Indium-assisted aluminium-based stereoselective allylation of prostereogenic α,α-disubstituted cycloalkanones and imines

Article abstract of DOI:10.1039/c4ra04293j

The use of a catalytic amount of InCl₃in combination with Al⁰for the allylation of a variety of prostereogenic α,α-disubstituted (hindered) cycloalkanones, 1,2-dione-based systems and various imino systems (CN functional groups) is reported. The stereoselective InCl₃-catalyzed Al-based allylation of various 2-substituted-2-carbethoxycycloalkanones gave the corresponding products with moderate to excellent diastereoselectivity. The allylation and propargylation of imines including α-imino esters using a catalytic amount of InCl₃in combination with Al⁰gave the corresponding allylated and propargylated compounds in moderate to good yields. If γ-substituted allylic halides were added to imino compounds, low to very good diastereoselectivity was obtained. The allylation of chiral N-tert-butylsulfinyl imine systems gave the corresponding products in moderate yields with good to excellent diastereoselectivity. This journal is

Full text of DOI:10.1039/c4ra04293j

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Indium-assisted aluminium-based stereoselective
allylation of prostereogenic a,a-disubstituted
cycloalkanones and imines†
Cite this: RSC Adv., 2014, 4, 40199
*
Chennakesava Reddy, Srinivasarao Arulananda Babu and Nayyar Ahmad Aslam
The use of a catalytic amount of InCl3 in combination with Al0 for the allylation of a variety of prostereogenic
a,a-disubstituted (hindered) cycloalkanones, 1,2-dione-based systems and various imino systems (C]N
functional groups) is reported. The stereoselective InCl3-catalyzed Al-based allylation of various 2-
substituted-2-carbethoxycycloalkanones gave the corresponding products with moderate to excellent
diastereoselectivity. The allylation and propargylation of imines including a-imino esters using a catalytic
amount of InCl3 in combination with Al0 gave the corresponding allylated and propargylated compounds
in moderate to good yields. If g-substituted allylic halides were added to imino compounds, low to very
good diastereoselectivity was obtained. The allylation of chiral N-tert-butylsulfinyl imine systems gave
the corresponding products in moderate yields with good to excellent diastereoselectivity.
Received 8th May 2014
Accepted 6th August 2014
DOI: 10.1039/c4ra04293j
www.rsc.org/advances
preparation of allylmetal reagents is not necessary and the
allylation reaction can be achieved by directly reacting the
Introduction
carbonyl compound or imine, metal powder and allylic halide.
Notably, since the report by Araki in 1988,6a the indium-based
Barbier-type addition of allylic reagents to carbonyl (C]O)
and imino (C]N) systems frequently offered very high stereo-
selectivity and has been applied for the synthesis of a variety of
functionalized molecules containing one or more stereo-
centers.1,2,6 Generally, the stoichiometric amount of allylmetal
reagents or metals (e.g., Bi, Ga, and In, and so on) are required
for performing the Grignard or Barbier-type of allylation
reactions.1–11
Apart from using indium in organic synthesis, there has
been an increased use of indium-based materials in informa-
tion technology industries which are involved in developing
liquid crystal display (LCD) and television (TV) screens, solar
energy technology, semiconductors, and so on. Because of this
reason the cost of indium metal has increased.
In view of the previously mentioned points, there is a need
for nding alternative metals, especially, for replacement of Ga
and In, and if the In-based organic transformations can be
performed using a catalytic amount of In, then the practicality
and adaptability of In metal in organic synthesis could be
increased.12 The use of a catalytic amount of indium in
combination with other metals such as Al or Zn, and so on,
could be an alternative strategy12,13 and notably, Al metal14 is
relatively inexpensive and is considered to be less toxic when
compared to other metals such as Ga or In. In recent years, there
have been some remarkable reports demonstrating the allyla-
tion of carbonyl compounds using a catalytic amount of In0 or
In(III) salts in combination with Al or Zn or other metals.12
The addition of organometallic reagents to carbonyl (C]O) and
imino (C]N) functional groups is one of the most important
types of organometallic reactions. The addition of the allylme-
tals to carbonyl (C]O) and imino (C]N) functional groups is
considered to be an imperative C–C bond forming protocol.
This method is widely used for assembling functionalized
acyclic- or cyclic-homoallylic alcohols/amines which have one or
more stereocenters with a high degree of stereo- and regio-
control.1 Notably, the allylation step is considered to show
immense scope in multi-step synthesis, aer the allylation
reaction, the olen moiety present in the product can be sub-
jected to a wide range of functional group transformations.
A variety of allylmetal reagents prepared using metals such
as B, Ce, Cu, Li, Mg, Mn, Pb, Sn, Ti and Zn, and so on, have been
very well utilized and thoroughly documented for performing,
typically, the Grignard-type allylation of the carbonyl (C]O)
and imino (C]N) functional groups.1,2 However, in recent
years, the Barbier-type addition reaction3–5 of allylmetals
involving some of the previously mentioned metals together
with other metals6–11 such as Bi, Ga and In, and so on, to
carbonyl (C]O) and imino (C]N) functional groups has been
widely recognized. This protocol has a benet as the prior
Department of Chemical Sciences, Indian Institute of Science Education and Research
(IISER) Mohali, Manauli P.O., Sector 81, SAS Nagar, Knowledge City, Mohali, Punjab
140306, India. E-mail: sababu@iisermohali.ac.in; Fax: +91-172-2240266; Tel: +91-
172-2240266
† Electronic supplementary information (ESI) available: Copies of NMR spectra.
CCDC 1001586 and 1001554. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c4ra04293j
´
Research by Butsugan, Hirashita, Preite, Knochel, Auge, and
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 40199–40213 | 40199

View Article Online
RSC Advances
Paper
Scheme 1 Examples from literature demonstrating different methods
for the allylation of carbonyl compounds using a catalytic amount of
In0 or In(III) salts in combination with Al or Zn or other metals.
Scheme 2 Diagrammatic representation of the InCl3/Al system for the
stereoselective allylation of prostereogenic a,a-disubstituted cyclo-
alkanones and imino compounds (C]N systems).
Takai has demonstrated the allylation of carbonyl compounds
using a catalytic amount of In0 or In(III) salts in combination
with Al and other metals (Scheme 1).13
type allylation of the substrate 1a or 1b using Al0 powder in
the absence of any catalyst gave the products 3a and 4a, with
yields 65 and 20%, respectively (entries 1 and 2, Table 1).
However, the Barbier-type allylation of substrate 1a with InCl3
(40 mol%) in the absence of Al0 powder did not give any product
(entry 3, Table 1). The Barbier-type allylation of the substrates 1a
or 1b using Al0 powder (0.5–1 mmol) in the presence of a cata-
lytic amount of InCl3 or InBr3 (5 or 10 mol%) in anhydrous
tetrahydrofuran (THF) successfully gave the product 3a or 4a (dr
98 : 2, trans isomer) with a yield of 95% (entries 4–6, Table 1).
Subsequently, the Barbier-type allylation of 1b using Al0
powder (0.55 mmol) in the presence of just 2 mol% of InCl3 in
anhydrous THF gave the product 4a (dr 98 : 2, trans isomer) with
a yield of 95% (entry 7, Table 1). Furthermore, the allylation of
1b in other solvents such as DCM or DMF or MeCN gave the
product 4a (dr 98 : 2, trans isomer) with yields of 91%, <5%,
90%, respectively (entries 8–10, Table 1). The allylation of 1b
using Al0 powder in the presence of catalytic amount of InCl3 in
THF–water mixture did not give any product (entry 11, Table 1).
Then, we tried to use different catalysts instead of InCl3 for
Although Al metal belongs to the same group as In and Ga,
except in the research by Knochel et al. on the use of InCl3 in
combination with Al, the direct use of Al0 powder for the ster-
eoselective allylation of carbonyl compounds to give more than
one stereocenter has not been extensively explored using a
Barbier-type reaction.12–14 Furthermore, to the best of our
knowledge, the allylation of imino (C]N bond systems) func-
tional groups has not been reported using In in combination
with Al metal powder. Continuing our interest in exploring the
In-based stereoselective allylation of carbonyl (C]O) and imino
(C]N) functional groups, we report in this paper on our efforts
to use InCl3/Al as an economically alternative bimetallic system
for the stereoselective allylation of prostereogenic a,a-disub-
stituted cycloalkanones15,16 and various imino compounds
(C]N bond systems).17,18a,b
Results and discussion
Initially, it was envisaged that the use of a catalytic amount of the Barbier-type allylation of 1b. We found that the allylation of
InCl3 in combination with Al for the diastereofacial selective 1b using Al0 powder in the presence of a catalytic amount of
allylation of prostereogenic a,a-disubstituted (hindered) cyclo- SnCl2 or ZnCl2 or GaClO4 was ineffective (entries 12–14, Table
alkanones and the stereoselective construction of a stereoarray 1). However, the allylation of 1b progressed smoothly when we
having consecutively attached, tertiary carbinol- and an all used Al0 powder in the presence of a catalytic amount of
carbon-based stereocenter in functionalized carbocyclic In(OTf)3 or In(OAc)3 and gave the product 4a (dr 98 : 2, trans
compounds, would be investigated.15,16 We performed the isomer) with a yield of 95% (entries 15 and 16, Table 1). When
optimization reactions using the substrate 2-benzyl-2- we used BiCl3 (8 mol%) as a catalyst, the product 4a was
carbethoxycyclopentanone (1a) or 2-allyl-2-carbethoxycy- obtained with a yield of 30% (entry 17, Table 1).
clopentanone (1b), allyl bromide, Al metal powder and a catalyst
Subsequently, we carried out the Barbier-type allylation of 1a
under Barbier-type reaction conditions (Table 1). The Barbier- using Al0 powder (1 mmol) in the presence of catalytic amounts
40200 | RSC Adv., 2014, 4, 40199–40213
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Table 1 InCl3/Al-based Barbier-type allylation of substrates 1a/1b and optimization of reaction conditionsa
Entry
R
Metal0 (mmol)
Catalyst (mol%)
Solvent (mL)
Temp (ꢀC)
t (h)
Yield (%) (dr)
1
2
3
4
5
6
7
8
Benzyl
Allyl
Benzyl
Benzyl
Allyl
Benzyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Benzyl
Allyl
Allyl
Benzyl
Al (0.5)
Al (1)
Nil
Nil
Nil
THF (1.5)
THF (1.5)
THF (1.5)
THF (1.5)
THF (1.5)
THF (1.5)
THF (1.5)
DCM (1.5)
DMF (1.5)
MeCN (1.5)
THF (3)/H2O (1)
THF (1.5)
THF (1.5)
THF (1.5)
THF (1.5)
THF (1.5)
THF (1.5)
THF (1.5)
THF (1.5)
THF (1.5)
THF (1.5)
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
10
12
10
12
15
4
1
2
1.5
7
9
12
7
2
1
2
26
9
7
8
12
65 (98 : 2)
20 (N.D.)
0 (—)
95 (98 : 2)
95 (98 : 2)
95 (98 : 2)
95 (98 : 2)
91 (98 : 2)
<5 (—)
90 (98 : 2)
0 (—)
0 (—)
0 (—)
0 (—)
95 (98 : 2)
95 (98 : 2)
30 (N.D.)
95 (98 : 2)
85 (98 : 2)
40 (N.D.)
0 (—)
InCl3 (40)
InCl3 (10)
InCl3 (5)
InBr3 (10)
InCl3 (2)
InCl3 (2)
InCl3 (3.5)
InCl3 (2)
InCl3 (5)
SnCl2 (5)
ZnCl2 (20)
Ga(ClO4) (5)
In(OTf)3 (1)
In(OAc)3 (1)
BiCl3 (8)
In (10)
Al (0.5)
Al (0.5)
Al (1)
Al (0.55)
Al (0.5)
Al (0.5)
Al (0.5)
Al (0.75)
Al (1)
Al (0.75)
Al (0.55)
Al (0.55)
Al (0.55)
Al (0.55)
Al (1)
9
10
11
12
13
14
15
16
17
18
19
20
21
Al (0.5)
Al (1)
Al (1)
Bi (20)
Zn (10)
Sn (10)
a
All the reactions were carried out under Barbier-type reaction conditions. The substrate 1a or 1b was treated with allyl bromide, Al0 and a catalytic
amount of InCl3 or In0 or other catalyst in one pot. N.D. ¼ not determined; DCM ¼ dichloromethane; DMF ¼ dimethylformamide; In(OTf)3
indium(III) triuoromethanesulfonate, In(OAc)3 ¼ indium triacetate.
¼
of In0 powder (10 mol%) in anhydrous THF which gave the catalytic amount of InCl3 (1–2 mol%) and Al0 powder (0.55
product 3a (95%, dr 98 : 2, trans isomer) (entry 18, Table 1). mmol) gave the products 3j–m which had a relatively low dia-
Similarly, the allylation of the substrate 1b using Al0 powder stereoselectivity (entries 10–13, Table 2).
(0.5–1 mmol) in the presence of catalytic amounts of other
Next, the allylation of the substrate 1b with 2,3-
metals such as Bi0 or Zn0 (10–20 mol%) gave the product 4a with dibromoprop-1-ene (2c) failed to give the expected product 3n
yields of 85% and 40%, respectively (entries 19 and 20, Table 1). (entry 14). The allylation of 2-allyl-2-carbethoxycyclopentanone
The allylation of 1a using a catalytic amount of Sn0 powder (1b) and ethyl 2-acetyl-2-benzylpent-4-enoate (1o) gave the ally-
together with Al0 powder did not give the product 3a (entry 21, lated products 4a (96%, dr 98 : 2) and 3o (81%, dr 55 : 45),
Table 1).
respectively (entries 15 and 16, Table 2). Consequently, the
Next, the scope and applicability of this allylation protocol allylation of ethyl 3-allyl-1-benzyl-4-oxopiperidine-3-carboxylate
using a catalytic amount of InCl3 in combination with Al0 (1p) gave the piperidine derivative 3p with a yield of 55% (dr
powder was tested with a variety of prostereogenic a,a-disub- 60 : 40, entry 17, Table 2).
stituted (hindered) cycloalkanones and the construction of
The allylation of a relatively hindered cyclopentanone system
functionalized carbocycles having consecutively attached ethyl 1-benzhydryl-2-oxocyclopentanecarboxylate (1q) was per-
tertiary carbinol- and an all carbon-based stereocenter is shown formed and the product 3q was obtained with a yield of 87% (dr
in Table 2. Under the optimized reaction conditions, we carried 95 : 5, entry 18). For the substrates 1k–p, the corresponding
out the Barbier-type allylation of various prostereogenic 2- products 3j–m and 3o, 3p were obtained with a lower diaster-
benzyl-2-carbethoxycyclopentanones 1a–h and 2-alkyl-2- eoselectivity than the products 3a–i, 4a, and 3q; this may be
carbethoxycyclopentanones 1i, 1j with 2a or 2b using a cata- because of the involvement of a less rigid transition state16c
lytic amount of InCl3 (1–2 mol%) in combination with Al0 under the experimental conditions. The Barbier-type allylation
powder (0.55 mmol) in anhydrous THF. These reactions pro- of the substrates 1a and 1c using allyl chloride, Al metal powder
ꢀ
gressed smoothly and gave the corresponding products 3a–i and a catalytic amount of InCl3 (3 mol%) in THF at 35 C and
(trans isomers) with yields of 66–95% (entries 1–9, Table 2) with 45 ꢀC progressed smoothly and gave the products 3a and 3b
very high diastereoselectivity (dr 98 : 2). The Barbier-type ally- with a yield of 90% (entries 19 and 20, Table 2).
lation of 2-alkyl/aryl-2-carbethoxycyclohexanones 1k–n using a
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 40199–40213 | 40201

View Article Online
RSC Advances
Table 2 Indium-catalyzed Al-based allylation of a,a-disubstituted cycloalkanones and the construction of functionalized carbocyclesa
Paper
Entry
1
Ketone
Allyl bromide
Product
Yield (%) (dr)
3a; 95 (98 : 2)
2
3
4
5
6
3b; R3, R4 ¼ H, R5 ¼ Br, 92 (98 : 2)
3c; R4, R5 ¼ H, R3 ¼ F, 85 (98 : 2)
3d; R3, R4 ¼ H, R5 ¼ Me, 87 (98 : 2)
3e; R3, R4 ¼ H, R5 ¼ NO2, 76 (98 : 2)
3f; R4, R5 ¼ Cl, R3 ¼ H, 78 (98 : 2)
7
3g; R3, R5 ¼ Cl, R4 ¼ H, 66 (98 : 2)
8
3h: 78 (98 : 2)
3i: 87 (98 : 2)
3j: 89 (60 : 40)
9
10
11
12
3k; R3, R4 ¼ H, R5 ¼ Br, 91 (56 : 44)
3l; R3, R5 ¼ H, R4 ¼ Cl, 89 (60 : 40)
13
14
15
3m: 60 (60 : 40)
3n: 0
4a: 96 (98 : 2)
16
17
3o: 81 (55 : 45)
3p: 55 (60 : 40)
18
3q: 87 (95 : 5)
3a: 90 (98 : 2)
19b
40202 | RSC Adv., 2014, 4, 40199–40213
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Table 2 (Contd.)
Entry
Ketone
Allyl bromide
Product
Yield (%) (dr)
20c
3b; R3, R4 ¼ H, R5 ¼ Br, 90 (98 : 2)
a
All the reactions were carried out under Barbier-type reaction conditions. Substrate 1 was treated with allyl bromide, Al0 and a catalytic amount of
InCl3 in one pot. b The reaction was performed using Al0 (0.55 mmol) and InCl3 (3 mol%) at 35 ꢀC for 15 h. c The reaction was performed using Al0
(0.55 mmol) and InCl3 (3 mol%) at 45 ꢀC for 7 h.
Next, we performed the allylation of prostereogenic ethyl 1- products 8a and 8b were obtained with yields of 50% and 55%,
(2-ethoxy-2-oxoethyl)-2-oxocycloalkanecarboxylates, 1r and 1s respectively (Scheme 4). The cinnamylation of 7a gave the
with allyl bromide by using a catalytic amount of InCl3 in product 8b which had good diastereoselectivity (dr 90 : 10,
combination with Al0 powder in anhydrous THF. The allylation Scheme 4). The allylation of the dicarbonyl compound 7b with
of 1r and 1s gave both the allylation products 5a, 5b as well as allyl bromide using a catalytic amount of InCl3 in combination
the bicyclic lactones 6a, 6b, respectively (eqn (1), (2) and Scheme with Al0 gave the bis-allylated compound 8c (98%, Scheme 4).
3).18a In these reactions, the bicyclic lactones 6a (65%) and 6b Additionally, the scope of this protocol was tested for the
(42%) were obtained because the substrates 1r and 1s have an propargylation of the substrate 1a (Scheme 5). The prop-
ester group at an appropriate distance and thereby underwent argylation of cyclic ketone 1a gave the allene product 9 and the
an in situ lactonization18a during the allylation reaction under propargylated product 10 with a yield of 90% (combined yield of
the experimental conditions. In order to increase the yield of the 9/10). Our efforts to separate these two products were not
bicyclic lactone 6b, a catalytic amount of In0 was used instead of successful and the products 9/10 were isolated as a mixture of
InCl3, however, there was no improvement in the yield of the compounds. Furthermore, we decided to perform the click
lactone 6b (eqn (3), Scheme 3).
reaction19c and Glaser–Eglinton–Hay sp–sp coupling19d with a
Subsequently, the allylation reactions of the dicarbonyl mixture of compounds 9/10. Accordingly, the corresponding
compound 7a (N-methylisatin) with allyl bromide and cinnamyl products 11 (59% yield) and 12 (60% yield) were isolated in a
bromide using a catalytic amount of InCl3 in combination with pure form aer the column chromatography purication
Al0 powder were performed. In these reactions the oxindole (Scheme 5).
Scheme
3 Indium-catalyzed allylation of ethyl 1-(2-ethoxy-2-
oxoethyl)-2-oxocycloalkanecarboxylates 1r, 1s. All the reactions were
carried out under the Barbier-type reaction conditions. The substrate Scheme 4 InCl3-catalyzed Al0-based allylation of 1,2-diones. In all the
1r or 1s was treated with allyl bromide, Al0 powder and a catalytic reactions, the allylmetal was first prepared separately and then the
amount of InCl3 in one pot.
dione 7a or 7b was added.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 40199–40213 | 40203

View Article Online
RSC Advances
Paper
Scheme 5 InCl3/Al0-based propargylation of 1a followed by click and
Glaser–Eglinton–Hay reactions. The substrate 1a was treated with
propargyl bromide, Al0 powder and a catalytic amount of InCl3 in one
pot.
Next, we focused our attention on investigating the C–C
bond forming protocol and the synthesis of homoallylic amines
via the allylation of imino (C]N) functional groups using a
catalytic amount of InCl3 in combination with Al0 metal
powder. There have been some exceptional reports in the
literature on the In-catalyzed allylation of carbonyl
compounds,12 however, to the best of our knowledge, the ally-
lation of imino (C]N bond systems) functionality has not been
explored using a catalytic amount of In in combination with a
cheap metal such as Al.6,17,18a,b To start with, a series of C]N
bond systems, such as the imine compounds 15a–e, oxime 15f
and nitrone 15g (Scheme 6), were prepared. The corresponding
imino compounds 15a–g were added to a THF solution of cor-
responding allylmetal reagents which were prepared separately
from allyl bromide (2a) or 3-bromocyclohex-1-ene (2f), a cata-
lytic amount of InCl3 (3–4 mol%) and Al0 metal powder (0.75
mmol). All these reactions successfully gave the homoallylic
amines 16a–h with a yield of 50–93%. For the allylation of
substrates 15a and 15e with 3-bromocyclohex-1-ene (2f), the
corresponding products 16e and 16f were obtained with a
moderate diastereoselectivity under the experimental condi-
tions used.
Next, we prepared the next series of C]N bond systems such
as the isatin-derived imine [(E)-3-(phenylimino)indolin-2-one]
(17) and the ethyl glyoxalate-derived imino systems (E)-ethyl 2-
(2-tosylhydrazono)acetate (18) and (E)-ethyl 2-(2-benzoylhy-
drazono)acetate (19) (Scheme 7). Then, we added imino
compounds 17–19 to a THF solution of allylmetal reagent
prepared separately from allyl bromide (2a), InCl3 (3–4 mol%)
and Al0 metal powder (0.75 mmol). The allylation of 17 gave the
product 3-allyl-3-(phenylamino)indolin-2-one (20) with a yield of
80%. The product ethyl 2-(2-tosylhydrazinyl)pent-4-enoate (21)
was obtained with a yield of only 20%. The allylation of N-
acylhydrazono ester 19 gave the product ethyl 2-(2-
benzoylhydrazinyl)pent-4-enoate (22) with a yield of 58%
(Scheme 7). We also carried out the In-catalyzed Al-based pre-
nylation of N-aryl a-imino ester 23a and the propargylation of a
series of N-aryl a-imino esters 23a–c (Scheme 8). These reactions
Scheme 6 InCl3-catalyzed Al0-based allylation of C]N bond systems
15a–g. In all the reactions imino compounds 15a–g and allylmetal
were prepared separately and then the corresponding imino
compounds 15a–g were added to the round bottomed flask con-
taining the allylmetal reagent obtained from 2a or 2f.
led to the synthesis of g,d-unsaturated b,b0-dimethyl N-aryl a-
amino acid derivative 24a (with a yield of 57%) and a variety of
propargylated products, ethyl 2-((aryl)amino)pent-4-ynoates
24b–d with yields of 38–58% (Scheme 8).
40204 | RSC Adv., 2014, 4, 40199–40213
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Scheme 7 InCl3-catalyzed Al0-based allylation of C]N bond systems
17–19. In all the reactions the imino compounds 17–19 and the
allylmetals were prepared separately and then the corresponding
imino compounds 17–19 were added to the round bottomed flask
containing the allylmetal reagent.
Scheme 9 InCl3-catalyzed Al0-based stereoselective addition to N-aryl
a-imino ester 23a, 23d. The a-imino esters 23a, 23d, were prepared
separately and then the corresponding a-imino esters 23a, 23d were
treated with 2d or 2f or 2h, Al0 and InCl3 in one pot.
of the involvement of a less rigid transition state (TS) under the
present experimental conditions involving the combination of
InCl3 and Al0. However, the addition of a-imino esters 23a, 23d
to cinnamyl bromide (2d), InCl3 and Al0 powder in one pot gave
g,d-unsaturated b,b0-disubstituted N-aryl a-amino acid deriva-
tives 25c (yield of 68%, dr 90 : 10) and 25d (yield of 60%, dr
85 : 15) with very good diastereoselectivity (Scheme 9).
Additionally, we also tested the combination of InCl3 and Al0
for the stereoselective addition of allylmetals to a series of chiral
N-tert-butylsulnyl imino systems 23e–i, prepared from the
condensation of ethyl glyoxal or aromatic aldehydes and (R)-N-
tert-butylsulnyl amine or (S)-N-tert-butylsulnyl amine. The
addition reaction of various chiral imino systems including
imino esters 23e–i to a THF solution of allylmetal reagent
prepared separately from allyl bromide and InCl3/Al0 success-
fully gave the g,d-unsaturated N-tert-butylsulnyl a-amino acid
derivatives 26a, 26e, 26f and homoallylic amines 26b–d, 26g
with very high diastereoselectivity (Scheme 10).
Scheme 8 InCl3-catalyzed Al0-based propargylation of C]N bond
systems. The imino compounds 23a–c were prepared separately. In
the reactions involving the formation of products 24a, 24b, imine 23a
was treated with 2g or 2e, Al0 and InCl3 in one pot. In the reactions
involving the formation of products 24c, 24d, imines 23b, 23c were
added to propargyl metal reagents prepared separately.
Then, we attempted the addition of g-substituted allylic
halides to N-aryl a-imino esters and the construction of g,d-
unsaturated b,b0-disubstituted N-aryl a-amino acid derivatives
bearing two contiguous stereocenters (Scheme 9). The addition
of crotyl bromide (2h) or cyclohexenyl bromide (2f) to a-imino
ester 23a in the presence of InCl3 and Al0 powder in one pot gave
the products, g,d-unsaturated b,b0-disubstituted N-aryl a-amino
acid derivatives 25a (yield of 64%, dr 60 : 40) and 25b (yield of
70%, dr 65 : 35). In these cases, the products 25a and 25b were
obtained with a low diastereoselectivity and this may be because
Stereochemistry
The stereochemistry of the compound 3g prepared in this
research was unequivocally conrmed based on the X-ray
structure analysis (Fig. 1). The stereochemistry of other prod-
ucts 3a–l,16b 3p,16b 3q,16b 6a, 6b,16b 4a,16b and 25a–d (ref. 18a)
obtained in this research using the Al/InCl3 system was
assigned by comparing their spectral data with our previously
published work,16b,18a where the stereochemistry and structure
of various compounds have been already unambiguously
conrmed on the basis of X-ray structure analysis.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 40199–40213 | 40205

View Article Online
RSC Advances
Paper
Fig. 1 X-ray structures of compounds 3g and 26c.
were also assembled in a similar manner to 26b and based on the
observed very high diastereoselectivity, the stereochemistry of
compounds 26d and 26g was assigned aer assigning the
stereochemistry of 26b. In this way, the stereochemistry of
the product (S)-N-((R)-1-(3,4-dimethoxyphenyl)but-3-en-1-yl)-2-
methylpropane-2-sulnamide (26c) which is not reported in the
literature was unambiguously established from the single crystal
X-ray structure analysis (Fig. 1). Similarly, the compound (R)-ethyl
2-((R)-1,1-dimethylethylsulnamido)pent-4-enoate (26a) obtained
in this work was reported in the literature by the same group (Sun
et al.)20f as discussed previously. The stereochemistry of
compound 26a has been assigned on the basis of the similarity of
the spectral data pattern of compound 26a obtained using the Al/
InCl3 system and the results in the literature.20f Consequently,
because the compounds 26e (starting from (S)-ethyl 2-((tert-
Scheme 10 In the reaction involving the preparation of 26a, the
reaction was performed in one pot by treating 23e (0.25 mmol), InCl3/
Al0 and 2a (2 equiv.). In the reactions involving the preparation of 26b–
g, the reactions were performed by treating 23e–i (0.25 mmol) with a
THF solution of allylmetal reagent prepared separately.
The compound (R)-2-methyl-N-((S)-1-(p-tolyl)but-3-en-1-yl) butylsulnyl)imino)acetate) and 26f (starting from (R)-ethyl 2-
propane-2-sulnamide (26b) obtained in this research was ((tert-butylsulnyl)imino)acetate) were also assembled in a
previously reported in the literature.20f We have prepared the similar manner to 26a and based on the very high diaster-
compound 26b using the procedure reported by Sun et al.20f and eoselectivity observed and the similarity in their spectral data
recorded its specic rotation ([a]2D8 ¼ ꢁ91.7 (c 0.024, DCM). The pattern, the stereochemistry of compounds 26e and 26f was
spectral data of compound 26b obtained in this work using assigned aer assigning the stereochemistry of 26a. Further-
the Al/InCl3 system was found to be similar to the spectral data of more, the compounds 26e ([a]2D8 ¼ +25.0 (c 0.024, DCM)) and 26f
26b reported in the literature.20f Next, we recorded the specic ([a]2D6 ¼ ꢁ25.0 (c 0.024, DCM)) are enantiomers and their specic
rotation of the compound 26b prepared using the Al/InCl3 system rotational values were found to have the opposite sign, which
[a]2D8 ¼ ꢁ91.7 (c 0.024, DCM). Since the spectral data as well as the further clearly validated the assigned stereochemistry and
specic rotation of the compound 26b prepared using the Al/ revealed that the allylation of the compounds 23i and 23e is
InCl3 system and the reported method are similar, the stereo- highly stereoselective.
chemistry of compound 26b has been assigned as reported in the
The preparation as well as stereochemistry of the
literature.20f Additionally, the compound 26d has also been compounds 26a and 26b are reported by Sun et al. using the
reported in the literature.20f Because the compounds 26d and 26g corresponding imines 23e and 23f.20f Although the imine
40206 | RSC Adv., 2014, 4, 40199–40213
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Scheme 11 Plausible mechanism for the indium-catalyzed Al-based addition to carbonyl- and imino compounds.12,13,18c–l
systems 23e and 23f have been prepared using the same chiral cases, perhaps, the allylation could be proceeding via mecha-
amine ((R)-N-tert-butylsulnyl amine), the conguration at the nism II, as it is also proposed in the literature that catalytic
homoallyic chiral carbon in the corresponding products, e.g., amounts of InCl3 activate the Al surface thereby leading to the
26a and 26b, is opposite. The reason for this may be that the formation of an allylmetal reagent.13a,c,f,k In view of these points,
allylation of 23e is proceeding via a well-known chelation we also believe that in our reactions, the allylation reaction
controlled TS model18a 27 (Scheme 12) comprising an ester proceeds through mechanism II by involving an allylic
group, thereby giving the compound 26a which has the opposite aluminium reagent as an intermediate and InCl3 may be acting
stereochemistry when compared to the product 26b where there as an activator.12,13a,c,f,k
would not be assistance from chelation. Presumably, the aryl
group, being a relatively bulky group, occupies the equatorial
position in the six-membered cyclic TS18a 28, thereby giving the
compound 26b.
Conclusion
In summary, we have demonstrated the use of a catalytic
amount of InCl3 in combination with Al0 powder for the dia-
stereofacial selective allylation of prostereogenic a,a-disubsti-
tuted (hindered) cycloalkanones and the stereoselective
construction of a stereoarray having consecutively attached
tertiary carbinol- and an all carbon-based stereocenter in func-
tionalized carbocyclic compounds. The allylation of various 2-
substituted-2-carbethoxycyclopentanones gave the correspond-
ing products with an excellent diastereoselectivity and, the
allylation of various 2-substituted-2-carbethoxycyclohexanones
gave the corresponding products with low diastereoselectivity.
We have also reported the C–C bond forming protocol and the
synthesis of homoallylic amines via the allylation of imino
(C]N) functional groups using a catalytic amount of InCl3 in
combination with Al0 powder. For the addition of g-substituted
allylic halides to a-imino esters low to very good diaster-
eoselectivity was obtained. The allylation of chiral N-tert-butyl-
sulnyl imino systems including a-imino esters gave allylated
products with an excellent diastereoselectivity. Considering that
the aluminium metal is relatively inexpensive and less toxic
when compared to other metals, further work and developments
are anticipated, which will prove the effectiveness of the
combination of In and Al as an efficient alternative for per-
forming Barbier-type allylation reactions.
In agreement with reports in the literature, in which the
mechanism of generation of the allylmetal reagent from the
InCl3/Al0 system is proposed,12,13,18c–l plausible mechanisms for
the allylation of prostereogenic a,a-disubstituted cyclo-
alkanones and imino compounds using the InCl3/Al0 system are
proposed in Scheme 11. The involvement of both types of
mechanisms, such as mechanism I and mechanism II, is highly
possible.13 For example, the substrate 1a or 1b (Tables 1 and 2)
was reacted with allyl bromide, Al0 and a catalytic amount of
InCl3 or In0 in one pot. Perhaps, in this case, the allylation could
be proceeding via allylic indium generated in situ involving the
mechanism I.13 However, in some cases we prepared the allyl-
metal reagent separately from allyl bromide, Al0 and a catalytic
amount of InCl3 and then it was treated with imines. For
example, the imino compounds 15a–f (Schemes 6–10) were
treated with a THF solution of allylmetal reagent prepared from
allyl bromide, Al0 and a catalytic amount of InCl3. In these
Experimental section
General considerations
Melting points are uncorrected. Fourier-transform infrared
(FT-IR) spectra were recorded using thin lms or KBr pellets.
1H-NMR and 13C-NMR spectra were recorded on 400 MHz and
Scheme 12 Plausible transition states (TS) for the stereoselectivity
observed.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 40199–40213 | 40207

View Article Online
RSC Advances
Paper
100 MHz spectrometers, respectively. Column chromatography atmosphere and the reaction mixture was stirred at room
was carried out on silica gel (100–200 mesh) or neutral alumina. temperature. Aer 15 min the corresponding imine/carbonyl
Thin layer chromatography (TLC) was performed on silica compound (0.5 mmol) was added to the above reaction
plates or neutral alumina and components were visualized by mixture at a specic temperature for an appropriate time as
observation under iodine. Anhydrous solvents were prepared indicated in the respective Tables/Schemes. Aer this period,
using standard drying methods. Reactions were carried out in the reaction mixture was quenched by adding water (2 mL). The
anhydrous solvents under
a nitrogen atmosphere where reaction mixture was transferred into a separating funnel and
required. Solutions were dried using anhydrous sodium sulfate. extracted with ethyl acetate (3 ꢂ 8 mL). The combined organic
Reagents were added to the reaction ask with the help of a layers were dried over anhydrous Na2SO4. Then the solvent was
syringe. Yields were not optimized and the ratios of diastereo- evaporated under vacuum. Purication of the resulting crude
mers were determined from the NMR spectra of crude reaction reaction mixture by column chromatography on silica gel
mixtures or aer isolation. The ratio of diastereoselectivity (dr (EtOAc/hexane as eluent) gave the product (see the corre-
98 : 2) refers to the predominant presence of the major diaste- sponding Tables/Schemes for specic reactions).
reomer and only traces of the corresponding minor isomer in
Procedure D. Synthesis of triazole 11. To the solution of a
the NMR spectrum of the crude reaction mixture. All the start- mixture of compounds 9/10 (0.5 mmol), CuSO4$5H2O (30
ing materials were prepared using standard procedures previ- mol%) and (+)-sodium L-ascorbate in THF–H2O (2 : 1, 6 mL) was
ously reported in the literature.
added benzyl azide (0.75 mmol) and the reaction mixture was
Procedure A. General Procedure for the preparation of stirred overnight at room temperature. Aer the completion of
compounds 3a–3q, 4a, 5b, 6a, 6b and 9/10. To a solution of the reaction, the reaction mixture was transferred into a sepa-
cyclic ketone (0.5 mmol) in anhydrous THF (1.5 mL) were added rating funnel and extracted with ethyl acetate (3 ꢂ 8 mL). The
InCl3 (1–2 mol%), Al powder (0.55 mmol) and allyl/propargyl combined organic layers were dried over anhydrous Na2SO4.
bromide (1.0 mmol) under a nitrogen atmosphere and this Then the solvent was evaporated under vacuum. Purication of
reaction mixture was stirred at room temperature for an the resulting crude reaction mixture by column chromatog-
appropriate time as indicated in the respective Tables/Schemes. raphy on silica gel (EtOAc/hexane as eluent) gave product 11.
Aer the completion of the reaction, the reaction mixture was
Procedure E. Preparation of compound 12. To the solution of
quenched by adding water (2 mL). The reaction mixture was a mixture of compounds 9/10 (0.5 mmol) in dimethyl sulfoxide
transferred into a separating funnel and extracted with ethyl (DMSO, 3 mL) was added Cu(OAc)2 (40 mol%) and the reaction
acetate (3 ꢂ 8 mL). The combined organic layers were dried over mixture was stirred under an open atmosphere for 24 h at 105
anhydrous Na2SO4. Then the solvent was evaporated under ꢀC. Aer completion of the reaction, the solvent was evaporated
vacuum. Purication of the resulting crude reaction mixture under vacuum. Purication of the resulting crude reaction
was by column chromatography on silica gel (EtOAc/hexane as mixture by column chromatography on silica gel (EtOAc/hexane
eluent) to give the corresponding product (see the correspond- as eluent) gave the product 12.
ing Tables/Schemes for specic reactions).
Copies of the NMR spectra of all the known and unknown
Procedure B. General Procedure for the preparation of compounds reported in this work can be found in the ESI.† In
compounds 24a, 24b, 25a–d and 26a. To a solution of InCl3 (3–4 Table 2, except for compounds 3e, 3g, 3h, 3m, 3o and 3q, all the
mol%), Al powder (0.75 mmol) and allyl bromide/prenyl other compounds were found in the literature and their spectral
bromide/crotyl
bromide/cinnamyl
bromide/propargyl data were compared with the spectral data reported in our
bromide/cyclohexenyl bromide (1.0 mmol) in anhydrous THF previous research.16b The spectral data of the known
(1.5 mL), the corresponding imine (0.5 mmol) was added at an compounds 8a,19a 8b,19b 9/10,16b 16a,20a 16b,20b 16d,20c 22,20d 24a,2f
appropriate temperature as indicated in the corresponding 25a,18a 25b,20e 25c,18a 25d,18a 26a,20f 26b,20f and 26d (ref. 20f) were
Tables/Schemes and the reaction mixture was stirred for an compared with the spectral data reported in the literature. The
appropriate time under a nitrogen atmosphere as mentioned in compound 5a could not be isolated in pure form. The
the respective Tables/Schemes. Aer this period, the reaction compound 8b was obtained as a mixture of diastereomers (dr
mixture was quenched by adding water (2 mL). The reaction 90 : 10).
mixture was transferred into a separating funnel and extracted
Ethyl (1S*,2S*)-2-allyl-2-hydroxy-1-(4-nitrobenzyl)cyclopen-
with ethyl acetate (3 ꢂ 8 mL). The combined organic layers were tanecarboxylate (3e). Following the general procedure
A
dried over anhydrous Na2SO4. Then the solvent was evaporated described previously, 3e (anti, major isomer) was obtained aer
under vacuum. Purication of the resulting crude reaction purication by silica gel column chromatography
mixture by column chromatography on silica gel (EtOAc/hexane (EtOAc : hexane ¼ 07 : 93) as a semi-solid (126 mg, yield: 76%);
as eluent) gave the corresponding product (see the corre- FT-IR (neat): 3543, 1716, 1519 and 1347 cmꢁ1 1H-NMR (400
;
sponding Tables/Schemes for specic reactions).
MHz, deuterated chloroform (CDCl3)): d 8.12 (d, 2H, J ¼ 8.6 Hz),
Procedure C. General Procedure for the preparation of 7.32 (d, 2H, J ¼ 8.6 Hz), 6.00–5.90 (m, 1H), 5.24–5.15 (m, 2H),
compounds 8a–c, 16a–h, 20–22, 24c, 24d and 26b–g. To a 4.17–4.09 (m, 2H), 3.51 (d, 1H, J ¼ 13.5 Hz), 2.91 (d, 1H, J ¼ 13.5
solution of InCl3 (3–4 mol%) and Al powder (0.75 mmol) in Hz), 2.34–2.23 (m, 2H), 2.14 (br s, 1H), 2.01–1.75 (m, 6H), 1.24 (t,
anhydrous THF (1.5 mL) was added allyl bromide/prenyl 3H, J ¼ 7.2 Hz); 13C-NMR (100 MHz, CDCl3): d 174.7, 146.9,
bromide/crotyl
bromide/cinnamyl
bromide/propargyl 146.7, 133.5, 130.7, 123.3, 119.4, 83.1, 61.6, 60.8, 42.0, 37.8, 34.8,
bromide/cyclohexenyl bromide (1.0 mmol) under nitrogen 29.9, 18.6, 14.2; high-resolution mass spectroscopy
–
40208 | RSC Adv., 2014, 4, 40199–40213
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
electrospray ionisation (HRMS (ESI)): calculated for 55.0, 43.6, 40.4, 39.3, 38.8, 23.7, 20.9, 17.5, 17.4, 14.0, 13.9;
18H23NNaO5 [M + Na]+ 356.1474, actual 356.1441. HRMS (ESI): calculated for C17H23BrNaO3 [M + Na]+ 377.0728,
Ethyl (1S*,2S*)-1-(2,4-dichlorobenzyl)-2-hydroxy-2-(2- actual 377.0696. NMR values are given for both the
methylallyl)cyclopentanecarboxylate (3g).21 Following the diastereomers.
C
general procedure A described previously, 3g (anti, major
Ethyl (1S*,2S*)-2-allyl-1-benzhydryl-2-hydroxycyclopentane-
isomer) was obtained aer purication by silica gel column carboxylate (3q). Following the general procedure A described
chromatography (EtOAc : hexane ¼ 06 : 94) as a white solid (122 previously, 3q (anti, major isomer) was obtained aer purica-
ꢀ
mg, yield: 66%); mp ¼ 80–82 C; FT-IR (KBr): 3500, 1716, 1473 tion by silica gel column chromatography (EtOAc : hexane ¼
and 889 cmꢁ1; 1H-NMR (400 MHz, CDCl3): d 7.40 (d, 1H, J ¼ 2.2 05 : 95) as a white solid (158 mg, yield: 87%); mp ¼ 80–82 C;
ꢀ
Hz), 7.14 (dd, 1H, J1 ¼ 8.4 Hz, J2 ¼ 2.2 Hz), 7.07 (d, 1H, J ¼ 8.4 FT-IR (KBr): 3528, 1722, 1495 and 704 cmꢁ1; 1H-NMR (400 MHz,
Hz), 4.97 (s, 1H), 4.80 (s, 1H), 4.18 (q, 2H, J ¼ 7.1 Hz), 3.37 (d, CDCl3): d 7.51 (d, 2H, J ¼ 7.1 Hz), 7.42 (d, 2H, J ¼ 7.4 Hz), 7.29–
1H, J ¼ 14.5 Hz), 3.23 (d, 1H, J ¼ 14.5 Hz), 2.28 (s, 1H), 2.21 (d, 7.13 (m, 6H), 5.97–5.87 (m, 1H), 5.18–5.07 (m, 2H), 5.09 (s, 1H),
1H, J ¼ 3.8 Hz), 2.07–1.64 (m, 6H), 1.88 (s, 3H), 1.26 (t, 3H, J ¼ 3.95–3.86 (m, 2H), 2.79–2.65 (m, 2H), 2.30 (dd, 1H, J1 ¼ 14.1 Hz,
7.1 Hz); 13C-NMR (100 MHz, CDCl3): d 175.6, 142.6, 136.0, 135.4, J2 ¼ 8.1 Hz), 2.21 (s, 1H), 2.18–2.12 (m, 1H), 1.76–1.12 (m, 4H),
132.6, 131.5, 129.4, 126.9, 115.3, 83.5, 61.6, 60.8, 44.8, 34.2, 33.6, 0.93 (t, 3H, J ¼ 7.1 Hz); 13C-NMR (100 MHz, CDCl3): d 174.8,
28.5, 24.5, 18.6, 14.2; HRMS (ESI): calculated for C19H25Cl2O3 [M 143.8, 142.7, 133.8, 130.9, 129.1, 128.1, 128.1, 126.5, 126.1,
+ H]+ 371.1181, actual 371.1001.
Ethyl
(1R*,2S*)-2-hydroxy-2-(2-methylallyl)-1-pentylcyclo- (ESI): calculated for C24H28NaO3 [M + Na]+ 387.1936, actual
118.7, 84.0, 64.2, 60.6, 53.2, 43.0, 34.0, 28.4, 18.7, 13.6; HRMS
pentanecarboxylate (3h). Following the general procedure A 387.1911. This compound was isolated together with its minor
described previously, 3h (anti, major isomer) was obtained isomer.
aer purication by silica gel column chromatography
Ethyl 2-allyl-1-(2-ethoxy-2-oxoethyl)-2-hydroxycyclohexane-
(EtOAc : hexane ¼ 05 : 95) as a colourless liquid (119 mg, yield: carboxylate (5b). Following the general procedure A described
1
78%); FT-IR (neat): 3534, 2958, 1721 and 1463 cmꢁ1; H-NMR previously, 5b was obtained as a pure compound aer puri-
(400 MHz, CDCl3): d 4.90 (s, 1H), 4.73 (s, 1H), 4.23–4.09 (m, cation by silica gel column chromatography (EtOAc : hexane ¼
2H), 2.20–2.06 (m, 3H), 2.05 (s, 1H), 1.99–1.84 (m, 2H), 1.82 (s, 05 : 95) as a colourless liquid (39 mg, yield: 26%); FT-IR (neat):
3H), 1.77–1.62 (m, 4H), 1.44–1.37 (m, 1H), 1.33–1.24 (m, 5H), 3512, 1737, 1715 and 1176 cmꢁ1; 1H-NMR (400 MHz, CDCl3): d
1.28 (t, 3H, J ¼ 7.1 Hz), 1.07–1.00 (m, 1H), 0.87 (t, 3H, J ¼ 6.8 Hz); 5.96–5.86 (m, 1H), 5.12–5.05 (m, 2H), 4.29–4.15 (m, 2H), 4.10 (q,
13C-NMR (100 MHz, CDCl3): d 175.9, 142.9, 1144.9, 82.6, 60.9, 2H, J ¼ 7.2 Hz), 3.86 (s, 1H), 2.79 (d, 1H, J ¼ 15.0 Hz), 2.56 (d, 1H,
60.3, 44.9, 34.5, 32.5, 32.0, 29.8, 25.0, 24.5, 22.5, 18.8, 14.3, 14.0; J ¼ 15.0 Hz), 2.52 (dd, 1H, J1 ¼ 13.7 Hz, J2 ¼ 5.6 Hz), 2.25–2.16
HRMS (ESI): calculated for C17H30NaO3 [M + Na]+ 305.2093, (m, 2H), 1.74–1.34 (m, 7H), 1.30 (t, 3H, J ¼ 7.1 Hz), 1.24 (t, 3H, J
actual 305.2059.
¼ 7.1 Hz); 13C-NMR (100 MHz, CDCl3): d 175.9, 171.3, 133.8,
3-(2-Allyl-2-hydroxy-1-methylcyclohexyl)propane nitrile (3m). 117.8, 74.3, 61.1, 60.5, 52.8, 39.4, 38.5, 33.1, 31.6, 21.8, 21.7,
Following the general procedure A described previously, 3m was 14.1, 14.0; HRMS (ESI): calculated for C16H26O5Na [M + Na]+
obtained as a mixture of diastereomers (dr 60 : 40) aer puri- 321.1678, actual 321.1682.
cation by silica gel column chromatography (EtOAc : hexane ¼
1,2-Diallyl-1,2-dihydroacenaphthylene-1,2-diol (8c). Following
20 : 80) as a light yellow liquid (62 mg, yield: 60%); FT-IR (neat): the general procedure C described previously, 8c was obtained
3512, 2939, 2246 and 1462 cmꢁ1; 1H-NMR (400 MHz, CDCl3): d aer purication by silica gel column chromatography
5.91 5.80 (m, 1H), 5.21 5.10 (m, 2H), 2.45 2.19 (m, 4H), 2.07 1.71 (EtOAc : hexane ¼ 20 : 80) as a white solid (65 mg, yield: 98%);
(m, 2H), 1.60 1.37 (m, 8H), 0.94 (s, 3H); 13C-NMR (100 MHz, mp ¼ 143–145 ꢀC; FT-IR (KBr): 3362, 1638, 1374 and 1057 cmꢁ1
;
CDCl3): d 133.8, 133.7, 121.2, 120.8, 119.7, 119.3, 75.0, 74.9, 1H-NMR (400 MHz, CDCl3): d 7.76 (d, 2H, J ¼ 8.3 Hz), 7.58 (dd,
39.9, 39.7, 39.4, 38.8, 33.6, 32.9, 32.6, 32.6, 32.2, 22.0, 21.5, 21.0, 2H, J1 ¼ 8.3 Hz, J2 ¼ 6.9 Hz), 7.42 (d, 2H, J ¼ 6.9 Hz), 5.90–5.79
21.0, 20.6, 18.8, 12.6; HRMS (ESI): calculated for C13H21NNaO (m, 2H), 5.20–5.14 (m, 4H), 2.88–2.82 (m, 2H), 2.69 (s, 2H), 2.60
[M + Na]+ 230.1521, actual 230.1363. NMR values are given for (dd, 2H, J1 ¼ 13.9 Hz, J2 ¼ 7.9 Hz); 13C-NMR (100 MHz, CDCl3): d
both the diastereomers.
144.7, 134.3, 134.1, 130.6, 128.1, 124.6, 119.5, 119.5, 86.4, 43.8;
Ethyl 2-(4-bromobenzyl)-3-hydroxy-2,3-dimethylhex-5-enoate HRMS (ESI): calculated for C18H17O2 [M ꢁ H]+ 265.1229, actual
(3o). Following the general procedure A described previously, 3o 265.1337.
was obtained as a mixture of diastereomers (dr 55 : 45) aer
Ethyl
(1S*,2S*)-1-benzyl-2-((1-benzyl-1H-1,2,3-triazol-5-yl)
purication by silica gel column chromatography methyl)-2-hydroxycyclopentanecarboxylate (11). Following the
(EtOAc : hexane ¼ 07 : 93) as a colourless liquid (144 mg, yield: general procedure D described previously, 11 was obtained aer
1
81%); FT-IR (neat): 3486, 1714, 1488 and 1012 cmꢁ1; H-NMR purication by silica gel column chromatography
(400 MHz, CDCl3): d 7.36 (d, 2H, J ¼ 8.0 Hz), 6.97 (d, 2H, J ¼ (EtOAc : hexane ¼ 30 : 70) as a brownish yellow solid (124 mg,
ꢀ
8.0 Hz), 6.06–5.91 (m, 1H), 5.17–5.03 (m, 2H), 4.06–3.95 (m, 2H), yield: 59%); mp ¼ 83–85 C; FT-IR (KBr): 3409, 1716, 1454 and
3.83 (s, 1H), 3.51 (d, 1H, J ¼ 13.2 Hz), 2.58 (d, 1H, 13.2 Hz), 2.34 703 cmꢁ1; 1H-NMR (400 MHz, CDCl3): d 7.44 (s, 1H), 7.38–7.35
(dd, 1H, J1 ¼ 13.9 Hz, J2 ¼ 8.2 Hz), 2.17–2.09 (m, 1H), 1.18 (s, (m, 3H), 7.28–7.19 (m, 5H), 7.12–7.10 (m, 2H), 5.52 (s, 2H), 4.14–
3H), 1.12 (t, 3H, J ¼ 7.1 Hz), 1.09 (s, 3H); 13C-NMR (100 MHz, 4.00 (m, 2H), 3.79 (br s, 1H), 3.26 (d, 1H, J ¼ 13.5 Hz), 2.98 (d,
CDCl3): d 177.2, 176.8, 137.0, 136.8, 134.3, 134.1, 132.0, 132.0, 1H, J ¼ 18.7 Hz), 2.95 (d, 1H, J ¼ 18.7 Hz), 2.80 (d, 1H, J ¼ 13.5
131.1, 131.1, 120.5, 120.5, 118.0, 117.9, 76.0, 75.3, 61.0, 55.5, Hz), 2.06–1.70 (m, 6H), 1.18 (t, 3H, J ¼ 7.1 Hz); 13C-NMR (100
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 40199–40213 | 40209

View Article Online
RSC Advances
Paper
MHz, CDCl3): d 175.4, 144.8, 138.6, 134.8, 129.9, 129.1, 128.7, 5.64–5.57 (m, 1H), 4.34–4.31 (m, 1H), 4.03 (s, 1H), 2.64 (s, 1H),
128.1, 128.0, 126.3, 122.7, 83.2, 61.9, 60.6, 54.1, 38.0, 35.5, 33.2, 2.22 (s, 3H), 2.19 (s, 3H), 2.10 (s, 2H), 1.87–1.54 (m, 4H); 13C-
30.0, 18.5, 14.1; HRMS (ESI): calculated for C25H29N3NaO3 [M + NMR (100 MHz, CDCl3): d 145.9, 145.6, 141.7, 141.2, 137.3,
Na]+ 442.2107, actual 442.2104. The stereochemistry of the 137.2, 132.3, 131.4, 130.8, 130.3, 130.2, 129.0, 128.6, 128.4,
products 9/10 had been reported previously16b and based on this 128.3, 125.9, 125.6, 125.1, 115.6, 114.9, 110.8, 110.3, 61.7, 61.1,
the stereochemistry of 11 was assigned.
43.2, 42.9, 27.7, 25.3, 25.3, 23.7, 22.0, 21.8, 20.1, 18.7; HRMS
Preparation of compound 12. Following the general proce- (ESI): calculated for C21H25ClN [M + H]+ 326.1676, actual
dure E described previously, 12 was obtained aer purication 326.1646. NMR values are given for both the isomers.
by silica gel column chromatography (EtOAc : hexane ¼ 25 : 75)
N-(1-(4-Bromophenyl)but-3-en-1-yl)-O-methylhydroxylamine
as a white solid (175 mg, yield: 60%); mp ¼ 117–119 C; FT-IR (16g). Following the general procedure C described previously,
ꢀ
(KBr): 3493, 2979, 1716 and 738 cmꢁ1 1H-NMR (400 MHz, 16g was obtained aer purication by silica gel column chro-
;
CDCl3): d 7.26–7.22 (m, 6H), 7.14–7.12 (m, 4H), 4.16–4.08 (m, matography (EtOAc : hexane ¼ 07 : 93) as a colourless liquid (96
4H), 3.42 (d, 2H, J ¼ 13.6 Hz), 2.81 (d, 2H, J ¼ 13.6 Hz), 2.62 (d, mg, yield: 75%); FT-IR (KBr): 1639, 1485, 1104 and 739 cmꢁ1
;
2H, J ¼ 16.8 Hz), 2.56 (d, 2H, J ¼ 16.8 Hz), 2.41 (s, 2H), 2.11–1.68 1H-NMR (400 MHz, CDCl3): d 7.50 (d, 2H, J ¼ 8.4 Hz), 7.19 (d,
(m, 12H), 1.24 (t, 6H, J ¼ 7.2 Hz); 13C-NMR (100 MHz, CDCl3): d 2H, J ¼ 8.4 Hz), 5.81–5.70 (m, 1H), 5.09–5.04 (m, 2H), 4.18–4.14
174.6, 138.1, 129.9, 128.2, 126.5, 82.5, 74.0, 67.8, 61.1, 60.8, 37.8, (m, 1H), 3.23 (s, 3H), 2.60–2.36 (m, 2H); 13C-NMR (100 MHz,
35.8, 29.6, 29.6, 18.1, 14.1; HRMS (ESI): calculated for CDCl3): d 140.8, 134.3, 131.5, 128.5, 121.4, 117.3, 83.0, 56.7,
C
36H42NaO6 [M + Na]+ 593.2879, actual 593.2894. The stereo- 42.4. The NH proton could not be detected in this compound.
chemistry of the products 9/10 had been reported previously16b
and based on this the stereochemistry of 12 was assigned.
N-(1-(4-Bromophenyl)but-3-en-1-yl)-N-methylhydroxylamine
(16h). Following the general procedure C described previously,
3,4-Dichloro-N-(1-(3,4-dimethoxyphenyl)but-3-en-1-yl)aniline 16h was obtained aer purication by silica gel column chro-
(16c). Following the general procedure C described previously, matography (EtOAc : hexane ¼ 10 : 90) as a yellowish brown
16c was obtained aer purication by silica gel column chro- solid (63 mg, yield: 50%); mp ¼ 72–74 ꢀC; FT-IR (KBr): 3224,
matography (EtOAc : hexane ¼ 15 : 85) as a light yellow liquid 1487, 1011 and 739 cmꢁ1; 1H-NMR (400 MHz, CDCl3): d 7.48 (d,
(163 mg, yield: 93%); FT-IR (neat): 3385, 1597, 1514 and 1027 2H, J ¼ 8.4 Hz), 7.19 (d, 2H, 8.4 Hz), 5.64–5.54 (m, 1H), 5.03–4.96
cmꢁ1; 1H-NMR (400 MHz, CDCl3): d 7.10 (d, 1H, J ¼ 8.7 Hz), 6.89 (m, 2H), 3.57 (dd, 1H, J1 ¼ 9.2 Hz, J2 ¼ 5.0 Hz), 2.88–2.81 (m,
(dd, 1H, J1 ¼ 8.4 Hz, J2 ¼ 1.8 Hz), 6.86–6.84 (m, 2H), 6.60 (d, 1H, 1H), 2.57–2.49 (m, 1H), 2.54 (s, 3H); 13C-NMR (100 MHz, CDCl3):
J ¼ 2.7 Hz), 6.35 (dd, 1H, J1 ¼ 8.7 Hz, J2 ¼ 2.7 Hz), 5.81–5.71 (m, d 134.6, 131.5, 130.4, 121.6, 117.3, 73.3, 46.0, 38.1; HRMS (ESI):
1H), 5.24–5.17 (m, 2H), 4.30–4.23 (m, 1H), 4.23 (s, 1H), 3.88 (s, calculated for C11H15BrNO [M + H]+ 256.0337, actual 256.0155.
3H), 3.88 (s, 3H), 2.64–2.45 (m, 2H); 13C-NMR (100 MHz, CDCl3): d The OH proton could not be detected in this compound.
149.3, 148.1, 146.9, 135.0, 134.3, 132.5, 130.4, 119.9, 118.7, 118.2,
3-Allyl-3-(phenylamino)indolin-2-one (20). Following the
114.8, 113.1, 111.3, 109.1, 56.9, 55.9, 55.9, 43.2; HRMS (ESI): general procedure C described previously, 20 was obtained
calculated for C18H20Cl2NO2 [M + H]+ 352.0871, actual 352.0601. aer purication by silica gel column chromatography
N-((4-Bromophenyl)(cyclohex-2-en-1-yl)methyl)-4-methyl- (EtOAc : hexane ¼ 20 : 80) as a white solid (106 mg, yield: 80%);
aniline (16e). Following the general procedure C described mp ¼ 163–165 ꢀC; FT-IR (KBr): 3312, 1603, 1716 and 1470 cmꢁ1
;
previously, 16e was obtained as a mixture of diastereomers (dr 1H-NMR (400 MHz, CDCl3): d 9.60 (s, 1H), 7.29–7.23 (m, 2H),
70 : 30) aer purication by silica gel column chromatography 7.07–6.98 (m, 3H), 6.90 (d, 1H, J ¼ 7.7 Hz), 6.69–6.65 (m, 1H),
(EtOAc : hexane ¼ 05 : 95) as a light yellow liquid (129 mg, yield: 6.32 (dd, 1H, J1 ¼ 8.7 Hz, J2 ¼ 1.0 Hz), 5.86–5.76 (m, 1H), 5.29–
73%); FT-IR (neat): 3414, 1618, 1519 and 806 cmꢁ1
;
1H-NMR 5.22 (m, 2H), 4.73 (s, 1H), 2.80 (dd, 1H, J1 ¼ 13.3 Hz, J2 ¼ 7.1 Hz),
(400 MHz, CDCl3): d 7.48 (d, 2H, J ¼ 8.5 Hz), 7.26 (d, 2H, J ¼ 2.66 (dd, 1H, J1 ¼ 13.3 Hz, J2 ¼ 7.7 Hz); 13C-NMR (100 MHz,
8.5 Hz), 6.95 (d, 2H, J ¼ 8.1 Hz), 6.43 (d, 2H, J ¼ 8.1 Hz), 5.98– CDCl3): d 181.0, 145.2, 139.8, 130.3, 129.1, 129.0, 124.0, 123.0,
5.91 (m, 1H), 5.60 (dd, 1H, J1 ¼ 10.2 Hz, J2 ¼ 1.5 Hz), 4.30–4.27 121.2, 118.8, 114.4, 111.0, 64.3, 44.7; HRMS (ESI): calculated for
(m, 1H), 4.04 (s, 1H), 2.24 (s, 3H), 2.08 (s, 2H), 1.85–1.80 (m, 2H),
1.61–1.48 (m, 2H); 13C-NMR (100 MHz, CDCl3): d 145.4, 145.0,
C
17H16N2NaO [M + Na]+ 287.1160, actual 287.1125.
Ethyl 2-(2-tosylhydrazinyl)pent-4-enoate (21). Following the
142.0, 141.6, 132.5, 131.5, 131.0, 130.8, 129.7, 129.6, 128.9, general procedure C described previously, 21 was obtained
128.8, 128.7, 126.8, 126.3, 125.8, 120.5, 113.7, 113.1, 61.8, 61.2, aer purication by silica gel column chromatography
43.1, 42.8, 27.6, 25.3, 25.2, 23.7, 21.9, 21.8, 20.4; HRMS (ESI): (EtOAc : hexane ¼ 30 : 70) as yellowish thick liquid (31 mg,
1
calculated for C20H23BrN [M + H]+ 356.1014, actual 356.0970. yield: 20%); FT-IR (neat): 3300, 3249, 1727 and 738 cmꢁ1; H-
NMR values are given for both the isomers.
NMR (400 MHz, CDCl3): d 7.82 (d, 2H, J ¼ 8.3 Hz), 7.33 (d,
N-[(4-Chlorophenyl)(cyclohex-2-en-1-yl)methyl]-3,4-dimethy-
2H, J ¼ 8.0 Hz), 6.36 (s, 1H), 5.71–5.61 (m, 1H), 5.10–5.06 (m,
laniline (16f). Following the general procedure C described 2H), 4.20 (q, 2H, J ¼ 7.2 Hz), 3.92 (dd, 1H, J1 ¼ 9.7 Hz, J2 ¼ 2.9
previously, 16f was obtained as a mixture of diastereomers (dr Hz), 3.64–3.59 (m, 1H), 2.45 (s, 3H), 2.44-2.32 (m, 2H), 1.29 (t,
70 : 30) aer purication by silica gel column chromatography 3H, J ¼ 7.2 Hz); 13C-NMR (100 MHz, CDCl3): d 173.4, 144.0,
(EtOAc : hexane ¼ 10 : 90) as a reddish brown liquid (130 mg, 135.0, 132.6, 129.5, 128.2, 118.5, 62.9, 61.4, 34.8, 21.6, 14.2;
yield: 80%); FT-IR (neat): 3418, 1617, 1510 and 801 cmꢁ1; H- HRMS (ESI): calculated for C14H20N2NaO4S [M + Na]+ 335.1041,
1
NMR (400 MHz, CDCl3): d 7.37–7.35 (m, 4H), 6.92 (d, 1H, J ¼ actual 335.1013.
7.9 Hz), 6.42 (s, 1H), 6.28–6.27 (m, 1H), 5.98 (d, 1H, J ¼ 9.6 Hz),
40210 | RSC Adv., 2014, 4, 40199–40213
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
Ethyl
RSC Advances
FT-IR (neat): 3402, 1738 and 1056 cmꢁ1
;
1H-NMR (400 MHz,
2-((4-methoxyphenyl)amino)pent-4-ynoate
(24b).
CDCl3): d 4.85 (s, 1H), 4.77 (s, 1H), 4.24 (q, 2H, J ¼ 7.2 Hz), 4.11–
4.04 (m, 2H), 2.54–2.38 (m, 2H), 1.76 (s, 3H), 1.31 (t, 3H, J ¼ 7.2
Hz), 1.25 (s, 9H); 13C-NMR (100 MHz, CDCl3): d 173.2, 140.3,
114.6, 61.7, 56.2, 42.5, 22.6, 22.1, 14.1; HRMS (ESI): calculated
for C12H24NO3S [M + H]+ 262.1477, actual 262.1480.
Following the general procedure B described previously, 24b
was obtained aer purication by silica gel column chroma-
tography (EtOAc : hexane ¼ 20 : 80) as a reddish black thick
liquid (71 mg, yield: 58%); FT-IR (neat): 3286, 1738, 1514 and
1241 cmꢁ1; 1H-NMR (400 MHz, CDCl3): d 6.80 (d, 2H, J ¼ 9.0 Hz),
6.67 (d, 2H, J ¼ 9.0 Hz), 4.29–4.20 (m, 2H), 4.19 (t, 1H, J ¼ 5.4
Hz), 3.77 (s, 3H), 2.78 (dd, 2H, J1 ¼ 5.4 Hz, J2 ¼ 2.6 Hz), 2.11 (t,
1H, J ¼ 2.6 Hz), 1.33 (t, 3H, J ¼ 7.1 Hz); 13C-NMR (100 MHz,
CDCl3): d 172.2, 153.1, 140.1, 115.7, 114.9, 78.9, 71.6, 61.5, 56.3,
55.7, 22.9, 14.2; HRMS (ESI): calculated for C14H18NO3 [M + H]+
248.1287, actual 248.1268. The NH proton could not be detected
in this compound.
Ethyl 2-[(3,4-dimethylphenyl)amino]pent-4-ynoate (24c).
Following the general procedure C described previously, 24c
was obtained aer purication by neutral alumina column
chromatography (EtOAc : hexane ¼ 10 : 90) as a brownish black
thick liquid (46 mg, yield: 38%); FT-IR (neat): 3391, 1738, 1510
and 1209 cmꢁ1; 1H-NMR (400 MHz, CDCl3): d 6.97 (d, 1H, J ¼ 8.0
Hz), 6.53 (d, 1H, J ¼ 2.4 Hz), 6.45 (dd, 1H, J1 ¼ 8.0 Hz, J2 ¼ 2.4
Hz), 4.29–4.24 (m, 3H), 2.79 (dd, 2H, J1 ¼ 5.1 Hz, J2 ¼ 2.7 Hz),
2,22 (s, 3H), 2.18 (s, 3H), 2.10 (t, 1H, J ¼ 2.7 Hz), 1.31 (t, 3H, J ¼
7.1 Hz); 13C-NMR (100 MHz, CDCl3): d 172.1, 144.1, 137.5, 130.4,
126.9, 115.9, 111.3, 78.9, 71.5, 61.5, 55.4, 22.9, 20.0, 18.8, 14.3;
HRMS (ESI): calculated for C15H20NO2 [M + H]+ 246.1494, actual
246.1458. The NH proton could not be detected in this
compound.
Ethyl 2-[(4-bromophenyl)amino]pent-4-ynoate (24d). Following
the general procedure C described previously, 24d was obtained
aer purication by neutral alumina column chromatography
(EtOAc : hexane ¼ 10 : 90) as a light yellow liquid (59 mg, yield:
40%); FT-IR (neat): 3392, 3295, 1737 and 651 cmꢁ1; 1H-NMR (400
MHz, CDCl3): d 7.29 (d, 2H, J ¼ 8.9 Hz), 6.55 (d, 2H, J ¼ 8.9 Hz),
4.49 (s, 1H), 4.30–4.21 (m, 3H), 2.79 (dd, 2H, J1 ¼ 5.2 Hz, J2 ¼ 2.6
Hz), 2.11 (t, 1H, J ¼ 2.6 Hz), 1.31 (t, 3H, J ¼ 7.1 Hz); 13C-NMR (100
MHz, CDCl3): d 171.5, 145.1, 132.1, 115.4, 110.5, 78.6, 71.9, 61.8,
54.9, 22.7, 14.2; HRMS (ESI): calculated for C13H15BrNO2 [M + H]+
296.0286, actual 296.0265.
(S)-N-((R)-1-(3,4-Dimethoxyphenyl)but-3-en-1-yl)-2-methyl-
propane-2-sulnamide (26c).21 Following the general procedure
C described previously, 26c was obtained aer purication by
silica gel column chromatography (EtOAc : hexane ¼ 90 : 10) as
a white solid (36 mg, yield: 46%); [a]2D8 ¼ +54.6 (c 0.044, DCM);
Ethyl (R)-2-((R)-1,1-dimethylethylsulnamido)-4-methylpent-
4-enoate (26f). Following the general procedure C described
previously, 26f was obtained aer purication by silica gel
column chromatography (EtOAc : hexane ¼ 65 : 30) as a col-
ourless liquid (34 mg, yield: 52%); ([a]2D6 ¼ ꢁ25.0 (c 0.024, DCM);
FT-IR (neat): 3406, 1738 and 1054 cmꢁ1 1H-NMR (400 MHz,
;
CDCl3): d 4.85 (s, 1H), 4.77 (s, 1H), 4.24 (q, 2H, J ¼ 7.1 Hz), 4.10–
4.04 (m, 2H), 2.54–2.38 (m, 2H), 1.77 (s, 3H), 1.31 (t, 3H, J ¼ 7.1
Hz), 1.25 (s, 9H); 13C-NMR (100 MHz, CDCl3): d 173.2, 140.3,
114.6, 61.7, 56.2, 42.5, 22.6, 22.1, 14.1; HRMS (ESI): calculated
for C12H24NO3S [M + H]+ 262.1477, actual 262.1481.
(R)-2-methyl-N-((S)-3-methyl-1-(p-tolyl)but-3-en-1-yl)propane-
2-sulnamide (26g). Following the general procedure
C
described previously, 26g was obtained aer purication by
silica gel column chromatography (EtOAc : hexane ¼ 60 : 40) as
a white solid (33 mg, yield: 47%); [a]2D8 ¼ ꢁ87.5 (c 0.032, DCM);
mp ¼ 51–53 ꢀC; FT-IR (KBr): 3414, 1645, 1063 and 738 cmꢁ1; 1H-
NMR (400 MHz, CDCl3): d 7.25 (d, 2H, J ¼ 8.0 Hz), 7.17 (d, 2H,
J ¼ 7.8 Hz), 4.95 (s, 1H), 4.89 (s, 1H), 4.51 (dd, 1H, J1 ¼ 8.2 Hz, J2
¼ 5.7 Hz), 3.73 (s, 1H), 2.44–2.35 (m, 2H), 2.36 (s, 3H), 1.81 (s,
3H), 1.21 (s, 9H); 13C-NMR (100 MHz, CDCl3): d 142.2, 139.2,
137.3, 129.2, 127.4, 114.9, 55.6, 54.2, 48.0, 22.6, 21.8, 21.2;
HRMS (ESI): calculated for C16H26NOS [M + H]+ 280.1735, actual
280.1707. This compound was isolated as a mixture of diaste-
reomers and the NMR values are given for the major
diastereomer.
Acknowledgements
This work was funded by IISER Mohali. We thank IISER Mohali
for the use of their NMR, X-ray and HRMS facilities. We also
thank the single crystal X-ray facility of the Department of
Chemical Sciences, IISER Mohali. C. R. and N. A. Aslam thank
the CSIR-UGC, New Delhi, for their SRF fellowships.
References
mp ¼ 103–105 ꢀC; FT-IR (KBr): 3417, 1638, 1421 and 738 cmꢁ1
;
1 For some selected articles/books on metal-mediated
additions to C]O and C]N systems see; (a) S. R. Chemler
and W. R. Roush, in Modern Carbonyl Chemistry, ed. J.
Otera, Wiley-VCH, Weinheim, 2000, ch. 10; (b)
S. E. Denmark and N. G. Almstead, in Modern Carbonyl
Chemistry, ed. J. Otera, Wiley-VCH, Weinheim, 2000, ch. 11;
(c) G. Helmchen, R. Hoffmann, J. Mulzer and
E. Schaumann, Houben-Weyl Methods in Organic Chemistry:
Stereoselective Synthesis (Methods of Organic Chemistry),
Thieme, Stuttgart, 1996, vol. 3; (d) B. M. Trost,
Comprehensive Organic Syntheses, Pergamon Press, Oxford,
U.K., 1991, vol. 1 and 2; (e) Y. Yamamoto and N. Asao,
Chem. Rev., 1993, 93, 2207; (f) S. E. Denmark and J. Fu,
1H-NMR (400 MHz, CDCl3): d 6.90 (dd, 1H, J1 ¼ 8.0 Hz, J2 ¼ 1.9
Hz), 6.86 (d, 1H, J ¼ 1.9 Hz), 6.84 (d, 1H, J ¼ 8.0 Hz), 5.81–5.70
(m, 1H), 5.22–5.17 (m, 2H), 4.44–4.40 (m, 1H), 3.89 (s, 3H), 3.88
(s, 3H), 3.68 (br s, 1H), 2.62–2.41 (m, 2H), 1.22 (s, 9H); 13C-NMR
(100 MHz, CDCl3): d 148.9, 148.4, 134.4, 134.1, 119.9, 119.2,
110.8, 110.3, 56.6, 55.8, 55.8, 55.5, 43.6, 22.6; HRMS (ESI):
calculated for C16H26NO3S [M + H]+ 312.1633, actual 312.1607.
Ethyl (S)-2-((S)-1,1-dimethylethylsulnamido)-4-methylpent-
4-enoate (26e). Following the general procedure C described
previously, 26e was obtained aer purication by silica gel
column chromatography (EtOAc : hexane ¼ 70 : 30) as a light
yellow liquid (16 mg, yield: 25%); [a]2D8 ¼ +25.0 (c 0.024, DCM);
´
Chem. Rev., 2003, 103, 2763; (g) M. Yus, J. C. Gonzalez-
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 40199–40213 | 40211

View Article Online
RSC Advances
Paper
´
Gomez and F. Foubelo, Chem. Rev., 2013, 113, 5595; (h)
2012, 10, 3991; (c) A. Wolan, A. Joachimczak, M. Budny and
A. Kozakiewicz, Tetrahedron Lett., 2011, 52, 1195; (d)
W. Zhou, W. Yan, J.-X. Wang and K. Wang, Synlett, 2008, 131.
9 For a recent paper on Mg-mediated reaction, see S. Li,
J.-X. Wang, X. Wen and X. Ma, Tetrahedron, 2011, 67, 849.
L. F. Tietze, T. Kinkel and C. C. Brazel, Acc. Chem. Res.,
2009, 42, 367; (i) G. K. Friestad and A. K. Mathies,
Tetrahedron, 2007, 63, 2541; (j) H. Ding and G. K. Friestad,
Synthesis, 2005, 2815; (k) H. Yamamoto and M. Wadamoto,
Chem.–Asian J., 2007, 2, 692; (l) M. Kanai, R. Wada, 10 For some papers on Ga-mediated reaction, see; (a)
T. Shibuguci and M. Shibasaki, Pure Appl. Chem., 2008, 80,
1055; (m) H. Lachance and D. G. Hall, Org. React., 2008, 73,
1; (n) S. Kobayashi, Y. Mori, J. S. Fossey and M. M. Salter,
Chem. Rev., 2011, 111, 2626; (o) D. G. Hall, Synlett, 2007,
1644; (p) M. T. Reetz, Angew. Chem., Int. Ed., 1984, 23, 556;
D. Goswami, A. Chattopadhyay, A. Sharma and
S. Chattopadhyay, J. Org. Chem., 2012, 77, 11064; (b)
P. C. Andrews, A. C. Peatt and C. L. Taston, Tetrahedron
Lett., 2004, 45, 243; (c) Z. Wang, S. Yuan and C.-J. Li,
Tetrahedron Lett., 2002, 43, 5097.
´
´
(q) M. Yus, J. C. Gonzalez-Gomez and F. Foubelo, Chem. 11 For some recent papers on tin-mediated reactions, see (a)
Rev., 2011, 111, 7774.
Z. Zha, S. Qiao, J. Jiang, Y. Wang, Q. Miao and Z. Wang,
Tetrahedron, 2005, 61, 2521; (b) R. Slaton, A. Petrone and
R. Manchanayakage, Tetrahedron Lett., 2011, 52, 5073; (c)
2 For some selected articles on metal-mediated additions to
C]O and C]N systems see; (a) T. Vilaivan,
W. Bhanthumnavin and Y. Sritana-Anant, Curr. Org. Chem.,
2005, 9, 1315; (b) T. R. Ramadhar and R. A. Batey,
Synthesis, 2011, 1321; (c) H. Miyabe and Y. Takemoto,
˜
R. L. Guimaraes, D. J. P. Lima, M. E. S. B. Barros,
L. N. Cavalcanti, F. Hallwass, M. Navarro, L. W. Bieber and
I. Malvestiti, Molecules, 2007, 12, 2089.
Synlett, 2005, 1641; (d) P. Merino, T. Tejero, J. I. Delso and 12 For some recent papers on bimetallic system-based
V. Mannucci, Curr. Org. Synth., 2005, 2, 479; (e) O. Riant
and J. Hannedouche, Org. Biomol. Chem., 2007, 5, 873; (f)
X. Piao, J.-K. Jung and H.-Y. Kang, Bull. Korean Chem. Soc.,
2007, 28, 139.
allylation of carbonyl compounds involving metals other
than indium, see; (a) L. M. Fleury, A. D. Kosal,
J. T. Masters and B. L. Ashfeld, J. Org. Chem., 2013, 78, 253;
´
´
´
˜
(b) A. Martınez-Peragon, A. Millan, A. G. Campana,
´
´
3 G. Molle and P. Bauer, J. Am. Chem. Soc., 1982, 104, 3481.
4 P. Barbier, C. R. Acad. Sci., Ser. II: Mec., Phys., Chim., Sci. Terre
Univers, 1899, 128, 110.
5 V. Grignard, C. R. Acad. Sci., Ser. II: Mec., Phys., Chim., Sci.
Terre Univers, 1900, 130, 1322.
I. Rodrıguez-Marquez, S. Resa, D. Miguel, L. A. de
Cienfuegos and J. M. Cuerva, Eur. J. Org. Chem., 2012,
´
´
´
1499; (c) C. Vilanova, M. Sanchez-Peris, S. Roldan,
B. Dhotare, M. Carda and A. Chattopadhyay, Tetrahedron
Lett., 2013, 54, 6562.
6 For some selected reviews/papers on indium-based 13 For some recent papers on bimetallic system-based indium-
catalyzed allylation of carbonyl compounds, see; (a) Z. Peng,
reactions, see; (a) S. Araki, H. Ito and Y. Butsugan, J. Org.
Chem., 1988, 53, 1831; (b) B. C. Ranu, Eur. J. Org. Chem.,
2000, 2347; (c) V. Nair, S. Ros, C. N. Jayan and B. S. Pillai,
Tetrahedron, 2004, 60, 1959; (d) J. Podlech and T. C. Maier,
Synthesis, 2003, 633; (e) T.-P. Loh, Sci. Synth., 2004, 7, 413;
(f) J. A. Marshall, J. Org. Chem., 2007, 72, 8153; (g) C.-J. Li,
Chem. Rev., 2005, 105, 3095; (h) S. H. Kim, H. S. Lee,
K. H. Kim, S. H. Kim and J. N. Kim, Tetrahedron, 2010, 66,
7065; (i) W. J. Bowyer, B. Singaram and A. M. Sessler,
Tetrahedron, 2011, 67, 7449; (j) J. S. Yadav, A. Antony,
J. George and B. V. Subba Reddy, Eur. J. Org. Chem., 2010,
591; (k) U. K. Roy and S. Roy, Chem. Rev., 2010, 110, 2472;
(l) R. B. Kargbo and G. R. Cook, Curr. Org. Chem., 2007, 11,
1287; (m) P. H. Lee, Bull. Korean Chem. Soc., 2007, 28, 17;
(n) C.-J. Li, Green Chem., 1998, 234; (o) S. A. Babu,
M. Yasuda, I. Shibata and A. Baba, Org. Lett., 2004, 6, 4475;
(p) S. A. Babu, M. Yasuda and A. Baba, J. Org. Chem., 2007,
72, 10264; (q) L. A. Paquette, Synthesis, 2003, 765; (r)
S. A. Babu, Synlett, 2002, 531.
¨
T. D. Blumke, P. Mayer and P. Knochel, Angew. Chem., Int.
Ed., 2010, 49, 8516; (b) R. G. Soengas and A. M. S. Silva,
Synlett, 2012, 23, 873; (c) K. Takai and Y. Ikawa, Org. Lett.,
2002, 4, 1727; (d) J. Auge, N. Lubin-Germain, S. Marque
and L. Seghrouchni, J. Organomet. Chem., 2003, 679, 79; (e)
T. Hirashita, Y. Sato, D. Yamada, F. Takahashi and
S. Araki, Chem. Lett., 2011, 40, 506; (f) S. Araki, S.-J. Jin,
Y. Idou and Y. Butsugan, Bull. Chem. Soc. Jpn., 1992, 65,
1736; (g) M. D. Preite, H. A. Jorquera-Geroldi and A. Perez-
Carvajal, ARKIVOC, 2011, 380, for papers dealing on
activation of Al powder by PbCl2, SnCl2, TiCl4 and
´
insertion into allyl halides, see:
; (h) K. Uneyama,
N. Kamaki, A. Moriya and S. Torii, J. Org. Chem., 1985, 50,
5396; (i) H. Tanaka, T. Nakahara, H. Dhimane and S. Torii,
Tetrahedron Lett., 1989, 30, 4161; (j) H. Tanaka, K. Inoue,
U. Pokorski, M. Taniguchi and S. Torii, Tetrahedron Lett.,
1990, 31, 3023; (k) T. D. Blumke, Y.-H. Chen, Z. Peng and
P. Knochel, Nat. Chem., 2010, 2, 313.
¨
7 For some recent works on bismuth-mediated reactions, see; 14 Organoaluminium based reaction, see; (a) L.-N. Guo, H. Gao,
(a) H. Suzuki, N. Komatsu, T. Ogawa, T. Murafuji, T. Ikegami
and Y. Matano, Organobismuth Chemistry, Elsevier,
Amterdam, 2001; (b) K. Smith, S. Lock, G. A. El-Hiti,
M. Wada and N. Miyoshi, Org. Biomol. Chem., 2004, 2, 935.
P. Mayer and P. Knochel, Chem.–Eur. J., 2010, 16, 9829; (b)
Z.-L. Shen, Z. Peng, C.-M. Yang, J. Helberg, P. Mayer,
I. Marek and P. Knochel, Org. Lett., 2014, 16, 956; (c)
S. Saito, Sci. Synth., 2004, 7, 5.
8 For some papers on zinc-mediated reactions, see; (a) 15 For some works on the indium-based and other
K. Takao, T. Miyashita, N. Akiyama, T. Kurisu, K. Tsunoda
and K. Tadano, Heterocycles, 2012, 86, 147; (b) Y. Gao,
X. Wang, L. Sun, L. Xie and X. Xu, Org. Biomol. Chem.,
organometallic reagents addition to cycloalkanones see; (a)
K. Maruoka, T. Itoh, M. Sakurai, K. Nonoshita and
H. Yamamoto, J. Am. Chem. Soc., 1988, 110, 3588; (b)
40212 | RSC Adv., 2014, 4, 40199–40213
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
F. A. Carey and R. J. Sundberg, Advanced Organic Chemistry,
Parts A and B, Springer, New York, 2007; (c) L. A. Paquette
U. Schneider, I.-H. Chen and S. Kobayashi, Org. Lett., 2008,
10, 737.
and P. C. Lobben, J. Am. Chem. Soc., 1996, 118, 1917; (d) 18 For some recent papers on metal-mediated allylation of a-
A. Bellomo, R. Daniellou and D. Plusquellec, Tetrahedron
Lett., 2010, 51, 4934; (e) M. T. Reetz and H. Haning, J.
Organomet. Chem., 1997, 541, 117.
imino esters or related systems, see; (a) N. A. Aslam,
V. Rajkumar, C. Reddy, M. Yasuda, A. Baba and S. A. Babu,
Eur. J. Org. Chem., 2012, 4395 and references therein; (b)
N. A. Aslam, S. A. Babu, J. S. Arya, M. Yasuda and A. Baba,
Tetrahedron, 2013, 69, 6598 and references therein; (c) For
some reports on active indium species see, T. D. Haddad,
L. C. Hirayama and B. Singaram, J. Org. Chem., 2010, 75,
642; (d) M. Yasuda, M. Haga and A. Baba, Organometallics,
2009, 28, 1998; (e) M. Yasuda, M. Haga and A. Baba, Eur. J.
Org. Chem., 2009, 5513; (f) M. Yasuda, M. Haga,
Y. Nagaoka and A. Baba, Eur. J. Org. Chem., 2010, 5359; (g)
S. A. Babu, M. Yasuda, I. Shibata and A. Baba, J. Org.
Chem., 2005, 70, 10408; (h) S. A. Babu, M. Yasuda,
Y. Okabe, I. Shibata and A. Baba, Org. Lett., 2006, 8, 3029;
(i) K. Koszinowski, J. Am. Chem. Soc., 2010, 132, 6032; (j)
T. H. Chan and Y. Yang, J. Am. Chem. Soc., 1999, 121, 3228;
(k) G. Hilt, K. I. Smolko and C. Waloch, Tetrahedron Lett.,
2002, 43, 1437; (l) F. -X. Felpin and J. Lebreton, Eur. J. Org.
Chem., 2003, 3693.
16 For some recent papers on metal-mediated allylation of 2-
alkyl-2-carbethoxycycloalkanone, see; (a) R. Matovic,
A. Ivkovic, M. Manojlovic, Z. Tokic-Vujosevic and
R. N. Saicic, J. Org. Chem., 2006, 71, 9411; (b) C. Reddy,
S. A. Babu, N. A. Aslam and V. Rajkumar, Eur. J. Org.
Chem., 2013, 2362 and references therein; (c) The allylation
of various cyclopentanone systems afforded the respective
products with an excellent diastereoselectivity while the
allylation of various cyclohexanone systems gave the
corresponding
products
with
relatively
lower
diastereoselectivity. A similar trend was observed in our
previous work; see the ref. 16b. Though, we are unable to
predict the exact reason for this, however, the
conformational ipping in cyclohexane system could be
the possible reason for the involvement of a less rigid TS
thereby affording the products with relatively low
diastereoselectivity when compared to the cyclopentane 19 (a) B. Alcaide, P. Almendros and R. Rodriguez-Acebes, J. Org.
systems.
Chem., 2006, 71, 2346; (b) V. Nair, S. Ros, C. N. Jayan and
S. Viji, Synthesis, 2003, 16, 2542; (c) V. V. Rostovtsev,
L. G. Green, V. V. Fokin and K. B. Sharpless, Angew. Chem.,
Int. Ed., 2002, 41, 2596; (d) Naveen, S. A. Babu, G. Kaur,
N. A. Aslam and M. Karanam, RSC Adv., 2014, 4, 18904.
17 For some papers on indium-based allylation of imino
compounds, see; (a) A. Hietanen, T. Saloranta,
S. Rosenberg, E. Laitinen, R. Leino and L. T. Kanerva, Eur.
J. Org. Chem., 2010, 909; (b) P. C. Andrews, A. C. Peatt and
´
C. L. Raston, Green Chem., 2004, 6, 119; (c) V. Cere, F. Peri, 20 (a) T. Wang, X.-Q. Hao, X.-Q. Zhang, J.-F. Gong and
S. Pollicino and A. Ricci, Synlett, 1999, 1585; (d) B. Alcaide,
P. Almendros and C. Aragoncillo, Eur. J. Org. Chem., 2010,
2845; (e) T. Vilaivan, C. Winotapan, V. Banphavichit,
T. Shinada and Y. Ohfune, J. Org. Chem., 2005, 70, 3464; (f)
J. G. Lee, K. I. Choi, A. N. Pae, H. Y. Koh, Y. Kang and
Y. S. Cho, J. Chem. Soc., Perkin Trans. 1, 2002, 1314; (g)
T.-P. Loh, D. S.-C. Ho, K.-C. Xu and K.-Y. Sim, Tetrahedron
Lett., 1997, 38, 865; (h) H. Miyabe, A. Nishimura, M. Ueda
and T. Naito, Chem. Commun., 2002, 1454; (i) D. J. Ritson,
R. J. Cox and J. Berge, Org. Biomol. Chem., 2004, 2, 1921; (j)
M.-P. Song, Dalton Trans., 2011, 40, 8964; (b)
V. V. Kouznetsov, L. Y. V. Mendez, M. Sortino, Y. Vasquez,
M. P. Gupta, M. Freile, R. D. Enriz and S. A. Zhacchino,
Bioorg. Med. Chem., 2008, 16, 794; (c) T. J. Barker and
E. R. Jarvo, Org. Lett., 2009, 11, 1047; (d) T. Hamada,
K. Manabe and S. Kobayashi, Angew. Chem., Int. Ed., 2003,
42, 3927; (e) S. Zhu, X. Lu, Y. Luo, W. Zhang, H. Jiang,
M. Yan and W. Zeng, Org. Lett., 2013, 15, 1440; (f)
X. W. Sun, M. Liu, M. H. Xu and G. Q. Lin, Org. Lett., 2008,
10, 1259.
T. Hirashita, Y. Hayashi, K. Mitsui and S. Araki, J. Org. 21 Crystallographic data of the X-ray structures of the
Chem., 2003, 68, 1309; (k) R. Yanada, A. Kaieda and
Y. Takemoto, J. Org. Chem., 2001, 66, 7516; (l)
compounds 3g (CCDC 1001586) and 26c (CCDC 1001554).†
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 40199–40213 | 40213