Syntheses of imidazo-, oxa-, and thiazepine ring systems via ring-opening of aziridines/Cu-catalyzed C-N/C-C bond formation

Article abstract of DOI:10.1021/jo500888j

A simple and unpredicted synthetic pathway toward racemic and scalemic tetrahydrodibenzoimidazoazepines has been invented serendipitously proceeding through an S_N2-type ring-opening of N-activated aziridines with 2-bromobenzylamine followed by a hitherto unprecedented cascade cyclization reaction sequence comprising a Cu-catalyzed cross dehydrogenation C-N coupling and an Ullmann C-C bond formation reaction. The tetrahydrobenzoxazepine and the tetrahydrobenzothiazepine derivatives have also been synthesized via the ring-opening of aziridines with 2-bromobenzyl alcohols and -mercaptan, respectively, followed by Cu-catalyzed N-arylation reaction.

Full text of DOI:10.1021/jo500888j

Article
pubs.acs.org/joc
Syntheses of Imidazo‑, Oxa‑, and Thiazepine Ring Systems via Ring-
Opening of Aziridines/Cu-Catalyzed C−N/C−C Bond Formation
Manas K. Ghorai,* Ashis Kumar Sahoo, and Aditya Bhattacharyya
Department of Chemistry, Indian Institute of Technology, Kanpur, Uttar Pradesh 208016, India
S
* Supporting Information
ABSTRACT: A simple and unpredicted synthetic pathway toward racemic and scalemic tetrahydrodibenzoimidazoazepines has
been invented serendipitously proceeding through an SN2-type ring-opening of N-activated aziridines with 2-bromobenzylamine
followed by a hitherto unprecedented cascade cyclization reaction sequence comprising a Cu-catalyzed cross dehydrogenation
C−N coupling and an Ullmann C−C bond formation reaction. The tetrahydrobenzoxazepine and the tetrahydrobenzothiazepine
derivatives have also been synthesized via the ring-opening of aziridines with 2-bromobenzyl alcohols and -mercaptan,
respectively, followed by Cu-catalyzed N-arylation reaction.
nonracemic products in excellent enantiomeric excess.9 In
INTRODUCTION
■
continuation of our research activities in the field of the ring-
The medium-sized ring compounds containing oxygen, sulfur,
opening followed by the metal-catalyzed C−N bond
or nitrogen atoms are important synthetic targets, as these are
formation for the synthesis of aza-heterocycles,9c,e,f we
frequently found in various biologically active natural products
anticipated that the tetrahydrobenzoxazepines, -thiazepines,
and synthetic intermediates.1 For example, the seven-
and tetrahydrobenzodiazepines could be easily synthesized via
membered benzo-fused heterocyclic moieties viz. the tetrahy-
the ring-opening of N-activated aziridines with 2-bromobenzyl
drobenzoxazepine, the tetrahydrobenzothiazepine, and the
alcohol, 2-bromobenzyl mercaptan, and 2-bromobenzylamine,
tetrahydrobenzodiazepine rings are often present in pharma-
respectively, followed by the metal-catalyzed intramolecular
ceutical agents as the core structural motifs.2 In particular 1, a
C−N bond formation reactions.
series of synthesized compounds, have been found to possess
antiproliferative activity against the MCF-7 human breast
cancer cells (Figure 1).2d Compound 2 containing the 5,5-
dimethylbenzoxazepinone as the core is active as nonsteroidal
progesterone receptor antagonists.2e CGP-37157 (3), a
trifunctional neuroprotective compound, is the most potent
inhibitor of mitochondrial sodium−calcium exchanger
(mNCE).2f−h The imidazole substituted tetrahydrobenzodia-
zepine BMS3 (4), a farnesyl transferase inhibitor, acts as an
anticancer agent.3 In spite of having potent biological
activities, the synthetic approaches toward the benzo-fused
seven-membered rings are scarce in the literature, and they
mostly rely on the sigmatropic rearrangement,4a intra-
molecular α-arylation,4b and Pd−Cu catalysis.4c,d A few
reports are available in the literature for the construction of
the tetrahydrobenzoxazepine, tetrahydrobenzothiazepine, and
tetrahydrobenzodiazepine moieties.2c,i,3,5
■
RESULTS AND DISCUSSION
While developing a general strategy for the synthesis of the
tetrahydrobenzoxazepines and the tetrahydrobenzothiazepines
(Scheme 1, X = O, S), we serendipitously invented an
unexpected, unprecedented and exciting synthetic route
toward the tetrahydrodibenzoimidazoazepines (Scheme 1, X
= NH). Herein, we report our results as an article.
To test the viability of our approach, at the onset of our
experimental venture we carried out the ring-opening of the
2-phenyl-N-tosylaziridine 5a with 2-bromobenzyl alcohol 6a in
the presence of 30 mol % Cu(OTf)2 in CH2Cl2 following our
reported method (Scheme 2) to obtain the corresponding
ring-opened product 7a.9i
Next, we opted for the metal-catalyzed cyclization of 7a via
intramolecular C−N bond formation with a desire to obtain
the corresponding tetrahydrobenzoxazepine product 8a. For
this purpose different reaction conditions were screened, and
the results are shown in Table 1. At first, we used 10 mol %
The activated aziridines6,7 provide prevailing synthetic
pathways toward aza-heterocyclic systems via the ring-opening
cyclization protocol.8 Over the years we have been exploring
the Lewis acid (LA)-assisted SN2-type ring-opening of the
racemic and enantiopure N-activated aziridines by a number
of nucleophiles to generate the corresponding racemic and
Received: April 21, 2014
© XXXX American Chemical Society
A
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Figure 1. Selected biologically active compounds.
arylamination. When we performed the reaction with 10 mol
% CuI, L-proline as the ligand (20 mol %), and K2CO3 as the
base in DMF, gratifyingly we obtained our desired product in
moderate yield. Then we explored other bases such as
Cs2CO3, K3PO4, and NaH where NaH was found to be most
effective one (entry 6). Changing the solvent to dioxane,
toluene or DMSO did not improve the result (entries 7−9).
Various other bidentate ligands such as ethylenediamine,
glycine, and 1,10-phenanthroline were screened (entries 10−
12) and L-proline was found to be the best ligand affording 8a
in 85% yield at 90 °C in 12 h. So, the best result was
obtained using CuI as the catalyst, L-proline as the ligand and
NaH as the base in DMF as the solvent (entry 6).10 The
structure of 8a was unambiguously confirmed by spectral data
as well as X-ray crystallographic analysis.11
Next, to generalize this approach the ring-opening of other
aziridines 5a−e with various substituted 2-bromobenzyl
alcohols 6a,b were studied (Scheme 3), and the results are
shown in Table 2. Then, under the optimized reaction
condition Cu-catalyzed intramolecular arylamination of 7a−g
afforded the corresponding tetrahydrobenzoxazepines 8a−g in
good yields (Table 2).
Similarly, when the ring-opening of the aziridines 5a,b were
carried out with 2-bromobenzyl mercaptan 6c (Scheme 4)
followed by the Cu-catalyzed intramolecular arylamination of
the corresponding ring-opened products 7h,i, the correspond-
ing tetrahydrobenzothiazepines 8h,i were obtained in good
yields (Table 3).
After our successful attempts for the synthesis of
tetrahydrobenzoxazepines, and tetrahydrobenzothiaxazepines
in high yields we turned our attention to another important
class of benzofused ring systems, tetrahydrobenzodiazepines
(X = NH, Scheme 1).3 For this purpose when 5a was reacted
with of 2-bromobenzylamine, the corresponding ring-opening
product 7j did not form at all under the aforementioned
reaction conditions. After the initial hiccup we rigorously
screened the literature and succeeded to obtain the desired
product 7j in very high yield when the reaction was
performed in the presence of 30 mol % LiClO4 as the
Lewis acid in CH3CN (Scheme 5).12
Scheme 1. Retrosynthetic Analysis for the Synthesis of
Benzo-Fused Seven-Membered Aza-Heterocycles
Scheme 2. Regioselective Ring-Opening of 5a with 2-
Bromobenzyl Alcohol 6a
Table 1. Optimization of Reaction Conditions for the
a
Formation of 8a
metal source (10 mol %), ligand (20 mol %),
base (2.5 equiv), solvent, temp (°C), time (h)
8a yield
[%]
entry
1
Pd(OAc)2, PPh3, K2CO3, toluene, 120, 15
Pd(OAc)2, BINAP, K2CO3, toluene, 120, 15
CuI, L-proline, K2CO3, DMF, 90, 24
CuI, L-proline, Cs2CO3, DMF, 90, 26
CuI, L-proline, K3PO4, DMF, 90, 20
CuI, L-proline, NaH, DMF, 90, 12
CuI, L-proline, NaH, DMSO, 90, 24
CuI, L-proline, NaH, dioxane, 90, 24
CuI, L-proline, NaH, toluene, 90, 12
CuI, glycine, NaH, DMF, 90, 26
nr
nr
78
68
73
85
nr
44
nr
37
nr
nr
2
3
4
5
6
7
8
9
10
11
12
CuI, 1,10-phen, NaH, DMF, 90, 24
CuI, EDA, NaH, DMF, 90, 26
a
EDA = ethylenediamine; 1,10-phen = 1,10-phenanthroline.
of palladium catalyst and 20 mol % of the ligand (entries 1, 2)
as per our reported protocol, but unfortunately no reaction
was observed. After suffering a setback with Pd-catalyzed
intramolecular C−N bond formation we turned our attention
toward copper-catalysis, a cheaper alternative of Pd catalyzed
Next, with a lot of enthusiasm and having the ring-opened
product 7j in hand, we set out for the metal-catalyzed
Scheme 3. Synthesis of Tetrahydrobenzoxazepines
B
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Table 2. Synthesis of Tetrahydrobenzoxazepines
Scheme 4. Synthesis of Tetrahydrobenzothiazepines
cyclization of 7j using the newly established copper-catalyzed
C−N bond formation reaction. When 7j was treated with 10
mol % CuI, 20 mol % L-proline and 2.5 equiv of NaH in
DMF at 90 °C, to our great surprise we observed the
formation of a completely unexpected and new class of highly
substituted and functionalized aza-heterocyclic core tetrahy-
Scheme 5. LiClO4-Catalyzed Regioselective Ring-Opening
of 5a with 2-Bromobenzylamine 6d
C
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Table 3. Synthesis of Tetrahydrobenzothiazepines
Scheme 6. Synthesis of Tetrahydrodibenzoimidazoazepine 9a
Table 4. LiClO4-Catalyzed Regioselective Ring-Opening of 5 with 2-Bromobenzylamine 6d
D
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Scheme 7. Synthesis of Enantiopure Tetrahydrodibenzoimidazoazepine (S)-9a
Scheme 8. Mechanistic Pathway for the Formation of Tetrahydrobenzoxazepines and Tetrahydrobenzothiazepines
drodibenzoimidazoazepine 9a containing four fused rings
altogether, instead of the expected tetrahydrobenzodiazepine
(Scheme 6). The compound 9a, obtained as the only product
from the reaction mixture, was fully characterized by
spectroscopic data, and its structure was further confirmed
by X-ray crystallographic analysis.11 To the best of our
knowledge compounds such as 7-phenyl-5-tosyl-5,6,7,9-
tetrahydro-4bH-dibenzo[c,e]imidazo[1,2-a]azepine (9a) are
unknown until date. The dibenzoimidazoazepines that
resemble the core structure of 9a specifically bind to the
histamine-1 and histamine-2 receptors and can be used as
antithrombotics, antiallergics, sedative, and antiulcer agents.13
Interestingly epinastine having the similar dihydrodibenzimi-
dazoazepine core is a well-known second-generation antihist-
amine and mast cell stabilizer and is used in the treatment of
allergic conjunctivitis.14
Scheme 9. Plausible Reaction Mechanism for the
Formation of 9a
The newly developed synthetic strategy was generalized
with other 2-aryl-N-sulfonylaziridines 5c−f, and to our great
pleasure, we obtained the corresponding unprecedented
products 9b−e in very high yields in all the cases. The
results are shown in Table 4.
Further synthetic significance of our protocol was
demonstrated by the synthesis of chiral tetrahydrodibenzimi-
dazoazepine from (R)-5a. When (S)-7j, generated from the
enantiopure aziridine (R)-5a, was treated with the newly
developed catalyst system (10 mol % CuI, 20 mol % L-proline
and 2.5 equiv of NaH in DMF at 90 °C) to our great delight,
the corresponding tetrahydrodibenzimidazoazepine (S)-9a was
obtained in high yield with excellent stereoselectivity (de, ee
>99%, Scheme 7).
MECHANISM
■
Synthesis of Tetrahydrobenzoxazepine and Tetrahy-
drobenzothiazepines. We believe that the formation of the
tetrahydrobenzoxazepine and the tetrahydrobenzothiazepine
derivatives proceed through the well-established Cu(I)-
catalyzed C−N coupling reaction10o as depicted in Scheme
8. SN2-type ring-opening of activated aziridines by 2-
bromobenzyl alcohol and -thiol generate the corresponding
E
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Scheme 10. Alternative Plausible Mechanistic Pathway for the Formation of Tetrahydrodibenzoimidazoazepines
Visualization was accomplished with UV lamp or I2 stain. Silica gel
230−400 mesh size was used for flash column chromatography using
the combination of ethyl acetate and petroleum ether as eluent.
Unless noted, all reactions were carried out in oven-dried glassware
under an atmosphere of nitrogen/argon using anhydrous solvents.
Where appropriate, all reagents were purified prior to use following
the guidelines of Perrin and Armerego.17 Cu(OTf)2 used in all
reactions was prepared using literature procedure.18 All aziridines
were prepared by following earlier reports.19 All commercial reagents
were used as received. Proton nuclear magnetic resonance (1H
NMR) spectra were recorded at 400 MHz/500 MHz. Chemical
shifts were recorded in parts per million (ppm, δ) relative to
ring-opened products, which subsequently undergo Cu(I)-
catalyzed intramolecular C−N coupling to produce the
corresponding tetrahydrobenzoxazepines and tetrahydroben-
zothiazepines, respectively.
Synthesis of Tetrahydrodibenzoimidazoazepines. A
plausible reaction mechanism for the formation of the
unprecedented products 9 is described in Scheme 9. First
the chiral aziridine (R)-5a undergoes SN2-type ring-opening
reaction with 2-bromobenzylamine in the presence of Lewis
acid to furnish the ring-opened product (S)-7j. Then 7j
undergoes SET reaction in the presence of Cu catalyst to
afford the corresponding iminium ion B via the formation of a
radical cation A through cross dehydrogenation coupling
(CDC) mechanism.15 Then another molecule of the ring-
opened product attacks the intermediate B as a nucleophile to
generate the species C. Then two NH-units of C facilitate
chelation with copper and the diamine-copper complex D is
eliminated on attack of nitrogen on the homobenzylic carbon
of C to afford the dibromo compound E. Now E with two
ortho-bromo groups undergoes intramolecular C−C bond
formation via Cu-catalyzed Ullmann reaction16 to furnish the
tetrahydrodibenzoimidazoazepine (S)-9a.
1
tetramethyl silane (δ 0.00). H NMR splitting patterns are designated
as singlet (s), doublet (d), doublet of doublet (dd), triplet (t),
quartet (q), multiplet (m), etc. Carbon nuclear magnetic resonance
(13C NMR) spectra were recorded at 100 MHz/125 MHz. Mass
spectra (MS) were obtained using ESI mass spectrometer (TOF). IR
spectra were recorded in KBr for solids. Melting points were
determined using a hot stage apparatus and are uncorrected. Optical
rotations were measured using a 6.0 mL cell with a 1.0 dm path
length and are reported as [α]25 (c in g per 100 mL of solvent) at
D
25 °C. Enantiomeric excess were determined by HPLC using
chiralpak AS-H and Cellulose 2 analytical column (detection at 254
nm).
Method A: General Procedure for the Ring-Opening of
Aziridines with 2-Bromobenzyl Alcohol and 2-Bromobenzyl
Mercaptan. A solution of the aziridine (200 mg, 0.731 mmol (for
5a), 1.0 equiv) in 1.0 mL of CH2Cl2 was added to a suspension of
anhydrous Cu(OTf)2 (264.2 mg, 0.731 mmol, 1.0 equiv) and 2-
bromobenzyl alcohol (150.3 mg, 0.804 mmol, 1.1 equiv)/2-
bromobenzyl mercaptan (0.10 mL, 0.804 mmol, 1.1 equiv) in 3.0
mL of CH2Cl2 at an appropriate temperature under an argon
atmosphere. The mixture was stirred for an appropriate time (Table
2), and then the reaction was quenched with saturated aqueous
NaHCO3 solution. The aqueous layer was extracted with CH2Cl2 (3
× 5.0 mL) and dried over anhydrous Na2SO4. The crude product
was purified by flash column chromatography on silica gel (230−400
mesh) using 15% ethyl acetate in petroleum ether to provide the
pure product.
Method B: General Procedure for Cu-Catalyzed Cyclization.
A corresponding N-(2-(2-bromobenzyloxy)-2-phenylethyl)-4-methyl-
benzenesulfonamide (100 mg, 0.217 mmol (for 7a), 1.0 equiv), N-
(2-(2-bromobenzylthio)-2-phenylethyl)-4-methylbenzenesulfonamide
(100 mg, 0.209 mmol (for 7h), 1.0 equiv), N-(2-(2-bromobenzyla-
mino)-2-phenylethyl)-4-methylbenzenesulfonamide (250 mg, 0.544
mmol (for 7j), 1.0 equiv) in dry DMF (2.0 mL) was added to a
suspension of CuI (4.1 mg, 10 mol %), L-Proline (4.9 mg, 20 mol %)
and NaH (13.0 mg, 2.5 equiv) in 6.0 mL of dry DMF under argon
at room temperature. The reaction mixture was heated at 90 °C for
the appropriate time, and the reaction was monitored by TLC. It was
cooled to room temperature, poured into water, and extracted with
An alternative mechanistic pathway could also be possible
involving an intermolecular C−C bond formation via Cu(I)-
catalyzed Ullmann C−C coupling reaction as the first step.
Then subsequent cross dehydrogenation coupling involving
two C−N bond formation reactions gives rise to the final
tetrahydrodibenzoimidazoazepine derivatives as shown in
Scheme 10.
CONCLUSION
■
In summary, we have developed an efficient and novel
strategy for the synthesis of the tetrahydrobenzoxazepines, the
tetrahydrobenzothiazepines, and the tetrahydrodibenzoimida-
zoazepines via an SN2-type ring-opening of N-activated
aziridines followed by an intramolecular C−N/C−C bond
formation reaction. We do believe that this protocol will find
considerable applications in organic synthesis for the stereo-
selective construction of seven-membered aza-heterocycles.
Further exploration on the scopes and limits of the synthetic
applications of our methodology for the synthesis of
biologically active compounds are in progress.
EXPERIMENTAL SECTION
General Procedures. Analytical thin layer chromatography
(TLC) was carried out using silica gel 60 F254 precoated plates.
■
F
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ethyl acetate (3 × 10 mL). The combined organic extract was
washed with H2O (3 × 10 mL) and brine (30 mL) and dried over
Na2SO4. The solvent was removed under reduced pressure to give
crude product, which was purified by flash column chromatography
on silica gel (230−400 mesh) using ethyl acetate in petroleum ether
to afford the pure products as white solids.
Method C: General Procedure for the Synthesis of
Tetrahydrodibenzoimidazoazepines. A solution of the aziridine
(200 mg, 0.730 mmol (for 5a), 1.0 equiv) in 1.0 mL of CH3CN was
added to a suspension of anhydrous LiClO4 (23.3 mg, 0.219 mmol,
0.3 equiv) and 2-bromobenzylamine (149.4 mg, 0.803 mmol, 1.1
equiv) in 3.0 mL of CH3CN at an appropriate temperature under an
argon atmosphere. The mixture was stirred for an appropriate time
(Table 3), and then the reaction was quenched with saturated
aqueous NaHCO3 solution. The aqueous layer was extracted with
CH2Cl2 (3 × 5.0 mL) and dried over anhydrous Na2SO4. The crude
product was purified by flash column chromatography on silica gel
(230−400 mesh) using 15% ethyl acetate in petroleum ether to
provide the pure product.
3-(4-Chlorophenyl)-1-tosyl-1,2,3,5-tetrahydrobenzo[e][1,4]-
oxazepine (8b). The general method B described above was
followed when 7b (100 mg, 0.202 mmol) was reacted with CuI (10
mol %), L-proline (20 mol %) and NaH (12.12 mg, 0.505 mmol) at
90 °C for 14 h to afford 8b (68 mg, 0.164 mmol) as a white solid in
81% yield: mp 156−160 °C; Rf 0.48 (20% ethyl acetate in petroleum
ether); IR νmax (KBr, cm−1) 3422, 2937, 2901, 2858, 1596, 1490,
1453, 1422, 1406, 1383, 1346, 1325, 1255, 1197, 1161, 1125, 1108,
1086, 1039, 1015, 951, 923, 880, 843, 816, 802, 770, 751, 729, 708,
1
690, 652, 618, 573, 551, 526, 455; H NMR (500 MHz, CDCl3) δ
2.43 (s, 3H), 3.05−3.10 (m, 1H), 4.38 (t, J = 14.0 Hz, 2H), 4.60 (d,
J = 13.4 Hz, 1H), 4.72 (d, J = 10.0 Hz, 1H), 7.23−7.33 (m, 10H),
7.66 (d, J = 7.9 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 21.7,
57.5, 72.9, 82.3, 127.2, 127.5, 128.2, 128.6, 128.7, 129.1, 129.9, 130.0,
133.8, 137.8, 138.3, 138.5, 139.8, 144.0; HRMS (ESI-TOF) calcd for
C22H21ClNO3S (M + H)+ 414.0931, found 414.0937.
N-(2-(2-Bromobenzyloxy)-2-p-tolylethyl)-4-methylbenzenesulfo-
namide (7c). The general method A described above was followed
when 5c (200 mg, 0.695 mmol) reacted with 2-bromobenzyl alcohol
6a (143.1 mg, 0.765 mmol) at rt for 4 h to afford 7c (270 mg, 0.569
mmol) as a white solid in 82% yield: mp 126−128 °C; Rf 0.41 (20%
ethyl acetate in petroleum ether); IRνmax (KBr, cm−1) 3289, 3051,
3023, 2961,2920, 2868, 1924, 1907, 1805, 1739, 1660, 1597, 1568,
1512, 1490, 1469, 1439, 1423, 1391, 1358, 1325, 1291, 1269, 1247,
1206, 1156, 1120, 1093, 1043, 1018, 942, 846, 813, 793, 751, 728,
712, 662, 645, 592, 568, 551, 538, 483, 465, 453, 433; 1H NMR
(500 MHz, CDCl3) δ 2.34 (s, 3H), 2.40 (s, 3H), 3.02−3.07 (m,
1H), 3.20−3.25 (m, 1H), 4.26 (d, J = 11.9 Hz, 1H) 4.35−4.39 (m,
2H), 4.99−5.01 (m, 1H), 7.12−7.19 (m, 5H), 7.24−7.25 (m, 2H),
7.28−7.32 (m, 2H), 7.55 (d, J = 7.5 Hz, 1H), 7.67 (d, J = 8.2 Hz,
2H); 13C{1H} NMR (125 MHz, CDCl3) δ 21.2, 21.6, 49.5, 70.3,
80.1, 123.5, 126.7, 127.1, 127.5, 129.5, 129.8, 130.0, 132.9, 135.0,
136.9, 137.0, 138.5, 143.4; HRMS (ESI-TOF) calcd for
C23H28BrN2O3S (M + NH4)+ 491.1004, found 491.1007.
N-(2-((2-Bromobenzyl)oxy)-2-phenylethyl)-4-methylbenzenesul-
fonamide (7a). The general method A described above was followed
when 5a (200 mg, 0.730 mmol) reacted with a 2-bromobenzyl
alcohol 6a (150.3 mg, 0.803 mmol) at rt for 3 h to afford 7a (292
mg, 0.634 mmol) as a white solid in 87% yield: mp 118−120 °C; Rf
0.34 (20% ethyl acetate in petroleum ether); IR νmax (KBr, cm−1)
3300, 3056, 2918, 1596, 1567, 1493, 1453, 1404, 1365, 1324, 1279,
1241, 1205, 1185, 1165, 1091, 1075, 1053, 1024, 922, 882, 813, 766,
1
751, 705, 671, 631, 601, 578, 554, 546, 428; H NMR (500 MHz,
CDCl3) δ 2.40 (s, 3H), 3.0−3.09 (m, 1H), 3.23−3.28 (m, 1H), 4.28
(d, J = 11.9 Hz, 1H), 4.38−4.41 (m, 2H), 5.02−5.05 (m, 1H), 7.16−
7.20 (m, 1H), 7.24−7.26 (m, 4H), 7.28−7.7.36 (m, 5H), 7.55 (d, J =
7.9 Hz, 1H), 7.68 (d, J = 8.2 Hz, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 21.6, 49.4, 70.5, 80.3, 123.5, 126.7, 127.1, 127.5, 128.7,
128.8, 129.6, 129.8, 130.1, 132.9, 136.8, 137.0, 138.1, 143.5; HRMS
(ESI-TOF) calcd for C22H22BrNNaO3S (M + Na)+ 482.0401, found
482.0406.
3-Phenyl-1-tosyl-1,2,3,5-tetrahydrobenzo[e][1,4]oxazepine (8a).
The general method B described above was followed when 7a
(100 mg, 0.217 mmol) was reacted with CuI (10 mol %), L-proline
(20 mol %) and NaH (13.2 mg, 0.542 mmol) at 90 °C for 12 h to
afford 8a (70 mg, 0.184 mmol) as a white solid in 85% yield: mp
165−167 °C; Rf 0.52 (20% ethyl acetate in petroleum ether); IR νmax
(KBr, cm−1) 3422, 3060, 2962, 2928, 2872, 1920, 1597, 1488, 1452,
1417, 1378, 1341, 1315, 1249, 1192, 1160, 1150, 1121, 1105, 1089,
1074, 1050, 1034, 1013, 918, 879, 828, 816, 801, 769, 750, 714, 701,
657, 648, 613, 576, 545, 521, 496, 462; 1H NMR (500 MHz,
CDCl3) δ 2.43 (s, 3H), 3.11−3.17 (m, 1H), 4.35 (d, J = 13.4 Hz,
1H), 4.43 (dd, J = 15.0, 1.8 Hz, 1H), 4.61 (d, J = 13.4 Hz, 1H), 4.72
(dd, J = 10.0,1.5 Hz, 1H), 7.26−7.36 (m, 11H), 7.67 (d, J = 8.2 Hz,
2H); 13C{1H} NMR (125 MHz, CDCl3) δ 21.6, 57.6, 72.9, 82.9,
126.1, 127.2, 128.0, 128.1, 128.6, 128.7, 129.0, 129.8, 129.9, 138.4,
138.7, 139.3, 139.9, 143.9; HRMS (ESI-TOF) calcd for
C22H21NNaO3S (M + Na)+ 402.1140, found 402.1146.
3-p-Tolyl-1-tosyl-1,2,3,5-tetrahydrobenzo[e][1,4]oxazepine (8c).
The general method B described above was followed when 7c
(100 mg, 0.210 mmol) was reacted with CuI (3.99 mg, 0.0210
mmol), L-proline (4.83 mg, 0.0420 mmol) and NaH (12.6 mg, 0.525
mmol) at 90 °C for 14 h to afford 8c (70 mg, 0.177 mmol) as a
white solid in 84% yield: mp 166−168 °C; Rf 0.50 (20% ethyl
acetate in petroleum ether); IRνmax (KBr, cm−1) 3428, 3060, 2922,
2861, 1596, 1514, 1490, 1451, 1422, 1383, 1345, 1300, 1254, 1197,
1182, 1161, 1126, 1101, 1089, 1039, 1018, 948, 923, 872, 838, 804,
1
766, 709, 695, 653, 616, 574, 543, 527, 496, 479; H NMR (500
MHz, CDCl3) δ 2.32 (s, 3H), 2.43 (s, 3H), 3.10−3.15 (m, 1H),
4.32−4.42 (m, 2H), 4.59 (d, J = 13.1 Hz, 1H), 4.68 (d, J = 9.5 Hz,
1H), 7.12−7.18 (m, 4H), 7.27−7.32 (m, 5H), 7.36 (d, J = 7.1 Hz,
1H), 7.67 (d, J = 8.3 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ
21.2, 21.6, 57.6, 72.9, 82.8, 126.0, 127.2, 128.0, 128.7, 129.0, 129.2,
129.8, 129.9, 136.4, 137.9, 138.4, 138.7, 139.9, 143.8; HRMS (ESI-
TOF) calcd for C23H24NO3S (M + H)+ 394.1477, found 394.1478.
N-(2-(2-Bromobenzyl)oxy)-2-(4-fluorophenyl)ethyl)-4-methylben-
zenesulfonamide (7d). The general method A described above was
followed when 5d (200 mg, 0.686 mmol) reacted with 2-bromo
benzyl alcohol 6a (141.2 mg, 0.754 mmol) at rt for 5 h to afford 7d
(280 mg, 0.585 mmol) as a white solid in 85% yield: mp 124−126
°C; Rf 0.44 (20% ethyl acetate in petroleum ether); IRνmax (KBr,
cm−1) 3281, 3067, 2918, 2857, 1924, 1603, 1569, 1510, 1456, 1439,
1416, 1328, 1288, 1221, 1190, 1164, 1090, 1067, 1044, 1026, 921,
N-(2-((2-Bromobenzyl)oxy)-2-(4-chlorophenyl)ethyl)-4-methyl-
benzenesulfonamide (7b). The general method A described above
was followed when 5b (200 mg, 0.649 mmol) reacted with a 2-
bromobenzyl alcohol 6a (133.5 mg, 0.713 mmol) at rt for 6 h to
afford 7b (260 mg, 0.527 mmol) as a white solid in 81% yield: mp
126−128 °C; Rf 0.40 (20% ethyl acetate in petroleum ether); IR νmax
(KBr, cm−1) 3288, 2960, 2922, 2871, 1598, 1488, 1440, 1414, 1391,
1355, 1326, 1206, 1156, 1119, 1090, 1054, 1027, 1015, 844, 812,
1
882, 837, 819, 774, 747, 675, 573, 553, 500, 472; H NMR (500
MHz, CDCl3) δ 2.41 (s, 3H), 3.01−3.06 (m, 1H), 3.20−2.25 (m,
1H), 4.28 (d, J = 11.7 Hz, 1H), 4.36−4.41 (m, 2H), 5.00−5.02 (m,
1H), 6.99−7.04 (m, 2H), 7.16−7.31 (m, 7H), 7.55 (d, J = 8.5 Hz,
1H), 7.68 (d, J = 8.3 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ
21.6, 49.4, 70.5, 79.6, 115.7, 115.9, 123.5, 127.1, 127.6, 128.4, 128.5,
129.7, 129.8, 130.1, 133.0, 133.9, 136.6, 137.0, 143.5, 161.8, 163.8;
HRMS (ESI-TOF) calcd for C22H21BrFNNaO3S (M + Na)+
500.0307, found 500.0306.
1
749, 664, 551, 475; H NMR (500 MHz, CDCl3) δ 2.43 (s, 3H),
3.00−3.05 (m, 1H), 3.20−3.25 (m, 1H), 4.28 (d, J = 11.9 Hz, 1H),
4.37−4.41 (m, 1H), 4.99−5.01 (m, 1H), 7.16−7.21 (m, 2H), 7.24−
7.26 (m, 1H), 7.30−7.32 (m, 5H), 7.55 (d, J = 7.9 Hz, 1H), 7.66 (d,
J = 8.2 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 21.6, 49.3,
70.6, 79.7, 123.5, 127.1, 127.6, 128.0, 128.1, 129.1, 129.7, 129.8,
130.1, 132.9, 134.4, 136.5, 136.7, 136.9, 143.6; HRMS (ESI-TOF)
calcd for C22H22BrClNO3S (M + H)+ 494.0192, found 494.0198.
3-(4-Fluorophenyl)-1-tosyl-1,2,3,5-tetrahydrobenzo[e][1,4]-
oxazepine (8d). The general method B described above was
G
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followed when 7d (100 mg, 0.209 mmol) was reacted with CuI (3.98
mg, 0.020 mmol), L-proline (4.81 mg, 0.041 mmol) and NaH (12.54
mg, 0.522 mmol) at 90 °C for 16 h to afford 8d (70 mg, 0.176
mmol) as a white solid in 84% yield: mp 162−165 °C; Rf 0.54 (20%
ethyl acetate in petroleum ether); IRνmax (KBr, cm−1) 3417, 3066,
2955, 2924, 2860, 1600, 1508, 1489, 1453, 1425, 1381, 1347, 1325,
1300, 1254, 1230, 1214, 1199, 1181, 1162, 1125, 1109, 1089, 1038,
1016, 953, 924, 881, 840, 816, 805, 770, 751, 715, 708, 695, 653,
0.062 mmol), L-proline (14.43 mg, 0.125 mmol) and NaH (37.6 mg,
1.56 mmol) at 90 °C for 16 h to afford 8f (210 mg, 0.528 mmol) as
a white solid in 84% yield: mp 165−167 °C; Rf 0.52 (20% ethyl
acetate in petroleum ether); IRνmax (KBr, cm−1) 3036, 2958, 2928,
2872, 1916, 1594, 1490, 1453, 1422, 1342, 1304, 1287, 1260, 1243,
1202, 1160, 1153, 1111, 1098, 1088, 1074, 1052, 1015, 942, 925,
1
902, 839, 779, 706, 697, 660, 643, 626, 547, 537, 487, 471; H NMR
(500 MHz, CDCl3) δ 2.43 (s, 3H), 3.09−3.14 (m, 1H), 4.27 (d, J =
13.4 Hz, 1H), 4.42−4.54 (m, 2H), 4.71 (d, J = 10.3 Hz, 1H), 6.97−
7.01 (m, 2H), 7.25−7.53 (m, 8H), 7.65 (d, J = 8.3 Hz, 2H);
13C{1H} NMR (125 MHz, CDCl3) δ 21.6, 57.4, 72.4, 83.1, 115.4,
115.6, 116. 7, 126.0, 127.2, 128.2, 128.6, 130.0, 130.7, 130.8, 135,7,
138.4, 139.1, 140.8, 144.0, 160.6, 162.9; HRMS (ESI-TOF) calcd for
C22H21FNO3S (M + H)+ 398.1226, found 398.1226.
1
615, 575, 542, 530, 497, 480; H NMR (500 MHz, CDCl3) δ 2.43
(s, 3H), 3.07−3.12 (m, 1H), 4.36−4.42 (m, 2H), 4.60 (d, J = 13.2
Hz, 1H), 4.73 (d, J = 9.2 Hz, 1H), 7.00−7.03 (m, 2H), 7 0.25−7.33
(m, 8H), 7.67 (d, J = 8.3 Hz, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 21.6, 57.6, 72.9, 82.8, 115.4, 115.5, 127.2, 127.8, 128.1,
128.6, 129.1, 129.8, 129.9, 135.2, 138.3, 138.6, 139.8, 143.9, 161.5,
163.5; HRMS (ESI-TOF) calcd for C22H21FNO3S (M + H)+
398.1226, found 398.1223.
N-(2-(2-Bromo-5-fluorobenzyloxy)-2-(4-chlorophenyl)ethyl)-4-
methylbenzenesulfonamide (7g). The general method A described
above was followed when 5b (200 mg, 0.649 mmol) reacted with 2-
bromo 5-fluoro benzyl alcohol 6b (146.5 mg, 0.714 mmol) at rt for
6 h to afford 7g (280 mg, 0.546 mmol) as a white solid in 84% yield:
mp 122−123 °C; Rf 0.43 (20% ethyl acetate in petroleum ether);
IRνmax (KBr, cm−1) 3300, 3096, 2937, 2865, 1582, 1490, 1471, 1453,
1423, 1387, 1318, 1271, 1157, 1123, 1091, 1028, 1013, 960, 916,
868, 818, 807, 703, 665, 619, 591, 553, 541, 476, 456; 1H NMR
(500 MHz, CDCl3) δ 2.41 (s, 3H), 3.05−3.10 (m, 1H), 3.22−3.28
(m, 1H), 4.28 (q, J = 12.6 Hz, 2H), 4.44 (dd, J = 8.9, 3.7 Hz, 1H),
4.93 (dd, J = 3.7, 9.0 Hz, 1H), 6.88−6.92 (m, 1H), 7.07−7.10 (m,
1H), 7.18 (d, J = 8.3 Hz, 2H), 7.26 (t, J = 8.0 Hz, 2H), 7.31 (d, J =
8.3 Hz, 2H), 7.46−7.49 (m, 1H), 7.68 (d, J = 8.3 Hz, 2H); 13C{1H}
NMR (125 MHz, CDCl3) δ 21.6, 49.2, 70.0, 80.1, 116.3, 116.5,
116.6, 127.0, 128.0, 129.1, 129.8, 133.9, 134.0, 134.6, 136.4, 136.9,
138.9, 143.7, 161.1, 163.0; HRMS (ESI-TOF) calcd for
C22H20BrClFNNaO3S (M + Na)+ 533.9918, found 533.9914.
3-(4-Chlorophenyl)-7-fluoro-1-tosyl-1,2,3,5-tetrahydrobenzo[e]-
[1,4]oxazepine (8g). The general method B described above was
followed when 7g (100 mg, 0.195 mmol) was reacted with CuI (3.71
mg, 0.019 mmol), L-proline (3.71 mg, 0.039 mmol) and NaH (11.7
mg, 0.487 mmol) at 90 °C for 16 h to afford 8g (68 mg, 0.157
mmol) as a white solid in 81% yield: mp 164−167 °C; Rf 0.50 (20%
ethyl acetate in petroleum ether); IR νmax (KBr, cm−1) 3445, 3061,
2930, 1597, 1495, 1427, 1408, 1354, 1295, 1261, 1201, 1164, 1118,
1090, 1023, 1014, 998, 944, 909, 865, 844, 829, 816, 803, 769, 733,
N-(2-(2-Bromobenzyloxy)-2-(4-tert-butylphenyl)ethyl)-4-methyl-
benzenesulfonamide (7e). The general method A described above
was followed when 5e (200 mg, 0.607 mmol) reacted with 2-bromo
benzyl alcohol 6a (125.01 mg, 0.668 mmol) at rt for 5 h to afford 7e
(260 mg, 0.503 mmol) as a white solid in 83% yield: mp 128−130
°C; Rf 0.43 (20% ethyl acetate in petroleum ether); IR νmax (KBr,
cm−1) 3279, 3062, 2961, 2923, 2867, 1914, 1598, 1569, 1510, 1455,
1439, 1419, 1395, 1362, 1326, 1287, 1271, 1238, 1207, 1162, 1096,
1
1043, 1024, 922, 886, 832, 812, 747, 661, 572, 550, 511, 430; H
NMR (500 MHz, CDCl3) δ 1.30 (s, 9H), 2.40 (s, 3H), 3.03−3.08
(m, 1H), 3.21−3.26 (m, 1H), 4.27 (d, J = 11.9, 1H), 4.35−4.41 (m,
2H), 5.02 (d, J = 7.6 Hz, 1H), 7.16−7.19 (m, 3H), 7.24−7.26 (m,
2H), 7.28−7.36 (m, 4H), 7.55 (d, J = 7.9 Hz, 1H), 7.68 (d, J = 7.9
Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 21.6, 31.4, 34.7, 49.4,
70.4, 80.0, 123.5, 125.7, 126.4, 127.1, 127.5, 129.5, 129.8, 130.1,
132.9, 135.0, 137.0, 137.1, 143.4, 151.7 ; HRMS (ESI-TOF) calcd for
C26H34BrN2O3S (M + NH4)+ 533.1474, found 533.1479.
3-(4-tert-Butylphenyl)-1-tosyl-1,2,3,5-tetrahydrobenzo[e][1,4]-
oxazepine (8e). The general method B described above was
followed when 7e (100 mg, 0.193 mmol) was reacted with CuI
(3.67 mg, 0.019 mmol), L-proline (4.44 mg, 0.038 mmol) and NaH
(11.58 mg, 0.482 mmol) at 90 °C for 16 h to afford 8e (70 mg,
0.160 mmol) as a white solid in 83% yield: mp 163−165 °C; Rf 0.49
(20% ethyl acetate in petroleum ether); IR νmax (KBr, cm−1) 2959,
2925, 2856, 1732, 1599, 1491, 1455, 1348, 1254, 1195, 1162, 1129,
1100, 1018, 922, 870, 815, 802, 769, 752, 722, 692, 653, 617, 576,
1
718, 680, 641, 574, 566, 551, 540, 529, 458; H NMR (500 MHz,
1
CDCl3) δ 2.44 (s, 3H), 3.02−3.07 (m, 1H), 4.29 (d, J = 13.4 Hz,
1H), 4.40 (d, J = 15.2 Hz, 1H), 4.52 (d, J = 13.4 Hz, 1H), 4.71 (d, J
= 10.3 Hz, 1H), 6.97−6.99 (m, 2H), 7.22−7.33 (m, 7H), 7.64 (d, J
= 8.3 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 21.7, 57.4,
72.4, 82.5, 115.5, 115.7, 116.5, 116.7, 127.2, 127.4, 128.8, 130.0,
130.6, 130.7, 133.9, 135.6, 137.6, 138.3, 140.7, 144.1, 160.6, 162.6;
HRMS (ESI-TOF) calcd for C22H23ClFN2O3S (M + NH4)+
449.1102, found 449.1107.
545; H NMR (500 MHz, CDCl3) δ 1.29 (s, 9H), 2.43 (s, 3H),
3.14−3.19 (m, 1H), 4.35 (d, J = 13.4 Hz, 1H), 4.41−4.45 (m, 1H),
4.60 (d, J = 13.4 Hz, 1H), 4.68−4.70 (m, 1H), 7.21−7.23 (m, 3H),
7.25−7.37 (m, 8H), 7.68 (d, J = 8.2 Hz, 2H); 13C{1H} NMR (125
MHz, CDCl3) δ 21.6, 31.4, 34.6, 57.4, 72.9, 82.8, 125.5, 125.9, 127.2,
128.0, 128.7, 129.0, 129.8, 129.9, 136.3, 138.4, 138.7, 139.9, 143.8,
151.2; HRMS (ESI-TOF) calcd for C26H30NO3S (M + H)+
436.1946, found 436.1942.
N-(2-(2-Bromobenzylthio)-2-phenylethyl)-4-methylbenzenesulfo-
namide (7h). The general method A described above was followed
when 5a (200 mg, 0.730 mmol) reacted with 2-bromobenzyl
mercaptan 6c (0.10 mL, 0.803 mmol) rt for 5 h to afford 7h (290
mg, 0.608 mmol) as a white solid in 83% yield: mp 104−106 °C; Rf
0.45 (20% ethyl acetate in petroleum ether); IR νmax (KBr, cm−1)
3282, 3058, 3029, 2923, 2852, 15908, 1566, 1492, 1468, 1453, 1439,
1426, 1375, 1324, 1291, 1239, 1152, 1092, 1073, 1045, 1024, 906,
N-(2-((2-Bromo-5-fluorobenzyl)oxy)-2-phenylethyl)-4-methylben-
zenesulfonamide (7f). The general method A described above was
followed when 5a (200 mg, 0.730 mmol) reacted with a 2-bromo-5-
fluorobenzyl alcohol 6b (164.8 mg, 0.803 mmol) at rt for 6 h to
afford 7f (290 mg, 0.606 mmol) as a white solid in 83% yield: mp
120−122 °C; Rf 0.42 (20% ethyl acetate in petroleum ether); IR νmax
(KBr, cm−1) 3312, 3031, 2901, 1597, 1581, 1470, 1456, 1404, 1355,
1329, 1287, 1270, 1223, 1185, 1164, 1152, 1117, 1090, 1073, 1027,
1
1
846, 819, 764, 738, 695, 659, 552, 519, 485, 441; H NMR (500
962, 920, 808, 767, 706, 614, 592, 573, 466; H NMR (500 MHz,
MHz, CDCl3) δ 2.42 (s, 3H), 3.29−3.35 (m, 2H), 3.60−3.68 (m,
1H), 3.64 (q, J = 13.2, 1H), 3.79 (t, J = 7.4 Hz, 1H), 4.60 (t, J = 6.0
Hz, 1H), 7.07−7.10 (m, 1H), 7.15−7.32 (m, 9H), 7.51 (d, J = 8.0
Hz, 1H), 7.65 (d, J = 8.3 Hz, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 21.6, 36.0, 47.6, 49.6, 124.5, 127.1, 127.6, 128.0, 128.1,
128.9, 129.0, 129.8, 130.7, 133.2, 136.8, 136.9, 138.7, 143.6; HRMS
(ESI-TOF) calcd for C22H23BrNO2S2 (M + H)+ 476.0354, found
476.0356.
CDCl3) δ 2.41 (s, 3H), 3.08−3.13 (m, 1H), 3.25−3.30 (m, 1H),
4.29 (q, J = 12.5 Hz, 2H) 4.42−4.45 (m, 1H), 4.95−4.98 (m, 1H),
6.89 (td, J = 8.2, 3.0 Hz, 1H), 7.10 (dd, J = 9.3, 3.3 Hz, 1H), 7.23−
7.28 (m, 4H), 7.32−7.37 (m, 3H), 7.47 (q, J = 5.2 Hz, 1H), 7.70 (d,
J = 8.5 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 21.6, 49.4,
69.9, 80.7, 116.2, 116.3, 116.5, 116.6, 126.7, 127.1, 128.8, 128.9,
129.8, 133.8, 133.9, 137.1, 137.8, 139.2; HRMS (ESI-TOF) calcd for
C22H21BrFNNaO3S (M + Na)+ 500.0307, found 500.0306.
3-Phenyl-1-tosyl-1,2,3,5-tetrahydrobenzo[e][1,4]thiazepine (8h).
The general method B described above was followed when 7h (100
mg, 0.209 mmol) was reacted with CuI (3.98 mg, 0.020 mmol), L-
7-Fluoro-3-phenyl-1-tosyl-1,2,3,5-tetrahydrobenzo[e][1,4]-
oxazepine (8f). The general method B described above was followed
when 7f (300 mg, 0.627 mmol) was reacted with CuI (11.94 mg,
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proline (4.81 mg, 0.041 mmol) and NaH (12.54 mg, 0.522 mmol) at
90 °C for 14 h to afford 8h (68 mg, 0.171 mmol) as a white solid in
82% yield: mp 158−162 °C; Rf 0.53 (20% ethyl acetate in petroleum
ether); IR νmax (KBr, cm−1) 3426, 3058, 3028, 2958, 2925, 1972,
1910, 1597, 1490, 1451, 1423, 1408, 1346, 1304, 1283, 1264, 1234,
1219, 1183, 1153, 1089, 1039, 1018, 993, 967, 895, 887, 869, 807,
1004, 911, 877, 842, 816, 753, 703, 669, 587, 544, 529, 506; 1H
NMR (500 MHz, CDCl3) δ 2.46 (s, 3H), 2.64 (d, 1H), 3.22−3.27
(m, 2H), 3.78 (t, J = 9.1 Hz, 1H), 4.03 (t, J = 7.6 Hz, 1H), 5.5 (s,
1H), 7.00−7.01 (m, 1H), 7.18 (d, J = 7.3 Hz, 1H), 7.24−7.33 (m,
7H), 7.44−7.52 (m, 5H), 7.62 (d, J = 8.2 Hz, 2H), 7.84 (d, J = 6.4
Hz, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 21.7, 51.8, 56.5, 65.2,
77.7, 126.9, 127.7, 128.0, 128.3, 128.4, 128.5, 128.7, 128.7, 128.9,
129.7, 133.9, 134.1, 135.4, 137.9, 138.3, 140.3, 143.7; HRMS (ESI-
TOF) calcd for C29H27N2O2S (M + H)+ 467.1793, found 467.1792.
N-(2-((2-Bromobenzyl)amino)-2-(p-tolyl)ethyl)-4-methylbenzene-
sulfonamide (7k). The general method C described above was
followed when 5c (200 mg, 0.717 mmol) reacted with a 2-
bromobenzylamine 6d (146.8 mg, 0.789 mmol) rt for 6 h to afford
7k (300 mg, 0.633 mmol) as a white solid in 88% yield: mp 125−
128 °C; Rf 0.34 (20% ethyl acetate in petroleum ether); IR νmax
(KBr, cm−1) 3344, 3254, 2898, 1906, 1596, 1566, 1513, 1445, 1395,
1360, 1317, 1288, 1200, 1186, 1155, 1093, 1057, 1043, 1022, 926,
884, 843, 817, 797, 749, 727, 660, 606, 576, 558, 541, 489, 474, 441;
1H NMR (500 MHz, CDCl3) δ 2.33 (s, 3H), 2.40 (s, 3H), 2.98−
3.03 (m, 1H), 3.10−3.14 (m, 1H), 3.53 (d, J = 13,4 Hz, 1H), 3.58−
3.61 (m, 1H), 3.68 (d, J = 13.4 Hz, 1H), 4.93 (s, 1H), 7.07 (d, J =
7.9 Hz, 2H), 7.10−7.13 (m, 3H), 7.20−7.26 (m, 4H), 7.51 (d, J =
7.9 Hz, 1H), 7.65 (d, J = 8.2 Hz, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 21.2, 21.6, 48.8, 51.3, 60.8, 124.1, 127.0, 127.1, 127.5,
128.9, 129.5, 129.7, 130.6, 132.9, 136.8, 137.0, 137.7, 138.8, 143.4;
HRMS (ESI-TOF) calcd for C23H26BrN2O2S (M + H)+ 473.0898,
found 473.0892.
7-(p-Tolyl)-5-tosyl-5,6,7,9-tetrahydro-4bH-dibenzo[c,e]imidazo-
[1,2-a]azepine (9b). The general method B described above was
followed when 7k (200 mg, 0.422 mmol) was reacted with CuI (10
mol %), L-proline (20 mol %) and NaH (25.3 mg, 1.05 mmol) at 90
°C for 14 h to afford 9b (173 mg, 0.359 mmol) as a white solid in
85% yield: mp 164−166 °C; Rf 0.61 (20% ethyl acetate in petroleum
ether); IR νmax (KBr, cm−1) 3447, 3023, 2920, 2812, 1906, 1596,
1511, 1494, 1466, 1450, 1372, 1347, 1307, 1250, 1235, 1190, 1161,
1130, 1110, 1088, 1065, 1028, 1014, 964, 949, 911, 877, 842, 814,
777, 745, 717, 708, 668, 644, 608, 589, 561, 543, 526, 502, 484, 437;
1H NMR (500 MHz, CDCl3) δ 2.31 (s, 3H), 2.46 (s, 3H), 2.63 (d, J
= 11.0 Hz, 1H), 3.23 (t, J = 9.5 Hz, 2H), 3.75 (t, J = 9.1 Hz, 1H),
4.00 (t, J = 8.8 Hz, 1H), 6.90 (d, J = 7.9 Hz, 2H), 7.06 (d, J = 7.9
Hz, 2H), 7.17 (d, J = 7.0 Hz, 1H), 7.25−7.33 (m, 4H), 7.44−7.52
(m, 5H), 7.62 (d, J = 7.9 Hz, 2H), 7.83 (d, J = 6.7 Hz, 2H);
13C{1H} NMR (125 MHz, CDCl3) δ 21.2, 21.6, 51.7, 56.5, 64.9,
1
767, 723, 703, 693, 651, 638, 588, 574, 542, 520, 509, 482, 458; H
NMR (500 MHz, CDCl3) δ 2.44 (s, 3H), 3.28 (bs, 1H), 3.46 (d, J =
14 Hz, 1H), 4.11 (d, J = 12.8, 1H), 4.50−4.62 (m, 2H), 7.04 (d, J =
7.9 Hz, 1H), 7.18−7.33 (m, 10H), 7.68 (m, 2H); 13C{1H} NMR
(125 MHz, CDCl3) δ 21.6, 35.3, 52.5, 57.2, 127.3, 127.8, 128.1,
128.2, 128.9, 129.1, 129.2, 129.9, 138.5, 138.6, 139.3, 143.8; HRMS
(ESI-TOF) calcd for C22H22NO2S2 (M + H)+ 396.1092, found
396.1090.
N-(2-(2-Bromobenzylthio)-2-(4-chlorophenyl)ethyl)-4-methylben-
zenesulfonamide (7i). The general method A described above was
followed when 5b (200 mg, 0.649 mmol) reacted with 2-bromo
benzyl mercaptan 6c (0.09 mL, 0.713 mmol) rt for 4 h to afford 7i
(290 mg, 0.567 mmol) as a white solid in 87% yield: mp 106−108
°C; Rf 0.43 (20% ethyl acetate in petroleum ether); IR νmax (KBr,
cm−1) 3271,2922, 1599, 1490, 1467, 1441, 1412, 1327, 1235, 1156,
1
1120, 1088, 1024, 1013, 847, 811, 794, 760, 668, 551, 527; H NMR
(500 MHz, CDCl3) δ 2.42 (s, 3H), 3.22−3.31 (m, 2H), 3.64 (q, J =
13.2 Hz, 1H), 3.79 (t, J = 7.4 Hz, 1H), 4.63 (t, J = 6.3 Hz, 1H),
7.09−7.31 (m, 9H), 7.51 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 8.3 Hz,
2H); 13C{1H} NMR (125 MHz, CDCl3) δ 21.6, 36.0, 47.5, 49.0,
124.5, 127.1, 127.6, 129.0, 129.4, 129.8, 130.7, 133.2, 133.8, 136.6,
136.8, 137.4, 143.7; HRMS (ESI-TOF) calcd for
C22H21BrClNNaO2S2 (M + Na)+ 531.9783, found 531.9789.
3-(4-Chlorophenyl)-1-tosyl-1,2,3,5-tetrahydrobenzo[e][1,4]-
thiazepin (8i). The general method B described above was followed
when 7i (200 mg, 0.391 mmol) was reacted with CuI (7.44 mg,
0.039 mmol), L-proline (9.0 mg, 0.078 mmol) and NaH (23.46 mg,
0.977 mmol) at 90 °C for 12 h to afford 8i (135 mg, 0.313 mmol)
as a white solid in 82% yield: mp 158−162 °C; Rf 0.53 (20% ethyl
acetate in petroleum ether); IRνmax (KBr, cm−1) 3196, 2920, 1589,
1489, 1454, 1408, 1339, 1215, 1183, 1150, 1104, 1088, 1012, 895,
868, 841, 818, 772, 732, 712, 685, 649, 574, 544, 524; 1H NMR
(500 MHz, CDCl3) δ 2.44 (s, 3H), 3.23 (bs, 1H), 3.46 (d, J = 14.9
Hz, 1H), 4.12 (d, J = 10.3, 1H), 4.50−4.59 (m, 2H), 7.13−7.20 (m,
3H), 7.25−7.31 (m, 7H), 7.68 (m, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 21.7, 35.3, 52.0, 57.0, 127.1, 127.3, 128.2, 128.8, 128.9,
129.1, 129.2, 129.6, 129.8, 129.9, 137.1, 138.3, 143.9; HRMS (ESI-
TOF) calcd for C22H21ClNO2S2 (M + H)+ 430.0702, found
430.0703.
77.7, 126.9, 127.6, 127.9, 128.0, 128.2, 128.3, 128.5, 128.6, 128.9,
129.4, 129.6, 134.0, 134.2, 134.8, 135.5, 138.1, 138.3, 140.4, 143.7;
HRMS (ESI-TOF) calcd for C30H29N2O2S (M + H)+ 481.1950,
found 481.1953.
N-(2-((2-Bromobenzyl)amino)-2-phenylethyl)-4-methylbenzene-
sulfonamide (7j). The general method C described above was
followed when 5a (200 mg, 0.730 mmol) reacted with a 2-
bromobenzylamine 6d (149.4 mg, 0.803 mmol) rt for 4 h to afford
7j (280 mg, 0.609 mmol) as a white solid in 83% yield: mp 126−128
°C; Rf 0.33 (20% ethyl acetate in petroleum ether); IR νmax (KBr,
cm−1) 3345, 3249, 3058, 3023, 2985, 2902, 1924, 1810, 1597, 1563,
1493, 1446, 1398, 1361, 1317, 1288, 1219, 1200, 1187, 1155, 1135,
1093, 1075, 1055, 1041, 1021, 989, 950, 926, 884, 841, 817, 763,
N-(2-((2-Bromobenzyl)amino)-2-(4-fluorophenyl)ethyl)-4-methyl-
benzenesulfonamide (7l). The general method C described above
was followed when 5d (200 mg, 0.607 mmol) reacted with a 2-
bromobenzylamine 6d (124.2 mg, 0.667 mmol) rt for 4 h to afford
7l (240 mg, 0.502 mmol) as a white solid in 83% yield: mp 126−128
°C; Rf 0.32 (20% ethyl acetate in petroleum ether) IR νmax (KBr,
cm−1) 3343, 3249, 2914, 1603, 1565, 1508, 1447, 1397, 1361, 1322,
1225, 1157, 1102, 1040, 926, 883, 836, 755, 720, 660, 576, 558, 542,
1
749, 699, 663, 598, 575, 561, 541, 488, 471, 436; H NMR (500
1
MHz, CDCl3) δ 2.40 (s, 3H), 3.00−3.05 (m, 1H), 3.12−3.16 (m,
1H), 3.54 (d, J = 13.4 Hz, 1H), 3.62−3.70 (m, 2H), 4.96 (s, 1H),
7.10−7.33 (m, 10H), 7.51 (d, J = 7.6 Hz, 1H), 7.66 (d, J = 8.2 Hz,
2H); 13C{1H} NMR (125 MHz, CDCl3) δ 21.6, 48.8, 51.3, 61.2,
124.1, 127.1, 127.5, 128.0, 128.9, 129.7, 130.6, 132.9, 136.8, 138.7,
140.1, 143.4; HRMS (ESI-TOF) calcd for C22H24BrN2O2S (M +
H)+ 459.0742, found 459.0742.
7-Phenyl-5-tosyl-5,6,7,9-tetrahydro-4bH-dibenzo[c,e]imidazo-
[1,2-a]azepine (9a). The general method B described above was
followed when 7j (250 mg, 0.544 mmol) was reacted with CuI (10
mol %), L-proline (20 mol %) and NaH (32.64 mg, 1.36 mmol) at
90 °C for 14 h to afford 9a (204 mg, 0.437 mmol) as a white solid
in 80% yield: mp 160−164 °C; Rf 0.60 (20% ethyl acetate in
petroleum ether); IR νmax (KBr, cm−1) 3445, 3026, 2924, 2853,
1702, 1597, 1493, 1452, 1347, 1288, 1192, 1159, 1132, 1089, 1039,
482 H NMR (500 MHz, CDCl3) δ 2.40 (s, 3H), 2.98−3.03 (m,
1H), 3.08−3.13 (m, 1H), 3.54 (d, J = 13.4 Hz, 1H), 3.63−3.68 (m,
3H), 4.90 (s, 1H), 6.97−6.99 (m, 2H), 7.10−7.28 (m, 7H), 7.50−
7.55 (m, 1H), 7.65 (d, J = 8.2 Hz, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 21.6, 48.9, 51.3, 53.8, 60.5, 115.6, 115.8, 124.1, 127.1,
127.3, 127.5, 128.5, 128.7, 129.0, 129.4, 129.8, 130.6, 133.0, 135.9,
136.7, 138.5, 143.5, 163.4; HRMS (ESI-TOF) calcd for
C22H23BrFN2O2S (M + H)+ 477.0648, found 477.0646.
7-(4-Fluorophenyl)-5-tosyl-5,6,7,9-tetrahydro-4bH-dibenzo[c,e]-
imidazo[1,2-a]azepine (9c). The general method B described above
was followed when 7l (100 mg, 0.209 mmol) was reacted with CuI
(10 mol %), L-proline (20 mol %) and NaH (12.54 mg, 0.522
mmol) at 90 °C for 14 h to afford 9c (80 mg, 0.165 mmol) as a
white solid in 79% yield: mp 160−164 °C; Rf 0.65 (20% ethyl
acetate in petroleum ether) IR νmax (KBr, cm−1) 2956, 2924, 2854,
I
dx.doi.org/10.1021/jo500888j | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1600, 1509, 1456, 1346, 1260, 1224, 1157, 1092, 1015, 814, 754,
705, 668, 587, 546 H NMR (500 MHz, CDCl3) δ 2.46 (s, 3H),
(m, 1H), 5.59 (s, 1H), 6.96 (d, J = 6.6 Hz, 2H), 7.17−7.34 (m, 7H),
7.45−7.53 (m, 5H), 7.66 (d, J = 8.0 Hz, 2H), 7.81−7.83 (m, 1H);
13C{1H} NMR (125 MHz, CDCl3) δ 31.1, 35.2, 51.8, 56.5, 65.3,
77.9, 126.0, 126.8, 127.6, 127.9, 128.0, 128.2, 128.4, 128.5, 128.7,
128.8, 133.8, 134.1, 135.5, 138.3, 140.4; HRMS (ESI-TOF) calcd for
C32H33N2O2S (M + H)+ 509.2263, found 509.2265.
1
3.17−3.22 (m, 2H), 3.75−3.78 (m, 1H), 4.00−4.03 (m, 1H), 6.91−
6.97 (m, 4H), 7.16−7.18 (m, 1H), 7.25−7.34 (m, 3H), 7.45−7.52
(m, 5H), 7.62 (d, J = 7.9 Hz, 2H), 7.81−7.83 (m, 1H); 13C{1H}
NMR (125 MHz, CDCl3) δ 21.7, 51.7, 56.5, 64.5, 77.7, 115.6, 115.8,
126.8, 128.0, 128.3, 128.4, 128.6, 128.7, 128.8, 129.2, 129.7, 133.7,
133.9, 135.2, 138.3, 140.3, 143.8, 161.6; HRMS (ESI-TOF) calcd for
C29H26FN2O2S (M + H)+ 485.1699, found 485.1698.
(S)-N-(2-((2-Bromobenzyl)amino)-2-phenylethyl)-4-methylbenze-
nesulfonamide ((S)-7j). The general method C described above was
followed when (R)-5a (200 mg, 0.730 mmol) reacted with a 2-
bromobenzylamine 6d (149.4 mg, 0.803 mmol) rt for 4 h to afford
(S)-7j (280 mg, 0.609 mmol) as a white solid in 83% yield: mp
126−128 °C; Rf 0.43 (20% ethyl acetate in petroleum ether); Rf 0.33
N-(2-((2-Bromobenzyl)amino)-2-(4-(tert-butyl)phenyl)ethyl)-4-
methylbenzenesulfonamide (7m). The general method C described
above was followed when 5e (200 mg, 0.649 mmol) reacted with a
2-bromobenzylamine 6d (132.8 mg, 0.713 mmol) rt for 4 h to afford
7m (270 mg, 0.523 mmol) as a white solid in 81% yield: mp 128−
130 °C; Rf 0.40 (20% ethyl acetate in petroleum ether); IR νmax
(KBr, cm−1) 3329, 3251, 2959, 2866, 1597, 1566, 1509, 1460, 1447,
1390, 1314, 1269, 1187, 1156, 1126, 1062, 1023, 834, 821, 748, 718,
(20% ethyl acetate in petroleum ether); [α]25 = +96.02 (c 0.53,
D
CHCl3); IR νmax (KBr, cm−1) 3345, 3249, 3058, 3023, 2985, 2902,
1924, 1810, 1597, 1563, 1493, 1446, 1398, 1361, 1317, 1288, 1219,
1200, 1187, 1155, 1135, 1093, 1075, 1055, 1041, 1021, 989, 950,
926, 884, 841, 817, 763, 749, 699, 663, 598, 575, 561, 541, 488, 471,
1
1
436; H NMR (500 MHz, CDCl3) δ 2.40 (s, 3H), 3.00−3.05 (m,
700, 659, 610, 572, 550, 533, 499; H NMR (500 MHz, CDCl3) δ
1H), 3.12−3.16 (m, 1H), 3.54 (d, J = 13.4 Hz, 1H), 3.62−3.70 (m,
2H), 4.96 (s, 1H), 7.10−7.33 (m, 10H), 7.51 (d, J = 7.6 Hz, 1H),
7.66 (d, J = 8.2 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 21.6,
48.8, 51.3, 61.2, 124.1, 127.1, 127.5, 128.0, 128.9, 129.7, 130.6, 132.9,
136.8, 138.7, 140.1, 143.4; HRMS (ESI-TOF) calcd for
C22H24BrN2O2S (M + H)+ 459.0742, found 459.0742; ee >99%.
The enantiomeric excess was determined by chiral HPLC analysis
(cellulose 2), n-hexane/i-propanol = 95:5, flow rate = 1.0 mL/min, tR
(1) = 59.49 min (major).
1.30 (s, 9H), 2.40 (s, 3H), 2.99−3.04 (m, 1H), 3.11−3.16 (m, 1H),
3.54 (d, J = 13.4 Hz, 1H), 3.59−3.62 (m, 1H), 3.69 (d, J = 13.4 Hz,
1H), 4.96 (s, 1H), 7.09−7.12 (m, 3H), 7.23−7.25 (m, 4H), 7.31−
7.33 (m, 2H), 7.51 (d, J = 7.7 Hz, 1H), 7.66 (d, J = 8.0 Hz, 2H);
13C{1H} NMR (125 MHz, CDCl3) δ 21.6, 31.4, 34.6, 48.7, 51.4,
60.8, 124.2, 125.7, 126.7, 127.2, 127.5, 128.8, 129.7, 130.6, 132.9,
136.8, 137.0, 138.9, 143.4, 150.9; HRMS (ESI-TOF) calcd for
C26H32BrN2O2S (M + H)+ 515.1368, found 515.1360.
7-(4-(tert-Butyl)phenyl)-5-tosyl-5,6,7,9-tetrahydro-4bH-dibenzo-
[c,e]imidazo[1,2-a]azepine (9d). The general method B described
above was followed when 7m (100 mg, 0.193 mmol) was reacted
with CuI (10 mol %), L-proline (20 mol %) and NaH (11.58 mg,
0.482 mmol) at 90 °C for 14 h to afford 9d (78 mg, 0.149 mmol) as
a white solid in 77% yield: mp 168−170 °C; Rf 0.65 (20% ethyl
acetate in petroleum ether); IR νmax (KBr, cm−1) 3028, 2958, 2925,
2855, 1598, 1510, 1494, 1461, 1351, 1304, 1261, 1115, 1160, 1115,
(7S)-7-Phenyl-5-tosyl-5,6,7,9-tetrahydro-4bH-dibenzo[c,e]-
imidazo[1,2-a]azepine ((S)-9a). The general method B described
above was followed when (S)-7j (250 mg, 0.544 mmol) was reacted
with CuI (10 mol %), L-proline (20 mol %) and NaH (32.64 mg,
1.36 mmol) at 90 °C for 14 h to afford (R)-9a (204 mg, 0.437
mmol) as a white solid in 80% yield: mp 160−164 °C; Rf 0.60 (20%
ethyl acetate in petroleum ether); [α]25 = +25.7 (c 0.43, CH2Cl2);
D
IR νmax (KBr, cm−1) 3445, 3026, 2924, 2853, 1702, 1597, 1493,
1
1090, 1017, 916, 878, 833, 833, 813, 755, 705, 669, 587, 506; H
1452, 1347, 1288, 1192, 1159, 1132, 1089, 1039, 1004, 911, 877,
NMR (500 MHz, CDCl3) δ 1.29 (s, 9H), 2.46 (s, 3H), 2.62 (d, J =
10.8 Hz, 1H), 3.26 (t, J = 9.4 Hz, 2H), 3.75−3.78 (m, 1H), 3.98−
4.01 (m, 1H), 5.52 (s, 1H), 6.95 (d, J = 8.3, 2H), 7.19−7.32 (m,
6H), 7.44−7.52 (m, 4H), 7.63 (d, J = 8.05, 2H), 7.84 (d, J = 6.6,
2H); 13C{1H} NMR (125 MHz, CDCl3) δ 21.7, 31.4, 34.6, 51.8,
56.4, 64.8, 77.7, 125.6, 127.0, 127.4, 127.9, 128.0, 128.2, 128.3, 128.4,
128.6, 128.9, 129.7, 134.0, 134.2, 134.6, 135.5, 138.3, 140.4, 143.7,
151.3; HRMS (ESI-TOF) calcd for C33H35N2O2S (M + H)+
523.2419, found 523.2410.
1
842, 816, 753, 703, 669, 587, 544, 529, 506; H NMR (500 MHz,
CDCl3) δ 2.46 (s, 3H), 2.64 (d, 1H), 3.22−3.27 (m, 2H), 3.78 (t, J
= 9.1 Hz, 1H), 4.03 (t, J = 7.6 Hz, 1H), 5.5 (s, 1H), 7.00−7.01 (m,
1H), 7.18 (d, J = 7.3 Hz, 1H), 7.24−7.33 (m, 7H), 7.44−7.52 (m,
5H), 7.62 (d, J = 8.2 Hz, 2H), 7.84 (d, J = 6.4 Hz, 1H); 13C{1H}
NMR (125 MHz, CDCl3) δ 21.7, 51.8, 56.5, 65.2, 77.7, 126.9, 127.7,
128.0, 128.3, 128.4, 128.5, 128.7, 128.7, 128.9, 129.7, 133.9, 134.1,
135.4, 137.9, 138.3, 140.3, 143.7; HRMS (ESI-TOF) calcd for
C29H27N2O2S (M + H)+ 467.1793, found 467.1792; ee >99%. The
enantiomeric excess was determined by chiral HPLC analysis
(cellulose 2), n-hexane/i-propanol = 90:10, flow rate = 1.0 mL/
min, tR (1) = 29.69 min (major).
N-(2-((2-Bromobenzyl)amino)-2-phenylethyl)-4-(tert-butyl)-
benzenesulfonamide (7n). The general method C described above
was followed when 5f (200 mg, 0.634 mmol) reacted with a 2-
bromobenzylamine 6d (129.7 mg, 0.697 mmol) rt for 5 h to afford
7n (250 mg, 0.498 mmol) as a white solid in 78% yield: mp 128−
130 °C; Rf 0.36 (20% ethyl acetate in petroleum ether) IR νmax (KBr,
cm−1) 3284, 3061, 3029, 2963, 2868, 1736, 1595, 1567, 1493, 1454,
1398, 1364, 1329, 1198, 1164, 1112, 1088, 1025, 835, 752, 701, 632,
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H and 13C{1H} NMR spectra of the compounds,
1
581, 551; H NMR (500 MHz, CDCl3) δ 1.32 (s, 9H), 3.02−3.16
HPLC chromatograms for ee determination and crystal
structures (CIF). This material is available free of charge via
the Internet at http://pubs.acs.org.
(m, 2H), 3.55−3.71 (m, 3H), 4.99 (s, 1H), 7.11−7.34 (m, 10H),
7.43−7.70 (m, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 31.1, 35.2,
48.7, 48.8, 51.3, 61.2, 124.2, 125.6, 125.7, 126.1, 127.0, 127.1, 127.5,
128.0, 128.4, 128.6, 128.9, 130.6, 133.0, 136.7, 138.7, 140.2; HRMS
(ESI-TOF) calcd for C25H30BrN2O2S (M + H)+ 501.1211, found
501.1213.
AUTHOR INFORMATION
■
5-((4-(tert-Butyl)phenyl)sulfonyl)-7-phenyl-5,6,7,9-tetrahydro-
4bH-dibenzo[c,e]imidazo[1,2-a]azepine (9e). The general method B
described above was followed when 7n (100 mg, 0.199 mmol) was
reacted with CuI (10 mol %), L-proline (20 mol %) and NaH (11.9
mg, 0.497 mmol) at 90 °C for 14 h to afford 9e (82 mg, 0.161
mmol) as a white solid in 81% yield: mp 160−162 °C; Rf 0.66 (20%
ethyl acetate in petroleum ether) IR νmax (KBr, cm−1) 3062, 3029,
2962, 2926, 1741, 1595, 1492, 1453, 1400, 1351, 1307, 1262, 1196,
1113, 1087, 1024, 911, 877, 838, 800, 756, 701, 637, 609, 588, 542,
Corresponding Author
*Fax: (+91)-512-2597436. Phone: (+91)-512-2597518. E-
mail: mkghorai@iitk.ac.in.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
1
Dedicated to Prof. Sabyasachi Sarkar on the occasion of his
67th birthday. M.K.G. is grateful to IIT-Kanpur, DST and
526, 499; H NMR (500 MHz, CDCl3) δ 1.3 (s, 9H), 2.63 (d, J =
10.9 Hz, 1H), 3.20−3.27 (m, 2H), 3.77−3.78 (m, 1H), 4.01−4.04
J
dx.doi.org/10.1021/jo500888j | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Irving, E.; Scheinmann, F. Org. Lett. 2003, 5, 2927. (e) Forbeck, E.
CSIR, India. A.K.S. and A.B. thank CSIR, India, for research
fellowships.
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M.; Evans, C. D.; Gilleran, J. A.; Li, P.; Joullie, M. M. J. Am. Chem.
Soc. 2007, 129, 14463. (f) Moss, T. A.; Fenwick, D. R.; Dixon, D. J.
J. Am. Chem. Soc. 2008, 130, 10076. (g) Paixao, M. W.; Nielsen, M.;
̃
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