The Ti-BINOLate-catalyzed, enantioselective ring-opening of meso-aziridines with amines

Article abstract of DOI:10.1039/c3ob40222c

The titanium-BINOLate-catalyzed, highly enantioselective ring-opening reaction of meso-aziridines has been developed which furnishes trans-1,2-diamines in typically good yields and excellent enantioselectivities. N-Aryl aziridines attached to a 5- or 6-me

Full text of DOI:10.1039/c3ob40222c

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The Ti-BINOLate-catalyzed, enantioselective
ring-opening of meso-aziridines with amines†
Cite this: DOI: 10.1039/c3ob40222c
Saravanan Peruncheralathan, Sandra Aurich, Henrik Teller and Christoph Schneider*
The titanium-BINOLate-catalyzed, highly enantioselective ring-opening reaction of meso-aziridines has
been developed which furnishes trans-1,2-diamines in typically good yields and excellent enantioselectivi-
ties. N-Aryl aziridines attached to a 5- or 6-membered carbocyclic ring are among the best substrates for
this process providing the products in up to >99% ee. The chiral catalyst is easily prepared in situ from
commercially available components and does not require any laborious ligand synthesis. Structural inves-
tigations into the catalyst composition reveal an oligomeric structure of the active Ti-complex.
Received 31st January 2013,
Accepted 1st March 2013
DOI: 10.1039/c3ob40222c
www.rsc.org/obc
complex was developed for the ring-opening with malonates.9e
RajanBabu and co-workers successfully designed a dinuclear,
Introduction
Nucleophilic ring-opening reactions of small-ring heterocycles structurally fully characterized, chiral yttrium-bissalicylimine
such as epoxides1 and aziridines2 continue to enjoy a promi- complex for the addition of trimethylsilyl cyanide and tri-
nent position in synthetic organic chemistry as they furnish methylsilyl azide to N-benzoyl aziridines giving rise to 1,2-
valuable 1,2-difunctionalized fine chemicals in just one step. cyano amides and 1,2-azido amides, respectively, with excep-
Whereas synthetic efforts were largely devoted to epoxide tional enantioselectivities of up to 99% ee.10 Antilla et al.
opening reactions initially, the attention within the synthetic revealed the capacity of chiral phosphoric acids to catalyze the
community has shifted to aziridine ring-opening reactions in enantioselective ring-opening of N-benzoyl aziridines with tri-
recent years. Highly valuable compounds such as 1,2-di- methylsilyl azide which proceeded with up to 95% ee.11
amines,3 1,2-amino alcohols,4 1,2-cyano amines5 and 1,2-amino
Non-silylated heteronucleophiles have only recently been
sulfides6 are easily accessible upon treatment with suitable shown to add to meso-aziridines using a variety of chiral cata-
nucleophiles according to this strategy. By using meso- lysts. Thus, Kobayashi et al. developed niobium-, zirconium-,
aziridines as starting materials an enantioselective process and titanium-catalyzed protocols for the enantioselective
can be envisioned in the presence of a chiral catalyst which is addition of anilines to N-aryl-aziridines furnishing 1,2-di-
capable of differentiating the enantiotopic carbon atoms amines with typically moderate, in select cases however excel-
within the aziridine in a symmetry-breaking operation.
lent enantioselectivities of up to 95% ee.12 In each of these
In the last decade or so quite a number of exceptional con- protocols specifically designed and individually prepared tri-
tributions in this area have been made which largely rest on and tetradentate BINOL-ligands were employed as chiral
silylated nucleophiles.7 Jacobsen et al. reported the chromium- ligands. The enantioselective ring-opening of aziridines with
catalyzed, enantioselective addition of trimethylsilyl azide to thiols to give rise to 1,2-mercapto amines as reported recently
N-benzyl aziridines proceeding with up to 94% ee.8 A whole by the groups of Antilla, Della Salla, and Tan could be accom-
series of highly enantioselective processes both for the azide plished through either Brønsted acid- or Brønsted base-cataly-
and cyanide addition to N-benzoyl aziridines was developed by sis, respectively, with excellent selectivity.13 Enantioselective
Shibasaki et al.9 As chiral catalysts they employed dinuclear halogen additions to meso-aziridines have very recently been
gadolinium- and yttrium-carbohydrate-phosphinoxide com- made possible through the work of Jacobsen and Ooi who
plexes, respectively, which were assembled in situ, and pro- employed phosphinothioureas and triazolium chlorides,
vided the products with up to 98% ee. In addition, a respectively, as chiral catalysts.14
heterodinuclear chiral lanthanumyttrium bissalicylimine
We have recently discovered the titanium-BINOLate-cata-
lyzed, highly enantioselective ring-opening of meso-aziridines
with anilines furnishing 1,2-diamines in typically good yields
and with up to >99% ee.15 In particular, aziridines with a
5- and 6-membered ring attached gave rise to exceptional
enantioselectivities and delivered cyclic 1,2-trans-diamines
Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig,
Germany. E-mail: schneider@chemie.uni-leipzig.de
†Electronic supplementary information (ESI) available: 1H- and 13C-NMR spectra
of new subtances. See DOI: 10.1039/c3ob40222c
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which were almost enantiomerically pure. In addition, the reactive as well as more selective. Whereas the background
direct and user-friendly in situ preparation of the chiral catalyst reaction with Ti(OiPr)4 alone furnished only trace amounts of
from commercially available components made this protocol product after 12 h, a 1 : 1-mixture of Ti(OiPr)4 and (R)-BINOL
extremely simple as no laborious ligand synthesis was catalyzed the reaction within 30 min at rt and yielded 83% of
required. We now provide a full account of our work and the product with an appreciable selectivity of 48% ee (entry 4).
report an extended product spectrum, a modified catalyst Lowering the reaction temperature to −40 °C further improved
design, and detailed spectroscopic investigations into the cata- the enantioselectvity to 79% ee (entry 5).
lyst structure.
Eventually, the key to success was a change in the metal–
ligand ratio. Mixing 2.2 equiv. of (R)-BINOL relative to Ti-
(OiPr)4 (10 mol%) in CH2Cl2 for 1 h at rt furnished a highly
reactive as well as enantioselective chiral catalyst. At rt the cata-
lyzed reaction was very rapid, but only marginally more selec-
tive than with the previous Ti-BINOLate-catalyst (entry 6). At
−40 °C, however, this in situ prepared catalyst gave rise to
trans-1,2-diamino cyclohexane (3a) in 81% yield and 97% ee
within 5 h (entry 7).20 Reaction temperatures above −40 °C led
to significantly decreased selectivity whereas below −40 °C
reaction times increased and yields eroded. When we
employed only 1.1 equiv. of aniline a significant enhancement
in yield to 94% was observed while the high enantioselectivity
was almost maintained (entry 8). Hence, these conditions were
used for the remaining optimization studies. Ti(OtBu)4 in
combination with (R)-BINOL slightly increased the selectivity
to 98% ee whereas Ti(OEt)4/(R)-BINOL gave rise to only 87% ee
(entries 9 and 10). The enantioselectivity remained constant at
97–98% ee throughout the entire reaction ruling out that the
gradually formed 1,2-diamine may act as a competitive chiral
ligand for titanium.
Additives which had been found beneficial in many other
Ti-BINOLate-catalyzed reactions were investigated next. With
molecular sieves (4 Å) no change in yield or enantioselectivity
was observed whereas the addition of water (10–20 equiv.) led
to a dramatic drop in enantioselectivity indicating that anhy-
drous conditions were important for the success of the reac-
tion. Optimal reaction conditions thus found called for mixing
the Lewis acid Ti(OtBu)4 (10 mol%) and (R)-BINOL (22 mol%)
in CH2Cl2 (0.25 M towards aziridine) for 1 h at room temp-
erature before the amine (1.1 equiv.) was added with sub-
sequent stirring at rt for 30 min. The reaction mixture was
then cooled down to −40 °C before aziridine 1a was added and
stirring was continued at −40 °C for the indicated period of
time.
Results and discussion
Based upon the well established capacity of early transition
metal alkoxides to be highly reactive catalysts for transamida-
tion reactions of amides16 and ring-opening reactions of epox-
ides with amines17 we expected them to be reactive in
aziridine ring-opening as well. They are known to display
strong Lewis acidity even in the presence of amines, have rela-
tively short metal–ligand bond lengths, and their complexes
with the chiral diol BINOL have been used in enantioselective
catalysis many times.18
The ring-opening of 7-phenyl-7-azabicyclo[4.1.0]heptane
(1a) with aniline (2a) (2 equiv.) was employed as a model reac-
tion (Table 1). Complexes prepared in situ from Zr(OiPr)4 and
Zr(OtBu)4 with (R)-BINOL catalyzed the reaction, but both the
reaction rate and the enantioselectivity were less than satisfac-
tory (entries 1 and 2). Interestingly, the enantioselectivity was
significantly enhanced by adding N-methyl imidazole as a co-
ligand for zirconium albeit at the expense of yield (entry 3).19
Complexes of Ti(OiPr)4 and (R)-BINOL proved to be both more
Table 1 Optimization studies, effect of metal alkoxide, metal–ligand ratio, and
temperature
M(OR)4/
BINOL
Yieldb
[%]
eec
[%]
Entrya
M(OR)4
T [°C]
t [h]
Having optimal reaction conditions for the ring-opening of
meso-aziridines with amines in our hands we evaluated the
substrate scope of this process (Table 2). A broad range of sub-
stituted anilines 2 were reacted with various 7-aryl-7 azabicyclo-
[4.1.0]heptanes 1. In general, best results were obtained with
para-substituted anilines giving rise to both good to excellent
yields and high enantioselectivities of up to 99% ee (entries
1–10). Anilines carrying electron-withdrawing substituent
groups furnished products with lower enantiomeric excess
(entries 7–9). The reaction with 4-aminobenzenethiol displayed
1
Zr(OiPr)4
Zr(OtBu)4
Zr(OtBu)4
Ti(OiPr)4
Ti(OiPr)4
Ti(OiPr)4
Ti(OiPr)4
Ti(OiPr)4
Ti(OtBu)4
Ti(OEt)4
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
rt
rt
rt
rt
−40
rt
−40
−40
−40
−40
12
12
12
0.5
14
76
95
35
83
51
81
81
94
92
91
12
28
70
48
79
50
97
96
98
87
2
3d
4
5
6
7
0.25
5
5
5
5
8e
9e
10e
a Reaction conditions: meso-aziridine 1a (1.0 equiv.), aniline 2a (2.0
equiv.), M(OR)4 (10 mol%), (R)-BINOL (11 or 22 mol%, respectively), an interesting chemoselectivity aspect: only the aminolysis of
0.25 M in CH2Cl2. b Yield of isolated product. c Determined by HPLC
the aziridine occurred and no thiol addition was observed
(entry 10). meta-Substituted anilines performed almost equally
using chiral stationary phases (see Experimental). d 22 mol% of N-
methyl imidazole were used as an additive. e Reaction was carried out
with 1.1 equiv. aniline 2a.
well with enantioselectivities ranging between 82 and 91% ee
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Table 2 Titanium-BINOLate-catalyzed ring-opening of 7-azabicyclo[4.1.0]hep-
tanes 1
Table 3 Titanium-BINOLate-catalyzed ring-opening of meso-aziridines 1
Aniline 2
Ar =
Yieldb
[%]
eec
[%]
meso-Aziridine 1 Aniline 2
Product Yieldb eec
Entrya
1
meso-Aziridine 1
Product
Entrya Ar1 =
Ar2 =
3
[%]
[%]
Ph
4a
90
99
1
2
3
4
5
6
Ph (1a)
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
92
85
86
92
69
91
93
65
90
80
89
88
93
90
90
79
90
75
86
88
81
84
70
89
86
79
98
99
98
95
88
91
83
60
77
93
86
91
83
82
47
56
76
22
77
65
98
98
98
98
98
88
(4-Me-)Ph
(4-MeO-)Ph
(4-F-)Ph
(4-Cl-)Ph
(4-Br-)Ph
(4-CF3)-Ph
(4-CN)-Ph
(4-COOMe-)Ph
(4-SH-)Ph
(3-Me-)Ph
(3-MeO-)Ph
(3-Br-)Ph
(3-CF3-)Ph
(2-Me-)Ph
(2-MeO-)Ph
(2-F-)Ph
2
3
4
5
1d
1d
1d
1d
(4-Me-)Ph
(4-MeO-)Ph
(4-CF3-)Ph
(4-SH-)Ph
4b
4c
4d
4e
83
77
71
76
99
97
94
99
7
8d
9
6
Ph
4f
80
57
10
11
12
13
14
15
16
17
18
19d
20
21
22
23e
24
25
26d
3k
3l
3m
3n
3o
3p
3q
3r
3s
3t
3u
3v
7
Ph
4c
96
99
8
9
1f
(4-MeO-)Ph
Ph
4g
5a
75
78
99
89
(2-COOMe-)Ph
1-Naphthyl
(2,4-F2-)Ph
(3,4-(MeO)2-)Ph
(3,4,5-(MeO)3-)-Ph 3w
10
11
1g
1g
(4-Me-)Ph
(4-MeO-)Ph
5b
5c
89
78
90
87
(1,4-(NH2)2)-Ph
(4-MeO-)-Ph (1b) Ph
3x
3c
3y
3q
85d
1b
(4-MeO-)Ph
12
Ph
6a
76
(2-MeO-)-Ph (1c) Ph
a Reaction conditions: meso-aziridine 1 (1.0 equiv.), aniline 2 (1.1
equiv.), Ti(OtBu)4 (10 mol%), (R)-BINOL (22 mol%), 0.25 M in CH2Cl2,
−40 °C. b Yield of isolated product. c Determined by HPLC using chiral
stationary phases (see Experimental). d Reaction was carried out with
2.0 equiv. aniline. e Reaction was carried out with 0.5 equiv. aniline.
13
Ph
7a
87
90
14
15
1i
(4-SH-)Ph
Ph
7b
8a
74
80
53
48
(entries 11–14). ortho-Substituted anilines, however, generally
furnished 1,2-diamines with only moderate enantioselectivity
probably for steric reasons (entries 15–18). More highly substi-
tuted anilines provided 1,2-diamines in high yields and excel-
lent selectivities of up to 98% ee as long as the ortho-position
was unsubstituted (entries 19–22). With bifunctional benzene-
1,4-diamine (0.5 equiv.) as the nucleophile a double ring-
opening occurred with 1a to furnish tetramine 3w in 70% yield
and 98% ee and only small amounts of the corresponding
meso-compound were formed (entry 23). Other N-aryl groups
may be employed as well. N-2-Methoxyphenyl aziridine 1c as
well as N-4-methoxyphenyl aziridine 1b were readily ring-
opened with both aniline and para-anisidine to deliver pro-
ducts with up to 98% ee (entries 24 and 25).
16
17
Ph
Ph
9a
85
20
17
90
10a
a Reaction conditions: meso-aziridine
1
(1.0 equiv.), aniline
2
(1.1 equiv.), Ti(OtBu)4 (10 mol%), (R)-BINOL (22 mol%), 0.25 M in
CH2Cl2, −40 °C. b Yield of isolated product. c Determined by HPLC
using chiral stationary phases (see Experimental). d After
crystallization.
aziridines which reacted only very sluggishly under these
Whereas the substrate scope was quite broad for anilines conditions.
other amines such as for example aliphatic amines failed to
Subsequently we extended the substrate range to other
participate in this reaction which we attribute to their higher cyclic as well as acyclic aziridines (Table 3). In particular,
basicity and hence stronger coordination to the Lewis acid 6-aryl-6-azabicyclo[3.1.0]hexanes proved to be excellent sub-
preventing fast turnover. The same holds true for N-alkyl strates for this process. Thus, various anilines reacted with
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1d–1f, respectively, to deliver trans-1,2-diamino cyclopentanes
4 in good yields and almost perfect enantioselectivity (entries
1–5 and 7–8). Aziridines with N-ortho-arylsubstituent retarded
the reaction and significantly diminished the selectivity (entry
6). 7-Phenyl-7-azabicyclo[4.1.0]hept-3-ene 1g behaved similarly
as its saturated analogue and furnished products with around
90% ee (entries 9–11). The acyclic aziridine 1i was ring-opened
with aniline in good yield with 90% ee whereas the analogous
reaction with 4-aminobenzenethiol delivered the 1,2-diamine
7b with high chemoselectivity but only 53% ee (entries 13 and
14, respectively). Bisaziridine 1k carrying both an N-aryl and
an N-tosyl group was ring-opened exclusively on the aryl-substi-
tuted aziridine ring with only moderate enantioselectivity
which may be caused by the Lewis basic heteroatoms of the
sulfonyl group coordinating additionally to the chiral Lewis
acid (entry 15). This effect may also be the origin for the low
selectivity observed in the ring-opening of aziridine 1l with a
furyl backbone (entry 16). On the other hand, aziridine 1m
attached to a seven-membered ring with an acetal moiety was
ring-opened in poor yield, but excellent enantioselectivity
(entry 17).
Table 4 Optimization of the reaction conditions with linked bis-BINOL 11
Entrya
Ti(OtBu)4/bis-BINOL 11
T [°C]
Yieldb [%]
eec [%]
1
2
3
4
5
2 : 1
1 : 1
2 : 3
1 : 1
1 : 1
−40
−40
−40
−20
rt
60
95
55
99
79
79
79
72
54
n.d.
a Reaction conditions: meso-aziridine 1a (1.0 equiv.), aniline 2a (1.1
equiv.), Ti(OtBu)4 (10 mol%), linked bis-BINOL 11 (11 mol%), 0.25 M
in CH2Cl2. b Yield of isolated product. c Determined by HPLC using
chiral stationary phases (see Experimental). n.d.: not determined.
At this point of the investigation we began to speculate
about the exact structure of the chiral catalyst and wondered
whether we could enhance its performance by further struc-
We then repeated some of the ring-opening reactions with
tural modifications. In particular, we became attracted to the this new catalyst system which we had performed earlier with
observations reported by Shibasaki et al. who had reported the the Ti(OtBu)4/(R)-BINOL-combination – in particular those
preparation and application of a linked bis-BINOL-ligand 11 with previously less satisfactory results (Table 5). In general,
coordinated to gallium(III) in epoxide opening21 and to zinc(II) reactions which were efficiently catalyzed with the Ti(OtBu)4/
in aldol reactions,22 respectively, which often provided better (R)-BINOL-combination at −40 °C did not give rise to improved
yields and enantioselectivities in the indicated reactions com- results with the new catalyst (entries 1–8). As an exception elec-
pared to the parent BINOL. In addition, Kobayashi et al. had tron-poor anilines which had earlier provided products with
shown that Mannich reactions were efficiently catalyzed with significantly diminished selectivity gave rise to similar or
Zr(OtBu)4 and a similar linked BINOL-ligand.23 The underlying slightly improved enantioselectivity (entries 3, 4, 10, 11). A dra-
reason for this idea rested mainly on the 1 : 2-stoichiometry of matic improvement of enantioselectivity was observed solely
Ti/BINOL which we had found important both for high rates for 4,4-dimethyl-8-phenyl-3,5-dioxa-8-azabicyclo[5.1.0]octane
and excellent enantioselectivities in the ring-opening reaction. (1m) at −20 °C which now provided 1,2-diamines 10a–10c with
In this respect the linked bis-BINOL-ligand 11 would ideally good yields and 68–88% ee (entries 9–11). It appears that in
resemble two BINOL-ligands and possibly form a more stable this case the titanium catalyst benefits from additional coordi-
and discrete Ti-complex for which additional structural infor- nation to the Lewis basic acetal oxygens.
mation might be obtained. Accordingly, the Shibasaki-ligand
11 was prepared in a six-step sequence from (R)-BINOL based rally well defined and characterized dinuclear titanium-BINO-
upon literature reports.21
Late-complex in our aziridine ring-opening reactions which
For the sake of comparison we finally investigated a structu-
In the model reaction of 7-phenyl-7-azabicyclo[4.1.0]- Maruoka had developed earlier for the enantioselective allyla-
heptane (1a) with aniline (2a) the new chiral ligand was tested tion of aldehydes.24 This chiral catalyst was prepared in situ
in combination with Ti(OtBu)4 (Table 4). Using various Ti/ from Ti(OiPr)3Cl, Ag2O and (R)-BINOL and its structure was
ligand-ratios it became obvious that only the reaction rate was unambiguously proven to be the μ-oxo-bridged dinuclear
affected with a 1 : 1-ratio providing the most reactive catalyst complex 12 through positive ESI-mass spectrometry by the
and the optimal yield of 95%. The enantioselectivity, however, group of Maruoka.24
remained constant at 79% ee throughout these reactions indi-
In our ring-opening reaction of meso-aziridine 1a, this cata-
cating the rapid formation of a very stable, likely tetracoordi- lyst displayed good reactivity and furnished the 1,2-diamine
nate chiral catalyst irrespective of the amount of ligand used product 3a with excellent yields, but with only 65% ee at
(entries 1–3). More importantly, this selectivity only slightly −40 °C. Lower as well as higher reaction temperatures did not
eroded at higher temperature furnishing 1,2-diamine 3a still improve the selectivity. This observation suggests that our
with 72% ee at −20 °C providing the opportunity to employ chiral titanium-BINOLate catalyst made in situ from 2 equiv. of
this chiral catalyst in reactions with less reactive aziridines BINOL differs in constitution from the Maruoka catalyst sig-
which required higher reaction temperatures (entry 4).
nificantly (Scheme 1).
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Table 5 Comparison of aminolyses of meso-aziridines with Ti(OtBu)4–BINOL
and Ti(OtBu)4–bis-BINOL 11 complexes
Aziridine Aniline 2
Yieldb eec
Entrya
1
(Ar)
Product t [d]
[%]
[%]
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1d
1f
Ph
3a
3c
3h
(A) 0.2 92
98
79
98
79
60
69
77
78
91
84
56
55
>99
35
89
62
90
87
40
88
31
78
16
68
(B) 1
(A) 1
(B) 4
(A) 1
(B) 4
(A) 1
(B) 4
(A) 1
(B) 2
(A) 1
(B) 2
(A) 1
(B) 4
(A) 5
(B) 8
(A) 4
(B) 8
(A) 2d
(B) 3d
(A) 5
(B) 2d
(A) 6
(B) 3d
95
86
35
65
84
90
72
88
92
79
90
90
18
78
35
20
17
88
85
87
66
62
69
(4-MeO-)Ph
(4-CN-)Ph
Fig. 1 Positive ESI-MS of
(1 : 2.2 : 10) in CH2Cl2–MeCN.
a
mixture of Ti(OtBu)4, (R)-BINOL, and aniline
(4-COOMe-)-Ph 3i
ESI-MS-experiments were carried out with a mixture of
Ti(OtBu)4, (R)-BINOL and aniline (1 : 2.2 : 10) in CH2Cl2, which
had been prepared according to the general synthetic protocol
(Fig. 1). In the positive ESI-MS mode prominent signals at m/z
1582 and m/z 1930 were observed representing trinuclear and
tetranuclear titanium complexes with the formal structures
[5BINOL + 3Ti + O + H]+ and [6BINOL + 4Ti + 2O + H]+, respect-
ively. The additional small peak at m/z 1966 has been esta-
blished before and proven to be a μ-oxo-complex with the
composition [6BINOL + 4Ti + 2O + 2H2O + H]+ by X-ray- and
MS-studies.25e Upon addition of acetonitrile which facilitated
ionization of the reaction sample in the mass spectrometer an
additional peak at m/z 1850 with the formal structure of
[6BINOL + 3Ti + H]+ was observed in low intensity.
When the sample preparation included the addition of
meso-aziridine 1a as a potential ligand to titanium a signal at
m/z 2764 was detected in the positive ESI-MS-mode indicating
the formation of a complex with the formal composition
[6BINOL + 4Ti + 2O + 2H2O + 3aziridine + 3aniline + H]+. A
split-off of Δm 266 representing the combined mass of one
aziridine and one aniline molecule was observed three succes-
sive times in LR-ESI-MS/MS further supporting the proposed
composition. This analysis supports the assumption that a
chiral oligomeric titanium complex binds to and activates
both components and delivers the amine onto the aziridine in
an intramolecular, highly enantioselective fashion.26 All pro-
posed structures were unambiguously proven by ESI-MS/MS
(see the ESI†).
(3-OMe-)Ph
3m
(2-OMe-)Ph
3p
4a
Ph
Ph
Ph
5a
1l
10a
10
11
1l
1l
(4-COOMe-)-Ph 10b
(4-CN-)Ph 10c
a Reaction conditions: meso-aziridine 1 (1.0 equiv.), aniline 2 (1.1
equiv.), Ti(OtBu)4 (10 mol%), (R)-BINOL (22 mol%) or bis-BINOL 11
(11 mol%), 0.25 M in CH2Cl2. b Yield of isolated product. c Determined
by HPLC methods using chiral stationary phases (see Experimental).
d Reaction was carried out at −20 °C.
In agreement with the formation of oligomeric Ti-BINOL
complexes observed in the ESI-MS experiments we found a
positive nonlinear effect (NLE) in the reaction using BINOL-
ligands with varying enantiomeric excess (Fig. 2). The weak,
but still significant positive nonlinear effect is an indication
that more than one chiral ligand is involved within the active
chiral metal catalyst.
Scheme 1 Aminolysis of 7-azabicyclo[4.1.0]heptane 1a catalyzed through the
dinuclear Maruoka-catalyst (12).
When we studied the complex prepared in situ from
In an attempt to shed some light on the catalyst compo- Ti(OtBu)4, the linked bis-BINOL ligand 11 and aniline
sition we finally performed some spectroscopic studies on the (1 : 1.1 : 10) prepared and measured in CH2Cl2 according to the
complex formed in situ in the reaction of Ti(OtBu)4 and general synthetic protocol, we observed a very prominent
(R)-BINOL or the linked bis-BINOL 11, respectively, and aniline single signal at m/z 1333 in the negative ESI-mode for which
in CH2Cl2.25
the formal composition [2 11 + 2Ti + H2O − H]− is assigned
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Experimental
General methods
All experiments were carried out in oven-dried glassware under
1
an argon atmosphere. H and 13C NMR spectra were recorded
in CDCl3 solution using a Varian Gemini 2000 spectrometer
(200 or 300 MHz) and a Brucker Avance DRX 400 (400 MHz).
The signals were referenced to residual chloroform (7.26 ppm,
1H, 77.00 ppm, 13C). Chemical shifts are reported in ppm, mul-
tiplicities are indicated by s (singlet), d (doublet), t (triplet), q
(quartet), p (pentet), m (multiplet) and brs (broad singlet).
Melting points were determined uncorrected on a Boetius
heating table. IR spectra were obtained with an FTIR spec-
trometer (Genesis ATI Mattson/Unicam). UV spectra were
recorded on a UV spectrometer (DU-650 Beckmann). Optical
rotations were measured using a Polarotronic polarimeter
(Schmidt & Haensch). High resolution ESI mass spectra were
recorded on a Brucker APEX II FT-ICR, low resolution ESI-MS
and ESI-MS/MS spectra were recorded on an ESQUIRE 3000
Plus (Bruker Daltonics). All EI mass spectra were recorded on a
Finnigan MAT 8230. HPLC analyses were carried out on a
Jasco MD-2010 plus instrument with a chiral stationary phase
column (Daicel Chiralcel OD-H column or Daicel Chiralcel
AD-H column). The solvents were distilled from the indicated
drying reagents: dichloromethane (CaH2). Diethyl ether, ethyl
acetate, petroleum ether and n-hexane were technical grade
and distilled from KOH, excepting ethyl acetate (distilled from
CaCl2). All reactions were monitored by TLC. Flash column
chromatography was performed by using Merck silica gel 60
230-400 mesh (0.040–0.063 mm). Spots were monitored by
thin-layer chromatography on precoated silica gel SILG/UV254
plates (Machery-Nagel & Co.), were visualized by UV and were
treated with a solution of phosphomolybdic acid hydrate (5 g
in 250 mL methanol) in methanol or vanilline (3.75 g, 75 mL
glacial acetic acid, 36 mL sulfuric acid in 750 mL methanol) in
methanol. The corresponding racemic products were prepared
using racemic BINOL (Aldrich) as a catalyst. All meso-N-aryl-
aziridines were prepared according to literature procedures.3j
Fig. 2 Positive nonlinear effect of the Ti(OtBu)4–BINOL catalyzed aminolysis of
meso-aziridine 1a with aniline 2a.
Fig. 3 Negative ESI-MS of a mixture of Ti(OtBu)4, bis-BINOL 11, and aniline
(1 : 1.1 : 10) in CH2Cl2.
(Fig. 3). After addition of acetonitrile for a more effective ioni-
zation additional signals at m/z 1317 and at m/z 659 were
detected representing the formal structures [2 11 + 2Ti + H]+
and [11 + Ti + H]+, respectively. Upon addition of aziridine 1a
to the solution in CH2Cl2 an additional signal was cleanly
detected in the positive ESI-mode at m/z 1583 for the structure
[2 11 + 2Ti + aziridine + aniline + H]+. In LR-ESI(+)-MS/MS this
signal underwent a split-off of Δm 266 comprising one aziri-
dine and one aniline molecule. Thus, the complex of two TiIV
and two linked bis-BINOL ligands appears to be the reactive
catalyst in the ring-opening reaction.
General procedure for ring-opening of meso-N-aryl-aziridines
To a stirred solution of (R)-BINOL (31.5 mg, 0.11 mmol) in dry
CH2Cl2 (0.8 mL) in a flame-dried round-bottom flask under an
Conclusions
We have developed a highly enantioselective ring-opening reac- argon atmosphere was added Ti(OtBu)4 (19 μL, 0.05 mmol) as
tion of meso-aziridines with anilines to furnish a broad a solution in CH2Cl2 (0.4 mL) at rt. The color of the reaction
range of trans-1,2-diamines in good to excellent yields and up mixture immediately became intensely red-brown and the solu-
to 99% ee. The chiral catalyst was easily prepared in situ from tion was stirred for 1 h at the same temperature. Sub-
the commercially available components Ti(OiPr)4 or Ti(OtBu)4 sequently the aniline 2 (0.55 mmol) in CH2Cl2 (0.4 mL) was
and (R)-BINOL in a 1 : 2-ratio. We also employed a chiral Ti- added and the mixture was stirred for an additional 30 min at
catalyst composed of a linked bis-BINOL ligand 11 as originally rt. Then the reaction was cooled to −40 °C and meso-aziridine
reported by Shibasaki which afforded higher yields and/ 1 (0.50 mmol) in CH2Cl2 (0.4 mL) was added. After the starting
or enantioselectivities in select cases. Investigations con- material had been completely consumed as judged by TLC-
cerning the structure of the metal catalyst based upon analysis the reaction was quenched through the addition of
HR-ESI-MS-experiments point to an oligomeric complex 0.5 mL Et3N at −40 °C, then warmed to room temperature and
with dual activation of both components which is further the resulting yellow solution was purified by flash chromato-
supported through the observation of a positive nonlinear graphy using n-hexane–ethyl acetate with 1% Et3N as the
effect.
eluent to afford the trans-1,2-diamine product.
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(1S,2S)-N,N′-Diphenylcyclohexane-1,2-diamine (3a).3j Yield: CH-N), 2.31–2.36 (m, 2H, CH2), 1.77–1.80 (m, 2H, CH2),
122 mg (92%), 98% ee as a colourless oil, reaction time 5 h.
[α]2D0 = −64.3 (c = 0.61, C6H6) [lit.12a [α]2D0 = −61.9 (c = 0.92,
>99.9% ee, C6H6)].
1.39–1.44 (m, 2H, CH2), 1.18–1.27 (m, 2H, CH2).
13C-NMR (100 MHz, CDCl3): δ = 152.5, 147.9, 141.8, 129.4,
117.7, 115.4, 115.0, 113.7, 58.5, 57.5, 55.9, 32.75, 32.70, 24.7
(2C).
Rf (EtOAc–petroleum ether, 1/10): 0.48.
UV (CH3CN): λmax (lg ε) = 296 (4.392), 250 (3.697) nm.
IR (film): ν (cm−1) = 3386, 3084, 3050, 3019, 2930, 2855,
1600, 1497, 1448, 1318, 1255.
MS (ESI, MeOH): m/z = 297 [M + H]+, 319.0 [M + Na]+.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 11.59 min;
1H-NMR (400 MHz, CDCl3): δ = 7.19 (t, J = 8.0 Hz, 4H, 3,5- major enantiomer (1S,2S) tR = 13.33 min.
ArH), 6.74 (t, J = 7.6 Hz, 2H, 4-ArH), 6.64 (d, J = 8.0 Hz, 4H, 2,6-
(1S,2S)-N-(4-Fluorophenyl)-N′-phenylcyclohexane-1,2-
ArH), 3.82 (brs, 2H, NH), 3.19–3.23 (m, 2H, CH-N), 2.36–2.39 diamine (3d).12a Yield: 129 mg (92%), 95% ee as a colorless
(m, 2H, CH2), 1.77–1.87 (m, 2H, CH2), 1.41–1.46 (m, 2H, CH2), solid; m.p.: 63–65 °C.
1.21–1.29 (m, 2H, CH2).
13C-NMR (100 MHz, CDCl3): δ = 147.8, 129.4, 117.6, 113.6, 59% ee, CHCl3)].
[α]2D0 = −7.8 (c = 1.28, CHCl3) [lit.12a [α]2D3 = −6.8 (c = 0.80,
57.3, 32.6, 24.7.
Rf (EtOAc–petroleum ether, 1/10): 0.40.
UV (CH3CN): λmax (lg ε) = 301 (3.826), 250 (4.548), 233
MS (ESI, MeOH): m/z = 267 [M + H]+, 289 [M + Na]+.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow (3.867) nm.
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 6.09 min;
major enantiomer (1S,2S) tR = 7.40 min.
IR (KBr): ν (cm−1) = 3397, 3054, 2935, 2851, 1600, 1502,
1431, 1320, 1291, 1199.
(1S,2S)-N-Phenyl-N′-p-tolylcyclohexane-1,2-diamine (3b).3j Yield:
119 mg (85%), 99% ee as a pale yellow oil.
1H-NMR (400 MHz, CDCl3): δ = 7.19 (t, J = 7.6 Hz, 2H, 3,5-
ArH), 6.89 (t, J = 8.8 Hz, 2H, 3′,5′-ArH), 6.73 (t, J = 7.2 Hz, 1H,
[α]2D0 = −40.5 (c = 0.89, CHCl3) [lit.12a [α]2D0 = −13.8 (c = 0.72, 4-ArH), 6.64 (d, J = 7.6 Hz, 2H, 2,6-ArH), 6.55 (dd, J = 4.4, 8.8
48% ee, CHCl3)].
Hz, 2H, 2′,6′-ArH), 3.75 (brs, 2H, NH), 3.21 (dt, J = 3.6, 10.0 Hz,
Rf (EtOAc–petroleum ether, 1/10): 0.46.
1H, CH-N), 3.11 (dt, J = 3.6, 10.0 Hz, 1H, CH-N), 2.30–2.36 (m,
UV (CH3CN): λmax (lg ε) = 298 (3.961), 251 (4.467), 231 2H, CH2), 1.77–1.80 (m, 2H, CH2), 1.39–1.44 (m, 2H, CH2),
(3.747) nm.
1.18–1.27 (m, 2H, CH2).
1
IR (as film in CCl4): ν (cm−1) = 3385, 3051, 3020, 2931,
13C-NMR (100 MHz, CDCl3): δ = 156.0 (d, JCF = 233.9 Hz),
2
2856, 1601, 1502, 1462, 1449, 1316, 1291, 1253.
147.8, 144.2, 129.4, 117.8, 115.8 (d, JCF = 22.3 Hz), 114.7
1H-NMR (400 MHz, CDCl3): δ = 7.20 (t, J = 7.6 Hz, 2H, 3,5- (d, 3JCF = 7.3 Hz), 113.7, 58.3, 57.4, 32.72, 32.64, 24.9, 24.7.
ArH), 7.02 (d, J = 8.4 Hz, 2H, 3′,5′-ArH), 6.74 (t, J = 7.6 Hz, 1H,
4-ArH), 6.65 (d, J = 7.6 Hz, 2H, 2,6-ArH), 6.58 (d, J = 8.4 Hz, 2H,
MS (ESI, MeOH): m/z (%) = 285 [M + H]+, 307 [M + Na]+.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
2′,6′-ArH), 3.80 (brs, 2H, NH), 3.22 (dt, J = 3.6, 9.0 Hz, 1H, CH- rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 6.94 min;
N), 3.19 (dt, J = 3.6, 9.0 Hz, 1H, CH-N), 2.36–2.39 (m, 2H, CH2), major enantiomer (1S,2S) tR = 8.77 min.
2.28 (s, 3H, CH3), 1.79–1.82 (m, 2H, CH2), 1.42–1.47 (m, 2H,
CH2), 1.21–1.29 (m, 2H, CH2).
(1S,2S)-N-(4-Chlorophenyl)-N′-phenylcyclohexane-1,2-diamine
(3e).3j Yield: 104 mg (69%), 81% ee as a pale yellow oil; reac-
13C-NMR (100 MHz, CDCl3): δ = 147.9, 145.5, 129.9, 129.4, tion time: 48 h.
127.0, 117.6, 113.9, 113.6, 57.7, 57.4, 32.71, 32.67, 24.77, 24.73,
[α]2D0 = −57.7 (c = 0.78, CHCl3).
20.5.
Rf (EtOAc–petroleum ether, 1/10) = 0.40.
UV (CH3CN): λmax (lg ε) = 287 (3.686), 257 (4.419) nm.
IR (as film): ν (cm−1) = 3850, 3741, 3685, 3645, 3394, 3050,
MS (ESI, MeOH): m/z = 281 [M + H]+, 303 [M + Na]+, 319
[M + K]+.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow 3022, 2922, 2855, 2661, 2577, 1921, 1865, 1605, 1431, 1402,
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 6.14 min; 1384, 1327, 1255, 1204, 1177, 1154, 1137, 1089, 1028, 1002,
major enantiomer (1S,2S) tR = 7.53 min.
993, 954, 875, 853, 824, 753, 694, 672, 631, 565, 505.
(1S,2S)-N-(4-Methoxyphenyl)-N′-phenylcyclohexane-1,2-diamine
(3c).3j Yield: 127 mg (86%), 98% ee as a yellow oil.
1H-NMR (400 MHz, CDCl3): δ = 7.21 (t, J = 7.2 Hz, 2H, 3,5-
ArH), 7.14 (d, J = 7.6 Hz, 2H, 3′,5′-ArH), 6.76 (t, J = 7.2 Hz, 1H,
[α]2D0 = −40.6 (c = 0.69, CHCl3) [lit.12a [α]2D0 = −26.4 (c = 1.33, 4-ArH), 6.65 (d, J = 8.0 Hz, 2H, 2,6-ArH), 6.55 (d, J = 7.6 Hz, 2H,
70% ee, CHCl3)].
2′,6′-ArH), 3.81 (brs, 2H, NH), 3.24 (dt, J = 3.2, 9.6 Hz, 1H, CH-
N), 3.15 (dt, J = 3.2, 9.6 Hz, 1H, CH-N), 2.32–2.38 (m, 2H, CH2),
1.80–1.82 (m, 2H, CH2), 1.41–1.46 (m, 2H, CH2), 1.23–1.41
Rf (EtOAc–petroleum ether, 1/10): 0.22.
UV (CH3CN): λmax (lg ε) = 298 (4.357), 250 (3.658) nm.
IR (as film in CCl4): ν (cm−1) = 3371, 3051, 2932, 2855, (m, 2H, CH2).
2831, 1601, 1511, 1463, 1450, 1357, 1290, 1241, 1179.
13C-NMR (100 MHz, CDCl3): δ = 147.6, 146.4, 129.4, 129.1,
1H-NMR (400 MHz, CDCl3): δ = 7.19 (t, J = 7.6 Hz, 2H, 3,5- 122.0, 117.8, 114.6, 113.6, 57.6, 57.2, 32.60, 32.45, 24.70, 24.67.
ArH), 6.79 (dd, J = 2.4, 7.6 Hz, 2H, 3′,5′-ArH), 6.73 (t, J = 7.2 Hz,
1H, 4-ArH), 6.64 (d, J = 7.6 Hz, 2H, 2,6-ArH), 6.62 (dd, J = 2.4,
MS (EI, MeOH): m/z = 301 [M + H]+, 323 [M + Na]+, 339 [M + K]+.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
7.6 Hz, 2H, 2′,6′-ArH), 3.76 (s, 3H, OCH3), 3.75 (brs, 2H, NH), rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 7.33 min;
3.19 (dt, J = 3.6, 9.6 Hz, 1H, CH-N), 3.11 (dt, J = 3.6, 9.6 Hz, 1H, major enantiomer (1S,2S) tR = 9.87 min.
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(1S,2S)-N-(4-Bromophenyl)-N′-phenylcyclohexane-1,2-diamine
IR (as film): ν (cm−1) = 3349, 3050, 2935, 2856, 2206, 1601,
1517, 1498, 1477, 1450, 1421, 1384, 1352, 1337, 1312, 1260,
1170, 1153, 1139, 1111, 1093, 992, 951, 874, 823, 746, 693, 542,
504.
(3f).15a Yield: 157 mg (91%), 91% ee as a pale yellow oil.
[α]2D0 = −64.3 (c = 0.93, CHCl3).
Rf (EtOAc–petroleum ether, 1/10): 0.44.
UV (CH3CN): λmax (lg ε) = 298 (4.015), 256 (4.539), 238
(3.779) nm.
1H-NMR (400 MHz, CDCl3): δ = 7.38 (d, J = 8.4 Hz, 2H, 3′,5′-
ArH), 7.17 (t, J = 8.4 Hz, 2H, 2,4-ArH), 6.72 (t, J = 7.2 Hz, 1H,
IR (as film): ν (cm−1) = 3394, 3052, 2934, 2857, 1604, 1495, 4-ArH), 6.61 (d, J = 8.8 Hz, 2H, 2,6-ArH), 6.53 (d, J = 8.8 Hz, 2H,
1431, 1384, 1295, 1178.
2′,6′-ArH), 4.39 (brd, 1H, NH), 3.58 (brs, 1H, NH), 3.28 (dt, J =
1H-NMR (400 MHz, CDCl3): δ = 7.25 (d, J = 8.8 Hz, 2H, 3′,5′- 3.6, 9.8 Hz, 1H, CH-N), 3.19–3.24 (m, 1H, CH-N), 2.28–2.34 (m,
ArH), 7.19 (t, J = 7.6 Hz, 2H, 3,5-ArH), 6.74 (t, J = 7.2 Hz, 1H, 2H, CH2), 1.79–1.82 (m, 2H, CH2), 1.28–1.45 (m, 2H, CH2),
4-ArH), 6.63 (d, J = 7.6 Hz, 2H, 2,6-ArH), 6.49 (d, J = 8.8 Hz, 2H, 1.22–1.28 (m, 2H, CH2).
2′,6′-ArH), 3.79 (brs, 2H, NH), 3.22 (dt, J = 3.6, 9.8 Hz, 1H, CH-
13C-NMR (100 MHz, CDCl3): δ = 151.0, 147.3, 133.8, 129.5,
N), 3.14 (dt, J = 3.6, 9.8 Hz, 1H, CH-N), 2.30–2.36 (m, 2H, CH2), 120.5, 117.9, 113.5, 1112.7, 98.8, 57.1, 57.0, 32.6, 32.2, 24.7,
1.78–1.81 (m, 2H, CH2), 1.40–1.45 (m, 2H, CH2), 1.19–1.27 (m, 24.5.
2H, CH2).
HR-MS (ESI, MeOH): calcd for C19H22N3 ([M + H]+):
13C-NMR (100 MHz, CDCl3): δ = 147.6, 146.8, 132.0, 129.4, 292.39808; found: 292.18107. calcd for C19H21N3Na ([2M +
117.8, 115.1, 113.6, 109.1, 57.5, 57.2, 32.63, 32.44, 24.72, 24.63. Na]+): 605.33687; found: 605.33556.
MS (ESI, MeOH): m/z = 345 [M + H]+, 367 [M + Na]+, 382
HPLC: Chiralcel OD-H column, hexane–i-PrOH = 70/30,
flow rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR
HR-MS (ESI, MeOH): calcd for C18H22N2Br ([M + H]+): 7.31 min; major enantiomer (1S,2S) tR = 12.05 min.
345.09611, found: 345.09611. (1S,2S)-N-(4-Carbomethoxyphenyl)-N′-phenylcyclohexane-1,2-
[M + K]+.
=
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow diamine (3i). Yield: 146 mg (90%), 77% ee as a colourless
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 7.74 min; viscous oil; reaction time: 48 h.
major enantiomer (1S,2S) tR = 10.75 min.
[α]2D0 = −102.9 (c = 0.58, CHCl3).
(1S,2S)-N-(Phenyl)-N′-(4-trifluoromethylphenyl)-cyclohexane-
1,2-diamine (3g).15e Yield: 155 mg (93%), 86% ee as a color-
less solid; reaction time: 36 h.
Rf (EtOAc–petroleum ether, 1/3) = 0.30.
UV (CH3CN): λmax (lg ε) = 245 (4.110) nm.
IR (as film): ν (cm−1) = 3366, 3054, 3023, 2936, 2857,
1697, 1601, 1523, 1502, 1434, 1384, 1337, 1310, 1282, 1258,
1176, 1140, 1107, 1028, 993, 969, 955, 875, 837, 787, 694, 639,
506.
[α]2D0 = −35.8 (c = 1.23, CHCl3).
Rf (EtOAc–petroleum ether, 1/10) = 0.38.
UV (CH3CN): λmax (lg ε) = 261 (4.310) nm.
IR (KBr): ν (cm−1) = 3346, 3052, 2934, 2850, 1619, 1602,
1H-NMR (400 MHz, CDCl3): δ = 7.86 (d, J = 8.4 Hz, 2H, 3′,5′-
1536, 1503, 1462, 1452, 1432, 1339, 1257, 1192, 1154, 1138, ArH), 7.20 (t, J = 7.6 Hz, 2H, 2,4-ArH), 6.73 (t, J = 7.2 Hz, 1H,
1093, 1066, 1003, 991, 953, 870, 820, 746, 693, 637, 589, 500. 4-ArH), 6.62 (d, J = 8.8 Hz, 2H, 2,6-ArH), 6.54 (d, J = 7.6 Hz, 2H,
1H-NMR (400 MHz, CDCl3): δ = 7.40 (d, 2H, J = 8.5 Hz, 3′,5′- 2′,6′-ArH), 4.36 (brs, 1H, NH), 3.85 (s, 3H, OCH3), 3.71 (brs,
ArH), 7.19 (dd, 2H, J = 7.5, 8.5 Hz, 3,5-ArH), 6.74 (t, 1H, J = 7.5 1H, NH), 3.23–3.28 (m, 2H, CH-N), 2.32–2.36 (m, 2H, CH2),
Hz, 4-ArH), 6.63–6.65 (m, 4H, 2,6-ArH, 2′,6′-ArH), 4.11 (d, 1H, J 1.80–1.81 (m, 2H, CH2), 1.41–1.46 (m, 2H, CH2), 1.23–1.41 (m,
= 4.0 Hz, NH), 3.64 (s, 2H, HC-N), 3.73 (s, 1H, NH), 2.27 (dt, 2H, CH2).
2H, J = 8.0, 13.5 Hz, CHH), 1.84 (quin, 2H, J = 8.0 Hz, CH2),
1.53–1.61 (m, 2H, CHH).
13C-NMR (100 MHz, CDCl3): δ = 167.2, 151.6, 147.4, 131.6,
129.4, 118.2, 117.6, 113.4, 111.9, 57.0, 56.8, 51.5, 32.4, 32.3,
13C-NMR (100 MHz, CDCl3): δ = 150.3, 147.5, 129.5, 126.9 24.6, 24.5.
3
1
2
(q, JCF = 4.4 Hz), 125.1 (q, JCF = 270.5 Hz), 119.1 (q, JCF
33.2 Hz), 117.9, 113.5, 112.4, 57.21, 57.15, 32.64, 32.39, 24.71, 347.17355; found: 347.17294.
24.57. HPLC: Chiralcel OD-H column, hexane–i-PrOH = 70/30,
HR-MS (ESI, MeOH): calcd for C18H21F3N2 ([M + H]+): flow rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR
335.17351; found: 335.17313, calcd for C18H21F3N2Na ([M + 12.91 min; major enantiomer (1S,2S) tR = 16.88 min.
Na]+): 357.15545; found: 357.15495.
4-((1S,2S)-2-(Phenylamino)cyclohexylamino)benzenethiol
=
HR-MS (ESI, MeOH): calcd for C20H24N2NaO2 ([M + Na]+):
=
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow (3k). Yield: 127 mg (80%), 93% ee as a pale yellow oil.
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 6.64 min;
major enantiomer (1S,2S) tR = 9.02 min.
(1S,2S)-N-(4-Cyanophenyl)-N′-phenylcyclohexane-1,2-diamine
(3h). With bis-BINOL 11: 61 mg (84%), 69% ee, reaction time
93 h.
[α]2D0 = −83.3 (c = 1.74, CHCl3).
Rf (EtOAc–petroleum ether, 1/10): 0.32.
UV (CH3CN): λmax (lg ε) = 260 (4.321) nm.
IR (as film in CCl4): ν (cm−1) = 3391, 3053, 3022, 2934,
2857, 1598, 1498, 1449, 1431, 1384, 1317, 1295, 1254, 1181,
1155, 1138, 1103, 1028, 873, 786, 693, 505.
[α]2D0 = −95.0° (c = 1.01, CHCl3).
Rf (EtOAc–petroleum ether, 1/3) = 0.32.
1H-NMR (300 MHz, CDCl3): δ = 7.17–7.22 (m, 4H, 3,5-ArH,
UV (CH3CN): λmax (lg ε) = 288 (4.598), 248 (4.216), 247 3′,5′-ArH), 6.73 (t, J = 7.2 Hz, 1H, 4-ArH), 6.63 (d, J = 8.7 Hz,
(4.215) nm.
2H, 2,6-ArH), 6.52 (d, J = 8.7 Hz, 2H, 2′,6′-ArH), 3.74 (brs, 2H,
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NH), 3.31 (s, 1H, SH), 3.23 (dt, J = 3.6, 9.3 Hz, 1H, CH-N), 3.14
13C-NMR (100 MHz, CDCl3): δ = 160.8, 149.6, 149.0, 129.9,
(dt, J = 3.6, 9.3 Hz, 1H, CH-N), 2.30–2.37 (m, 2H, CH2), 129.2, 117.4, 113.4, 106.4, 102.5, 99.4, 57.2, 57.1, 55.0, 32.5,
1.77–1.80 (m, 2H, CH2), 1.39–1.46 (m, 2H, CH2), 1.18–1.29 (m, 34.4, 24.5 (2C).
2H, CH2).
13C-NMR (100 MHz, CDCl3): δ = 147.5, 146.7, 133.2, 129.3, H]+): 297.19669; found: 297.19614, calcd for C19H24N2NaO
117.6, 114.7, 114.0, 113.4, 57.3, 57.1, 32.4, 32.3, 24.55, 24.50. ([M
Na]+): 319.17863; found: 319.17808, calcd for
HR-MS (ESI, MeOH): calcd for C18H23N2S ([M + H]+): C38H48F2N4NaO ([2M + Na]+): 615.36750; found: 615.36695.
299.15819; found: 299.15765, calcd for C18H22N2NaS ([M + HPLC: Chiralcel AD-H column, hexane–i-PrOH = 90/10, flow
HR-MS (ESI, CHCl3–MeOH): calcd for C19H25N2O ([M +
+
Na]+): 321.14014; found: 321.13958, calcd for C36H44N4NaS2 rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 8.34 min;
([2M + Na]+): 619.29051; found: 619.28996.
major enantiomer (1S,2S) tR = 9.64 min.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
(1S,2S)-N-(3-Bromophenyl)-N′-phenylcyclohexane-1,2-
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 10.71 min; diamine (3n).3j Yield: 160 mg (93%), 83% ee as a pale
major enantiomer (1S,2S) tR = 14.57 min.
(1S,2S)-N-Phenyl-N′-m-tolylcyclohexane-1,2-diamine (3l). Yield:
126 mg (89%), 86% ee as a pale yellow oil.
[α]2D0 = −25.5 (c = 0.549, CHCl3).
yellow oil.
[α]2D0 = −34.2 (c = 0.729, CHCl3).
Rf (EtOAc–petroleum ether, 1/10): 0.42.
IR (film): ν (cm−1) = 3392, 3053, 3021, 2933, 2857, 1595,
1498, 1480, 1448, 1384, 1317, 1254, 1204, 1179, 1155, 1137,
1106, 1028, 986, 889, 842, 825, 787, 761, 693.
Rf (EtOAc–petroleum ether, 1/10): 0.45.
UV (CH3CN): λmax (lg ε) = 253 (4.146) nm.
IR (film): ν (cm−1) = 3386, 3049, 2932, 2856, 1601, 1502,
1H-NMR (300 MHz, CDCl3): δ = 7.20 (dd, J = 7.5, 8.4 Hz, 2H,
1431, 1383, 1321, 1256, 1204, 1179, 1136, 1105, 1071, 1028, 3,5-ArH), 7.02 (t, J = 8.1 Hz, 1H, 5′-ArH), 6.83 (ddd, J = 0.9, 1.6,
993, 866, 692. 7.8 Hz, 1H, 4′-ArH), 6.72–6.77 (m, 2H, 2′-ArH, 4-ArH), 6.63 (d, J
1H-NMR (400 MHz, CDCl3): δ = 7.18 (dd, J = 7.6, 8.2 Hz, 2H, = 8.0 Hz, 2H, 2,6-ArH), 6.51 (ddd, J = 0.9, 1.8, 7.3 Hz, 1H,
3,5-ArH), 7.07 (dd, J = 7.6, 8.4 Hz, 1H, 5′-ArH), 6.72 (t, J = 6′-ArH), 3.80 (brs, 2H, NH), 3.23 (dt, J = 3.6, 9.3 Hz, 1H, CH-N),
7.6 Hz, 1H, 4-ArH), 6.62 (d, J = 7.6 Hz, 2H, 2,6-ArH), 6.54 (d, J = 3.16 (dt, J = 3.6, 9.3 Hz, 1H, CH-N), 2.31–2.37 (m, 2H, CH2),
7.2 Hz, 1H, 6′-ArH), 6.43–6.45 (m, 2H, 3′,4′-ArH), 3.79 (brs, 2H, 1.78–1.82 (m, 2H, CH2), 1.39–1.47 (m, 2H, CH2), 1.21–1.25 (m,
NH), 3.16–3.24 (m, 2H, CH-N), 2.33–2.37 (m, 2H, CH2), 2.28 (s, 2H, CH2).
3H, CH3), 1.76–1.80 (m, 2H, CH2), 1.40–1.46 (m, 2H, CH2),
1.20–1.27 (m, 2H, CH2).
13C-NMR (75 MHz, CDCl3): δ = 149.8, 147.5, 130.5 129.3,
123.3, 120.1, 117.7, 115.7, 113.5, 112.2, 57.2, 57.0, 32.4, 32.3,
13C-NMR (100 MHz, CDCl3): δ = 147.6 (2C), 138.9, 129.2, 24.5, 24.4.
129.1, 118.4, 117.4, 114.2, 113.4, 110.4, 57.1, 57.0, 32.5, 32.4,
24.54, 24.50, 21.5.
HR-MS (ESI, CHCl3–MeOH): calcd for C18H22Br N2 ([M +
H]+): 345.09664, found: 345.09609, calcd for C18H22BrN2Na ([M
HR-MS (ESI, CHCl3, MeOH): calcd for C19H25N2 ([M + H]+): + Na]+): 367.07858; found: 367.07803, calcd for C38H42Br2N4Na
281.20177; found: 281.20123, calcd for C19H24N2Na ([M + ([2M + Na]+): 711.16739; found: 711.16684.
Na]+): 303.18372; found: 303.18317, calcd for C38H48N4Na
([2M + Na]+): 584.37767; found: 583.37712.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 6.98 min;
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow major enantiomer (1S,2S) tR = 8.17 min.
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 6.05 min;
major enantiomer (1S,2S) tR = 6.87 min.
(1S,2S)-N-Phenyl-N′-(3-trifluoromethylphenyl)cyclohexane-
1,2-diamine (3o). Yield: 150 mg (90%), 82% ee as a colourless
(1S,2S)-N-(3-Methoxyphenyl)-N′-phenylcyclohexane-1,2- viscous liquid.
diamine (3m).12a Yield: 117 mg (88%), 91% ee as a pale
yellow oil.
[α]2D0 = −15.9 (c = 2.819, CHCl3).
Rf (EtOAc–petroleum ether, 1/10): 0.33.
[α]2D0 = −28.0 (c = 3.24, CHCl3). [lit.12a [α]2D5 = −14.1 (c = 1.19,
56% ee, CHCl3)].
UV (CH3CN): λmax (lg ε) = 253 (4.146) nm.
IR (film): ν (cm−1) = 3393, 3053, 2936, 2858, 1601, 1502,
1433, 1383, 1341, 1317, 1255, 1165, 1125, 1069, 1028, 994, 899,
865, 824, 787, 696, 662, 500, 451.
Rf (EtOAc–petroleum ether, 1/10): 0.23.
UV (CH3CN): λmax (lg ε) = 294 (3.734), 250 (4.344) nm.
IR (as film in CCl4): ν (cm−1) = 3384, 3050, 2930, 2855,
1H-NMR (400 MHz, CDCl3): δ = 7.26 (t, J = 8.0 Hz, 1H, 5′-
1914, 1614, 1487, 1450, 1358, 1258, 1212, 1161, 1137, 1106, ArH), 7.21 (dd, J = 7.6, 8.4 Hz, 2H, 3,5-ArH), 6.95 (d, J = 7.6 Hz,
1049, 992, 953.
1H, 4′-ArH), 6.81 (s, 1H, 2′-ArH), 6.73–6.77 (m, 2H, 4-ArH, 6′-
1H-NMR (300 MHz, CDCl3): δ = 7.21 (t, J = 7.5 Hz, 2H, 3,5- ArH), 6.65 (d, J = 8.0 Hz, 2H, 2,6-ArH), 4.06 (brs, 1H, NH), 3.67
ArH), 7.11 (t, J = 7.8 Hz, 1H, 5′-ArH), 6.75 (dt, J = 0.9, 7.2 Hz, (brs, 1H, NH), 3.22–3.28 (m, 2H, CH-N), 2.33–2.37 (m, 2H,
1H, 4-ArH), 6.65 (d, J = 8.4 Hz, 2H, 2,6-ArH), 6.32 (dd, J = 2.4, CH2), 1.81–1.84 (m, 2H, CH2), 1.43–1.48 (m, 2H, CH2),
8.1 Hz, 1H, 6′-ArH), 6.26 (dd, J = 2.4, 8.1 Hz, 1H, 4′-ArH), 6.21 1.25–1.31 (m, 2H, CH2).
(t, J = 2.1 Hz, 1H, 2′-ArH), 3.87 (brs, 2H, NH), 3.79 (s, 3H,
2
13C-NMR (100 MHz, CDCl3): δ = 147.9, 147.4, 131.5 (q, JCF
1
OCH3), 3.21–3.23 (m, 2H, CH-N), 2.36–2.41 (m, 2H, CH2), = 31.6 Hz), 129.6, 129.3, 124.2 (q, JCF = 271 Hz), 117.7, 116.3,
3
3
1.79–1.82 (m, 2H, CH2), 1.41–1.48 (m, 2H, CH2), 1.23–1.27 113.7 (q, JCF = 3.8 Hz), 113.4, 109.3 (q, JCF = 3.8 Hz), 57.2,
(m, 2H, CH2).
57.0, 32.4, 32.2, 24.5, 24.4.
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HR-MS (ESI, CHCl3–MeOH): calcd for C19H22F3N2 ([M +
Rf (EtOAc–petroleum ether, 1/10): 0.40.
H]+): 335.17351; found: 335.17296, calcd for C19H21F3N2Na ([M
+ Na]+): 357.15545; found: 357.15490, calcd for C38H42F6N4Na
([2M + Na]+): 691.32114; found: 691.32059.
UV (CH3CN): λmax (lg ε) = 290 (3.691), 248 (4.297) nm.
IR (film): ν (cm−1) = 3396, 3049, 3021, 2929, 2856, 2631,
1918, 1826, 1746, 1619, 1495, 1449, 1384, 1358, 1334, 1254,
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow 1206, 1186, 1156, 1136, 1106, 1080, 1033, 993, 954, 939, 914,
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 5.33 min; 976, 839, 784, 745, 693, 620, 550, 504, 445.
major enantiomer (1S,2S) tR = 6.04 min.
1H-NMR (400 MHz, CDCl3): δ = 7.23 (t, J = 7.6 Hz, 2H, 3,5-
(1S,2S)-N-Phenyl-N′-o-tolylcyclohexane-1,2-diamine ArH), 6.98–7.07 (m, 2H, 3′,5′-ArH), 6.76–6.84 (m, 2H, 4′,6′-ArH),
(3p).3j Yield: 126 mg (90%), 47% ee as a pale yellow oil.
[α]2D0 = +5.8° (c = 0.69, CHCl3).
6.67–6.71 (m, 3H, 2,4,6-ArH), 4.05 (brs, 1H, NH), 3.87 (brs, 1H,
NH), 3.29 (brs, 2H, CH-N), 2.33–2.43 (m, 2H, CH2),
1.81–1.84 (m, 2H, CH2), 1.45–1.50 (m, 2H, CH2), 1.29–1.36 (m,
2H, CH2).
Rf (EtOAc–petroleum ether, 1/10): 0.46.
UV (CH3CN): λmax (lg ε) = 292 (3.827), 252 (4.453) nm.
IR (film): ν (cm−1) = 3382, 2931, 2856, 1762, 1602, 1502,
1383, 1318, 1256, 1139, 1052, 875, 824, 786, 747, 692.
1
13C-NMR (100 MHz, CDCl3): δ = 151.9 (d, JCF = 237 Hz),
2
4
147.6, 136.9 (d, JCF = 11.5 Hz), 129.2, 124.4 (d, JCF = 3.3 Hz),
1H-NMR (300 MHz, CDCl3): δ = 7.16–7.26 (m, 3H, 3,5-ArH, 117.5, 116.8 (d, JCF = 7.0 Hz), 114.7 (d, JCF = 18.7 Hz), 113.5,
3
2
5′-ArH), 7.09 (dd, J = 0.6, 6.9 Hz, 1H, 3′-ArH), 6.66–6.79 (m, 5H, 112.6 (d, 3JCF = 3.2 Hz), 57.0, 56.8, 32.3, 32.2, 24.5, 24.3.
4-ArH, 4′-ArH, 2,6-ArH, 6′-ArH), 3.79 (brs, 2H, NH), 3.37 (dt, J =
HR-MS (ESI, CHCl3–MeOH): calcd for C18H22FN2 ([M + H]+):
3.6, 9.0 Hz, 1H, CH-N), 3.28 (dt, J = 3.6, 9.0 Hz, 1H, CH-N), 285.17670; found: 285.17616, calcd for C18H21FN2Na ([M +
2.37–2.46 (m, 2H, CH2), 2.04 (s, 3H, CH3), 1.82–1.86 (m, 2H, Na]+): 307.15865; found: 307.15810, calcd for C36H42F2N4Na
CH2), 1.46–1.52 (m, 2H, CH2), 1.28–1.37 (m, 2H, CH2).
([2M + Na]+): 591.32752; found: 591.32697.
13C-NMR (75 MHz, CDCl3): δ = 147.9, 145.7, 130.3, 129.3,
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
126.9, 122.8, 117.5, 116.9, 113.4, 110.1, 57.7, 57.1, 32.70, 24.7, rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 5.48 min;
24.6, 17.5.
HR-MS (ESI, CHCl3–MeOH): calcd for C19H25N2 ([M + H]+):
major enantiomer (1S,2S) tR = 6.91 min.
(1S,2S)-N-(2-Carbomethoxyphenyl)-N′-phenylcyclohex-
281.20177; found: 281.20123, calcd for C19H24N2Na ([M + ane-1,2-diamine (3s). Yield: 240 mg (75%), 22% ee as a
Na]+): 303.18372; found: 303.18317, calcd for C38H48N4Na colourless solid; m.p.: 105–106 °C.
([2M + Na]+): 584.37767; found: 583.37712.
[α]2D4 = −15.2 (c = 0.987, CHCl3).
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 5.01 min;
major enantiomer (1S,2S) tR = 6.50 min.
Rf (EtOAc–petroleum ether, 1/5): 0.28.
UV (CH3CN): λmax (lg ε) = 432 (2.951), 350 (3.701), 250
(4.135), 231 (3.937) nm.
(1S,2S)-N-(2-Methoxyphenyl)-N′-phenylcyclohexane-1,2-
IR (KBr): ν (cm−1) = 3385, 3344, 3085, 3028, 2943, 2925,
diamine (3q).12a Yield: 117 mg (79%), 56% ee as a colourless 2853, 1680, 1598, 1579, 1518, 1495, 1438, 1308, 1253, 1236,
solid; m.p.: 94–95 °C.
1200, 1180, 1165, 1135, 1102, 1077, 1048, 990, 875, 846, 797,
[α]2D0 = not measurable (c = 0.90, CHCl3) [lit.2 [α]2D5 = −4.1 743, 702, 690, 629, 558, 526, 478.
(c = 1.25, 99% ee, CHCl3)].
1H-NMR (300 MHz, CDCl3): δ = 7.87–7.90 (m, 2H, 3′-ArH,
Rf (EtOAc–petroleum ether, 1/10): 0.24.
UV (CH3CN): λmax = 294, 252, 234 nm.
NH), 7.33 (dt, J = 2.4, 7.8 Hz, 1H, 5′-ArH), 7.14 (dd, J = 7.2,
7.2 Hz, 2H, 3,5-ArH), 6.77 (d, J = 8.7 Hz, 1H, 6′-ArH), 6.67 (t, J =
IR (as film in CCl4): ν (cm−1) = 3374, 3337, 3015, 2922, 7.2 Hz, 1H, 4′-ArH), 6.54–6.61 (m, 3H, 2,6-ArH, 4-ArH), 3.79 (brs,
1599, 1504, 1452, 1255, 1222, 1116.
2H, NH), 3.37 (dt, J = 3.6, 9.0 Hz, 1H, CH-N), 3.28 (dt, J = 3.6,
1H-NMR (400 MHz, CDCl3): δ = 7.16–7.20 (m, 2H, 3,5-ArH), 9.0 Hz, 1H, CH-N), 2.37–2.46 (m, 2H, CH2), 1.82–1.86 (m, 2H,
6.87–6.91 (m, 1H, 4-ArH), 6.61–6.78 (m, 6H, 2,6-ArH, 3′,4′,5′,6′- CH2), 1.46–1.52 (m, 2H, CH2), 1.28–1.37 (m, 2H, CH2).
ArH), 4.33 (brs, 1H, NH), 3.94 (brs, 1H, NH), 3.77 (s, 3H,
13C-NMR (100 MHz, CDCl3): δ = 168.9, 150.6, 147.0, 134.4,
OCH3), 3.26–3.28 (m, 2H, CH-N), 2.31–2.41 (m, 2H, CH2), 131.9, 129.1, 117.7, 114.5, 113.9, 111.5, 110.4, 56.4, 54.5, 51.4,
1.78–1.80 (m, 2H, CH2), 1.42–1.47 (m, 2H, CH2), 1.26–1.28 (m, 30.9, 26.8, 23.8, 23.5.
2H, CH2).
13C-NMR (100 MHz, CDCl3): δ = 148.0, 147.4, 137.6, 129.3, 325.19105; found: 325.19089, calcd for C20H24N2O2 ([M + Na]+):
121.2, 117.4, 116.6, 113.7, 110.3, 109.8, 57.2, 56.8, 55.4, 32.5, 347.17300; found: 347.17273, calcd for 20H42F2N4Na
HR-MS (ESI, MeOH): calcd for C20H25N2O2 ([M + H]+):
C
32.4, 24.8, 24.5.
([2M + Na]+): 671.35678; found: 671.35636.
MS (ESI, acetone): m/z = 297 [M + H]+, 319 [M + Na]+, 335
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 98/2, flow
rate = 1.0 mL min−1; major enantiomer (1S,2S) tR = 8.72;
[M + K]+.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow minor enantiomer (1R,2R) tR = 9.78 min.
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 6.08 min;
major enantiomer (1S,2S) tR = 9.60 min.
(1S,2S)-N-(1-Naphthyl)-N′-phenylcyclohexane-1,2-diamine
(3t).3j Yield: 142 mg (86%), 77% ee as a colorless solid; reac-
(1S,2S)-N-(2-Fluorophenyl)-N′-phenylcyclohexane-1,2-diamine tion time: 48 h.
(3r). Yield: 126 mg (89%), 76% ee as a colourless oil.
[α]2D0 = −31.3 (c = 0.606, CHCl3).
Rf (EtOAc–petroleum ether, 1/10) = 0.40.
UV (CH3CN): λmax (lg ε) = 332 (4.037), 251 (4.546) nm.
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IR (KBr): ν (cm−1) = 3374, 3055, 2917, 2849, 1913, 1600,
1H-NMR (300 MHz, CDCl3): δ = 7.20 (m, 2H, 3,5-ArH),
1581, 1527, 1508, 1480, 1436, 1407, 1373, 1357, 1337, 1316, 6.72–6.79 (m, 2H, 4-ArH, 6′-ArH), 6.66 (d, J = 8.4 Hz, 2H, 2,6-
1305, 1295, 1255, 1178, 1169, 1153, 1135, 1114, 1085, 1070, ArH), 6.26 (d, J = 2.7 Hz, 1H, 2′-ArH), 6.21 (dd, J = 2.7, 8.4 Hz,
1037, 1026, 1017, 991, 949, 863, 848, 787, 771, 746, 692, 642, 1H, 5′-ArH), 3.88 (brs, 1H, NH), 3.83 (s, 6H, OCH3), 3.68 (brs,
601, 573, 502, 466, 420.
1H, NH), 3.18–3.25 (m, 1H, CH-N), 3.13 (dt, J = 3.3, 9.5 Hz, 1H,
1H-NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 8.0 Hz, 1H, ArH), CH-N), 2.28–2.34 (m, 2H, CH2), 1.78–1.82 (m, 2H, CH2),
7.70 (d, J = 8.0 Hz, 1H, ArH), 7.42–7.45 (m, 1H, ArH), 7.37–7.39 1.40–1.43 (m, 2H, CH2), 1.22–1.26 (m, 2H, CH2).
(m, 2H, ArH), 7.20–7.28 (m, 3H, ArH), 6.77 (t, J = 7.2 Hz, 1H,
13C-NMR (75 MHz, CDCl3): δ = 149.9, 147.6, 142.3, 141.6,
ArH), 6.69–6.71 (m, 3H, ArH), 4.71 (brs, 1H, NH), 3.87 (brs, 1H, 129.1, 117.4, 113.4, 113.0, 104.1, 100.1, 58.0, 57.1, 56.5, 55.5,
NH), 3.50 (dt, J = 3.2, 9.8 Hz, 1H, CH-N), 3.37 (dt, J = 3.2, 9.8 32.4, 32.3, 24.4 (2C).
Hz, 1H, CH-N), 2.55 (d, J = 14 Hz, 1H, CH2), 2.41 (d, J = 14 Hz,
1H, CH2), 1.84–1.86 (m, 2H, CH2), 1.47–1.53 (m, 2H, CH2), H]+): 327.20725; found: 327.20670, calcd for C20H26N2NaO2
1.29–1.35 (m, 2H, CH2). ([M
Na]+): 349.18920; found: 349.18865, calcd for
13C-NMR (100 MHz, CDCl3): δ = 147.6, 142.9, 134.5, 129.5, C40H52N4NaO4 ([2M + Na]+): 675.38863; found: 675.38808.
HR-MS (ESI, CHCl3–MeOH): calcd for C20H27N2O2 ([M +
+
125.8, 124.8, 124.1, 120.3, 118.0, 117.6, 114.0, 105.0, 57.9, 57.3,
32.70, 32.12, 25.03, 24.66.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 85/15, flow
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 11.15 min;
major enantiomer (1S,2S) tR = 12.57 min.
MS (EI, 70 eV): m/z (%) = 317 (100) [M + H]+, 224, 174.
HPLC: Chiralcel OD-H column, hexane–i-PrOH = 85/15,
(1S,2S)-N-Phenyl-N′-(3,4,5-trimethoxyphenyl)cyclohexane-
1,2-diamine (3w).15d Yield: 126 mg (84%), 98% ee as a pale
yellow oil.
flow rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR
8.63 min; major enantiomer (1S,2S) tR = 19.51 min.
=
(1S,2S)-N-(2,4-Difluorophenyl)-N′-phenylcyclohexane-1,2-
diamine (3u). Yield: 126 mg (83%) as a pale yellow oil; ee:
65%.
[α]2D0 = −25.2 (c = 2.857, CHCl3).
Rf (EtOAc–petroleum ether, 1/3): 0.22.
UV (CH3CN): λmax (lg ε) = 248 (4.556) nm.
[α]2D0 = −24.1 (c = 0.706, CHCl3).
Rf (EtOAc–petroleum ether, 1/10): 0.25.
IR (film): ν (cm−1) = 3369, 3052, 2933, 2856, 1601, 1506,
1463, 1451, 1430, 1412, 1384, 1315, 1278, 1236, 1204, 1184,
1127, 1011, 868, 787, 694, 633, 525.
UV (CH3CN): λmax (lg ε) = 297 (3.716), 249 (4.297) nm.
IR (film): ν (cm−1) = 3395, 3052, 3021, 2933, 2857, 2661,
1H-NMR (400 MHz, CDCl3): δ = 7.18 (d, J = 7.2, 8.8 Hz, 2H,
1826, 1602, 1503, 1431, 1383, 1304, 1265, 1213, 1196, 1179, 3,5-ArH), 6.72 (t, J = 7.2 Hz, 1H, 4-ArH), 6.64 (d, J = 8.8 Hz, 2H,
1141, 1098, 1083, 1028, 993, 960, 910, 872, 848, 825, 798, 749, 2,6-ArH), 5.86 (s, 2H, 2′,6′-ArH), 3.84 (brs, 2H, NH), 3.80 (s, 6H,
722, 693, 586, 539, 500, 450.
OCH3), 3.77 (s, 3H, OCH3), 3.21 (dt, J = 3.2, 9.8 Hz, 1H, CH-N),
1H-NMR (400 MHz, CDCl3): δ = 7.18 (dd, J = 7.6, 8.6 Hz, 2H, 3.15 (dt, J = 3.2, 9.8 Hz, 1H, CH-N), 2.33–2.36 (m, 2H, CH2),
3,5-ArH), 6.62–6.79 (m, 7H, 4′,6′,3′,5′,2,4,6-ArH), 3.80 (brs, 2H, 1.78–1.81 (m, 2H, CH2), 1.41–1.46 (m, 2H, CH2), 1.22–1.28
NH), 3.25 (dt, J = 3.6, 9.8 Hz, 1H, CH-N), 3.14–3.18 (m, 1H, CH- (m, 2H, CH2).
N), 2.33–2.36 (m, 2H, CH2), 1.77–1.79 (m, 2H, CH2), 1.40–1.45
13C-NMR (100 MHz, CDCl3): δ = 153.9, 147.6, 144.3, 130.2,
(m, 2H, CH2), 1.23–1.39 (m, 2H, CH2).
129.2, 117.5, 113.4, 91.2, 60.9, 57.6, 57.1, 55.9 (2C), 32.6, 32.3,
= 11, 237 24.48, 24.46.
1,3
13C-NMR (100 MHz, CDCl3): δ = 154.3 (dd,
J
CF
1,3
2,4
Hz), 151.4 (dd,
J
CF
= 11.5, 240 Hz), 147.5, 132.5 (dd,
J
CF
=
HR-MS (ESI, CHCl3–MeOH): calcd for C21H29N2O3 ([M +
3,3
2.8, 11.5 Hz), 129.2, 117.6, 113.6, 113.0 (dd,
J
= 4.4, H]+): 357.21782; found: 357.21727, calcd for C21H28N2NaO3
CF
2,2
2,4
8.9 Hz), 110.5 (dd,
26.3 Hz), 57.5, 57.1, 32.3, 32.2, 24.4, 24.3.
HR-MS (ESI, CHCl3–MeOH): calcd for C18H21F2N2 ([M +
J
= 3.7, 21.6 Hz), 103.6 (dd,
J
= 23, ([M
+
Na]+): 379.19976; found: 379.19921, calcd for
CF
CF
C42H56N4NaO6 ([2M + Na]+): 735.40976; found: 735.40976.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 85/15, flow
H]+): 303.16728; found: 303.16673, calcd for C18H20F2N2Na ([M rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 14.98 min;
+ Na]+): 325.14922; found: 325.14868, calcd for C36H40F4N4Na major enantiomer (1S,2S) tR = 16.50 min.
([2M + Na]+): 627.30868; found: 627.30813.
(1S,1′S,2S,2′S)-N1,N1′-(1,4-Phenylene)bis(N2-phenylcyclohex-
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow ane-1,2-diamine) (3x). Yield: 136 mg (70%), 98% ee as a
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 5.88 min; colourless solid; m.p.: 120–121 °C.
major enantiomer (1S,2S) tR = 7.29 min.
(1S,2S)-N-(3,4-Dimethoxyphenyl)-N′-phenylcyclohexane-1,2-
diamine (3v). Yield: 126 mg (81%), 98% ee as a pale yellow
oil.
[α]2D0 = −131.4 (c = 0.837, CHCl3).
Rf (EtOAc–petroleum ether, 1/5): 0.34.
UV (CH3CN): λmax (lg ε) = 256 (4.507) nm.
IR (film): ν (cm−1) = 3387, 3347, 3014, 2925, 2851, 1600,
1502, 1447, 1429, 1357, 1312, 1293, 1245, 1204, 1176, 1152,
1132, 1102, 991, 872, 825, 748, 692, 641, 566, 507, 477.
1H-NMR (400 MHz, CDCl3): δ = 7.19 (dd, J = 7.2, 8.4 Hz, 4H,
[α]2D0 = −111.6 (c = 0.197, CHCl3).
Rf (EtOAc–petroleum ether, 1/3): 0.25.
UV (CH3CN): λmax (lg ε) = 297 (3.716), 249 (4.297) nm.
IR (film): ν (cm−1) = 3370, 3051, 2997, 2932, 2855, 2831, 3,5-ArH), 6.72 (t, J = 7.2 Hz, 2H, 4-ArH), 6.65 (d, J = 8.4 Hz, 4H,
1601, 1513, 1463, 1383, 1295, 1258, 1235, 1210, 1168, 1139, 2,6-ArH), 6.58 (s, 4H, 2′,3′,5′,6′-ArH), 3.69 (brs, 4H, NH), 3.18
1104, 1127, 993, 954, 867, 825, 752, 694, 568, 504, 462.
(dt, J = 3.6, 9.8 Hz, 2H, CH-N), 3.07 (dt, J = 3.6, 9.8 Hz, 2H,
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CH-N), 2.26–2.31 (m, 4H, CH2), 1.76–1.79 (m, 4H, CH2),
1.38–1.44 (m, 4H, CH2), 1.17–1.26 (m, 4H, CH2).
[α]2D2 = +28.1 (c = 1.02, CHCl3).
Rf (ether–petroleum ether, 1/4) = 0.30.
UV (CHCl3): λmax (lg ε) = 250 (4.424), 295 (3.778) nm.
IR (film): ν (cm−1) = 3391, 3018, 2957, 1601, 1504, 1430,
13C-NMR (100 MHz, CDCl3): δ = 147.9, 140.9, 129.2, 117.5,
116.0, 113.6, 58.5, 57.3, 32.6, 32.5, 24.68, 24.64.
HR-MS (ESI, CHCl3, MeOH): calcd for C30H38N4 ([M]+): 1316, 1242, 1180.
454.30965; found: 454.30915, calcd for C30H38N4Na ([M +
1H-NMR (400 MHz, CDCl3): δ = 7.19 (dd, J = 7.5, 8.5 Hz, 2H,
Na]+): 477.29942; found: 477.29911, calcd for C60H77N8 ([2M + 3,5-ArH), 7.00 (d, J = 8.0 Hz, 2H, 3′,5′-ArH), 6.73 (t, J = 7.5 Hz,
H]+): 909.62712; found: 909.62624, calcd for C60H76N8Na 1H, 4-ArH), 6.65 (d, J = 7.5 Hz, 2H, 2,6-ArH), 6.58 (d, J = 8.5 Hz,
([2M + Na]+): 931.60906; found: 931.60871.
2H, 2′,6′-ArH), 3.72 (brs, 2H, NH), 3.57–3.63 (m, 2H, HC-N),
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 80/20, flow 2.21–2.30 (m, 5H, CHH,CH3), 1.82 (quin, J = 7.5 Hz, 2H, CH2),
rate = 1.0 mL min−1; minor enantiomer (1R,1′R,2R,2′R) tR
=
1.54 (dt, J = 7.5, 13.5 Hz, 2H, CHH).
18.94 min; meso isomer tR = 25.6 min; major enantiomer
(1S,1′S,2S,2′S) tR = 35.91 min.
(1S,2S)-N,N′-Di(4-methoxyphenyl)cyclohexane-1,2-diamine
13C-NMR (100 MHz, CDCl3): δ = 147.8, 145.4, 129.8, 129.3,
126.8, 117.5, 113.6, 113.4, 60.99, 60.66, 31.19 (2C), 21.4, 20.3.
MS (EI, 70 eV): m/z (%) = 266 (73), 189 (72), 174 (100), 160
(3y). Yield: 140 mg (86%), 98% ee as a colorless solid; m.p.: (79), 132 (16), 91 (9), 77 (12).
67–68 °C.
HR-MS (ESI, MeOH): calcd for C18H23N2 ([M + H]+):
[α]2D0 = −35.0 (c = 0.97, CHCl3).
Rf (EtOAc–petroleum ether, 1/3) = 0.37.
267.18049; found: 267.18548.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
UV (CH3CN): λmax (lg ε) = 244 (4.234), 247 (4.231), 312 rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 11.28 min;
(3.608) nm.
IR (KBr): ν (cm−1) = 3347, 3025, 2950, 1508, 1465, 1352,
1242, 1180.
major enantiomer (1S,2S) tR = 12.93 min.
(1S,2S)-N-(4-Methoxyphenyl)-N′-phenylcyclopentane-1,2-
diamine (4c).15a Yield: 136 mg (96%), >99% ee as a yellow oil.
[α]2D2 = +24.4 (c = 1.02, CHCl3).
1H-NMR (400 MHz, CDCl3): δ = 6.79 (dd, J = 2.4, 6.8 Hz, 4H,
3,5-ArH), 6.63 (dd, J = 2.4, 6.8 Hz, 4H, 2,6-ArH), 3.76 (s, 6H,
OCH3), 3.66 (brs, 2H, NH), 3.07–3.09 (m, 2H, CH-N), 2.30–2.33
(m, 2H, CH2), 1.70–1.76 (m, 2H, CH2), 1.37–1.41 (m, 2H, CH2),
1.19–1.21 (m, 2H, CH2).
Rf (ether–petroleum ether, 1/4): 0.14.
UV (CHCl3): λmax (lg ε) = 248 (4.350), 300 (3.653) nm.
IR (film): ν (cm−1) = 3386, 3050, 2954, 1602, 1512, 1440,
1316, 1234, 1179.
13C-NMR (100 MHz, CDCl3): δ = 152.5, 141.9, 115.6, 115.0,
58.7, 55.9, 32.8, 24.8.
1H-NMR (300 MHz, CDCl3): δ = 7.19 (t, 2H, 3,5-ArH),
6.61–6.82 (m, 7H, ArH), 3.76 (s, 3H, OCH3), 3.75 (brs, 2H, NH),
HR-MS (ESI, MeOH): calcd for C20H27N2O2 ([M + H]+): 3.57 (m, 2H, HC-N), 2.24 (dt, J = 7.0, 13.5 Hz, 2H, CHH), 1.81
327.20670; found: 327.20660.
(quin, J = 7.5 Hz, 2H, CH2), 1.53 (dt, J = 7.5, 13.5 Hz, 2H,
HPLC: Chiralcel OD-H column, hexane–i-PrOH = 70/30, CHH).
flow rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR
81.12 min; major enantiomer (1S,2S) tR = 109.05 min.
=
13C-NMR (100 MHz, CDCl3): δ = 152.3, 147.8, 141.9, 129.3,
117.5, 114.9, 114.8, 113.4, 61.6, 60.6, 55.8, 31.25, 31.19, 21.4.
MS (EI, 70 eV): m/z (%) = 282 (32), 190 (100), 160 (91), 132
(13), 123 (7), 93 (6); 77 (8).
HR-MS (ESI, MeOH): calcd for C18H23N2O: 283.18104 ([M +
H]+); found: 283.18028.
(1S,2S)-N,N′-Diphenylcyclopentane-1,2-diamine (4a).3j Yield:
130 mg (90%), >99% ee as a yellow oil.
[α]2D2 = +45.5 (c = 0.99, CHCl3).
Rf (ether–petroleum ether, 1/4): 0.26.
UV (CH3CN): λmax (lg ε) = 201 (4.325), 206 (4.304), 251
(4.402) nm.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 21.01 min;
IR (film): ν (cm−1) = 3393, 3050, 2958, 2871, 1601, 1431, major enantiomer (1S,2S) tR = 26.05 min.
1384, 1321, 1179.
(1S,2S)-N-Phenyl-N′-(4-trifluoromethylphenyl)-cyclopen-
1H-NMR (400 MHz, CDCl3): δ = 7.16 (dd, J = 7.5, 8.5 Hz, 4H, tane-1,2-diamine (4d).15a Yield: 114 mg (71%), 95% ee as a
3,5-ArH), 6.71 (t, J = 8.5 Hz, 2H, 4-ArH), 6.63 (d, J = 8.5 Hz, 4H, yellow oil.
2,6-ArH), 3.77 (brs, 2H, NH), 3.57–3.63 (m, 2H, HC-N), 2.25
(dq, J = 7.5, 13.5 Hz, 2H, CHH), 1.81 (quin, J = 7.5 Hz, 2H,
CH2), 1.53 (dq, J = 7.5 Hz, 13.5 Hz, 2H, CHH).
[α]2D2 = +23.6 (c = 1.02, CHCl3).
Rf (ether–petroleum ether, 1/4): 0.10.
UV (CHCl3): λmax (lg ε) = 259 (4.259), 287 (3.610), 341 (2.591)
13C-NMR (100 MHz, CDCl3): δ = 147.7, 129.3, 117.5, 113.4, nm.
60.6, 31.2, 21.4.
IR (film): ν (cm−1) = 3396, 2960, 1615, 1503, 1432, 1326,
MS (EI, 70 eV): m/z (%) = 252 (11), 160 (100), 149 (10), 132 1158, 1108.
(85), 118 (48), 106 (65), 93 (85).
1H-NMR (400 MHz, CDCl3): δ = 7.40 (d, J = 8.5 Hz, 2H, 3′,5′-
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow ArH), 7.19 (dd, J = 7.5, 8.5 Hz, 2H, 3,5-ArH), 6.74 (t, J = 7.5 Hz,
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 11.62 min; 1H, 4-ArH), 6.63–6.65 (m, 4H, 2,6-ArH, 2′,6′-ArH), 4.11 (d, J =
major enantiomer (1S,2S) tR = 13.52 min.
4.0 Hz, 1H, NH), 3.73 (brs, 1H, NH), 3.64 (s, 2H, HCN), 2.27
(1S,2S)-N-Phenyl-N′-p-tolylcyclopentane-1,2-diamine (dt, J = 8.0, 13.5 Hz, 2H, CHH), 1.84 (quin, J = 8.0 Hz, 2H,
(4b).15a Yield: 110 mg (83%), >99% ee as a yellow oil.
CH2), 1.53–1.61 (m, 2H, CHH).
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13C-NMR (100 MHz, CDCl3): δ = 150.2, 147.4, 129.4,
(1S,2S)-N,N′-Bis(4-methoxyphenyl)cyclopentane-1,2-diamine
3
1
126.6 (q, JCF = 3.7 Hz), 124.9 (q, JCF = 268.8 Hz), 118.9 (4g).15a Yield: 117 mg (75%), >99% ee as a brown solid; m.p.:
2
(q, JCF = 33.0 Hz), 117.8, 113.4, 112.4, 60.71, 60.32, 31.23, 127–128 °C.
31.08, 21.5.
MS (EI, 70 eV): m/z (%) = 320 (17), 228 (100), 200 (9), 160
[α]2D2 = + 10.0 (c = 1.02, CHCl3).
Rf (EtOAc–petroleum ether, 1/3): 0.33.
(68), 132 (17), 106 (11), 77 (7).
UV (CHCl3): λmax (lg ε) = 203 (4.339), 248 (4.370), 314 (3.677)
HR-MS (ESI, MeOH): calcd for C18H20F3N2 ([M + H]+): nm.
321.15786; found: 321.15712.
IR (film): ν (cm−1) = 3373, 2965, 1615, 1509, 1464, 1312,
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow 1258, 1229, 1174, 1029.
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 14.87 min;
major enantiomer (1S,2S) tR = 18.31 min.
1H-NMR (300 MHz, CDCl3): δ = 6.77 (d, J = 9.0 Hz, 4H, 3,5-
ArH), 6.61 (d, J = 9.0 Hz, 4H, 2,6-ArH), 3.75 (s, 6H, OCH3),
4-((1S,2S)-2-(Phenylamino)cyclopentylamino)benzenethiol 3.48–3.54 (m, 4H, HC-N), 2.21 (dt, J = 7.0, 13.5 Hz, 2H, CHH),
(4e). Yield: 97 mg (68%), 99% ee as a pale yellow oil.
1.79 (quin, J = 7.5 Hz, 2H, CH2), 1.51 (dt, J = 7.5, 13.5 Hz, 2H,
CHH).
[α]2D0 = −3.2 (c = 0.936, CHCl3).
Rf (EtOAc–petroleum ether, 1/10): 0.29.
UV (CH3CN): λmax (lg ε) = 256 (4.368) nm.
IR (as film in CCl4): ν (cm−1) = 3394, 3052, 3021, 2961,
13C-NMR (75 MHz, CDCl3): δ = 152.3, 141.9, 114.9, 114.8,
61.6, 55.8, 31.2, 21.4.
MS (EI, 70 eV): m/z (%) = 312 (40), 190 (100), 162 (11), 123
2872, 1599, 1500, 1431, 1384, 1316, 1293, 1181, 1154, 1126, (7), 108 (8).
871, 786, 693, 506.
HR-MS (ESI, MeOH): calcd for C19H25N2O2 ([M + H]+):
1H-NMR (400 MHz, CDCl3): δ = 7.19 (dd, J = 7.2, 8.6 Hz, 4H, 313.19160; found: 313.19080.
3,5-ArH, 3′,5′-ArH), 6.73 (t, J = 7.2 Hz, 1H, 4-ArH), 6.64 (d, J =
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
8.8 Hz, 2H, 2,6-ArH), 6.54 (d, J = 8.8 Hz, 2H, 2′,6′-ArH), 3.76 rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 31.39 min;
(brs, 2H, NH), 3.55–3.63 (m, 2H, CH-N), 3.30 (s, 1H, SH), major enantiomer (1S,2S) tR = 37.69 min.
2.19–2.29 (m, 2H, CH2), 1.78–1.86 (m, 2H, CH2), 1.49–1.59 (m,
2H, CH2).
(1S,2S)-N,N′-Diphenylcyclohex-4-ene-1,2-diamine
(5a).1 5 a Yield: 103 mg (78%), 89% ee as a colorless solid;
13C-NMR (100 MHz, CDCl3):
δ
=
147.5, 146.7, m.p.: 89–91 °C.
133.2, 129.2, 117.6, 114.8, 114.0, 113.3, 60.65, 60.63, 31.1, 31.0,
21.4.
[α]2D0 = +122.0 (c = 1.18, CHCl3).
Rf (EtOAc–petroleum ether, 1/10): 0.42.
HR-MS (ESI, MeOH): calcd for C17H20N2NaS ([M + Na]+):
307.12449; found: 307.12394, calcd for C34H40N4NaS2 ([2M +
Na]+): 591.25921; found: 591.25866.
UV (CHCl3): λmax (lg ε) = 295 (4.46), 252 (3.808) nm.
IR (KBr): ν (cm−1) = 3372, 3049, 3014, 2925, 2846, 1696,
1498, 1427, 1317, 1289, 1107.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
1H-NMR (400 MHz, CDCl3): δ = 7.21 (dd, J = 7.2, 8.6 Hz, 4H,
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 24.10 min; 3,5-ArH), 6.75 (t, J = 7.2 Hz, 2H, 4-ArH), 6.64 (d, J = 7.6 Hz, 4H,
major enantiomer (1S,2S) tR = 30.11 min.
2,6-ArH), 5.72 (s, 2H, CHvCH), 3.85 (brs, 2H, NH), 3.76 (brs,
(1S,2S)-N-(2-Methoxyphenyl)-N′-phenylcyclopentan-1,2- 2H, CH-N), 2.71 (d, J = 46.0 Hz, 2H, CH2), 2.07 (d, J = 46.0 Hz,
diamine (4f ).12a Yield: 112 mg (80%), 57% ee as a yellow oil; 2H, CH2).
m.p.: 127–128 °C, reaction time 24 h.
13C-NMR (100 MHz, CDCl3): δ = 147.5, 129.6, 124.8, 117.8,
113.6, 50.9, 30.4.
[α]2D2 = 21.7° (c = 1.00, CHCl3).
Rf (ether–petroleum ether 1/4) = 0.33.
UV (CHCl3): λmax (lg ε) = 251 (4.399), 292 (3.892) nm.
IR (film): ν (cm−1) = 3396, 3049, 2957, 2869, 2833, 1601,
MS (ESI, acetone): m/z = 265 [M + H]+, 287 [M + Na]+, 303
[M + K]+.
HR-MS (ESI, MeOH): calcd for C18H21N2 ([M + H]+):
1506, 1455, 1430, 1309, 1243, 1222, 1179, 1127, 1075, 1049, 265.16993; found: 265.17001, calcd for C18H20N2Na ([M +
1028, 993, 872, 810, 747, 693, 508.
Na]+): 287.15187; found: 287.15208.
1H-NMR (400 MHz, CDCl3): δ = 7.18 (dd, 2H, J = 7.5, 8.5 Hz,
HPLC: Chiralcel OD-H column, hexane–i-PrOH = 95/5, flow
2′-CH), 6.64–6.88 (m, 7H, ArH), 4.33 (s, 1H, NH), 3.84 (s, 3H, rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 17.61 min;
OCH3), 3.61–3.70 (m, 2H, HC-N), 2.21–2.33 (m, 2H, CH2), 1.79 major enantiomer (1S,2S) tR = 22.25 min.
(m, 2H, CH2), 1.53–1.63 (m, 2H, CH2).
1S,2S)-N-Phenyl-N′-p-tolylcyclohex-4-ene-1,2-diamine
13C-NMR (100 MHz, CDCl3): δ = 147.8 (C-4′), 146.9 (C-10′), (5b).15a Yield: 124 mg (89%), 90% ee as a pale yellow oil.
137.6 (C-5′), 129.2 (C-2′), 121.2 (C-7′), 117.4 (C-8′), 116.6 (C-1′),
113.4 (C-3′), 110.6 (C-6′), 109.4 (C-9′), 60.65 (HC-N), 60.38,
55.31 (OCH3), 31.35 (CH2), 31.27, 21.59.
[α]1D8 = +83.6 (c = 1.1, CHCl3).
Rf (EtOAc–petroleum ether, 1/10) = 0.29.
UV (CHCl3): λmax (lg ε) = 296 (3.957), 250 (4.351), 234 (3.808)
MS (70 eV, EI): m/z (%) = 282 (12), 190 (55), 174 (38), 160 nm.
(100), 132 (18), 93 (12), 77 (16), 41 (7).
IR (film): ν (cm−1) = 3383, 3023, 2918, 1601, 1431, 1384,
HPLC: Chiralcel OD-H column, hexane–i-PrOH = 95/5, flow 1181.
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 16.6 min;
1H-NMR (400 MHz, CDCl3): δ = 7.22 (dd, J = 7.2, 8.4 Hz, 2H,
major enantiomer (1S,2S) tR = 22.2 min.
3,5-ArH), 7.04 (d, J = 8.4 Hz, 2H, 3′,5′-ArH), 6.76 (t, J = 7.2 Hz,
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1H, 4-ArH), 6.69 (d, J = 7.6 Hz, 2H, 2,6-ArH), 6.63 (d, J = 8.4 Hz,
HR-MS (ESI, MeOH): calcd for C22H23N2 ([M + H]+):
2H, 2′,6′-ArH), 5.73 (s, 2H, CHvCH), 3.90 (brs, 1H, NH), 3.74 315.18612; found: 315.18558.
(brs, 3H, NH, CH-N), 2.71 (brd, 2H, CH2), 2.29 (s, 3H, CH3),
2.07 (brd, 2H, CH2).
HPLC: Chiralcel OD-H column, hexane–i-PrOH = 95/5, flow
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 29.3 min;
13C-NMR (100 MHz, CDCl3): δ = 147.5, 145.1, 130.0, 129.5, major enantiomer (1S,2S) tR = 34.3 min.
127.1, 124.86, 124.75, 117.7, 113.83, 113.54, 51.1, 50.8, 30.3
(2C), 20.5.
(2S,3S)-N,N′-Diphenylbutane-2,3-diamine (7a).15a Yield:
104 mg (87%), 90% ee as a colorless oil.
[α]2D0 = +24.5 (c = 1.27, CHCl3).
HR-MS (ESI, MeOH): calcd for C19H23N2 ([M + H]+):
279.17830; found: 279.18568, calcd for C19H22N2Na ([M +
Na]+): 301.16807; found: 301.16746.
Rf (EtOAc–petroleum ether, 1/10): 0.29.
UV (CHCl3): λmax (lg ε) = 294 (3.949), 251 (4.363), 238 (3.671)
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow nm.
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 7.84 min;
IR (film): ν (cm−1) = 3394, 3050, 2969, 1600, 1428, 1384,
major enantiomer (1S,2S) tR = 9.13 min.
1253, 1179.
(1S,2S)-N-(4-Methoxyphenyl)-N′-phenylcyclohex-4-ene-1,2-
1H-NMR (400 MHz, CDCl3): δ = 7.21 (dd, J = 7.6, 8.4 Hz, 4H,
diamine (5c).15a Yield: 115 mg (78%), 87% ee as a pale 3,5-ArH), 6.74 (t, J = 7.2 Hz, 2H, 4-ArH), 6.67 (d, J = 8.0 Hz, 4H,
yellow oil.
[α]1D8 = +108.8 (c = 0.68, CHCl3).
Rf (EtOAc–petroleum ether, 1/5): 0.32.
2,6-ArH), 3.64 (brs, 2H, NH), 3.58–3.63 (m, 2H, CHN), 1.25
(d, J = 6.0 Hz, 6H, CH3).
13C-NMR (100 MHz, CDCl3): δ = 147.7, 129.5, 117.7, 113.7,
UV (CH3CN): λmax (lg ε) = 302 (3.813), 249 (4.362), 227 52.7, 17.1.
(3.669) nm.
MS (ESI, MeOH): m/z (%) = 241 [M + H]+, 263 [M + Na]+.
IR (film): ν (cm−1) = 3373, 3024, 2915, 2831, 1601, 1502,
HR-MS (ESI, MeOH): calcd for C16H21N2 ([M + H]+):
241.16993; found: 241.16998, calcd for C16H20N2Na ([M +
1432, 1384, 1233, 1179.
1H-NMR (400 MHz, CDCl3): δ = 7.21 (dd, J = 7.6, 8.6 Hz, 2H, Na]+): 263.15187; found: 263.15198.
3,5-ArH), 6.81 (dd, J = 2.4, 6.8 Hz, 2H, 3′,5′-ArH), 6.74 (t, J =
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
7.2 Hz, 1H, 4-ArH), 6.64–6.68 (m, 4H, 2,6-ArH, 2′,6′-ArH), 5.71 (s, rate = 1.0 mL min−1; minor enantiomer (2R,3R) tR = 10.37 min;
2H, CHvCH), 3.90 (brs, 1H, NH), 3.77 (s, 3H, OCH3), major enantiomer (2S,3S) tR = 11.69 min.
3.59–3.73 (m, 3H, NH, CH-N), 2.63–2.72 (m, 2H, CH2), 2.07
(dd, J = 4.0, 16.0 Hz, 2H, CH2).
4-[(2S,3S)-3-(Phenylamino)butan-2-ylamino]benzenethiol
(7b). Yield: 83 mg (61%), 53% ee as a pale yellow color-
13C-NMR (100 MHz, CDCl3): δ = 152.5, 147.5, 141.5, 129.5, less oil.
124.89, 124.74, 117.7, 115.29, 115.11, 113.6, 55.9, 51.97, 51.05,
30.37, 30.36.
[α]2D0 = −4.1 (c = 3.42, CHCl3).
Rf (EtOAc–petroleum ether, 1/10): 0.26.
HR-MS (ESI, MeOH): calcd for C19H23N2O ([M + H]+):
295.17321; found: 295.18061, calcd for C19H22N2ONa ([M +
Na]+): 317.16298; found: 317.16247.
UV (CHCl3): λmax (lg ε) = 260 (4.294) nm.
IR (film): ν (cm−1) = 3390, 3051, 3019, 2970, 2928, 2554,
1598, 1497, 1383, 1318, 1252, 1181, 1145, 1076, 1019, 993, 873,
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow 813, 788, 751, 693, 632, 507.
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 13.62 min;
major enantiomer (1S,2S) tR = 15.94 min.
1H-NMR (400 MHz, CDCl3): δ = 7.21 (t, J = 8.0 Hz, 4H, 3,5-
ArH, 3′,5′-ArH), 6.70 (t, J = 7.6 Hz, 1H, 4-ArH), 6.66 (dd, J = 1.2,
(2S,3S)-N2,N3-Diphenyl-1,2,3,4-tetrahydronaphthalen-2,3- 8.6 Hz, 2H, 2,6-ArH), 6.56 (dd, J = 1.2, 8.6 Hz, 2H, 2′,6′-ArH),
diamine (6a).15e Yield: 119 mg (76%), 76% ee as a colorless 3.67 (brs, 2H, NH), 3.53–3.61 (m, 2H, CH-N), 3.32 (s, 1H, SH),
solid; m.p.: 129 °C.
1.22 (d, J = 6.4 Hz, 6H, CH3).
[α]2D2 = +100.1° (c = 0.86, CHCl3).
13C-NMR (100 MHz, CDCl3): δ = 147.3, 146.5, 133.3, 129.3,
117.6, 114.7, 114.1, 113.5, 52.5, 52.4, 16.9, 16.8.
HR-MS (ESI, MeOH): calcd for C16H21N2S ([M + H]+):
Rf (EtOAc–petroleum ether, 1/5): 0.53.
UV (CHCl3): λmax (lg ε) = 207 (4.430), 250 (4.472), 295 (3.625) nm.
IR (KBr): ν (cm−1) = 3391, 3050, 2904, 1924, 1822, 1723, 273.14253; found: 273.14200, calcd for C16H20N2NaS
1602, 1509, 1494, 1453, 1430, 1336, 1317, 1264, 1238, 1222, ([M
1177, 1110, 1099, 1071, 1035, 992, 955, 870, 822, 767, 753, 736, for C32H40N4NaS2 ([2M
+
Na]+): 295.12449; found: 295.12394, calcd
Na]+): 567.25921; found:
+
692, 584, 503, 435.
567.25866.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 95/5, flow
1H-NMR (300 MHz, CDCl3): δ = 7.11–7.24 (m, 8H, ArCH),
6.75 (t, 2H, J = 7.5 Hz, ArCH), 6.69 (d, 4H, J = 8.5 Hz, ArCH), rate = 1.0 mL min−1; minor enantiomer (2R,3R) tR = 14.07 min;
3.89 (br s, 4H, HC-N, NH), 3.44 (d, 2H, J = 17.5 Hz, CHH), 2.80 major enantiomer (2S,3S) tR = 11.63 min.
(dd, 2H, J = 5.0, 17.5 Hz, CHH).
(1R,3S,4S,6S)-N,N′-Diphenyl-7-tosyl-7-azabicyclo[4.1.0]-
13C-NMR (75 MHz, CDCl3): δ = 147.2 (Cq), 133.6 (Cq), 129.5 heptane-3,4-diamine (8a). Yield: 173 mg (80%), 48% ee as a
(ArCH), 129.3 (ArCH), 126.5 (ArCH), 117.9 (ArCH), 113.6 colorless solid, m.p.: 84.8 °C.
(ArCH), 51.95 (HC-N), 34.28 (CH2) ppm.
MS (ESI, 70 eV): m/z (%) = 314 (19), 222 (100), 157 (15), 129
(9), 106 (70), 77 (21), 57 (7).
[α]2D0 = +8.2 (c = 0.973, CHCl3).
Rf (ether–petroleum ether, 1/1): 0.3.
UV (CHCl3): λmax (lg ε) = 248 (4.188), 293 (3.487) nm.
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IR (KBr): ν (cm−1) = 3383, 3050, 2923, 1731, 1600, 1498,
1H-NMR (400 MHz, CDCl3): δ = 7.17–7.24 (m, 4H, 3′-ArH),
1434, 1320, 1304, 1249, 1182, 1159, 1091, 1019, 992, 971, 935, 6.62–6.79 (m, 6H, 2′-ArH, 4′-ArH), 4.41 (bs, 2H, NH), 4.01 (d, J
875, 847, 815, 750, 715, 693, 667, 582, 549, 508 cm−1
.
= 12.5 Hz, 2H, 4-CHH, 7-CHH), 3.54–3.60 (m, 2H, 4-CHH,
1H-NMR (400 MHz, CDCl3): δ = 7.87 (d, J = 8.0 Hz, 2H, 2′,6′- 7-CHH), 3.51 (bs, 2H, 5-CH-NH, 6-CH-NH), 1.42 (s, 6H, CH3),
ArH), 7.38 (d, J = 8.0 Hz, 2H, 3′,5′-ArH), 7.17 (ddd, J = 7.5, 8.5 ppm.
Hz, 4H, 3,5-ArH), 6.74 (dt, J = 7.5 Hz, 2H, 4-ArH), 6.59 (d, J =
13C-NMR (100 MHz, CDCl3): δ = 146.5 (1′-ArC), 129.7 (3′-
8.5 Hz, 2H, 2,6-ArH), 6.56 (d, J = 8.5 Hz, 2H, 2,6-ArH), 4.09 (d, J ArC), 117.8 (4′-ArC), 113.6 (2′-ArC), 60.55 (4-CH2, 7-CH2), 102.1
= 8.5 Hz, 1H, NH), 3.71 (d, J = 7.5 Hz, 1H, NH), 3.61 (m, 1H, (2-C), 54.14 (5-CH-NH, 6-CH-NH), 24.92 (CH3) ppm.
CH-NH), 3.48 (m, 1H, CH-NH), 3.14 (m, 1H, CH-N), 3.08 (t, J =
6.0 Hz, 1H, CH-N), 2.58 (t, J = 6.0 Hz, 1H, CHH), 2.52 (dd, J =
MS (ESI in MeOH–CH2Cl2): m/z = 311.0 [M − H]−.
HPLC: Chiralcel OD-H column, hexane–i-PrOH (95/5), flow
5.5, 12.0 Hz, 1H, CHH), 2.48 (s, 3H, CH3), 1.81 (d, J = 6.0 Hz, rate = 1.0 mL min−1; minor enantiomer tR = 7.01 min; major
1H, CHH), 1.77 (d, J = 6.0 Hz, 1H, CHH).
enantiomer tR = 7.97 min.
(5S,6S)-Methyl-4-((-2,2-dimethyl-6-(phenylamino)-1,3-dioxe-
13C-NMR (100 MHz, CDCl3): δ = 146.9, 146.6, 144.6, 135.3,
129.8, 129.4, 127.6, 118.2, 118.0, 113.5, 113.4, 51.0, 48.9, 38.9, pan-5-yl)amino)benzoate (10b). With bis-BINOL 11: 51 mg
38.7, 28.5, 27.6, 21.6. (66%), 78% ee, colorless solid, m.p.: 55–58 °C, reaction time: 2
MS (70 eV, EI): m/z (%) = 433 (10), 278 (100), 223 (22), 185 d, −20 °C.
(13), 173 (70), 106 (38), 91 (26), 65 (7).
[α]2D4: +173.4° (c = 0.87, CHCl3).
HR-MS (ESI, CHCl3–MeOH): calcd for C25H27N3O2NaS ([M +
Na]+): 456.17217; found: 456.17162.
Rf (n-hexane–EtOAc 2 : 1): 0.34.
IR (KBr): ν (cm−1) = 3407, 2987, 2943, 2360, 1705, 1606,
HPLC: Chiralcel OD column, hexane–i-PrOH = 80/20, flow 1525, 1505, 1434, 1376, 1317, 1276, 1216, 1176, 1112, 1045,
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 49.7 min; 953, 878, 83 7, 771, 749, 694, 667, 505.
major enantiomer (1S,2S) tR = 92.3 min.
1H-NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 9.0 Hz, 2H, 3′′-
(3S,4S)-N,N′-Diphenyltetrahydrofuran-3,4-diamine ArH), 7.46–7.08 (m, 2H, 3′-ArH), 6.88–6.61 (m, 5H, ArCH), 4.91
(9a).15e Yield: 108 mg (85%), 17% ee as a yellow oil, reaction (d, J = 8.5 Hz, 1H, NH), 4.43 (s, 1H, NH), 4.02 (dd, J = 15.5, 12.0
time: 48 h.
[α]2D2 = +3.9° (c 1.03, CHCl3).
Hz, 2H, CH2), 3.86 (s, 3H, COOCH3), 3.64–3.52 (m, 3H, CH2,
CHN), 3.49 (s, 1H, CHN), 1.42 (s, 6H, CH3) ppm.
Rf (EtOAc–petroleum ether = 3/7) = 0.08.
UV (CHCl3): λmax (lg ε) = 248 (4.386), 293 (3.750) nm.
13C-NMR (100 MHz, CDCl3): δ = 167.3 (COOMe), 150.3 (1′-
ArC), 146.3 (1′′-ArC), 132.0 (3′′-ArC), 129.8 (3′-ArC), 118.9 (4′′-
IR (KBr): ν (cm−1) = 3383, 3329, 3023, 2878, 1602, 1522, ArC), 118.2 (4′-ArC), 113.7 (ArCH), 112.1 (ArCH), 102.3 (2-C),
1498, 1434, 1380, 1314, 1292, 1272, 1249, 1176, 1153, 1132, 60.54 (CH2), 60.27 (CH2), 53.99 (CHN), 53.54 (CHN), 51.73
1077, 1027, 1004, 913, 875, 751, 694, 514.
(COOCH3), 24.92 (CH3), 24.87 (CH3) ppm.
1H-NMR (200 MHz, CDCl3): δ = 7.21 (dd, 2H, J = 7.5, 8.5 Hz,
HR-MS (ESI in MeOH–CHCl3): calcd for C21H27N2O4 ([M +
3,5-ArH), 6.79 (t, 2H, J = 7.5 Hz, 4-ArH), 6.65 (d, 4H, J = 8.5 Hz, H]+): 371.19653; found: 371.19644.
2,6-ArH), 4.21 (dd, 2H, J = 4.5, 10.0 Hz, CHH), 3.91 (m, 4H,
HC-N, NH), 3.76 (dd, 2H, J = 1.5, 10.0 Hz, OCHH).
HPLC: Chiralcel OD-H column, hexane–i-PrOH (60/40), flow
rate = 1.0 mL min−1; minor enantiomer tR = 5.95 min; major
13C-NMR (50 MHz, CDCl3): δ = 146.5 (1-ArCq), 129.4 (3,5- enantiomer tR = 7.23 min.
ArCH), 118.3 (4-ArCH), 113.6 (2,6-ArCH), 72.82 (OCH2), 60.09
(HC-N).
(5S,6S)-4-(2,2-Dimethyl-6-(phenylamino)-1,3-dioxepan-5-
ylamino)benzonitrile (10c). With bis-BINOL 11: 58 mg
MS (70 eV, EI): m/z (%) = 254 (18), 162 (32), 119 (100), 77 (69%), 68% ee colorless solid, m.p.: 165–168 °C, reaction time:
(16), 51 (6). 3 d, −20 °C.
[α]2D4: +165.6° (c = 0.93, CHCl3).
Rf (n-hexane–EtOAc 2 : 1): 0.39.
IR (KBr): 3381, 3338, 2993, 2942, 2360,
(cm−1
HR-MS (ESI, CHCl3–MeOH): calcd for C16H18N2ONa ([M +
Na]+): 277.13168; found: 277.13113.
HPLC: Chiralcel AD-H column, hexane–i-PrOH = 98/2, flow
ν
) =
rate = 1.0 mL min−1; minor enantiomer (1R,2R) tR = 71.2 min; 2209, 1604, 1519, 1497, 1377, 1335, 1309, 1277, 1255, 1220,
major enantiomer (1S,2S) tR = 74.4 min.
1175, 1126, 1057, 1048, 882, 844, 795, 760, 694, 589, 552, 500,
(5S,6S)-2,2-Dimethyl-N,N′-diphenyl-1,3-dioxepan-5,6-diamine 419.
(10a).15e With bis-BINOL 11: 65 mg (85%), 88% ee, colorless
1H-NMR (300 MHz, CDCl3): δ = 7.46 (d, J = 9.0 Hz, 2H, 3′′-
oil, reaction time: 3 d, −20 °C.
[α]2D4 +118.8° (c = 0.96, CHCl3).
Rf (n-hexane–EtOAc 1 : 1): 0.59.
ArH), 7.33–7.18 (m, 2H, 3′-ArH), 6.77 (t, J = 7.5 Hz, 1H, 4′-ArH),
6.69 (t, J = 9.0 Hz, 4H, ArH), 4.97 (d, J = 8.5 Hz, 1H, NH), 4.42
(s, 1H, NH), 4.01 (dd, J = 16.0, 12.0, 2H, CH2), 3.72–3.36 (m,
UV (CH3CN): λmax (lg ε) = 203 nm (4.30), 247 nm (4.19), 301 4H, CHN, CH2), 1.42 (s, 1H, CH3) ppm.
(3.22).
13C-NMR (100 MHz, CDCl3): δ = 149.8 (1′′-ArC), 146.1 (1′-
IR (KBr): ν (cm−1) = 3415, 3051, 3020, 2989, 2940, 1921, ArC), 134.0 (3′′-ArC), 129.7 (3′-ArC), 120.3 (CN), 118.3 (ArCH),
1602, 1506, 1450, 1432, 1375, 1317, 1278, 1217, 1180, 1156, 113.7 (ArCH), 112.7 (ArCH), 102.4 (2-C), 99.22 (4′′-ArC), 60.43
1129, 1046, 994, 953, 878, 831, 787, 750, 692, 619, 567, 537, (CH2), 60.02 (CH2), 53.95 (CHN), 53.42 (CHN), 24.85 (CH3),
509.
24.78 (CH3) ppm.
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HR-MS (ESI in MeOH–CHCl3: calcd for C20H24N3O2 ([M +
406; (b) S. Matsukawa, H. Takahashi and T. Harada, Org.
Biomol. Chem., 2012, 10, 4886; (c) Y. Hayashi,
T. Kumamoto, T. Ishikawa, M. Kawahata and
K. Yamaguchi, Tetrahedron, 2010, 66, 3836; (d) I. Fujimori,
T. Mita, K. Maki, M. Shiro, A. Sato, S. Furusho, M. Kanai
and M. Shibasaki, Tetrahedron, 2007, 63, 5820;
(e) S. Minakata, Y. Okada, Y. Oderaotoshi and M. Komatsu,
Org. Lett., 2005, 7, 3509; (f) S. H. Kang, M. Kim and
D. H. Ryu, Synlett, 2003, 8, 1149.
H]+): 338.18630; found: 338.18621, calcd for C40H47N6O4
([2M + H]+): 675.36533; found: 675.36549.
HPLC: Chiralcel OD-H column, hexane–i-PrOH (60/40), flow
rate = 1.0 mL min−1; minor enantiomer tR = 5.55 min; major
enantiomer tR = 6.21 min.
Acknowledgements
6 For select catalytic processes see: (a) Y. Zhang, C. W. Kee,
R. Lee, X. Fu, J. Y. T. Soh, E. M. F. Loh, K. W. Huang and
C. H. Tan, Chem. Commun., 2011, 3897; (b) F. Zeng and
H. Alper, Org. Lett., 2010, 12, 5567; (c) J. S. Yadav,
B. V. S. Reddy, G. Baishya, P. Venkatram Reddy and
A. V. Narsaiah, Catal. Commun., 2006, 7, 807; (d) J. Wu,
X. Sun and Y. Li, Eur. J. Org. Chem., 2005, 4271;
(e) J. S. Yadav, B. V. Subba Reddy, G. Baishya, P. V. Reddy
and S. J. Harshavardhan, Synthesis, 2004, 1854;
(f) X.-L. Hou, R.-H. Fan and L.-X. Dai, J. Org. Chem., 2002,
67, 5295; (g) J. Wu, X.-L. Hou and L.-X. Dai, J. Chem. Soc.,
Perkin Trans. 1, 2001, 1314.
This work was generously supported by the Deutsche For-
schungsgemeinschaft (SCHN 441/9-1). We gratefully acknowl-
edge the support of Dr C. Birkemeyer (University of Leipzig)
for obtaining and interpreting the MS data and the Alexander
von Humboldt Foundation for a postdoctoral fellowship
awarded to S. P. We thank Evonik, Chemetall, and BASF for
the generous donation of chemicals.
Notes and references
1 Select reviews: (a) C. Schneider, Synthesis, 2006, 3919;
(b) I. M. Pastor and M. Yus, Curr. Org. Chem., 2005, 9, 1;
(c) E. N. Jacobsen and M. H. Wu, in Comprehensive
Asymmetric Catalysis, ed. E. N. Jacobsen, A. Pfaltz and
H. Yamamoto, 1999, vol. 2, p. 649.
7 Recent short review: C. Schneider, Angew. Chem., Int. Ed.,
2009, 48, 2082.
8 Z. Li, M. Fernandez and E. N. Jacobsen, Org. Lett., 1999, 1,
1611.
2 Select reviews: (a) C. Schneider, Angew. Chem., Int. Ed.,
2009, 48, 2082; (b) A. K. Yudin, Aziridines and Epoxides in
Organic Synthesis, Wiley-VCH, Weinheim, Germany, 2006;
(c) M. Pineschi, Eur. J. Org. Chem., 2006, 4979; (d) X. E. Hu,
Tetrahedron, 2004, 60, 2701; (e) W. McCoull and F. A. Davis,
Synthesis, 2000, 1347.
3 For select catalytic processes see: (a) D. Hong, X. Lin,
Y. Zhu, M. Lei and Y. Wang, Org. Lett., 2009, 11, 5678;
(b) A. Bisai, B. A. Bhanu Prasad and V. K. Singh, Tetra-
hedron Lett., 2005, 46, 7935; (c) J. Wu, X. Sun and Y. Li,
9 (a) K. Yabu, S. Masumoto, S. Yamasaki, Y. Hamashima,
M. Kanai, W. Du, D. P. Curran and M. Shibasaki, J. Am.
Chem. Soc., 2001, 123, 9908; (b) T. Mita, I. Fujimori,
R. Wada, J. Wen, M. Kanai and M. Shibasaki, J. Am. Chem.
Soc., 2005, 127, 11252; (c) Y. Fukuta, T. Mita, N. Fukuda,
M. Kanai and M. Shibasaki, J. Am. Chem. Soc., 2006, 128,
6312; (d) I. Fujimori, T. Mita, K. Maki, M. Shiro, A. Sato,
S. Furusho, M. Kanai and M. Shibasaki, J. Am. Chem. Soc.,
2006, 128, 16438; (e) Y. Xu, L. Lin, M. Kanai, S. Matsunaga
and M. Shibasaki, J. Am. Chem. Soc., 2011, 133, 5791.
Eur. J. Org. Chem., 2005, 4271; (d) I. D. G. Watson and A. 10 (a) B. Wu, J. C. Gallucci, J. R. Parquette and
K. Yudin, J. Org. Chem., 2003, 68, 5160; (e) N. R. Swamy and
Y. Venkateswarlu, Synth. Commun., 2003, 33, 547;
(f) J. S. Yadav, B. V. S. Reddy, K. V. Rao, K. S. Raj and
T. V. RajanBabu, Angew. Chem., Int. Ed., 2009, 48, 1126;
(b) B. Wu, J. R. Parquette and T. V. RajanBabu, Science,
2009, 326, 1662.
A. R. Prasad, Synthesis, 2002, 1061; (g) J. Cossy, V. Bellosta, 11 E. B. Rowland, G. B. Rowland, E. Rivera-Otero and
V. Alauze and J. R. Desmurs, Synthesis, 2002, 2211; J. C. Antilla, J. Am. Chem. Soc., 2007, 129, 12084.
(h) X.-L. Hou, R.-H. Fan and L.-X. Dai, J. Org. Chem., 2002, 12 (a) K. Arai, S. Lucarini, M. S. Salter, K. Ohta, Y. Yamashita
67, 5295; (i) M. Chandrasekhar, G. Sekar and V. K. Singh,
Tetrahedron Lett., 2000, 41, 10079; ( j) G. Sekar and
V. K. Singh, J. Org. Chem., 1999, 64, 2537; (k) M. Meguro,
N. Asao and Y. Yamamoto, Tetrahedron Lett., 1994, 35, 7395.
4 For select catalytic processes see: (a) S. Bhadra, L. Adak,
and S. Kobayashi, J. Am. Chem. Soc., 2007, 129, 8103;
(b) R. Yu, Y. Yamashita and S. Kobayashi, Adv. Synth.
Catal., 2009, 351, 147; (c) K. Seki, R. Yu, Y. Yamazaki,
Y. Yamashita and S. Kobayashi, Chem. Commun., 2009,
5722.
S. Samanta, A. K. M. Maidul Islam, M. Mukherjee and 13 (a) S. E. Larson, J. C. Baso, G. Li and J. C. Antilla, Org. Lett.,
B. C. Ranu, J. Org. Chem., 2010, 75, 8533; (b) M. Bera and
S. Roy, J. Org. Chem., 2009, 74, 8814; (c) B. A. Bhanu Prasad,
R. Sanghi and V. K. Singh, Tetrahedron, 2002, 58, 7355;
(d) X.-L. Hou, R.-H. Fan and L.-X. Dai, J. Org. Chem., 2002,
67, 5295; (e) B. A. Bhanu Prasad, G. Sekar and V. K. Singh,
Tetrahedron Lett., 2000, 41, 4677.
2009, 11, 5186; (b) G. Della Sala and A. Lattanzi, Org. Lett.,
2009, 11, 3330; (c) Y. Zhang, C. W. Kee, R. Lee, X. Fu,
J. Y.-T. Soh, E. M. F. Loh, K.-W. Huang and C.-H. Tan,
Chem. Commun., 2011, 47, 3897; for previous work in this
area see: (d) Z.-B. Luo, X.-L. Hou and L.-X. Dai, Tetra-
hedron: Asymmetry, 2007, 18, 443; (e) Z. Wang, X. Sun, S. Ye,
W. Wang, B. Wang and J. Wu, Tetrahedron: Asymmetry.,
2008, 19, 964.
5 For select catalytic processes see: (a) S. Matsukawa,
H. Takahashi and T. Harada, Synth. Commun., 2013, 43,
Org. Biomol. Chem.
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Paper
14 (a) T. Mita and E. N. Jacobsen, Synlett, 2009, 1680; 22 N. Kumagai, S. Matsunaga, T. Kinoshita, S. Harada,
(b) K. Ohmatsu, Y. Hamajima and T. Ooi, J. Am. Chem. Soc.,
2012, 134, 8794.
S. Okada, S. Sakamoto, K. Yamaguchi and M. Shibasaki,
J. Am. Chem. Soc., 2003, 125, 2169.
15 (a) S. Peruncheralathan, H. Teller and C. Schneider, Angew. 23 Y. Ihori, Y. Yamashita, H. Ishitani and S. Kobayashi, J. Am.
Chem., Int. Ed., 2009, 48, 4849; for additional work from Chem. Soc., 2005, 127, 15528.
our group in this area see: (b) S. Peruncheralathan, 24 H. Hanawa, T. Hashimoto and K. Maruoka, J. Am. Chem.
M. Henze and C. Schneider, Synlett, 2007, 2289; Soc., 2003, 125, 1708.
(c) S. Peruncheralathan, M. Henze and C. Schneider, Tetra- 25 For previous structural investigations into Ti-BINOLate-
hedron Lett., 2007, 48, 6743; (d) A. Marti and C. Schneider,
Synlett, 2011, 2513; (e) A. Marti, S. Peruncheralathan and
C. Schneider, Synthesis, 2012, 44, 27.
complexes see e.g.: (a) T. J. Boyle, D. L. Barnes,
J. A. Heppert, L. Morales, F. Takusagawa and J. W. Conolly,
Organometallics, 1992, 11, 1112; (b) T. J. Boyle,
N. W. Eilerts, J. A. Heppert and F. Takusagawa, Organome-
tallics, 1994, 13, 2218; (c) K. Mikami, M. Ueki,
Y. Matsumoto and M. Terada, Chirality, 2001, 13, 541;
(d) T. J. Davis, J. Balsells, P. J. Carroll and P.
J. Walsh, Org. Lett., 2001, 3, 699; (e) G. Pescitelli,
L. Di Bari and P. Salvadori, J. Organomet. Chem., 2006,
691, 2311.
16 (a) C. Han, J. P. Lee, E. Lobkovsky and J. A. Porco, J. Am.
Chem. Soc., 2005, 127, 10039; (b) S. E. Eldred, D. A. Stone,
S. H. Gellman and S. S. Stahl, J. Am. Chem. Soc., 2003, 125,
3422.
17 S. Sagawa, H. Abe, Y. Hase and T. Inaba, J. Org. Chem.,
1999, 64, 4962.
18 Select recent reviews: (a) J. M. Brunel, Chem. Rev., 2005,
105, 857; (b) D. J. Ramon and M. Yus, Chem. Rev., 2006, 26 For previous examples of cooperative bimetallic catalysis
106, 2126; (c) L. Pu, Chem. Rev., 1998, 98, 2405.
19 H. Ishitani, M. Ueno and S. Kobayashi, J. Am. Chem. Soc.,
2000, 122, 8180.
20 Diamine 3a has been employed as a chiral ligand, see:
B. M. Trost and T. M. Lam, J. Am. Chem. Soc., 2012, 134,
11319–11321.
21 S. Matsunaga, J. Das, J. Roels, E. M. Vogl, N. Yamamoto,
T. Iida, K. Yamaguchi and M. Shibasaki, J. Am. Chem. Soc.,
2000, 122, 2252–2260.
see the following reviews: (a) J.-A. Ma and D. Cahard,
Angew. Chem., Int. Ed., 2004, 43, 4566–4583;
(b) H. Steinhagen and G. Helmchen, Angew. Chem., Int. Ed.,
1996, 35, 2339–2342; select articles in the field of epoxide
and aziridine ring-opening: (c) B. W. McCleland, W.
A. Nugent and M. G. Finn, J. Org. Chem., 1998, 63, 6656–
6662; (d) K. B. Hansen, J. L. Leighton and E. N. Jacobsen,
J. Am. Chem. Soc., 1996, 118, 10924–10925; (e) See ref. 9c;
(f) See ref. 9d; (g) See ref. 10a.
This journal is © The Royal Society of Chemistry 2013
Org. Biomol. Chem.