Preparation and facile addition reactions of iminium salts derived from amino ketene silyl acetal and amino silyl enol ether

Article abstract of DOI:10.1039/d0ra05768a

While iminium salts generated by the oxidation of amino ketene silyl acetals show intriguing reactivities to give useful γ-oxo-α-amino esters via reactions with silyl enol ethers in good yields, new iminium salts are also prepared by the oxidation of amin

Full text of DOI:10.1039/d0ra05768a

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Preparation and facile addition reactions of
iminium salts derived from amino ketene silyl acetal
Cite this: RSC Adv., 2020, 10, 27874
and amino silyl enol ether†
ab
Shingo Hata,b Koichi Kondo,b Kazuhiro Murakami,b
*
Makoto Shimizu,
Isao Mizota
b
and Yusong Zhua
Received 2nd July 2020
Accepted 20th July 2020
While iminium salts generated by the oxidation of amino ketene silyl acetals show intriguing reactivities to
give useful g-oxo-a-amino esters via reactions with silyl enol ethers in good yields, new iminium salts are
also prepared by the oxidation of amino silyl enol ethers. They undergo facile addition reaction with various
nucleophiles to give a-amino ketone derivatives in good yields.
DOI: 10.1039/d0ra05768a
rsc.li/rsc-advances
We now reexamined the reaction with other silyl enol ethers and
found that an acceptable range of product yields was obtained
1 Introduction
under carefully controlled conditions. We did not study generation
and reaction of the iminium salts derived from amino silyl enol
ethers, either, although these iminium salts are highly attractive in
terms of reactivity and chemoselectivity on an addition reaction
with nucleophiles. This paper describes addition reactions of the
alkoxycarbonyl iminium salts with silyl enol ethers to produce g-
oxo-a-amino esters (eqn (2)). Reactions of the iminium salts
derived from amino silyl enol ethers with various nucleophiles are
also presented to give addition products (eqn (3)).
Iminium salts are usually very reactive species and used widely
in organic synthesis. Several methods are known to generate
these useful species. Among them the synthesis of natural
products, such as alkaloids, was reported using cyclization
mediated by iminium salts as a crucial step.1 Representative
examples using iminium species involve the addition of
organometallic reagents for the synthesis of b-amino acids,2a,b
b-amino ketones, 1,3-amino alcohols,2c and so on.2dꢀj The
synthesis of a-monosubstituted a-amino acids was reported by
the nucleophilic addition of boronates to the iminium ions,
which were prepared by the condensation of primary or
secondary amines with ethyl glyoxylate in situ.3 Although the use
of iminium salts is a promising procedure, it is not trivial to
generate these species in a chemo- and regioselective manner
under mild reaction conditions.
2 Results and discussion
The starting amino ketene silyl acetal 1 was readily prepared
according to the reported procedures in good overall yield.4b,f
We have been interested in the generation of iminium salts and
have already disclosed several intriguing features.4 In these
studies, we focused on the generation of iminium species by
oxidizing a readily accessible and stable enol derivative with
oxidants and found that the alkoxycarbonyl iminium salts from
amino ketene silyl acetals were reasonably stable5 and highly
reactive to give addition products with metal cyanides, Grignard
reagents, allyl metals,4b ketene silyl acetals,4g and indoles4c (eqn (1),
Scheme 1). However, we have not fully studied reactions with silyl
enol ethers, since an initial examination using the silyl enol ether
derived from cyclopentanone met with a disappointing result
where only a trace amount of the addition product was obtained.
aSchool of Energy Science and Engineering, Nanjing Tech University, Nanjing 211816,
Jiangsu Province, China
bDepartment of Chemistry for Materials, Graduate School of Engineering, Mie
University, Tsu, Mie 514-8507, Japan. E-mail: mshimizu@chem.mie-u.ac.jp
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d0ra05768a
Scheme 1 Previous and present works.
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Table 1 Reaction of the iminium salt with cyclic ketene silyl acetals
Entry
n
Sia
Yieldb (%)
syn/anti
1
2
3
4
5
6
1
2
2
2
3
4
TMS
TMS
TBS
TIPS
TMS
TMS
2a: 9
100/0
66/34
45/55
45/55
57/43
60/40
2b: 73
2b: 59
2b: 61
2c: 71
2d: 68
Scheme 2 Possible transition state models.
a
Abbrebiations, TMS: trimethylsilyl, TBS: tert-butyldimethylsilyl, TIPS:
use of bulky substituents such as TBS and TIPS did not improve
the diastereoselectivity (entries 3 and 4). Reactions of acyclic
silyl enol ethers were next examined. Table 2 summarizes the
results.
triisopropylsilyl. b Isolated yield.
First, silyl enol ethers derived from cyclic ketones were sub-
jected to the addition reaction, and Table 1 summarizes the
results.
Although an initial examination was carried out with the
TMS enol ether derived from cyclopentanone, only a small
amount of the desired addition product was obtained (entry 1).
Switching the ring size from 5 to 6, 7, and 8 resulted in the
formation of the desired products in 73, 71, and 68% yields,
respectively (entries 2, 5, and 6). We next examined the effect of
the silyl substituent on the diastereoselectivity.6 However, the
In terms of the product yields using the silyl enol ether
derived from 1-cyclohexylpropan-1-one, the reaction in EtCN
did not give a satisfactory result (entry 1), whereas the use of
DMF in the absence of a Lewis acid gave better results (entries 2
and 4). The effects of a Lewis acid are not prominent on the
diastereoselctivity, giving the addition products with moderate
selectivities (entries 2 to 5).7 Regarding the silyl enol ether
derived from propiophenone, both TMS and TIPS derivatives in
DMF in the absence of a Lewis acid gave high yields of the
product (entries 8 and 16). In general, the TIPS derivative
recorded good syn-selectivities (entries 13 to 15). Among them
the reaction in the presence of a Lewis acid (BF3$Et2O or Et2-
AlCl) gave the syn-adduct with good selectivities (entries 14 and
15), whereas the presence of a Lewis acid destroyed selectivities
in certain cases (entries 6, 10, and 18). For the explanation of the
Table 2 Reaction of the iminium salt with acyclic ketene silyl acetals
syn-selectivity, Scheme
2 shows possible transition state
models.
In the absence of a Lewis acid or in the presence of BF3$Et2O
Entry
R
Si
Z/E
Solv. Lewis acid Yield (%)a syn/anti (monodentate Lewis acid), the non-chelation model would
explain the preferred formation of the syn-isomer 3 due to the
1
2
3
4
5
6
7
8
Cy TMS
Cy TMS
Cy TMS
Cy TBS
Cy TBS
Ph TMS
Ph TMS
Ph TMS
Ph TBS
Ph TBS
Ph TBS
Ph TBS
Ph TIPS
Ph TIPS
Ph TIPS
Ph TIPS
85/15 EtCN
85/15 DMF
85/15 DME BF3$Et2O
85/15 DMF
85/15 DME BF3$Et2O
90/10 DME BF3$Et2O
90/10 DME Et2AlCl
90/10 DMF
90/10 DME
90/10 DME BF3$Et2O
90/10 DME Et2AlCl
90/10 DMF
85/15 DME
85/15 DME BF3$Et2O
—
—
3a: 32
3a: 67
3a: 22
3a: 62
3a: 25
3b: 57
3b: 30
3b: 78
3b: 8
3b: 38
3b: 31
3b: 64
3b: 13
3b: 60
3b: 30
3b: 79
3b: 57
3b: 40
3b: 62
52/48
77/23
76/24
78/22
65/35
57/43
66/34
51/49
60/40
58/42
72/28
56/44
92/8
less steric congestion. In the cases where the reaction was
carried out in the presence of Et2AlCl (bidentate Lewis acid), the
chelation model would also support the formation of the syn-
isomer 3. On the basis of the above transition state models, the
—
—
—
9
10
11
12
13
14
15
16
17
18
19
—
—
86/14
88/12
60/40
73/27
51/49
59/41
85/15 DME Et2AlCl
85/15 DMF
—
—
Ph DMSb 88/12 DME
Ph DMS
Ph DMS
88/12 DME BF3$Et2O
88/12 DMF
—
a
Isolated yield. b Abbrebiation, DMS: dimethylsilyl.
Scheme 3 Generation of a new iminium salt.
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Table 4 Reaction with various ketene silyl(thio) acetas
Scheme 4 Preparation of the amino silyl enol ether 5.
formation of the syn-isomer 3 would be preferred regardless of
the presence of Lewis acids.
Entry
R1
R2
Product
Yielda (%)
During investigations into the reactivity of iminium salts 4
derived from amino ketene silyl acetals, new iminium salts
from amino silyl enol ethers intrigued us (Scheme 3). However,
no reliable reports are available for the generation of the imi-
nium salts of type 6. We therefore investigated the generation of
this type of iminium salt using a method similar to those from
amino ketene silyl acetals.
1
2
3
4
5
6
7
Me
Me
Me
Me
MeO
EtO
H
OMe
OEt
OiPr
OtBu
OMe
OEt
8a
8b
8c
8d
8e
8f
80
82
73
57
73
70
63
StBu
8g
The amino silyl enol ether 5 was readily prepared as follows
in good yield (Scheme 4).
a
Isolated yields.
First, the formation of the iminium salt followed by addition
reactions using the amino silyl enol ether 5 was examined to
nd the best reaction conditions involving the oxidation
reagent and a Lewis acid. Table 3 summarizes the results.
Iodosylbenzene did not effect the oxidation, while the use of
BPO,4a NCS, and DBDMH gave the desired product in low yields
(entries 1 to 4). DDQ4b,8 which was used for the oxidation of the
amino ketene silyl acetal 1 effected the reaction to give the
addition product 8a in 24% yield (entry 5). Among the oxidation
reagents examined here the use of NBS recorded the best result
(entry 6).4f We next examined the use of a Lewis acid for the
present transformation. Et2AlCl was not effective, while an
increased amount of the addition product was obtained in the
presence of TiCl4 (entries 7 and 8). A better result was obtained
when the reaction was carried out with NBS in the presence of
BF3$Et2O, and the addition product was obtained in 74% yield
(entry 9). The amounts of ketene silyl acetal and BF3$Et2O were
further examined. The use of the reduced amounts of the ketene
silyl acetal (1.5 equiv.) and BF3$Et2O (1.2 equiv.) gave a slightly
better result (entry 10). Regarding the reaction temperature, the
reaction at a higher temperature gave a reduced amount of the
desired product (entry 13). The best result was obtained when
the reaction was carried out with the ketene silyl acetal (1.5
equiv.) and BF3$Et2O (2.0 equiv.) at rt, and the addition product
8a was obtained in 80% yield (entry 15). Under the optimized
Table 3 Examination of the reaction conditions
Entry
Oxidant
Nu (equiv.)
Lewis acid (equiv.)
Temp
Yielda (%)
1
2
3
4
5
6
7
8
PhIO
BPO
NCS
DBDMH
DDQ
NBS
NBS
NBS
NBS
NBS
NBS
NBS
NBS
NBS
NBS
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.5
1.5
1.2
1.5
1.5
1.5
—
—
—
—
—
—
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
0
7
2
10
24
27
10
48
74
76
69
53
40
77
80
Et2AlCl (2.0)
TiCl4 (2.0)
BF3$Et2O (2.0)
BF3$Et2O (1.2)
BF3$Et2O (1.5)
BF3$Et2O (2.0)
BF3$Et2O (2.0)
BF3$Et2O (2.0)
BF3$Et2O (2.0)
9
10
11
12
13
14
15
50 ꢁ
C
0 ꢁC to rt
rt
a
Isolated yield.
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Table 6 Optimization of the ethylation conditions
conditions, various ketene silyl acetals were subjected to this
addition reaction, and Table 4 summarizes the results.
As shown in Table 4, tetra-substituted ketene silyl acetals
underwent addition reaction readily to give the adducts in good
yields. Regarding the ester alkoxy part, methyl and ethyl esters
were obtained in good yields (entries 1 and 2), whereas a bulky
tbutyl derivative recorded a decreased yield of the product (entry
4). Di-substituted thioester also participated in the present
addition to give the adduct in moderate yield (entry 7). We next
examined the use of indole derivatives as nucleophiles, since
indole skeletons are oen found in many biologically active
compounds such as tryptophan, indomethacin, and dragmaci-
din derivatives, and several methodologies have been reported
to functionalize indoles.9 Table 5 summarizes the results.
N-TIPS indole was subjected to the present reaction condi-
tions to give a moderate yield of the addition product 9a (entry
1). The bestꢁresult was obtained when the reaction was con-
ducted at 0 C to rt for 5 h (entry 2). An electron-withdrawing
group, 5-nitro substituent decreased the product yield consid-
erably (entry 5), whereas 5-MeO, 5-Br, and 6-Br groups did not
affect the addition reaction to give the adducts in good yields
(entries 6 to 8). However, N–H free and N-Ts derivatives were not
suitable for the present reaction, presumably due to the
decreased electron-density at the 3-position of the indole skel-
eton (entries 9 and 10). We next examined the use of Grignard
reagents as nucleophiles.
Entry
EtMgBr (equiv.)
Time (min)
Yielda (%)
1
2
3
4
5
3.0
2.5
2.0
2.0
2.0
60
60
60
30
10
60
72
70
74
71
a
Isolated yield.
Under the optimized conditions, a variety of Grignard reagents
were subjected to the alkylation, and Table 7 summarizes the
results.
Methyl, ethyl, npropyl, iso-propyl, cyclohexyl, and 2-thiehyl
Grignard reagents recorded good product yields (entries 1–4, 6,
and 10), whereas cylopropyl, benzyl, and 4-tolyl derivatives gave
the addition products in moderate yields (entries 5, 6, and 9).
However, phenyl and ethylnylmagnesium bromides did not give
the desired products but gave complex mixtures (entries 8 and
11). Compared with the results obtained from the reactions of
the iminium salts generated by the oxidation of amino ketene
silyl acetals with Grignard reagents,4b this a-amino ketone-
derived iminium salt appears to be only a little bit less reac-
tive than ester-derived ones. Thus, the present iminium salt
derived from a-amino ketone shows good reactivity as an elec-
trophile to give a variety of addition products. The following
Scheme 5 shows possible reaction pathways.
Treatment of the amino silyl enol ether 5 with NBS followed
by ethylmagnesium bromide in the presence of BF3$Et2O actu-
ally gave the ethylated product 10b. Table 6 summarizes the
optimization of reaction conditions.
As can be seen form Table 6, the best conditions were found
when the amino silyl enol ether 5 was treated with NBS (1.1
equiv.) and ethylmagnesium bromide (2.0 equiv.) in the pres-
ence of BF3$Et2O (2.0 equiv.) in EtCN at rt for 30 min, and the
ethylation product 10b was obtained in 74% yield (entry 4).
Regarding the formation of the iminium salt 4 derived from
a-amino ester, DDQ oxidizes the amino ketene silyl acetal 1 to
Table 5 Reaction with various indoles
Table 7 Alkylation of the iminium salt
Entry
R
Product
Yielda (%)
Yieldb (%)
Entry
R1
R2
Temp (ꢁC)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
Me
Et
nPr
iPr
10a
10b
10c
10d
10e
10f
10g
10h
10i
46
74
71
63
27
58
30
0
64
—
62
63
35
60
43
0
1
2
3
4
5
6
7
8
9
10
9a: TIPS
9a: TIPS
9a: TIPS
9a: TIPS
9b: TIPS
9c: TIPS
9d: TIPS
9e: TIPS
9f: H
H
H
H
H
5-NO2
5-MeO
5-Br
6-Br
H
rt
0 to rt
5
5
3
5
5
5
5
5
5
5
43
77
51
70
13
67
75
73
0
0
0
0
0
0
0
0
0
cPr
Cy
Bnc
Ph
9
10
11
4-MeC6H4
2-Thienyl
Ethynyl
46
64
0
38
45
0
10j
10k
9f: Ts
H
0
a
RMgBr (2.0 equiv.) was used. b RMgBr (2.5 equiv.) was used. c BnMgCl
a
Isolated yields.
was used.
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tetramethylsilane as an internal standard. Mass spectra were
recorded on a JEOL MS-700D spectrometer. Propionitrile (EtCN)
was distilled from phosphorus pentaoxide and then from
ꢀ
calcium hydride, and stored over molecular sieves 4 A. Dimethyl
formamide (DMF) was distilled from calcium hydride and
ꢀ
stored over molecular sieves 4 A. Dimethoxyethane (DME) was
distilled from calcium hydride and then cupper(I) chloride, and
stored over sodium. 1-Ethoxy-2-dibenzylamino-1-tbutyldime-
thylsiloxyethylene 13b was synthesized by the reported proce-
dure. Purication of products was performed by column
chromatography on silica gel (Kanto Silica Gel 60N) and/or
preparative TLC on silica gel (Merck Kiesel Gel GF254 or
Wako Gel B-5F).
Synthesis of ethyl 2-(dibenzylamino)-2-(2-oxocyclohexyl)
acetate 2b (general procedure for the addition reaction with
cyclic silyl enol ethers)
In a 30 mL two-necked round-bottomed ask equipped with
a magnetic stirring bar, a rubber septum, and an argon balloon
was introduced a solution of 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (DDQ) (37.4 mg, 0.165 mmol) in EtCN (1.0 mL).
The solution was cooled to ꢀ55 ꢁC, and to it were added
successively solutions of 1-ethoxy-2-dibenzylamino-1-tbutyldi-
methylsiloxyethylene 1 (59.6 mg, 0.150 mmol) in EtCN (1 mL)
and 1-cyclohexenyloxytrimethylsilane (25.0 mg, 0.150 mmol) in
EtCN (1 mL). The reaction mixture was allowed to warm to room
temperature with stirring for 14 h. The reaction was quenched
with 10% aq. Na2CO3, and the whole mixture was extracted with
ethyl acetate (10 mL ꢂ 3). The combined extracts were washed
with brine (15 mL), dried (Na2SO4), and concentrated in vacuo.
The crude product was puried by preparative TLC on silica gel
(CH2Cl2 : nhexane ¼ 6 : 1) to give the title compound (syn-2b
(27.2 mg, 48%) and anti-2b (14.0 mg, 25%)).
Scheme 5 Proposed reaction pathways.
form the N,O-acetal 11, which collapses to form the iminium
salt 4. This iminium salt 4 is responsible for the formation of
the addition products with silyl enol ethers. In the case of a-
amino ketone, NBS reacts with the amino silyl enol ether 5 to
form the bromide 12. An activation with BF3$Et2O promotes the
elimination of a Br ion to form the iminium salt 6, which reacts
with a variety of nucleophiles.
3 Conclusions
In conclusion, the iminium salt prepared from amino ketene
silyl acetal showed good reactivity and reacted with silyl enol
ethers to give g-oxo-a-amino esters in good yields. Regarding
the diastereoseletivity of the reactions with the silyl enol ethers
derived from ethyl ketones, a good syn-selectivitiy was observed.
In particular, in the case with the TIPS enol ether derived from
propiophenone, the presence of Lewis acids improved the syn-
selectivity. The formation of the iminium salt derived from 2-
aminoacetophenone was readily carried out via the oxidation of
its TBS enol ether with NBS. The presence of BF3$Et2O facili-
tated the reaction to give addition products in good yields.
These results indicate that the iminium salts possessing an
electron-withdrawing groups next to the iminium carbon are
readily prepared via the oxidation of their trialkylsilyl enolates
with certain oxidants. These iminium species are reasonably
reactive and act as good acceptors of nucleophiles to give
addition products with ketene silyl acetals, indoles, and
Grignard reagents in good yields.
Syn-2b. Yield 48% (27.2 mg); colorless oil; Rf ¼ 0.26 (nhex-
1
ane : ethyl acetate ¼ 5 : 1); H NMR (400 MHz, CDCl3) d 1.02–
1.61 (m, 6H including triplet at 1.40 ppm, J ¼ 7.3 Hz, 3H), 1.86–
2.05 (m, 2H), 2.26–2.35 (m, 2H), 2.59–2.63 (m, 1H), 2.96–2.98
(m, 1H), 3.37 (d, J ¼ 13.7 Hz, 2H), 3.39 (d, J ¼ 10.7 Hz, 1H), 3.86
(d, J ¼ 13.7 Hz, 2H), 4.29 (dq, J ¼ 7.3, 10.9 Hz, 1H), 4.30 (dq, J ¼
7.3, 10.9 Hz, 1H), 7.22–7.37 (m, 10H); 13C NMR (100 MHz,
CDCl3) d 14.8, 25.2, 28.1, 31.1, 42.5 50.0, 54.8, 60.3, 60.5, 127.2,
128.4, 129.1, 139.2, 170.9, 212.2; IR (neat) 1712, 1637, 1453,
1176, 1150, 1030, 799, 700, 621, 496, 470, 438, 420 cmꢀ1; HRMS
(EI) calcd for C24H29NO3 (M)+ 379.2147, found 379.2164.
Anti-2b. Yield 25% (14.0 mg); colorless oil; Rf ¼ 0.54 (nhex-
1
ane : ethyl acetate ¼ 5 : 1); H NMR (500 MHz, CDCl3) d 1.35–
1.81 (m, 10H including triplet at 1.56 ppm, J ¼ 7.3 Hz), 2.02–2.05
(m, 1H), 3.04–3.08 (m, 1H), 3.32 (d, J ¼ 13.1 Hz, 2H), 3.88 (d, J ¼
11.0 Hz, 1H), 3.96 (d, J ¼ 13.1 Hz, 2H), 4.27 (dq, J ¼ 7.3, 10.7 Hz,
1H), 4.35 (dq, J ¼ 7.3, 10.7 Hz, 1H), 7.22–7.33 (m, 10H); 13C NMR
(126 MHz, CDCl3) d 14.8, 20.7, 28.0, 38.0, 49.5, 53.6, 54.5, 60.6,
61.2, 127.3, 128.5, 129.0, 139.2, 170.5, 219.0; IR (neat) 2860,
4 Experimental
General aspects
Infrared spectra were determined on a JASCO FT/IR-460 plus 1710, 1638, 1494, 1451, 1373, 1335, 1307, 1233, 1175, 1135,
spectrometer. 1H NMR and 13C NMR spectra were recorded with 1027, 969, 794, 744, 699, 501 cmꢀ1; HRMS (EI) calcd for
a JEOL ECX-400P, or a JEOL A-500 spectrometer using
C
24H29NO3 (M)+ 379.2147, found 379.2148.
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128.2, 129.2, 138.7, 170.0, 216.0; IR (neat) 2930, 1727, 1702,
1494, 1453, 1154, 1135, 1028, 749, 699 cmꢀ1; HRMS (EI) calcd
for C26H33NO3 (M)+ 407.2460, found 407.2460.
Ethyl 2-(dibenzylamino)-2-(2-oxocyclopentyl)acetate 2a
Syn-2a. Yield 9% (4.9 mg); yellow oil; Rf ¼ 0.33 (nhex-
ane : ethyl acetate ¼ 5 : 1); 1H NMR (500 MHz, CDCl3) d 1.41 (t, J
¼ 7.0 Hz, 3H), 1.59–1.67 (m, 1H), 1.75–1.83 (m, 1H), 1.92–2.07
(m, 2H), 2.24–2.30 (m, 1H), 2.35–2.41 (m, 1H), 2.90–2.96 (m,
1H), 3.19 (d, J ¼ 11.0 Hz, 1H), 3.36 (d, J ¼ 13.7 Hz, 2H), 3.92 (d, J
¼ 13.7 Hz, 2H), 4.28–4.41 (m, 2H), 7.23–7.39 (m, 10H); 13C NMR
(126 MHz, CDCl3) d 14.6, 20.5, 27.8, 37.9, 49.4 54.3, 60.4, 61.0,
127.2, 128.3, 128.8, 139.0, 170.3, 218.9; IR (neat) 3029, 2931,
Synthesis of ethyl 4-cyclohexyl-2-(dibenzylamino)-3-methyl-4-
oxobutanoate 3a (general procedure for the addition reaction
with acyclic silyl enol ethers)
In a 30 mL two-necked round-bottomed ask equipped with
a magnetic stirring bar, a rubber septum, and an argon balloon
was introduced a solution of DDQ (37.4 mg, 0.165 mmol) in
EtCN (1.0 mL). The solution was cooled to ꢀ55 ꢁC, and to it were
added successively solutions of 1-ethoxy-2-dibenzylamino-
1-tbutyldimethylsiloxyethylene 1 (59.6 mg, 0.150 mmol) in EtCN
(1 mL) and (Z)-((1-cyclohexylprop-1-en-1-yl)oxy)trimethylsilane
(63.6 mg, 0.150 mmol) in EtCN (1 mL). The reaction mixture
was allowed to warm to room temperature with stirring for 14 h.
The reaction was quenched with 10% aq. Na2CO3, and the
whole mixture was extracted with ethyl acetate (10 mL ꢂ 3). The
combined extracts were washed with brine (15 mL), dried
(Na2SO4), and concentrated in vacuo. The crude product was
puried by preparative TLC on silica gel (CH2Cl2 : nhexane ¼
5 : 1) to give the title compound (syn-3a (32.5 mg, 52%) and anti-
3a (9.7 mg, 15%)).10
Syn-3a. Yield 52% (32.7 mg); colorless oil; Rf ¼ 0.35 (nhex-
ane : ethyl acetate ¼ 5 : 1); 1H NMR (400 MHz, CDCl3) d 0.86 (d, J
¼ 6.9 Hz, 3H), 0.95–1.37 (m, 9H including a triplet at 1.29 ppm, J
¼ 7.1 Hz, 3H), 1.61–1.82 (m, 4H), 2.14–2.22 (m, 1H), 3.22–3.31
(m, 3H including a doublet at 3.29 ppm, J ¼ 14.2 Hz, 3H), 3.59
(d, J ¼ 11.0 Hz, 1H), 3.95 (d, J ¼ 14.2 Hz, 2H), 4.11–4.26 (m, 2H),
7.15–7.26 (m, 10H); 13C NMR (100 MHz, CDCl3) d 14.5, 15.0,
25.2, 25.8, 25.9, 28.0, 28.7, 43.7, 51.0, 55.2, 60.2, 65.0, 127.1,
128.2, 128.8, 138.5, 170.4, 213.9; IR (neat) 3027, 2933, 2852,
1728, 1711, 1495, 1450, 1375, 1027, 994, 732, 698 cmꢀ1; HRMS
(EI) calcd for C27H35NO3 (M)+ 421.2617, found 421.2623.
Anti-3a. Yield 15% (9.5 mg); colorless oil; Rf ¼ 0.56 (nhex-
ane : ethyl acetate ¼ 5 : 1); 1H NMR (500 MHz, CDCl3) d 0.97 (t, J
¼ 7.1 Hz, 3H), 1.06 (d, J ¼ 7.3 Hz, 3H), 1.37 (t, J ¼ 7.1 Hz, 3H),
2.40–2.58 (m, 2H), 3.01–3.09 (m, 1H), 3.45 (d, J ¼ 13.3 Hz, 2H),
3.53 (d, J ¼ 11.0 Hz, 1H), 3.85 (d, J ¼ 13.3 Hz, 2H), 4.14–4.32 (m,
2H), 7.22–7.36 (m, 10H); 13C NMR (126 MHz, CDCl3) d 17.6, 14.6,
14.8, 34.9, 45.1, 55.2, 60.4, 62.7, 127.2, 128.3, 129.2, 138.9, 171.9,
214.0; IR (neat) 2931, 2851, 1725, 1495, 1452, 1368, 1027, 914,
698 cmꢀ1; HRMS (EI) calcd for C27H35NO3 (M)+ 421.2617, found
421.2619.
1731, 1494, 1452, 1371, 1311, 1030, 966, 743, 698, 598 cmꢀ1
;
HRMS (EI) calcd for C23H27NO3(M)+ 365.1991, found 365.2003.
Ethyl 2-(dibenzylamino)-2-(2-oxocycloheptyl)acetate 2c
Syn-2c. Yield 40% (23.9 mg); yellow oil; Rf ¼ 0.31 (nhex-
1
ane : ethyl acetate ¼ 5 : 1); H NMR (400 MHz, CDCl3) d 0.85–
0.99 (m, 1H), 1.09–1.18 (m, 1H), 1.21–1.40 (m, 5H including
triplet at 1.38 ppm, J ¼ 7.3 Hz, 3H), 1.60–1.94 (m, 4H), 2.23–2.32
(m, 1H), 2.53–2.60 (m, 1H), 3.08–3.15 (m, 1H), 3.45 (d, J ¼
13.8 Hz, 2H), 3.48 (d, J ¼ 11.0 Hz, 1H), 3.85 (d, J ¼ 13.8 Hz, 2H),
4.16–4.35 (m, 2H), 7.21–7.34 (m, 10H); 13C NMR (100 MHz,
CDCl3) d 14.8, 23.3, 27.6, 28.7, 29.3, 43.6, 50.4, 55.6, 60.4, 61.9,
127.2, 128.4, 129.3, 139.2, 171.7, 215.0; IR (neat) 3029, 2929,
2853, 1453, 1375,1183, 1134, 1024, 938, 750, 700 cmꢀ1; HRMS
(EI) calcd for C25H31NO3 (M)+ 393.2304, found 393.2327.
Anti-2c. Yield 31% (13.0 mg); yellow oil; Rf ¼ 0.51 (nhex-
1
ane : ethyl acetate ¼ 5 : 1); H NMR (500 MHz, CDCl3) d 1.03–
1.40 (m, 6H including a triplet at 1.38 ppm, J ¼ 7.0 Hz, 3H),
1.56–1.79 (m, 5H), 2.02–2.15 (m, 2H), 3.13–3.21 (m, 1H), 3.28 (d,
J ¼ 13.3 Hz, 2H), 3.60 (d, J ¼ 11.4 Hz, 1H), 3.96 (d, J ¼ 13.3 Hz,
2H), 4.21–4.37 (m, 2H), 7.18–7.32 (m, 10H); 13C NMR (126 MHz,
CDCl3) d 14.8, 25.7, 26.8, 28.0, 29.6, 41.2, 52.3, 54.8, 60.5, 63.6,
127.2, 128.3, 129.4, 139.1, 169.9, 212.7; IR (neat) 3027, 2933,
2855, 1722, 1494, 1451, 1370, 1326, 1236, 1170, 1025, 750 cmꢀ1
;
HRMS (EI) calcd for C25H31NO3 (M)+ 393.2304, found 393.2324.
Ethyl 2-(dibenzylamino)-2-(2-oxocyclooctyl)acetate 2d
Syn-2d. Yield 41% (24.5 mg); yellow oil; Rf ¼ 0.32 (nhex-
1
ane : ethyl acetate ¼ 5 : 1); H NMR (400 MHz, CDCl3) d 0.92–
0.95 (m, 1H), 1.08–1.13 (m, 1H), 1.17–1.26 (m, 1H), 1.37–1.57
(m, 9H including triplet at 1.38 ppm, J ¼ 7.0 Hz, 3H), 1.69–1.73
(m, 1H), 2.00–2.04 (m, 1H), 2.14 (d,d,d, J ¼ 2.8 Hz, 7.6 Hz,
15.1 Hz, 1H), 3.19 (d,t, J ¼ 3.7 Hz, 10.6 Hz, 1H), 3.46 (d, J ¼
13.4 Hz, 2H), 3.58 (d, J ¼ 10.6 Hz, 1H), 3.85 (d, J ¼ 13.4 Hz, 2H),
4.17–4.32 (m, 2H), 7.23–7.34 (m, 10H); 13C NMR (100 MHz,
CDCl3) d 14.7, 22.8, 24.4, 25.1, 28.5, 31.8 43.9, 48.0, 55.6, 60.4,
Ethyl 2-(dibenzylamino)-3-methyl-4-oxo-4-phenylbutanoate 3b 10
63.8, 127.2, 128.3, 129.3, 139.0, 171.8, 219.2; IR (neat) 2931, A mixture of syn- and anti-isomers (35.4 mg, 57%, syn : anti ¼
2854, 1719, 1696, 1647,1454, 1027, 748, 698 cmꢀ1; HRMS (EI) 57 : 43, ratio determined by 1H NMR). Yellow oil; Rf ¼ 0.52
calcd for C26H33NO3 (M)+ 407.2460, found 407.2457.
(nhexane : ethyl acetate ¼ 5 : 1); IR (neat) 3061, 2979, 1724,
Anti-2d. Yield 27% (16.3 mg); yellow oil; Rf ¼ 0.51 (nhex- 1683, 1495, 1027, 748, 698 cmꢀ1; HRMS (EI) calcd for
1
ane : ethyl acetate ¼ 5 : 1); H NMR (500 MHz, CDCl3) d 1.26–
1.85 (m, 13H including a triplet at 1.38 ppm, J ¼ 7.0 Hz, 3H),
C
27H29NO3 (M)+ 415.2147, found 415.2136.
Syn-3b. 1H NMR (400 MHz, CDCl3) d 1.16 (d, J ¼ 7.3 Hz, 3H),
2.04–2.19 (m, 2H), 3.25 (d, J ¼ 13.7 Hz, 2H), 3.27 (d, J ¼ 10.8 Hz, 1.29 (t, J ¼ 7.1 Hz, 3H), 3.56 (d, J ¼ 13.3 Hz, 2H), 3.79 (d, J ¼
1H), 3.56 (d, J ¼ 11.6 Hz, 1H), 3.98 (d, J ¼ 13.7 Hz, 2H), 4.21–4.37 10.5 Hz, 1H), 3.86–3.97 (m, 3H including a doublet at 3.96 ppm,
(m, 2H), 7.22–7.34 (m, 10H); 13C NMR (126 MHz, CDCl3) d 14.7, J ¼ 13.3 Hz, 2H),4.10–4.38 (m, 2H), 7.02–7.58 (m, 13H), 7.87–
24.6, 25.8, 26.1, 26.7, 28.9, 41.1, 50.4, 54.8, 60.3, 63.8, 127.1, 7.96 (m, 2H); 13C NMR (100 MHz, CDCl3) d 14.5, 15.8, 40.4, 55.3,
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60.3, 63.4, 60.4, 62.7, 126.9, 127.9, 128.2, 128.5, 128.8, 138.2, 128.2, 128.3, 128.7, 129.0, 132.8, 139.4, 141.2, 177.7, 202.1; IR
136.2, 138.9, 171.7, 203.3.
(neat) 2949, 1729, 1678, 1451, 1268, 1145, 970, 745, 700 cmꢀ1
;
Anti-3b. 1H NMR (500 MHz, CDCl3) d 1.08 (d, J ¼ 6.4 Hz, 3H), HRMS (EI) calcd for C26H26NO2 (M-CH3O)+ 384.1958, found
1.39 (t, J ¼ 7.1 Hz, 3H), 3.34 (d, J ¼ 13.8 Hz, 2H), 3.86–3.94 (m, 384.1961.
3H), 4.10–4.38 (m, 3H), 7.02–7.58 (m, 13H), 7.87–7.96 (m, 2H);
13C NMR (126 MHz, CDCl3) d 14.7, 15.4, 39.5, 55.5, 60.2, 65.5,
Ethyl 3-(dibenzylamino)-2,2-dimethyl-4-oxo-4-
phenylbutanoate 8b
127.2, 128.1, 128.3, 128.7, 129.2, 132.9, 137.3, 138.5, 170.4,
201.0.
Yield 82% (35.1 mg); white solid; mp ¼ 65ꢀ67 ꢁC; Rf ¼ 0.41
(nhexane : ethyl acetate ¼ 5 : 1); 1H NMR (400 MHz, CDCl3)
Synthesis of (E)-N,N-dibenzyl-2-[(tert-butyldimethylsilyl)oxy]-
2-phenylethen-1-amine 5
d 1.06 (t, J ¼ 7.3 Hz, 3H), 1.08 (s, 3H), 1.46 (s, 3H), 3.26 (d, J ¼
14.2 Hz, 2H), 3.90 (dq, J ¼ 7.3, 10.5 Hz, 1H), 3.97–4.05 (m, 3H,
Under an argon atmosphere, to a solution of 2-(dibenzylamino)-
including doublet at 4.01 ppm J ¼ 14.2 Hz, 2H), 4.67 (s, 1H),
1-phenylethanone 7 (4.00 g, 12.7 mmol) in CH2Cl2 (19.0 mL)
7.22–7.35 (m, 10H), 7.52–7.56 (m, 2H), 7.59–7.64 (m, 1H), 7.88–
7.90 (m, 2H); 13C NMR (100 MHz, CDCl3) d 13.9, 21.3, 25.9, 46.5,
56.8, 60.5, 64.4, 127.2, 128.2, 128.4, 128.6, 129.0, 132.8, 139.4,
were successively added triethylamine (3.54 mL, 25.4 mmol)
and TBSOTf (3.50 mL, 15.2 mmol) at 0 ꢁC. The reaction mixture
was allowed to warm to ambient temperature with stirring for
141.3, 177.3, 202.2; IR (neat): 3061, 3028, 2980, 2842, 1735, 1675,
1455, 1274, 1152, 968, 748, 699 cmꢀ1; HRMS (EI) calcd for
21 h. It was quenched with sat. aq. NaHCO3 (20 mL). The layers
C
26H26NO2 (M–C2H5O)+ 384.1958, found 384.1957.
were separated, and the aqueous layer was extracted with
CH2Cl2 (30 mL ꢂ 3). The combined extracts were washed with
brine (20 mL), dried over anhydrous Na2SO4, and concentrated
in vacuo. The crude product was puried by column chroma-
tography on silica gel (nhexane : AcOEt : Et3N ¼ 20 : 1 : 1.1) to
Isopropyl 3-(dibenzylamino)-2,2-dimethyl-4-oxo-4-
phenylbutanoate 8c
ꢁ
give the title amino silyl enol ether 5 (89%, 4.84 g, E : Z ¼ Yield 73% (32.6 mg); white solid mp ¼ 112ꢀ113 C; Rf ¼ 0.55
89 : 11).
(nhexane : ethyl acetate ¼ 5 : 1); 1H NMR (400 MHz, CDCl3)
ꢁ
Yield 89% (4.84 g); yellow solid; mp ¼ 55–56 C; Rf ¼ 0.75 d 1.01 (d, J ¼ 6.4 Hz, 3H), 1.02 (s, 3H), 1.08 (d, J ¼ 6.4 Hz, 3H),
(nhexane : ethyl acetate ¼ 5 : 1); 1H NMR (400 MHz, CDCl3): 1.49 (s, 3H), 3.26 (d, J ¼ 14.2 Hz, 2H), 4.00 (d, J ¼ 14.2 Hz, 2H),
d 0.15 (s, 6H), 1.11 (s, 9H), 4.33 (s, 4H), 5.82 (s, 1H), 7.32–7.45 4.64 (s, 1H), 4.84 (sept, J ¼ 6.4 Hz, 1H), 7.22–7.36 (m, 10H), 7.52–
(m, 15H); 13C NMR (100 MHz, CDCl3): d ꢀ3.9, 18.3, 26.0, 55.8, 7.56 (m, 2H), 7.60–7.64 (m, 1H), 7.88–7.91 (m, 2H); 13C NMR
123.4, 124.5, 125.5, 126.9, 127.9, 128.2, 128.7, 133.1, 139.0, (100 MHz, CDCl3) d 20.7, 21.3, 21.6, 26.5, 46.4, 56.8, 64.5, 67.8,
140.4; IR (neat): 3059, 3031, 2926, 2854, 1649, 1453, 1349, 1257, 127.2, 128.2, 128.4, 128.6, 129.0, 132.7, 139.4, 141.4, 176.9,
1162, 1058, 1024, 923, 749, 703 cmꢀ1. HRMS (EI) calcd for 202.3; IR (neat): 3063, 3030, 2981, 2855, 1711, 1676, 1455, 1281,
C
28H35NOSi (M)+ 429.2488, found 429.2500.
1165, 1107, 970, 749, 694 cmꢀ1; HRMS (EI): calcd for C26H26NO2
(M-C3H7O)+ 384.1958, found 384.1957.
Synthesis of methyl 3-(dibenzylamino)-2,2-dimethyl-4-oxo-4-
phenylbutanoate 8a (general procedure for the reaction of the
amino silyl enol ether with ketene silyl acetals)
tert-Butyl 3-(dibenzylamino)-2,2-dimethyl-4-oxo-4-
phenylbutanoate 8d
ꢁ
Under an argon atmosphere, to N-bromosuccinimide (19.6 mg,
0.11 mmol) were successively added a solution of the amino silyl
enol ether 5 (42.9 mg, 0.10 mmol) in EtCN (1.0 mL), BF3$Et2O
(0.025 mL, 0.20 mmol), and a solution of [(1-methoxy-2-
methylprop-1-en-1-yl)oxy]trimethylsilane (26.1 mg, 0.10 mmol)
in EtCN (1.0 mL) at room temperature. The reaction mixture
was stirred for 16 h. It was quenched with sat. aq. NaHCO3 (10
mL). The layers were separated, and the aqueous layer was
extracted with ethyl acetate (30 mL ꢂ 3). The combined organic
extracts were washed with brine (5 mL), dried over anhydrous
Na2SO4, and concentrated in vacuo. The crude product was
puried by preparative TLC on silica gel (developed twice with
nhexane : AcOEt ¼ 6 : 1) to give methyl 3-(dibenzylamino)-2,2-
dimethyl-4-oxo-4-phenylbutanoate 8a (80%, 33.4 mg).
Yield 57% (26.3 mg); white solid; mp ¼ 115ꢀ117 C; Rf ¼ 0.58
(nhexane : ethyl acetate ¼ 5 : 1); 1H NMR (400 MHz, CDCl3)
d 0.98 (s, 3H), 1.27 (s, 9H), 1.47 (s, 3H), 3.28 (d, J ¼ 14.2 Hz, 2H),
3.98 (d, J ¼ 14.2 Hz, 2H), 4.62 (s, 1H), 7.22–7.37 (m, 10H), 7.51–
7.56 (m, 2H), 7.59–7.63 (m, 1H), 7.88–7.90 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 20.6, 26.8, 27.8, 46.9, 56.7, 64.6, 80.5, 127.2,
128.2, 128.5, 128.6, 129.0, 132.6, 139.4, 141.5, 176.6, 202.4; IR
(neat): 2976, 1678, 1456, 1247, 1146, 968, 848, 698 cmꢀ1; HRMS
(EI) calcd for C30H35NO3 (M)+ 457.2617, found 457.2607.
Methyl 3-(dibenzylamino)-2,2-dimethoxy-4-oxo-4-
phenylbutanoate 8e
Yield 73% (32.6 mg); colorless oil; Rf ¼ 0.38 (nhexane : ethyl
Yield 80% (33.4 mg); white solid; mp ¼ 73ꢀ74 ꢁC; Rf ¼ 0.48 acetate ¼ 5 : 1); 1H NMR (400 MHz, CDCl3) d 3.17 (s, 3H), 3.27 (s,
(nhexane : ethyl acetate ¼ 5 : 1); 1H NMR (400 MHz, CDCl3) 3H), 3.65 (d, J ¼ 13.7 Hz, 2H), 3.71 (s, 3H), 4.26 (d, J ¼ 13.7 Hz,
d 1.11 (s, 3H), 1.44 (s, 3H), 3.26 (d, J ¼ 14.4 Hz, 2H), 3.49 (s, 3H), 2H), 4.92 (s, 1H), 7.17–7.28 (m, 10H), 7.39–7.43 (m, 2H), 7.53–
4.01 (d, J ¼ 14.4 Hz, 2H), 4.68 (s, 1H), 7.23–7.37 (m, 10H), 7.52– 7.57 (m, 1H), 7.76–7.79 (m, 2H); 13C NMR (100 MHz, CDCl3)
7.57 (m, 2H), 7.60–7.65 (m, 1H), 7.87–7.90 (m, 2H); 13C NMR d 51.0, 51.2, 52.5, 55.5, 63.4, 103.8, 127.0, 128.0, 128.2, 128.8,
(100 MHz, CDCl3): d 21.6, 25.6, 46.6, 51.8, 56.9, 64.4, 127.2, 129.4, 132.9, 139.1, 139.6, 168.4, 200.9; IR (neat) 2950, 2821,
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1757, 1681, 1547, 1214, 1073, 749, 696 cmꢀ1; HRMS (EI) calcd 128.2, 129.1, 130.6, 132.5, 137.0, 140.6, 141.4, 201.7; IR (neat)
for C27H29NO5 (M)+ 447.2046, found 447.2047.
3060, 3026, 2948, 2868, 1685, 1494, 1449, 1165, 1144, 1074, 967,
882, 746, 696, 664 cmꢀ1; HRMS (EI) calcd for C39H46N2OSi (M)+
586.3380, found 586.3379.
Ethyl 3-(dibenzylamino)-2,2-diethoxy-4-oxo-4-
phenylbutanoate 2–8f
Yield 70% (34.1 mg); white solid mp ¼ 84ꢀ85 ꢁC; Rf ¼ 0.46
2-(Dibenzylamino)-2-[5-nitro-1-(triisopropylsilyl)-1H-indol-3-
yl]-1-phenylethan-1-one 9b
1
(nhexane : ethyl acetate ¼ 5 : 1); d H NMR (400 MHz, CDCl3):
d 1.06 (t, J ¼ 6.9 Hz, 6H), 1.20 (t, J ¼ 7.3 Hz, 3H), 3.30–3.40 (m,
2H), 3.48 (dq, J ¼ 6.9, 9.1 Hz, 1H), 3.61 (dq, J ¼ 6.9, 9.1 Hz, 1H),
3.72 (d, J ¼ 13.7 Hz, 2H), 4.05 (dq, J ¼ 7.3, 10.5 Hz, 1H), 4.23–
4.32 (m, 3H, including doublet at 4.27 ppm J ¼ 13.7 Hz, 2H),
4.89 (s, 1H), 7.20–7.27 (m, 10H), 7.35–7.39 (m, 2H), 7.49–7.53
(m, 1H), 7.72–7.74 (m, 2H); 13C NMR (100 MHz, CDCl3) d 13.9,
14.8, 15.1, 55.5, 58.9, 59.2, 61.5, 64.7, 103.0, 126.8, 127.8, 127.9,
128.8, 129.5, 132.4, 139.5, 139.9, 168.2, 201.5; IR (neat) 2979,
1750, 1682, 1559, 1452, 1249, 1122, 1062, 748, 696 cmꢀ1; HRMS
(EI) calcd for C28H30NO4 (M–C2H5O)+ 444.2169, found 444.2170.
Yield 13% (15.9 mg); yellow oil; Rf ¼ 0.43 (nhexane : ethyl
acetate ¼ 6 : 1); 1H NMR (400 MHz, CDCl3) d 0.92–1.00 (m, 18H),
1.49–1.60 (m, 3H), 3.96 (dd, J ¼ 13.8, 29.1 Hz, 4H), 5.80 (s, 1H),
7.04–8.65 (m, 19H); 13C NMR (100 MHz, CDCl3) d 12.5, 17.7,
17.8, 54.8, 59.0, 113.7, 115.5, 116.8, 117.6, 127.1, 128.1, 128.4,
128.5, 129.1, 130.3, 133.0, 135.2, 136.9, 140.0, 141.9, 144.5,
201.2; IR (neat) 3064, 3025, 2945, 2866, 1683, 1508, 1447, 1338,
1264, 1206, 1136, 970, 808, 688, 659 cmꢀ1; HRMS (EI) calcd for
C
30H39N3O3Si (M)+ 631.3230, found 631.3239.
2-(Dibenzylamino)-2-[5-methoxy-1-(triisopropylsilyl)-1H-indol-
3-yl]-1-phenylethanone 9c
S-tert-Butyl 3-(dibenzylamino)-4-oxo-4-phenylbutanethioate 8g
Yield 63% (30.0 mg); colorless oil; Rf ¼ 0.64 (nhexane : ethyl
1
Yield 67% (82.7 mg); yellow oil; Rf ¼ 0.55 (nhexane : ethyl
acetate ¼ 6 : 1); 1H NMR (400 MHz, CDCl3) d 0.92 (d, J ¼ 7.6 Hz,
9H), 0.96 (d, J ¼ 7.6 Hz, 9H), 1.50 (sept, J ¼ 7.6 Hz, 3H), 3.89 (s,
3H), 3.99 (s, 4H), 5.73 (s, 1H), 6.80–6.83 (m, 2H), 7.05–7.07 (m,
1H), 7.18–7.33 (m, 13H), 7.38–7.40 (m, 1H), 7.68–7.70 (m, 2H);
13C NMR (100 MHz, CDCl3) d 12.5, 17.8, 17.9, 54.7, 55.7, 60.0,
99.9, 100.9, 112.3, 113.1, 114.7, 126.8, 128.1, 128.3, 129.3, 131.1,
132.5, 133.0, 136.2, 137.1, 140.9, 154.2, 202.0; IR (neat) 3061,
3027, 2950, 2867, 1674, 1618, 1485, 1447, 1216, 1038, 1019, 884,
794, 744, 693, 660, 583 cmꢀ1; HRMS (EI) calcd for C40H48N2O2Si
(M)+ 616.3485, found 616.3482.
acetate ¼ 5 : 1); H NMR (400 MHz, CDCl3) d 1.45 (s, 9H), 2.97
(dd, J ¼ 3.6, 15.5 Hz, 1H), 3.30 (dd, J ¼ 8.7, 15.5 Hz, 1H), 3.46 (d,
J ¼ 13.3 Hz, 2H), 3.66 (d, J ¼ 13.3 Hz, 2H), 4.83 (dd, J ¼ 3.6,
8.7 Hz, 1H), 7.10–7.13 (m, 4H), 7.23–7.32 (m, 8H), 7.47–7.50 (m,
1H), 7.51–7.56 (m, 2H); 13C NMR (100 MHz, CDCl3) d 29.8, 38.3,
48.2, 54.5, 59.0, 127.3, 128.1, 128.2, 129.0, 129.3, 132.7, 136.4,
138.5, 198.6, 198.9; IR (neat) 3061, 3028, 2980, 2842, 1735, 1675,
1455, 1274, 1152, 968, 748, 699 cmꢀ1; HRMS (EI) calcd for
C
28H31NO2S (M)+ 445.2076, found 445.2077.
Synthesis of 2-(dibenzylamino)-1-phenyl-2-[1-
(triisopropylsilyl)-1H-indol-3-yl]ethenone 9a (general
procedure for the reaction of the amino silyl enol ether with
indoles)
2-[5-Bromo-1-(triisopropylsilyl)-1H-indol-3-yl]-2-
(dibenzylamino)-1-phenylethan-1-one 9d
Under an argon atmosphere, to a solution of N-bromosuccini-
mide (39.2 mg, 0.22 mmol) in EtCN (1.0 mL) were successively
added a solution of the amino silyl enol ether 5 (85.9 mg, 0.20
mmol) in EtCN (1.0 mL), BF3$Et2O (0.025 mL, 0.20 mmol), and
a solution of 1-(triisopropylsilyl)-1H-indole (43.1 mg, 0.22
mmol) in EtCN at 0 ꢁC. The reaction mixture was allowed to
warm to ambient temperature with stirring for 5 h. It was
quenched with sat. aq. NaHCO3 (10 mL). The layers were
separated, and the aqueous layer was extracted with ethyl
acetate (30 mL ꢂ 3). The combined organic extracts were
washed with brine, dried over anhydrous Na2SO4, and concen-
trated in vacuo. The crude product was puried by preparative
TLC on silica gel (developed twice with nhexane : AcOEt ¼ 6 : 1)
to give 2-(dibenzylamino)-1-phenyl-2-[1-(triisopropylsilyl)-1H-
indol-3-yl]ethanone 9a (77%, 90.7 mg).
Yield 75% (100.0 mg); yellow oil; Rf ¼ 0.63 (nhexane : ethyl
acetate ¼ 6 : 1); 1H NMR (400 MHz, CDCl3) d 0.94–0.99 (m, 18H),
1.53 (q, J ¼ 7.6 Hz, 3H), 3.97 (dd, J ¼ 13.6, 32.2 Hz, 4H), 5.71 (s,
1H), 6.92 (s, 1H), 7.15–7.48 (m, 16H), 7.68–7.79 (m, 2H); 13C
NMR (100 MHz, CDCl3) d 12.6, 17.9, 18.0, 54.8, 59.5, 113.0,
113.5, 115.4, 122.4, 124.9, 127.1, 128.2, 128.3, 128.5, 129.3,
132.6, 132.8, 133.6, 137.0, 140.1, 140.5, 201.5; IR (neat) 3061,
3026, 2947, 2867, 1688, 1597, 1495, 1445, 1199, 1159, 1135, 967,
881, 795, 750, 718, 701, 689, 653, 567 cmꢀ1; HRMS (EI) calcd for
C
30H39N2OSiBr (M)+ 664.2485, found 664.2452.
2-[6-Bromo-1-(triisopropylsilyl)-1H-indol-3-yl]-2-
(dibenzylamino)-1-phenylethan-1-one 9e
Yield 73% (97.0 mg); yellow oil; Rf ¼ 0.62 (nhexane : ethyl
Yield 77% (90.7 mg); yellow oil; Rf ¼ 0.61 (nhexane : ethyl acetate ¼ 6 : 1); 1H NMR (400 MHz, CDCl3) d 0.88–1.09 (m, 18H),
acetate ¼ 6 : 1); 1H NMR (400 MHz, CDCl3) d 0.95 (d, J ¼ 7.3 Hz, 1.47–1.59 (m, 3H), 3.96 (dd, J ¼ 13.7, 34.8 Hz, 4H), 5.73 (s, 1H),
9H), 0.99 (d, J ¼ 7.3 Hz, 9H), 1.55 (sept, J ¼ 7.3 Hz, 3H), 3.94 (d, J 6.84–7.68 (m, 18H); 13C NMR (100 MHz, CDCl3) d 3047, 2948,
¼ 13.7 Hz, 2H), 4.02 (d, J ¼ 13.7 Hz, 2H), 5.78 (s, 1H), 6.91 (s, 2868, 1686, 1599, 1456, 1151, 1073, 967, 883, 814, 750, 695, 599;
1H), 7.16–7.30 (m, 14H), 7.34–7.37 (m, 1H), 7.44–7.46 (m, 1H), IR (neat) 3047, 2948, 2868, 1686, 1599, 1456, 1151, 1073, 967,
7.65–7.68 (m, 3H); 13C NMR (100 MHz, CDCl3) d 12.6, 17.8, 17.9, 883, 814, 750, 695, 599 cmꢀ1; HRMS (EI) calcd for C30H39N2-
54.8, 59.8, 113.0, 113.9, 119.5, 119.9, 121.9, 126.7, 128.0, 128.1, OSiBr (M)+ 664.2485, found 664.2488.
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7.67 (m, 2H); 13C NMR (100 MHz, CDCl3) d 20.3, 20.4, 27.8, 54.3,
65.4, 126.9, 128.1, 128.2, 128.5, 128.6, 133.0, 139.6, 139.9, 203.1;
IR (neat): 3059, 3032, 2979, 2950, 2840, 1668, 1494, 1444, 1218,
1093, 976, 839, 737, 730, 699 cmꢀ1; HRMS (EI) calcd for
Synthesis of methyl 2-(dibenzylamino)-1-phenylbutan-1-one
10b (general procedure for the reaction of the amino silyl enol
ether with grignard reagents)
Under an argon atmosphere, to a solution of N-bromosuccini-
mide (19.6 mg, 0.11 mmol) in EtCN (1.0 mL) were successively
added a solution of amino silyl enol ether 5 (42.9 mg, 0.10
mmol) in EtCN (1.0 mL), BF3$OEt2 (0.025 mL, 0.20 mmol), and
a solution of EtMgBr in Et2O (0.93 M, 0.22 mL, 0.20 mmol) at
room temperature. The reaction mixture was stirred for 30 min.
It was quenched with sat. aq. NH4Cl (10 mL). The layers were
separated, and the aqueous layer was extracted with ethyl
acetate (30 mL ꢂ 3). The combined organic extracts were
washed with brine, dried over anhydrous Na2SO4, and concen-
trated in vacuo. The crude product was puried by preparative
TLC on silica gel (developed twice with nhexane : AcOEt ¼
15 : 1) to give 2-(dibenzylamino)-1-phenylbutan-1-one 10b
(74%, 25.5 mg).
C
19H22NO (M–C6H5)+ 252.1747, found 252.1741.
2-Cyclopropyl-2-(dibenzylamino)-1-phenylethanone 10e
Yield 35% (12.4 mg); colorless oil; Rf ¼ 0.64 (nhexane : ethyl
1
acetate ¼ 6 : 1); H NMR (400 MHz, CDCl3) d ꢀ0.02–0.04 (m,
1H), 0.51–0.58 (m, 2H), 0.75–0.84 (m, 1H), 1.28–1.37 (m, 1H),
3.45 (d, J ¼ 9.6 Hz, 1H), 3.79 (d, J ¼ 13.8 Hz, 2H), 3.94 (d, J ¼
13.8 Hz, 2H), 7.20–7.36 (m, 12H), 7.50–7.61 (m, 3H); 13C NMR
(100 MHz, CDCl3) d 2.9, 5.3, 8.5, 54.7, 66.7, 127.0, 128.1, 128.2,
128.6, 129.0, 132.7, 137.5, 139.8, 201.7; IR (neat) 3081, 3027,
2927, 2840, 1681, 1597, 1495, 1450, 1220, 744, 696 cmꢀ1; HRMS
(EI) calcd for C19H20NO (M–C6H5)+ 250.1590, found 250.1591.
Yield 74% (25.5 mg); colorless oil; Rf ¼ 0.63 (nhexane : ethyl
acetate ¼ 6 : 1); 1H NMR (400 MHz, CDCl3) d 0.93 (t, J ¼ 7.3 Hz,
3H), 1.80–1.89 (m, 1H), 1.93–2.02 (m, 1H), 3.69 (s, 4H), 4.14 (dd,
J ¼ 4.9, 8.5 Hz, 1H), 7.20–7.34 (m, 12H), 7.48–7.52 (m, 1H), 7.56–
7.58 (m, 2H); 13C NMR (100 MHz, CDCl3): d 11.5, 17.8, 54.3, 62.6,
127.0, 128.2, 128.2, 128.5, 129.1, 132.6, 137.7, 139.6, 201.4; IR
(neat): 3062, 3026, 2978, 2936, 2835, 1684, 1494, 1448, 1378,
1225, 1143, 936, 749, 732, 695 cmꢀ1; HRMS (EI) calcd for
2-Cyclohexyl-2-(dibenzylamino)-1-phenylethanone 10f
ꢁ
Yield 60% (23.9 mg); colorless solid, mp ¼ 88–89 C; Rf ¼ 0.65
(nhexane : ethyl acetate ¼ 6 : 1); 1H NMR (500 MHz, CDCl3)
d 0.76–0.84 (m, 1H), 1.04–1.37 (m, 5H), 1.54–1.56 (m, 1H), 1.63–
1.66 (m, 1H), 1.79–1.83 (m, 1H), 2.09–2.17 (m, 1H), 2.42–2.45
(m, 1H), 3.36 (d, J ¼ 14.7 Hz, 2H), 4.05 (d, J ¼ 14.7 Hz, 2H), 4.16
(d, J ¼ 10.4 Hz, 1H), 7.22–7.39 (m, 12H), 7.52–7.55 (m, 1H), 7.63–
7.65 (m, 2H); 13C NMR (126 MHz, CDCl3) d 26.0, 26.1, 26.6, 30.4,
31.0, 37.4, 54.3, 64.2, 126.8, 128.1, 128.2, 128.5, 128.6, 133.0,
139.6, 139.9, 203.4; IR (neat) 3061, 3028, 2926, 2850, 1675, 1494,
1446, 1234, 1201, 907, 844, 735, 698 cmꢀ1; HRMS (EI): calcd for
C
18H20NO (M–C6H5)+ 238.1590, found 238.1589.
2-(Dibenzylamino)-1-phenylpropan-1-one 10a
Yield 64% (22.2 mg); colorless oil; Rf ¼ 0.63 (nhexane : ethyl
acetate ¼ 6 : 1); 1H NMR (400 MHz, CDCl3) d 1.34 (d, J ¼ 6.6 Hz,
3H), 3.54 (d, J ¼ 13.5 Hz, 2H), 3.68 (d, J ¼ 13.5 Hz, 2H), 4.34 (q, J
¼ 6.6 Hz, 1H), 7.15–7.34 (m, 12H), 7.48–7.52 (m, 1H), 7.58–7.61
(m, 2H); 13C NMR (100 MHz, CDCl3) d 8.4, 54.3, 57.2, 127.1,
128.0, 128.2, 128.8, 129.2, 132.5, 136.9, 139.3, 202.0; IR (neat)
3062, 3026, 2978, 2936, 2835, 1684, 1494, 1448, 1378, 1225,
1143, 936, 749, 732, 695 cmꢀ1; HRMS (EI) calcd for C17H18NO
(M–C6H5)+ 224.1434, found 224.1438.
C
22H26NO (M–C6H5)+ 292.2060, found 292.2056.
2-(Dibenzylamino)-1,3-diphenylpropan-1-one 10g
Yield 43% (17.4 mg); white solid mp ¼ 84–85 ꢁC; Rf ¼ 0.61
(nhexane : ethyl acetate ¼ 6 : 1); 1H NMR (400 MHz, CDCl3):
d 3.12 (dd, J ¼ 4.3, 13.4 Hz, 1H), 3.36 (dd, J ¼ 9.2, 13.4 Hz, 1H),
3.71 (d, J ¼ 13.4 Hz, 2H), 3.78 (d, J ¼ 13.4 Hz, 2H), 4.54 (dd, J ¼
4.3, 9.2 Hz, 1H), 7.12–7.14 (m, 5H), 7.18–7.27 (m, 12H), 7.43–
7.47 (m, 3H); 13C NMR (100 MHz, CDCl3) d 30.2, 54.3, 62.9,
126.0, 127.2, 128.1, 128.2, 128.3, 128.6, 129.2, 129.5, 132.6,
137.3, 139.1, 139.2, 199.7; IR (neat) 3060, 3025, 2931, 2815, 1688,
2-(Dibenzylamino)-1-phenylpentan-1-one 10c
Yield 71% (25.4 mg); colorless oil; Rf ¼ 0.64 (nhexane : ethyl
acetate ¼ 6 : 1); 1H NMR (400 MHz, CDCl3) d 0.92 (t, J ¼ 7.3 Hz,
3H), 1.29–1.39 (m, 2H), 1.74–1.82 (m, 1H), 1.88–1.97 (m, 1H),
3.70 (s, 4H), 4.24 (dd, J ¼ 5.5, 8.7 Hz, 1H), 7.21–7.34 (m, 12H),
7.48–7.58 (m, 3H). 13C NMR (100 MHz, CDCl3): d 14.2, 20.1, 27.0,
54.3, 60.5, 127.0, 128.2, 128.2, 128.5, 129.1, 132.6, 137.5, 139.7,
201.7. IR (neat): 3061, 3028, 2957, 2832, 1684, 1494, 1447, 1373,
1245, 1209, 1072, 947, 751, 695 cmꢀ1. HRMS (EI): calcd for
1600, 1494, 1455, 1233, 1116, 1072, 1027, 957, 750, 700 cmꢀ1
;
HRMS (EI) calcd for C23H22NO (M–C6H5)+ 300.1747, found
300.1761.
2-(Dibenzylamino)-1-phenyl-2-p-tolylethanone 10i
ꢁ
Yield 46% (18.7 mg); yellow solid, mp ¼ 112–113 C; Rf ¼ 0.62
C
19H22NO (M–C6H5)+ 252.1747, found 252.1753.
(nhexane : ethyl acetate ¼ 6 : 1); 1H NMR (400 MHz, CDCl3)
d 2.30 (s, 3H), 3.75 (d, J ¼ 13.7 Hz, 2H), 3.96 (d, J ¼ 13.7 Hz, 2H),
5.43 (s, 1H), 7.11–7.31 (m, 16H), 7.42–7.44 (m, 1H), 7.67–7.69
2-(Dibenzylamino)-3-methyl-1-phenylbutan-1-one 10d
Yield 63% (22.5 mg); colorless oil; Rf ¼ 0.63 (nhexane : ethyl (m, 2H); 13C NMR (100 MHz, CDCl3) d 21.1, 54.4, 66.5, 126.9,
acetate ¼ 6 : 1); 1H NMR (400 MHz, CDCl3) d 0.75 (d, J ¼ 6.7 Hz, 128.2, 128.3, 128.4, 128.9, 129.2, 129.9, 132.8, 133.3, 136.9,
3H), 1.24 (d, J ¼ 6.7 Hz, 3H), 2.35–2.46 (m, 1H), 3.34 (d, J ¼ 137.5, 140.1, 201.7; IR (neat): 3059, 3026, 2922, 2844, 1689, 1595,
14.7 Hz, 2H), 4.02 (d, J ¼ 10.4 Hz, 1H), 4.04 (d, J ¼ 14.7 Hz, 2H), 1494, 1447, 1226, 1138, 961, 804, 747, 700 cmꢀ1; HRMS (EI):
7.21–7.29 (m, 10H), 7.37–7.40 (m, 2H), 7.54–7.57 (m, 1H), 7.65– calcd for C23H22NO (M–C6H5)+ 300.1747, found 300.1744.
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¨
M. Sodelgren and M. Scobie, Tetrahedron Lett., 2002, 43,
5969–5970; (g) H. Jourdan, G. Gouhier, L. V. Hije,
P. Angibaud and S. R. Piettre, Tetrahedron Lett., 2005, 46,
2-(Dibenzylamino)-1-phenyl-2-(thiophen-2-yl)ethanone 10j
Yield 64% (25.5 mg); colorless solid, mp ¼ 108ꢀ109 ꢁC; Rf ¼
0.64 (nhexane : ethyl acetate ¼ 6 : 1); 1H NMR (400 MHz, CDCl3)
d 3.67 (d, J ¼ 13.7 Hz, 2H), 3.91 (d, J ¼ 13.7 Hz, 2H), 5.69 (s, 1H),
6.90–6.92 (m, 1H), 6.96–6.99 (m, 1H), 7.23–7.37 (m, 13H), 7.48–
7.52 (m, 1H), 7.67–7.69 (m, 2H); 13C NMR (100 MHz, CDCl3)
d 54.5, 61.3, 126.3, 126.5, 127.1, 128.3, 128.4, 128.6, 129.0, 133.1,
136.5, 137.5, 139.4, 198.9. IR (neat): 3061, 3027, 2928, 2840,
1685, 1595, 1494, 1447, 1214, 957, 750, 699 cmꢀ1; HRMS (EI)
calcd for C20H18NOS (M–C6H5)+ 292.1154, found 292.1140.
8027–8031; (h) T. J. Southwood, M.
C Curry and
C. A. Hutton, Tetrahedron, 2006, 62, 236–242. For
asymmetric Petasis reaction: ; (i) S. Lou and S. E. Schaus, J.
Am. Chem. Soc., 2008, 130, 6922–6923.
4 (a) Y. Niwa and M. Shimizu, J. Am. Chem. Soc., 2003, 125,
3720–3721; (b) M. Shimizu, H. Itou and M. Miura, J. Am.
Chem. Soc., 2005, 127, 3296–3297; (c) T. Iwao and
M. Shimizu, Heterocycles, 2009, 77, 767–772; (d)
M. Shimizu, H. Itou, T. Iwao and Y. Umeda, Chem. Lett.,
2009, 38, 732–733; (e) M. Shimizu, I. Hachiya and I. Mizota,
Chem. Commun., 2009, 874–889; (f) S. Hata, H. Koyama and
M. Shimizu, J. Org. Chem., 2011, 76, 9670–9677; (g)
M. Shimizu, T. Kusunoki, M. Yoshida, K. Kondo and
I. Mizota, Chem. Lett., 2011, 40, 351–353; (h) I. Mizota and
M. Shimizu, Chem. Rec., 2016, 16, 688–702; (i) M. Shimizu,
H. Imazato, I. Mizota and Y. Zhu, RSC Adv., 2019, 9, 17341–
17346; (j) M. Shimizu, M. Mushika, I. Mizota and Y. Zhu,
RSC Adv., 2019, 9, 23400–23407; (k) M. Shimizu,
Y. Furukawa, I. Mizota and Y. Zhu, New J. Chem., 2020, 44,
152–161; (l) M. Shimizu, T. Morimoto, Y. Yanagi, I. Mizota
and Y. Zhu, RSC Adv., 2020, 10, 9955–9963.
Conflicts of interest
There are no conicts to declare.
Acknowledgements
This work was supported by Grants-in-Aid for Scientic
Research (B) and on Innovative Areas “Organic Synthesis Based
on Reaction Integration. Development of New Methods and
Creation of New Substances” from JSPS and MEXT.
Notes and references
5 We have already reported the formation of the iminium salt
by 1H and 13C NMR spectra and a possible ionic mechanism
by the ineffectiveness of radical scavengers.4b
1 For iminium ion cyclization, see: (a) E. J. Corey and
R. D. Balanson, J. Am. Chem. Soc., 1974, 96, 6516–6517; (b)
S. Yamada, M. Konda and T. Shioiri, Tetrahedron Lett.,
1972, 13, 2215–2218. For N-acyl iminium ion cyclization,
see; (c) J. Dijkink, H. E. Shoemeker and W. N. Speckamp,
Tetrahedron Lett., 1975, 16, 4043–4046; (d) J. Dijkink and
W. N. Speckamp, Tetrahedron Lett., 1975, 16, 4047–4050.
2 (a) H. H. Mooiweer, H. Hiemstra and W. N. Speckamp,
Tetrahedron, 1989, 45, 4627–4636; (b) H. H. Mooiweer,
E. C. Roots, H. Hiemstra and W. N. Speckamp, J. Org.
Chem., 1992, 57, 6769–6778; (c) M. Okuda, H. Hioki,
W. Miyagi and S. Ito, Tetrahedron Lett., 1993, 34, 6131–
6134; (d) J. Yoshida, S. Suga and M. Okajima, Tetrahedron
Lett., 2001, 42, 2173–2176; (e) J. Yoshida, S. Suga and
M. Watanabe, J. Am. Chem. Soc., 2002, 124, 14824–14825;
(f) P. Knochel, N. Millot, C. Piazza and S. Avolio, Synthesis,
2002, 941–944; (g) L. W. Bieber and I. H. S. Estevam,
Tetrahedron Lett., 2003, 44, 667–670; (h) M. Suginome,
L. Uehlin and M. Murakami, Org. Lett., 2004, 6, 1167–1169;
(i) T. Murai, Y. Mutoh, Y. Ohta and M. Murakami, J. Am.
Chem. Soc., 2004, 126, 5968–5969; (j) M. Suginome,
L. Uehlin and M. Murakami, J. Am. Chem. Soc., 2004, 126,
13196–13197.
6 Effects of the silyl substituents on the reactivity of silyl enol
ethers, see: (a) I. Kuwajima and E. Nakamura, Acc. Chem.
Res., 1985, 18, 181–187; (b) M. B. Boxer and H. Yamamoto,
J. Am. Chem. Soc., 2006, 128, 48–49; (c) M. Akakura,
M. B. Boxer and H. Yamamoto, ARKIVOC, 2007, 337–347.
7 For the diastereoselecitivity of the Mannich reaction, see: (a)
A. Ting and S. E. Schaus, Eur. J. Org. Chem., 2007, 5797–5815;
(b) J. M. M. Verkade, L. J. C. van Hemert,
P. J. L. M. Quaedieg and F. P. J. T. Rutjes, Chem. Soc. Rev.,
2008, 37, 29–41; (c) Y. Gnas and F. Glorius, Synthesis, 2006,
¨
1899–1930; (d) B. T. Hahn, R. Frohlich, K. Harms and
F. Glorius, Angew. Chem., Int. Ed., 2008, 47, 9985–9988.
8 The reaction of enolates and enols with DDQ was reported,
see: (a) J. M. Williams, G. Marchesini, R. A. Reamer,
U.-H. Dolling and E. J. J. Grabowski, J. Org. Chem., 1995,
60, 5337–5340; (b) A. Bhattacharya, L. M. DiMichele,
U.-H. Dolling, A. W. Douglas and E. J. J. Grabowski, J. Am.
Chem. Soc., 1988, 110, 3318–3319; (c) H.-D. Becker, J. Org.
Chem., 1965, 30, 989–994.
9 (a) M. Bandini, A. Melloni, S. Tommasi and A. Umani-
Ronchi, Synlett, 2005, 1199; (b) J. C. Badenock and
G. W. Gribble, Adv. Heterocycl. Chem., 2016, 120, 99–136,
and references cited therein.
10 For determination of the relative stereochemistry, see: (a)
J. Delbos-Krampe, N. Risch and U. Florke, Z. Naturforsch.,
B: J. Chem. Sci., 2004, 59, 414–423; (b) M. Feroci, J. Lessard,
M. Orsini and A. Inesi, Tetrahedron Lett., 2005, 46, 8517–
8519.
3 For Petasis reactions including the synthesis of a-
monosubstituted amino acids, see: (a) N. A. Petasis and
I. Akritopoulou, Tetrahedron Lett., 1993, 34, 583–586; (b)
N. A. Petasis and I. A. Zavialov, J. Am. Chem. Soc., 1997,
119, 445–446; (c) N. A. Petasis, A. Goodman and
I. A. Zavialov, Tetrahedron, 1997, 53, 16463–16470; (d)
N. A. Petasis and I. A. Zavialov, J. Am. Chem. Soc., 1998,
120, 11798–11799; (e) N. A. Petasis and S. Boral,
Tetrahedron Lett., 2001, 42, 539–542; (f) T. Koolmeister,
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RSC Adv., 2020, 10, 27874–27883 | 27883