Synthesis of 2-amino-1,3-dienes by chromium-catalyzed addition of silylated propargyl bromides to imines

Article abstract of DOI:10.1016/j.tet.2011.08.010

(Silyl)methylallenic amines were synthesized by the chromium-catalyzed addition of (4-bromobutynyl)trimethylsilane to tosyl imines. Regioisomeric mixtures of the desired allene and the corresponding alkyne were obtained. Allenic imines were then treated w

Full text of DOI:10.1016/j.tet.2011.08.010

Tetrahedron 67 (2011) 7901e7908
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Synthesis of 2-amino-1,3-dienes by chromium-catalyzed addition of silylated
propargyl bromides to imines
*
ꢀ
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María Duran-Galvan, Brian T. Connell
Department of Chemistry, Texas A&M University, PO Box 30012, College Station, TX 77842-3012, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 July 2011
Received in revised form 2 August 2011
Accepted 3 August 2011
Available online 7 August 2011
(Silyl)methylallenic amines were synthesized by the chromium-catalyzed addition of (4-bromobutynyl)
trimethylsilane to tosyl imines. Regioisomeric mixtures of the desired allene and the corresponding
alkyne were obtained. Allenic imines were then treated with TBAF to afford 2-aminomethyl-1,3-dienes in
good yields (62e92%). In the presence of a Lewis acid, silylallenic imines were added to benzaldehyde
dimethylacetal to give highly functionalized dienes with excellent yields and good to excellent di-
astereomeric ratios.
Keywords:
Chromium
Dienes
Ó 2011 Elsevier Ltd. All rights reserved.
Allenes
Imines
Regioselectivity
1. Introduction
method is broad and, in the presence of acid, imines can be formed
in situ from aniline and the corresponding aldehyde to afford the
The addition of carbon nucleophiles to imines is a powerful and
well-studied transformation for the preparation of nitrogen-
containing organic compounds and for the synthesis of bi-
ologically active natural products.1 However, methods for the
preparation of 2-aminomethyl-1,3-dienes are still uncommon.
An early report describes the palladium-catalyzed coupling of
amines with 2 equiv of propadiene gas to afford 2-aminomethyl-
1,3-dienes along with bis(dienyl)amine byproducts.2 Hosomi et al.3
reported the Kumada cross-coupling of Grignard reagents prepared
from 2-bromo-3-aminopropene to vinyl halides for the synthesis of
2-aminomethyl-1,3-dienes. This method proved to be efficient for
the synthesis of 1,3-dienes, which were further used in DielseAlder
cycloaddition reactions. Unfortunately, the synthesis of the starting
2-bromo-3-aminopropene is not convenient. Although both
methods afford the desired products with moderate to good yield,
the substrate scope is limited. More recently, metathesis of aryl
propargylic amines with ethylene, in the presence of Grubbs’ cat-
alyst, was utilized for the synthesis of 2-aminomethyl-1,3-dienes.4
These dienes can also be obtained by a regioselective titanium-
mediated cross-coupling of aryl imines with homoallenic alco-
hols.5 One of the advantages of this method is the ability to use
a range of protecting groups on nitrogen. Unfortunately, the use of
excess titanium complex is required. Finally, 2-aminomethyl-1,3-
dienes have been efficiently prepared by an indium mediated6 re-
action of imines with 1,4-dibromo-2-butyne. The scope of this
desired dienes in a three-component reaction.
In view of the limited number of methods for the synthesis of 2-
aminomethyl-1,3-dienes and aiming to expand the scope of the
chromium-catalyzed7e9 synthesis of substituted 1,3-butadienes
from aldehydes and ketones previously developed in our labora-
tory,10,11 we studied the reaction of imine electrophiles with (4-
bromobut-2-yn-1-yl)trimethylsilane 8.
2. Results and discussion
Metal-catalyzed additions to imines are well-known trans-
formations (e.g., allylation, alkylation, propargylation, etc.)1 Zinc,
magnesium, tin, palladium,12 and boron13 are examples of metals
used for this purpose. However, only one example of a stoichio-
metric chromium-mediated addition to imines has been reported
(Eq. 1).14 Therefore, we decided to first employ allyl bromide in
a chromium-catalyzed synthesis of homoallylic amines to establish
baseline reactivity in a catalytic process.
R
O
HN
1. R'NH2, MS 4
Br
H
2.
Å, THF
, BF3•OEt2
(1)
Ph
Ph
6
1
2
CrCl2 (2.5 equiv)
45-75%
* Corresponding author. E-mail address: connell@chem.tamu.edu (B.T. Connell).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.010

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M. Duran-Galvan, B.T. Connell / Tetrahedron 67 (2011) 7901e7908
Table 2
When N-phenyl and N-benzyl imines 3a or 4a were combined
Allenylation of iminesa
with allyl bromide in the presence of a catalytic amount of CrCl3,
2 equiv of Mn0 and TMSCl, the desired product was not observed,
albeit the imines were consumed as indicated by TLC (Table 1, en-
tries 1 and 2). On the contrary, when N-tosyl imine 5a was used, the
desired product was obtained in 80% conversion. It was suspected
that the product from the allylation of imines 3a and 4a was being
formed but may be coordinating to the chromium salts present in
the reaction mixture. If this were the case, the product would be
lost after filtration of the reaction mixture though silica. In order to
recover the desired adducts, an excess of Et3N and DMF was added
to the mixture prior to filtration, expecting the additives would
coordinate to the chromium salts and release the desired products
(entries 4e6). This procedure increased the yield in all cases, but we
observed that tosyl imine 5a (entry 7), activated by the presence of
an electron-withdrawing group, afforded the corresponding adduct
with higher conversion than the N-benzyl or N-phenyl derivatives.
Encouraged by these results, we directed our attention to the
synthesis of (silylmethyl)allenic amines. The corresponding imines
were mixed with (4-bromobut-2-yn-1-yl)trimethylsilane (8) in the
presence of CrCl2 (10 mol %), Mn0 (2 equiv) and TMSCl. A consid-
erable decrease in the reactivity of imines 3a and 4a, with respect to
the allylation reaction, was observed (Table 2). In addition, after
36 h, only traces of product were observed when electron deficient
3b was used. On the other hand, when tosyl imine 5a was used, the
desired adduct was obtained with 64% conversion. Thus, the
presence of the electron withdrawing tosyl group appears to be
necessary to increase the electrophilicity of the substrate under
these reaction conditions. The conversion did not improve when
the temperature of the reaction was increased to 60 ꢀC. Further-
more, addition of excess propargyl bromide 8 after 12 h did not
improve substrate conversion.
R1
R1
HN
R2
N
CrCl2, Mn0
Br
R2
H
TMSCl, THF, 36 h;
1 M HCl
TMS
3-5
8
9
TMS
Entry
R1
R2
Imine
Conversionb (%)
1
2
3
4
Ph
Ph
Bn
Ts
Ph
3a
3b
4a
5a
10
d
8
4-CF3eC6H4
Ph
Ph
64
a
Imine (1 equiv), propargyl bromide 8 (1.5 equiv), CrCl2 (10 mol %), Mn (2 equiv),
TMSCl (1.1 equiv), 36 h; then 1 M HCl (2 mL).
Determined by 1H NMR spectroscopy.
b
of propargylic reagents to electrophiles for the synthesis of allenic
compounds has been previously limited by low regioselectivity.
Interestingly, regioisomeric mixtures were never observed in our
previous studies of the allenylation of aldehydes and ketones.10,11
The reaction conditions were optimized as described in Table 3.
It was observed that increasing the amount of chromium catalyst
accelerates the reaction rate and favors the formation of the desired
allene 9a (entries 1e5) up to 30 mol % catalyst. When the reaction is
cooled to 0 ꢀC, alkyne 10a is obtained as a single product albeit with
low conversion (entry 6). Increasing the reaction temperature does
not favor allene 9a (entry 7). A large excess of propargyl bromide 8
reduces the reaction time to 16 h yet affords a 1:1.6 mixture of
regioisomers (entry 10). It was also observed that using CrCl3 in
place of CrCl2 or increasing the equiv of TMSCl have no effect on the
regioisomeric ratio. Also, use of additives, including Et3N and pyr-
idine, does not improve the ratio however it does slow down the
reaction. The reaction conditions can be tailored to afford the
propargylic amine as the major product. The formation 10a is
favored when the amount of catalyst if reduced. Absence of TMSCl,
the use of TESCl, or the use of large excess of Mn0 all favors the
formation of this regioisomer. This effect is equally observed when
propargyl bromide 11, containing a DMPS group in place of TMS, is
utilized (Table 4).
TMS
8a
TMS
Table 1
Table 3
Chromium-catalyzed allylation of iminesa
Optimization of allenylation conditionsa
R
R
NHTs
HN
N
CrCl3, Mn0, TMSCl
NTs
Br
Ph
Ph
H
Br
CrCl2, Mn0
Ph
THF, 16 h; then
7
1 M TBAF, 10 min
9a
6
3-5
Ph
H
TMSCl, THF, 48 h;
TMS
TMS
2 M HCl
5a
8
NHTs
Entry
R
Imine
Additiveb
Conversionc (%)
TMS
1
2
3
4
5
6
7
Ph
Bn
Ts
Ph
Bn
Bn
Ts
3a
4a
5a
3a
4a
4a
5a
d
d
Ph
10a
d
d
d
80
46
36
38
88
Entry
CrCl2 (%)
T (ꢀC)
Conversionb (%)
Ratiob (9a:10a)
DMF
DMF
Et3N
Et3N
1
2
5
10
15
30
50
10
10
30
30
30
rt
rt
rt
rt
rt
0
70
rt
rt
rt
87
99
91
99
99
27
99
23
82
91
1:1
2.5:1
2.6:1
3.5:1
3.5:1
0:1
2:1
2:1
2.5:1
1:1.6
3
4c
5
a
Imine (1 equiv), allyl bromide (1.5 equiv), CrCl3 (10 mol %), Mn (2 equiv), TMSCl
(1.1 equiv), 16 h.
b
6
7
Added after 16 h; then TBAF (1 M in THF, 1 equiv).
c
Determined by 1H NMR spectroscopy.
8d
9e
10f
The homo-coupled adduct, dienyne 8a, derived from 2 equiv of
8, was observed when unreactive substrates 3a, 3b, or 4a were
employed. A byproduct from the reaction of tosyl imine 5a and
propargyl bromide 8 was identified as the corresponding homo-
propargyl amine 10 (Table 2, entry 2). The mixture of regioisomers
was observed in a 2.5:1 ratio. It is known that propargylic organ-
ometallic reagents exist as an equilibrium mixture of allenic and
propargylic species.15,16 Hence, the use of metal-catalyzed additions
a
Imine 5a (1 equiv), propargyl bromide 8 (1.5 equiv), CrCl2 (30 mol %), Mn
(2 equiv), TMSCl (1.1 equiv), 48 h; then 1 M HCl (2 mL).
b
Determined by 1H NMR spectroscopy.
Propargyl bromide (2 equiv).
Solvent: CH3CN.
Mn (5 equiv).
c
d
e
f
Propargyl bromide 8 (3 equiv), reaction time: 16 h.

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M. Duran-Galvan, B.T. Connell / Tetrahedron 67 (2011) 7901e7908
7903
Ts
after 3 days (entry 4).
a
,
b
-unsaturated imine 9e is a poor substrate
Ts
TMSN
R
HN
for the allenylation reaction giving the corresponding allene in only
16% yield (entry 5). On the contrary, aliphatic allene 9f was
obtained in excellent yield with 10:1 regioselectivity in favor of the
desired allene (entry 6). When the more sterically hindered ortho-
substituted imine 5g is utilized, a 1.3:1 mixture of products 9g and
10g is observed (Eq. 4).
TBAF (1.5 equiv)
10-30 min
(2)
(3)
R
TMS
9
TMS
silylated-9
Ts
Ts
TMSN
R
HN
TMS
TBAF (1.5 equiv)
10-30 min
Ts
H3C
HN
R
14
silylated-10
Br
9g
Ts
H
8
TMS
SiMe3
H3C
N
35%
Table 4
CrCl2 (30 mol%), Mn0(2 equiv)
TMSCl (1.1 equiv), THF, 48 h;
1 M TBAF, THF, 10 min
90%
Use of propargyl bromide 11a
(4)
Ts
H3C
HN
NHTs
5g
Ts
N
1.3:1
Ph
CrCl2, Mn0
Br
10g
12
DMPS
TMSCl, THF, 48 h;
2 M HCl
33%
Ph
H
DMPS
NHTs
11
5a
DMPS
Ph
13
These (silylmethyl)allenic amines were successfully trans-
formed to the desired 2-aminomethyl-1,3-dienes by treatment
with TBAF in good to excellent yields (Table 6). This method was
equally efficient for desilylation of aromatic and aliphatic allenic
amines. 2-aminomethyl-1,3-diene 15b was obtained in 62% yield
albeit a 74% conversion (entry 2). This reaction was not allowed to
go to completion to avoid decomposition of the product. Electron
rich diene 15d was obtained in 84% yield (entry 3). Aliphatic
allene was successfully transformed to the diene in excellent yield
(entry 4). Finally, allenic imine 9g afforded the desired diene in the
presence of an ortho-substituent (entry 5).
Entry
CrCl2 (%)
Ratiob (12:13)
Yieldb (%)
1
30
10
3:1
1:3.3
52
42
2c
Imine 5a (1 equiv), propargyl bromide 11 (1.5 equiv), Mn0 (2 equiv), 16 h; then
a
2 M HCl (2 mL).
b
Determined by 1H NMR spectroscopy.
No TMSCl added.
c
Due to the difficulty separating 9 from 10, the unpurified N-
silylated mixture of isomers was treated with 1.5 equiv of TBAF.
After w10 min, silylated-10 reacted with TBAF to give the corre-
sponding bis(desilylated) allene 14. While mono(desilylation) of
the more hindered silylated-9 occurred quickly, reaction of the
allylsilane was significantly slower. Hence, the resulting mixture of
allenes 9 and 14 could be easily separated by column chromatog-
raphy (Eqs. 2 and 3).
A sampling of tosyl imines was treated to the standard reaction
conditions. Aromatic imines give the corresponding adducts in
good yields (Table 5, entries 1 and 2). Imine 5c, containing an
electron withdrawing group, is consumed after 16 h under the re-
action conditions albeit affording allene 9c in low yield (entry 3).
The presence of an electron donating group in the substrate in-
creases the reaction time, thus allene 9d was obtained in 53% yield
Table 6
Synthesis of 2-aminomethyl-1,3-dienesa
Ts
Ts
HN
HN
TBAF (2 equiv)
THF, 24 h
R
R
9
15
TMS
Entry
Allene
R
Product
Yieldb (%)
1
2
3
4
5
9a
9b
9d
9f
Ph
15a
15b
15d
15f
81
62
84
92
73
p-BreC6H4
p-MeOeC6H4
PhCH2CH2
o-MeeC6H4
9g
15g
a
Allene 9 (1 equiv) TBAF (1 M in THF, 1 equiv and 1 more equiv after 3 h).
Isolated yields.
b
Table 5
Synthesis of allenic sulfonamidesa
(Silylmethyl)allenes are known to react with several electro-
Ts
philes including acyl iminium ions,17 halogens,18,19 aldehydes, and
acetals20 to afford highly functionalized dienes. To further illustrate
the usefulness of (silylmethyl)allenes 9 for the synthesis of highly
functionalized 1,3-dienes, allenic amine 9a was mixed with differ-
ent electrophiles in the presence of a Lewis acid (Table 7). The
corresponding dienes were not obtained in the presence of benz-
aldehyde or 3-phenylpropanal (entries 1 and 2). However, the de-
sired product was formed in 46% conversion using benzaldehyde
dimethylacetal with TiCl4 as a Lewis acid (entry 3). To increase the
yield of the reaction and avoid the formation of byproducts, the
milder Lewis acid BF3$OEt2 was successfully employed to deliver
diene 16a with 100% conversion.
Ts
HN
N
CrCl2 (30 mol%), Mn0
Br
R
TMSCl, THF, 48 h;
R
H
TMS
1 M TBAF, 10- 30 min
9
5
8
TMS
Entry
Imine
R
Product
Conversionb (%)
Yieldc (%)
1
2
5a
5b
5c
5d
5e
5f
Ph
9a
9b
9c
9d
9e
9f
78
73
38
56
d
73
56
25
53
16
84
p-BreC6H4
3
p-CF3eC6H4
p-MeOeC6H4
trans-PhCH]CH
PhCH2CH2
4d
5
6
91
a
Imine
5 (1 equiv), propargyl bromide 8
(2 equiv), CrCl3 (30 mol %), Mn0
To study the scope of this dienylation reaction, we exposed
several allenic sulfonamides to benzaldehyde dimethylacetal in the
presence of 1 equiv of BF3$OEt2 at ꢁ78 ꢀC (Table 8). The desired
products were obtained after 2e3 h in excellent yields for both
(2 equiv), TMSCl (1.1 equiv), 48 h; then TBAF (1 M in THF, 1.5 equiv).
b
Determined by 1H NMR.
Isolated yield.
Reaction time: 3 days, propargyl bromide (3 equiv), 1 equiv added after 48 h.
c
d

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M. Duran-Galvan, B.T. Connell / Tetrahedron 67 (2011) 7901e7908
7904
Table 7
purification system. Other commercially available reagents were
Synthesis of highly functionalized 1,3-dienesa
used as received. Reactions were monitored by analytical thin layer
chromatography using 0.25 mm glass-backed silica gel plates. Flash
column chromatography was performed using silica gel
(230e400 mesh). Visualization was accomplished by UV light and
potassium permanganate.
TsHN
Ph
TsHN
Ph
electrophile (1.5 equiv)
Lewis acid (1.5 equiv)
R1
CH2Cl2, – 78 °C
R2
9a
TMS
16
1H NMR spectra were recorded at 300 MHz and referenced to
CDCl3 (d
7.27). 1H NMR coupling constants (J) are reported in hertz
Entry
Electrophile
Lewis acid
R1
R2
Yieldb (%)
(Hz) and multiplicities are indicated by: s (singlet), d (doublet), t
(triplet), q (quartet), quint (quintet), m (multiplet), dt (doublet of
triplets), td (triplet of doublets), tt (triplet of triplets), dq (doublet of
quadruplets), br (broad), dd (doublet of doublets). Proton-
decoupled 13C NMR spectra were recorded at 75 MHz and repor-
1
2
3
4
PhCHO
TiCl4
TiCl4
TiCl4
BF3$OEt2
Ph
OH
OH
OMe
OMe
d
PhCH2CH2CHO
PhCH(OMe)2
PhCH(OMe)2
CH2CH2Ph
Ph
Ph
d
46
100
a
Imine 9a (1 equiv), electrophile (1.6 equiv), TiCl4 (1.5 equiv), ꢁ78 ꢀC, 16 h.
b
Determined by 1H NMR spectroscopy.
ted relative to CDCl3 (d 77). Infrared spectra were obtained as thin
film on NaCl plates.
Table 8
Dienylation with benzaldehyde dimethylacetala
4.2. Preparation of tosyl imines
TsHN
OMe
TsHN
4.2.1. N-Benzylideneaniline (3a)23. Prepared following the pro-
cedure described for the synthesis of compound 3b. Product
obtained as a light yellow solid (3 g, 16.5 mmol, 60%) 1H NMR
BF3•OEt2 (1.5 equiv)
Ph
OMe
R
Ph
OMe
R
CH2Cl2, – 78°C
9
16
TMS
(CDCl3, 300 MHz)
d 8.50 (s, 1H), 7.99 (m, 2H), 7.55e7.49 (m, 3H),
major diastereomer
7.47e7.40 (m, 2H), 7.28e7.22 (m, 3H); 13C NMR (75 MHz, CDCl3)
160.4, 152.0, 136.2, 131.3, 129.1, 128.8, 128.7, 125.9, 120.8.
Entry
Allene
R
Product
Yieldb (%)
drc
1
2
3
4
9a
9b
9d
9f
Ph
16a
92
93
95
78
1:3
1:3
1:3
1:9
4.2.2. N-(4-(Trifluoromethyl)benzylidene)aniline (3b)24. p-(Trifluoro-
methyl)benzaldehyde (1.36 mL, 10 mmol) and aniline (0.8 mL,
9 mmol) were dissolved in toluene (100 mL) and stirred under reflux
for 16 h. The solution was cooled to rt and toluene was removed
under reduced pressure. After recrystallization from hexanes the
product was obtained as a white solid (1.93 g, 7.75 mmol, 77%). 1H
p-BreC6H4
p-MeOeC6H4
PhCH2CH2
16b
16c
16d
a
Imine (1 equiv), aldehyde/acetal (1.6 equiv), BF3$OEt2 (1.5 equiv), ꢁ78 ꢀC.
Isolated yields.
b
c
syn/anti; determined by 1H NMR spectroscopy.
NMR (CDCl3, 300 MHz)
d
8.54 (s, 1H), 8.06 (d, J¼8.0 Hz, 2H), 7.77 (d,
J¼8.2 Hz, 2H), 7.49e7.41 (m, 2H), 7.34e7.29 (m, 3H); 13C NMR
(75 MHz, CDCl3) 158.5, 129.2, 128.9, 126.5, 125.6 (q, J¼4.3 Hz), 120.8.
aromatic and aliphatic substrates. A 1:3 diastereomeric mixture was
obtained for the aromatic substrates (entries 1e3), while aliphatic
substrate 9f afforded the desired diene in a 1:9 dr (entry 4). We have
tentatively assigned the major diastereomer as the anti isomer,
based on the strong precedent provided by several studies of chiral
allylsilane additions to aldehydes in the presence of BF3$OEt2.21,22
4.2.3. N-Benzylidene-1-phenylmethanamine (4a)25. A mixture of
benzaldehyde (2.6 mL, 25.6 mmol), benzylamine (2.8 mL,
25.6 mmol), and MgSO4 (7 g) in 25 mL of benzene was stirred at rt
for 24 h. After this time, MgSO4 was removed by filtration and
rinsed with CH2Cl2. The solution was then concentrated under re-
duced pressure to give a yellow oil. The residue was distilled under
reduced pressure (105e120 ꢀC at 320 mTorr) to afford a clear oil
3. Conclusions
(2.6 g, 13.3 mmol, 51%). 1H NMR (CDCl3, 300 MHz)
d 8.44 (t,
The presence of an electron withdrawing tosyl group is funda-
mental to increase the reactivity of the imines toward nucleophilic
additions catalyzed by chromium. Interestingly, the regioselectivity
of the allenylation reaction was drastically affected by the presence
of a bulky tosyl group in the substrate leading to the formation of
regioisomeric mixtures not observed with aldehydes or ketones.
The nature of the substituent on the imine affects the isomer ratio,
with smaller substituents favoring the formation of the desired
allenic amine. Allenic imines can be desilylated to deliver of 2-
aminomethyl-1,3-dienes and furthermore, benzaldehyde dime-
thylacetal can be used in the preparation of more complex 1,3-
dienes in excellent yields. The development of this methodology
provided a novel route for the preparation of a variety of highly
functionalized 1,3-dienes, making this transformation a valuable
tool for the synthesis of complex organic compounds.
J¼1.4 Hz, 1H), 7.85e8.81 (m, 2H), 7.49e7.44 (m, 3H), 7.40e7.38 (m,
4H), 7.32 (m, 1H), 4.87 (d, J¼1.4 Hz, 2H); 13C NMR (75 MHz, CDCl3)
162.0, 139.2, 136.1, 130.7, 128.6, 128.4, 128.2, 127.9, 126.9, 65.0.
4.2.4. N-Benzylidene-4-methylbenzenesulfonamide (5a)26. Following
the procedure reported by Wynne et al., p-toluenesulfonamide
(4.5 g, 26.3 mmol) was mixed with dry toluene (70 mL). Next,
benzaldehyde (2.4 mL, 26.3 mmol) was added via syringe and the
mixture was heated to reflux with a DeaneStark trap for 24 h or until
completion of the reaction as judged by 1H NMR. After the solution
was cooled down, toluene was removed under reduced pressure to
afford a white solid. The compound was recrystallized from diethyl
ether to afford the pure imine as white (6.16 g, 23.7 mmol, 90%). 1H
NMR (CDCl3, 300 MHz)
d
9.02 (s, 1H), 7.91 (m, 4H), 7.6 (t, J¼7.0 Hz,
1H), 7.48 (t, J¼7.6 Hz, 2H), 7.34 (d, J¼8.3 Hz, 2H), 2.43 (s, 3H); 13C
NMR (75 MHz, CDCl3)
128.0, 126.2, 21.6.
d 170.1, 144.5, 134.4, 132.3, 131.2, 129.7, 129.1,
4. Experimental section
4.1. General information
4.2.5. N-(4-Bromobenzylidene)-4-methylbenzenesulfonamide
(5b)27. Following a modification of the procedure reported by
Duguet et al.,27 p-toluenesulfonamide (1.4 g, 7.78 mmol) was mixed
with dry toluene (70 mL). Next aldehyde (7.78 mmol) and BF3$OEt2
All reactions were performed under an argon atmosphere in
oven-dried glassware with magnetic stirring. TMSCl was distilled
from CaH2 before use. THF and CH2Cl2 were dried with a solvent
(300 ml) were sequentially added to the reaction mixture via

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M. Duran-Galvan, B.T. Connell / Tetrahedron 67 (2011) 7901e7908
7905
syringe. Mixture was heated to reflux with a DeaneStark trap for
24 h or until completion of the reaction as judged by 1H NMR. After
the solution was cooled down, EtOAc was added to completely
dissolve the newly formed precipitate (if any). The solution was
washed with 1 M NaOH and brine. The organic phase was dried
over Mg2SO4 and concentrated under reduced pressure. The solid
was recrystallized from a mixture of EtOAc and hexanes to afford
the pure imine. Obtained as a white solid (1.4 g, 4.18 mmol, 53%) 1H
(75 MHz, CDCl3) d 168.6, 144.4, 142.2, 135.4, 134.5, 131.4, 130.46,
130.4, 129.7, 128.0, 126.5, 21.5, 19.6.
4.2.11. 4-Methyl-N-(1-phenylbut-3-en-1-yl)benzenesulfonamide
(7)12. Inside a nitrogen atmosphere drybox, a mixture of CrCl3
(4.5 mg, 0.03 mmol) and Mn powder 325-mesh (33 mg, 0.66 mmol)
were added to a 2-dram vial. The vial was capped with a Teflon lid
and it was removed from the drybox. Tosyl imine 5a (77 mg,
0.3 mmol) was added to the mixture and the vial was flushed with
argon. Dry THF (2 mL) was added via syringe and a brown suspen-
NMR (CDCl3, 300 MHz)
J¼8.7 Hz, 2H), 7.65 (d, J¼8.3 Hz, 2H), 7.65 (d, J¼8.5 Hz, 2H), 2.45 (s,
d
9.98 (s, 1H), 7.89 (d, J¼8.7 Hz, 2H), 7.79 (d,
3H); 13C NMR (75 MHz, CDCl3)
131.2, 130.2, 129.8, 128.1, 21.6.
d
168.8, 144.8, 134.8, 132.5, 132.3,
sion was formed. This was followed by addition of TMSCl (42
ml,
0.33 mmol) and freshly distilled allyl bromide (40 L, 0.45 mmol).
m
The mixture was stirred at rt for 16 h. EtOAc (1e2 mL) was added to
the gray suspension and the mixture was filtered through a path of
silica to remove solids. The resulting clear solution was concentrated
under reduced pressure and the residue was redissolved in THF
(3 mL). TBAF (1 M in THF, 0.3 mL, 0.3 mmol) was added and the
mixture was stirred for 10 min. A saturated solution of NH4Cl was
added and the mixture was extracted with EtOAc. The organic
phases were dried over Mg2SO4, filtered though a path of silica and
concentrated under reduced pressure. The residue was purified by
flash chromatography using a gradient of EtOAc in hexanes (15e20%)
to afford the desired product as a clear oil (80 mg, 0.27 mmol, 88%)
4.2.6. 4-Methyl-N-(4-(trifluoromethyl)benzylidene)benzenesulfona-
mide (5c)28. Obtained as a white solid (1.95 g, 5.9 mmol, 31%) 1H
NMR (CDCl3, 300 MHz)
J¼8.2 Hz, 2H), 7.76 (d, J¼8.5 Hz, 2H), 7.38 (d, J¼7.9 Hz, 2H), 2.4 (s,
3H); 13C NMR (75 MHz, CDCl3)
168.4, 145.1, 134.4, 131.3, 129.9,
d
9.1 (s, 1H), 8.06 (d, J¼8.5 Hz, 2H), 7.91 (d,
d
128.3, 126.2 (q, J¼3.9 Hz), 19.4; MS (ESI) calcd for C15H12F3NO2S
237.0541, found 237.9835.
4.2.7. N-(4-Methoxybenzylidene)-4-methylbenzenesulfonamide
(5d)29. Obtained as white crystals (4.1 g, 14 mmol, 85%) 1H NMR
(CDCl3, 300 MHz)
J¼8.4 Hz, 2H), 7.34 (d, J¼8.2 Hz, 2H), 6.78 (d, J¼9.1 Hz, 2H), 3.9 (s,
3H), 2.4 (s, 3H); 13C NMR (75 MHz, CDCl3)
169.2, 165.2, 144.5,
d
9.95 (s, 1H), 7.9 (d, J¼8.1 Hz, 2H), 7.8 (d,
1H NMR (CDCl3, 300 MHz)
d
7.57 (d, J¼7.6 Hz, 2H), 7.20e7.05 (m, 7H),
5.51 (m, 1H), 5.23 (d, J¼7.0 Hz, 1H), 5.13 (m, 2H), 4.46 (q, J¼6.8 Hz,
d
1H), 2.46 (q, J¼6.2 Hz, 2H), 2.37 (s, 3H); 13C NMR (75 MHz, CDCl3)
135.8, 133.7, 129.7, 127.9, 125.2, 114.6, 55.6, 21.7; HRMS (ESI) calcd
d 143.0, 140.3, 137.5, 133.1, 129.2, 128.3, 127.3, 127.1, 126.5, 119.1, 57.2,
for C15H15NO3S (MþH) 290.0851, found 290.0860.
41.8, 21.4.
4.2.8. 4-Methyl-N-((E)-3-phenylallylidene)benzenesulfonamide
(5e)27. Obtained as light brown crystals (0.83 g,1.33 mmol, 25%). 1H
NMR (CDCl3, 300 MHz)
d
9.78 (d, J¼9.4 Hz, 1H), 7.86 (d, J¼8.8 Hz,
4.3. General method for the preparation of (silylmethyl)
allenic amines (9)
2H), 7.58e7.51 (m, 2H), 7.47e7.41 (m, 4H), 7.34 (d, J¼8.0 Hz, 2H)
6.99 (dd, J¼9.4, 15.8 Hz, 2H), 2.43 (s, 3H); 13C NMR (75 MHz, CDCl3)
d
170.9, 153.8, 144.5, 135.3, 134.1, 131.7, 129.8, 129.2, 128.6, 128.0,
Inside a nitrogen atmosphere drybox, a mixture of CrCl2 (11 mg,
0.09 mmol) and Mn powder 325-mesh (33 mg, 0.66 mmol) were
added to a 2-dram vial. The vial was capped with a Teflon lid and it
was removed from the drybox. The tosyl imine (0.3 mmol) was
added to the mixture and the vial was flushed with argon. Dry THF
(2 mL) was added via syringe and a brown suspension was formed.
124.7, 21.7; HRMS (ESI) calcd for C16H15NO2S (MþH) 286.0902,
found 286.0913.
4.2.9. 4-Methyl-N-(3-phenylpropylidene)benzenesulfonamide
(5f)30. Prepared following the procedure described for the prepa-
ration of compound 5g as previously described by Wipf.30 Obtained
This was followed by addition of TMSCl (42 mL, 0.33 mmol) and (4-
as
a
white solid after recrystallization from hexanes (1.4 g,
bromo-2-butyn-1-yl)trimethylsilane (120 mg, 0.6 mmol). The
mixture was stirred at rt for 48 h Et3N (1 mL) and EtOAc (1e2 mL)
were added to the gray suspension and the brown mixture was
filtered trough a path of silica using EtOAc as eluent. The resulting
clear solution was concentrated under reduced pressure and the
residue was redissolved in THF (3 mL). TBAF (1 M in THF, 0.45 mL,
0.45 mmol) was added to the solution in two parts over 10 min. The
mixture was stirred for a maximum of 30 min or until the majority
of propargylamine is consumed to afford the corresponding
homoallenic amine as judged by TLC (eluent 20% EtOAc in hexanes).
The yellow solution was again filtered through a path of silica using
EtOAc as eluent. The resulting solution was concentrated under
reduced pressure to give a yellow oil. The residue was purified by
flash chromatography using a gradient of EtOAc in hexanes
(0e10%).
4.9 mmol, 49%). 1H NMR (CDCl3, 300 MHz)
d
8.62 (t, J¼4.1 Hz, 1H),
7.77 (d, J¼8.5 Hz, 2H), 7.33 (J¼8.1 Hz, 2H), 7.28e7.10 (m, 5H),
2.98e2.92 (m, 2H), 2.88e2.80 (m, 2H), 2.4 (s, 3H); 177.4, 144.7,
139.6, 134.3, 129.8, 128.6, 128.3, 128.1, 126.4, 37.3, 30.6, 21.6; IR (thin
film) 2925,1629,1453,1090 cmꢁ1; HRMS (ESI) calcd for C16H17NO2S
(MþLi) 294.1140, found 294.1127.
4.2.10. 4-Methyl-N-(2-methylbenzylidene)benzenesulfonamide
(5g)31. Prepared following the procedure described by Chemla
et al.32 Sodium p-toluenesulfinate (1.78 g, 10 mmol), p-toluene-
sulfonamide (1.71 g, 10 mmol), and o-methylbenzaldehyde
(1.15 mL, 10 mmol) were dissolved in a 1:1 solution of formic acid/
H2O (30 mL). The mixture was stirred at rt for 1 week until the
aldehyde was consumed as judged by TLC. After this time, the white
precipitate was collected by filtration and rinsed with water and
hexanes. The white solid was dissolved in CH2Cl2 (50 mL), a satu-
rated solution of NaHCO3 (50 mL) was added and the mixture was
stirred for 2 h. The aqueous layer was extracted with CH2Cl2. The
combined organic phases were washed with brine dried over
MgSO4 and concentrated under reduced pressure. The desired
imine was obtained as a white solid and was used without further
purification (2.02 g, 7.4 mmol, 74%) 1H NMR (CDCl3, 300 MHz)
4.3.1. 4-Methyl-N-(1-phenyl-2-((trimethylsilyl)methyl)buta-2,3-
dien-1-yl)benzenesulfonamide (9a). Obtained as
a
white solid
(83 mg, 22 mmol, 73%). 1H NMR (CDCl3, 300 MHz)
d 7.60 (d, 2H),
7.25e7.13 (m, 7H), 5.06 (d, J¼8.0 Hz, 1H), 4.95e4.88 (dq, J¼2.84,
9.8 Hz,1H), 4.84e4.77 (dq, J¼3.0, 9.8 Hz,1H), 4.64 (dt, J¼2.5, 7. 7 Hz,
1H), 2.39 (s, 3H), 1.07 (dt, J¼3.0, 15.1 Hz, 1H), 0.99 (dt, J¼2.99,
15.1 Hz, 1H), ꢁ0.07 (s, 9H); 13C NMR (75 MHz, CDCl3)
d 204.9,
d
9.95 (s, 1H), 7.9 (d, J¼8.1 Hz, 2H), 7.8 (d, J¼8.4 Hz, 2H), 7.34 (d,
142.99, 139.3, 137.7, 129.2, 128.4, 127.7, 127.6, 127.1, 102.7, 80.5, 59.3,
J¼8.2 Hz, 2H), 6.78 (d, J¼9.1 Hz, 2H), 3.9 (s, 3H), 2.4 (s, 3H); 13C NMR
21.4, 18.3, ꢁ1.3; IR (thin film) 3277, 2954, 1955, 1330, 1162 cmꢁ1
;

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M. Duran-Galvan, B.T. Connell / Tetrahedron 67 (2011) 7901e7908
7906
HRMS (MALDI) calcd for C21H27NO2SSi (MþNa) 408.1429, found
J¼8.4 Hz, 2H), 7.16 (J¼8.3 Hz, 2H), 7.13e7.03 (m, 4H), 4.96 (s, 2H),
4.86 (m, 1H) 4.62 (m, 1H), 2.38 (s, 3H), 2.33 (s, 3H), 1.16 (dt, J¼3.0,
15.1 Hz, 1H), 0.89 (dt, J¼2.8, 15.2 Hz, 1H), ꢁ0.05 (s, 0H); 13C NMR
408.1439.
4.3.2. N-(1-(4-Bromophenyl)-2-((trimethylsilyl)methyl)buta-2,3-
(75 MHz, CDCl3) d 205.3, 142.8, 137.9, 137.1, 136.4, 130.6, 129.1, 127.6,
dien-1-yl)-4-methylbenzenesulfonamide (9b). Obtained as a clear oil
127.3, 127.1, 126.0, 102.5, 80.3, 56.1, 21.4, 19.1, 18.2, ꢁ1.3; IR (thin
film) 3280, 1955, 1599, 1331, 1161 cmꢁ1; HRMS (ESI) calcd for
C19H21NO2S (MþNa) 422.1586, found 422.1598.
(81 mg, 0.17 mmol, 58%) 1H NMR (CDCl3, 300 MHz)
d
1H NMR
(CDCl3, 300 MHz)
d
7.55 (d, J¼8.4 Hz, 2H), 7.31 (d, J¼8.4 Hz, 2H), 7.17
(d, J¼8.0 Hz, 2H), 7.06 (d, J¼8.4 Hz, 2H), 5.14 (d, J¼8.1 Hz, 1H), 4.9
(dq, J¼2.9, 10.0 Hz, 1H), 4.8 (dq, J¼2.9, 10.1 Hz, 1H), 4.59 (dt, J¼3.2,
7.4 Hz, 1H), 2.39 (s, 3H), 1.15 (dt, J¼3.2, 15.0 Hz, 1H), 0.9 (dt, J¼2.9,
4.3.8. 4-Methyl-N-(1-(o-tolyl)penta-3,4-dien-1-yl)benzenesulfona-
mide (14g). Obtained as a white solid (34 mg, 0.10 mmol, 35%) 1H
15.1 Hz, 1H), ꢁ0.7 (s, 9H); 13C NMR (75 MHz, CDCl3)
d
204.7, 143.2,
NMR (CDCl3, 300 MHz)
d
7.53 (d, J¼8.3 Hz, 2H), 7.12 (d, J¼7.9 Hz,
138.3, 137.5, 131.4, 129.4, 129.3, 127.1, 121.7, 102.3, 80.9, 58.8, 21.4,
18.3, ꢁ1.2; IR (thin film) 3277, 1958, 1334, 1163 cmꢁ1; HRMS
(MALDI) calcd for C21H26NO2SSi (MþNa) 486.0535, found
486.0552.
2H), 7.09e6.98 (m, 4H), 4.87 (d, J¼6.3 Hz, 1H), 4.85 (quint, J¼7.0 Hz,
1H), 4.65 (m, 3H), 2.38 (m, 2H), 2.36 (s, 3H), 2.21 (s, 3H); 13C NMR
(75 MHz, CDCl3) d 209.7,143.1, 138.2, 137.4, 134.8, 130.3, 129.2, 127.2,
127.0, 126.1, 124.9, 85.1, 75.3, 53.5, 36.0, 21.4, 19.1; IR (thin film)
3276, 1956, 1331, 1158 cmꢁ1; HRMS (ESIþ) calcd for C19H21NO2S
(MþH) 328.1371, found 328.1360.
4.3.3. 4-Methyl-N-(1-(4-(trifluoromethyl)phenyl)-2-((trimethylsilyl)
methyl)buta-2,3-dien-1-yl)benzenesulfonamide (9c). Obtained as
a clear oil (27 mg, 0.06 mmol, 20%); 1H NMR (CDCl3, 300 MHz)
4.3.9. 4-Methyl-N-(1-phenyl-5-(trimethylsilyl)pent-3-yn-1-yl)ben-
d
7.50 (d, J¼8.3 Hz, 2H), 7.48 (d, J¼7.9 Hz, 2H), 7.21 (d, J¼8.1 Hz, 2H),
zenesulfonamide (10a). Obtained as a white solid. 1H NMR (CDCl3,
7.11 (d, J¼8.1 Hz, 2H), 5.16 (d, J¼7.2 Hz, 1H), 4.93 (dq, J¼2.9, 10.2 Hz,
1H), 4.87 (dq, J¼3.0, 10.2 Hz, 1H), 4.67 (dt, J¼3.0, 7.3 Hz, 1H), 2.34 (s,
3H), 1.16 (dt, J¼2.9, 15.1 Hz, 1H), 0.96 (dt, J¼2.7, 15.1 Hz, 1H), ꢁ0.06
300 MHz)
d
7.61 (d, J¼8.3 Hz, 2H), 7.22e7.14 (m, 7H), 5.15 (d,
J¼7.1 Hz, 1H), 4.42 (q, J¼6.0 Hz, 1H), 2.58 (dt, J¼2.7, 5.9 Hz, 2H), 2.39
(s, 3H), 1.38 (t, J¼2.7 Hz, 2H), ꢁ0.03 (s, 9H); 13C NMR (75 MHz,
(s, 9H); 13C NMR (75 MHz, CDCl3)
d
204.6, 143.2, 137.3, 129.2, 128.0,
CDCl3) d 143.1, 139.7, 137.3, 129.3, 128.3, 128.2, 127.6, 127.5, 127.1,
127.0, 125.1 (q, J¼3.6 Hz) 102.2, 81.0, 58.9, 21.3, 18.3, ꢁ1.3; IR (thin
film) 2956, 1956, 1326, 1162 cmꢁ1; HRMS (MALDI) calcd for
C22H26F3NO2SSi (MþNa) 476.1303, found 476.1292.
126.6, 82.1, 72.8, 56.0, 27.6, 21.4, 6.9, ꢁ2.1; IR (thin film) 3257, 3032,
2223, 1330, 1161 cmꢁ1; HRMS (ESI) calcd for C21H27NO2SSi (MþNa)
408.1429, found 408.1204.
4.3.4. N-(1-(4-Methoxyphenyl)-2-((trimethylsilyl)methyl)buta-2,3-
4.3.10. N-(2-((Dimethyl(phenyl)silyl)methyl)-1-phenylbuta-2,3-
dien-1-yl)-4-methylbenzenesulfonamide (12). After the reaction
mixture was stirred for 48 h as described in the general procedure,
HCl (2 M, 1 mL) and EtOAc (1e2 mL) were added to the gray sus-
pension and the green mixture was stirred for 1 h. The resulting
mixture was extracted with three portions of EtOAc. Combined
organic phases were washed with brine, dried over MgSO4, and
concentrated under reduced pressure. The residue was purified by
flash chromatography using a gradient of EtOAc in hexanes (0e10%)
to give the desired product as a white solid (69 mg, 0.15 mmol,
dien-1-yl)-4-methyl benzenesulfonamide (9d). Obtained as a clear
oil (66 mg, 0.16 mmol, 53%) 1H NMR (CDCl3, 300 MHz)
d 7.59 (d,
J¼8.45 Hz, 2H), 7.18 (d, J¼7.74 Hz, 2H), 7.06 (d, J¼9.45 Hz, 2H), 6.47
(d, J¼8.80 Hz, 2H), 5.09 (d, J¼7.60 Hz, 1H), 4.9 (dq, J¼3.0, 9.71 Hz,
1H), 4.7 (dq, J¼3.0, 9.78 Hz, 1H), 4.59 (dt, J¼3.18, 7.54 Hz, 1H), 3.77
(s, 3H), 2.38 (s, 3H), 1.16 (dt, J¼2.95, 15.21 Hz, 1H), 0.89 (dt, J¼2.71,
15.2 Hz, 1H), ꢁ0.06 (s, 9H); 13C NMR (75 MHz, CDCl3)
d 201.8, 159.1,
142.8, 137.8, 131.4, 129.2, 128.8, 127.2, 113.7, 102.7, 80.4, 58.8, 55.2,
21.4, 18.4, ꢁ1.2; IR (thin film) 3277, 3033, 2898, 1956, 1328,
1161 cmꢁ1
438.1535, found 438.1555.
;
HRMS (MALDI) calcd for C22H29NO2SSi (MþNa)
52%). 1H NMR (CDCl3, 300 MHz)
d
7.52 (d, J¼8.4 Hz, 2H), 7.42e7.31
(m, 5H), 7.20e7.12 (m, 5H), 7.01 (m, 2H), 4.99 (d, J¼7.6 Hz, 1H), 4.83
(dq, J¼2.6, 9.9 Hz, 1H), 4.7 (dq, J¼3.0, 10.0 Hz, 1H), 4.57 (dt, J¼3.2,
7.7 Hz, 1H), 2.38 (s, 3H), 1.43 (dt, J¼2.7, 15.2 Hz, 1H), 1.17 (dt, J¼2.8,
15.1 Hz, 1H), 0.23 (s, 3H), 0.19 (s, 3H); 13C NMR (75 MHz, CDCl3)
4.3.5. 4-Methyl-N-(1-phenyl-4-((trimethylsilyl)methyl)hexa-1,4,5-
trien-3-yl)benzenesulfonamide (9e). Obtained as a clear oil (20 mg,
0.05 mmol, 16%) 1H NMR (CDCl3, 300 MHz)
d
7.71 (d, J¼8.5 Hz, 2H),
d 205.0, 142.8, 139.1, 138.2, 137.6, 133.5, 129.2, 129.1, 128.3, 127.7,
7.30e7.14 (m, 7H), 6.33 (d, J¼15.7 Hz, 1H), 5.76 (dd, J¼7.8, 15.6 Hz,
1H), 4.83 (m, 2H), 4.77 (d, J¼8.1 Hz, 1H), 4.21 (m, 1H), 2.34 (s, 3H),
1.29 (dt, J¼1.3, 15.0 Hz, 1H), 1.16 (dt, J¼2.7, 15.1 Hz, 1H), ꢁ0.02 (s,
127.6, 127.5, 127.1, 102.2, 80.5, 59.1, 21.4, 17.5, ꢁ2.7, ꢁ3.0; IR (thin
film) 3774, 2955, 1955, 1329, 1161 cmꢁ1; HRMS (MALDI) calcd for
C26H29NO2SSi (MþNa) 470.1586, found 470.1601.
9H); 13C NMR (75 MHz, CDCl3)
d 205.07, 143.2, 136.1, 132.2, 129.4,
128.4, 127.8, 127.3, 127.2, 126.4, 101.1, 80.1, 58.0, 21.3, 18.07, ꢁ1.2; IR
(thin film) 3272, 2953,1953,1329,1161 cmꢁ1; HRMS (ESIꢁ) calcd for
C23H29NO2SSi (MꢁH) 440.1610, found 440.1623.
4.3.11. N-(5-(Dimethyl(phenyl)silyl)-1-phenylpent-3-yn-1-yl)-4-
methyl-benzenesulfonamide (13). Inside a nitrogen atmosphere
drybox, a mixture of CrCl2 (3.6 mg, 0.03 mmol) and Mn powder
325-mesh (33 mg, 0.66 mmol) were added to a 2-dram vial. The vial
was capped with a Teflon lid and it was removed from the drybox.
The tosyl imine (0.3 mmol) was added to the mixture and the vial
was flushed with argon. Dry THF (2 mL) was added via syringe and
4.3.6. 4-Methyl-N-(1-phenyl-4-((trimethylsilyl)methyl)hexa-4,5-
dien-3-yl)benzenesulfonamide (9f). Obtained as a clear oil (103 mg,
0.25 mmol, 84%) 1H NMR (CDCl3, 300 MHz)
d
7.74 (d, J¼8.26 Hz,
2H), 7.32e7.08 (m, 7H), 4.82e4.63 (m, 3H), 3.6 (m, 1H), 2.63 (dt,
J¼5.8, 9.6 Hz, 2H), 2.42 (s, 3H), 1.96 (m, 1H), 1.73 (m, 1H), 1.14 (dt,
J¼3.1, 15.3 Hz, 1H), 0.9 (dt, J¼3.0, 15.2 Hz, 1H), ꢁ0.1 (s, 9H); 13C NMR
a brown suspension was formed. This was followed of (4-
bromobut-2-yn-1-yl)dimethyl(phenyl)silane (120 mg, 0.45 mmol).
The mixture was stirred at rt for 48 h. HCl (2 M, 1 ml) and EtOAc
(1e2 mL) were added to the gray suspension and the green mixture
was stirred for 1 h. The resulting mixture was extracted with three
portions of EtOAc. Combined organic phases were washed with
brine, dried over MgSO4, and concentrated under reduced
pressure to give a tan oil. The residue was purified by flash chro-
matography using a gradient of EtOAc in hexanes (0e10%) to give
the desired product as a yellow oil (56 mg, 0.12 mmol, 42%). 1H NMR
(75 MHz, CDCl3)
d 205.4, 143.2, 141.4, 137.9, 129.4, 128.4, 128.3,
127.3, 125.8, 101.7, 79.3, 55.9, 36.1, 31.6, 21.4, 17.6, ꢁ1.3; IR (thin film)
3278, 1955.9, 1333, 1163 cmꢁ1
;
HRMS (MALDI) calcd for
C23H31NO2SSi (MþNa) 436.1743, found 436.1750.
4.3.7. 4-Methyl-N-(1-(o-tolyl)-2-((trimethylsilyl)methyl)buta-2,3-
dien-1-yl)benzenesulfonamide (9g). Obtained as
a
white solid
7.59 (d,
(35 mg, 0.09 mmol, 30%) 1H NMR (CDCl3, 300 MHz)
d
(CDCl3, 300 MHz)
d
7.58 (d, J¼8.2 Hz, 2H), 7.49 (m, 2H), 7.39 (m, 3H),

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M. Duran-Galvan, B.T. Connell / Tetrahedron 67 (2011) 7901e7908
7907
7.20e7.15 (m, 5H), 7.09e7.05 (m, 2H), 5.05 (d, J¼7.1 Hz, 1H), 4.42
(q, J¼5.7, 11.8 Hz, 1H), 2.57 (dt, J¼2.6, 2.6, 5.6 Hz, 2H), 2.39 (s, 3H),
1.63 (t, J¼2.5 Hz, 2H), 0.29 (s, 3H), 0.27 (s, 3H); 13C NMR (75 MHz,
J¼8.3 Hz, 2H), 7.11e6.94 (m, 4H), 6.26 (dd, J¼11.18, 17.9 Hz, 1H), 5.52
(d, J¼7.0 Hz, 1H), 5.19 (d, J¼17.6 Hz, 1H), 5.19 (s, 1H), 5.04 (d,
J¼11.1 Hz, 1H), 4.88 (s, 1H), 4.74 (d, J¼7.1 Hz, 1H), 2.37 (s, 3H), 2.22
CDCl3)
d
146.6, 143.1, 140.9, 136.9, 133.0, 132.9, 132.8, 131.7, 131.4,
(s, 3H); 13C NMR (75 MHz, CDCl3)
d 144.4, 143.1, 137.7, 136.7, 135.9,
130.9, 130.5, 130.1; IR (thin film) 3277, 3068, 2223, 1331, 1161 cmꢁ1
;
135.7, 130.6, 129.6, 127.6, 127.1, 126.6, 125.9, 118.6, 115.3, 54.6, 21.4,
18.9; IR (thin film) 3271, 3064, 1596, 1319, 1186 cmꢁ1; HRMS (ESIþ)
calcd for C19H21NO3S (MþH) 328.1371, found 328.1379.
HRMS (MALDI) calcd for C26H29NO2SSi (MþNa) 470.1586, found
470.3550.
4.4. General method for the preparation of 2-aminomethyl-
1,3-dienes
4.5. General method for the preparation of 2,3-disubstituted-
1,3-butadienes
Allene (0.21 mmol) was dissolved in THF (2 mL). TBAF (1 M in
THF, 0.21 mL, 0.21 mmol) was added and the solution. After 3 h one
extra equivalent of TBAF (1 M in THF, 0.21 mL, 0.21 mmol) was
added and the mixture was stirred for 21 h at rt. The yellow solu-
tion was filtered though a path of silica using EtOAc as eluent. The
filtrate was concentrated under reduced pressure and the residue
was purified by column chromatography using a gradient of EtOAc
in hexanes (0e12%) to afford the desired diene.
The allene (0.15 mmol) was dissolved in CH2Cl2 (1 mL) and
cooled to e78 ꢀC. Then, a solution of benzaldehyde dimethyla-
cetal (0.16 mmol) and BF3$Et2O (0.16 mmol) in CH2Cl2 (1 mL) was
added to the allene solution dropwise. The mixture was stirred at
e78 ꢀC for 1 h. After this time, one more portion of benzaldehyde
dimethylacetal (0.15 mmol) and BF3$Et2O (0.16 mmol) were
added to the reaction mixture. Reaction was monitored by TLC
and after completion, a saturated solution of NaHCO3 (1 mL) and
EtOAc (1 mL) were added to the red solution. The mixture was
extracted with three portions of EtOAc. The combined organic
phased were washed with brine, dried over MgSO4, and con-
centrated under reduced pressure. The residue was purified by
column chromatography (0e12% EtOAc in hexanes) to give the
desired diene.
4.4.1. 4-Methyl-N-(2-methylene-1-phenylbut-3-en-1-yl)benzene-
sulfonamide (15a). Obtained as a white solid (53 mg, 0.17 mmol,
81%). 1H NMR (CDCl3, 300 MHz)
d
7.68 (d, J¼8.4 Hz, 2H), 7.23 (m,
5H) 7.16 (m, 2H), 6.18 (dd, J¼11.4, 17.7 Hz, 1H), 5.26e5.22 (m, 3H),
5.13 (d, J¼0.8 Hz,1H), 5.08 (d, J¼18.0 Hz,1H), 5.02 (d, J¼11.5 Hz,1H),
4.84 (d, J¼7.9 Hz, 1H), 2.4 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 144.4,
143.2, 139.0, 137.4, 135.5, 129.4, 128.5, 127.7, 127.2, 127.1, 118.2, 116.0,
58.6, 21.5; IR (thin film) 3283, 1637, 1599, 1326, 1160 cmꢁ1; HRMS
(ESI) calcd for C18H19NO2S (MþNa) 336.1034, found 336.1028.
4.5.1. N-(3-(Methoxy(phenyl)methyl)-2-methylene-1-phenylbut-3-
en-1-yl)-4-methylbenzenesulfonamide (16a). Obtained as a clear oil
(60 mg, 0.13 mmol, 92%). 1H NMR (CDCl3, 300 MHz)
d 7.53 (d,
J¼7.5 Hz, 2H), 2.33e7.12 (m, 10H), 7.01 (m, 2H), 5.19e4.85 (m, 6H),
4.4.2. N-(1-(4-Bromophenyl)-2-methylenebut-3-en-1-yl)-4-
4.70 (s, 1H), 3.24 (d, J¼0.6 Hz, 3H), 2.38 (s, 3H); 13C NMR (75 MHz,
methylbenzenesulfonamide (15b). Obtained as a white solid (49 mg,
CDCl3) d 145. 4, 145.0, 143.0, 139.0, 139.1, 137.4, 129.3, 128.3, 127.8,
0.13 mmol, 65%, 74% conversion). 1H NMR (CDCl3, 300 MHz)
d
7.61
127.5, 127.4, 127.3, 117.4, 116.5, 85.0, 60.4, 56.9, 21.5; IR (thin film)
(d, J¼8.3 Hz, 2H), 7.33 (d, J¼8.6 Hz, 2H), 7.21 (d, J¼8.6 Hz, 2H), 7.02
3278, 3062, 1599, 1328, 1186 cmꢁ1 HRMS (ESIþ) calcd for
;
(d, J¼8.6 Hz, 2H), 6.18 (dd, J¼11.3, 17.7 Hz, 1H), 5.24e4.99 (m, 6H),
C26H27NO3S (MþLi) 440.1872, found 440.1861.
2.42 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 144.1, 143.5, 138.0, 135.2,
131.5, 129.4, 128.9, 127.2, 121.6, 118.6, 116.3, 58.0, 21.5; IR (thin film)
3277, 1597, 1328, 1184 cmꢁ1; HRMS (ESIꢁ) calcd for C18H18BrNO2S
(MꢁH) 390.0163, found 390.0175.
4.5.2. N-(1-(4-Bromophenyl)-3-(methoxy(phenyl)methyl)-2-
methylenebut-3-en-1-yl)-4-methylbenzenesulfonamide(16b). Obtained
as a clear oil (43 mg, 0.084 mmol, 93%). 1H NMR (CDCl3, 300 MHz)
d
7.5 (d, J¼8.21 Hz, 2H), 7.33e7.12 (m, 10H), 6.88 (d, J¼8.4 Hz, 2H),
5.17e5.91 (m, 5H), 4.81 (s, 1H), 4.70 (s, 1H), 3.26 (s, 3H), 2.40 (s, 2H);
13C NMR (75 MHz, CDCl3)
145.3, 144.8, 143.33, 139.1, 138.1, 137.2,
131.3, 129.3, 129.2, 129.0, 128.3, 127.9, 127.2, 127.1, 117.8, 116.9, 85.2,
4.4.3. N-(1-(4-Methoxyphenyl)-2-methylenebut-3-en-1-yl)-4-
methylbenzenesulfonamide (15d). Obtained as a white solid (53 mg,
d
0.16 mmol, 84%). 1H NMR (CDCl3, 300 MHz)
d
7.64 (d, J¼8.5 Hz, 2H),
7.21 (d, J¼8.14 Hz, 2H), 7.02 (d, J¼9.3 Hz, 2H), 6.72 (d, J¼8.5 Hz, 2H),
6.19 (dd, J¼11.3, 18.0 Hz, 1H), 5.22 (s, 1H), 5.17 (d, J¼7.7 Hz, 1H), 5.15
(s, 1H), 5.05 (d, J¼17.9 Hz, 1H), 5.00 (d, J¼11.4 Hz, 1H) 4.88 (d,
J¼7.0 Hz, 1H), 3.79 (s, 3H), 2.41 (s, 3H); 13C NMR (75 MHz, CDCl3)
60.0, 56.9, 21.5; IR (thin film) 3278, 3089, 1600, 1332, 1187 cmꢁ1
;
HRMS (ESIþ) calcd for C26H26BrNO3S (MþLi) 518.0977 found 518.0971.
4.5.3. N-(3-(Methoxy(phenyl)methyl)-1-(4-methoxyphenyl)-2-
d
159.1, 144.5, 143.2, 137.5, 135.6, 131.1, 129.3, 128.4, 127.2, 117.8,
methylenebut-3-en-1-yl)-4-methylbenzenesulfonamide (16c). Obtained
115.8, 113.9, 58.0, 55.2, 21.5; IR (thin film) 3435, 1611, 1511, 1323,
1158 cmꢁ1; HRMS (ESIꢁ) calcd for C19H21NO3S (MþLi) 350.1402,
found 350.1408.
as a clear oil (49 mg, 0.10 mmol, 95%). 1H NMR (CDCl3, 300 MHz)
d 7.56
(d, J¼8.2 Hz, 2H), 7.39e7.15 (m, 8H), 6.95 (d, J¼8.7 Hz, 2H), 6.72 (d,
J¼8.7 Hz, 2H), 5.20e4.93 (m, 6H), 4.73 (s, 1H), 3.78 (s, 3H), 3.28 (s, 3H),
2.42 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 159.0, 145.4, 145.4, 145.1,
4.4.4. 4-Methyl-N-(4-methylene-1-phenylhex-5-en-3-yl)benzene-
143.0, 139.5, 139.5, 137.5, 131.2, 129.3, 128.3, 127.8, 127.3, 127.2, 116.5,
113.7, 85.1, 59.8, 56.9, 55.2, 21.5; IR (thin film) 3280, 3062, 1599, 1325,
1160 cmꢁ1; HRMS (ESIþ) calcd for C27H29NO4S (MþLi) 470.1977 found
470.1971.
sulfonamide (15f). Obtained as a white solid (78 mg, 0.23 mmol,
92%). 1H NMR (CDCl3, 300 MHz)
d
7.73 (d, J¼8.3 Hz, 2H), 7.31e7.20
(m, 5H), 7.11 (d, J¼6.8 Hz, 2H), 6.15 (dd, J¼10.9, 17.8 Hz, 1H), 5.17 (d,
J¼8.1 Hz, 1H), 5.05 (d, J¼18.0 Hz, 1H), 5.03 (s, 1H), 5.0 (d, J¼12.0 Hz,
1H), 4.89 (s, 1H), 4.09 (q, J¼7.2 Hz, 1H), 2.62 (m, 2H), 2.44 (s, 3H),
4.5.4. N-(5-(Methoxy(phenyl)methyl)-4-methylene-1-phenylhex-5-
1.92 (m. 2H); 13C NMR (75 MHz, CDCl3)
d
145.4, 142.2, 141.0, 137.7,
en-3-yl)-4-methylbenzenesulfonamide (16d). Obtained as a clear oil
135.5, 129.4, 128.5, 128.4, 127.2, 126.0, 115.7, 114.8, 54.4, 37.1, 31.9,
21.5; IR (thin film) 3276, 2864, 1597, 1318, 1162 cmꢁ1; HRMS (ESIþ)
calcd for C20H2NO2S (MþH) 342.1528, found 342.1537.
(79 mg, 0.17 mmol, 78%). 1H NMR (CDCl3, 300 MHz)
d 7.62 (d,
J¼8.3 Hz, 2H), 7.35e7.18 (m, 10H), 7.07 (d, J¼8.9 Hz, 2H), 5.30 (d,
J¼7.8 Hz, 1H), 5.16 (s, 1H), 5.04 (s, 1H), 4.9 (s, 1H), 4.83 (s, 1H), 4.7 (s,
1H), 4.0 (q, J¼7.2 Hz, 1H), 3.3 (s, 3H), 2.51 (m, 2H), 2.43 (s, 3H), 1.77
4.4.5. 4-Methyl-N-(2-methylene-1-(o-tolyl)but-3-en-1-yl)benzene-
(m, 2H); 13C NMR (75 MHz, CDCl3)
d 146.7, 146.1, 143.0, 141.2, 139.2,
sulfonamide (15g). Obtained as a white solid (24 mg, 0.073 mmol,
137.8,129.4,128.5,128.3,128.2,127.8,127.3,127.2,125.9,115.7,115.3,
84.7, 56.9, 56.2, 36.7, 31.8, 21.5; IR (thin film) 3282.7, 3085.7, 1599.5,
73%). 1H NMR (CDCl3, 300 MHz)
d
7.59 (d, J¼8.5 Hz, 2H), 7.16 (d,

ꢀ ꢀ
M. Duran-Galvan, B.T. Connell / Tetrahedron 67 (2011) 7901e7908
7908
1323.5, 1158.4 cmꢁ1; HRMS (ESIþ) calcd for C28H31NO3S (MþLi)
ꢀ
ꢀ
11. Duran-Galvan, M.; Worlikar, S. A.; Connell, B. T. Tetrahedron 2010, 66,
7707e7719.
468.2185 found 468.2177.
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Acknowledgements
The Robert A. Welch Foundation (A-1623) is gratefully
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Supplementary data
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