Nucleophilic addition reactions of nitriles to nitrones under mild silylation conditions

Article abstract of DOI:10.1055/s-0034-1378274

In the presence of triethylsilyl trifluoromethanesulfonate and triethylamine, aliphatic nitriles undergo addition reactions with aldonitrones under non-basic, mild conditions, providing O-triethylsilyl ethers of β-N-hydroxyamino nitriles with high yield.

Full text of DOI:10.1055/s-0034-1378274

LETTER
▌1863
lNettuer cleophilic Addition Reactions of Nitriles to Nitrones under Mild Silylation
Conditions
Nucleophilic Addition Reactions of Nitriles to Nitrones
Fumihiko Yoshimura,*a Taiki Abe,b Keiji Tanino*a
a
Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
Fax +81(11)7064920; E-mail: fumi@sci.hokudai.ac.jp; E-mail: ktanino@sci.hokudai.ac.jp
b
Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan
Received: 09.04.2014; Accepted after revision: 07.05.2014
terest for the last decade.4 Although a number of consid-
Abstract: In the presence of triethylsilyl trifluoromethanesulfonate
erable drawbacks remain in their handling and storage due
and triethylamine, aliphatic nitriles undergo addition reactions with
to the high tendency toward hydrolysis, N-silyl ketene im-
aldonitrones under non-basic, mild conditions, providing O-tri-
ethylsilyl ethers of β-N-hydroxyamino nitriles with high yield. The
ines react with a range of carbonyl electrophiles as well as
reaction appears to proceed through formation of an N-silyl ketene N-acylhydrazones and N-arylaldimines,5 giving rise to the
imine in situ followed by a Mannich-type reaction.
corresponding α-substituted nitriles under mild condi-
tions.
Key words: nucleophilic addition, nitriles, nitrones, amines,
hydroxylamine
In the course of our studies on the development of new
synthetic reactions using α-cyano carbanions,6 we recent-
ly reported the intramolecular conjugate addition of α,β-
unsaturated lactones having an alkanenitrile side chain
promoted by TMSOTf and triethylamine (Et3N) (Scheme
2, 1→2).7 The cyclization reaction is thought to proceed
through formation of the N-silyl ketene imine intermedi-
ate under the influence of TMSOTf and Et3N. Indeed, a
85:15 diastereomeric mixture of acyclic nitrile 3 was
found to undergo isomerization to afford a 60:40 mixture
of the diastereomers under similar conditions.8 These re-
sults suggested that the combined use of TMSOTf and
Et3N shows promise for generating an N-silyl ketene im-
ine from the corresponding nitrile without requiring a
strong base such as lithium diisopropylamide (LDA).9
The addition reaction of nucleophiles to nitrones is one of
the most powerful and reliable methods for the synthesis
of α-branched N,N-disubstituted hydroxylamine deriva-
tives.1 Among various nucleophiles, organometallic re-
agents such as Grignard and organolithium reagents are
frequently used in these types of reactions under basic
(anionic) conditions (Scheme 1).1,2 Similar to the
Mukaiyama aldol reaction and the Hosomi–Sakurai al-
lylation reactions, silyl enol ethers, silyl ketene acetals,
and allylsilanes are also used in this process under acidic
conditions (Scheme 1).1,2 On the other hand, the addition
reactions of nitrones with nitriles have rarely been ex-
plored under both basic and acidic conditions.3
O
O
a) under basic condition
EtMgBr
O
O
TMSOTf
Et3N
H
Ph
Ph
O–
CN
Me
CN
Me
MgBr2
O
O
Et
*
(ref. 2c)
N
Me
Me
DCE
50 °C
Et2O, THF
–78 °C
80%
H
Bn
Et2N
Et2N
N
Bn
OH
84%
1
3
2
dr = 67:33
b) under acidic condition
Me
TMSOTf
Et3N
OTBS
Me
Me
Me
Me
*
Me
Me
Me
Boc
Boc
N
3
OMe
TBSOTf
N
N
Ph
C
TMS
Ph
CN
DCE
50 °C
N
dr = 60:40
O
O
H
4
(ref. 2a)
CO2Me
93%
dr = 85:15
CH2Cl2
–60 °C
92%
N
–O
Bn
TBSO
Bn
Scheme 2 TMSOTf–Et3N promoted intramolecular conjugate addi-
tion and its mechanistic investigation
dr = 86:14
Scheme 1 Typical examples of nucleophilic addition to nitrones
Based on these findings, we envisaged that the addition
reaction between nitrones and nitriles would proceed un-
der mild neutral conditions. Namely, treatment of a mix-
ture of nitrones 5 and nitriles 6 with trialkylsilyl triflate
and Et3N would directly yield O-trialkylsilyl β-hydroxy-
amino nitrile 7 through the formation of N-siloxyiminium
ion 810 and N-silyl ketene imine 9 in situ (Scheme 3). This
process would provide a simple and efficient synthetic
As a highly competent nitrile anion equivalent, N-silyl ke-
tene imines, which are prepared by trapping of the anion
with a bulky trialkylsilyl chloride, have been of much in-
SYNLETT 2014, 25, 1863–1868
Advanced online publication: 24.06.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0034-1378274; Art ID: st-2014-u0300-l
© Georg Thieme Verlag Stuttgart · New York

1864
F. Yoshimura et al.
LETTER
method for the generation of β-aminonitrile derivatives as the use of tert-butyldimethylsilyl trifluoromethanesul-
that are useful synthetic intermediates and important fonate (TBSOTf) led to poor results (entry 4), triethylsilyl
structural motifs in biologically active compounds, in- trifluoromethanesulfonate (TESOTf) gave promising re-
cluding β-amino acids and 1,3-diamines.11
sults, with the stable O-TES β-hydroxyamino nitrile 14c
formed in 80% yield along with 12% yield of amide 12
(entry 5). After optimization of the reaction conditions,
the best result was obtained at –30 °C, providing 14c in
94% yield (dr 55:45) after purification (entry 6).
R53SiO
R1
R2
R53SiOTf
Et3N
–O
R1
R2
H
+
N
R4
N
+
CN
R3
CN
R3 R4
5
6
Note that the reaction with 1.1 equivalents of TESOTf and
Et3N at –30 °C resulted in the formation of 14c only in
19% yield along with 49% of 12, indicating that the use of
two equivalents of both reagents, i.e., stoichiometric
amounts, is of critical importance for this reaction. Unfor-
tunately, although the reaction proceeded with excellent
yield, diastereoselectivity was not induced, likely due to
low level of stereodiscrimination in the addition step.
7
R53SiO
R1
R2
–OTf
+
N
R4
SiR5
N
R3
C
3
H
8
9
Scheme 3 Proposal for addition reactions of nitriles to nitrones
Table 1 Evaluation of Silylating Agents for the Addition Reaction
of Nitrile 13 to Nitrone 10a
To ascertain the feasibility of the expected addition reac-
tion, we initially attempted the reaction of N-benzyliden-
emethanamine N-oxide (10) with propionitrile (Scheme
4). To our delight, the desired O-TMS β-hydroxyamino
nitrile 11 was obtained in 75% yield as a 59:41 diastereo-
meric mixture when nitrone 10 (1 equiv) and propionitrile
(1 equiv) were treated with TMSOTf (2 equiv) and Et3N
(2 equiv). However, a considerable amount of amide 12,
arising from 10 through a rearrangement pathway,12,13
was formed in 22% yield. The reaction of 10 with 2-phen-
ylpropanenitrile (13) gave similar results, and addition
product 14a, having a quaternary carbon atom, was ob-
tained in 75% yield along with 12 (25% yield).
Me
OSiR3
–O
Me
+
silylating agent
Et3N
N
Me
O
N
CN
+
+
Ph
Ph
CN
Ph
NHMe
12
Ph
H
DCE
temp.
Ph Me
14
10
13
Entry Silylating agent Temp. (°C) Yield (%)b
14 (dr)c
12
1
2
3
4
5
6
TMSOTf
TMSBr
0 → r.t. 14a
0 → 80 14a
0 → r.t. 14a
75 (56:44)
0
25
75
6
TMSNTf2
TBSOTf
TESOTf
TESOTf
93 (59:41)
57 (51:49)
80 (54:46)
94d (55:45)
TMSOTf
Et3N
–O
Ph
Me
H
0
0
14b
14c
14c
42
12
0
Me
Ph
OTMS
CN
O
N
N
+
+
EtCN
Ph
NHMe
DCE
0 °C to r.t.
10
12 (22%*)
–30
Me
11 (75%*)
dr = 59:41
a Reaction conditions: nitrone 10 (0.2 mmol), nitrile 13 (0.2 mmol),
Et3N (0.4 mmol), DCE (1 mL), silylating agent (0.4 mmol).
b Yield determined by 1H NMR analysis of the crude product mixture
using pyrazine as internal standard.
Me
OTMS
TMSOTf
Et3N
N
Me
+
12 (25%*)
+
CN
10
c Diastereomeric ratios of 14 given in parentheses. The relative con-
figuration was not determined.
Ph
Ph
CN
DCE
0 °C to r.t.
Ph Me
13
d Isolated yield after silica gel column chromatography on 0.4 mmol
scale.
14a (75%*)
dr = 56:44
* NMR yields
Scheme 4 Preliminary results
The synthetic advantage of our new method over the con-
ventional method under anionic conditions3 is demon-
strated in Scheme 5. Thus, the addition reaction of 4-
methoxyphenylacetonitrile (15b) to nitrone 10 under the
influence of TESOTf and Et3N gave base-sensitive β-hy-
droxyamino nitrile 16 in good yield after removal of the
TES group under acidic conditions (85% yield for two
steps). In contrast, the α-cyano carbanion generated from
15b by LDA underwent the addition reaction with nitrone
10 to afford 16 only in 48% yield, along with the β-elimi-
nation product 17 (10% yield) and recovery of the sub-
strates (10: 21%; 15b: 35%).
With a view to diminishing the competitive rearrange-
ment pathway, the reactions of nitrile 13 and nitrone 10
with various silylating agents were explored as shown in
Table 1. The use of TMSBr failed to promote the addition
reaction, and amide 12 was obtained as the major product
(entry 2). On the other hand, the reaction mediated by
TMSNTf214 afforded O-TMS β-hydroxyamino nitrile 14a
in excellent yield (93% by NMR spectroscopic analysis of
the crude mixture; entry 3). However, purification of the
crude product by silica gel column chromatography led to
hydrolysis of the silyloxy group, which prompted us to
employ the use of more bulky silylating reagents. Where-
Synlett 2014, 25, 1863–1868
© Georg Thieme Verlag Stuttgart · New York

LETTER
Nucleophilic Addition Reactions of Nitriles to Nitrones
1865
Table 2 Reactions of Nitrone 10 with Nitriles 15a
1) TESOTf, Et3N
DCE, –30 °C
99% (dr = 64:36)
–O
Ph
Me
H
N
CN
Me
OTES
CN
–O
Me
H
TESOTf
Et3N
+
N
+
R2
N
2) 1 M HCl, THF
20 min
MeO
+
R1
CN
Ph
10
15b
(1 equiv)
DCE
–30 °C
Ph
(1 equiv)
R1 R2
18
10
15
Me
OH
OMe
OMe
N
Entry Nitrile 15
18
Yield drc
+
(%)b
Ph
Ph
CN
CN
1
2
15a
15b
EtCN
18a
18b
94
60:40
64:36
16
17
4%
(dr = 76:24)
85%
CN
LDA
(1 equiv)
99
96
MeO
10
15b
+
17
10%
16
+
(1 equiv) (1 equiv)
(dr = 88:12)
THF
0 °C, 1 h
CN
48%
3
4
15c
15d
18c
18d
58:42
74:26
MeO2C
Scheme 5 Comparison with a conventional method
CN
We next applied the optimized reaction conditions using
TESOTf to the reactions of nitrone 10 with a series of ni-
triles (Table 2). Gratifyingly, simple alkanenitrile 15a, α-
aryl acetonitriles 15b−d, and α-heteroaryl acetonitriles
15e–g afforded the corresponding O-TES β-hydroxyami-
no nitriles 18 in good to excellent yields (entries 1–7), al-
though the diastereomeric ratios of 18 were rather low
(74:26 to 58:42). In the case of the reaction of 2-pyridyl-
acetonitrile (15e), TESOTf–Et3N reagent triggered the
elimination reaction of O-TES hydroxylamine from the
desired product 18e, giving (Z)-3-phenyl-2-(pyridin-2-
yl)acrylonitrile (19; Figure 1) in 38% yield along with 18e
(entry 5). α,α-Disubstituted nitriles, including isobutyro-
nitrile (15h) and diphenylacetonitrile (15i), gave addition
products having the newly formed quaternary carbon
atom in good yields (entries 8 and 9), although two equiv-
alents of nitrile 15h were required because of its low reac-
tivity (entry 8). Note that the neutral reaction conditions
using TESOTf–Et3N allows the use of nitriles with vari-
ous functional groups, and chloroacetonitirile (15j) and
N-(diphenylmethylene)aminoacetonitrile (15k) afforded
the desired products in excellent yields (entries 10 and
11).
95
N
S
CN
CN
5
6
15e
15f
18e
18f
58d 69:31
95
59:41
68:32
CN
7
15g
18g
100
N
Me
8
9
15h
15i
15j
i-PrCNe
18h
18i
18j
79f
84h
99
–
Ph2CHCNg
–
10
ClCH2CN
79:21
Ph
11
15k
18k
98
73:27
Ph
N
CN
a Reaction conditions: nitrone 10 (0.4 mmol), nitrile 15 (0.4 mmol),
TESOTf (0.8 mmol), Et3N (0.8 mmol), DCE (2 mL), –30 °C, 0.5 to
1.5 h.
b Isolated yield after purification.
c Determined by 1H NMR analysis of the crude product; relative ste-
reochemistry not assigned.
Ph
N
d (Z)-3-Phenyl-2-(pyridin-2-yl)acrylonitrile (19; Figure 1) was ob-
tained in 38% yield.
CN
19
e Nitrile (2 equiv.) was used.
f Yield based on 10. Amide 12 was obtained in 13% yield.
g Reaction conditions: –30 to 0 °C, 1.5 h.
h Amide 12 was obtained in 6% yield.
Figure 1 Structure of 19
The scope of the reaction with respect to nitrones was then
examined by using nitrile 15b as a nucleophile (Table 3).
Addition of 15b to aromatic nitrones 20a–c proceeded
smoothly to furnish the corresponding O-TES β-hydroxy-
amino nitriles in good to excellent yields (entries 1–3).
Chemoselective addition to the nitrone moiety was
achieved in the reaction of 20c, keeping the ester group in-
tact (entry 3). The reaction of endocyclic nitrone 20d pro-
vided tetrahydroisoquinoline derivative 21d as a single
diastereomer (entry 4).15,16 Addition to α,β-unsaturated ni-
trone 20e occurred exclusively in a 1,2-fasion (entry 5).
Whereas the addition reaction was applicable to an α,α-di-
substituted aliphatic nitrone (entry 6), aliphatic nitrone
20g, bearing an acidic α-proton, failed to react with nitrile
15b, resulting in decomposition under the reaction condi-
tions (entry 7).17
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1863–1868

1866
F. Yoshimura et al.
LETTER
Finally, transformations of the O-TES β-hydroxyamino In addition, nitrile 18h was converted into β-amino acid
nitriles were briefly examined to evaluate the synthetic 25 through isoxazolidin-5-one formation followed by N–O
utility and versatility of the addition products (Scheme 6). cleavage under hydrogenation. Furthermore, 1,3-diamine
Nitrile 18h was converted into the corresponding amine derivative 26 was obtained by reduction of the cyano
22 by treatment with Zn/H2SO4, whereas the reaction of group using LiAlH4. Conversely, upon treatment with
18h with Zn/TFA in MeOH at 60 °C afforded amide 23. LDA at 0 °C, nitrile 18a underwent a 3-exo-tet ring-
Table 3 Reactions of Nitrones 20 with Nitrile 15ba
TESO
R2
OMe
–O
R2
TESOTf
Et3N
+
N
N
CN
+
R1
R1
H
DCE
–30 °C
MeO
20
CN
15b
21
Entry
1
Nitrone
Product
Yield (%)b
drc
TESO
Ph
Bn
OMe
OMe
–O
Bn
N
+
N
100
74:26
Ph
H
CN
20a
21a
TESO
t-Bu
–O
t-Bu
N
+
N
Ph
2
3
85
96
91:9
Ph
H
CN
20b
21b
–O
+
N
Me
H
TESO
Me
OMe
N
56:44
CN
MeO2C
MeO2C
20c
21c
N
OTES
N+
O–
CN
4
81
100:0
20d
MeO
21d
TESO
Me
N
OMe
OMe
OMe
–O
Me
H
+
N
Ph
5
6
7
77
83
0
50:50
58:42
–
Ph
CN
20e
21e
–O
+
Me
TESO
Me
N
N
BnO
BnO
H
Me Me
Me Me
CN
20f
21f
TESO
Me
–O
Me
H
N
+
N
Ph
Ph
CN
20g
21g
a Reaction conditions: nitrone 20 (1 equiv), nitrile 15b (1 equiv), TESOTf (2 equiv), Et3N (2 equiv), DCE (0.2 M), –30 to 0 °C, 0.5 to 3 h.
b Isolated yield after purification.
c Determined by 1H NMR analysis of the crude product; relative stereochemistry not assigned.
Synlett 2014, 25, 1863–1868
© Georg Thieme Verlag Stuttgart · New York

LETTER
Nucleophilic Addition Reactions of Nitriles to Nitrones
(2) For typical examples, see: (a) Merino, P.; Franco, S.;
1867
closure reaction,18 giving rise to N-methylaziridine 27
Merchan, F. L.; Tejero, T. J. Org. Chem. 2000, 65, 5575.
(b) Murahashi, S.; Imada, Y.; Kawakami, T.; Harada, K.;
Yonemushi, Y.; Tomita, N. J. Am. Chem. Soc. 2002, 124,
2888. (c) Kazuta, Y.; Abe, H.; Matsuda, A.; Shuto, S. J. Org.
Chem. 2004, 69, 9143. (d) Fu, Y.; Liu, Y.; Chen, Y.; Hügel,
H. M.; Wang, M.; Huang, D.; Hu, Y. Org. Biomol. Chem.
2012, 10, 7669.
with high diastereoselectivity.
In conclusion, we have developed a novel method for nu-
cleophilic addition reaction of nitriles to nitrones promot-
ed by TESOTf and Et3N under mild conditions.19 The
reaction appears to proceed through N-silyl ketene imine
formation in situ followed by a Mannich type addition re-
action. In contrast to the conventional addition reactions
using strong bases, the nonbasic, mild reaction conditions
of the present method tolerates various functional groups
and usually provides the β-aminonitrile derivatives in
high yields without causing β-elimination reactions or ret-
ro-addition reactions. The new method is expected to of-
fer an efficient route to base-sensitive β-aminonitrile
derivatives, which serve as useful intermediates in the
synthesis of biologically important compounds, including
β-amino acids and 1,3-diamines.
(3) (a) Aurich, H. G.; Schmidt, M.; Schwerzel, T. Chem. Ber.
1985, 118, 1086. (b) Babu, Y. S.; Chand, P.; Ghosh, A. K.;
Kotian, P. L.; Kumar, S. Y. PCT Int. Appl WO 2006002231,
2006. (c) Behr, J.; Chavaria, D.; Plantier-Royon, R. J. Org.
Chem. 2013, 78, 11477.
(4) For an excellent review of N-silyl ketene imines, see:
Denmark, S. E.; Wilson, T. W. Angew. Chem. Int. Ed. 2012,
51, 9980.
(5) (a) Notte, G. T.; Baxter Vu, J. M.; Leighton, J. L. Org. Lett.
2011, 13, 816. (b) Zhao, J.; Liu, X.; Luo, W.; Xie, M.; Lin,
L.; Feng, X. Angew. Chem. Int. Ed. 2013, 52, 3473.
(6) (a) Tanino, K.; Tomata, Y.; Shiina, Y.; Miyashita, M. Eur. J.
Org. Chem. 2006, 328. (b) Yamada, T.; Yoshimura, F.;
Tanino, K. Tetrahedron Lett. 2013, 54, 522.
Me
Ph
Me
Ph
OTES
CN
Me
Ph
Zn
H2SO4
Zn
TFA
NH
N
NH
O
(7) Yoshimura, F.; Torizuka, M.; Mori, G.; Tanino, K. Synlett
2012, 23, 251.
CN
NH2
MeOH
0 °C
(8) We could not detect N-silyl ketene imine 4 when monitoring
the reaction by 1H and 13C NMR spectroscopy. The
isomerization of 3 did not proceed in the absence of either
TMSOTf or Et3N. Accordingly, very reactive intermediate 4
was immediately protonated by triethylamine salt of triflic
acid generated in situ as a proton source, providing the
isomerized product 3.
(9) In this connection, Emde and Simchen reported that
silylation of acetonitrile with excess TMSOTf and Et3N in
ether gave a mixture of (Me3Si)2C=C=N(SiMe3) (44%) and
(Me3Si)3CCN (56%), see: Emde, H.; Simchen, G. Synthesis
1977, 6363.
(10) It is reported that the reactions of aldonitrones with TMSOTf
afford the corresponding N-trimethylsiloxyiminium ions,
which can be identified by NMR spectroscopy, see:
Camiletti, C.; Dhavale, D. D.; Gentilucci, L.; Trombini, C.
J. Chem. Soc., Perkin Trans. 1 1993, 3157.
(11) (a) Muller, G. W.; Shire, M. G.; Wong, L. M.; Corral, L. G.;
Patterson, R. T.; Chen, Y.; Stirling, D. I. Bioorg. Med. Chem.
Lett. 1998, 8, 2669. (b) Liu, M.; Sibi, M. P. Tetrahedron
2002, 58, 7991. (c) Fleming, F. F.; Yao, L.; Ravikumar, P.
C.; Funk, L.; Shook, B. C. J. Med. Chem. 2010, 53, 7902.
(12) Interestingly, the combination of TMSOTf and Et3N
smoothly promoted rearrangement of an aromatic
aldonitrone to the isomeric amide (Scheme 7).
MeOH
60 °C
86%
Me Me
Me Me
Me Me
71%
22
18h
23
Me
Me
OTES
Me
H2
Pd/C
N
N
O
NH
O
1 M HCl
CN
Ph
O
Ph
Ph
OH
MeOH
72%
THF
81%
Me Me
Me Me
Me Me
18h
24
25
Me
OH
N
LiAlH4
THF
60 °C
89%
Ph
NH2
Me Me
26
Me
Me
Ph
OTES
N
Ph
LDA
N
CN
CN
H
THF
0 °C
78%
Me
27
Me
18a
(dr = 90:10)
(dr = 60:40)
Scheme 6 Transformations of the addition products
Acknowledgment
TMSOTf (2 equiv)
Et3N (2 equiv)
–O
Ph
Me
H
We acknowledge Dr. Eri Fukushi and Mr. Yusuke Takata (GC-MS
& NMR Laboratory, Faculty of Agriculture, Hokkaido University)
for their mass spectral measurements. This work was supported by
JSPS KAKENHI Grant Number 24510290 and the Mitsubishi
Tanabe Pharma Award in Synthetic Organic Chemistry, Japan.
O
+
N
Ph
NHMe
DCE
0 °C to r.t., 75 min
85%
12
10
Scheme 7
Supporting Information for this article is available online
(13) Hamer, J.; Macaluso, A. Chem. Rev. 1964, 64, 473.
(14) (a) Mathieu, B.; Ghosez, L. Tetrahedron Lett. 1997, 38,
5497. (b) Ishii, A.; Kotera, O.; Saeki, T.; Mikami, K. Synlett
1997, 1145.
(15) All attempts to determine the relative stereochemistry of
nitrile 21d were unsuccessful.
at
http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000083.SunpfgIpi
o
o
nr
i
References and Notes
(1) For reviews, see: (a) Bloch, R. Chem. Rev. 1998, 98, 1407.
(b) Merino, P.; Franco, S.; Merchan, F. L.; Tejero, T. Synlett
2000, 442. (c) Lombardo, M.; Trombini, C. Synthesis 2000,
759. (d) Merino, P.; Tejero, T. Synlett 2011, 1965.
(16) The reason for the high stereoselectivity observed in the
formation of nitrile 21d is not yet clear.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1863–1868

1868
F. Yoshimura et al.
LETTER
(17) It is assumed that aliphatic nitrone 20g decomposed through
formation of the corresponding N-triethylsiloxyenamine
derivative and subsequent self-condensation or
mmol) in DCE (2 mL), was added TESOTf (0.8 mmol) at
–30 °C, and the reaction mixture was stirred at this
temperature for 30 min. Sat. aq sodium bicarbonate (1 mL)
was added to the mixture, and the product was extracted with
EtOAc. The combined organic layers were dried over
MgSO4 and concentrated under reduced pressure.
Purification by flash column chromatography (SiO2;
hexane–Et2O, 15:1) afforded O-TES β-hydroxyamino nitrile
14c (0.377 mmol, 94%).
polymerization.
(18) For related aziridinations, see: (a) Tsuge, O.; Sone, K.;
Urano, S.; Matsuda, K. J. Org. Chem. 1982, 47, 5171.
(b) Bew, S. P.; Hughes, D. L.; Savic, V.; Soapi, K. M.;
Wilson, M. A. Chem. Commun. 2006, 3513.
(19) General Procedure (Table 1, entry 6): To a mixture of
nitrone 10 (0.4 mmol), nitrile 13 (0.4 mmol), and Et3N (0.8
Synlett 2014, 25, 1863–1868
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