Asymmetric aziridination of chalcone promoted by binaphthalene-based chiral amines

Article abstract of DOI:10.1055/s-0033-1339643

Aminimines derived in situ from a number of enantiomerically pure binaphthalene-based tertiary amines have been used for the asymmetric aziridination of chalcone, providing N-unprotected aziridines with ee values of up to 43%. A chiral hydrazinium salt has been isolated for the first time and shown to provide similar yield and enantioselectivity to the in situ process in reaction with chalcone. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1339643

LETTER
▌2067
lAettserymmetric Aziridination of Chalcone Promoted by Binaphthalene-Based
Chiral Amines
Asymmetric Aziridination of Chalcone
Philip C. Bulman Page,*a Céline Bordogna,a Ian Strutt,a Yohan Chan,a Benjamin R. Buckleyb
a
School of Chemistry, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK
b
Department of Chemistry, Loughborough University, Loughborough, Leicestershire LE11 3TU, UK
E-mail: p.page@uea.ac.uk
Received: 02.07.2013; Accepted after revision: 21.07.2013
chalcone to give the corresponding N-unsubstituted aziri-
Abstract: Aminimines derived in situ from a number of enantio-
dine.
merically pure binaphthalene-based tertiary amines have been used
for the asymmetric aziridination of chalcone, providing N-unpro-
tected aziridines with ee values of up to 43%. A chiral hydrazinium
salt has been isolated for the first time and shown to provide similar
yield and enantioselectivity to the in situ process in reaction with
chalcone.
2,2-Disubstituted 1,1′-binaphthyls constitute the back-
bone of a large number of chiral auxiliaries and ligands
used for asymmetric synthesis. We have reported a range
of azepinium salt catalysts containing the binaphthyl
backbone, developed for use as catalysts in asymmetric
epoxidation reactions,9 and we conjectured that applica-
tion of this backbone might also be interesting for amini-
mine generation. Accordingly, we selected the simplest
such chiral tertiary amine (S)-1 as our initial target. The
compound was prepared in four steps from (S)-BINOL via
the known dibromide (S)-2.10 The ring closure from (S)-2
was performed using methylamine and potassium carbon-
ate to afford tertiary amine (S)-1 in 85% yield (Scheme 1).
Key words: chalcone, aziridination, binaphthalene-based tertiary
amines
The vast majority of biologically active molecules contain
nitrogen in their framework. Aziridines are interesting
versatile synthetic intermediates due to their ability to be
converted into a variety of multifunctional compounds by
regioselective and stereospecific ring-opening reactions
using various nucleophiles.1,2 Despite the well-known ad-
vantages of aziridines, they have enjoyed limited applica-
tions in synthesis compared with the corresponding
epoxides, perhaps due to perceived difficulties in their
preparation; this is particularly true for the synthesis of
non-racemic and N-unsubstituted aziridines.3 In 1980,
Ikeda reported that ammonium amide ylids (often called
aminimines or aminimides) generated from hydrazines in
situ by reaction with propylene oxide could directly ami-
nate electron-deficient olefins to form N-unsubstituted
aziridines in good yields.4 Armstrong and Shi subsequent-
ly independently showed that ylids of this type could be
generated by treatment of tertiary amines with O-func-
tionalized hydroxylamines as nitrogen transfer agents fol-
lowed by addition of base; use of enantiomerically pure
chiral amines provided an enantioselective aziridination
system. Armstrong reported ee values of up to 56% using
quinine as the chiral tertiary amine and diphenylphosphi-
nyl hydroxylamine (DppONH2) as N-transfer agent,5
while Shi used (+)-Troger’s base and O-mesitylenesulfo-
nylhydroxylamine (MSH) as N-transfer agent, and ob-
tained ee values of up to 55%.6 Cinnamates7 and α,β,γ,δ-
unsaturated aryl ketones8 are also successful substrates.
Herein we report the syntheses of several new enantio-
merically pure tertiary amines containing the binaphthyl
grouping as precursors of chiral ammonium amide ylids,
which are used in enantioselective reactions with trans-
Br
MeNH2, K2CO3
N
Me
THF, reflux
85%
Br
(S)-2
(S)-1
Scheme 1 Synthesis of chiral tertiary amine (S)-1
The aziridination reaction was tested with (S)-1 using
DppONH2 as amine transfer agent and chalcone as sub-
strate; a catalytic cycle is shown in Scheme 2. DppONH2
is easily prepared by the reaction of diphenylphosphinyl
chloride with hydroxylamine hydrochloride in the pres-
ence of sodium hydroxide.11
The reaction was performed in dichloromethane solution
using sodium hydroxide or sodium hydride–isopropanol
as base (Table 1).
Table 1 Asymmetric Aziridination of Chalcone using Amine (S)-1a
Base
Temp
Time (h) Conversion (%) ee (%)b
NaOH
r.t.
16
16
48
100
100
21
12
11
14
NaH–i-PrOH
NaOH
r.t.
0 °C
a Reaction conditions: chalcone (1 mmol), (S)-1 (1 equiv), base (1.1
equiv), DppONH2 (1.1 equiv), CH2Cl2. Conversions were based on 1H
NMR spectroscopy of the crude reaction mixture.
b Enantioselectivities were determined by HPLC on chiral stationary
phase.
SYNLETT 2013, 24, 2067–2072
Advanced online publication: 26.08.2013
DOI: 10.1055/s-0033-1339643; Art ID: ST-2013-D0613-L
© Georg Thieme Verlag Stuttgart · New York
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6

2068
P. C. B. Page et al.
LETTER
the selectivity of our chiral amines without increasing the
steric hindrance directly around the nitrogen atom, we
also prepared new amines (S)-6, (S)-7, (S)-8 and (S)-9,
each containing one 3-phenyl or 3-(1-naphthyl) substitu-
ent, in eight steps from (S)-BINOL via the corresponding
known bistriflated binaphthyl species (S)-10 and (S)-11.
Thus, Kumada coupling to give the bismethylated deriva-
tives (S)-12 and (S)-13 was followed by bismonobromina-
tion to afford the two dibromo derivatives (S)-14 and (S)-
15 in 85% and 58% yields, respectively. Reaction with
methylamine or isopropylamine as before afforded the
four new chiral amines in excellent yields (Scheme 3).14
O
NH
Ph
Ph
DppONH2
N
Me
Me
Me
N
N
NH2
NH
O
Ph
Ph
R
R
MeMgBr
O
OTf
OTf
base
Me
NH
N
NiCl2(dppp)
Et2O, r.t.
Ph
Ph
(S)-10, R = Ph
(S)-11, R = 1-naphthyl
(S)-12, R = Ph, 54%
(S)-13, R = 1-naphthyl, 44%
Scheme 2 Catalytic cycle for the aziridination of trans-chalcone us-
ing amine (S)-1
NBS
AIBN
PhH
reflux
At room temperature, amine (S)-1 was reactive regardless
of the base used, but gave the (2R,3S)-2-benzoyl-3-
phenylaziridine product with low enantioselectivities.12
At lower temperature, the conversion dropped to 21%
with no significant improvement in the enantioselectivity.
These results do, however, show the potential efficiency
of this new type of chiral tertiary amine for the aziridina-
tion of chalcones.
R
Br
Br
(S)-14, R = Ph, 85%
(S)-15, R = 1-naphthyl, 58%
i-PrNH2
MeNH2
K2CO3
THF
K2CO3
MeCN
reflux
In an attempt to improve the enantioselectivity of the re-
action, a range of new chiral amines was prepared. These
included (S)-3 with an N-hydroxyethyl substituent,
bridged dimeric system (S)-4, and (S)-5 with an N-isopro-
pyl substituent, each prepared in very high yields using
the procedure described above (Figure 1).
reflux
R
R
N
N
Me
(S)-6, R = Ph, 94%
(S)-8, R = 1-naphthyl, 88%
(S)-7, R = Ph, 99%
(S)-9, R = 1-naphthyl, 90%
N
N
OH
Scheme 3 Synthesis of amines (S)-6, (S)-7, (S)-8 and (S)-9
(S)-3, 94%
(S)-5, 95%
Further, in order to reduce the number of possible transi-
tion states, we also prepared two C-2 symmetric 3,3′-sub-
stituted binaphthyl amines, (S)-16 and (S)-17. The known
dibromide (S)-18, which has been used for the preparation
of ammonium salts used as phase-transfer catalysts,15 was
treated with methylamine or isopropylamine to afford the
two chiral amines (S)-16 and (S)-17 in 51% and 83%
yield, respectively (Scheme 4).
N
N
(S)-4, 96%
Figure 1
As an alternative, we also investigated the introduction of
bulkier N-substituents in the absence of substitution in the
binaphthyl unit. Catalysts (S)-19 to (S)-22 (Figure 2) were
prepared using our standard cyclization procedure in 83–
95% yields.
3-Substituted binaphthyl derivatives have been used in
asymmetric catalysis, and have been reported to increase
enantioselectivity and to prevent the formation of unreac-
tive aggregates.13 Accordingly, with a view to improving
Synlett 2013, 24, 2067–2072
© Georg Thieme Verlag Stuttgart · New York

LETTER
Asymmetric Aziridination of Chalcone
2069
CF3
CF3
Br
i-PrNH2, K2CO3
N
MeCN, reflux
CF3
CF3
CF3
CF3
Br
82%
RNH2
Br
Br
K2CO3
N
R
(S)-24
(S)-26
MeCN
reflux
Br
i-PrNH2, K2CO3
N
MeCN, reflux
CF3
CF3
Br
92%
(S)-18
(S)-16, R = Me, 51%
(S)-17, R = i-Pr, 83%
(S)-27
(S)-25
Scheme 4 Synthesis of amines (S)-16 and (S)-17
Scheme 5 Generation of amines (S)-24 and (S)-25
Table 2 Use of Chiral Tertiary Amines (S)-3, (S)-4, and (S)-5a
Amine Solvent, base
Temp Time
Conversion ee
(%)
(%)
N
R
(S)-3
(S)-4
(S)-5
CH2Cl2, NaOH
CH2Cl2, NaOH
CH2Cl2, NaOH
r.t.
r.t.
r.t.
18 h
100
16
6
6
1 week
24 h
19, R = cyclohexyl (Cy), 95%
20, R = benzyl, 92%
38
34
21, R = phenyl, 94%
22, R = 4-methoxyphenyl (PMP), 83%
a Reaction conditions: chalcone (1 mmol), (S)-1 (1 equiv), base (1.1
equiv), DppONH2 (1.1 equiv), CH2Cl2. Conversions are based on 1H
NMR spectroscopy of the crude reaction mixture.
b Enantioselectivities were determined by HPLC on chiral stationary
phase.
Figure 2
The new chiral amines (S)-3, (S)-4, and (S)-5 were tested
in the aziridination of chalcone, using DppONH2 as nitro-
gen transfer agent in dichloromethane solution (Table 2).
Finally, the effect of the binaphthyl backbone was probed
by the synthesis of amines (S)-24 and (S)-25 from the di-
bromides (S)-2616 and (S)-2717 (Scheme 5).
All of these new amines were able to transfer nitrogen to
trans-chalcone. The best conversion was provided by
amine (S)-3 but no significant enantiomeric excess was
Table 3 Asymmetric Aziridination of trans-Chalcone using Amine (S)-5a
Aminating agent
Base
Solvent
Temp
Time
Conversion (%) ee (%)b
DppONH2
DppONH2
DppONH2
DppONH2
DppONH2
MSH
NaH–i-PrOH
NaOH
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
r.t.
24 h
30
20
17
9
33
37
36
38
–
0 °C
0 °C
r.t.
5 d
NaH–i-PrOH
NaOH
5 d
1 week
2 weeks
48 h
NaOH
CHCl3
r.t.
–
NaOH
CH2Cl2
MeCN
r.t.
35
26
–
30
32
–
MSH
NaOH
r.t.
48 h
MSH
NaOH
CHCl3
r.t.
1 week
1 week
48 h
MSH
NaOH
MeCN–CH2Cl2
CH2Cl2
MeCN
r.t.
–
–
MSH
NaH–i-PrOH
NaH–i-PrOH
NaOH
r.t.
–
–
MSH
r.t.
48 h
–
–
MSH
CH2Cl2
0 °C
20 h
9
37
a Reaction conditions: chalcone (1 mmol), (S)-5 (1 equiv), base (1.1 equiv), nitrogen transfer agent (1.1 equiv). Conversions are based on 1H
NMR spectroscopy of the crude reaction mixture.
b Enantioselectivities were determined by HPLC on chiral stationary phase.
© Georg Thieme Verlag Stuttgart · New York
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P. C. B. Page et al.
LETTER
observed. Amine (S)-4 was not very reactive, presumably over five days. Amine (S)-17 was unreactive despite a
due to steric hindrance around the nitrogen atom. Encour- two-week reaction time, presumably as a result of the
aging enantioselectivity was shown by amine (S)-5, and combined steric hindrance induced by the 3,3′-substitu-
we therefore varied the reaction conditions and the nitro- ents and the isopropyl moiety.
gen transfer agent in order to try to improve this result
(Table 3).
Catalyst (S)-19 showed an encouraging enantioselectivity
of 37% ee in the aziridination of chalcone in dichloro-
O-Mesitylenesulfonylhydroxylamine (MSH) has been methane solution using DppONH2 and NaOH as base
proved to be an efficient aminating reagent for a range of while retaining a good 70% conversion over 48 hours. The
tertiary amines,18,19 but its use did not significantly im- cyclohexyl substituent thus appears to convey a reason-
prove the efficiency of the reaction. A small improvement able balance of reactivity and selectivity in both formation
in enantioselectivity was observed when the reaction was of the aminimide and the subsequent nitrogen transfer to
performed at 0 °C, but extended reaction times and re- trans-chalcone. Catalyst (S)-20 provided complete con-
duced conversions were observed as a consequence. The version, but racemic product. Catalysts (S)-21 and (S)-22,
use of acetonitrile and O-(diphenylphosphinyl)hydroxyl- however, induced no conversion to aziridine. We conjec-
amine gave 38% enantiomeric excess but poor conver- tured that this may be attributed to slow formation of the
sion. Optimum conditions appeared to be the use of intermediate hydrazinium salt compared with catalysts
DppONH2 as aminating reagent and sodium hydroxide as (S)-5 and (S)-19. Scheme 6 shows 1H NMR spectra illus-
base in dichloromethane at room temperature.
trating the development of hydrazinium salts derived from
(S)-19 and (S)-22 using DppONH2 in CD2Cl2 solution at
room temperature.
Aziridination reactions were therefore next attempted us-
ing amines (S)-6, (S)-7, (S)-8 and (S)-9 in dichlorometh-
ane solution using NaOH as base and DppONH2, but gave In Scheme 6, for the N-cyclohexyl substrate, the disap-
disappointing results, only (S)-7 giving a non-racemic pearance of the pair of doublets at δ = 3.25 and 3.90 ppm
product (20% ee). Amine (S)-9 was not able to transfer ni- and the formation of four doublets at δ = 4.12, 4.21, 5.47,
trogen to chalcone at all, presumably for reasons of steric and 5.58 ppm, corresponding to the four non-equivalent
hindrance, and none of these new chiral amines gave bet- benzylic protons in the hydrazinium salt, can be seen to
ter conversions or better enantioselectivities than did (S)- be largely complete within five minutes. In the case of the
5. Both (S)-6 and (S)-7 were also rather unreactive, sug- N-PMP azepine, the corresponding pair of doublets at
gesting that even medium-sized N-substituents are too δ = 3.76 and 4.38 ppm give way to doublets at δ = 4.21,
crowded in combination with a 3-substituent. Curiously, 4.52, 4.86, and 5.21 ppm, but the process is incomplete af-
(S)-8 was much more reactive than (S)-6, but neither pro- ter four hours.
vided any observed enantioselectivity. Aziridination of
trans-chalcone was attempted using amines (S)-16 and
(S)-17 under a range of conditions. Amine (S)-16 gave
Amines (S)-24 and (S)-25 provided very similar conver-
sions (70% and 68%, respectively, over 48 h) in the azirid-
ination of chalcone as observed for (S)-5, but no
conversions of up to 61% over two days when using
improvement in enantioselectivity, at 35% ee and 33% ee
MSH. Use of DppONH2 gave higher enantioselectivity
respectively. A selection of the results observed with all of
(up to 43% ee), but only 10% conversion was observed
the new catalysts is presented in Table 4.
Scheme 6 Development of hydrazinium salts
Synlett 2013, 24, 2067–2072
© Georg Thieme Verlag Stuttgart · New York

LETTER
Asymmetric Aziridination of Chalcone
2071
Table 4 Asymmetric Aziridination of trans-Chalcone using New
Catalystsa
DppONH2 (1.1 equiv)
N
N
Amine Base, solvent
Aminating
agent
TempTime Conv.ee
(°C) (h) (%) (%)
CH2Cl2, r.t., 18 h
NH2
77%
OP(O)Ph2
(S)-1 NaOH, CH2Cl2
(S)-3 NaOH, CH2Cl2
(S)-4 NaOH, CH2Cl2
(S)-5 NaOH, CH2Cl2
DppONH2
DppONH2
DppONH2
DppONH2
r.t.
r.t.
16 100
18 100
0
0
6
(S)-5
(S)-23
Scheme 7 Synthesis of hydrazinium salt (S)-23 from tertiary amine
(S)-5 and DppONH2
r.t. 168 16
r.t.
r.t.
0
24 38 34
24 30 33
120 20 37
120 20 37
Use of this hydrazinium salt with either counterion as an
aziridination reagent with chalcone as the substrate in di-
chloromethane solution and NaOH as base provided the
same ee and yield as were obtained when forming the hy-
drazinium salt in situ, supporting the conjecture that the
hydrazinium salt is an intermediate in the catalytic cycle,
as suggested by Ikeda3 and Armstrong.19
(S)-5 NaH–i-PrOH, CH2Cl2 DppONH2
(S)-5 NaOH, CH2Cl2 DppONH2
(S)-5 NaH–i-PrOH, CH2Cl2 DppONH2
0
(S)-5 NaOH, MeCN
(S)-5 NaOH, CH2Cl2
(S)-5 NaOH, MeCN
(S)-6 NaOH, CH2Cl2
(S)-7 NaOH, CH2Cl2
(S)-8 NaOH, CH2Cl2
(S)-9 NaOH, CH2Cl2
(S)-16 NaOH, CH2Cl2
(S)-17 NaOH, CH2Cl2
(S)-19 NaOH, CH2Cl2
(S)-20 NaOH, CH2Cl2
(S)-21 NaOH, CH2Cl2
(S)-22 NaOH, CH2Cl2
(S)-24 NaOH, CH2Cl2
(S)-25 NaOH, CH2Cl2
DppONH2
MSH
r.t. 168
9 38
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
48 35 30
48 26 32
In summary, a range of new tertiary amines has been syn-
thesized and used for asymmetric aziridination of chal-
cone using the in situ aminimide-mediated aziridination
process.21 Amines (S)-1, (S)-3 and (S)-8 have shown the
best reactivity towards chalcone, whereas amine (S)-5 and
(S)-16 gave the best enantiomeric excesses, 39% and 43%
respectively, with (S)-19 perhaps providing the best bal-
ance of ee and conversion. In one case, the intermediate
hydrazinium salt (S)-23 was isolated and shown to act as
an aziridinating agent with similar yield and enantiomeric
excess to the in situ system.22
MSH
DppONH2
DppONH2
DppONH2
DppONH2
DppONH2
DppONH2
DppONH2
DppONH2
DppONH2
DppONH2
DppONH2
DppONH2
18 27
18
15 100
48
0
20
0
9
0
–
48 10 43
r.t. 336
0 –
r.t.
r.t.
48 70 37
24 100
Acknowledgment
0
This investigation has enjoyed the support of Loughborough Uni-
versity, the University of East Anglia, The Royal Society (PCBP:
Industry Fellowship), and the ERDF (IS:CE-Chem & INTERREG
IVa Programme 4061). We are also indebted to the EPSRC Mass
Spectrometry Unit, Swansea.
r.t. 168
r.t. 168
0
0
–
–
r.t.
r.t.
48 70 35
48 68 33
Supporting Information for this article is available online at
a Reaction conditions: chalcone (1 mmol), catalyst (1 equiv), base (1.1
equiv), nitrogen transfer agent (1.1 equiv). Conversions are based on
1H NMR spectroscopy of the crude reaction mixture.
b Enantioselectivities were determined by HPLC on chiral stationary
phase.
http://www.thieme-connect.com/ejournals/toc/synlett.SnuIpofoiprmntgirStanoIuifpog
r
t
iornat
References and Notes
(1) For an overview of aziridine chemistry, see: (a) Tanner, D.
Angew. Chem. Int. Ed. 1994, 33, 599. (b) Sweeney, J. B.
Chem. Soc. Rev. 2002, 31, 247. (c) Hu, X. E. Tetrahedron
2004, 60, 2701.
(2) Osborn, H. M. I.; Sweeney, J. B. Tetrahedron: Asymmetry
1997, 8, 1693.
(3) Pellissier, H. Tetrahedron 2010, 66, 1509.
(4) Ikeda, I.; Machh, Y.; Okahara, M. Synthesis 1980, 650.
(5) Armstrong, A.; Baxter, C. A.; Lamont, S. G.; Pape, A. R.;
Wincewicz, R. Org. Lett. 2007, 9, 351.
(6) Shen, Y. M.; Zhao, M. X.; Xu, J.; Shi, Y. Angew. Chem. Int.
Ed. 2006, 45, 8005.
(7) Armstrong, A.; Ferguson, A. Beilstein J. Org. Chem. 2012,
8, 1747.
(8) Armstrong, A.; Pullin, R. D. C.; Jenner, C. R.; Scutt, J. N. J.
Org. Chem. 2010, 75, 3499.
(9) (a) Page, P. C. B.; Buckley, B. R.; Blacker, A. J. Org. Lett.
2004, 6, 1543. (b) Page, P. C. B.; Farah, M. M.; Buckley, B.
R.; Blacker, A. J. J. Org. Chem. 2007, 72, 4424. (c) Page, P.
Armstrong has shown that achiral hydrazinium salts may
be generated and used as stoichiometric aziridination re-
agents.20 We have found that chiral hydrazinium salts may
be easily prepared and isolated from our binaphthyl-
derived amines. For example, we were able to prepare
hydrazinium salt (S)-23 from amine (S)-5 in 77% yield
simply by stirring the tertiary amine with 1.1 equivalents
of DppONH2 in dichloromethane overnight; filtration
then gave the pure salt (S)-23 (Scheme 7). Counterion ex-
change using sodium tetraphenylborate in acetonitrile
provided the corresponding tetraphenylborate salt in
quantitative yield, which has proven to be stable over a
two-year period.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 2067–2072

2072
P. C. B. Page et al.
LETTER
C. B.; Farah, M. M.; Buckley, B. R.; Blacker, A. J.; Lacour,
J. Synlett 2008, 1381. (d) Page, P. C. B.; Buckley, B. R.;
Farah, M. M.; Blacker, A. J. Eur. J. Org. Chem. 2009, 3413.
(e) Page, P. C. B.; Bartlett, C. J.; Chan, Y.; Day, D. P.;
Parker, P.; Buckley, B. R.; Rassias, G. A.; Slawin, A. M. Z.;
Allin, S. M.; Lacour, J.; Pinto, A. J. Org. Chem. 2012, 77,
6128. (f) Farah, M. M.; Page, P. C. B.; Buckley, B. R.;
Blacker, A. J.; Elsegood, M. R. J. Tetrahedron 2013, 69,
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(20) Armstrong, A.; Carbery, D. R.; Lamont, S. G.; Pape, A. R.;
Wincewicz, R. Synlett 2006, 2504.
(21) General Procedure with the in situ Hydrazinium Salt:
The aminating agent (0.3 mmol) and base (0.6 mmol) were
added to a stirred solution of the tertiary amine (0.2 mmol)
in CH2Cl2 (4 mL). After stirring for 20 min at r.t., the
chalcone substrate (0.2 mmol) was added as a solution in
CH2Cl2 (1 mL). The reaction mixture was stirred for 48 h at
r.t. Sat. aq NH4Cl was added to the reaction mixture, and the
organic phase was separated and washed sequentially with
H2O (3 × 10 mL) and brine (10 mL) before being dried
(MgSO4), filtered and concentrated in vacuo to give a crude
residue that was purified by column chromatography
[column packed with 5% Et3N in petroleum ether and eluted
with petroleum ether–EtOAc, (19:1)] to give the NH-
aziridine as a colourless solid; mp 99–100 °C. IR: 3308,
3222, 3084, 3063, 3012, 2339, 1987, 1966, 1907, 1888,
1819, 1774, 1659, 1596, 1578 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 2.65–2.71 (br t, J = 8.0 Hz, 1 H, NH), 3.17 (br
d, J = 8.0 Hz, 1 H, CHNH), 3.52 (br d, J = 7.0 Hz, 1 H,
CHNH), 7.32–7.38 (m, 5 H, ArH), 7.48 (t, J = 8.0 Hz, 2 H,
ArH), 7.62 (t, J = 7.0 Hz, 1 H, ArH), 8.00 (d, J = 7.0 Hz, 2
H, ArH). 13C NMR (75 MHz, CDCl3): δ = 43.5, 44.0, 126.3,
128.0, 128.4, 128.6, 128.9, 133.9, 136.0, 138.4, 195.9.
(22) General Procedure with the Preformed Hydrazinium
Salt: The hydrazinium salt (0.2 mmol) and base (0.6 mmol)
were dissolved in CH2Cl2 (4 mL) and stirred for 20 min at r.t.
The chalcone substrate (0.2 mmol) was added as a solution
in CH2Cl2 (1 mL). The reaction mixture was stirred for 48 h
at r.t. Sat. aq NH4Cl was added to the reaction mixture and
the organic phase was separated and washed sequentially
with H2O (3 × 10 mL) and brine (10 mL) before being dried
(MgSO4), filtered and concentrated in vacuo to give a crude
residue that was purified by column chromatography
[column packed with 5% Et3N in petroleum ether and eluted
with petroleum ether–EtOAc (19:1)] to give the NH-
aziridine as a colourless solid.
(10) (a) Ohta, T.; Ito, M.; Inagaki, K.; Takaya, H. Tetrahedron
Lett. 1993, 34, 1615. (b) Sengupta, S.; Leite, M.; Rasian, D.
S.; Quesnelle, C.; Snieckus, V. J. Org. Chem. 1992, 57,
4066. (c) Mecca, T.; Superchi, S.; Giorgio, E.; Rosini, C.
Tetrahedron: Asymmetry 2001, 12, 1225. (d) Clyne, D. S.;
Jin, J.; Genest, E.; Gallucci, J. C.; RajanBabu, T. V. Org.
Lett. 2000, 2, 1125.
(11) Colvin, E. W.; Kirby, G. W.; Wilson, A. C. Tetrahedron
Lett. 1982, 23, 3835.
(12) For the assignment of absolute configuration based on sign
of optical rotation, see: Jin, X. L.; Sugihara, H.; Daikai, K.;
Tateishi, H.; Jin, Y. Z.; Furuno, H.; Inanaga, J. Tetrahedron
2002, 58, 8321.
(13) (a) Harada, T.; Kanda, K. Org. Lett. 2006, 8, 3817.
(b) Ishihara, K.; Kurihara, H.; Matsumoto, M.; Yamamoto,
H. J. Am. Chem. Soc. 1998, 120, 6920. (c) Zhang, Y. L.;
Zhang, F.; Tang, W. J.; Wu, Q. L.; Fan, Q. H. Synthesis
2006, 1250.
(14) Saha, B.; RajanBabu, T. V. J. Org. Chem. 2007, 72, 2357.
(15) Ooi, T.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc. 2003,
125, 5139.
(16) Denmark, S. E.; Matsuhashi, H. J. Org. Chem. 2002, 67,
3479.
(17) Prepared in 99% yield from the known diol by the action of
PBr3 in toluene at 70 °C over 3 h. See: Novikov, R.; Lacour,
J.; Bernardinelli, G. Adv. Synth. Catal. 2008, 350, 1113.
(18) For the preparation of MSH, see: Johnson, C. R.; Kirchhoff,
R. A.; Corkins, H. G. J. Org. Chem. 1974, 39, 2458.
(19) (a) Tamura, Y.; Minamikawa, J.; Kita, Y.; Kim, J. H.; Ikeda,
M. Tetrahedron 1973, 29, 1063. (b) Tamura, Y.;
Minamikawa, J.; Ikeda, M. Synthesis 1977, 1.
Synlett 2013, 24, 2067–2072
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