Diastereo- and regioselective addition of thioamide dianions to imines and aziridines: Synthesis of N-thioacyl-1,2-diamines and N-thioacyl-1,3-diamines

Article abstract of DOI:10.1002/chem.201203470

Addition reactions of thioamide dianions that were derived from N-arylmethyl thioamides to imines and aziridines were carried out. The reactions of imines gave the addition products of N-thioacyl-1,2-diamines in a highly diastereoselective manner in good-to-excellent yields. The diastereomeric purity of these N-thioacyl-1,2-diamines could be enriched by simple recrystallization. The reduction of N-thioacyl-1,2-diamines with LiAlH₄ gave their corresponding 1,2-diamines in moderate-to-good yields with retention of their stereochemistry. The oxidative-desulfurization/cyclization of an N-thioacyl-1,2-diamine in CuCl₂/O₂ and I ₂/pyridine systems gave the cyclized product in moderate yield and the trans isomer was obtained as the sole product. On the other hand, a similar cyclization reaction with antiformin (aq. NaClO) as an oxidant gave the cis isomer as the major product. The reactions of N-tosylaziridines gave the addition products of N-thioacyl-1,3-diamines with low diastereoselectivity but high regioselectivity and in good-to-excellent yields. The use of AlMe ₃ as an additive improved the efficiency and regioselectivity of the reaction. The stereochemistry of the obtained products was determined by X-ray diffraction.

Full text of DOI:10.1002/chem.201203470

DOI: 10.1002/chem.201203470
Diastereo- and Regioselective Addition of Thioamide Dianions to Imines and
Aziridines: Synthesis of N-Thioacyl-1,2-diamines and N-Thioacyl-1,3-
diamines
Fumitoshi Shibahara,* Shun-ichiro Kobayashi, Toshifumi Maruyama, and
Toshiaki Murai*[a]
Abstract: Addition reactions of thio-
ACHTUNGTRENNUNGamide dianions that were derived from
moderate-to-good yields with retention
of their stereochemistry. The oxidative-
desulfurization/cyclization of an N-
cyclization reaction with antiformin
(aq. NaClO) as an oxidant gave the cis
isomer as the major product. The reac-
tions of N-tosylaziridines gave the ad-
dition products of N-thioacyl-1,3-di-
N-arylmethyl thioamides to imines and
aziridines were carried out. The reac-
tions of imines gave the addition prod-
ucts of N-thioacyl-1,2-diamines in a
highly diastereoselective manner in
good-to-excellent yields. The diastereo-
meric purity of these N-thioacyl-1,2-di-
amines could be enriched by simple re-
crystallization. The reduction of N-
thioACHTNUGTRNEUNGacyl-1,2-diamine in CuCl2/O2 and
I2/pyridine systems gave the cyclized
product in moderate yield and the
trans isomer was obtained as the sole
product. On the other hand, a similar
AHCTUNGTRENNaGUN mines with low diastereoselectivity
but high regioselectivity and in good-
to-excellent yields. The use of AlMe3
as an additive improved the efficiency
and regioselectivity of the reaction.
The stereochemistry of the obtained
products was determined by X-ray dif-
fraction.
Keywords: addition reactions · car-
banions · diamines · diastereoselec-
tivity · regioselectivity
thioACHTUNGTRENNUNGacyl-1,2-diamines with LiAlH4 gave
their corresponding 1,2-diamines in
Introduction
(1, [Eq. (1)]).[5] Thioamide dianions have previously been
shown to lead to N-thioacyl amino alcohols, amines, and a-
silylmethylamines by treatment with their corresponding
electrophiles, such as aldehydes, oxiranes, alkyl halides, and
silyl chlorides. Herein, we describe the diastereo- and regio-
selective addition of thioamide dianions to imines or aziri-
dines, thereby leading to N-thioacyl-1,2- or 1,3-diamines,
and the synthetic application of the resulting products,
thereby leading to their corresponding diamines and hetero-
cycles.
Vicinal (1,2-) and 1,3-diamines are important structural
motifs in natural products, pharmaceuticals, and ligands for
catalysts and supramolecules.[1] Many methods for the prep-
aration of these motifs have been reported.[2] Among them,
the addition of carbanions that are a to the nitrogen atom
to imines or aziridines is one of the most efficient ap-
proaches for obtaining diverse diamines, owing to the ready
availability of these electrophiles. However, probably owing
to the selectivity of these processes for the generation of
carbanions from primary and secondary amine derivatives,
as well as the lability of the carbanions,[3] the previous re-
ports on addition reactions to imines have been limited to
those of carbanions from tertiary amides and carbamates.[2c,d]
Furthermore, to the best of our knowledge, the addition of
such carbanions to aziridines has never been reported.[4] Re-
cently, we described the synthetic applications of a-nitrogen
carbanions, N-arylmethyl thioamide dianions (1’), which
were generated by the treatment of 2 equivalents of BuLi
with their corresponding secondary N-arylmethyl thioamides
Results and Discussion
Initial investigation of the reaction between a thioamide di-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
carried out (Scheme 1). The reaction proceeded smoothly to
give the corresponding N-thioacyl-1,2-diamine (3aa) in
quantitative yield. In this case, no diastereoselectivity was
observed (d.r.=1:1). The reaction even proceeded at À78 or
À958C and showed significantly improved d.r. values of 4:1
and 9:1, respectively. Further enrichment of the major dia-
stereomer of compound 3aa was observed after recrystalli-
zation of the crude mixture. For example, diastereomerically
[a] Prof. Dr. F. Shibahara, S.-i. Kobayashi, T. Maruyama,
Prof. Dr. T. Murai
Department of Chemistry, Faculty of Engineering
Gifu University, Yanagido, Gifu 501-1193 (Japan)
Fax : (+81)58-293-2794
E-mail: fshiba@gifu-u.ac.jp
mtoshi@gifu-u.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201203470.
304
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Chem. Eur. J. 2013, 19, 304 – 313

FULL PAPER
imine that contained an o-methoxyphenyl group on the
imino carbon atom (2e) gave the corresponding product
(3ae) in 63% yield, similar to the reaction of compound 2c
but with higher diastereoselectivity (Table 1, entry 5). The
reactions between compound 1a’ and aliphatic imines 2 f
and 2g also afforded adducts 3af and 3ag in good yields, al-
though 2 equivalents of the imines were required to achieve
good conversions of compound 1a’ (Table 1, entries 6 and
7); in this case, the reaction of a tert-butyl-substituted imine
(2g) with compound 1a’ showed complete diastereoselectivi-
Scheme 1. Initial investigation of the reaction between thioamide dianion
1a’ and imine 2a.
Table 1. Reactions
between
thioamide
1a
and
imines
2.[a,b]
and analytically pure compound 3aa (d.r.>20:1)
was obtained in 74% yield from the crude mixture
of the reaction at À958C after a single recrystalliza-
tion process. The stereochemistry of the major
isomer was determined to be (S*,S*) by single-crys-
tal X-ray analysis (Figure 1).
Entry
Imine
Conversion
[%][c]
Yield [%][d]
1
2
3
4
5
R1 =Ph
R2 =Ph
2a quant. (9:1)
2b 89 (9:1)
2c quant. (4:1)
2d 90 (9:1)
2e quant. (9:1)
74 (>20:1)
74 (>20:1) 3ab
78 (9:1) 3ac
71 (20:1) 3ad
63 (>20:1) 3ae
3aa
R1 =4-F3CC6H4 R2 =Ph
Scope of the substrates in the coupling reactions of
thioamide dianions with imines: Next, the coupling
reactions between thioamide 1a and several imines
(2) were examined at À958C (Table 1). The reac-
tion of compound 1a’ with an imine that contained
a trifluoromethylphenyl group on the imino carbon
atom (2b) gave the corresponding product (3ab) in
good yield with high diastereoselectivity (Table 1,
entry 2). Again, diastereomerically pure product
(S*,S*)-3ab was obtained in 74% yield after a
R1 =PMP
R1 =4-MeC6H4
R1 =o-
R2 =Ph
R2 =Ph
R2 =Ph
MeOC6H4
6[e]
7[e]
8
R1 =iPr
R2 =Ph
2 f
94 (1:1)
67 (1:1)[f] 3af
91 (>20:1)[f] 3ag
78 (9:1) 3ah
R1 =tBu
R1 =Ph
R2 =Ph
2g 86 (>20:1)
2h quant. (9:1)
R2 =PMP
R2 =4-CF3C6H4
R2 =4-BrC6H4
R2 =o-
9
R1 =Ph
2i
90 (2:3)
76 (2:3)
3ai
10[e]
11
R1 =Ph
2j quant. (1:1)
2k quant. (1:1)
80 (3:1)[f] 3aj
83 (1:1) 3ak
R1 =Ph
MeOC6H4
single recrystallization process. Although these re- 12
R1 =Ph
R2 =tBu
2l
no reaction
actions also furnished adducts 3ac and 3ad in good
[a] The reactions were carried out with 1.1 equiv of imines 2. [b] The generation of
thio
amide dianion 1a’ was carried out in a 0.5m solution. [c] Determined by 1H NMR
AHCTUNGTRENNUNG
yields, the use of electron-rich imines 2c and 2d,
which were derived from p-methoxy- and p-methyl-
benzaldehydes, respectively, slightly decreased the
d.r. values of both the crude mixtures and the iso-
lated products (Table 1, entries 3 and 4). Mean-
while, the reaction between compound 1a and an
spectroscopy with reference to unconsumed starting thioamides in the crude mixture
and 1,1,2,2-tetrachloroethane as an internal standard. The d.r. values of the isolated
products are given in parentheses. [d] Yield of the isolated product after recrystalliza-
tion; the d.r. values of the products are given in parentheses. [e] To complete the reac-
tion, 2 equiv of imine were used. [f] Isolated by column chromatography on silica gel.
ty. The substituents on the nitrogen atoms of the imine
groups significantly affected the reactivity and selectivity of
the reaction, compared to those on the imino carbon atoms.
The reaction with N-p-methoxyphenyl (PMP) imine 2h still
furnished the product with a high d.r. under the standard
conditions (Table 1, entry 8); in contrast, almost no diaster-
eoselectivity was observed in the reaction of 4-trifluorome-
thylphenyl-substituted imine 2i with compound 1a’ (Table 1,
entry 9). The reaction of 4-bromophenyl-substituted imine
2j with compound 1a’ also showed poor diastereoselectivity,
but, notably, the bromine atom on the substrate remained
intact under the reaction conditions to result in the forma-
tion of compound 3aj in good yield. The reaction of com-
pound 1a’ with N-o-methoxyphenyl imine 2k showed the
complete absence of diastereoselectivity (Table 1, entry 11).
The reaction of N-tert-butyl imine 2l did not afford any
product at all (Table 1, entry 12).
Figure 1. ORTEP of compound 3aa;[6] thermal ellipsoids are set at 50%
Next, we turned our attention to the scope of the thioa-
probability.
mides (1; Table 2). The substituents on thioamides 1 affected
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305

F. Shibahara, T. Murai et al.
Table 2. Reactions
of
thioamides
1
with
imines
2.[a,b]
the (S*,S*)-isomer (Scheme 2, left). A similar mechanism
for stereoselection in the reaction between imines and a-ni-
trogen carbanions of tertiary carbamates was proposed by
Kise, Yoshida, and co-workers.[2c]
Synthetic applications of N-thioacyl-1,2-diamines (3): The
products (3) can be transformed into their corresponding
1,2-diamine derivatives. For example, the reduction of com-
pounds 3 with LiAlH4 gave 1,2-diamines 4 in moderate-to-
good yields with the retention of stereochemistry
([Eq. (2)]).[7] Unsymmetrical 1,2-diamines that were similar
to compounds 4 were synthesized by aldimine cross-coupling
or by the reduction of 1,2-diimine, but their diastereoselec-
tivities depended on the substituents. Therefore, this method
can be used as a complementary process for the synthesis of
stereochemically defined unsymmetrical 1,2-diamines (4).[8]
Oxidative-desulfurization/cyclization[9] of compound 3aa al-
lowed us to access imidazoline trans-5 in moderate yields
([Eq. (3)]). The configuration of trans-5 was determined by
X-ray analysis (Figure 2). In contrast, a similar cyclization
Entry
1[e]
2
3
4
Thioamide
Imine
d.r.[c]
Yield[%][d]
1b
1c
1d
2a
2b
2c
2a
2b
2c
2a
9:1
66 (>20:1)
3ba
3bb
3bc
3ca
3cb
3cc
3da
4:1[f]
4:1
68 (19:1)
81 (4:1)[g]
84 (13:1)
78 (3:1)[g]
74 (4:1)[g]
62 (2:3)
4:1
3:1
5
6[e]
7
4:1
1:2[h]
[a] The reactions were carried out with 1.1 equiv of imines 2. Unless oth-
erwise noted, the reactions were performed under the conditions given in
the running text. [b] The generation of thioamide dianion 1a’ was carried
out in a 0.5m solution. [c] The diastereomeric ratios of the crude products
were determined by 1H NMR spectroscopy. [d] Yield of the isolated
product after recrystallization; the d.r. values of the products are given in
parentheses. [e] Owing to the solubility of dianion 1’, the reaction was
carried out in 0.125m solution. [f] 94% Conversion. [g] Isolated mixture.
the crystal formation in the products. For example, product
3bc barely crystallized and was obtained as a sticky oil,
even after purification by column chromatography on silica
gel, and thus recrystallization did not increase its d.r.
(Table 2, entry 3). In contrast, the d.r. values of compounds
3ba and 3bb improved after recrystallization (Table 2, en-
tries 1 and 2). A similar tendency for crystallization was ob-
served for the products that were obtained from the reac-
tions of compound 1c with imines 2a–2c (Table 2, entries 4-
6). In addition, the reaction between alkyl-substituted thioa-
mide 1d and compound 2a showed low diastereoselectivity
(Table 2, entry 7).
Consideration of stereocontrol in the coupling of thioamide
dianions with imines: The high diastereoselectivity in the
formation of compound 3 can be explained if the reaction
passes through a chelation transition state during the addi-
tion step of thioamide dianion 1’ to imines 2 (Scheme 2).
The conformation of the thioamide dianions (1’) may be
fixed by intramolecular chelation of the benzylic lithium
moiety to a sulfur atom. The ligation of the imino nitrogen
atom to the benzylic lithium moiety of the dianion, followed
by the addition reaction, should favor the formation of a
less-crowded transition-state structure, thereby resulting in
Figure 2. ORTEP of compound trans-5;[6] thermal ellipsoids are set at
50% probability.
reaction of compound 3aa with antiformin (aq. NaClO) as
the oxidant gave cis-5 as the major product ([Eq. (4)]). Al-
though all of the stereochemistry was lost, the aromatization
of compound 5 by 2,3-dichloro-5,6-dicyano-1,4-benzoqui-
none (DDQ) led to the corresponding tetraphenylated imi-
dazole (6; [Eq. (5)]).
Reactions between thioamide
dianion 1a’ and aziridines 7:
The reactions between dianion
1a’ and N-protected 2-methyl-
aziridines 7 instead of imines
were investigated under the
standard conditions described
in Table 3. Initial investigation
Scheme 2. Proposed stereocontrol pathway through chelation control.
306
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Synthesis of N-Thioacyl-1,2- and -1,3-diamines
FULL PAPER
thioacyl-1,3-diamine (8c) in 56% yield with good regioselec-
tivity (Table 3, entry 3). In this case, the reaction preferred
to proceed at the less-crowded 3-position of compound
7c.[10] Unfortunately, the efficiency of the reaction did not
improve when the reaction was carried out at 08C (Table 3,
entry 4). To improve the yield and diastereoselectivity of
this reaction, several Lewis acids, such as BF3·OEt2, Cu-
AHCTUNTGRENGUN(N TfO)2, and AlMe3, were tested as additives (Table 3, en-
tries 5–7). However, only AlMe3 showed a positive effect as
an additive in the reaction, thereby affording compound 8c
in an improved yield of 79% and better regioselectivity, but
the d.r. did not improve at all (Table 3, entry 7). The reac-
tion still showed good regioselectivity and the yield of
adduct 8c was improved to 99% at 08C (Table 3, entry 8).
Presumably, AlMe3 not only activated the reaction but also
avoided side-reactions. In fact, when the reaction was run in
the absence of AlMe3 at 08C, the crude mixture was found
to be contaminated by a small amount of unidentified by-
products, as well as by trace amounts of the regioisomer
(Table 3, entry 4).
Scope of the substrates in the reactions between thioamide
dianion 1a’ and aziridines 9 in the presence of AlMe3 as an
additive: Benzyl (9a)-, isopropyl (9b)-, and tert-butyl-substi-
tuted aziridines (9c) were also used as electrophiles in the
reactions with dianion 1’ to give compounds 10a–10c, re-
spectively, in moderate-to-high yields (Table 4). In these
Table 4. Reactions between compound 1a and aziridines 9.[a,b]
Table 3. Reactions between thioamide 1a and N-protected 2-methylaziri-
dines 7.[a]
Entry
7
T [8C] Additive Conversion [%][b] Yield [%][c] 8:8’
1
2
3
4
5
6
7
8
7a À95
7b À95
7c À95
–
–
–
–
complex mixture
no reaction
85
quant.
56[d]
5:1
5:1
7c
0
66
complex mixture
complex mixture
79
[a] The reactions were carried out with 1.1 equiv of aziridines 9. [b] Yield
of isolated product after column chromatography on silica gel.
7c À95
7c À95
7c À95
BF3·OEt2
CuACTHNUTRGENUG(N OTf)2
AlMe3
AlMe3
96
quant.
13:1
5:1
7c
0
99
cases, relatively sterically hindered aziridines 9b and 9c af-
forded the products (10b and 10c) with exclusive regioselec-
tivity, whereas the reaction of compound 9a gave compound
10a together with a small amount of the regioisomer, similar
to the reaction of compound 7c. On the other hand, the re-
action of compound 1a’ with styrene-derived aziridine 9d
gave the other regioisomer (10d) as the major product, as
confirmed by X-ray analysis (Figure 3). Similar regioselec-
tivity was observed in the reaction between b-methylstyr-
ene-derived trans-9e and dianion 1a’.[11] That is, the reac-
[a] The reactions were carried out with 1.1 equiv of aziridines 7. Unless
otherwise noted, the reactions gave a 1:1 diastereomeric mixture. [b] De-
termined by 1H NMR spectroscopy, with reference to unconsumed start-
ing thioamides in the crude mixture and 1,1,2,2-tetrachloroethane as an
internal standard. [c] Yield of isolated product. [d] d.r.=2:1.
of the protecting groups on the nitrogen atom of aziridines 7
(Table 3, entries 1–3) showed that N-tosyl aziridine 7c was
an appropriate electrophile and gave its corresponding N-
Chem. Eur. J. 2013, 19, 304 – 313
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307

F. Shibahara, T. Murai et al.
Materials: Unless otherwise noted, the reagents were commercially avail-
able and were used without further purification. THF (dehydrated) was
purchased from Kanto Chemical Co. and used without further purifica-
tion. DMSO was distilled over calcium hydride under reduced pressure.
The imines were prepared according to standard procedures. N-tert-
butoxycarbonyl-2-methylaziridine (7a),[14] N-benzyl-2-methylaziridine
(7b),[15] 2-methyl-N-tosylaziridine (7c),[16] 2-benzyl-N-tosylaziridine
(9a),[17] 2-isopropyl-N-tosylaziridine (9b),[18] 2-tert-butyl-N-tosylaziridine
(9c),[19] 2-phenyl-N-tosylaziridine (9d),[20] and trans-2-methyl-3-phenyl-N-
tosylaziridine (9e)[21] were prepared according to literature procedures.
Column chromatography was performed on silica gel 60 N (Spherical,
Neutral, 100–210 mm or 40–50 mm) from Kanto Chemical Co., Inc.
General procedure for the reaction between thioamide dianion 1’ and
imines 2: To a 0.25m solution of thioamide 1 in THF was added nBuLi
(1.6m in n-hexane, 2 equiv) at 08C and the mixture was stirred at 08C for
5 min. A 0.2m solution of aldimine 2 (1 equiv) in THF was added to the
reaction mixture at À958C and the solution was stirred at that tempera-
ture for 1 h. The reaction mixture was poured onto water and extracted
with CH2Cl2. The organic layer was washed with brine, dried over
MgSO4, filtered, and concentrated in vacuo. The residue was purified by
recrystallization or by column chromatography on silica gel to give the
N-thioacyl-1,2-diamines.
Figure 3. ORTEP of compound 10d;[6] thermal ellipsoids are set at 50%
probability.
tions of styrene-derived aziridines proceeded at the position
a to the phenyl group, probably owing to the electrophilicity
of the benzylic position.[12,13] In addition, the diastereomers
of products 10d and 10e could be easily separated by con-
ventional flash column chromatography on silica gel or by
preparative HPLC.
N-(1,2-Diphenyl-2-phenylaminoethyl)benzenecarbothioamide (3aa): Pu-
rified by recrystallization from
a solution in CH2Cl2 and n-hexane.
Yellow solid; 74% yield; d.r.>20:1; Rf =0.43 (n-hexane/EtOAc, 5:1);
m.p. 194.8–195.58C; 1H NMR (CDCl3): d=4.77 (brs, 1H; PhNH), 5.00
(d, J=8.1 Hz, 1H; PhNHCH), 6.14 (t, J=8.1 Hz, 1H; C(=S)NHCH),
6.57 (d, J=7.6 Hz, 2H; Ar), 6.67 (t, J=7.3 Hz, 1H; Ar), 7.08 (dd, J=8.6,
7.3 Hz, 2H; Ar), 7.14 (dd, J=6.8, 3.5 Hz, 2H; Ar), 7.18–7.31 (m, 8H;
Ar), 7.35 (dd, J=7.8, 7.3 Hz, 2H; Ar), 7.45 (t, J=7.8 Hz, 1H; Ar), 7.63
(d, J=7.1 Hz, 2H; Ar), 8.10 ppm (d, J=8.1 Hz, 1H; NH); 13C NMR
(CDCl3): d=62.8, 64.7 (CH), 113.9, 118.2, 126.6, 127.6, 127.7, 127.8,
128.3, 128.5, 128.6, 128.8, 129.2, 131.2, 137.0, 139.3, 142.0, 146.7 (Ar)
199.7 ppm (C=S); IR (KBr): n˜ =3333, 3282, 3029, 2925, 1761, 1604, 1506,
1496, 1484, 1454, 1389, 1342, 1314, 1274, 1252, 1219, 1189, 1156, 1117,
1065, 1029, 954, 926, 873, 849, 619, 593, 518, 469 cmÀ1; MS (EI): m/z: 408
[M]+; HRMS (EI): m/z calcd for C27H24N2S: 408.1660 [M]+; found:
408.1642.
Conclusion
In conclusion, the addition of thioamide dianions to imines
and aziridines has been achieved. These reactions gave a va-
riety of N-thioacyl-1,2- and 1,3-diamines in moderate-to-
high yields. Coupling between the thioamide dianions and
imines proceeded in a diastereoselective manner and, nota-
bly, the d.r. values were readily improved by simple recrys-
tallization. On the other hand, the reactions between thio-
ACHTUNGTRENNUNGamide dianions and aziridines showed poor diastereoselec-
tivity but they proceeded in a regioselective manner. These
reactions may lead to highly substituted sterically defined
1,2- and 1,3-diamine derivatives from readily available start-
ing materials. Their use in enantioselective addition reac-
tions and in further synthetic applications, such as the ster-
eodefined construction of heavily substituted nitrogen-con-
taining heterocycles, are underway in our laboratory.
N-[1-Phenyl-2-phenylamino-2-(4-trifluoromethylphenyl)ethyl]benzene-
carbothioamide (3ab): Purified by recrystallization from a solution in
CH2Cl2 and n-hexane. Yellow solid; 74% yield; d.r.>20:1; Rf =0.45 (n-
hexane/EtOAc, 5:1); m.p. 187.8–188.18C; 1H NMR (CD3CN): d=5.20
(dd, J=9.8, 8.8 Hz, 1H; PhNHCH), 5.57 (d, J=8.8 Hz, 1H; PhNH), 5.97
(dd, J=9.8, 7.8 Hz, 1H; C(=S)NHCH), 6.61 (t, J=7.3 Hz, 1H; Ar), 6.65
(d, J=7.8 Hz, 2H; Ar), 7.06 (dd, J=8.3, 7.3 Hz, 2H; Ar), 7.22–7.24 (m,
5H; Ar), 7.39–7.43 (m, 4H; Ar), 7.48–7.50 (m, 3H; Ar), 7.76 (d, J=
8.1 Hz, 2H; Ar); 9.46 ppm (d, J=7.8 Hz, 1H; C(=S)NH); 13C NMR
(CDCl3): d=62.9, 64.6 (CH), 113.7, 118.4 (Ar), 124.0 (q, J=272.1 Hz;
CF3), 125.4 (q, J=4.1 Hz; CCCF3), 126.7, 127.7, 128.0, 128.68, 128.71,
129.1, 129.3, 130.0 (q, J=32.3 Hz; CCF3), 131.5, 136.6, 141.8, 143.8, 146.3
(Ar), 200.4 ppm (C=S); 19F NMR (CD3CN): d=À63.3 ppm; IR (KBr):
n˜ =3352, 2360, 1601, 1508, 1446, 1327, 1256, 1167, 1119, 1067, 1017, 840,
758, 695 cmÀ1; MS (EI): m/z: 476 [M]+; HRMS (EI): m/z calcd for
C28H23F3N2S: 476.1534 [M]+; found: 476.1561.
Experimental Section
General remarks: IR spectra were obtained on a JASCO FTIR 410 spec-
trometer. 1H NMR spectra were recorded on a JEOL a-400 (400 MHz)
in CDCl3; the chemical shifts (d) were referenced to tetramethylsilane as
an internal standard. 13C NMR spectra were measured on a JEOL a-400
(100 MHz) in CDCl3. 19F NMR spectra were measured on a JEOL a-400
(376 MHz) in CDCl3 and with CF3COOH as an external standard. MS
and HRMS were performed on a JMS-700 mass spectrometer. Elemental
analysis was carried out by the Elemental Analysis Center of Kyoto Uni-
versity. Melting points were determined by using a Yanaco seisakusho
MP-S2 micro melting point apparatus and are uncorrected. HPLC was
performed on a Japan Analytical Industry LC-908 recycling preparative
HPLC that was coupled to an RI indicator and a UV detector (256 nm)
with a Mightysil Si 60 column (250 mmꢁ20 mm). Preparative recycling
gel-permeation chromatography (GPC) was performed on a Japan Ana-
lytical Industry LC-908 recycling preparative HPLC that was equipped
with JAIGEL-1H and JAIGEL-2H columns and LC9201R/U recycling
preparative HPLC (CHCl3).
N-[2-(4-Methoxyphenyl)-1-phenyl-2-phenylaminoethyl]benzenecarbo-
thioamide (3ac): Purified by recrystallization from a solution in CH2Cl2
and n-hexane. Yellow solid; 78% yield; d.r.=9:1; Rf =0.33 (n-hexane/
EtOAc, 5:1); m.p. 166.1–166.98C; 1H NMR (CDCl3, major isomer): d=
3.78 (s, 3H; OCH3), 4.78 (brs, 1H; PhNH), 4.99 (d, J=7.8 Hz, 1H;
PhNHCH), 6.09 (t, J=7.8 Hz, 1H; C(=S)NHCH), 6.57 (d, J=8.3 Hz,
2H; Ar), 6.66 (t, J=7.3 Hz, 1H; Ar), 6.82 (d, J=8.3 Hz, 2H; Ar), 7.04–
7.10 (m, 4H; Ar), 7.20–7.25 (m, 5H; Ar), 7.35 (dd, J=8.3, 7.3 Hz, 2H;
Ar), 7.42 (t, J=8.1 Hz, 1H; Ar), 7.62 (d, J=8.3 Hz, 2H; Ar), 8.02 ppm
(d, J=7.8 Hz, 1H; C(=S)NH); 13C NMR (CDCl3, major isomer): d=55.2
(CH3), 62.5, 64.1 (CH), 113.9, 114.2, 116.4, 118.1, 126.6, 127.6, 127.7,
128.5, 128.6, 128.9, 129.2, 131.2, 139.3, 142.0, 146.7, 159.4 (Ar), 199.5 ppm
(C=S); IR (KBr): n˜ =3327, 3292, 1714, 1602, 1507, 1387, 1251, 829, 760,
308
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 304 – 313

Synthesis of N-Thioacyl-1,2- and -1,3-diamines
FULL PAPER
697, 524 cmÀ1; MS (FAB): m/z: 439 [M+H]+; HRMS (FAB): m/z calcd
for C28H27N2OS: 439.1844 [M+H]+; found: 439.1860.
5:1); m.p. 180.5–181.38C; 1H NMR (CDCl3, major isomer): d=3.68 (s,
3H; OCH3), 4.35 (brs, 1H; ArNH), 4.92 (d, J=7.3 Hz, 1H; ArNHCH),
6.08 (dd, J=7.8, 7.3 Hz, 1H; C(=S)NHCH), 6.52 (d, J=8.8 Hz, 2H; Ar),
6.67 (d, J=8.8 Hz, 2H; Ar), 7.14–7.48 (m, 13H; Ar), 7.66 (d, J=6.8 Hz,
2H; Ar), 8.20 ppm (d, J=7.8 Hz, 1H; C(=S)NH); 13C NMR (CDCl3,
major isomer): d=55.6 (CH3), 63.3, 64.7 (CH), 114.7, 115.5, 126.6, 127.45,
125.47, 127.8, 128.1, 128.50, 128.52, 128.8, 131.2, 137.1, 139.3, 140.5, 141.9,
152.6 (Ar), 199.4 ppm (C=S); IR (KBr): n˜ =3394, 3290, 3028, 2838, 2358,
1602, 1507, 1496, 1448, 1385, 1316, 1244, 1230, 955, 752, 694 cmÀ1; MS
(FAB): m/z: 439 [M+H]+; HRMS (FAB): m/z calcd for C28H27N2OS:
439.1844 [M+H]+; found: 439.1840.
N-[2-(4-Methylphenyl)-1-phenyl-2-phenylaminoethyl]benzenecarbothio-
ACHTUNGTRENNUNGamide (3ad): Purified by recrystallization from a solution in CH2Cl2 and
n-hexane. Yellow solid; 71% yield; d.r.=20:1; Rf =0.43 (n-hexane/
EtOAc, 5:1); m.p. 194.0–194.48C; 1H NMR (CDCl3): d=2.28 (s, 3H;
CH3), 4.68 (brs, 1H; PhNH), 4.97 (d, J=7.8 Hz, 1H; PhNHCH), 6.11
(dd, J=8.3, 7.8 Hz, 1H; C(=S)NHCH), 6.57 (d, J=7.8 Hz, 2H; Ar), 6.67
(t, J=7.3 Hz, 1H; Ar), 7.03–7.10 (m, 5H; Ar), 7.14–7.15 (m, 3H; Ar),
7.24–7.30 (m, 3H; Ar), 7.35 (dd, J=7.8, 7.3 Hz, 2H; Ar), 7.44 (t, J=
7.3 Hz, 1H; Ar), 7.63 (d, J=7.3 Hz, 2H; Ar), 8.10 ppm (d, J=8.3 Hz,
1H; C(=S)NH); 13C NMR (CDCl3): d=21.1 (CH3), 62.2, 64.5 (CH),
113.9, 118.1, 126.6, 127.4, 127.7, 128.2, 128.5, 128.7, 129.16, 129.18, 131.2,
136.0, 137.0, 137.4, 141.9, 146.7 (Ar), 199.5 ppm (C=S); IR (KBr): n˜ =
3332, 3279, 3027, 2924, 1603, 1498, 1484, 1446, 1388, 1317, 1258, 1066,
1028, 955, 818, 754, 720, 694, 651, 576, 514 cmÀ1; MS (EI): m/z: 422 [M]+;
HRMS (EI): m/z calcd for C28H26N2S: 422.1817 [M]+; found: 422.1817.
N-[2-(4-Trifluoromethylphenylamino)-1,2-diphenylethyl]benzenecarbo-
thioamide (mixture of diastereomers) (3ai): Purified by column chroma-
tography on silica gel (n-hexane/EtOAc, 5:1; Rf =0.35). Yellow solid;
76% yield; d.r.=2:3; 1H NMR (CDCl3): d=5.01–5.06 (m, 1H;
ArNHCH), 5.02 (d, J=7.3 Hz, 1.5H; ArNH), 5.23 (dd, J=7.3, 3.4 Hz,
1.5H; ArNHCH), 5.57 (d, J=6.3 Hz, 1H; ArNH), 6.22 (dd, J=8.8,
8.3 Hz, 1H; C(=S)NHCH), 6.40 (dd, J=8.3, 3.4 Hz, 1.5H; C(=S)NHCH),
6.55–6.59 (m, 5H; Ar), 6.98–7.00 (m, 3H; Ar), 7.09–7.14 (m, 7H; Ar),
7.18–7.20 (m, 4H; Ar), 7.26–7.45 (m, 23.5H; Ar), 7.61 (d, J=8.3 Hz, 2H;
Ar), 7.68 (d, J=8.3 Hz, 3H; Ar), 8.17–8.22 (brs, 1H; C(=S)NH), 8.17–
8.22 ppm (brs, 1.5H; C(=S)NH); 13C NMR (CDCl3): d=61.3, 62.7, 63.6,
64.5 (CH), 112.7, 113.3 (Ar), 119.1 (q, J=33.1 Hz; CCF3), 119.9 (q, J=
33.1 Hz; CCF3), 124.7 (q, J=271.3 Hz; CF3), 124.8 (q, J=270.5 Hz; CF3),
126.48 (q, J=4.1 Hz; CCCF3), 126.53 (q, J=4.1 Hz; CCCF3), 126.65,
126.68, 127.2, 127.3, 127.5, 127.8, 128.0, 128.2, 128.39, 128.49, 128.51,
128.55, 128.63, 128.67, 128.70, 128.9, 131.4, 131.5, 135.3, 136.5, 137.1,
138.5, 141.5, 141.7, 149.1, 149.3 (Ar), 199.5, 200.3 ppm (C=S); 19F NMR
(CDCl3): d=À61.6, À61.5 ppm; IR (KBr): n˜ =3374, 3060, 3030, 1703,
N-[2-(2-Methoxyphenyl)-1-phenyl-2-phenylaminoethyl]benzenecarbo-
thioamide (3ae): Purified by recrystallization from a solution in CH2Cl2
and n-hexane. Yellow solid; 63% yield; d.r.>20:1; Rf =0.33 (n-hexane/
EtOAc, 5:1); m.p. 175.5–176.38C; 1H NMR (CDCl3): d=3.75 (s, 3H;
OCH3), 4.75 (brs, 1H; PhNH), 5.30 (d, J=7.3 Hz, 1H; PhNHCH), 6.13
(t, J=7.3 Hz, 1H; C(=S)NHCH), 6.60 (d, J=8.8 Hz, 2H; Ar), 6.67 (t, J=
7.3 Hz, 1H; Ar), 6.81 (t, J=7.8 Hz, 2H; Ar), 7.07–7.11 (m, 3H; Ar),
7.14–7.26 (m, 6H; Ar), 7.33 (t, J=7.3 Hz, 2H; Ar), 7.42 (dd, J=7.8,
7.3 Hz, 1H; Ar), 7.63 (d, J=7.8 Hz, 2H; Ar), 8.44 ppm (d, J=7.3 Hz,
1H; C(=S)NH); 13C NMR (CDCl3): d=55.4 (CH3), 57.6, 63.7 (CH),
110.8, 114.0, 118.3, 120.8, 126.7, 126.9, 127.5, 127.7, 128.3, 128.5, 128.7,
128.9, 129.2, 131.1, 137.6, 142.1, 146.9, 156.9 (Ar), 199.4 ppm (C=S); IR
(KBr): n˜ =3334, 3292, 2929, 2854, 1505, 1484, 1455, 1379, 1292, 1233,
1033, 818, 775, 725, 699 cmÀ1; MS (FAB): m/z: 439 [M+H]+; HRMS
(FAB): m/z calcd for C28H27N2OS: 439.1844 [M+H]+; found: 439.1859.
1616, 1530, 1484, 1450, 1367, 1322, 1278, 1109, 1064, 825, 768, 698 cmÀ1
;
elemental analysis calcd (%) for C28H23F3N2S: C 70.57, H 4.86, N 5.88;
found: C 70.74, H 4.85, N 5.86.
N-[2-(4-Bromophenylamino)-1,2-diphenylethyl]benzenecarbothioamide
(mixture of diastereomers) (3aj): Purified by recrystallization from a sol-
ution in CH2Cl2 and n-hexane. Yellow solid; 80% yield; d.r.=3:1; Rf =
0.34 (n-hexane/EtOAc, 5:1); 1H NMR (CDCl3, major isomer): d=4.95
(d, J=8.3 Hz, 1H; ArNHCH), 4.96 (brs, 1H; ArNH), 6.15 (t, J=8.3 Hz,
1H; C(=S)NHCH), 6.43 (d, J=8.8 Hz, 2H; Ar), 7.09–7.14 (m, 6H; Ar),
7.19–7.22 (m, 3H; Ar), 7.27–7.29 (m, 3H; Ar), 7.35 (dd, J=8.3, 6.8 Hz,
2H; Ar), 7.45 (t, J=7.3 Hz, 1H; Ar), 7.62 (d, J=7.8 Hz, 2H; Ar),
8.00 ppm (d, J=8.3 Hz, 1H; C(=S)NH); 13C NMR (CDCl3, major
isomer): d=62.8, 64.5 (CH), 109.7, 115.3, 126.6, 127.5, 127.7, 128.0,
128.48, 128.52, 128.6, 128.9, 131.4, 131.9, 136.6, 138.7, 141.8, 145.6 (Ar),
199.9 ppm (C=S); IR (KBr): n˜ =3354, 3286, 2925, 1593, 1478, 1453, 1380,
1311, 1251, 1065, 955, 816, 769, 697, 643, 585, 512 cmÀ1; MS (FAB): m/z:
N-[3-Methyl-1-phenyl-2-(phenylamino)butyl]benzenecarbothioamide
(mixture of diastereomers) (3af): Purified by column chromatography on
silica gel (n-hexane/EtOAc, 10:1; Rf =0.18). Yellow solid; 67% yield;
d.r.=1:1; 1H NMR (CDCl3): d=0.89 (d, J=6.8 Hz, 3H; CH3), 1.05 (d,
J=6.8 Hz, 3H; CH3), 1.11 (d, J=6.8 Hz, 3H; CH3), 1.29 (d, J=6.8 Hz,
3H; CH3), 1.50 (dsept, J=6.8, 2.4 Hz, 1H; CH3CH), 1.82 (dsept, J=6.8,
2.9 Hz, 1H; CH3CH), 3.45 (d, J=9.3 Hz, 1H; PhNHCH), 3.88–3.95 (m,
2H; PhNHCH, PhNH), 4.05 (brs, 1H; PHNH), 6.16–6.20 (m, 2H; C(=
S)NHCH), 6.67 (d, J=7.8 Hz, 2H; Ar), 6.72–6.78 (m, 4H; Ar), 7.14–7.51
(m, 22H; Ar), 7.60 (d, J=7.8 Hz, 2H; Ar), 7.88 (d, J=8.3 Hz, 1H; C(=
S)NH), 8.40 ppm (d, J=7.3 Hz, 1H; C(=S)NH); 13C NMR (CDCl3): d=
15.9, 19.9, 20.5, 20.8 (CH3), 29.6, 32.1 (CH3CH), 61.2, 62.3, 63.0, 64.9
(NHCH), 112.9, 113.3, 117.9, 118.1, 126.5, 126.6, 127.5, 128.21, 128.24,
128.25, 128.27, 128.4, 128.8, 129.2, 129.6, 129.8, 130.7, 131.0, 136.7, 139.2,
141.7, 142.1, 149.8, 149.5 (Ar), 197.6, 199.6 ppm (C=S); IR (KBr): n˜ =
3389, 3362, 3059, 3030, 2959, 2930, 1598, 1507, 1448, 1377, 1310, 1278,
487 (51) [MACTHNUTRGENNUG ACHTUNGTRENNGUN
(79Br)+H]+, 489 (49) [M(81Br)+H]+; HRMS (EI): m/z calcd
for C27H23BrN2S: 486.0765 [M]+; found: 486.0762.
N-[2-(2-Methoxyphenylamino)-1,2-diphenylethyl]benzenecarbothioamide
(mixture of diastereomers) (3ak): Purified by column chromatography
on silica gel (n-hexane/EtOAc, 5:1; Rf =0.45). Yellow solid; 83% yield;
1248, 1183, 1151, 1068, 1029, 944, 922, 870, 769, 750, 695, 652, 565 cmÀ1
;
MS (EI): m/z: 374 [M]+; HRMS (EI): m/z calcd for C24H26N2S: 374.1817
[M]+; found: 374.1814.
1
d.r.=1:1; H NMR (CDCl3): d=3.83 (s, 3H; OCH3), 3.88 (s, 3H; OCH3),
4.97–5.03 (m, 2H; ArNH, PhCH), 5.15 (brs, 1H; ArNH), 5.28 (dd, J=
9.3, 2.9 Hz, 1H; PhCH), 6.06 (dd, J=7.8, 7.1 Hz, 1H; C(=S)NHCH), 6.25
(dd, J=7.8, 3.7 Hz, 1H; C(=S)NHCH), 6.47 (dd, J=7.4, 1.8 Hz, 1H; Ar),
6.51 (dd, J=7.2, 2.1 Hz, 1H; Ar), 6.67–6.81 (m, 6H; Ar), 6.97–7.51 (m,
26H; Ar), 7.71 (d, J=7.3 Hz, 2H; Ar), 7.78 (d, J=7.3 Hz, 2H; Ar), 8.29
(d, J=7.1 Hz, 1H; C(=S)NH), 8.62 ppm (d, J=7.8 Hz, 1H; C(=S)NH);
13C NMR (CDCl3): d=55.5, 55.6 (CH3), 60.5, 62.4, 64.2, 64.7 (CH), 109.7,
109.7, 111.9, 112.3, 117.8, 118.1, 121.1, 121.2, 126.8, 126.8, 127.1, 127.55,
127.69, 127.73, 127.77, 127.9, 128.1, 128.35, 128.48, 128.52, 128.58, 128.62-
N-[3,3-Dimethyl-1-phenyl-2-(phenylamino)butyl]benzenecarbothioamide
(3ag): Purified by column chromatography on silica gel (n-hexane/
EtOAc, 10:1; Rf =0.33). Yellow solid; 91% yield; d.r.>20:1; m.p. 134.9–
135.88C; 1H NMR (CDCl3): d=1.09 (s, 9H; CH3), 3.53 (brs, 1H;
PhNHCH), 3.79 (brs, 1H; PhNH), 6.20 (dd, J=8.8, 2.1 Hz, 1H; C(=
S)NHCH), 6.25 (d, J=7.8 Hz, 2H; Ar), 6.68 (t, J=7.3 Hz, 1H; Ar), 7.00
(dd, J=8.3, 7.6 Hz, 2H; Ar), 7.28–7.34 (m, 7H; Ar), 7.44 (dd, J=7.6,
7.1 Hz, 1H; Ar), 7.66 (d, J=8.3 Hz, 2H; Ar), 8.55 ppm (d, J=8.8 Hz,
1H; C(=S)NH); 13C NMR (CDCl3): d=27.0 (CH3), 36.9 ((CH3)3C), 58.2,
70.7 (CH), 114.1, 118.8, 126.5, 126.6, 127.6, 128.6, 129.1, 129.3, 131.0,
141.7, 142.2, 149.0 (Ar), 197.9 ppm (C=S); IR (KBr): n˜ =3337, 2958,
1601, 1496, 1478, 1370, 1333, 1312, 1300, 1247, 1233, 1071, 1031, 981, 917,
744, 693 cmÀ1; MS (FAB): m/z: 389 [M+H]+; HRMS (FAB): m/z calcd
for C25H29N2S: 389.2051 [M+H]+; found: 389.2051.
AHCTUNGTERG(NNUN 3C), 131.18, 131.24, 135.3, 136.2, 136.6, 137.3, 138.2, 139.3, 141.9, 142.1,
147.4, 147.5 (Ar), 198.7, 199.4 ppm (C=S); IR (KBr): n˜ =3338, 3288,
2931, 2831, 1601, 1509, 1480, 1456, 1430, 1375, 1327, 1250, 1225, 1177,
1126, 1065, 1050, 1028, 957, 853, 772, 749, 736, 699, 645, 591 cmÀ1; MS
(FAB): m/z: 439 [M+H]+; HRMS (FAB): m/z calcd for C28H27N2OS:
439.1844 [M+H]+; found: 439.1859.
N-[2-(4-Methoxyphenylamino)-1,2-diphenylethyl]benzenecarbothioamide
(3ah): Purified by recrystallization from a solution in CH2Cl2 and n-
hexane. Yellow solid; 78% yield; d.r.=9:1; Rf =0.25 (n-hexane/EtOAc,
N-(1,2-Diphenyl-2-phenylaminoethyl)-4-methoxybenzenecarbothioamide
(3ba): Purified by recrystallization from a solution in CH2Cl2 and n-
Chem. Eur. J. 2013, 19, 304 – 313
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
309

F. Shibahara, T. Murai et al.
hexane. Yellow solid; 66% yield; d.r.>20:1; Rf =0.28 (n-hexane/EtOAc,
5:1); m.p. 169.5–170.18C; H NMR (CDCl3): d=3.82 (s, 3H; OCH3), 4.81
S)NHCH), 6.55 (d, J=8.3 Hz, 6H; Ar), 6.60 (d, J=8.3 Hz, 2H; Ar), 6.68
(t, J=7.3 Hz, 3H; Ar), 6.82–6.90 (m, 10H; Ar), 7.05–7.14 (m, 14H; Ar),
7.27–7.40 (m, 17H; Ar), 7.43–7.49 (m, 10H; Ar), 7.54 (d, J=7.8 Hz, 2H;
Ar), 7.63 (d, J=7.8 Hz, 6H; Ar), 7.71 (d, J=7.3 Hz, 2H; Ar), 8.07 (d, J=
8.3 Hz, 3H; C(=S)NH), 8.38 ppm (d, J=8.3 Hz, 1H; C(=S)NH);
13C NMR (CDCl3): d=55.1 (2C; OCH3), 60.3, 62.6, 63.3, 64.1 (CH),
113.6, 114.1, 114.3, 114.4, 118.2 119.0 (Ar), 124.0 (q, J=272.9 Hz; CF3),
125.3 (q, J=4.1 Hz; CCCF3), 125.4 (q, J=4.1 Hz; CCCF3), 128.3 (q, J=
272.1 Hz; CF3), 126.7 (2C), 127.6, 128.0, 128.49, 128.54, 128.58, 128.62,
128.9, 129.3, 129.4 (Ar), 129.8 (q, J=32.3 Hz; CCF3), 130.0 (q, J=
32.3 Hz; CCF3), 131.4 (2C), 141.6, 141.7, 142.8, 144.0, 146.0, 146.3,
159.55, 159.57 (Ar), 198.9, 200.0 ppm (C=S); 19F NMR (CDCl3): d=
À62.80, À62.77 ppm; IR (KBr): n˜ =3351, 2360, 1602, 1512, 1325, 1250,
1164, 1126, 1068, 1026, 842, 756, 723, 698, 419 cmÀ1; MS (EI): m/z: 506
[M]+; HRMS (FAB): m/z calcd for C29H24F3N2OS: 507.1718 [M+H]+;
found: 507.1735.
1
(brs, 1H; PhNH) J=4.98 (d, J=8.3 Hz, 1H; PhNHCH), 6.14 (dd, J=8.3,
7.8 Hz, 1H; C(=S)NHCH), 6.56 (d, J=8.8 Hz, 2H; Ar), 6.66 (t, J=
7.3 Hz, 1H; Ar), 6.84 (d, J=8.8 Hz, 2H; Ar), 7.08 (dd, J=8.3, 7.8 Hz,
2H; Ar), 7.13 (dd, J=7.3, 2.9 Hz, 2H; Ar), 7.19–7.29 (m, 6H; Ar), 7.39
(d, J=4.4 Hz, 2H; Ar), 7.66 (d, J=8.8 Hz, 2H; Ar), 8.02 ppm (d, J=
7.8 Hz, 1H; C(=S)NH); 13C NMR (CDCl3): d=55.5 (CH3), 62.8, 64.6
(CH), 113.7, 113.8, 118.1, 127.5, 127.6, 127.7, 128.2, 128.4, 128.5, 128.7,
129.2, 134.1, 137.2, 139.3, 146.7, 162.3 (Ar), 198.5 ppm (C=S); IR (KBr):
n˜ =3356, 2360, 1714, 1604, 1503, 1455, 1372, 1310, 1260, 1179, 1029, 943,
833, 748, 698, 525 cmÀ1; MS (FAB): m/z: 439 [M+H]+; HRMS (FAB): m/
z calcd for C28H27N2OS: 439.1844 [M+H]+; found: 439.1828.
N-[1-Phenyl-2-phenylamino-2-(4-trifluoromethylphenyl)ethyl]-4-meth-
ACHTUNGTRENNUNGoxyACHTUNGTRENNUNGbenzenecarbothioamide (3bb): Purified by recrystallization from a
solution in CH2Cl2 and n-hexane. Yellow solid; 68% yield; d.r.=19:1;
Rf =0.23 (n-hexane/EtOAc, 5:1); 1H NMR (CD3CN): d=3.81 (s, 3H;
OCH3), 5.16 (dd, J=9.6, 8.6 Hz, 1H; PhNHCH), 5.55 (d, J=8.6 Hz, 1H;
PhNH), 5.94 (dd, J=9.6, 7.3 Hz, 1H; C(=S)NHCH), 6.57–6.62 (m, 3H;
Ar), 6.92 (d, J=8.8 Hz, 2H; Ar), 7.04 (dd, J=8.8, 7.3 Hz, 2H; Ar), 7.21
(s, 5H; Ar), 7.38 (d, J=8.3 Hz, 2H; Ar), 7.47 (d, J=8.3 Hz, 2H; Ar),
7.76 (d, J=9.3 Hz, 2H; Ar), 9.28 ppm (d, J=7.3 Hz, 1H; C(=S)NH);
13C NMR (CDCl3): d=55.4 (CH3), 63.0, 64.6 (CH), 113.6, 113.8, 118.3
(Ar), 124.4 (q, J=272.1 Hz; CF3), 125.3 (q, J=4.1 Hz; CCCF3), 127.7,
128.0, 128.6 (2C), 129.1, 129.3, 129.9 (q, J=32.3 Hz; CCF3), 133.9, 136.8,
144.0, 146.4, 162.6 (Ar), 199.0 ppm (C=S); 19F NMR (CDCl3): d=
À63.3 ppm; IR (KBr): n˜ =3369, 3029, 1603, 1497, 1420, 1326, 1252, 1176,
1125, 1068, 1019, 957, 842, 751, 700, 417, 407 cmÀ1; MS (EI): m/z: 472
[MÀH2S]+; elemental analysis calcd (%) for C29H25F3N2OS: C 68.76,
H 4.97, N 5.53; found: C 68.98, H 5.27, N 5.39.
N-[1,2-Bis(4-methoxyphenyl)-2-(phenylamino)ethyl]benzenecarbothio-
AHCTUNGERTGaNNUN mide (mixture of diastereomers) (3cc): Purified by column chromatog-
raphy on silica gel (n-hexane/EtOAc, 5:1; Rf =0.38). Yellow solid; 74%
1
yield; d.r.=4:1; H NMR (CDCl3, major isomer): d=3.74 (s, 3H; OCH3),
3.77 (s, 3H; OCH3), 4.71 (brs, 1H; PhNH), 4.94 (d, J=7.8 Hz, 1H;
PhNHCH), 6.03 (dd, J=7.8, 7.3 Hz, 1H; C(=S)NHCH), 6.56–6.60 (m,
2H; Ar), 6.65 (t, J=7.3 Hz, 1H; Ar), 6.76 (d, J=8.3 Hz, 2H; Ar), 6.81
(d, J=8.8 Hz, 2H; Ar), 7.04 (d, J=8.8 Hz, 2H; Ar), 7.07–7.09 (m, 4H;
Ar), 7.33 (dd, J=7.8, 7.3 Hz, 2H; Ar), 7.43 (t, J=7.3 Hz, 1H; Ar), 7.62
(d, J=8.3 Hz, 2H; Ar), 8.01 ppm (d, J=7.3 Hz, 1H; C(=S)NH);
13C NMR (CDCl3, major isomer): d=55.06, 55.14 (CH3), 61.6, 64.1 (CH),
113.8, 113.9, 114.1, 114.4, 117.9, 126.7, 128.5, 128.7, 128.9, 129.0, 129.2,
131.2, 141.9, 146.7, 159.0, 159.3 (Ar), 199.4 ppm (C=S); IR (KBr): n˜ =
3350, 3277, 3001, 2955, 2930, 2894, 2835, 1604, 1587, 1513, 1481, 1461,
1448, 1377, 1305, 1278, 1249, 1179, 1034, 955, 911, 830, 770, 753, 727, 694,
647 cmÀ1; elemental analysis calcd (%)for C29H28N2O2S: C 74.33, H 6.02,
N 5.98; found: C 74.16, H 6.05, N 5.96.
N-[2-(4-Methoxyphenyl)-1-phenyl-2-phenylaminoethyl]-4-methoxy-
ACHTUNGTRENNUNGbenzeneACHTUNGTRENNUNGcarbothioamide (mixture of diastereomers) (3bc): Purified by re-
crystallization from a solution in CH2Cl2 and n-hexane . Yellow solid;
81% yield; d.r.=4:1; Rf =0.18 (n-hexane/EtOAc, 5:1); 1H NMR (CDCl3,
major isomer): d=3.74 (s, 3H; OCH3), 3.82 (s, 3H; OCH3), 4.76 (brs,
1H; PhNH), 4.94 (d, J=7.8 Hz, 1H; PhNHCH), 6.10 (dd, J=8.3, 7.8 Hz,
1H; C(=S)NHCH), 6.57 (d, J=7.8 Hz, 2H; Ar), 6.66 (t, J=7.3 Hz, 1H;
Ar), 6.76 (d, J=8.8 Hz, 2H; Ar), 6.85 (d, J=8.8 Hz, 2H; Ar), 6.96- 6.99
(m, 1H; Ar), 7.06–7.14 (m, 5H; Ar), 7.25–7.29 (m, 3H; Ar), 7.66 (d, J=
8.8 Hz, 2H; Ar), 8.01 ppm (d, J=7.8 Hz, 1H; NH); 13C NMR (CDCl3,
major isomer): d=55.1, 55.5 (CH3), 62.8, 64.6 (CH), 113.7, 113.80, 113.82,
118.0, 127.7, 128.1, 128.5, 128.6, 128.7, 129.2, 131.2, 134.1, 137.3, 146.7,
159.0, 162.3 (Ar), 198.3 ppm (C=S); IR (KBr): n˜ =3361, 2834, 1603, 1492,
1378, 1305, 1252, 1177, 1029, 834, 752, 696, 425 cmÀ1; MS (EI): m/z: 434
[MÀH2S]+; elemental analysis calcd (%) for C29H28N2O2S: C 74.33,
H 6.02, N 5.98; found: C 74.28, H 6.09, N 5.92.
N-(1,2-Diphenyl-2-phenylaminoethyl)-2,2-dimethylpropanethioACHTUNGTRENNUNGamide
(mixture of diastereomers) (3da): Purified by recrystallization from a sol-
ution in CH2Cl2 and n-hexane . Yellow solid; 62% yield; d.r.=2:3; Rf =
0.55 (n-hexane/EtOAc, 5:1); 1H NMR (CDCl3): d=1.29 (s, 9H; CH3),
1.34 (s, 13.5H; CH3), 4.48 (brs, 1.5H; PhNH), 4.68 (brs, 1H; PhNH),
4.89 (d, J=7.3 Hz, 1H; PhNHCH), 5.07 (brs, 1.5H; PhNHCH), 6.09 (dd,
J=7.8, 7.3 Hz, 1H; C(=S)NHCH), 6.26 (dd, J=8.3, 3.4 Hz, 1.5H; C(=
S)NHCH), 6.53 (d, J=8.8 Hz, 2H; Ar), 6.56 (d, J=8.3 Hz, 3H; Ar), 6.67
(t, J=7.3 Hz, 1H; Ar), 6.70 (t, J=7.3 Hz, 1.5H; Ar), 6.87–6.89 (m, 3H;
Ar), 7.06–7.28 (m, 27H; Ar), 7.91 (d, J=6.8 Hz, 1H; C(=S)NH),
8.15 ppm (d, J=7.3 Hz, 1.5H; C(=S)NH); 13C NMR (CDCl3): d=29.8,
29.9 (C(CH)3), 44.7, 44.8 (C(CH)3), 61.7, 62.5, 62.9, 63.6 (CH), 113.8,
114.3 118.1, 118.6, 127.1, 127.3, 127.5, 127.7, 127.8, 128.0 128.1, 128.36,
128.38, 128.4, 128.7, 128.8, 129.1, 129.2, 135.8, 136.9, 137.8, 139.2, 146.5,
146.7 (Ar), 213.4, 213.9 ppm (C=S); IR (KBr): n˜ =3347, 3024, 2966, 1601,
N-[1-(4-Methoxyphenyl)-2-phenyl-2-phenylaminoethyl]benzenecarbo-
ACHTUNGTRENNUNGthioACHTUNGTRENNUNGamide (3ca): Purified by recrystallization from a solution in CH2Cl2
1510, 1454, 1380, 1359, 1318, 1261, 1074, 1027, 1003, 822, 747, 699 cmÀ1
;
and n-hexane. Yellow solid; 84% yield; d.r.=13:1; Rf =0.33 (n-hexane/
EtOAc, 5:1); 1H NMR (CDCl3, major isomer): d=3.77 (s, 3H; OCH3),
4.88 (brs>, 1H; PhNH), 4.96 (d, J=7.8 Hz, 1H; PhNHCH), 6.08 (dd,
J=8.6, 7.8 Hz, 1H; C(=S)NHCH), 6.56 (d, J=8.3 Hz, 2H; Ar), 6.66 (t,
J=7.3 Hz, 1H; Ar), 6.81 (d, J=8.8 Hz, 2H; Ar), 7.04–7.10 (m, 4H; Ar),
7.18–7.26 (m, 5H; Ar), 7.34 (dd, J=7.8, 7.3 Hz, 2H; Ar), 7.44 (t, J=
7.3 Hz, 1H; Ar), 7.62 (d, J=7.3 Hz, 2H; Ar), 8.03 ppm (d, J=8.6 Hz,
1H; NH); 13C NMR (CDCl3, major isomer): d=55.2 (OCH3), 62.0, 64.7
(CH), 113.86, 113.88, 118.1, 126.6, 127.7, 128.2, 128.55, 128.60, 128.8,
129.2, 131.1, 131.2, 137.1, 141.9, 146.7, 159.0 (Ar) 199.5 ppm (C=S); IR
(KBr): n˜ =3329, 3291, 2925, 2359, 1602, 1507, 697, 460 cmÀ1; MS (EI): m/
z: 438 [M]+; HRMS (EI): m/z calcd for C28H26N2OS: 438.1766 [M]+;
found: 438.1736.
MS (EI): m/z: 389 [M+H]+; HRMS (EI): m/z calcd for C25H29N2S:
389.2051 [M+H]+; found: 389.2043.
General procedure for the reaction between LiAlH4 and diamines 3: To
a solution of N-thioacyl-1,2-diamine 3 (0.50 mmol) in 1,4-dioxane (7 mL)
was slowly added LiAlH4 (0.076 g, 2.0 mmol) at 08C under an Ar atmos-
phere. The mixture was stirred at reflux for 6 h. The reaction mixture
was quenched with 15% NaOH (aq., 1 mL) and water (5 mL), filtered
through a pad of Celite and then the pad was rinsed with CH2Cl2. The re-
sulting mixture was extracted with CH2Cl2 (3ꢁ3 mL). The organic layer
was washed with water (3ꢁ3 mL), dried over MgSO4, filtered, and con-
centrated in vacuo. The resulting solid was purified by column chroma-
tography on silica gel (n-hexane/EtOAc, 10:1) to give 1,2-diamine 4 as a
yellow oil.
N-[1-(4-Methoxyphenyl)-2-phenylamino-2-(4-trifluoromethylphenyl)
ACHTUNGTNEReNUNG th-
A
N-Benzyl-1,2-N’-triphenylethane-1,2-diamine (4aa):[22] 1H NMR (CDCl3):
d=1.83 (brs, 1H; CH2NH), 3.45 (d, J=13.4 Hz, 1H; PhCHH), 3.68 (d,
J=13.4 Hz, 1H; PhCHH), 3.86 (d, J=6.1 Hz, 1H; CH), 4.37 (d, J=
6.1 Hz, 1H; CH), 5.23 (brs, 1H; PhNH), 6.46 (d, J=7.8 Hz, 2H; Ar),
6.59 (t, J=7.3 Hz, 1H; Ar), 7.02 (dd, J=7.8, 7.3 Hz, 2H; Ar), 7.13–
7.28 ppm (m, 15H; Ar).
column chromatography on silica gel (n-hexane/EtOAc, 3:1; Rf =0.48).
Yellow solid; 78% yield; d.r.=3:1; 1H NMR (CDCl3): d=3.77 (s, 9H;
OCH3), 3.79 (s, 3H; OCH3), 4.42 (brs, 1H; PhNH), 5.07 (d, J=8.8 Hz,
3H; PhNHCH), 5.09 (brs, 3H; PhNH), 5.32 (brs, 1H; PhNHCH), 6.10
(dd, J=8.8, 8.3 Hz, 3H; C(=S)NHCH), 6.24 (dd, J=8.3, 2.9 Hz, 1H; C(=
310
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 304 – 313

Synthesis of N-Thioacyl-1,2- and -1,3-diamines
FULL PAPER
N-benzyl-2-(4-trifluoromethylphenyl)-1-N’-diphenylethane-1,2-diamine
(4ab): Purified by column chromatography on silica gel (n-hexane/
EtOAc, 10:1; Rf =0.30). Yellow oil; 77% yield; 1H NMR (CDCl3): d=
1.81 (brs, 1H; CH2NH), 3.46 (d, J=13.2 Hz, 1H; PhCHH), 3.69 (d, J=
13.2 Hz, 1H; PhCHH), 3.78 (d, J=6.8 Hz, 1H; CH), 4.38 (d, J=6.8 Hz,
1H; CH), 5.35 (brs, 1H; PhNH), 6.44 (d, J=7.8 Hz, 2H; Ar), 6.63 (t, J=
7.3 Hz, 1H; Ar), 7.04 (t, J=7.3 Hz, 2H; Ar), 7.12–7.31 (m, 12H; Ar),
7.41 ppm (d, J=8.3 Hz, 2H; Ar); 13C NMR (CDCl3): d=51.2 (CH2),
63.7, 67.6 (CH), 113.8, 117.8 (Ar), 124.1 (q, J=271.8 Hz; CF3), 125.2 (q,
J=3.9 Hz; CCCF3), 127.1, 127.5, 127.70, 127.73, 128.0, 128.4, 128.5, 129.0
(Ar), 129.3 (q, J=32.3 Hz; CCF3), 139.7, 139.9, 145.7, 147.3 ppm (Ar);
19F NMR (CDCl3): d=À62.6 ppm; IR (neat): n˜ =3333, 3027, 2922, 2850,
1602, 1504, 1455, 1428, 1325, 1164, 1121, 1066, 1017, 846, 751, 698,
610 cmÀ1; MS (FAB): m/z: 447 [M+H]+; HRMS (EI): m/z calcd for
C28H26F3N2: 447.2048 [M+H]+; found: 447.2068.
J=6.3 Hz, 1H; CH), 5.39 (d, J=6.3 Hz, 1H; CH), 6.81 (t, J=7.3 Hz, 1H;
Ar), 6.97 (d, J=7.8 Hz, 2H; Ar), 7.09 (dd, J=8.3, 7.3 Hz, 2H; Ar), 7.17–
7.23 (m, 10H; Ar), 7.40–7.46 (m, 3H; Ar), 8.02 ppm (d, J=6.8 Hz, 2H;
Ar); 13C NMR (CDCl3): d=66.3, 67.2 (CH), 118.8, 121.4, 126.8, 127.2,
127.8, 127.9, 128.1, 128.3, 128.5, 128.76, 128.84, 131.5, 136.1, 139.6, 140.9,
149.5 (Ar), 165.7 ppm (C=N); IR (KBr): n˜ =3060, 3030, 2925, 1593, 1492,
1449, 1248, 1030, 941, 908, 751, 691 cmÀ1; MS (EI): m/z: 374 [M]+; HRMS
(EI): m/z calcd for C27H24N2S: 374.1783 [M]+; found: 374.1772.
General procedure for the reaction between thioamide dianion 1a’ and
aziridines 7 and 9: To a solution of N-benzylbenzenecarbothioamide (1a;
0.11 g 0.50 mmol) in THF (1 mL) was added nBuLi (1.6m solution in n-
hexane, 0.63 mL, 1.0 mmol) at 08C. The mixture was stirred at 08C for
5 min. A solution of aziridine 7 or 9 (0.55 mmol) in THF (1 mL) and tri-
methylaluminum (2.0m solution in toluene, 0.28 mL, 0.55 mmol) was stir-
red at RT for 5 min before being added to the reaction mixture at 08C
and the solution was stirred at that temperature for 1 h. The reaction
mixture was poured onto water and extracted with CH2Cl2. The organic
layer was washed with brine, dried over MgSO4, filtered, and concentrat-
ed in vacuo. The resulting solid was purified by column chromatography
on silica gel to give a diastereomeric mixture of N-thioacyl-1,3-diamine 8
or 10 as a yellow solid.
N-Benzyl-2-(4-methoxyphenyl)-1-N’-diphenylthane-1,2-diamine
(4ac):
Purified by column chromatography on silica gel (n-hexane/EtOAc, 10:1;
Rf =0.20). Yellow oil; 79% yield; 1H NMR (CDCl3): d=1.83 (brs, 1H;
CH2NH), 3.45 (d, J=13.5 Hz, 1H; PhCHH), 3.68 (d, J=13.5 Hz, 1H;
PhCHH), 3.72 (s, 3H; OCH3), 3.82 (d, J=6.6 Hz, 1H; CH), 4.33 (d, J=
6.6 Hz, 1H; CH), 5.19 (brs, 1H; PhNH), 6.46 (d, J=8.8 Hz, 2H; Ar),
6.59 (t, J=7.3 Hz, 1H; Ar), 6.72 (d, J=8.8 Hz, 2H; Ar), 7.00–7.07 (m,
4H; Ar), 7.15–7.30 ppm (m, 10H; Ar); 13C NMR (CDCl3): d=51.1 (CH),
55.0 (CH3), 63.7, 67.6 (CH), 113.6, 113.7, 117.1, 126.9, 127.3, 127.8, 127.9,
128.0, 128.2, 128.3, 128.9, 133.0, 140.0, 140.5, 147.7, 158.5 ppm (Ar); IR
(neat): n˜ =3334, 3027, 2930, 2834, 1602, 1508, 1457, 1245, 1172, 1113,
1034, 747, 693 cmÀ1; MS (EI): m/z: 408 [M]+; HRMS (EI): m/z calcd for
C28H28N2O: 408.2202 [M]+; found: 408.2204.
N-[3-(4-Methylphenylsulfonylamino)-1-phenylbutyl]benzenecarbothio-
AHCTUNGERTGaNNUN mide (mixture of diastereomers) (8ac): Purified by column chromatog-
raphy on silica gel (n-hexane/EtOAc, 5:1; Rf =0.18). Yellow solid; 99%
yield; d.r.=3:2; 1H NMR (CDCl3): d=1.07 (d, J=6.3 Hz, 4.5H;
CHCH3), 1.17 (d, J=6.3 Hz, 3H; CHCH3), 1.95–2.05 (m, 1.5H; CH3CH),
2.18–2.30 (m, 1H; CH3CHCHH), 2.18–2.30 (m, 1.5H; CH3CHCHH),
2.37–2.46 (m, 1H; CH3CH), 2.37 (s, 4.5H; C6H4CH3), 2.41 (s, 3H;
C6H4CH3), 3.21 (m, 1H; CH3CHCHH), 3.26 (dt, 1.5H; CH3CHCHH),
5.07 (d, J=6.8 Hz, 1.5H; SNH), 5.45 (q, J=7.3 Hz, 1H; C(=S)NHCH),
5.57 (d, J=6.3 Hz, 1H; SNH), 5.84 (q, J=7.3 Hz, 1.5H; C(=S)NHCH),
7.04 (d, J=6.3 Hz, 2H; Ar), 7.19–7.23 (m, 5.5H; Ar), 7.26–7.37 (m,
15.5H; Ar), 7.39–7.46 (m, 2.5H; Ar), 7.60 (d, J=7.8 Hz, 3H; Ar), 7.68–
7.76 (m, 6.5H; Ar), 8.02 (d, J=6.8 Hz, 1H; C(=S)NH), 8.38 ppm (d, J=
6.8 Hz, 1.5H; C(=S)NH); 13C NMR (CDCl3): d=20.6, 20.9, 21.4, 22.4
(CH3), 41.4, 42.4 (CH2), 47.3, 47.5, 57.1, 57.2, (CH), 126.8, 126.9, 127.09,
127.13, 127.2, 128.0, 128.3, 128.4, 128.5, 129.00, 129.02, 129.7, 129.8 (2C),
131.1, 131.3, 137.1, 137.5, 139.2, 139.4, 141.4, 141.5, 143.3, 143.5 (Ar),
198.1, 198.3 ppm (C=S); IR (KBr): n˜ =3280, 3060, 3029, 2972, 2971, 1598,
1519, 1488, 1449, 1377, 1325, 1157, 1092, 815, 769, 721, 697, 665, 581,
Oxidative-desulfurization/cyclization of compound 3aa [Eq. (3)]: Meth-
od A. To a solution of N-(1,2-diphenyl-2-phenylaminoethyl)benzenecar-
bothioamide (3aa; 0.20 g, 0.50 mmol) in THF (3 mL) was added I2
(0.38 g, 1.5 mmol) and pyridine (0.12 mL, 1.5 mmol) at RT. The mixture
was stirred at RT for 30 min. The reaction mixture was poured onto
Na2S2O3 (aq.) and extracted with CH2Cl2 (3ꢁ3 mL). The organic layer
was washed with saturated NaHCO3 (aq., 3 mL), dried over MgSO4, and
concentrated in vacuo. The residue was purified by column chromatogra-
phy on silica gel (n-hexane/EtOAc, 3:1, with 1% of triethylamine v/v;
Rf =0.40) to give (4R*,5R*)-1,2,4,5-tetraphenyl-4,5-dihydro-1H-imidazole
(trans-5; 0.12 g, 63%) as a colorless solid.
Method B. A solution of copper(II) chloride (0.013 g, 20 mol%), 2,2’-bi-
pyridyl (0.016 g, 20 mol%), and N-(1,2-diphenyl-2-phenylaminoethyl)-
benzenecarbothioamide (3aa; 0.20 g, 0.50 mmol) in DMSO (2 mL) was
stirred at 808C for 8 h under an O2 atmosphere. The mixture was
quenched with aqueous ammonia (28%) and the aqueous layer was ex-
tracted with CH2Cl2 (3ꢁ3 mL). The combined organic layer was washed
with aqueous ammonia (28%, 3ꢁ3 mL), dried over MgSO4, filtered, and
concentrated in vacuo. The residue was purified by column chromatogra-
phy on silica gel (n-hexane/EtOAc, 3:1; Rf =0.41) to give (4R*,5R*)-
1,2,4,5-tetraphenyl-4,5-dihydro-1H-imidazole (trans-5; 0.087 g, 46%) as a
colorless solid. M.p. 165.2–165.58C; 1H NMR (CDCl3): d=4.77 (d, J=
5.9 Hz, 1H; CH), 5.11 (d, J=5.9 Hz, 1H; CH), 6.74 (d, J=7.8 Hz, 2H;
Ar), 6.94 (t, J=7.3 Hz, 1H; Ar), 7.04 (dd, J=7.8, 7.3 Hz, 2H; Ar), 7.25–
7.42 (m, 13H; Ar), 7.76 ppm (d, J=7.3 Hz, 2H; Ar); 13C NMR (CDCl3):
d=78.2, 78.3 (CH), 123.7, 124.5, 126.5, 126.6, 127.5, 127.9, 128.3, 128.80,
128.82, 129.18, 129.21, 130.4, 130.9, 143.3, 143.4, 143.7 (Ar), 163.1 ppm
(C=N); MS (EI): m/z: 374 [M]+; HRMS (EI): m/z calcd for C27H24N2S:
374.1783 [M]+; found: 374.1776.
551 cmÀ1
;
MS (EI): m/z: 438 [M]+; HRMS (EI): m/z calcd for
C24H26N2O2S2: 438.1436 [M]+; found: 438.1434.
N-[3-(4-Methylphenylsulfonylamino)-1,4-diphenylbutyl]benzenecarbo-
ACHUTNGRENtNUG hioACHUTNGTRENaNNGU mide (mixture of diastereomers) (10a): Purified by column chroma-
tography on silica gel (n-hexane/EtOAc, 5:1; Rf =0.18). Yellow solid;
69% yield; d.r.=2:1. The d.r. improved slightly to 5:2 by separating by
preparative HPLC that was equipped with mightysil (n-hexane/EtOAc,
3:1). 1H NMR (CDCl3): d=2.03–2.10 (m, 1H; SNHCH), 2.22–2.26 (m,
2.5H; SNHCH), 2.28 (s, 7.5H; CH3), 2.30 (s, 3H; CH3), 2.33–2.40 (m,
2.5H; BnCHCHH), 2.33–2.40 (m, 1H; BnCHCHH), 2.58 (dd, J=13.9,
7.6 Hz, 2.5H; PhCHH), 2.74–2.80 (m, 2.5H; PhCHH), 2.74–2.80 (m, 1H;
PhCHH), 2.89 (dd, J=13.7, 6.8 Hz, 1H; PhCHH), 3.15–3.28 (m, 1H;
BnCHCHH), 3.15–3.28 (m, 2.5H; BnCHCHH), 4.77 (d, J=6.8 Hz, 2.5H;
SNH), 5.29 (d, J=6.3 Hz, 1H; SNH), 5.49 (q, J=7.3 Hz, 1H; C(=
S)NHCH), 5.90 (q, J=7.3 Hz, 2.5H; C(=S)NHCH), 6.73 (d, J=7.8 Hz,
5H; Ar), 6.83 (d, J=7.3 Hz, 2H; Ar), 6.93 (d, J=6.6 Hz, 2H; Ar), 6.97–
7.10 (m, 17.5H; Ar), 7.13–7.19 (m, 4H; Ar), 7.23–7.32 (m, 24H; Ar),
7.34–7.41 (m, 5H; Ar), 7.67 (d, J=6.8 Hz, 2H; Ar), 7.70 (d, J=7.3 Hz,
5H; Ar), 7.88 (d, J=7.3 Hz, 1H; C(=S)NH), 8.31 ppm (d, J=7.3 Hz,
2.5H; C(=S)NH); 13C NMR (CDCl3): d=21.4 (2C; CH3), 39.1, 39.3, 40.0,
42.0 (CH2), 52.4, 52.9, 56.8, 57.0 (CH), 126.7, 126.80, 126.88, 126.94,
127.07, 127.09, 128.1, 128.4, 128.56, 128.63, 128.8, 129.0, 129.08, 129.11,
129.3, 129.7, 131.3, 131.5, 136.0, 136.4, 136.5, 137.0, 138.6, 139.4, 141.3,
141.6, 143.2, 143.5 (Ar), 198.2, 198.3 ppm (C=S) (some of the aromatic
peaks are overlapped); IR (KBr): n˜ =3296, 3027, 2920, 1598, 1517, 1495,
1449, 1325, 1154, 1090, 1030, 953, 813, 770, 747, 721, 698, 665, 581,
549 cmÀ1; MS (FAB): m/z: 515 [M+H]+; HRMS (FAB): m/z calcd for
C30H31N2O2S2: 515.1827 [M+H]+; found: 515.1815.
Method C [Eq. (4)]. To a solution of N-(1,2-diphenyl-2-phenylaminoe-
thyl)benzenecarbothioamide (3aa; 0.20 g, 0.50 mmol) in DMSO (3 mL)
was added aqueous NaClO (12%, 1.86 g, 3 mmol). The mixture was stir-
red at RT for 30 min. The reaction mixture was extracted with CH2Cl2
(3 mLꢁ3). The organic layer was washed with water (3 mLꢁ2) and brine
(3 mL), dried over MgSO4, and concentrated in vacuo. The residue was
purified by column chromatography on silica gel (n-hexane/EtOAc, 10:1)
to give (4R*,5S*)-1,2,4,5-tetraphenyl-4,5-dihydro-1H-imidazole (cis-5;
0.12 g, 63%, Rf =0.63) and (4R*,5R*)-1,2,4,5-tetraphenyl-4,5-dihydro-1H-
imidazole (trans-5; 0.037 g, 20%, Rf =0.13) as a brown oil and a colorless
solid, respectively. Major isomer (cis-5): 1H NMR (CDCl3): d=4.84 (d,
Chem. Eur. J. 2013, 19, 304 – 313
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311

F. Shibahara, T. Murai et al.
N-(4-Methyl-3-(4-methylphenylsulfonylamino)-1-phenylpentyl)benzene-
carbothioamide (mixture of diastereomers) (10b): Purified by column
chromatography on silica gel (n-hexane/EtOAc, 5:1; Rf =0.15). Yellow
solid; 86% yield; d.r.=7:3. The d.r. improved slightly to 5:2 by separat-
ing by preparative HPLC that was equipped with mightysil (n-hexane/
yellow solids in 31% (0.080 g; Rf =0.35) and 37% yield (0.095 g; Rf =
0.23), respectively. Minor isomer: M.p. 191.3–192.18C; H NMR (CDCl3):
1
d=0.89 (d, J=6.3 Hz, 3H; CHCH3), 2.29 (s, 3H; C6H4CH3), 3.55 (dd, J=
7.3, 2.9 Hz, 1H; CH3CHCH), 3.68 (dq, J=6.3, 2.9 Hz, 1H; CH3CH), 4.38
(brs, 1H; SNH), 6.33 (dd, J=8.3, 7.3 Hz, 1H; C(=S)NHCH), 7.05–7.43
(m, 15H; Ar), 7.55 (d, J=8.3 Hz, 2H; Ar), 7.85 (d, J=7.3 Hz, 2H; Ar),
9.03 ppm (d, J=8.3 Hz, 1H; C(=S)NH); 13C NMR (CDCl3): d=19.2, 21.4
EtOAc, 3:1). 1H NMR (CDCl3): d=0.55 (d, J=6.8 Hz, 6H; CH
0.71 (d, J=6.8 Hz, 15H; CH(CH3)2), 1.69–1.77 (m, 2.5H; (CH3)2CH),
ACHTUGNRTNE(NUNG CH3)2),
AHCTUNGTRENNUNG
(CH3), 50.1, 54.5, 60.9 (CH), 127.1, 127.2, 127.5, 127.6, 127.8, 128.5ACHTUNGTRENNUNG(2C),
1.93–2.01 (m, 1H; (CH3)2CH), 2.02–2.10 (m, 1H; SNHCHCHH), 2.02–
2.10 (m, 2.5H; SNHCHCHH), 2.15–2.24 (m, 1H; SNHCH), 2.31 (s,
7.5H; C6H4CH3), 2.33 (s, 3H; C6H4CH3), 2.33–2.38 (m, 2.5H; SNHCH),
2.82–2.96 (m, 1H; SNHCHCHH), 2.82–2.96 (m, 2.5H; SNHCHCHH),
4.68 (d, J=7.8 Hz, 2.5H; SNH), 5.26 (q, J=7.3 Hz, 1H; C(=S)NHCH),
5.38 (d, J=6.3 Hz, 1H; SNH), 5.75 (q, J=7.3 Hz, 2.5H; C(=S)NHCH),
6.92–6.95 (m, 2H; Ar), 7.11–7.14 (m, 6H; Ar), 7.21–7.41 (m, 27H; Ar),
7.49 (d, J=8.3 Hz, 5H; Ar), 7.58 (d, J=8.3 Hz, 2H; Ar), 7.67–7.69 (m,
7H; Ar), 7.92 (d, J=7.3 Hz, 1H; C(=S)NH), 8.12 ppm (d, J=7.3 Hz,
2.5H; C(=S)NH); 13C NMR (CDCl3): d=16.9, 17.7, 18.6, 21.4 (CH3),
29.6, 31.7 (CH2), 35.9, 36.6, 56.0, 56.3, 57.2, 57.6 (CH), 126.8, 126.9,
127.15 (2C), 127.21, 127.4, 128.1, 128.35, 128.44, 128.5, 129.0, 129.1, 129.6,
129.7, 131.2, 131.4, 137.0, 137.1, 139.0, 139.2, 141.3, 141.6, 143.3, 143.5
(Ar), 198.1, 198.2 ppm (C=S); IR (KBr): n˜ =3289, 2932, 1598, 1518, 1487,
1449, 1323, 1157, 1092, 1029, 947, 815, 770, 697, 666, 590, 550 cmÀ1; MS
(FAB): m/z: 467 [M+H]+; HRMS (FAB): m/z calcd for C26H31N2O2S2:
467.1827 [M+H]+; found: 467.1836.
128.6, 129.6, 129.9, 131.2, 136.5, 137.2, 139.2, 141.4, 144.0 (Ar), 197.9 ppm
(C=S); IR (KBr): n˜ =3303, 3060, 3029, 2922, 1598, 1520, 1494, 1450, 1374,
1325, 1158, 1091, 946, 909, 815, 761, 698, 670, 563, 550 cmÀ1; MS (FAB):
m/z: 515 [M+H]+; HRMS (FAB): m/z calcd for C30H31N2O2S2: 515.1827
[M+H]+; found: 515.1822. Major isomer: M.p. 115.8–117.08C; 1H NMR
(CDCl3): d=0.90 (d, J=6.8 Hz, 3H; CHCH3), 2.38 (s, 3H; C6H4CH3),
3.27 (dd, J=11.2, 2.9 Hz, 1H; CH3CHCH), 3.37–3.46 (m, 1H; CH3CH),
3.81 (d, J=10.3 Hz, 1H; SNH), 6.13 (dd, J=11.2, 8.8 Hz, 1H; C(=
S)NHCH), 6.91 (d, J=8.3 Hz, 2H; Ar), 7.03 (dd, J=7.8, 7.3 Hz, 2H;
Ar), 7.14–7.32 (m, 13H; Ar), 7.43 (d, J=8.8 Hz, 1H; C(=S)NH),
7.61 ppm (d, J=7.8 Hz, 2H; Ar); 13C NMR (CDCl3): d=21.3, 21.5
(CH3), 49.1, 56.7, 58.7 (CH), 126.3, 127.4, 128.18, 128.21, 128.24, 128.3,
128.8, 129.1, 129.8, 129.9, 130.7, 135.3, 137.7, 139.0, 142.3, 143.7 (Ar),
198.0 ppm (C=S); IR (KBr): n˜ =3294, 2924, 1599, 1496, 1449, 1337, 1158,
1092, 948, 814, 755, 702, 670, 550 cmÀ1; MS (FAB): m/z: 515 [M+H]+;
HRMS (FAB): m/z calcd for C30H31N2O2S2: 515.1827 [M+H]+; found:
515.1837.
N-[4,4-Dimethyl-3-(4-methylphenylsulfonylamino)-1-phenylpentyl]ben-
X-ray structure analysis: X-ray diffraction of compounds 3aa, trans-5,
and 10d was performed on a Rigaku/MSC Mercury CCD diffractometer
with graphite-monochromated MoKa radiation (l=0.71069 ꢂ). Reflection
data were collected at 133–293 K with a Rigaku XR-TCS-2–050 tempera-
ture controller. X-ray absorptions were corrected by using numerical
methods based on the crystal shape.[23] Single crystals that were suitable
for X-ray diffraction were obtained by the slow diffusion of n-hexane
into a solution of the compounds in CH2Cl2 at RT in air. The single crys-
tals were cut from the grown crystals and mounted on a MicroMount
(MiTeGen, LLC). The structures were solved and refined by using direct
methods with SHELX-97[24] and the Yadokari-XG crystallographic soft-
ware package from the Molecular Structure Corporation.[25] Hydrogen
atoms on carbon atoms were placed at idealized positions and treated as
ACHTUNGTRENNUNGzenecarbothioamide (mixture of diastereomers) (10c): Purified by
column chromatography on silica gel (n-hexane/EtOAc, 5:1; Rf =0.15).
1
Yellow solid; 83% yield; d.r.=1:1; H NMR (CDCl3): d=0.70 (s, 9H; C-
ACHTUNGTRENNUNG(CH3)3), 0.81 (s, 9H; CAHCUTNTGREG(NNUN CH3)3), 2.10 (ddd, J=15.1,7.1, 4.2 Hz, 1H;
CHH), 2.30 (dt, J=15.1, 6.4 Hz, 1H; CHH), 2.36 (s, 3H; C6H4CH3), 2.37
(s, 3H; C6H4CH3), 2.43 (dt, J=15.1, 4.2 Hz, 1H; CHH), 2.51 (ddd, J=
15.1,7.8, 4.1 Hz, 1H; CHH), 2.84 (ddd, J=8.1, 6.4, 4.1 Hz, 1H; SNHCH),
3.16 (ddd, J=9.0,7.1, 4.2 Hz, 1H; SNHCH), 4.87 (d, J=9.0 Hz, 1H;
SNH), 5.09 (d, J=8.1 Hz, 1H; SNH), 5.62 (ddd, J=7.8, 7.1, 6.4 Hz, 1H;
C(=S)NHCH), 5.96 (dt, J=7.8, 4.2 Hz, 1H; C(=S)NHCH), 7.08 (d, J=
8.3 Hz, 2H; Ar), 7.20 (d, J=8.3 Hz, 2H; Ar), 7.27–7.50 (m, 18H; Ar),
7.61 (d, J=8.3 Hz, 2H; Ar), 7.84 (d, J=8.3 Hz, 2H; Ar), 7.89 (d, J=
8.3 Hz, 2H; Ar), 8.73 (d, J=7.8 Hz, 1H; C(=S)NH), 8.83 ppm (d, J=
7.1 Hz, 1H; C(=S)NH); 13C NMR (CDCl3): d=21.37, 21.39, 26.2, 26.5
(CH3), 35.1, 35.3 (CH2), 37.8, 38.9 (CH3C), 57.8, 59.1, 59.3, 59.4 (CH),
126.9 (2C), 127.4, 127.1, 127.2, 127.3, 127.5, 128.0, 128.35, 128.44, 128.7,
128.9, 129.5, 129.6, 131.0, 131.3, 136.5, 137.5, 140.0, 140.2, 141.5, 141.8,
143.4, 143.5 (Ar), 198.47, 198.50 ppm (C=S); IR (KBr): n˜ =3295, 2962,
À
riding atoms with C H distances in the range 95–100 pm. Crystal data
and measurement description are summarized in the Supporting Informa-
tion, Table S1.
CCDC-903304 (3aa), CCDC-903305 (trans-5), and CCDC-903306 (10d)
contain the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge Crystallograph-
ic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
1598, 1479, 1449, 1324, 1154, 1093, 1025, 957, 814, 768, 698, 665, 549 cmÀ1
;
MS (FAB): m/z: 481 [M+H]+; HRMS (FAB): m/z calcd for
C27H33N2O2S2: 481.1983 [M+H]+; found: 481.1996.
N-[3-(4-Methylphenylsulfonylamino)-1,2-diphenylpropyl]benzenecarbo-
thioamide (10d): Purified by column chromatography on silica gel (n-
hexane/EtOAc, 5:1). Yellow solid; 36% yield; d.r.>20:1. Other diaster-
eomers of compound 10d were obtained as a diastereomeric mixture
after the major isomer had eluted (0.028 g, 11% yield, d.r.=3:2, Rf =
0.23). Major isomer of 10d: M.p. 221.5–223.28C; 1H NMR (CDCl3): d=
2.36 (s, 3H; CH3), 3.08 (dt, J=13.7, 6.8 Hz, 1H; CHH), 3.19 (dt, J=13.7,
6.8 Hz, 1H; CHH), 3.39 (dt, J=7.3, 6.8 Hz, 1H; CH2CH), 4.82 (t, J=
6.8 Hz, 1H; SNH), 6.04 (dd, J=8.8, 7.3 Hz, 1H; C(=S)NHCH), 6.96 (d,
J=6.8 Hz, 2H; Ar), 7.09 (d, J=6.8 Hz, 2H; Ar), 7.18–7.34 (m, 13H; Ar),
7.51 (d, J=8.3 Hz, 2H; Ar), 7.58 ppm (d, J=8.8 Hz, 1H; C(=S)NH);
13C NMR (CDCl3): d=21.5 (CH3), 45.1 (CH), 51.7 (CH2), 60.3 (CH),
126.5, 127.1, 127.4, 128.2, 128.3, 128.5, 128.6, 128.9, 129.2, 129.8, 131.2,
136.8, 136.9, 138.4, 141.8, 143.6 (Ar), 199.0 ppm (C=S); IR (KBr): n˜ =
3312, 3264, 2924, 2853, 1595, 1533, 1495, 1449, 1385, 1316, 1287, 1253,
1155, 1090, 945, 836, 811, 759, 727, 697, 660 cmÀ1; MS (FAB): m/z: 501
[M+H]+; HRMS (FAB): m/z calcd for C29H28N2O2S2: 501.1670 [M+H]+;
found: 501.1667.
Acknowledgements
This research was supported by MEXT, Grants-in-Aid for Scientific Re-
search on Innovative Areas “Organic Synthesis based on Reaction Inte-
gration. Development of New Methods and Creation of New Substances”
(2105), and by the JST, ACT-C.
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312
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Received: September 28, 2012
Published online: November 28, 2012
Chem. Eur. J. 2013, 19, 304 – 313
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313