Chiral aminated α-methylenebenzocycloalkenes from o-bromoaryl aldehydes and ketones

Article abstract of DOI:10.1002/ejoc.201201712

Chiral tert-butylsulfinyl imines 3, which are easily prepared from the corresponding bromo carbonyl compounds 1 and tert-butanesulfinamide (2), undergo a diastereoselective allylation by using indium metal and allyl bromide to give the corresponding homoallyl sulfinylamines 4. Treatment of compounds 4 with a catalytic amount of palladium acetate and triphenylphosphane gives exo-methylene-substitutedsulfinylamino)benzocycloalkenes 5 (five- to seven-membered rings) that are easily deprotected with hydrochloric acid to give chiral primary amines 6.

Full text of DOI:10.1002/ejoc.201201712

FULL PAPER
DOI: 10.1002/ejoc.201201712
Chiral Aminated α-Methylenebenzocycloalkenes from o-Bromoaryl Aldehydes
and Ketones
Juan Alberto Sirvent,[a] Francisco Foubelo,*[a] and Miguel Yus*[a]
Keywords: Fused-ring systems / Allylation / Cyclization / Diastereoselectivity / Chiral auxiliaries / Indium
Chiral tert-butylsulfinyl imines 3, which are easily prepared
from the corresponding bromo carbonyl compounds 1 and
compounds 4 with a catalytic amount of palladium acetate
and triphenylphosphane gives exo-methylene-substituted-
tert-butanesulfinamide (2), undergo
a
diastereoselective
sulfinylamino)benzocycloalkenes 5 (five- to seven-mem-
allylation by using indium metal and allyl bromide to give
bered rings) that are easily deprotected with hydrochloric
the corresponding homoallyl sulfinylamines 4. Treatment of
acid to give chiral primary amines 6.
nated carbonyl compound 1 with commercially available
enantiomerically pure (S)-tert-butanesulfinamide (2) in the
presence of titanium tetraethoxide at 23 and 76 °C for alde-
hydes and ketones, respectively (see Scheme 1). The reaction
worked well with results independent of the electronic ef-
fects of the aromatic ring (compare compounds 3a–3d), and
the reaction worked efficiently for both electron-poor and
electron-rich heterocycles (compare compounds 3e and 3f).
In all cases, the E configuration was obtained after purifica-
tion by column chromatography with the exception of com-
pound 3j, for which an E/Z mixture of 3:2 was isolated.
Once compounds 3 were prepared, we proceeded with
their allylation under standard conditions,[3a] that is, treat-
ment with allyl bromide in the presence of indium metal at
65 °C. Thus, the corresponding products 4 were obtained
with almost total diastereoselectivity in most cases, and the
attack of the intermediate allylindium occurred on the Re
face of the imine with the S configuration at the sulfur atom
(see Scheme 2). We observed this behavior as well with
other types of indium-promoted allylations of sulfinyl
imides. The diastereomeric ratios were easily determined by
1H NMR analysis of the crude reaction mixtures through
the comparison of the integrals of the tBu group and the
N–H for each of the diastereoisomers. (The largest chemical
shift difference was always observed for the diastereomeric
signals of the N–H). In all cases, the yields were good with
the exception of compound 4j. We do not have any explana-
tion for this, but the congestion around the C–N double
bond could play an important role. Importantly, the dia-
stereomeric ratio for compound 4j was in agreement with
the E/Z isomeric ratio of the starting imine 3j.
Introduction
Chiral sulfinyl imines have become important starting
materials for the syntheses of different enantiomerically
pure nitrogen-containing compounds through enantio- and
diastereoselective additions to prochiral C–N double
bonds.[1] Thus, the syntheses of a wide range of chiral amine
derivatives can be achieved by using this methodology.[2] In
the last few years, we have studied the indium-promoted
diastereoselective allylation of N-tert-butylsulfinyl aldimi-
nes[3] and ketimines[4] as well as its application to the syn-
theses of different natural alkaloids such as (+)-isosolenop-
sin,[3f] (–)- and (+)-aphanorphine,[3h] (+)-coniine,[3k] (–)-pel-
leterine,[3k] and 5-epi-(+)-cermizine C[3k] as well as to the
formal syntheses of (–)-cermizine C, (+)-lasubine II, (+)-
allosedridine,[3k] and tetraponerines T3 and T4.[3l] Herein,
we describe the indium-promoted allylation[5] of chiral sulf-
inyl imines that are derived from 2-bromoaryl- or hetero-
aryl-substituted aldehydes and ketones followed by a cycli-
zation under Heck-type conditions to afford chiral pro-
tected aminated α-methylene-benzocycloalkenes.
Results and Discussion
The starting tert-butylsulfinyl imines 3 were easily pre-
pared[6] in tetrahydrofuran (THF) by the reaction of bromi-
[a] Departamento de Química Orgánica, Facultad de Ciencias and
Instituto de Síntesis Orgánica (ISO), Universidad de Alicante,
Apdo. 99, 03080 Alicante, Spain
Fax: +34-965903549
E-mail: foubelo@ua.es; yus@ua.es
Homepage: http://iso.ua.es/es/personal/director-iso.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201712.
In fact, a one-pot transformation[3f,3j] from 1Ǟ4 was
also possible with comparable yields, but the process was
Eur. J. Org. Chem. 2013, 2461–2471
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2461

J. A. Sirvent, F. Foubelo, M. Yus
FULL PAPER
Scheme 2. Preparation of homoallylamine derivatives 4. [a] A dia-
stereomeric mixture (3:2) was obtained.
Scheme 1. Preparation of (S)-sulfinyl imines 3. [a] A mixture (E/Z,
3:2) was obtained.
of palladium(0) catalysts such as Pd(PPh3)4 and Pd(dba)3
without an additive (see Table 1, Entry 17) or with a dif-
ferent additives (see Table 1, Entries 18–20) did not improve
the previous best results.
not as clean as the two-step process, and the purification of
the corresponding product 4 was more difficult.
Once the best conditions to perform the Heck cyclization
were established (see Table 1, Entry 13), we applied the pro-
In the last part of this study, we carried out a Heck-type cedure to all compounds 4, and the expected methylene
reaction of compounds 4 under palladium catalysis. For a carbocycles were obtained in variable yields (see
5
model reaction, we optimized the cyclization of compound Scheme 3). Starting from both aldehyde (to give 5a–5h) and
4a by performing the reaction under different conditions ketone (to give 5j–5l) derivatives, the reaction successfully
(see Table 1). Using different loadings of palladium acetate provided five- (i.e., 5a–5f and 5j), six- (i.e., 5g and 5k), and
at around 80 °C, we realized that the best combination was seven-membered rings (i.e., 5h and 5l), but it failed to pro-
with THF and tetrabutylammonium acetate (TBAA) under vide eight-membered rings (i.e., 5i). Importantly, in the case
ligand-free conditions (see Table 1, Entries 1–5). Tri- of compound 5bЈ, which contained an electron-donating
phenylphosphane was effective as an additive, and after in- substituent on the aromatic ring, the best result was ob-
vestigating different solvents and bases (see Table 1, En- tained with 14% loading of the palladium catalyst, other-
tries 6–13), we found that complete conversion was wise the reaction did not progress. Surprisingly, the only
achieved by using triphenylphosphane as the additive and isolated product in this case was endo derivative 5bЈ. In the
TBAA as the base with a reasonable catalyst loading at presence of the excess amount of palladium, it seems that
90 °C for 20 h (see Table 1, Entry 13). Different additives an isomerization takes place from the exo isomer to the
such as titanium tetraethoxide and iron trichloride gave thermodynamically more stable endo isomer. This probably
worse results (see Table 1, Entries 14–16). Finally, the use occurs by the reaction of the initially formed exo product
2462
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2461–2471

Chiral Aminated α-Methylenebenzocycloalkenes
Table 1. Optimization of the preparation of compound 5.
Entry
T [°C]
t [h][a]
Catalyst [%]
Additive [%]
Base [equiv.]
Solvent
Conversion [%][b]
1
2
3
4
5
6
7
8
80
80
80–100
80
90
80
80
80
80
100
90
90
90
80
80
80
100
80
80
80
8
Pd(OAc)2 (17)
Pd(OAc)2 (10)
Pd(OAc)2 (2)
Pd(OAc)2 (3)
Pd(OAc)2 (4)
Pd(OAc)2 (10)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (4)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(PPh3)4 (10)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
–
–
–
–
Et3N (6)
THF
0
72
0
60
75
53
65
98
80
0
60
81
100
0
30
50
90
95[j]
10
50
16
15
15
17
72
24
48
40
3
72
21
20
24
24
24
24
20
48
16
K2CO3 (6)
K2CO3 (2.5)
K2CO3 (6)
TBAA (3)
K2CO3 (6)
K2CO3 (6)
K2CO3 (6)
K2CO3 (6)
NaOAc (3.5)
TBAA (2)
TBAA (1.5)
TBAA (1.5)
–
K2CO3 (4)
K2CO3 (6)
K2CO3 (6)
K2CO3 (6)
K2CO3 (6)
K2CO3 (6)
THF
DMF[c]
DMF[c]
THF
–
PPh3 (40)
PPh3 (45)
PPh3 (50)
PPh3 (20)
PPh3 (20)
PPh3 (4)
PPh3 (8)
PPh3 (16)
Ti(OEt)4 (100)
Ti(OEt)4 (100)
FeCl3 (110)[g]
–
MeCN
MeCN
MeCN[d]
THF
9
10
11
12
13
14
15
16
17[h]
18[h]
19
20
EtOH/H2O[e]
THF/H2O[f]
THF
THF
THF
THF
THF
THF/H2O[i]
THF/H2O[d]
MeCN
THF
InCl3 (119)
CuI (120)
PPh3
[k]
Pd2(dba)3 (2)
[a] Reaction time until progress of the reaction no longer observed. [b] Conversion deduced from the 1H NMR spectrum, unless otherwise
stated. [c] N,N-dimethylformamide. [d] Deoxygenated. [e] Ratio is 1:1. [f] Ratio is 20:1. [g] 20% of PPh3 was also added. [h] Starting
material 4g was used in this run. [i] Ratio is 10:1. [j] Partial isomerization of the double bond took place under these reaction conditions
to give an exo/endo ratio of 38:62. [k] Palladium(0) dibenzylideneacetone.
with the palladium hydride that is formed after a β-elimi- chiral auxiliary, we performed the series of reactions that
nation of the Pd intermediate.[7] A 3:1 mixture of dia- were used to obtain 5a. Thus, ent-5a was isolated with sim-
stereomers for starting material 4j (after enrichment by col- ilar results as those of its enantiomer but with the opposite
umn chromatography from the 3:2 mixture obtained from optical rotation, that is, [α]2D0 = +21 (c = 1.0, CH2Cl2) for
the allylation reaction) was used to give a mixture of four 5a and [α]2D0 = –23 (c = 1.0, CH2Cl2) for ent-5a (see
diastereomers. The configurations of these compounds have Scheme 6).
not yet been assigned, but the exo olefins are the major
In the final part of this study, we explored the use of
components in the mixture (see Scheme 4). The exo/endo substituted allylic bromides to prepare compounds 4 and 5,
isomerization was also observed for the six-membered car- and for this purpose, we started from imine 3a. Its reaction
bocycles 5g (exo/endo, 1.4:1) and 5k (exo/endo, 3.6:1).
with methallyl, prenyl, and cyclohex-2-enyl bromides gave
Compound 5a was then used to investigate the possibility the expected compounds 4m–4o (see Scheme 7). The reac-
of obtaining the deprotected amines, and treatment with a tion proceeded with high selectivity for the prenyl bromide
6 m solution of hydrochloric acid gave the expected primary to yield 4n as the only regioisomer. Remarkably, in the case
amine 6a (see Scheme 5).
of cyclohex-2-enyl bromide, a single diastereomer was ob-
Also, with regard to preparing compounds 5, we assayed tained after column purification, and the relative anti con-
a one-pot version of this process to obtain 5a from the cor- figuration was assigned on the basis of our experience with
responding imine 3a and even directly from aldehyde 1a. the indium-promoted addition of cyclohex-2-enyl bromide
Although there was good conversion (in MeCN or THF) to the N-tert-butylsulfinyl imine of 3-phenylpropanal.[3f] By
of imine 3a, it did not afford a clean reaction mixture. using the established optimal conditions, the final Heck-
When we started from aldehyde 1a, we were unable to iso- type reaction of these compounds afforded good results for
late the expected final product 5a.
compounds 5n and 5o, but fail to provide compound 5m.
To demonstrate that the corresponding enantiomers of Unfortunately, a mixture of three isomers was obtained in
compounds 3–5 can also be prepared by using ent-2 as the the case of 5o (see Scheme 7).
Eur. J. Org. Chem. 2013, 2461–2471
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2463

J. A. Sirvent, F. Foubelo, M. Yus
FULL PAPER
Scheme 6. Reactions for the preparation of ent-5a.
Scheme 7. Compounds 4m–4o and 5m–5o.
Conclusions
The indium-promoted allylation of chiral tert-butylsulf-
inyl imines, which were derived from brominated aldehydes
and ketones, followed by a palladium acetate-catalyzed
Scheme 3. Preparation of methylene-substituted carbocyles. Heck-type reaction yielded chiral aminated methylene-
[a] 14% of Pd(OAc)2 was used. [b] Conversion. [c] An exo/endo ra-
tio of 1.4:1 was obtained. [d] A mixture of four diastereomers was
mation of six-membered rings, we observed the partial
obtained (see text and Scheme 4). [e] An exo/endo ratio of 3.6:1 was
benzocycloalkenes through a two-step process. In the for-
isomerization from the exo to the endo double bond. Fi-
obtained.
Scheme 4. Mixture of diastereomers for 5j.
nally, the cyclization, which successfully afforded five-,
six-, and seven-membered rings, failed to yield the corre-
sponding cyclooctene-derived product.
Experimental Section
General Methods: All reactions that required anhydrous conditions
were performed in oven-dried glassware under argon. Unless other-
Scheme 5. Deprotection of compound 5a.
2464
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2461–2471

Chiral Aminated α-Methylenebenzocycloalkenes
wise indicated, all commercially available chemicals were purchased
from Across or Aldrich and were used without purification. The N-
tert-butanesulfinamides (SS and RS) were a gift from Medalchemy
(Ͼ99%ee by chiral HPLC on a Chiracel AS column; n-hexane/
iPrOH, 90:10; 1.2 mL/min; λ = 222 nm). TLC was performed on
Merck silica gel 60 F254 with aluminum plates and visualized by
using phosphomolybdic acid (PMA) stain. Chromatographic puri-
fication was performed by flash chromatography with Merck silica
gel 60 (0.040–0.063 mm) and n-hexane/AcOEt as the eluent. IR
spectra were recorded (film) with a Nicolet Impact 510 P-FT Spec-
trometer. Melting points were recorded in open-glass capillary
tubes with an OptiMelt (Stanford Research Systems) apparatus.
Gas chromatographic analyses (GLC) were recorded with a Hew-
lett–Packard HP-5890 instrument equipped with a flame ionization
detector (FID) and a 12 m capillary column (0.2 mm diam.,
0.33 μm film thickness) with nitrogen (2 mL/min) as the carrier gas
[injector temp. 275 °C, detector temp. 300 °C, column temp. 60 °C
(3 min) and 60–270 °C (15 °C/min), P = 40 kPa as routine working
117 (14), 89 (12), 88 (12), 75 (10), 63 (11), 62 (14). HRMS (EI):
calcd. for C8H679BrNO [M – C4H10OS]+ 210.9633; found 210.9638.
(S,E)-N-(2-Bromo-5-fluorobenzylidene)-tert-butanesulfinamide (3c):
The representative procedure was followed by using 2-bromo-5-
fluorobenzaldehyde (211 mg, 1.0 mmol) and (SS)-tert-butanesulfin-
amide (2, 133 mg, 1.1 mmol). Purification by column chromatog-
raphy (n-hexane/AcOEt, 10:1) yielded 3c (297 mg, 97%) as a white
solid; m.p. 56–58 °C. Rf = 0.71 (hexane/AcOEt, 2:1). [α]2D0 = +211
1
(c = 1.03, CH2Cl2). H NMR (300 MHz, CDCl3): δ = 8.92 (d, J =
2.2 Hz, 1 H), 7.75 (dd, J = 9.1, 3.1 Hz, 1 H), 7.62 (dd, J = 8.8,
5.0 Hz, 1 H), 7.10 (ddd, J = 8.8, 7.6, 3.1 Hz, 1 H), 1.29 (s, 9
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 162.0 (d, J = 248.4 Hz,
C), 161.5 (CH), 135.1 (d, J = 7.6 Hz, CH), 134.5 (d, J = 7.4 Hz,
C), 120.8 (d, J = 23.2 Hz, CH), 120.6 (C), 116.2 (d, J = 24.0 Hz,
CH), 58.4 (C), 22.9 (CH ) ppm. IR (ATR): ν = 3067, 1592, 1461,
˜
3
1255, 1084 cm–1. LRMS (EI): m/z (%) = 251 (17), 249 (16), 170
(38), 149 (13), 94 (10), 85 (12), 71 (19), 70 (14), 69 (12), 57 (100),
55 (12), 43 (45), 41 (24). HRMS (EI): calcd. for C7H579BrFNOS
[M – C4H8]+ 248.9259; found 248.9256.
1
conditions]. The H NMR spectroscopic data were recorded with
a Bruker AC-300 spectrometer using CDCl3 as the solvent and
TMS as the internal standard. The data is reported as s (singlet),
d (doublet), t (triplet), q (quartet), m (multiplet), unresolved, or br.
s (broad signal); coupling constant(s) in Hz; and integration. The
13C NMR spectroscopic data were recorded by 1H decoupling with
a Bruker 75 MHz spectrometer, and DEPT-135 experiments were
performed to assign CH, CH2, and CH3. Optical rotations were
measured with a Perkin–Elmer 341 polarimeter (concentration is
given in g/100 mL, solvent). HRMS (EI) were recorded with a Fin-
nigan MAT 95S. The starting bromoaryl carbonyl compounds 1a–
1f, 1k, and 1j were commercially available. Compound 1g[8] was
prepared by the oxidation of commercially available o-bromobenzyl
alcohol with Dess–Martin periodinane. Compounds 1h, 1i,[9] and
1l[10] were prepared from o-bromoiodobenzene through a palla-
dium-catalyzed coupling reaction with allyl alcohol, but-3-en-1-ol,
and but-3-en-2-ol, respectively.
(S,E)-N-(2-Bromo-6-fluorobenzylidene)-tert-butanesulfinamide (3d):
The representative procedure was followed by using 2-bromo-6-
fluorobenzaldehyde (211 mg, 1.0 mmol) and (SS)-tert-butanesulfin-
amide (2, 133 mg, 1.1 mmol). Purification by column chromatog-
raphy (n-hexane/AcOEt, 12:1) yielded 3d (281 mg, 92%) as a yellow
oil; Rf = 0.65 (hexane/AcOEt, 2:1). [α]2D0 = +132 (c = 1.05, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ = 8.84 (s, 1 H), 7.49 (d, J = 8.1 Hz,
1 H), 7.32 (td, J = 8.2, 5.6 Hz, 1 H), 7.18–7.11 (m, 1 H), 1.30 (s, 9
H) ppm. 13C NMR (101 MHz, CDCl3): δ = 161.8 (d, J = 262.8 Hz,
C), 158.4 (CH), 133.3 (d, J = 9.9 Hz, CH), 129.7 (d, J = 3.6 Hz,
CH), 125.4 (C), 122.5 (d, J = 11.2 Hz, C), 116.1 (d, J = 22.1 Hz,
CH), 58.1 (C), 22.66 (CH ) ppm. IR (ATR): ν = 1597, 1562, 1455,
˜
3
1083, 895 cm–1. LRMS (EI): m/z (%) = 201 (97), 199 (100), 120
(75), 100 (30), 93 (13), 75 (13). HRMS (EI): calcd. for C7H379BrFN
[M – C4H10OS]+ 198.9433; found 198.9446.
(S,E)-N-[(2-Bromopyridin-3-yl)methylene]-tert-butanesulfinamide
(3e): The representative procedure was followed by using 2-bromo-
3-pyridinecarbaldehyde (387 mg, 2.0 mmol) and (SS)-tert-butane-
sulfinamide (2, 270 mg, 2.2 mmol). Purification by column
chromatography (n-hexane/AcOEt, 5:1) yielded 3e (566 mg, 98%)
as a white solid; m.p. 43–46 °C. Rf = 0.40 (hexane/AcOEt, 2:1).
[α]2D0 = +150 (c = 1.14, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ
= 8.92 (s, 1 H), 8.49 (dd, J = 4.7, 2.0 Hz, 1 H), 8.31 (dd, J = 7.7,
2.0 Hz, 1 H), 7.40 (ddd, J = 7.7, 4.7, 0.6 Hz, 1 H), 1.29 (s, 9
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 161.1 (CH), 152.9 (CH),
144.9 (C), 137.7 (CH), 130.5 (C), 123.3 (CH), 58.5 (C), 22.8
General Procedure for the Synthesis of N-tert-Butylsulfinyl Imines
3: To a solution of tert-butanesulfinamide (2, 0.605 g, 5 mmol) and
the corresponding carbonyl compound 1 (4.5 mmol) in dry THF
(20 mL) under argon at 23 °C was slowly added titanium tetra-
ethoxide (2.005 g, 1.885 mL, 9 mmol). The reaction mixture was
stirred at the same temperature for 12 h for aldehydes and at 76 °C
for 5 h for ketones. The resulting mixture was hydrolyzed with brine
(30 mL), and the solution was extracted with ethyl acetate
(3ϫ15 mL). The combined organic extracts were dried with anhy-
drous MgSO4 and evaporated (15 Torr). The residue was purified
by column chromatography (silica gel, hexane/ethyl acetate) to
yield pure compounds 3. Imines 3a,[11] 3g,[12] 3h,[12] and 3j[13] were
characterized by comparing their physical and spectroscopic data
with those reported in the literature. The physical, spectroscopic,
and analytical data for the remaining imines 3 are below.
(CH ) ppm. IR (ATR): ν = 2866, 1589, 1572, 1387, 1335, 1080,
˜
3
1048 cm–1. LRMS (EI): m/z (%) = 184 (31), 182 (32), 103 (100), 76
(42), 75 (18), 51 (13). HRMS (EI): calcd. for C6H379BrN2 [M –
C4H10OS]+ 181.9480; found 181.9498.
(S,E)-N-(2-Bromo-5-methoxybenzylidene)-tert-butanesulfinamide
(3b): The representative procedure was followed by using 2-bromo-
5-methoxybenzaldehyde (222 mg, 1.0 mmol) and (SS)-tert-butane-
sulfinamide (2, 133 mg, 1.1 mmol). Purification by column
chromatography (hexane/AcOEt, 10:1) yielded 3b (313 mg, 98%)
as a yellow oil; Rf = 0.63 (hexane/AcOEt, 2:1). [α]2D0 = +133 (c =
1.06, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 8.93 (s, 1 H), 7.56
(d, J = 3.1 Hz, 1 H), 7.52 (d, J = 8.8 Hz, 1 H), 6.94 (dd, J = 8.8,
3.2 Hz, 1 H), 3.84 (s, 3 H), 1.28 (s, 9 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 162.2 (CH), 159.1 (C), 134.4 (CH), 133.4 (C), 120.3
(S,E)-N-[(3-Bromobenzo[b]thiophen-2-yl)methylene]-tert-butanesulf-
inamide (3f): The representative procedure was followed by using
3-bromobenzothiophene-2-carbaldehyde (507 mg, 2.0 mmol) and
(SS)-tert-butanesulfinamide (2, 267 mg, 2.2 mmol). Purification by
column chromatography (n-hexane/AcOEt, 12:1) yielded 3f
(692 mg, 98%) as a yellow solid; m.p. 112–114 °C. Rf = 0.66 (hex-
ane/AcOEt, 2:1). [α]2D0 = +115 (c = 1.01, CH2Cl2). 1H NMR
(300 MHz, CDCl3): δ = 7.96–7.90 (m, 1 H), 7.84–7.79 (m, 1 H),
7.52–7.45 (m, 2 H), 1.29 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 155.8 (CH), 139.8 (C), 138.5 (C), 134.9 (C), 128.4 (CH), 125.8
(CH), 117.2 (C), 113.7 (CH), 58.1 (C), 55.7 (CH3), 22.8 (CH3) ppm. (CH), 124.7 (CH), 123.0 (CH), 116.4 (C), 58.6 (C), 22.8 (CH3) ppm.
IR (ATR): ν = 2959, 1597, 1466, 1085, 1015 cm–1. LRMS (EI): m/z IR (ATR): ν = 2865, 1572, 1083, 730 cm–1. LRMS (EI): m/z (%) =
˜
˜
(%) = 213 (98), 211 (100), 198 (36), 196 (37), 170 (34), 168 (34), 241 (5), 240 (11), 239 (100), 238 (12), 237 (98), 158 (23), 114 (34).
Eur. J. Org. Chem. 2013, 2461–2471
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2465

J. A. Sirvent, F. Foubelo, M. Yus
HRMS (EI) calcd. for C9H479BrNS [M – C4H10OS]+ 236.9248; raphy (silica gel, hexane/AcOEt) to yield products 4. The yields and
FULL PAPER
found 236.9253.
the physical and spectroscopic data follow.
(SS,1R)-1-(2-Bromophenyl)-N-(tert-butylsulfinyl)but-3-en-1-amine
(4a): The representative procedure was followed by using imine 3a
(288 mg, 1 mmol), indium (143 mg, 1.25 mmol), and allyl bromide
(0.131 mL, 1.5 mmol). Purification by column chromatography
(hexane/AcOEt, 4:1) yielded 4a (303 mg, 92%) as a colorless oil;
(S,E)-N-[4-(2-Bromophenyl)butylidene]-tert-butanesulfinamide (3i):
The representative procedure was followed by using 4-(2Ј-bro-
mophenyl)butyraldehyde (550 mg, 2.46 mmol) and (SS)-tert-bu-
tanesulfinamide (2, 363 mg, 3.0 mmol). Purification by column
chromatography (n-hexane/AcOEt, 7:1) yielded 3i (700 mg, 87%)
as a yellow oil; Rf = 0.52 (hexane/AcOEt, 2:1). [α]2D0 = +150 (c =
1.14, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 8.11 (t, J =
4.5 Hz, 1 H), 7.53 (dd, J = 7.7, 1.1 Hz, 1 H), 7.28–7.17 (m, 2 H),
7.07 (ddd, J = 8.0, 6.5, 2.6 Hz, 1 H), 2.86–2.76 (m, 2 H), 2.60 (td,
J = 7.4, 4.5 Hz, 2 H), 2.04–1.91 (m, 2 H), 1.20 (s, 9 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 169.1 (CH), 140.8 (C), 133.0 (CH),
130.5 (CH), 127.9 (CH), 127.6 (CH), 124.5 (C), 56.7 (C), 35.7
1
Rf = 0.48 (hexane/AcOEt, 1:1). [α]2D0 = +110 (c = 1.1, CH2Cl2). H
NMR (400 MHz, CDCl3): δ = 7.55 (dd, J = 8.0, 1.1 Hz, 1 H), 7.39
(dd, J = 7.8, 1.6 Hz, 1 H), 7.31 (td, J = 7.5, 1.0 Hz, 1 H), 7.13 (td,
J = 7.7, 1.7 Hz, 1 H), 5.83–5.70 (m, 1 H), 5.24–5.16 (m, 2 H), 4.98
(ddd, J = 8.1, 4.9, 3.1 Hz, 1 H), 3.72 (d, J = 2.4 Hz, 1 H), 3.72 (d,
J = 2.4 Hz, 1 H), 2.75–2.65 (m, 1 H), 2.50–2.39 (m, 1 H), 1.21 (s,
9 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 140.9 (C), 133.9
(CH), 133.2 (CH), 129.0 (CH), 128.8 (CH), 127.5 (CH), 123.6 (C),
119.7 (CH2), 56.0 (C), 56.0 (CH), 41.7 (CH2), 22.7 (CH3) ppm. IR
(CH ), 35.6 (CH ), 25.6 (CH ), 22.5 (CH ) ppm. IR (ATR): ν =
˜
2
2
2
3
2865, 1621, 1471, 1084, 749 cm–1. LRMS (EI): m/z (%) = 225 (30),
223 (31), 185 (18), 184 (18), 183 (19), 182 (17), 171 (96), 170 (10),
169 (100), 144 (39), 116 (11), 115 (11), 104 (11), 103 (13), 91 (14),
90 (27), 89 (27), 77 (16), 63 (14), 51 (12). HRMS (EI): calcd. for
C10H1079BrN [M – C4H10OS]+ 222.9997; found 223.0007.
(ATR): ν = 3213, 1470, 1438, 1054, 1022, 913, 754 cm–1. LRMS
˜
(EI): m/z (%) = 233 (55), 231 (54), 194 (17), 184 (17), 182 (17), 152
(100), 134 (16), 130 (18), 129 (10), 116 (11), 115 (10), 103 (10), 102
(13), 91 (14), 77 (16). HRMS (EI): calcd. for C7H679BrNOS [M –
C7H14]+ 230.9353; found 230.9361.
(S,E)-N-[1-(2-Bromophenyl)propan-2-ylidene]-tert-butanesulfin-
amide (3k): The representative procedure was followed by using 2Ј-
bromophenylacetone (430 mg, 2.0 mmol) and (SS)-tert-butanesulfi-
namide (2, 267 mg, 2.2 mmol). Purification by column chromatog-
raphy (n-hexane/AcOEt, 8:1) yielded 3k (459 mg, 74%) as a yellow
oil; Rf = 0.59 (hexane/AcOEt, 2:1). [α]2D0 = +68 (c = 1.06, CH2Cl2).
1H NMR (300 MHz, CDCl3): δ = 7.55 (dd, J = 8.0, 0.9 Hz, 1 H),
7.29–7.17 (m, 2 H), 7.15–7.07 (m, 1 H), 3.85 (s, 2 H), 2.39 (s, 3 H),
1.09 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 181.9 (C),
136.1 (C), 132.8 (CH), 131.8 (CH), 128.7 (CH), 127.5 (CH), 125.2
(C), 56.9 (C), 49.6 (CH2), 22.9 (CH3), 22.2 (CH3) ppm. IR (ATR):
(RS,1S)-1-(2-Bromophenyl)-N-(tert-butylsulfinyl)but-3-en-1-amine
(ent-4a): The representative procedure was followed by using imine
ent-3a (288 mg, 1 mmol), indium (143 mg, 1.25 mmol), and allyl
bromide (0.131 mL, 1.5 mmol). Purification by column chromatog-
raphy (hexane/AcOEt, 4:1) yielded ent-4a (303 mg, 92%) as a color-
less oil. The physical and spectroscopic data were the same as the
data for 4a. [α]2D0 = –103 (c = 1.11, CH2Cl2).
(SS,1R)-1-(2-Bromo-5-methoxyphenyl)-N-(tert-butylsulfinyl)but-3-
en-1-amine (4b): The representative procedure was followed by
using imine 3b (160 mg, 0.5 mmol), indium (74 mg, 0.64 mmol),
and allyl bromide (0.090 mL, 1.0 mmol). Purification by column
chromatography (hexane/AcOEt, 3:1) yielded 4b (154 mg, 88%) as
a yellow oil; Rf = 0.31 (hexane/AcOEt, 1:1). [α]2D0 = +135 (c = 1.11,
ν = 2854, 1626, 1074, 749 cm–1. LRMS (EI): m/z (%) = 261 (31),
˜
259 (29), 181 (10), 180 (100), 171 (18), 169 (19), 162 (10), 138 (14),
132 (18), 131 (15), 90 (28), 89 (21), 57 (45), 44 (16), 41 (15). HRMS
(EI): calcd. for C9H1079BrN [M – C4H8OS]+ 210.9997; found
211.0023.
1
CH2Cl2). H NMR (300 MHz, CDCl3): δ = 7.43 (d, J = 8.8 Hz, 1
H), 6.97 (d, J = 3.1 Hz, 1 H), 6.70 (dd, J = 8.8, 3.1 Hz, 1 H), 5.86–
5.69 (m, 1 H), 5.26–5.16 (m, 1 H), 4.91 (ddd, J = 8.0, 4.8, 2.9 Hz,
1 H), 3.77 (s, 3 H), 3.71 (d, J = 2.7 Hz, 1 H), 2.76–2.63 (m, 1 H),
2.48–2.33 (m, 1 H), 1.23 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 159.1 (C), 142.0 (C), 134.0 (CH), 133.8 (CH), 119.7 (CH2),
114.6 (CH), 114.6 (CH), 113.8 (C), 56.02 (C), 55.97, 55.5, 41.7
(S,E)-N-[4-(2-Bromophenyl)butan-2-ylidene]-tert-butanesulfinamide
(3l): The representative procedure was followed by using 4-(2Ј-bro-
mophenyl)-2-butanone (355 mg, 1.56 mmol) and (SS)-tert-butane-
sulfinamide (2, 219 mg, 1.8 mmol). Purification by column
chromatography (n-hexane/AcOEt, 7:1) yielded 3l (422 mg, 82%)
as a yellow oil; Rf = 0.33 (hexane/AcOEt, 2:1). [α]2D0 = +97 (c =
1.12, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 7.53 (d, J =
7.9 Hz, 1 H), 7.26–7.18 (m, 2 H), 7.12–7.03 (m, 1 H), 3.07–2.99 (m,
2 H), 2.77–2.68 (m, 2 H), 2.36 (s, 3 H), 1.24 (s, 9 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 184.0 (C), 140.3 (C), 133.0 (CH),
130.4 (CH), 128.1 (CH), 127.7 (CH), 124.5 (C), 56.6 (C), 43.1
(CH ), 22.8 (CH ) ppm. IR (ATR): ν = 3215, 2957, 1594, 1571,
˜
2
3
1469, 1048, 1015 cm–1. LRMS (EI): m/z (%) = 305 (4), 303 (4), 263
(19), 261 (19), 224 (67), 215 (14), 214 (28), 113 (16), 212 (25), 184
(10), 183 (18), 182 (100), 166 (14), 164 (11), 160 (16), 91 (16), 63
+
(13). HRMS (EI): calcd. for C8H879BrNO2S [M – C7H14
260.9459; found 260.9477.
]
(SS,1R)-1-(2-Bromo-5-fluorophenyl)-N-(tert-butylsulfinyl)but-3-en-
1-amine (4c): The representative procedure was followed by using
imine 3c (214 mg, 0.7 mmol), indium (92 mg, 0.8 mmol), and allyl
bromide (0.090 mL, 1.0 mmol). Purification by column chromatog-
raphy (hexane/AcOEt, 3:1) yielded 4c (190 mg, 78%) as a colorless
oil; Rf = 0.45 (hexane/AcOEt, 1:1). [α]2D0 = +118 (c = 1.1, CH2Cl2).
(CH ), 32.2 (CH ), 23.3 (CH ), 22.3 (CH ) ppm. IR (ATR): ν =
˜
2
2
3
3
1624, 1360, 1071, 750 cm–1. LRMS (EI): m/z (%) = 226 (4), 224
(5), 212 (5), 210 (6), 171 (11), 169 (10), 147 (13), 146 (100), 131
(15), 130 (13), 77 (15), 70 (10). HRMS (EI): calcd. for
C10H1279BrNOS [M – C4H8]+ 272.9823; found 272.9829.
General Procedure for the Allylation of N-tert-Butylsulfinyl Imines 1H NMR (300 MHz, CDCl3): δ = 7.51 (dd, J = 8.8, 5.3 Hz, 1 H),
3. Synthesis of Homoallylamine Derivatives 4: A mixture of N-tert-
butylsulfinyl imine 3 (1.0 mmol), allyl bromide (166 mg, 0.132 mL,
7.13 (dd, J = 9.8, 3.1 Hz, 1 H), 6.88 (ddd, J = 8.7, 7.8, 3.1 Hz, 1
H), 5.84–5.69 (m, 1 H), 5.26–5.17 (m, 2 H), 4.98–4.89 (m, 1 H),
1.5 mmol), and indium (144 mg, 1.25 mmol) in dry THF (3 mL) 3.74 (d, J = 2.1 Hz, 1 H), 2.75–2.63 (m, 1 H), 2.46–2.32 (m, 1 H),
was stirred for 6 h at 65 °C. Then, the resulting mixture was hy-
drolyzed with H2O (5 mL), and the solution was extracted with
AcOEt (3 ϫ 5 mL). The combined organic phases were washed
with brine (3ϫ10 mL), dried with anhydrous MgSO4, and evapo-
rated (15 Torr). The residue was purified by column chromatog-
1.23 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 162.2 (d, J =
246.5 Hz, C), 143.3 (d, J = 6.7 Hz, CH), 134.4 (d, J = 7.7 Hz, C),
133.5 (CH), 120.2 (CH2), 117.4 (C), 116.3 (d, J = 22.6 Hz, ArCH),
115.9 (d, J = 24.0 Hz, CH), 56.2 (C), 55.7 (CH), 41.5 (CH2), 22.7
(CH ) ppm. IR (ATR): ν = 3215, 1466, 1053, 1027, 809 cm–1
.
˜
3
2466
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2461–2471

Chiral Aminated α-Methylenebenzocycloalkenes
LRMS (EI): m/z (%) = 251 (43), 249 (43), 212 (26), 203 (12), 202
(16), 201 (15), 200 (14), 171 (10), 170 (100), 152 (14), 148 (18), 134
(SS,2R)-1-(2-Bromophenyl)-N-(tert-butylsulfinyl)pent-4-en-2-amine
(4g): The representative procedure was followed by using imine 3g
(10), 122 (12), 121 (14), 95 (12), 94 (10), 91 (11). HRMS (EI): calcd. (453 mg, 1.5 mmol), indium (207 mg, 1.8 mmol), and allyl bromide
for C7H579BrFNOS [M – C4H8]+ 248.9259; found 248.9254.
(0.180 mL, 2.0 mmol). Purification by column chromatography
(hexane/AcOEt, 3:1) yielded 4g (378 mg, 73%) as a yellow solid;
m.p. 38–48 °C. Rf = 0.32 (hexane/AcOEt, 1:1). [α]2D0 = +9 (c = 1.08,
(SS,1R)-1-(2-Bromo-6-fluorophenyl)-N-(tert-butylsulfinyl)but-3-en-
1-amine (4d): The representative procedure was followed by using
imine 3d (214 mg, 0.7 mmol), indium (92 mg, 0.8 mmol), and allyl
bromide (0.090 mL, 1.0 mmol). Purification by column chromatog-
raphy (hexane/AcOEt, 3:1) yielded 4d (178 mg, 73%) as a white
solid; m.p. 67–70 °C. Rf = 0.44 (hexane/AcOEt, 1:1). [α]2D0 = +37 (c
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ = 7.53 (d, J = 8.5 Hz, 1
H), 7.25–7.21 (m, 2 H), 7.11–7.03 (m, 1 H), 5.93–5.79 (m, 1 H),
5.25–5.18 (m, 2 H), 3.72–3.63 (m, 1 H), 3.34 (d, J = 6.9 Hz, 1 H),
2.95 (dd, J = 7.2, 5.5 Hz, 2 H), 2.48 (t, J = 6.7 Hz, 2 H), 1.06 (s, 9
H) ppm. 13C NMR (101 MHz, CDCl3): δ = 138.3 (C), 133.9 (CH),
133.0 (CH), 132.0 (CH), 128.3 (CH), 127.4 (CH), 125.2 (C), 119.5
(CH2), 56.2 (CH), 56.0 (C), 41.8 (CH2), 40.7 (CH2), 22.6
1
= 1.04, CH2Cl2). H NMR (300 MHz, CDCl3): δ = 7.37 (dt, J =
7.9, 1.1 Hz, 1 H); 7.11 (td, J = 8.1, 5.9 Hz, 1 H), 7.01 (ddd, J =
10.7, 8.3, 1.1 Hz, 1 H), 5.83–5.65 (m, 1 H), 5.17–5.03 (m, 3 H),
3.98 (d, J = 6.9 Hz, 1 H), 2.92–2.66 (m, 2 H), 1.14 (s, 9 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 161.6 (d, J = 247.8 Hz, C), 133.5
(CH), 129.8 (d, J = 9.7 Hz, CH), 129.2 (C), 129.1 (CH), 124.1 (C),
119.0 (CH2), 115.7 (d, J = 23.1 Hz, CH), 58.3 (CH), 56.1 (C), 40.6
(CH ) ppm. IR (ATR): ν = 3216, 1736, 1472, 1045, 1024, 912,
˜
3
749 cm–1. LRMS (EI): m/z (%) = 247 (3), 245 (3), 208 (9), 184 (8),
182 (8), 171 (11), 169 (11), 118 (100), 91 (11), 90 (11), 89 (10).
+
HRMS (EI): calcd. for C8H879BrNOS [M – C7H14
found 244.9510.
]
244.9510;
(CH ), 22.5 (CH ) ppm. IR (ATR): ν = 3320, 1453, 1439, 1234,
˜
2
3
1187, 1058 cm–1. LRMS (EI): m/z (%) = 251 (60), 249 (59), 202 (SS,3S)-1-(2-Bromophenyl)-N-(tert-butylsulfinyl)hex-5-en-3-amine
(18), 200 (17), 171 (10), 170 (100), 152 (14), 148 (13), 134 (10), 122
(10), 95 (10), 75 (10). HRMS (EI): calcd. for C7H579BrFNOS [M –
C7H14]+ 248.9259; found 248.9266.
(4h): The representative procedure was followed by using imine 3h
(221 mg, 0.7 mmol), indium (100 mg, 0.87 mmol), and allyl brom-
ide (0.090 mL, 1.0 mmol). Purification by column chromatography
(hexane/AcOEt, 5:2) yielded 4h (202 mg, 81%) as a colorless oil;
(SS,1R)-1-(2-Bromopyridin-3-yl)-N-(tert-butylsulfinyl)but-3-en-1-
amine (4e): The representative procedure was followed by using im-
ine 3e (434 mg, 1.5 mmol), indium (215 mg, 1.87 mmol), and allyl
bromide (0.202 mL, 2.25 mmol). Purification by column
chromatography (hexane/AcOEt, 2:1) yielded 4e (478 mg, 90%) as
a yellow oil; Rf = 0.22 (hexane/AcOEt, 1:1). [α]2D0 = +111 (c = 0.97,
CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 8.30 (dd, J = 4.7,
2.0 Hz, 1 H), 7.70 (ddd, J = 7.7, 2.0, 0.3 Hz, 1 H), 7.28 (ddd, J =
7.7, 4.7, 0.3 Hz, 1 H), 5.83–5.68 (m, 1 H), 5.23–5.17 (m, 2 H), 4.95
(ddd, J = 8.0, 5.0, 3.0 Hz, 1 H), 3.81 (d, J = 2.3 Hz, 1 H), 2.81–
2.70 (m, 1 H), 2.54–2.42 (m, 1 H), 1.23 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 149.1 (CH), 143.2 (C), 138.4 (C), 137.3
(CH), 133.2 (CH), 123.0 (CH), 120.4 (CH2), 56.4 (C), 55.6 (CH),
1
Rf = 0.34 (hexane/AcOEt, 1:1). [α]2D0 = +43 (c = 0.95, CH2Cl2). H
NMR (400 MHz, CDCl3): δ = 7.52 (d, J = 7.9 Hz, 1 H), 7.26–7.19
(m, 2 H), 7.09–7.03 (m, 1 H), 5.87–5.75 (m, 1 H), 5.22–5.15 (m, 2
H), 3.46–3.37 (m, 1 H), 3.33 (d, J = 6.6 Hz, 1 H), 2.89 (ddd, J =
13.5, 11.1, 5.1 Hz, 1 H), 2.73 (ddd, J = 13.5, 11.1, 5.7 Hz, 1 H),
2.55–2.39 (m, 2 H), 1.91–1.70 (m, 2 H), 1.25 (s, 9 H) ppm. 13C
NMR (101 MHz, CDCl3): δ = 141.3 (ArC), 134.0 (CH), 133.0
(CH), 130.4 (CH), 127.9 (CH), 127.7 (CH), 124.5 (ArC), 119.4
(CH2), 56.1 (C), 55.1 (CH), 40.7 (CH2), 35.5 (CH2), 32.7 (CH2),
22.9 (CH ) ppm. IR (ATR): ν = 3215, 1471, 1439, 1052, 1022,
˜
3
749 cm–1. LRMS (EI): m/z (%) = 261 (29), 259 (29), 222 (46), 197
(37), 195 (37), 172 (16), 171 (97), 169 (100), 132 (39), 118 (23), 117
(49), 115 (10), 104 (12), 103 (14), 102 (15), 91 (24), 90 (28), 89 (17),
77 (26), 70 (21). HRMS (EI): calcd. for C9H1079BrNOS [M –
C7H14]+ 258.9666; found 258.9697.
41.2 (CH ), 22.8 (CH ) ppm. IR (ATR): ν = 3204, 1559, 1402,
˜
2
3
1045 cm–1. LRMS (EI): m/z (%) = 234 (100), 233 (10), 232 (97),
195 (11), 186 (13), 184 (14), 153 (91), 131 (13), 130 (47), 117 (12),
105 (83), 104 (23), 103 (28), 91 (14), 78 (43), 77 (27), 76 (19), 52
(SS,4R)-7-(2-Bromophenyl)-N-(tert-butylsulfinyl)hept-1-en-4-amine
(11), 51 (26). HRMS (EI): calcd. for C9H1179BrN2OS [M – (4i): The representative procedure was followed by using imine 3i
C4H8]+ 273.9775; found 273.9760.
(300 mg, 0.91 mmol), indium (131 mg, 1.14 mmol), and allyl brom-
ide (0.123 mL, 1.37 mmol). Purification by column chromatog-
raphy (hexane/AcOEt, 2:1) yielded 4i (318 mg, 94%) as a colorless
oil; Rf = 0.44 (hexane/AcOEt, 1:1). [α]2D0 = +40 (c = 1.06, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ = 7.56–7.50 (m, 1 H), 7.26–7.16
(m, 1 H), 7.10–7.01 (m, 1 H), 5.86–5.70 (m, 1 H), 5.20–5.11 (m, 2
H), 3.41–3.31 (m, 1 H), 3.22 (d, J = 6.0 Hz, 1 H), 2.72 (t, J =
7.6 Hz, 2 H), 2.46–2.38 (m, 1 H), 2.37–2.27 (m, 1 H), 1.80–1.51 (m,
4 H), 1.20 (s, 9 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 141.5
(C), 134.2 (CH), 132.9 (CH), 130.4 (CH), 127.7 (CH), 127.5 (CH),
124.5 (C), 119.1 (CH2), 55.9 (C), 54.7 (CH), 40.5 (CH2), 36.2
(SS,1R)-1-(3-Bromobenzo[b]thiophen-2-yl)-N-(tert-butylsulfinyl)but-
3-en-1-amine (4f): The representative procedure was followed by
using imine 3f (344 mg, 1.0 mmol), indium (140 mg, 1.22 mmol),
and allyl bromide (0.135 mL, 1.5 mmol). Purification by column
chromatography (n-hexane/AcOEt, 3:1) yielded 4f (336 mg, 80%)
as a mixture (dr 93:7) and as a yellow oil; Rf = 0.44 (hexane/AcOEt,
1:1). [α]2D0 = +102 (c = 1.02, CH2Cl2). 1H NMR (400 MHz, CDCl3):
δ = 7.78 (t, J = 8.7 Hz, 2 H), 7.44 (td, J = 7.6, 1.0 Hz, 1 H), 7.37
(td, J = 7.6, 1.2 Hz, 1 H), 5.89–5.77 (m, 1 H), 5.29–5.26 (m, 1 H),
5.26–5.20 (m, 1 H), 5.14 (ddd, J = 7.9, 5.4, 2.2 Hz, 1 H), 3.82 (d,
J = 1.6 Hz, 1 H), 2.83–2.74 (m, 1 H), 2.66–2.56 (m, 1 H), 1.24 (s,
9 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 141.9 (C), 138.3 (C),
137.5 (C), 133.2 (CH), 125.5 (CH), 125.2 (CH), 123.1 (CH), 122.6
(CH), 120.3 (CH2), 106.4 (C), 56.4 (C), 53.1 (CH), 42.2 (CH2), 22.8
(CH ), 34.7 (CH ), 25.9 (CH ), 22.8 (CH ) ppm. IR (ATR): ν =
˜
2
2
2
3
3217, 1471, 913, 750 cm–1. LRMS (EI): m/z (%) = 317 (20), 315
(19), 275 (11), 273 (11), 224 (10), 211 (29), 209 (30), 171 (25), 169
(25), 146 (12), 132 (11), 131 (100), 130 (18), 118 (24), 115 (16), 104
(29), 103 (18), 102 (15), 91 (40), 90 (21), 89 (16), 77 (25), 70 (14), 56
(15), 55 (10). HRMS (EI): calcd. for C13H1879BrNOS [M – C4H8]+
315.0292; found 315.0293.
(CH ) ppm. IR (ATR): ν = 3204, 2867, 1436, 1053, 752 cm–1
.
˜
3
LRMS (EI): m/z (%) = 331 (11), 329 (10), 289 (29), 287 (27), 282
(25), 280 (24), 251 (16), 250 (84), 242 (12), 241 (100), 240 (33), 239
(100), 238 (22), 214 (13), 212 (13), 208 (39), 187 (17), 186 (27), 185
(18), 172 (38), 171 (14), 159 (26), 133 (10), 132 (11), 115 (10), 89
(SS,2R)-2-(2-Bromophenyl)-N-(tert-butylsulfinyl)pent-4-en-2-amine
(4j): The representative procedure was followed by using imine 3j
(21). HRMS (EI): calcd. for C12H1279BrNOS2 [M – C4H8]+ (242 mg, 0.8 mmol), indium (115 mg, 1.0 mmol), and allyl bromide
328.9544; found 328.9536.
(0.108 mL, 1.2 mmol). Purification by column chromatography
Eur. J. Org. Chem. 2013, 2461–2471
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2467

J. A. Sirvent, F. Foubelo, M. Yus
FULL PAPER
(hexane/AcOEt, 3:1) yielded 4j (44 mg, 16%, diastereomeric mix-
ture, 3:1) as a yellow oil; Rf = 0.43 (hexane/AcOEt, 1:1). 1H NMR
(400 MHz, CDCl3, major isomer): δ = 7.62 (ddd, J = 7.9, 1.4 Hz,
1 H), 7.49 (dd, J = 8.0, 1.6 Hz, 1 H), 7.31–7.25 (m, 1 H), 7.11 (ddd,
J = 7.4, 6.5, 1.7 Hz, 1 H), 5.53–5.40 (m, 1 H), 5.18–5.09 (m, 1 H),
5.07–5.00 (m, 1 H), 4.58 (s, 1 H), 3.20 (dd, J = 13.9, 7.3 Hz, 1 H),
3.13 (dd, J = 13.9, 7.2 Hz, 1 H), 1.89 (s, 3 H), 1.23 (s, 9 H) ppm.
13C NMR (101 MHz, CDCl3, major isomer): δ = 142.5 (C), 136.0
(CH), 133.5 (CH), 129.05 (CH), 128.97 (CH), 127.5 (CH), 121.7
imine 3a (288 mg, 1.0 mmol), indium (143 mg, 1.25 mmol), and 3-
bromo-2-methylpropene (0.156 mL, 1.5 mmol). Purification by col-
umn chromatography (hexane/AcOEt, 3:1) yielded 4m (220 mg,
64%) as a white solid; m.p. 76–78 °C. Rf = 0.52 (hexane/AcOEt,
1:1). [α]2D0 = +165 (c = 1.02, CH2Cl2). 1H NMR (300 MHz, CDCl3):
δ = 7.55 (dd, J = 8.0, 1.2 Hz, 1 H), 7.48 (dd, J = 7.8, 1.6 Hz, 1 H),
7.30 (td, J = 7.5, 1.0 Hz, 1 H), 7.13 (td, J = 7.8, 1.7 Hz, 1 H), 5.00
(dd, J = 11.1, 3.8 Hz, 1 H), 4.96 (s, 1 H), 4.88 (s, 1 H), 3.72 (s, 1
H), 2.62 (dd, J = 13.7, 3.7 Hz, 1 H), 2.23 (dd, J = 13.8, 10.6 Hz, 1
H), 1.86 (s, 3 H), 1.22 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3):
(C), 119.6 (CH2), 61.1 (C), 56.4 (C), 45.4 (CH2), 26.3 (CH3), 23.0
1
(CH3) ppm. H NMR (400 MHz, CDCl3, minor isomer): δ = 7.60 δ = 142.3 (C), 141.4 (C), 133.2 (CH), 128.9 (CH), 128.7 (CH), 127.6
(dd, J = 8.3, 1.3 Hz, 1 H), 7.52 (dd, J = 8.0, 1.6 Hz, 1 H), 7.32–
7.25 (m, 1 H), 7.13–7.07 (m, 1 H), 5.53–5.40 (m, 1 H), 5.18–5.09
(m, 1 H), 5.08–5.00 (m, 1 H), 4.94 (s, 1 H), 3.02 (dd, J = 14.0,
(CH), 123.5 (C), 115.3 (CH2), 55.9 (C), 53.4 (CH), 46.1 (CH2), 22.7
(CH ), 21.5 (CH ) ppm. IR (ATR): ν = 3296, 1648, 1567, 1465,
˜
3
3
1060, 755 cm–1. LRMS (EI): m/z (%) = 233 (53), 231 (52), 225 (5),
7.2 Hz, 1 H), 2.93 (dd, J = 13.9, 7.3 Hz, 1 H), 1.83 (s, 3 H), 1.25 223 (6), 184 (15), 182 (14), 153 (89), 152 (100), 144 (14), 134 (14),
(s, 9 H) ppm. 13C NMR (101 MHz, CDCl3, minor isomer): δ =
142.7 (C), 135.7 (CH), 133.2 (CH), 129.4 (CH), 127.6 (CH), 122.0
(C), 118.9 (CH), 60.9 (C), 56.3 (C), 45.1 (CH2), 26.4 (CH3), 22.9
129 (13), 77 (12). HRMS (EI): calcd. for C11H1479BrNOS [M –
C4H8]+ 286.9979; found 286.9997.
(SS,1R)-1-(2-Bromophenyl)-N-(tert-butylsulfinyl)-2,2-dimethylbut-3-
en-1-amine (4n): The representative procedure was followed by
using imine 3a (242 mg, 0.84 mmol), indium (115 mg, 1.0 mmol),
and 3,3-dimethylallyl bromide (0.110 mL, 1.2 mmol). Purification
by column chromatography (hexane/AcOEt, 5:1) yielded 4n
(156 mg, 52%) as a yellow oil; Rf = 0.52 (hexane/AcOEt, 1:1). [α]
(CH ) ppm. IR (ATR): ν = 3217, 1638, 1462, 1427, 1061,
˜
3
1016 cm–1. LRMS (EI): m/z (%) = 274 (15), 272 (14), 247 (17), 245
(17), 208 (56), 184 (11), 182 (11), 167 (10), 166 (100), 144 (17), 130
(22), 129 (16), 115 (10), 103 (11), 102 (15), 91 (12). HRMS (EI):
calcd. for C10H1179BrNOS [M – C4H8]+ 271.9745; found 271.9752.
(SS,2R)-1-(2-Bromophenyl)-N-(tert-butylsulfinyl)-2-methylpent-4-
en-2-amine (4k): The representative procedure was followed by
using imine 3k (316 mg, 1.0 mmol), indium (143 mg, 1.25 mmol),
and allyl bromide (0.135 mL, 1.5 mmol). Purification by column
chromatography (hexane/AcOEt, 3:1) yielded 4k (237 mg, 66%) as
a colorless oil; Rf = 0.51 (hexane/AcOEt, 1:1). [α]2D0 = –20 (c = 1.04,
20
1
= +108 (c = 1.05, CH2Cl2). H NMR (300 MHz, CDCl3): δ =
D
7.57 (dd, J = 8.0, 1.2 Hz, 1 H), 7.33 (dd, J = 7.9, 2.0 Hz, 1 H), 7.28
(td, J = 7.5, 1.2 Hz, 1 H), 7.13 (ddd, J = 8.0, 7.0, 2.0 Hz, 1 H),
5.98 (dd, J = 17.5, 10.7 Hz, 1 H), 5.24 (dd, J = 10.7, 1.1 Hz, 1 H),
5.17 (dd, J = 17.5, 1.1 Hz, 1 H), 4.90 (d, J = 2.3 Hz, 1 H), 3.74 (d,
J = 1.6 Hz, 1 H), 1.14 (s, 9 H), 1.11 (s, 3 H), 1.03 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 145.5 (CH), 138.2 (C), 133.1
(CH), 131.1 (CH), 129.0 (CH), 126.7 (CH), 126.2 (C), 115.0 (CH2),
61.8 (CH), 55.8 (C), 43.1 (C), 25.8 (CH3), 22.7 (CH3), 20.5
1
CH2Cl2). H NMR (300 MHz, CDCl3): δ = 7.55 (d, J = 7.9 Hz, 1
H), 7.39 (dd, J = 7.7, 1.5 Hz, 1 H), 7.24 (t, J = 7.3 Hz, 1 H), 7.08
(td, J = 7.7, 1.6 Hz, 1 H), 6.06–5.89 (m, 1 H), 5.26 (s, 1 H), 5.24–
5.18 (m, 1 H), 3.60 (s, 1 H), 3.19 (d, J = 13.8 Hz, 1 H), 2.93 (d, J
= 13.8 Hz, 1 H), 2.57 (d, J = 7.4 Hz, 2 H), 1.29 (s, 3 H), 1.11 (s, 9
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 137.1 (C), 133.5 (CH),
133.1 (CH), 132.8 (CH), 128.3 (CH), 127.1 (CH), 126.5 (C), 120.0
(CH2), 59.0 (C), 56.1 (C), 47.5 (CH2), 45.8 (CH2), 25.0 (CH3), 22.7
(CH ) ppm. IR (ATR): ν = 3276, 1636, 1467, 1068, 1020 cm–1
.
˜
3
LRMS (EI): m/z (%) = 306 (11), 304 (11), 233 (66), 231 (65), 207
(17), 186 (64), 185 (14), 184 (83), 183 (11), 182 (17), 153 (10), 152
(100), 144 (10), 136 (20), 134 (12), 104 (12), 103 (10), 102 (15), 77
(17), 69 (10), 57 (28), 55 (12). HRMS (EI): calcd. for C7H679BrNOS
[M – C9H18]+ 232.9333; found 232.9328.
(CH ) ppm. IR (ATR): ν = 3222, 1436, 1048, 915, 747 cm–1. LRMS
˜
3
(EI): m/z (%) = 171 (5), 169 (5), 134 (5), 133 (7), 132 (100), 116 (6),
114 (6), 91 (6), 90 (11), 89 (8), 84 (6). HRMS (EI): calcd. for
C7H679Br [M – C9H18NOS]+ 168.9653; found 168.9658.
(SS,1R,1ЈR)-(2-Bromophenyl)-N-(tert-butylsulfinyl)(cyclohex-2-en-
1-yl)methanamine (4o): The representative procedure was followed
by using imine 3a (288 mg, 1 mmol), indium (143 mg, 1.25 mmol),
and 3-bromocyclohexene (0.155 mL, 1.5 mmol). Purification by
column chromatography (hexane/AcOEt, 4:1) yielded 4o (110 mg,
60%) as a white solid; m.p. 114–117 °C. Rf = 0.50 (hexane/AcOEt,
1:1). [α]2D0 = +150 (c = 0.93, CH2Cl2). 1H NMR (300 MHz, CDCl3):
δ = 7.55 (dd, J = 7.9, 1.2 Hz, 1 H), 7.40 (dd, J = 7.8, 1.8 Hz, 1 H),
7.31 (td, J = 7.5, 1.1 Hz, 1 H), 7.12 (td, J = 7.4, 1.8 Hz, 1 H), 6.02–
5.87 (m, 1 H), 5.55 (d, J = 10.0 Hz, 1 H), 4.75 (t, J = 4.4 Hz, 1 H),
3.64 (d, J = 4.3 Hz, 1 H), 2.73–2.60 (m, 1 H), 2.07–1.94 (m, 2 H),
1.93–1.75 (m, 2 H), 1.69–1.40 (m, 2 H), 1.20 (s, 9 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 141.4 (C), 133.2 (CH), 132.7 (CH),
129.2 (CH), 128.7 (CH), 127.2 (CH), 124.4 (CH), 123.5 (C), 61.4
(CH), 56.0 (C), 41.0 (CH), 27.0 (CH2), 25.2 (CH2), 22.8 (CH3),
(SS,3S)-1-(2-Bromophenyl)-N-(tert-butylsulfinyl)-3-methylhex-5-en-
3-amine (4l): The representative procedure was followed by using
imine 3l (369 mg, 1.11 mmol), indium (160 mg, 1.4 mmol), and allyl
bromide (0.151 mL, 1.68 mmol). Purification by column
chromatography (n-hexane/AcOEt, 1:1) yielded 4l (302 mg, 81%)
as a yellow oil; Rf = 0.47 (hexane/AcOEt, 1:1). [α]2D0 = +43 (c =
1.03, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 7.51 (d, J =
7.8 Hz, 1 H), 7.26–7.21 (m, 2 H), 7.10–7.00 (m, 1 H), 5.97–5.78 (m,
1 H), 5.25–5.09 (m, 2 H), 3.38 (s, 1 H), 2.94–2.64 (m, 2 H), 2.53–
2.36 (m, 2 H), 1.84–1.72 (m, 2 H), 1.40 (s, 3 H), 1.24 (s, 9 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 141.5 (C), 133.3 (CH), 132.9
(CH), 130.6 (CH), 127.8 (CH), 127.8 (CH), 124.4 (C), 119.8 (CH2),
57.6 (C), 56.1 (C), 46.8 (CH2), 41.5 (CH2), 30.7 (CH2), 25.7 (CH3),
21.7 (CH ) ppm. IR (ATR): ν = 3248, 1469, 1049, 1036 cm–1
.
˜
2
22.9 (CH ) ppm. IR (ATR): ν = 3222, 1637, 1471, 1053, 1023,
˜
3
LRMS (EI): m/z (%) = 251 (12), 249 (12), 234 (45), 233 (77), 232
(23), 231 (74), 186 (21), 185 (11), 184 (43), 183 (9), 182 (23), 171
(18), 170 (32), 169 (16), 153 (11), 152 (100), 142 (10), 141 (10), 136
(16), 134 (14), 129 (11), 128 (12), 115 (11), 104 (11), 102 (13), 81
(20), 79 (11), 77 (22), 67 (13). HRMS (EI): calcd. for
C13H1679BrNOS [M – C4H8]+ 313.0136; found 313.0101.
748 cm–1. LRMS (EI): m/z (%) = 317 (2) [M – 56 (81Br)]+, 315 (2),
302 (2), 300 (2), 275 (23), 273 (22), 236 (45), 226 (4), 224 (5), 211
(4), 209 (4), 194 (7), 171 (49), 169 (50), 146 (61), 133 (17), 132 (100),
131 (11), 116 (16), 104 (16), 103 (12), 91 (27), 90 (24), 89 (15), 84
(42), 77 (22), 55 (11). HRMS (EI): calcd. for C13H1879BrNOS [M –
C4H8]+ 315.0292; found 315.0320.
(SS,1R)-1-(2-Bromophenyl)-N-(tert-butylsulfinyl)-3-methylbut-3-en- General Procedure for the Intramolecular Heck Reaction of Homoal-
1-amine (4m): The representative procedure was followed by using lylamine Derivatives 4. Synthesis of Methylene Carbocycles 5: A
2468
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2461–2471

Chiral Aminated α-Methylenebenzocycloalkenes
mixture of homoallylamine derivative 4 (0.5 mmol), PPh3
(0.1 mmol, 26.2 mg), Pd(OAc)2 (0.025 mmol, 5.6 mg) and n-Bu4-
NOAc (0.8 mmol, 242 mg) in dry THF (3 mL) was stirred at 90 °C
under Ar for 16 h in a high-pressure tube. Then, the resulting mix-
ture was hydrolyzed with H2O (5 mL), and the solution was ex-
tracted with AcOEt (3 ϫ15 mL). The combined organic phases
were dried with anhydrous MgSO4 and evaporated (15 Torr). The
residue was purified by column chromatography (silica gel, hexane/
AcOEt) to yield products 5. The yields and the physical and spec-
troscopic data follow.
OEt, 2:1) yielded 5d (107 mg, 67%) as a brown solid; m.p. 94–
98 °C. Rf = 0.38 (hexane/AcOEt, 1:1). [α]2D0 = +31 (c = 1.01,
CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 7.46 (dd, J = 8.4,
5.1 Hz, 1 H), 7.08–7.03 (m, 1 H), 7.00 (J = 8.5, 2.4 Hz, 1 H), 5.41
(t, J = 2.3 Hz, 1 H), 5.0 (t, J = 1.8 Hz, 1 H), 4.84 (ddd, J = 9.8,
8.3, 5.7 Hz, 1 H), 3.40 (ddt, J = 17.0, 8.0, 1.9 Hz, 1 H), 3.38 (d, J
= 8.3 Hz, 1 H), 2.80 (ddt, J = 17.0, 5.2, 2.5 Hz, 1 H), 1.27 (s, 9
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 163.5 (d, J = 248.1 Hz,
C), 148.1 (d, J = 7.7 Hz, C), 145.2 (C), 136.5 (d, J = 2.4 Hz, C),
122.3 (d, J = 8.9 Hz, CH), 116.4 (d, J = 23.4 Hz, CH), 112.0 (d, J
= 22.5 Hz, CH), 104.1 (CH2), 59.5 (CH), 56.4 (C), 43.1 (CH2), 22.9
(SS,1R)-N-(tert-Butylsulfinyl)-3-methylene-2,3-dihydro-1H-inden-1-
amine (5a): The representative procedure was followed by using sul-
finamide 4a (165 mg, 0.5 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol),
PPh3 (21 mg, 0.08 mmol), and TBAA (242 mg, 0.8 mmol). Purifica-
tion by column chromatography (hexane/acetone, 4:1) yielded 5a
(77 mg, 62%) as a white solid; m.p. 77–81 °C. Rf = 0.34 (hexane/
(CH ) ppm. IR (ATR): ν = 3189, 1646, 1480, 1046, 1032, 862 cm–1.
˜
3
LRMS (EI): m/z (%) = 209 (18), 163 (24), 162 (59) [M – 105]+, 161
(55), 148 (56), 147 (67), 146 (100), 145 (13), 134 (21), 133 (78), 127
(20), 121 (10), 120 (10), 107 (12). HRMS (EI): calcd. for
C10H8FNOS [M – C4H8]+ 209.0311; found 209.0321.
1
AcOEt, 1:1). [α]2D0 = +21 (c = 1.00, CH2Cl2). H NMR (300 MHz,
(SS,1R)-N-(tert-Butylsulfinyl)-7-fluoro-3-methylene-2,3-dihydro-1H-
inden-1-amine (5d): The representative procedure was followed by
using sulfinamide 4d (210 mg, 0.6 mmol), Pd(OAc)2 (5.4 mg,
0.024 mmol), PPh3 (26 mg, 0.1 mmol), and TBAA (302 mg,
1.0 mmol). Purification by column chromatography (hexane/Ac-
OEt, 2:1) yielded 5d (93 mg, 58%) as a white solid; m.p. 70–75 °C.
CDCl3): δ = 7.56–7.49 (m, 1 H), 7.44–7.38 (m, 1 H), 7.35–7.28 (m,
2 H), 5.50 (t, J = 2.4 Hz, 1 H), 5.10 (t, J = 2.0 Hz, 1 H), 4.89 (ddd,
J = 10.3, 7.9, 5.1 Hz, 1 H), 3.42 (d, J = 9.9 Hz, 1 H), 3.38 (ddt, J
= 17.0, 7.9, 1.9 Hz, 1 H), 2.79 (ddt, J = 17.0, 5.0, 2.5 Hz, 1 H),
1.26 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 146.4 (C),
145.9 (C), 140.5 (C), 128.9 (CH), 128.8 (CH), 125.5 (CH), 120.8
(CH), 104.6 (CH2), 59.8 (CH), 56.3 (C), 42.7 (CH2), 22.9
(CH ) ppm. IR (ATR): ν = 3166, 1643, 1041, 859, 754 cm–1. LRMS
Rf = 0.32 (hexane/AcOEt, 1:1). [α]2D0 = +22 (c = 1.02, CH2Cl2). H
1
NMR (300 MHz, CDCl3): δ = 7.31 (t, J = 3.8 Hz, 1 H), 7.30 (t, J
= 3.4 Hz, 1 H), 7.00–6.90 (m, 1 H), 5.57 (t, J = 2.4 Hz, 1 H), 5.16
(t, J = 1.6 Hz, 1 H), 5.07 (ddd, J = 9.8, 8.1, 3.0 Hz, 1 H), 3.36 (d,
J = 10.2 Hz, 1 H), 3.33 (ddd, J = 17.5, 8.0, 2.4 Hz, 1 H), 2.93 (ddd,
J = 17.5, 5.0, 2.1 Hz, 1 H), 1.22 (s, 9 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 160.4 (d, J = 251.6 Hz, C), 146.0 (d, J = 2.1 Hz, C),
143.9 (d, J = 4.9 Hz, C), 131.8 (C), 130.9 (d, J = 7.2 Hz, CH),
116.6 (d, J = 3.6 Hz, CH), 115.5 (d, J = 20.1 Hz, CH), 106.4 (CH2),
˜
3
(EI): m/z (%) = 191 (17), 145 (25), 144 (61), 143 (52), 130 (53), 129
(73), 128 (100), 127 (28), 116 (21), 115 (69), 103 (14), 102 (12), 89
(14), 77 (20), 75 (11), 65 (11), 64 (14), 63 (32), 56 (32), 55 (14), 51
(26). HRMS (EI): calcd. for C10H9NOS [M – C4H10]+ 191.0405;
found 191.0405.
(RS,1S)-N-(tert-Butylsulfinyl)-3-methylene-2,3-dihydro-1H-inden-1-
amine (ent-5a): The representative procedure was followed by using
sulfinamide ent-4a (165 mg, 0.5 mmol), Pd(OAc)2 (4.5 mg,
0.02 mmol), PPh3 (21 mg, 0.08 mmol), and TBAA (242 mg,
0.8 mmol). Purification by column chromatography (hexane/ace-
tone, 4:1) yielded ent-5a (77 mg, 62%) as a white solid. The physical
57.7 (CH), 56.3 (C), 41.9 (CH ), 22.6 (CH ) ppm. IR (ATR): ν =
˜
2
3
3138, 1583, 1473, 1239, 1029 cm–1. LRMS (EI): m/z (%) = 209 (14),
163 (19), 162 (45), 161 (38), 149 (9), 148 (68), 147 (75), 146 (100),
145 (12), 134 (17), 133 (91), 128 (10), 127 (21), 120 (10), 115 (9),
+
107 (11). HRMS (EI): calcd. for C10H8FNOS [M – C4H10
209.0311; found 209.0315.
]
and spectroscopic data were the same as the data for 5a. [α]2D0
–23 (c = 1.00, CH2Cl2).
=
(SS,5R)-N-(tert-Butylsulfinyl)-7-methylene-6,7-dihydro-5H-cyclo-
penta[b]pyridin-5-amine (5e): The representative procedure was fol-
lowed by using sulfinamide 4e (200 mg, 0.6 mmol), Pd(OAc)2
(6.7 mg, 0.03 mmol), PPh3 (31 mg, 0.12 mmol), and TBAA
(302 mg, 1.0 mmol). Purification by column chromatography (hex-
ane/acetone, 3:1) yielded 5e (84 mg, 56%) as an orange oil; Rf =
(SS,1R)-N-(tert-Butylsulfinyl)-6-methoxy-3-methyl-1H-inden-1-
amine (5bЈ): The representative procedure was followed by using
sulfinamide 4b (116 mg, 0.32 mmol), Pd(OAc)2 (9.0 mg,
0.0432 mmol, 14 mol-%), PPh3 (42 mg, 0.16 mmol), and TBAA
(293 mg, 0.97 mmol). Purification by column chromatography
(hexane/acetone, 3:1) yielded 5bЈ (62 mg, 69%) as a brown solid;
m.p. 88–96 °C. Rf = 0.31 (hexane/AcOEt, 1:1). [α]2D0 = –124 (c =
0.94, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 7.13 (d, J =
8.2 Hz, 1 H), 7.04 (J = 2.4 Hz, 1 H), 6.85 (dd, J = 8.2, 2.4 Hz, 1
H), 6.18–6.16 (m, 1 H), 4.76 (d, J = 10.2 Hz, 1 H), 3.83 (s, 3 H),
3.24 (d, J = 10.2 Hz, 1 H), 2.07 (t, J = 1.8 Hz, 3 H), 1.26 (s, 9
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 158.9 (C), 147.4 (C),
140.9 (C), 137.4 (C), 130.7 (CH), 119.8 (CH), 112.7 (CH), 111.1
(CH), 63.1 (CH3), 56.4 (C), 55.8 (CH), 22.9 (CH3), 13.1
1
0.25 (AcOEt). [α]2D0 = –2 (c = 1.0, CH2Cl2). H NMR (300 MHz,
CDCl3): δ = 8.54 (d, J = 4.8 Hz, 1 H), 7.73 (ddd, J = 7.7, 1.4,
1.0 Hz, 1 H), 7.19 (dd, J = 7.7, 4.8 Hz, 1 H), 6.01 (t, J = 2.05 Hz,
1 H), 5.21 (t, J = 2.0 Hz, 1 H), 4.89 (td, J = 8.9, 4.8 Hz, 1 H), 3.63
(d, J = 9.6 Hz, 1 H), 3.41 (ddt, J = 17.3, 8.1, 2.1 Hz, 1 H), 2.83
(ddt, J = 17.3, 5.0, 2.6 Hz, 1 H), 1.25 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 158.4 (C), 150.6 (CH), 145.0 (C), 139.1 (C),
133.8 (CH), 123.2 (CH), 108.2 (CH2), 57.2 (CH), 56.4 (C), 40.6
(CH ), 22.8, (CH ) ppm. IR (ATR): ν = 3179, 1437, 1069,
˜
2
3
722 cm–1. LRMS (EI): m/z (%) = 192 (14), 146 (24), 145 (62), 144
(50), 143 (23), 131 (52), 130 (100), 129 (56), 128 (10), 118 (11), 117
(22), 116 (10), 104 (10), 103 (13), 90 (10), 89 (12), 77 (17), 63 (16),
56 (17), 51 (14). HRMS (EI): calcd. for C9H8N2OS [M – C4H10]+
192.0357; found 192.0378.
(CH ) ppm. IR (ATR): ν = 3191, 1612, 1480, 1274, 1049, 1030,
˜
3
822 cm–1. LRMS (EI): m/z (%) = 207 (15), 175 (10), 174 (18), 173
(100), 172 (21), 160 (17), 158 (31), 144 (12), 143 (15), 130 (27), 115
(15), 103 (21), 77 (14), 57 (11). HRMS (EI): calcd. for C15H21NO2S
279.1293; found 279.1294.
(SS,1R)-N-(tert-Butylsulfinyl)-6-fluoro-3-methylene-2,3-dihydro-1H-
inden-1-amine (5c): The representative procedure was followed by
using sulfinamide 4c (210 mg, 0.6 mmol), Pd(OAc)2 (5.4 mg,
(SS,3R)-N-(tert-Butylsulfinyl)-1-methylene-2,3-dihydro-1H-benzo[b]-
cyclopenta[d]thiophen-3-amine (5f): The representative procedure
was followed by using the sulfinamide 4f (170 mg, 0.44 mmol),
0.024 mmol), PPh3 (26 mg, 0.1 mmol), and TBAA (302 mg, Pd(OAc)2 (4.4 mg, 0.0198 mmol), PPh3 (21 mg, 0.08 mmol), and
1.0 mmol). Purification by column chromatography (hexane/Ac- TBAA (242 mg, 0.8 mmol). Purification by column chromatog-
Eur. J. Org. Chem. 2013, 2461–2471
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2469

J. A. Sirvent, F. Foubelo, M. Yus
FULL PAPER
raphy (hexane/acetone, 6:1) yielded 5f (32 mg, 24%) as a white so-
lid; m.p. 110–118 °C. Rf = 0.35 (hexane/AcOEt, 1:1). [α]2D0 = +36
(c = 1.01, CH2Cl2). H NMR (400 MHz, CDCl3): δ = 7.96 (d, J =
ferent products [major diastereoisomers: exo-5ja (52%) and endo-
5jb (22 %); minor diastereoisomers: exo-5jc (25 %) and endo-5jd
(1%)]. Purification by column chromatography (hexane/acetone,
1
7.7 Hz, 1 H), 7.80 (ddd, J = 8.0, 1.1, 0.7 Hz, 1 H), 7.43 (ddd, J = 6:1) yielded 5j (17 mg, 74%). It was possible to enrich the pro-
7.9, 7.2, 1.2 Hz, 1 H), 7.36 (ddd, J = 8.0, 7.2, 1.3 Hz, 1 H), 5.47 (t,
J = 2.2 Hz, 1 H), 5.11 (ddd, J = 9.7, 7.6, 3.4 Hz, 1 H), 5.07 (t, J =
portion of 5ja as a mixture of 5ja (75%), 5jb (5%), and 5jc (20%)
as a yellow oil; Rf = 0.26 (hexane/AcOEt, 1:1). Data for 5ja: 1H
1.8 Hz, 1 H), 3.70 (ddt, J = 16.7, 7.5, 1.9 Hz, 1 H), 3.57 (d, J = NMR (400 MHz, CDCl3): δ = 7.52–7.49 (m, 1 H), 7.38–7.34 (m, 1
9.4 Hz, 1 H), 3.16 (ddt, J = 16.7, 3.4, 2.1 Hz, 1 H), 1.24 (s, 9
H), 7.32–7.28 (m, 2 H), 5.50 (t, J = 2.4 Hz, 1 H), 5.09 (t, J =
1.9 Hz, 1 H), 3.44 (br. s, 1 H), 3.19 (dt, J = 16.4, 2.4 Hz, 1 H), 2.95
H) ppm. 13C NMR (101 MHz, CDCl3): δ = 151.7 (C), 145.8 (C),
142.6 (C), 141.0 (C), 132.6 (C), 125.2 (CH), 125.1 (CH), 123.9 (dt, J = 16.4, 1.9 Hz, 1 H), 1.60 (s, 1 H), 1.20 (s, 9 H) ppm. 13C
(CH), 122.8 (CH), 103.2 (CH2), 57.9 (CH), 56.5 (C), 46.8 (CH2), NMR (101 MHz, CDCl3): δ = 150.3 (C), 146.0 (C), 139.7 (C), 129.0
22.8 (CH ) ppm. IR (ATR): ν = 3152, 1634, 1034, 734 cm–1. LRMS
(CH), 128.7 (CH), 123.8 (CH), 120.8 (CH), 104.7 (CH2), 64.0 (C),
˜
3
(EI): m/z (%) = 207 (25), 202 (10), 201 (50), 200 (77), 199 (100), 55.8 (C), 49.2 (CH ), 28.2 (CH ), 22.7 (CH ) ppm. IR (ATR): ν =
˜
2
3
3
198 (12), 186 (35), 185 (17), 184 (38), 172 (20), 171 (42), 139 (10),
115 (10). HRMS (EI): calcd. for C12H11NOS2 [M – C4H8]+
249.0282; found 249.0310.
3202, 1645, 1472, 1364, 1049, 756 cm–1. LRMS (EI): m/z (%) = 207
(3), 167 (11), 145 (10), 144 (59), 143 (20), 142 (29), 141 (32), 130
(12), 129 (100), 128 (59), 127 (21), 115 (20), 71 (10), 63 (15), 56
(12). HRMS (EI): calcd. for C11H11NOS [M – C4H10]+ 205.0561;
found 205.0568.
(SS,2R)-N-(tert-Butylsulfinyl)-4-methylene-1,2,3,4-tetrahydronaphth-
alen-2-amine (5g): The representative procedure was followed by
using sulfinamide 4g (51 mg, 0.15 mmol), Pd(OAc)2 (1.3 mg,
0.006 mmol), PPh3 (6.3 mg, 0.024 mmol), and TBAA (68 mg,
(SS,2R)-N-(tert-Butylsulfinyl)-2-methyl-4-methylene-1,2,3,4-tetra-
hydronaphthalen-2-amine (5k): The representative procedure was
0.225 mmol). The conversion after 14 h was 80%, and the 1H NMR followed by using sulfinamide 4k (101 mg, 0.28 mmol), Pd(OAc)2
spectroscopic data of the crude material also showed a mixture of
isomers (exo/endo, 10:7). Purification by column chromatography
(hexane/acetone, 5:1) yielded 5g (18 mg, 45% overall yield). It was
possible to isolate 5 mg of the pure exo isomer as a yellow oil. Rf
= 0.32 (hexane/AcOEt, 1:1). [α]2D0 = +21 (c = 0.5, CH2Cl2). Data
(2.5 mg, 0.0112 mmol), PPh3 (11.7 mg, 0.045 mmol), and TBAA
(127 mg, 0.42 mmol). The 1H NMR spectroscopic data showed the
crude product as a mixture (exo/endo, 78:22, 91% conversion). Pu-
rification by column chromatography (hexane/acetone, 5:1) yielded
5k (38 mg, 49%, exo product) as a white solid; m.p. 91–99 °C. Rf
= 0.22 (hexane/AcOEt, 1:1). [α]2D0 = +46 (c = 0.98, CH2Cl2). 1H
1
for exo isomer: H NMR (300 MHz, CDCl3): δ = 7.68–7.61 (m, 1
H), 7.23–7.15 (m, 2 H), 7.13–7.06 (m, 1 H), 5.61 (s, 1 H), 5.08 (s, NMR (300 MHz, CDCl3): δ = 7.69–7.62 (m, 1 H), 7.22–7.13 (m, 2
1 H), 3.90–3.78 (m, 1 H), 3.32 (d, J = 5.8 Hz, 1 H), 3.17 (dd, J = H), 7.11–7.03 (m, 1 H), 5.62 (d, J = 0.8 Hz, 1 H), 5.04 (d, J =
16.4, 4.5 Hz, 1 H), 2.96–2.80 (m, 2 H), 2.64 (dd, J = 13.9, 8.4 Hz,
0.8 Hz, 1 H), 3.24 (s, 1 H), 3.12 (d, J = 16.6 Hz, 1 H), 2.93 (d, J =
1 H), 1.15 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 140.1 16.6 Hz, 1 H), 2.71–2.58 (m, 2 H), 1.46 (s, 3 H), 1.00 (s, 9 H) ppm.
(C), 134.1 (C), 134.0 (C), 129.7 (CH), 128.3 (CH), 126.6 (CH), 13C NMR (101 MHz, CDCl3): δ = 140.5 (C), 134.3 (C), 133.6 (C),
124.1 (CH), 111.3 (CH2), 55.8 (C), 51.2 (CH), 41.0 (CH2), 37.9
(CH ), 22.7 (CH ) ppm. IR (ATR): ν = 3201, 1629, 1052, 734 cm–1.
LRMS (EI): m/z (%) = 144 (20), 143 (100), 142 (22), 129 (19), 128
(34), 115 (14). HRMS (EI): calcd. for C11H11NOS [M – C4H10]+
205.0561; found 205.0570.
129.7 (CH), 128.2 (CH), 126.5 (CH), 123.8 (CH), 110.9 (CH2), 55.8
(C), 54.5 (C), 47.1 (CH2), 43.4 (CH2), 28.4 (CH3), 22.5 (CH3) ppm.
˜
2
3
IR (ATR): ν = 3213, 1628, 1455, 1051 cm–1. LRMS (EI): m/z (%)
˜
= 158 (24), 157 (100), 156 (11), 143 (21), 142 (21), 141 (10), 128
(13), 115 (11). HRMS (EI): calcd. for C12H15NOS [M – C4H8]+
221.0874; found 221.0898.
(SS,7S)-N-(tert-Butylsulfinyl)-5-methylene-6,7,8,9-tetrahydro-5H-
benzo[7]annulen-7-amine (5h): The representative procedure was fol-
lowed by using sulfinamide 4h (116 mg, 0.32 mmol), Pd(OAc)2
(3.6 mg, 0.016 mmol), PPh3 (16.8 mg, 0.064 mmol), and TBAA
(145 mg, 0.48 mmol). Purification by column chromatography
(hexane/acetone, 5:1) yielded 5h (62 mg, 70%) as a white solid; m.p.
78–84 °C. Rf = 0.33 (hexane/AcOEt, 1:1). [α]2D0 = +54 (c = 0.71,
CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 7.25–7.13 (m, 3 H),
(SS,7R)-N-(tert-Butylsulfinyl)-7-methyl-5-methylene-6,7,8,9-tetra-
hydro-5H-benzo[7]annulen-7-amine (5l): The representative pro-
cedure was followed by using sulfinamide 4e (186 mg, 0.5 mmol),
Pd(OAc)2 (5.6 mg, 0.025 mmol), PPh3 (26 mg, 0.1 mmol), and
TBAA (272 mg, 0.9 mmol). Purification by column chromatog-
raphy (hexane/acetone, 5:1) yielded 5e (99 mg, 68%) as a yellow
oil; Rf = 0.30 (hexane/AcOEt, 1:1). [α]2D0 = +19 (c = 0.98, CH2Cl2).
7.12–7.06 (m, 1 H), 5.25–5.22 (m, 1 H), 5.18 (d, J = 2.0 Hz, 1 H), 1H NMR (400 MHz, CDCl3): δ = 7.28–7.23 (m, 1 H), 7.18–7.14
3.79–3.64 (m, 1 H), 3.51 (s, 1 H), 2.95–2.74 (m, 2 H), 2.73–2.48 (m, (m, 2 H), 7.11–7.06 (m, 1 H), 5.27 (s, 1 H), 5.23 (s, 1 H), 3.64 (s, 1
2 H), 2.16–1.98 (m, 1 H), 1.94–1.65 (m, 1 H), 1.23 (s, 9 H) ppm. H), 2.87 (dd, J = 15.4, 10.4 Hz, 1 H), 2.69 (dd, J = 15.4, 10.4 Hz,
13C NMR (75 MHz, CDCl3): δ = 146.7 (C), 143.2 (C), 139.4 (C),
1 H), 2.67 (d, J = 13.0 Hz, 1 H), 2.50 (d, J = 12.9 Hz, 1 H), 1.92
(dd, J = 13.5, 9.5 Hz, 1 H), 1.81 (dd, J = 13.5, 9.5 Hz, 1 H), 1.48
129.2 (CH), 128.3 (CH), 127.5 (CH), 126.5 (CH), 117.5 (CH2), 55.8
(CH), 55.8 (C), 44.1 (CH2), 34.3 (CH2), 31.0 (CH2), 22.7 (s, 3 H), 1.22 (s, 9 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 146.1
(CH ) ppm. IR (ATR): ν = 3222, 1716, 1241, 1027, 751 cm–1
.
(C), 142.7 (C), 139.5 (C), 129.4 (CH), 128.2 (CH), 127.4 (CH),
126.4 (CH), 118.0 (CH2), 57.2 (C), 55.9 (C), 49.6 (CH2), 40.2
˜
3
LRMS (EI): m/z (%) = 221 (13), 158 (21), 157 (100), 143 (12), 142
(13), 141 (11), 131 (35), 130 (14), 129 (53), 128 (24), 116 (13), 115
(CH ), 30.4 (CH ), 22.8 (CH ) ppm. IR (ATR): ν = 3216, 1626,
˜
2 2 3
(26), 91 (25). HRMS (EI): calcd. for C12H15NOS [M – C4H8]+ 1050, 913 cm–1. LRMS (EI): m/z (%) = 235 (4), 172 (34), 171 (100),
221.0874; found 221.0884.
143 (27), 141 (11), 131 (44), 130 (16), 129 (40), 128 (27), 116 (11),
115 (25), 91 (23). HRMS (EI): calcd. for C13H15NOS [M –
C4H10]+ 233.0874; found 233.0880.
(SS,1R)-N-(tert-Butylsulfinyl)-1-methyl-3-methylene-2,3-dihydro-
1H-inden-1-amine (5j): The representative procedure was followed
by using sulfinamide 4j (30 mg, 0.087 mmol, diastereomeric mix-
ture, 3:1) Pd(OAc)2 (0.974 mg, 0.0043 mmol), PPh3 (4.6 mg,
0.0174 mmol), and TBAA (42 mg, 0.14 mmol). The 1H NMR spec-
troscopic data of the crude product showed a mixture of four dif-
(SS,1R)-N-(tert-Butylsulfinyl)-2,2-dimethyl-3-methylene-2,2-di-
hydro-1H-inden-1-amine (5n): The representative procedure was fol-
lowed by using sulfinamide 4n (40 mg, 0.11 mmol), Pd(OAc)2
(1.23 mg, 0.0055 mmol), PPh3 (5.8 mg, 0.0022 mmol), and TBAA
2470
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2461–2471

Chiral Aminated α-Methylenebenzocycloalkenes
(50 mg, 0.165 mmol). Purification by column chromatography
(hexane/AcOEt, 5:1) yielded 5n (25 mg, 83%) as a yellow oil; Rf =
0.53 (hexane/AcOEt, 1:1). [α]2D0 = +17 (c = 0.82, CH2Cl2). 1H NMR
genio (grant numbers 2010-CSD-2007-00006 and CTQ2011-
24165), the Generalitat Valenciana (grant number PROMETEO/
2009/039), the Fondos Europeos para el Desarrollo Regional
(300 MHz, CDCl3): δ = 7.52–7.46 (m, 1 H), 7.36–7.26 (m, 3 H), (FEDER), and the University of Alicante for the financial support.
5.49 (s, 1 H), 5.02 (s, 1 H), 4.51 (d, J = 11.1 Hz, 1 H), 3.66 (d, J =
11.0 Hz, 1 H), 1.48 (s, 3 H), 1.33 (s, 9 H), 1.09 (s, 3 H) ppm. 13C
[1] a) J. A. Ellman, T. D. Owens, T. P. Tang, Acc. Chem. Res. 2002,
NMR (75 MHz, CDCl3): δ = 156.6 (C), 143.5 (C), 139.0 (C), 128.9
35, 984–995; b) J. A. Ellman, Pure Appl. Chem. 2003, 75, 39–
(CH), 128.6 (CH), 124.8 (CH), 121.2 (CH), 102.9 (CH2), 70.7 (CH),
46; c) P. Zhou, B.-C. Chen, F. A. Davis, Tetrahedron 2004, 60,
56.7 (C), 47.8 (C), 25.1 (CH3), 25.0 (CH3), 23.1 (CH3) ppm. IR
8003–8030; d) F. A. Davis, J. Org. Chem. 2006, 71, 8993–9003;
(ATR): ν = 3238, 1713, 1639, 1603, 1464, 1059 cm–1. LRMS (EI):
˜
e) F. A. Davis, in: Asymmetric Synthesis, 2nd ed. (Eds.: M.
Christmann, S. Braese), Wiley-VCH, Weinheim, Germany,
2008, pp. 17–22; f) G.-Q. Lin, M.-H. Xu, Y.-W. Zhong, X.-W.
Sun, Acc. Chem. Res. 2008, 41, 831–840; g) F. Ferreira, C.
Botuha, F. Chemla, A. Pérez-Luna, Chem. Soc. Rev. 2009, 38,
1162–1186; h) M. Robak, M. A. Herbage, J. A. Ellman, Chem.
Rev. 2010, 110, 3600–3740.
m/z (%) = 219 (37), 173 (20), 172 (11), 171 (24), 170 (36), 160 (43),
159 (17), 158 (84), 157 (31), 156 (100), 155 (23), 154 (10), 144 (16),
143 (60), 142 (28), 141 (59), 130 (25), 129 (33), 128 (54), 127 (17),
116 (14), 115 (40). HRMS (EI): calcd. for C12H13NOS [M –
C4H10]+ 219.0718; found 219.0718.
Compound 5o: The representative procedure was followed by using
sulfinamide 4o (37 mg, 0.1 mmol), Pd(OAc)2 (1.12 mg,
0.005 mmol), PPh3 (5.2 mg, 0.02 mmol), and TBAA (45 mg,
0.15 mmol). The 1H NMR spectroscopic data of the crude material
showed a very complex mixture of isomers that could not be puri-
fied. Conversion of the starting material was completed. Column
chromatography (hexane/acetone, 4:1) was applied to the crude
product to obtain 5o (22 mg, 75%) as a brown oil; Rf = 0.50 (hex-
ane/AcOEt, 1:1). The 1H and 13C NMR spectroscopic data are
[2] Chiral Amine Synthesis Methods, Developments and Applica-
tions (Ed.: T. C. Nugent), Wiley-VCH, Weinheim, Germany,
2010.
[3] a) F. Foubelo, M. Yus, Tetrahedron: Asymmetry 2004, 15,
3823–3825; b) J. C. González-Gómez, F. Foubelo, M. Yus, Syn-
lett 2008, 2777–2780; c) M. Medjahdi, J. C. González-Gómez,
F. Foubelo, M. Yus, Heterocycles 2008, 76, 569–581; d) M.
Medjahdi, J. C. González-Gómez, F. Foubelo, M. Yus, J. Org.
Chem. 2009, 74, 7859–7865; e) H. K. Dema, F. Foubelo, M.
Yus, Heterocycles 2010, 80, 125–131; f) J. C. González-Gómez,
M. Medjahdi, F. Foubelo, M. Yus, J. Org. Chem. 2010, 75,
6308–6311; g) H. K. Dema, F. Foubelo, M. Yus, Heterocycles
2011, 82, 1411–1421; h) M. Medjahdi, J. C. González-Gómez,
F. Foubelo, M. Yus, Eur. J. Org. Chem. 2011, 2230–2234; i)
H. K. Dema, F. Foubelo, M. Yus, Jordan J. Chem. 2011, 6,
247–255; j) J. C. González-Gómez, F. Foubelo, M. Yus, Org.
Synth. 2012, 89, 88–97; k) I. Bosque, J. C. González-Gómez, F.
Foubelo, M. Yus, J. Org. Chem. 2012, 77, 780–784, and for a
correction, see: I. Bosque, J. C. González-Gómez, F. Foubelo,
M. Yus, J. Org. Chem. 2012, 77, 4190; l) I. Bosque, J. C.
González-Gómez, A. Guijarro, F. Foubelo, M. Yus, J. Org.
Chem. 2012, 77, 10340–10346.
included in the Supporting Information. IR (ATR): ν = 3226, 2922,
˜
1663, 1457, 1062, 748 cm–1. LRMS (EI): m/z (%) = 233 (13), 184
(9), 170 (30), 169 (100), 168 (15), 167 (14), 156 (11), 142 (25), 141
(43), 130 (10), 129 (15), 128 (18), 115 (16). HRMS (EI): calcd. for
C13H13NOS [M – C4H10]+ 231.0718; found 231.0721.
Desulfinylation of Compound 5a. Synthesis of (R)-3-Methylene-2,3-
dihydro-1H-inden-1-amine (6a): To
a solution of 5a (70 mg,
0.28 mmol) in dry THF (1 mL) at 0 °C was added HCl (6 m solu-
tion, 0.33 mL). The mixture was stirred at room temperature for
1 h. Then, it was cooled to 0 °C, and NaOH (2 m solution, 5 mL)
was added. The mixture was diluted with AcOEt (10 mL), and the
organic phase was separated. The aqueous phase was extracted
with AcOEt (2ϫ15 mL). Then, the organic phases were collected,
washed with NaOH (2 m solution, 10 mL) and H2O (10 mL), dried
with anhydrous MgSO4, and evaporated (15 Torr) to yield free
amine 6a (38 mg, 93%) as a yellow oil; Rf = 0.26 (CH2Cl2/MeOH,
9:1). [α]2D0 = +10.4 (c = 0.99, CH2Cl2). 1H NMR (400 MHz,
CDCl3): δ = 7.52–7.46 (m, 1 H), 7.41–7.36 (m, 1 H), 7.32–7.24 (m,
2 H), 5.47 (t, J = 2.4 Hz, 1 H), 5.06 (t, J = 2.0 Hz, 1 H), 4.40 (dd,
J = 7.6, 5.2 Hz, 1 H), 3.18 (ddt, J = 16.4, 7.7, 1.9 Hz, 1 H), 2.49–
2.40 (m, 1 H), 2.04 (s, 2 H) ppm. 13C NMR (101 MHz, CDCl3): δ
= 149.5 (C), 147.3 (C), 140.1 (C), 128.9 (CH), 127.9 (CH), 124.4
(CH), 120.7 (CH), 103.7 (CH2), 54.6 (CH), 43.6 (CH2) ppm. IR
[4] J. A. Sirvent, F. Foubelo, M. Yus, Chem. Commun. 2012, 48,
2543–2545.
[5] a) For a review of an enantioselective allylation of carbonyl
compounds and imines, see: M. Yus, J. C. González-Gómez, F.
Foubelo, Chem. Rev. 2011, 111, 7774–7854; b) for a review on
organoindium reagents, see: Z.-L. Shen, S.-Y. Wang, Y.-K.
Chok, Y.-H. Xu, T.-P. Loh, Chem. Rev. 2013, 113, 271–401.
[6] a) For a general procedure, see: D. A. Cogan, J. A. Ellman, J.
Am. Chem. Soc. 1999, 121, 268–269; b) for a very recent report
of a related microwave-assisted solvent-free methodology, see:
J. F. Collados, E. Toledano, D. Guijarro, M. Yus, J. Org. Chem.
2012, 77, 5744–5750.
[7] a) I. P. Beletskaya, A. V. Cheprakov, Chem. Rev. 2000, 100,
3009–3066; b) F. Alonso, I. P. Beletskaya, M. Yus, Tetrahedron
2005, 61, 11771–11835.
(ATR): ν = 3351, 3281, 1642, 867 cm–1. LRMS (EI): m/z (%) = 145
˜
(42), 144 (100), 143 (13), 130 (25), 129 (10), 128 (19), 127 (14), 115
(12). HRMS (EI): calcd. for C10H11N 145.0891; found 145.0878.
[8] R. Pedrosa, C. Andrés, M. J. Iglesia, J. Org. Chem. 2001, 66,
243–250.
[9] T. Jeffery, Tetrahedron Lett. 1991, 32, 2121–2124.
[10] M. P. Cooke, R. K. Widener, J. Org. Chem. 1987, 52, 1381–
1396.
[11] L. Cheng, L. Liu, Y. Sui, D. Dong Wang, Y.-J. Chen, Tetrahe-
dron: Asymmetry 2007, 18, 1833–1843.
Supporting Information (see footnote on the first page of this arti-
cle): Spectroscopic data for imines 3a, 3g, 3h, and 3j and copies of
1
the H and 13C NMR spectra of imines 3, homoallylamine deriva-
tives 4, and compounds 5 and 6a.
[12] G. S. Lemen, J. P. Wolfe, Org. Lett. 2011, 13, 3218–3221.
[13] Y.-B. Zhao, B. Mariampillai, D. A. Candito, B. Laleu, M. Li,
M. Lautens, Angew. Chem. 2009, 121, 1881; Angew. Chem. Int.
Ed. 2009, 48, 1849–1852.
Acknowledgments
The authors thank the Spanish Ministerio de Ciencia e Innovación
(MICINN) (grant number CTQ2007-65218), the Consolider In-
Received: December 19, 2012
Published Online: March 7, 2013
Eur. J. Org. Chem. 2013, 2461–2471
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2471