Synthesis of N,N′-Dialkylated Cyclohexane-1,2-diamines and Their Application as Asymmetric Ligands and Organocatalysts for the Synthesis of Alcohols

Article abstract of DOI:10.1055/s-0036-1588382

A series of N,N′-dialkylated derivatives of (1R,2R)-cyclohexane-1,2-diamine were synthesized, and a new approach to the one-pot preparation of this type of amine was demonstrated. The prepared diamines were used as organocatalysts for the two-step synthesis of α-hydroxy γ-keto esters from arenes, chlorooxoacetates, and ketones; they were also used as chiral ligands for Meervein-Ponndorf-Verley reductions and Henry reactions.

Full text of DOI:10.1055/s-0036-1588382

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© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–E
letter
A
A. A. Tsygankov et al.
Letter
Synlett
Synthesis of N,N′-Dialkylated Cyclohexane-1,2-diamines and
Their Application as Asymmetric Ligands and Organocatalysts for
the Synthesis of Alcohols
O
Alexey A. Tsygankova
Man-Seog Chunb
Alexandra D. Samoylovaa
Seongyeon Kwonb
Yuliya M. Kreschenovaa
Suhyeon Kimb
O
OMe
NH HN
MeO
Ph
O
Cl
1. AlCl3,
O
R
R
1
PhH
O
2. 1–10 mol% 1,
OH
K2CO3
RCHO
Rh2(OAc)4
CO
Euijin Shinb
Jinho Ohb
iPrOH
O
OH
H
Tatyana V. Strelkovac
Valerii S. Kolesovc
Fedor I. Zubkovd
Sergei E. Semenova
Ivan V. Fedyaninc
Denis Chusov*a,c,d
1 mol% Ru3(CO)12
5 mol% 1
15 mol% KOH
Ar
Ar
H3N
X–
NH3
X–
11 diamines were tested. Yields 67–98%. 72:28 to 87.5:12.5 e.r.
a Moscow Chemical Lyceum, Tamozhenniy proezd 4, Moscow, Russian Federation
b Korea Science Academy of KAIST, 105-47, Baegyanggwanmun-ro, Busanjin-gu,
47162 Busan, Republic of Korea
c A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of
Sciences, Vavilova str. 28, 119991 Moscow, Russian Federation
Chusov@ineos.ac.ru
d Peoples Friendship University of Russia, Dept Organic Chemistry, 6 Miklukho-Mak-
laya St, Moscow 117198, Russian Federation
Received: 05.10.2016
Accepted after revision: 29.11.2016
Published online: 15.12.2016
pound have not been well studied. In this context, we be-
came interested in the development of an enantioselective
method for the preparation of chiral tertiary alcohols
through aldol-type chemistry.
DOI: 10.1055/s-0036-1588382; Art ID: st-2016-b0664-l
Abstract A series of N,N′-dialkylated derivatives of (1R,2R)-cyclohex-
ane-1,2-diamine were synthesized, and a new approach to the one-pot
preparation of this type of amine was demonstrated. The prepared di-
amines were used as organocatalysts for the two-step synthesis of α-
hydroxy γ-keto esters from arenes, chlorooxoacetates, and ketones;
they were also used as chiral ligands for Meervein–Ponndorf–Verley re-
ductions and Henry reactions.
Mandelic acid has a long history of use as an antibacte-
rial agent, especially for the treatment of urinary tract in-
fections.5 It is also used as an oral antibiotic and as a com-
ponent of chemical face peels, along with other α-hydroxy
acids. Likewise, many derivatives of mandelic acid are
known to be pharmaceutically important compounds, e.g.
the vasodilator cyclandelate and the anticholinergic homa-
tropine.
These considerations prompted our choice of mandelic
acid analogues with a chiral quaternary carbon center as
synthetic targets. Methods for the synthesis of this type of
molecule through organocatalytic asymmetric aldol reac-
tions are rare, and most require 20–50 mol% of the catalyst;
in only a few instances can the catalytic loading be reduced
to 10–15 mol%.6
Key words aldol reaction, organocatalysis, asymmetric catalysis, hy-
droxy acids, diamines, Meervein–Ponndorf–Verley reaction, Henry re-
action
Asymmetric organocatalysis has become the main focus
of research in asymmetric synthesis since the pioneering
work of List et al.,1 who explored aldol reactions catalyzed
by a simple organic molecule, L-proline. The aldol reaction
is one of the most important C–C bond-formation reac-
tions,2,3 and consequently many asymmetric variants of this
reaction have been developed.4
Chiral tertiary alcohols are valuable as synthetic inter-
mediates in pharmaceutical chemistry, and therefore met-
al-free approaches to their synthesis are highly desirable;
however, organocatalytic syntheses of this type of com-
Here, we report a convenient synthesis of aldol-reaction
organocatalysts that were found to be active at loadings as
low as 1–10 mol%. For the synthesis of catalysts 3a–k, we
started from an inexpensive and readily available mixture
of cis- and trans-cyclohexane-1,2-diamine. Many deriva-
tives of cyclohexanediamine have been used as chiral li-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

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A. A. Tsygankov et al.
Letter
Synlett
gands, and reduced representatives of this group (salan li-
gands)7 are usually prepared by a two-step condensa-
tion/reduction route. We decided to elaborate a new one-
step protocol for the synthesis of these compounds directly
from cyclohexane-1,2-diamine salts.
O
O
O
O
O
O
AlCl3, CH2Cl2
+
Ar
O
H
Cl
R
Ar
R
O
O
O
O
O
O
HO
O
MeO
OEt
OEt
OEt
We were pleased to find that diamines 3 could be ob-
tained in one step from diamine salts 1 and the appropriate
aldehydes by reductive amination without an external hy-
drogen source, a method that we have recently devel-
oped.8,9 Although reductive amination can lead to mixtures
of polyalkylated diamines and Schiff bases, we found that
the desired diamines 3 were the main products of the reac-
tion, which proceeded in 24–87% yield.10 An alternate clas-
sical two-step approach led to a series of Schiff bases 2a–k,
which were subsequently reduced with sodium borohy-
dride to give diamines 3a–k.11 The two-step approach gave
overall yields of 16–85% (Table 1).12
OMe
OMe
OMe
4b
4a
4d
4c
Scheme 1 Synthesis of α-keto esters from arenes
Interestingly, when 1-fluoro-4-(trifluoromethyl)ben-
zene was used as a substrate, the expected product 4e was
not obtained (Scheme 2). 1H, 13C, and 19F NMR spectroscopy
and mass spectrometry revealed that 1-fluoro-4-(trichloro-
methyl)benzene (4f) was formed as the main product (iso-
lated in 80% yield). Apparently, AlCl3 induces substitution of
all three fluorine atoms in the trifluoromethyl group of 1-
fluoro-4-(trifluoromethyl)benzene, even at 0 °C (similar re-
actions have been previously reported).13
Table 1 Synthesis of Chiral Catalysts
H
O
O
O
NaBH4, MeOH
R
F
F
F
+
+H3N
X–
NH3
X–
O
O
NH HN
AlCl3 (1.8 equiv)
reflux
K2CO3
OEt
N
N
R
R
+
+
3
2 h, CH2Cl2
Cl
OEt
R
R
2
1
CF3
CF3
CCl3
not observed
main product
4e
4f
K2CO3, CO
RCHO, 1 mol% Rh2(OAc)4
4 h
Scheme 2 Friedel–Crafts acylation of 1-fluoro-4-(trifluoromethyl)ben-
zene versus substitution of the trifluoromethyl group by AlCl3
Entry
Product
R
One-step yield Two-step yield
(%) (%)
Having prepared the catalysts and substrates, we next
focused on the optimization of the conditions for the asym-
metric aldol reaction of methyl phenylglyoxylate (4a; Table
2). First, we checked the effect of solvents. In the presence
of catalyst 3a, the reaction in acetone (serving also as a re-
agent) gave hydroxy keto ester 5a with 81.5:18.5 e.r. (Table
2, entry 1). Chlorinated solvents were less favorable. The re-
actions in dichloromethane and chloroform gave 5a with
75:25 e.r. and 65:35 e.r., respectively (entries 2 and 3). Alco-
hols showed inconsistent results; the reaction proceeded
with 65:35 e.r. in methanol (entry 5) and 75.5:24.5 e.r. in
ethanol (entry 4). The reaction in ethyl acetate gave product
5a with 74:36 e.r. (entry 6). The best enantiomeric ratio
(87.5:12.5 e.r.) was achieved by using THF as a solvent;
however, only traces of the product were obtained in this
case (entry 7). Notably, in contrast to some reports in the
literature,14 no increase in enantioselectivity was observed
in the presence of a Brønsted acid (entries 8 and 9).
1
2
3a
3b
3c
3d
3e
3f
2-ClC6H4
61
76
4-MeOC6H4
3-MeOC6H4
1-naphthyl
4-ClC6H4
81
85
64
62
50
48
43
24
77
87
79
82
75
41
30
85
16
45
38
55
3
4
5
6
2-pyridyl
7
3g
3h
3i
3-pyridyl
8
4-Me2NC6H4
2-HOC6H4
Ph
9
10
11
3j
3k
3,4,5-(MeO)3C6H2
For the synthesis of α-hydroxy γ-keto esters, we chose
the Friedel–Crafts acylation of arenes by methyl or ethyl
chlorooxoacetate as a first step (see Scheme 1). The reaction
proceeded smoothly with benzene or p-xylene to give keto
esters 4a and 4d, respectively. However, in the case of the
more active substrate p-dimethoxybenzene, the monode-
methylation product 4c was obtained, together with the ex-
pected dimethoxy derivative 4b.
As a next step, we investigated the effects of the substit-
uents in catalysts 3a–k. The o-chlorobenzyl derivative 3a
gave an enantioselectivity similar to that obtained with cat-
alyst 3b, which has an electron-donating para-methoxy
substituent (Table 3, entries 1 and 2). The meta-methoxy
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

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A. A. Tsygankov et al.
Letter
Synlett
Table 2 Screening of Conditions for the Organocatalytic Asymmetric
Table 3 Screening of Various Diamines as Organocatalysts for the
Asymmetric Cross-Aldol Reaction of Acetone with Methyl Benzoylfor-
matea
Cross-Aldol Reaction of Acetone and Methyl Benzoylformatea
O
O
O
3a
O
HO
MeOOC
5a
O
+
10 mol% catalyst
1 mol% AcOH
HO
MeOOC
O
O
O
Ph
OMe
Ph
+
4a
Ph
OMe
Ph
4a
5a
Entry 3a (mol%) Solvent
Additive
Yield (%)
e.r.b
Entry
Catalyst
Yield (%)
e.r.b
81.5:18.5
1
10
10
10
10
10
10
10
5
acetone
CHCl3
–
–
–
–
–
–
–
75
81.5:18.5
1c
2
3a
3b
3c
3d
3e
3f
57–75
39
2
76
65:35
81.5:18.5
81:19
3
CH2Cl2
EtOH
39
75:25
3
96
4
64
75.5:24.5
65:35
4
30
82.5:17.5
81:19
5
MeOH
EtOAc
THF
32
5c
6
18–23
36
6
73
74:36
84:16
7c
8d
9d
trace
45–60
57–75
48
87.5:12.5
84:16
7c
8
3g
3h
3i
93–96
55
84:16
acetone
acetone
acetone
AcOH (5 mol%)
AcOH (1 mol%)
–
79:21
10
5
81.5:18.5
81:19
9c
10c
11c
12d
43–46
75–85
75–85
85
82:18
10
3j
81:19
a Reaction conditions: keto ester (0.15 mmol, 100 mol%), solvent (0.4 mL),
acetone (0.1 mL), 25 °С, 14–28 d.
3k
3g
81:19
b Determined by chiral HPLC.
87.5:12.5
c 70 days.
d Combined results of three experiments.
a Reaction conditions: 4a (0.15 mmol), catalyst (0.015 mmol), acetone (0.5
mL), AcOH (0.0015 mmol), 25 °C, 7 d.
b Determined by chiral HPLC.
c Combined results of three experiments.
d With 1 mol% of the catalyst.
derivative 3c also gave a similar result (entry 3). The 1-
naphthyl-substituted catalyst 3d gave an 82.5:17.5 e.r. (en-
try 4). Catalysts with para-substituents on the phenyl ring
showed similar efficiencies (entries 5 and 8). When the
phenyl groups were replaced with their pyridyl counter-
parts, a small increase in stereoselectivity was observed
(entries 6 and 7). Furthermore, we found that the catalyst
loading could be decreased to 1 mol% without loss of enan-
tioselectivity (entry 12); however, a somewhat lower yield
was obtained.
product 7 was obtained in 75:25 e.r. (Scheme 3). Substitut-
ed acetophenones (e.g., 3-methyl-, 3-chloro-, or 4-chloroac-
etophenones) showed similar results.
HO
O
O
NO2
10 mol% Cu(OTf)2
NO2
+
12 mol% 3f
10 mol% Et3N
neat, r.t., 24 h
MeOOC
Ph
OMe
Ph
4a
6
Under the optimized conditions (Table 3, entry 12),
product 5a was obtained in 85% yield and 87.5:12.5 e.r.15
Simple recrystallization increased the enantiomeric ratio of
the product to 96.5:3.5. The absolute configuration of
methyl (S)-2-hydroxy-4-oxo-2-phenylpentanoate (5a) was
established from anomalous scattering results in an analy-
sis of the X-ray diffraction using CuKα radiation. Substrates
4 with increased steric hindrance could not be used: no re-
action was observed for compounds 4b–d.
Yield 93%
e.r. 56:44
1 mol% Ru3(CO)12
O
OH
O
HO
H
5 mol% 3b
+
+
Ar
15 mol% KOH
reflux, 12 h
Ar
7
HO
HO
HO
H
HO
H
H
H
Diamines 3 can also be used as chiral ligands. We decid-
ed to examine their performance in the copper-catalyzed
Henry reaction of methyl oxo(phenyl)acetate with nitro-
methane (Scheme 3). Although the reaction rate was high,
the enantiomeric ratio of the product 6 was very low
(56:44). Better performance was observed in the case of the
Meervein–Ponndorf–Verley reduction of acetophenone:
when diamine ligand 3b was used in combination with
triruthenium dodecacarbonyl and potassium hydroxide,
Cl
Cl
Yield 98%
e.r. 72:28
Yield 97%
e.r. 75:25
Yield 88%
e.r. 78:22
Yield 67%
e.r. 78:22
Scheme 3 Asymmetric Henry and Meervein–Ponndorf–Verley reac-
tions
In summary, we have developed a one-step preparation
of N,N′-dialkylated cyclohexane-1,2-diamines directly from
cyclohexane-1,2-diamine salts. Although the yields from
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

D
A. A. Tsygankov et al.
Letter
Synlett
the novel protocol were similar to those of the classical
two-step route, the one-step procedure is operationally
more convenient and less time-consuming. The resulting
chiral amines were used as organocatalysts in two-step
syntheses of α-hydroxy γ-keto esters from arenes; this per-
mitted the preparation of methyl (S)-2-hydroxy-4-oxo-2-
phenylpentanoate in 96.5:3.5 e.r. The absolute configura-
tion of the product was determined by means of anomalous
X-ray scattering. Some of the prepared diamines were also
tested as chiral ligands for Henry and Meervein–Ponndorf–
Verley reactions.
(i) Clegg, W.; Harington, R. W.; North, M.; Pizzato, F.; Villuendas,
P. Tetrahedron: Asymmetry 2010, 21, 1262. (j) Zhu, X.; Lin, A.;
Fang, L.; Li, W.; Zhu, C.; Cheng, Y. Chem. Eur. J. 2011, 17, 8281.
(k) Viózques, S.; Bañón-Caballero, A.; Guillena, G.; Nájera, C.;
Gómez-Bengoa, E. Org. Biomol. Chem. 2012, 10, 4029. (l) Kang,
G.; Jiang, J.; Liu, H.; Wu, H. J. Braz. Chem. Soc. 2012, 23, 5.
(m) Mao, Z.; Zhu, X.; Lin, A.; Li, W.; Shi, Y.; Mao, H.; Zhu, C.;
Cheng, Y. Adv. Synth. Catal. 2013, 355, 2029.
(7) (a) Kumar, S.; Chauhan, M. S.; Yadav, G. D.; Singh, S. Synlett
2016, 27, 267. (b) Egami, H.; Katsuki, T. Synlett 2008, 1543.
(c) Shimada, Y.; Kondo, S.; Ohata, Y.; Matsumoto, K.; Katsuki, T.
Synlett 2007, 2445. (d) Atwood, D. A. Coord. Chem. Rev. 1997,
165, 267.
(8) Chusov, D.; List, B. Angew. Chem. Int. Ed. 2014, 53, 5199.
(9) Yagafarov, N. Z.; Usanov, D. L.; Moskovets, A. P.; Kagramanov, N.
D.; Maleev, V. I.; Chusov, D. ChemCatChem 2015, 7, 2590.
(10) Diamines 3a–k; One-Step General Procedure
Acknowledgment
The work was supported financially by the Russian Science Founda-
tion (Grant # 16-13-10393). We thank Dr. Dmitry Usanov for his
feedback on this manuscript.
A glass vial in a 10-mL stainless-steel autoclave was charged
with Rh2(OAc)4 (0.7 mg, 1.60 μmol, 1 mol%), (1R,2R)-cyclohex-
ane-1,2-diamine dihydrochloride (30.0 mg, 0.160 mmol, 100
mol%), K2CO3 (26.6 mg, 0.192 mmol, 120 mol%), i-PrOH (0.1 mL),
H2O (0.1 mL), and the appropriate aldehyde (0.320 mmol, 200
mol%). The autoclave was then sealed, flushed three times with
CO (5 atm), and pressurized with CO (50 atm). The reactor was
placed in a preheated oil bath (140 °C). After 4 h, the reactor was
cooled to r.t. and depressurized. The residue was collected by
filtration and analyzed by 1H NMR.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588382.
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References and Notes
(11) Schiff Bases 2a–k; General Procedure
A mixture of (1R,2R)-cyclohexane-1,2-diaminium (S)-tartrate
(1.0 equiv), K2CO3 (1.0 equiv), and H2O (0.66 mL per mmol of
K2CO3) was stirred until the solids were completely dissolved
and then MeOH (5.2 mL/mmol of tartrate) was added. The
mixture was heated to 65 °C and a solution of the appropriate
aldehyde (2 equiv) in MeOH (2.2 mL/mmol of tartrate) was
added over 30 min. The mixture was refluxed for an additional
4 h, then cooled to r.t. and concentrated in vacuo. The residue
was dissolved in EtOAc (4 mL/mmol of tartrate) and the solution
was washed with H2O (2 × 1 mL/mmol of tartrate), dried (Na2-
SO4), and concentrated in vacuo to give a beige-colored crude
product. The crude product containing some starting aldehyde
was used in the next step without further purification.
(1) List, B.; Lerner, R. A.; Barbas, C. F. III. J. Am. Chem. Soc. 2000, 122,
2395.
(2) Machajewski, T. D.; Wong, C.-H. Angew. Chem. Int. Ed. 2000, 39,
1352.
(3) Matsuo, J.-i.; Murakami, M. M. Angew. Chem. Int. Ed. 2013, 52,
9109.
(4) (a) List, B.; Pojarliev, P.; Castello, C. Org. Lett. 2001, 3, 573.
(b) Pidathala, C.; Hoang, L.; Vignola, N.; List, B. Angew. Chem. Int.
Ed. 2003, 42, 2785. (c) Mukherjee, S.; Yang, J. W.; Hoffman, S.;
List, B. Chem. Rev. 2007, 107, 5471. (d) Guellina, G.; Nájera, C.;
Ramón, D. Tetrahedron: Asymmetry 2007, 18, 2249. (e) Trost, B.
M.; Brindle, C. S. Chem. Soc. Rev. 2010, 39, 1600. (f) Ratjen, L.;
García-García, P.; Lay, F.; Beck, M. E.; List, B. Angew. Chem. Int.
Ed. 2011, 50, 754. (g) Bae, H. Y.; Sim, J. H.; Lee, J.-W.; List, B.;
Song, C. E. Angew. Chem. Int. Ed. 2013, 52, 12143. (h) Zhang, Z.;
List, B. Asian J. Org. Chem. 2013, 2, 957. (i) Martínez, A.;
Zumbansen, K.; Döhring, A.; van Gemmeren, M.; List, B. Synlett
2014, 25, 932. (j) Kalesse, M.; Cordes, M.; Symkenberg, G.; Lu,
H.-H. Nat. Prod. Rep. 2014, 31, 563. (k) Tap, A.; Blond, A.;
Wakchaure, V. N.; List, B. Angew. Chem. Int. Ed. 2016, 55, 8962.
(5) van Putten, P. L. Antonie van Leeuwenhoek 1979, 45, 622.
(6) (a) Tokuda, O.; Kano, T.; Gao, W.-L.; Ikemoto, T.; Maruoka, K.
Org. Lett. 2005, 7, 5103. (b) Tang, Z.; Cun, L.-F.; Cui, X.; Mi, A.-Q.;
Jiang, Y.-Z.; Gong, L.-Z. Org. Lett. 2006, 8, 1263. (c) Wang, F.;
Xiong, Y.; Liu, X.; Feng, X. Adv. Synth. Catal. 2007, 349, 2665.
(d) Xu, X.-Y.; Tang, Z.; Wang, Y.-Z.; Luo, S.-W.; Cun, L.-F.; Gong,
L.-Z. J. Org. Chem. 2007, 72, 9905. (e) Liu, J.; Yang, Z.; Wang, Z.;
Wang, F.; Chen, X.; Liu, X.; Feng, X.; Su, Z.; Hu, C. J. Am. Chem.
Soc. 2008, 130, 5654. (f) Liu, Q.-Z.; Wang, X.-L.; Luo, S.-W.;
Zheng, B.-L.; Qin, D.-B. Tetrahedron Lett. 2008, 49, 7434. (g) Raj,
M.; Parashari, G. S.; Singh, V. K. Adv. Synth. Catal. 2009, 351,
1284. (h) Jiang, Z.; Lu, Y. Tetrahedron Lett. 2010, 51, 1884.
(1R,2R)-2,2′-[Cyclohexane-1,2-diylbis(nitrilomethy-
lylidene)]diphenol (2i)
Yellow oil; yield: 3.1 g (82%). 1H NMR (300 MHz, CDCl3): δ = 8.32
(s, 2 H), 7.34–7.26 (m, 2 H), 7.21 (dd, J = 7.6, 1.5 Hz, 2 H), 6.95 (d,
J = 8.2 Hz, 2 H), 6.89–6.82 (m, 2 H), 3.43–3.32 (m, 2 H), 2.06–
1.88 (m, 4 H), 1.87–1.68 (m, 2 H), 1.62–1.46 (m, 2 H).
(12) Diamines 3a–k; General Procedure from Schiff Bases 2a–k
NaBH4 (2.1 equiv) was added portionwise over 40 min to a solu-
tion of the appropriate Schiff base 2 (1.0 equiv) in MeOH (4
mL/mmol of Schiff base) at r.t. The mixture was refluxed with
stirring for 1 h then cooled to r.t. H2O (5 mL/mmol of Schiff
base) was added, the mixture was extracted with CH2Cl2 (3 × 4
mL/mmol of Schiff base), and the organic layer was concen-
trated. If any aldehyde remained in the mixture, the residue was
dissolved in 35% aq HCl (1 mL/mmol of Schiff base) and the
solution was washed with CH2Cl2 (3 × 4 mL/mmol of Schiff
base). Excess K2CO3 (4.5 equiv) was added to the aqueous phase,
which was extracted with CH2Cl2 (3 × 3 mL/mmol of Schiff
base). The organic layers were combined, dried, and concen-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

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A. A. Tsygankov et al.
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Synlett
trated to give an oily product. If the product was not sufficiently
pure, it was purified by column chromatography.
(1R,2R)-N,N′-Bis(4-chlorobenzyl)cyclohexane-1,2-diamine
(3e)
J. Adv. Synth. Catal. 2013, 355, 274. (g) Pedrosa, R.; Andrés, J. M.;
Gamarra, A.; Manzano, R.; Pérez-López, C. Tetrahedron 2013, 69,
10811. (h) Deng, Y.-H.; Chen, J.-Q.; He, L.; Kang, T.-R.; Liu, Q.-Z.;
Luo, S.-W.; Yuan, W.-C. Chem. Eur. J. 2013, 19, 7143. (i) Guo, W.;
Wei, J.; Liu, Y.; Li, C. Tetrahedron 2014, 70, 6561. (j) Bayat, S.;
Salleh, A. B.; Malek, E. A.; Yousefi, S.; Rahman, M. B. A. Catal.
Lett. 2015, 145, 1750. (k) Kumar, T. P.; Shekhar, R. C.; Sander, K.
S.; Vadaparthi, R. Tetrahedron: Asymmetry 2015, 26, 543.
(l) Konda, S.; Guo, Q.-S.; Abe, M.; Huang, H.; Arman, H.; Zhao, J.
C.-G. J. Org. Chem. 2015, 80, 806. (m) Kochetkov, S. V.;
Kucherenko, A. S.; Zlotin, S. G. Mendeleev Commun. 2015, 25,
168. (n) Lisnyak, V. G.; Kucherenko, A. S.; Valeev, E. F.; Zlotin, S.
G. J. Org. Chem. 2015, 80, 9570. (o) Zhang, Y.; Zhu, J.; Yu, N.; Yu,
H. Chin. J. Chem. 2015, 33, 171. (p) Rojas Cabrera, H.; Huelgas, G.;
Hernández Pèrez, J. M.; Walsh, P. J.; Somanathan, R.; Anaya de
Parodi, C. Tetrahedron: Asymmetry 2015, 26, 163.
25
Yellow oil; yield: 2.45 g (48%); [α]D –64.7 (с 1.2, CHCl3). 1H
NMR (600 MHz, CDCl3): δ = 7.29 (d, J = 8.4 Hz, 4 H), 7.25 (d,
J = 8.4 Hz, 4 H), 3.88 (d, J = 13.4 Hz, 2 H), 3.64 (d, J = 13.4 Hz, 2
H), 2.28–2.24 (m, 2 H), 2.17–2.12 (m, 2 H), 1.76–1.71 (m, 2 H),
1.27–1.18 (m, 2 H), 1.11–0.97 (m, 2 H). 13C NMR (101 MHz,
CDCl3): δ = 139.6, 132.5, 129.5, 128.6, 61.2, 50.5, 32.0, 25.5; MS
(ESI): m/z = 363, 365, 367 [M + H]+.
(13) (a) Riera, J.; Castañer, J.; Carilla, J.; Robert, A. Tetrahedron Lett.
1989, 30, 3825. (b) Terao, J.; Nakamura, M.; Kambe, N. Chem.
Commun. 2009, 6011. (c) Adonin, N. Yu.; Shabalin, A. Yu.;
Bardin, V. V. J. Fluor. Chem. 2014, 168, 111.
(14) (a) Wang, C.; Jiang, Y.; Zhang, X.-x.; Huang, Y.; Li, B.-g.; Zhang,
G.-l. Tetrahedron Lett. 2007, 48, 4281. (b) Guillena, G.; Nájera, C.;
Viózquez, S. F. Synlett 2008, 3031. (c) Zhang, S.-p.; Fu, X.-k.; Fu,
S.-d. Tetrahedron Lett. 2010, 50, 1173. (d) Saha, S.; Moorthy, J. N.
Tetrahedron Lett. 2010, 51, 912. (e) Mino, T.; Omura, A.; Uda, Y.;
Wakui, K.; Haga, Y.; Sakamoto, M.; Fujita, T. Tetrahedron: Asym-
metry 2011, 22, 2024. (f) Paladhi, S.; Das, J.; Mishra, P. K.; Dash,
(15) Methyl (2S)-2-Hydroxy-4-oxo-2-phenylpentanoate (5a)
White crystals; yield: 31.5 mg (93%). 1H NMR (300 MHz, CDCl3):
δ = 7.56 (dd, J = 8.1, 1.2 Hz, 2 H), 7.41–7.27 (m, 3 H), 4.50–4.40
(br s, 1 H), 3.75 (s, 3 H), 3.56 (d, J = 17.7 Hz, 1 H), 3.01 (d, J = 17.7
Hz, 1 H), 2.21 (s, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E