphinic
amide
(3t). White solid (78.8 mg, 79%); mp 120−122 °C; Rf = 0.65 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, C6D6): δ = 8.04–7.92 (m, 4H), 7.85 (d, J = 7.3 Hz, 1H), 7.13 (t, J = 7.8
Hz, 2H), 7.07–6.93 (m, 9H), 6.93–6.86 (m, 2H), 6.85–6.75 (m, 3H), 6.71 (d, J = 7.0 Hz,
1H), 6.68–6.59 (m, 3H), 4.95 (td, J = 12.2, 2.2 Hz, 1H), 4.75 (dd, J = 6.9, 2.0 Hz, 1H), 3.43
(dd, J = 12.4, 6.4 Hz, 1H), 1.85 (s, 3H); 13C NMR (100 MHz, C6D6): δ = 148.0, 141.2 (d,
J
C-P = 8.2 Hz), 137.7 (d, JC-P = 5.1 Hz), 134.4, 133.2 (d, JC-P = 9.6 Hz), 133.1, 132.5, 132.1
(d, JC-P = 2.7 Hz), 131.7 (d, JC-P = 9.5 Hz), 131.1, 129.6, 129.5, 129.0, 128.9 (d, JC-P = 2.6
Hz), 128.7, 128.2, 127.4, 127.2, 125.9, 117.1, 113.8, 63.6, 59.9, 21.2; HRMS (ESI-TOF):
calculated for C33H32N2OP [M+H]+: m/z = 503.2247, found 503.2242.
N-(2-(N-(Phenyl)-2-(2-methylphenyl)-1-phenylethyl)-P,P-diphenylphosphinic
amide
(3u). White solid (69.8 mg, 70%); mp 145−146 °C; Rf = 0.62 (hexanes/ethyl acetate = 1/1);
1H NMR (400 MHz, CDCl3): δ = 7.91 (dd, J = 11.9, 7.5 Hz, 2H), 7.75 (dd, J = 12.1, 7.6 Hz,
2H), 7.56–7.50 (m, 1H), 7.50–7.41 (m, 4H), 7.36–7.27 (m, 5H), 7.23 (d, J = 6.9 Hz, 1H),
7.10–7.06 (m, 4H), 6.97 (d, J = 7.3 Hz, 1H), 6.80 (d, J = 7.2 Hz, 2H), 6.59 (t, J = 7.3 Hz,
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3H), 5.00 (s, 1H), 4.78 (t, J = 11.4 Hz, 1H), 3.79 (dd, J = 12.0, 7.3 Hz, 1H), 1.60 (s, 3H);
13C NMR (100 MHz, CDCl3): δ = 146.5, 139.9 (d, JC-P = 7.5 Hz), 137.6, 135.5, 133.2, 132.8
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(d, JC-P = 9.8 Hz), 132.3 (d, JC-P = 2.7 Hz), 132.2 (d, JC-P = 2.6 Hz), 131.9, 131.7 (d, JC-P
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9.6 Hz), 131.5, 130.5, 130.2, 129.1, 128.9, 128.7 (d, JC-P = 8.5 Hz), 128.6, 128.4, 127.7,
127.4 (d, JC-P = 10.5 Hz), 127.0, 125.9, 117.4, 113.7, 59.3, 58.3, 18.8; HRMS (ESI-TOF):
calculated for C33H32N2OP [M+H]+: m/z = 503.2247, found 503.2244.
N-(2-(N-(Phenyl)-2-(3,5-dimethylphenyl)-1-phenylethyl)-P,P-diphenylphosphinic
amide (3v). White solid (93.3 mg, 90%); mp 199−200 °C; Rf = 0.50 (hexanes/ethyl acetate
= 1/1); 1H NMR (400 MHz, C6D6): δ = 7.97 (dd, J = 11.9, 7.5 Hz, 4H), 7.89 (d, J = 7.2 Hz,
1H), 7.13 (d, J = 7.4 Hz, 2H), 7.09–6.94 (m, 9H), 6.93–6.86 (m, 2H), 6.69–6.59 (m, 5H),
6.55 (s, 1H), 4.95 (td, J = 12.3, 2.1 Hz, 1H), 4.73 (dd, J = 7.2, 2.2 Hz, 1H), 3.43 (dd, J =
12.4, 6.3 Hz, 1H), 1.82 (s, 6H); 13C NMR (100 MHz, C6D6): δ = 148.1, 141.4 (d, JC-P = 8.4
Hz), 137.6, 137.5, 134.6, 133.3 (d, JC-P = 9.7 Hz), 132.5, 132.13 (d, JC-P = 2.6 Hz), 132.08 (d,
J
C-P = 2.7 Hz), 131.7 (d, JC-P = 9.8 Hz), 131.2, 129.62, 129.58, 128.9 (d, JC-P = 6.1 Hz),
128.8 (d, JC-P = 6.4 Hz), 128.1, 127.3, 126.7, 117.0, 113.7, 63.7, 59.9, 21.1; HRMS
(ESI-TOF): calculated for C34H34N2OP [M+H]+: m/z = 517.2403, found 517.2406.
N-(2-(N-(Phenyl)-2-(3,4-dimethylphenyl)-1-phenylethyl)-P,P-diphenylphosphinic
amide (3w). White solid (93.0 mg, 90%); mp 123−124 °C; Rf = 0.50 (hexanes/ethyl acetate
= 1/1); 1H NMR (400 MHz, C6D6, major isomer): δ = 8.05–7.83 (m, 5H), 7.15–7.09 (m, 2H),
7.09–7.05 (m, 3H), 7.05–6.99 (m, 5H), 6.98–6.94 (m, 1H), 6.94–6.87 (m, 2H), 6.77 (d, J =
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