Iodocyclization of o -alkynylbenzamides revisited: Formation of isobenzofuran-1(3 H)-imines and 1 H -isochromen-1-imines instead of lactams

Article abstract of DOI:10.1021/jo3017378

The iodocyclization of o-alkynylbenzamides with various electrophiles has been reported to yield five- or six-membered lactams by nucleophilic attack of the amide nitrogen onto the triple bond. While the formation of an isobenzofuran-1(3H)-imine with two

Full text of DOI:10.1021/jo3017378

Article
pubs.acs.org/joc
Iodocyclization of o‑Alkynylbenzamides Revisited: Formation of
Isobenzofuran-1(3H)‑imines and 1H‑Isochromen-1-imines Instead of
Lactams
Claudine Schlemmer,† Lars Andernach,† Dieter Schollmeyer,† Bernd F. Straub,*,‡ and Till Opatz*,†
†Institute of Organic Chemistry, University of Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany
‡Institute of Organic Chemistry, University of Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany
S
* Supporting Information
ABSTRACT: The iodocyclization of o-alkynylbenzamides
with various electrophiles has been reported to yield five- or
six-membered lactams by nucleophilic attack of the amide
nitrogen onto the triple bond. While the formation of an
isobenzofuran-1(3H)-imine with two bulky substituents under
Larock conditions was initially attributed to steric hindrance,
we found out that cyclization via the amide oxygen is the rule
rather than the exception. Thus, the structures of the products
reported in the literature need to be revised.
indicated that this behavior is not due to the presence of the
nitro substituent.
INTRODUCTION
■
Intramolecular attack of nucleophiles onto triple bonds
activated by carbophilic electrophiles such as iodine,1 inter-
halogens,2 arylselenium halides,3 mercury ions,4 or gold
complexes5,6 is a powerful and frequently used tool for the
construction of five- and six-membered heterocycles.7−18 As an
example, the cyclization of o-alkynylbenzamides with iodine or
other soft electrophiles published by Larock and co-workers3
has been reported to furnish either 2-substituted 3-(1-
iodoalkylidene)-2,3-dihydro-1H-isoindolin-1-ones or 2,3-disub-
stituted 4-iodoisoquinolin-1(2H)-ones. The ratio of the
products of a 5-exo-dig or a 6-endo-dig cyclization strongly
depends on the substituents and the reaction conditions.
In a project on the synthesis of metabolically stable
glycomimetics, we chose an iodocyclization19,20 according to
Larock3 as the key step for the rapid construction of
diglycosylated heterocycles.21 More specifically, glycosylacety-
lenes such as 4 were reacted with N-galactosyl-2-iodobenza-
mides such as 5 in a Sonogashira22 coupling to furnish the
cyclization precursors 1 and 6 (Scheme 1).
Reaction with iodine in MeCN in the presence of NaHCO3
smoothly yielded compounds 3 and 8, which were initially
thought to be the corresponding isoindolinones21 2 and 7 as
judged by 2D NMR spectroscopy and comparison with
literature data.3 While 3 was an oil, its nitro-substituted
derivative 8 gave crystals suitable for X-ray crystallography, and
we were surprised to identify the product as an isobenzofuran
instead (Figure 1). Highly similar 15N chemical shifts for 3 and
8 (215.1 and 220.2 ppm) inconsistent with a lactam structure
A literature search on products of halocyclizations of alkynes
onto amides revealed N-attack to be broadly accepted.
However, in the case of bulky backbone substituents10 or
iodocyclizations on olefinic double bonds within conjugated
dienoic amides,23 O-attack was reported. Studies on iodocyc-
lization24 and Pd-catalyzed cyclization25 of allenoic amides by
Ma and co-workers also showed that sterically demanding
groups may favor O- over N-attack. To rule out the two bulky
glycosyl residues as the cause for the deviant reactivity of
compounds 1 and 6, we decided to resynthesize one of Larock’s
isoindolinones for comparison of the characteristic 15N
chemical shifts.
RESULTS AND DISCUSSION
■
(3E)-3-[Iodo(phenyl)methylidene]-2-phenyl-2,3-dihydro-1H-
isoindolin-1-one (10a) was prepared according to the published
procedure,3 and crystals were grown for X-ray structural
analysis. Again, the compound was found to be an O-cyclized
product instead, i.e., (1Z,3E)-3-[iodo(phenyl)methylidene]-N-
phenyl-2-benzofuran-1(3H)-imine (11a; Scheme 2, Figure 2).
This was repeated with an identical result for the cyclization of
N-methyl-2-(phenylethynyl)benzamide (12; Scheme 3), in
which the small N-methyl group was chosen to exclude steric
effects as the cause for the observed O/N-selectivity.
Received: August 16, 2012
© XXXX American Chemical Society
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Scheme 1. Attempted Preparation of
Diglycosylisoindolinones
Figure 1. Crystal structure of compound 8 (ORTEP plot).
Scheme 2. Iodocyclization of Compound 9
To check the identity of the corresponding six-membered
products, 2-(cyclohex-1-en-1-ylethynyl)-N-phenylbenzamide
(14) was used as the substrate as a preference for the 6-endo-
dig cyclization has been observed by Larock and Yao.3 Both
cyclization products 15a and 15b could be readily separated by
HPLC but were obtained as liquids (Scheme 4).
15N HMBC spectra showed similar chemical shifts for both
compounds which were in the same range as those of 8 and 11a
(11a, 223.8 ppm; 11b, 230.0 ppm; 13a, 209.7 ppm; 15a, 226.5
ppm; 15b, 229.1 ppm). NOESY data of 15b showed only weak
contacts between the phenyl and the cyclohexenyl residues,
which supports the presence of an isochromene core in this
product. The preferential O-attack also in the six-membered
series could be unequivocally proven by crystallographic
analysis of 11b and 13b (Figure 3, Supporting Information).
While the former compound was prepared by the action of
ICl on precursor 9 (97% yield, 11a:11b = 56:44), the latter
material crystallized as its hydrotriiodide salt. As the
spectroscopic data of compounds 11a, 11b, 13a, 15a, and
15b match those reported in the literature,3 the structural
Figure 2. Crystal structure of compound 11a (ORTEP plot).
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adduct. In the reaction, the iodonium center transfers a positive
formal charge to the substrate’s carboxamide fragment.
A Curtin−Hammett scenario emerged.36 The preferred
substrate conformation comprises a more favorable interaction
of the NH fragment with the alkyne’s π-system (Figure 4). The
weak interaction of the negatively polarized carbonyl oxygen
with the positively polarized aniline ortho hydrogen is also
energetically more beneficial than the repulsions of the oxygen’s
lone pair and the alkyne’s π-system and of the NH and the
ortho proton in the alternative conformer.
Scheme 3. Iodocyclization of Compound 12
Scheme 4. Iodocyclization of Compound 14
The exchange of collidine versus alkyne at the iodine cation,
presumably being the rate-determining step, leads to a low
concentration of an iodine π-complex. The nucleophilic attack
of the carbonyl’s oxygen and the concerted C−I single bond
formation proceed in a remarkably shallow energy hypersurface.
The transition states are characterized by C−O distances of 260
15 pm (five-membered cycle) and 298
5 pm (six-
membered cycle) with their kinetically controlled C−O bond
formation being irreversible. These 5-exo-dig and the 6-endo-dig
processes are both favorable according to Baldwin’s rules.37 The
activation energies are equal within the accuracy of the
computed scan of C−O distances. As a consequence, the
observed product ratios can significantly depend on the solvent
and counterion. The nucleophilic attack of an electron lone pair
of the carbonyl group features lower barriers than the C−N
bond formation pathways, which would lead to thermodynami-
cally more stable isomeric products after eventual deprotona-
tion (Figure 5).
The isoindolone formation is more disfavored than the
isoquinolone pathway. The loss of resonance energy renders
the C−N formation transition states noncompetitive. Remark-
ably, considering the transformation of the high-energy alkyne
fragment, the respective N-acylammonium intermediates plus
collidine are thermodynamically less stable than substrate 9 and
the iodonium cation. Thus, the hypothetical ammonium
intermediates would be extremely strong acids.
CONCLUSION
■
The iodocyclization of o-alkynylbenzamides leads to five-
membered and six-membered oxacycles instead of the reported
C−N bond formation. Previous investigations on other
electrophilic cyclizations of the same reactants revealed the
formation of lactones.4,9 Lactones could also be obtained from
the cyclic imidates described herein by acid hydrolysis of the
exocyclic CN bond, while the exergonic rearrangement of
the iodocyclization products to the corresponding lactams was
observed neither under acidic nor under basic conditions. DFT
model calculations find a Curtin−Hammett scenario of a more
stable, yet unreactive, conformer with an NH fragment oriented
toward the alkyne. Favored C−O bond formation pathways are
also predicted computationally, featuring a concerted formation
of a C−I single bond.
Figure 3. Crystal structure of compound 11b (ORTEP plot).
revision of similar products, including the glycomimetics
published earlier by us, will be necessary.21
Since O- and N-attacks have been observed in transition-
metal-catalyzed cyclizations of o-alkynylbenzamides,13,18 we
became interested in energetic aspects of Larock’s iodocycliza-
tion. As a system suitable for DFT calculations, we chose
bis(collidine)iodonium hexafluorophosphate26,27 in combina-
tion with compound 9 as an electrophile and starting material.
The cyclization was performed in CH2Cl2 as well as in MeCN
to give the two products 11a and 11b along with unreacted
alkyne. The conversion and the ratio of the five- versus the six-
membered ring were determined by 1H NMR spectroscopy. In
the former case, a conversion of 33% (reflux conditions, 16 h)
and a ratio of 11a to 11b of 10:1 were observed. In the latter
case (MeCN), the conversion amounted to 40% and the ratio
of the two products was 15:1.
The structure optimizations were performed at the PBE-D3/
LACV3P**++ level of theory in the Jaguar 7.9 program
package.28−35 Tolane derivative 9 was used as a model
substrate, enabling a direct comparison with experimental
results. The use of the cationic iodine source avoids charge
separation as would be the case in a neutral substrate−reagent
EXPERIMENTAL SECTION
■
General Procedure for Preparation of the o-(1-Alkynyl)-
benzamides.3 To a solution of the corresponding organic iodide (1.0
mmol) and the terminal alkyne (1.2 mmol, 1.2 equiv) in Et3N (4.00
mL) were added PdCl2(PPh3)2 (1.40 mg, 2 mol %) and CuI (2.00 mg,
1 mol %). The resulting mixture was then heated under an argon
atmosphere at 55 °C. The reaction was monitored by TLC to establish
completion. When the reaction was complete, the mixture was allowed
to cool to room temperature, and the reaction mixture was diluted
with ethyl acetate (20.0 mL) and water (10.0 mL). The organic phase
was washed twice with water (10.0 mL), dried over Na2SO4, and
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Figure 4. DFT energies for the iodocyclization onto amide oxygen.
Figure 5. DFT energies for the (hypothetical) iodocyclization onto amide nitrogen.
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filtered, the solvent was removed under reduced pressure, and the
residue was purified by flash column chromatography on silica gel to
afford the corresponding o-(1-alkynyl)benzamide.
128.4, 128.4, 128.2, 127.9, 127.9, 127.8, 127.8, 127.7, 127.6, 127.4
(CPh), 124.9 (C-4), 124.7 (C-7), 85.7 (C-I), 81.7 (C-1gal), 77.1 (C-
2
man), 75.0 (C-5man), 74.7 (C-4man), 73.1 (C-3man), 72.9 (CH2Ph), 72.4
General Procedure for Electrophilic Cyclization of the o-(1-
Alkynyl)benzamides by I2.3 The alkynylarenecarboxamide (0.30
mmol), I2 (3.0 equiv), NaHCO3 (3.0 equiv), and CH3CN (3.00 mL)
were placed in a Schlenk flask and flushed with argon. The reaction
mixture was stirred at room temperature for 1 h unless otherwise
indicated. The reaction mixture was then diluted with ether (50.0 mL),
washed with satd aq Na2S2O3 (25.0 mL), dried over Na2SO4, and
filtered. The solvent was evaporated under reduced pressure, and the
product was isolated by chromatography on a silica gel column or
HPLC.
General Procedure for Electrophilic Cyclization of the o-(1-
Alkynyl)benzamides by ICl.3 The alkynylarenecarboxamide (0.30
mmol) was placed into a Schlenk flask and dissolved in CH2Cl2 (3.00
mL) in an argon atmosphere. A solution of ICl (1.2 equiv) in CH2Cl2
(0.50 mL) was added dropwise to the flask by a syringe. The reaction
was stirred at room temperature for 30 min unless otherwise indicated.
The reaction mixture was then diluted with ether (50.0 mL), washed
with satd aq Na2S2O3 (25.0 mL), dried over Na2SO4, and filtered. The
solvent was evaporated under reduced pressure, and the product was
isolated by chromatography on a silica gel column.
(C-5gal), 71.9 (CH2Ph), 71.7 (CH2Ph), 71.6 (C-3gal), 69.9 (C-2gal),
68.8 (C-6man), 68.4 (C-1man), 67.6 (C-4gal), 61.9 (C-6gal), 20.9, 20.8,
20.7, 20.4 (4 × s, 4 × 3H, CH3acetyl) ppm; 15N HMBC (600/61 MHz,
CDCl 3) δ = 215.1 (CN) ppm; ESI-HRMS m/ z calcd for
C57H58INO15Na 1146.2749, found 1146.2758
(2,3,4-Tri-O-benzyl-α-L-fucopyranosyl)acetylene (4).21 Purifi-
cation by flash chromatography (eluent toluene/EtOAc, 30:1)
afforded the title compound (3.72 g, 91%) as a colorless oil: [α]D20
=
−129.3 ( c = 1.00, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ = 7.24−
7.39 (m, 15H, Ph), 4.96 (d, 1H, 2J = 11.5 Hz, CH2Ph), 4.87 (d, 1H, 2J
= 11.8 Hz, CH2Ph), 4.69−4.79 (m, 4H, H-1, 3 × CH2Ph), 4.63 (d,
1H, 2J = 11.5 Hz, CH2Ph), 4.07 (dd, 1H 3J2,1 = 5.8 Hz, 3J2,3 = 9.9 Hz,
H-2), 4.02 (qd, 1H, 3J5,4 = 1.2 Hz, 3 J5,6 = 6.4 Hz, H-5), 3.87 (dd, 1H,
3J3,4 = 2.8 Hz, 3J3,2 = 9.9 Hz, H-3), 3.64 (dd, 1H, 3 J4,5 = 1.2 Hz, 3J 4,3
=
4
2.8 Hz, H-4), 2.47 (d, 1H, J CCH,1 = 2.3 Hz, CCH), 1.13 (d, 3H,
3J6,5 = 6.4 Hz, H-6) ppm; 13C NMR (101 MHz, CDCl3) δ = 139.1,
138.8, 138.5 (3 × CqPh), 128.7, 128.6, 128.4, 128.2, 127.9, 127.8,
127.73, 127.70 (CPh), 80.8 (C-3), 79.6 (CCH), 77.8 (C-4), 76.0
(CCH), 75.3 (C-2), 75.2, 73.6, 73.4 (CH2Ph), 70.0 (C-5), 67.3 (C-
1), 17.1 (C-6) ppm; IR (ATR) ν (cm−1) = 3287, 2924, 1652, 1454,
1073; ESI-HRMS m/z calcd for C29H30O4Na 465.2036, found
465.2036.
N-(2,3,4,6-Tetra-O-acetyl-β-D-galactopyranosyl)-2-ethynyl-C-
(2,3,4,6-tetra-O-benzyl-α-D-mannopyranosyl)benzamide (1).21
Purification by flash chromatography (eluent cyclohexane/EtOAc, 2:1)
2-Iodo-5-nitro-N-(2,3,4,6-tetra-O-acetyl-β-D-galacto-
pyranosyl)benzamide (5). 2,3,4,6-Tetra-O-acetyl-β-D-galacto-
pyranosylamine (1.01 g, 2.91 mmol) was dissolved in anhydrous
THF (20.0 mL). To this solution was added N-ethylmorpholine (0.46
mL, 1.05 equiv), and the resulting mixture was stirred for 10 min. 2-
Iodo-5-nitrobenzoic acid chloride (1.18 g, 1.03 equiv)38 was dissolved
in anhydrous THF (10.0 mL) and precooled to 0 °C before addition
of the above mixture. After complete addition the reaction was stirred
for an additional 30 min. The hydrochloride was filtered off and
washed with THF. The resulting solution was concentrated under
reduced pressure, and the crude product was purified by flash
chromatography (eluent EtOAc/cylohexane, 3:1) to give the product
afforded the title compound (199 mg, 76%) as a colorless oil: [α]D22
=
1
+15.7 (c = 1.00, CHCl3); H NMR, COSY (400 MHz, CDCl3) δ =
7.44−7.20 (m, 24H, Ph, H-3ar, H-4ar, H-5ar, H-6ar), 7.17−7.19 (m, 1H,
NH), 5.37 (pseudo-t, 1H, 3J = 9.2 Hz, H-1gal), 5.31 (dd, 1H, 3J3,4 = 3.4
Hz, 3J4,5 = 0.8 Hz, H-4gal), 5.18 (dd, 1H, 3J1,2 = 9.2 Hz, 3J2,3 = 10.3 Hz,
H-2gal), 5.15 (d, 1H, 3J1,2 = 2.1 Hz, H-1man), 5.09 (dd, 1H, 3J2,3 = 10.3
Hz, 3J3,4 = 3.4 Hz, H-3gal), 4.92 (d, 1H, 2J = 10.6 Hz, CH2Ph), 4.81 (d,
1H, 2J = 12.6 Hz, CH2Ph), 4.77−4.71 (m, 3H, CH2Ph), 4.68 (d, 1H, 2J
= 12.0 Hz, CH2Ph), 4.58 (d, 1H, 2J = 10.6 Hz, CH2Ph), 4.56 (d, 1H, 2J
3
3
= 12.0 Hz, CH2Ph), 4.26 (dd, 1H, J3,4 = 9.3 Hz, J2,3 = 2.9 Hz, H-
3
man), 4.11 (pseudo-t, 1H, 3J3,4 = 9.3 Hz, 3J4,5 = 9.6 Hz, H-4man), 4.05−
4.01 (m, 4H, H-6agal, H-6bgal, H-5-man, H-2-man), 3.88 (dd, 1H, J5,6
=
3
(1.58 g, 87%) as a yellow foam: [α]2D2 = +16.3 (c = 1.00, CHCl3); H
1
3
3
2
4.4 Hz, J = 10.9 Hz, H-6aman), 3.78 (dd, 1H, J5,6 = 1.3 Hz, J = 10.9
Hz, H-6bman), 3.69 (dt, 1H, 3J4,5 = 0.8 Hz, H-5gal), 2.06, 2.01, 2.00, 1.98
(4 × s, 4 × 3H, CH3acetyl) ppm; 13C NMR, HSQC (101 MHz, CDCl3)
δ = 171.3, 170.4, 170.1, 169.8 (4 × COacetyl), 169.6 (COamide),
138.7, 138.6, 138.5, 138.2 (4 × CqPh), 134.2 (C-1), 129.1 (C-2),
128.4, 128.3, 128.2, 128.1, 128.0, 127.8, 127.7, 127.6, 127.5, 127.4 (C-
3ar, C-4ar, C-5ar, C-6ar, CPh), 90.3 (Calkyne-man), 83.2 (Calkyne-ar), 80.6
(C-3man), 79.2 (C-1gal), 77.4 (C-5man), 75.5 (CH2Ph), 75.4 (C-2man),
75.1 (C-4man), 73.6 (CH2Ph), 72.5 (C-5gal), 72.2 (CH2Ph), 71.9
(CH2Ph), 71.1 (C-3gal), 69.7 (C-6man), 68.7 (C-2gal), 67.4 (C-4gal),
67.0 (C-1man), 61.2 (C-6gal), 20.7, 20.6, 20.5, 20.4 (4 × CH3acetyl) ppm;
ESI-HRMS m/z calcd for C57H60NO15 998.3963, found 998.3965.
(1Z,3E)-3-[Iodo(2,3,4,6-tetra-O-benzyl-α-D-manno-
pyranosyl)methylidene]-N-(2,3,4,6-tetra-O-acetyl-β-D-galacto-
pyranosyl)-2-benzofuran-1(3H)-imine (3).21 After flash chroma-
tography (eluent cyclohexane/EtOAc, 2:1) the title compound (202
mg, 94%) was isolated as a colorless oil: [α]2D2 = +32.1 (c = 1.00,
NMR, COSY (400 MHz, CDCl3) δ = 8.15 (d, 1H, 4J4,6 = 2.6 Hz, H-6),
8.11 (d, 1H, 3J3,4 = 8.7 Hz, H-3), 7.96 (dd, 1H, 3J3,4 = 8.7 Hz, 4J4,6 = 2.6
3
3
Hz, H-4), 6.76 (d, 1H, JNH,1 = 9.0 Hz, NH), 5.48 (d, 1H, J3,4 = 2.3
Hz, H-4gal), 5.41 (pseudo-t, 1H, J1,2 = J1,NH = 9.0 Hz, H-1gal), 5.22−
5.15 (m, 2H, H-2gal, H-3gal), 4.19−4.10 (m, 3H, H-6a/bgal, H-5gal), 2.15,
2.14, 2.06, 2.01 (4 × s, 4 × 3H, CH3acetyl) ppm; 13C NMR, HSQC
(101 MHz, CDCl3) δ = 171.7, 170.5, 170.1, 169.9 (4 × COacetyl),
167.2 (COamide), 147.9 (C-5), 142.1 (C-1), 141.8 (C-3), 125.8 (C-
4), 122.5 (C-6), 100.9 (C-2), 78.9 (C-1gal), 72.7 (C-5gal), 70.8 (C-3gal),
68.5 (C-2gal), 67.1 (C-4gal), 61.1 (C-6gal), 21.3, 20.8, 20.7, 20.6 (4 ×
CH3acetyl) ppm; IR (ATR) ν (cm−1) = 3021, 1747, 1694, 1526, 1368,
1351, 1214, 1053, 745; ESI-HRMS m/z calcd for C21H23IN2O12Na
645.0193, found 645.0204.
3
3
N-(2,3,4,6-Tetra-O-acetyl-β-D-galactopyranosyl)-2-ethynyl-C-
(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-5-nitrobenzamide (6). 2-
Iodo-5-nitro-N-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-
benzamide (1.17 g, 1.88 mmol) was dissolved in anhydrous DMF
(33.0 mL) together with bis(triphenylphosphine)palladium(II)
chloride (3.8 mol %) and copper(I) iodide (7.2 mol %). To this
solution as added dropwise anhydrous Et3N (1.83 mL), and the
reaction mixture was stirred for 1 h at room temperature. Then 2-C-
(2,3,4,6-tetra-O-benzyl-α-L-fucopyranosyl)acetylene (1.2 equiv) dis-
solved in anhydrous DMF (33.0 mL) was added, and the solution was
warmed to 60 °C and stirred at this temperature overnight.39 The
resulting dark brown mixture was coevaporated twice with toluene
(30.0 mL). The crude product was redissolved in CHCl3, washed with
water (3 × 30.0 mL), dried over anhydrous Na2SO4, and concentrated
in vacuo. The residue was purified by flash chromatography (eluent
cylohexane/EtOAc, 3:1) to afford the product (1.43 g, 81%) as a green
oil: [α]2D2 = −105.1 (c = 1.00, CHCl3); 1H NMR, COSY, NOESY (500
MHz, CDCl3) δ = 8.79 (d, 1H, 4J2,4 = 2.4 Hz, H-2), 8.25 (dd, 1H, 3J4,5
= 8.5 Hz, 4J2,4 = 2.4 Hz, H-4), 7.98 (d, 1H, 3JNH,1 = 8.9 Hz, NH), 7.60
1
CHCl3); H NMR, COSY, NOESY (400 MHz, CDCl3) δ = 8.79 (d,
3
3
1H, J3,4 = 8.1 Hz, H-3), 7.99 (d, 1H, J5,6 = 7.7 Hz, H-6), 7.67
(pseudo-t, 1H, 3J4,3 = 8.1 Hz, 3J4,5 = 7.4 Hz, H-4), 7.58 (pseudo-t, 1H,
3J4,5 = 7.4 Hz, 3J5,6 = 7.7 Hz, H-5), 7.36−7.09 (m, 20H, Ph), 5.34−5.28
(m, 2H, H-2gal, H-4gal), 5.27 (d, 1H, J1,2 = 8.5 Hz, H-1gal), 5.09 (d,
3
1H, 3J1,2 = 9.1 Hz, H-1man), 5.05 (dd, 1H, 3J2,3 = 9.4 Hz, 3J3,4 = 3.3 Hz,
H-3gal), 4.66−4.58 (m, 4H, CH2Ph), 4.54 (d, 1H, 2J = 12.5 Hz,
CH2Ph), 4.45−4.32 (m, 4H, 3 × CH2Ph, H-5 man), 4.12−4.08 (m, 2H,
H-6agal, H-6aman), 4.05−3.99 (m, 3H, H-2man, H-3man, H-6bman), 3.97
(dd, 1H, 3J6b,5 = 6.8 Hz, 2J = 10.3 Hz, H-6bgal), 3.83 (dd, 1H, 3J3,4 = 2.9
3
3
Hz, J4,5 = 1.8 Hz, H-4man), 3.57 (t, 1H, J5,6 = 6.5 Hz, H-5gal), 2.14,
1.99, 1.91, 1.58 (4 × s, 4 × 3H, CH3acetyl) ppm; 13C NMR, HSQC,
HMBC (101 MHz, CDCl3) δ = 170.4, 170.3, 169.9, 169.8 (4 × C
O
acetyl), 155.9 (C-1), 150.2 (C-3), 138.4, 138.3, 138.2, 138.0 (4 ×
CqPh), 135.7 (C-3a), 132.5 (C-5), 131.5 (C-7a), 131.2 (C-6), 128.5,
E
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3
3
(d, 1H, J4,5 = 8.5 Hz, H-5), 7.41−7.39 (m, 3H, Ph), 7.36−7.28 (m,
o-Anil), 7.32 (t, 1H, Jm,p = 7.3 Hz, p-Ph), 7.29−7.26 (m, 2H, 2 × m-
12H, Ph), 5.44 (d, 1H, J3,4 = 3.3 Hz, H-4gal), 5.43 (pseudo-t, 1H,
Anil), 7.13 (t, 1H, Jm,p = 7.3 Hz, p-Anil) ppm; 13C NMR, HSQC,
3
3
3J1,NH = 3J1,2 = 9.3 Hz, H-1gal), 5.23 (pseudo-t, 1H, 3J1,2 = 3J2,3 = 9.8 Hz,
H-2gal), 5.21 (d, 1H, 3J 1,2 = 5.9 Hz, H-1fuc), 5.15 (dd, 1H, 3 J2,3 = 10.1
HMBC (151 MHz, CDCl3) δ = 151.9 (C-1), 147.6 (C-3), 144.8 (C-
1
Anil), 140.4 (C-1Ph), 135.6 (C-3a), 132.5 (C-7a), 131.9 (C-5), 130.7
(C-6), 130.3 (C-2Ph), 128.6 (C-3Anil), 128.5 (C-4Ph), 127.9 (C-3Ph),
125.3 (C-4Anil), 125.0 (C-4), 124.9 (C-2Anil), 123.9 (C-7), 75.1 (C-I)
ppm; 15N HMBC (600/61 MHz, CDCl3) δ = 223.8 ppm; IR (ATR) ν
(cm−1) = 1681, 1589, 1007, 745; ESI-HRMS m/z calcd for
C21H15INO 424.0198, found 424.0205.
Hz, J = 3.3 Hz, H-3gal), 4.99 (d, 1H, J = 11.5 Hz, CH2Ph), 4.88
3
2
3,4
(d, 1H, 2J = 12.0 Hz, CH2Ph), 4.85 (d, 1H, 2J = 11.9 Hz, CH2Ph), 4.82
(d, 1H, 2J = 12.0 Hz, CH2Ph), 4.78 (d, 1H, 2J = 11.9 Hz, CH2Ph), 4.66
(d, 1H, 2J = 11.5 Hz, CH2Ph), 4.22, (dd, 1H, 3J1,2 = 5.9 Hz, 3J2,3 = 9.8
Hz, H-2fuc), 4.14−4.02 (m, 4H, H-5fuc, H-5gal, 2 × H-6gal), 3.97 (dd,
1H, 3J2,3 = 9.8 Hz, 3J3,4 = 2.7 Hz, H-3fuc), 3.75 (d, 1H, 3J3,4 = 2.7 Hz, H-
4fuc), 2.06, 2.02, 1.99, 1.96 (4 × s, 4 × 3H, CH3acetyl), 1.23 (d, 3H,
3J5,CH3 = 6.4 Hz, CH3fuc) ppm; 13C NMR, HSQC, HMBC (126 MHz,
CDCl3) δ = 171.0, 170.5, 170.3, 169.9 (4 × COacetyl), 164.3 (C
(1Z)-4-Iodo-N,3-diphenyl-1H-isochromen-1-imine (11b).
After purification by flash chromatography (eluent petroleum ether/
EtOAC, 30:1) 948 mg (43%) of the product was obtained as yellow
crystals with spectral properties identical to those reported previously
(additionally, we assigned the 13C shift of 75.8 ppm to the quaternary
carbon connected to the double bond, originally reported as missing):
mp 132.8−134.2 °C (lit.3 mp 131.0−132.0 °C); 1H NMR, COSY (600
O
amide), 147.3 (C-3), 138.8, 138.5, 138.4 (3 × CqPh), 135.9 (C-1),
135.7 (C-5), 128.6, 128.5, 128.4, 128.0, 127.9, 127.8, 127.7, 127.6
(CPh), 126.6 (C-6), 125.6 (C-4), 124.9 (C-2), 98.8 (Calkyne-fuc), 83.8
(Calkyne-ar), 80.5 (C-3fuc), 79.5 (C-1gal), 77.4 (C-4fuc), 75.3 (C-2fuc),
75.1, 73.2, 73.0 (3 × CH2Ph), 72.9 (C-5fuc), 71.0 (C-5gal), 70.8 (C-
3gal), 68.4 (C-2gal), 68.0 (C-1fuc), 67.2 (C-4gal), 61.2 (C-6gal), 20.8, 20.7,
20.7, 20.6 (4 × CH3acetyl), 17.1 (CH3fuc) ppm; IR (ATR) ν (cm−1) =
3400, 3019, 2360, 1748, 1682, 1523, 1368, 1345, 1216, 746; ESI-
HRMS m/ z calcd for C50H52N2O 16Na 959.3215, found 959.3223.
(1Z,3E)-3-[Iodo(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-
methylidene]-N-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-
6-nitro-2-benzofuran-1(3H)-imine (8). Purification of the product
by flash chromatography (eluent cyclohexane/EtOAc, 3:1) afforded
the title compound (508 mg, 91%) as yellow crystals: mp 160.5−162.7
°C; [α]2D2 = +70.8 (c = 1.00, CHCl3); 1H NMR, COSY, NOESY (400
MHz, CDCl3) δ = 8.95 (d, 1H, 3J4,5 = 8.8 Hz, H-4), 8.79, (d, 1H, 4J5,7
= 1.9 Hz, H-7), 8.48 (dd, 1H, 3J4,5 = 8.8 Hz, 4J5,7 = 1.9 Hz, H-5), 7.44−
7.29 (m, 10H, Ph), 7.22−7.19 (m, 2H, o-Ph(C-3fuc)), 7.09−7.06 (m,
2H, m-Ph(C-3fuc)), 7.02−6.98 (m, 1H, p-Ph(C-3fuc)), 5.21 (dd, 1H,
3
4
MHz, CDCl3) δ = 8.40 (dd, 1H, J7,8 = 7.9 Hz, J6,8 = 1.0 Hz, H-8),
3
4
3
7.76 (dd. 1H, J5,6 = 7.9 Hz, J5,7 = 0.7 Hz, H-5), 7.64 (td, 1H, J5,6
=
3J6,7 = 7.9 Hz, 4J6,8 = 1.0 Hz, H-6), 7.61−7.60 (m, 2H, 2 × o-Ph), 7.49
(td, 1H, 3J6,7 = 3J7,8 = 7.9 Hz, 4J5,7 = 0.7 Hz, H-7), 7.42−7.38 (m, 3H, 2
× m-Ph, o-Ph), 7.32−7.29 (m, 2H, 2 × m-Anil), 7.23−7.22 (m, 2H, o-
3
Anil), 7.07 (t, 1H, Jm,p = 7.4 Hz, p-Anil) ppm; 13C NMR, HSQC,
HMBC (151 MHz, CDCl3) δ = 153.2 (C-3), 148.6 (C-1), 145.9 (C-
1
Anil), 135.4 (C-1Ph), 134.8 (C-4a), 133.1 (C-6), 131.1 (C-5), 130.0
(C-2Ph), 130.0 (C-4Ph), 129.3 (C-7), 128.7 (C-3Anil), 128.0 (C-3Ph),
127.5 (C-8), 123.9 (C-4Anil), 123.8 (C-8a), 122.9 (C-2Anil), 75.8 (C-I)
ppm; 15N HMBC (600/61 MHz, CDCl3) δ = 230.0 ppm; IR (ATR) ν
(cm−1) = 1655, 1590, 1085, 693.
N-Methyl-2-(phenylethynyl)benzamide (12). After flash chro-
matography (eluent cyclohexane/EtOAc, 2:1) the product (439 mg,
97%) could be obtained as colorless crystals with spectral properties
identical to those previously reported: mp 106.9−107.6 °C (lit.40 mp
3J1,2 = 8.6 Hz, J2,3 = 10.1 Hz, H-2gal), 5.15 (d, 1H, J1,2 = 2.0 Hz, H-
3
3
1
105.0−107.0 °C); H NMR (400 MHz, CDCl3) δ = 8.04−7.99 (m,
1fuc), 5.09−5.08 (m, 1H, H-4gal), 4.99 (d, 1H, J1,2 = 8.6 Hz, H-1gal),
3
1H), 7.59−7.55 (m, 1H), 7.53−7.49 (m, 2H), 7.44−7.40 (m, 2H),
2
2
4.92 (d, 1H, J = 12.9 Hz, CH2Ph), 4.78 (d, 1H, J = 12.9 Hz,
CH2Ph), 4.76 (dd, 1H, 3J2,3 = 10.1 Hz, 3J3,4 = 3.4 Hz, H-3gal), 4.66 (d,
1H, 2J = 11.9 Hz, CH2Ph), 4.59 (d, 1H, 2J = 11.9 Hz, CH2Ph), 4.55 (d,
1H, 2J = 12.2 Hz, CH2Ph), 4.50 (m, 1H, H-5fuc), 4.39 (d, 1H, 2J = 12.2
Hz, CH2Ph), 4.11 (dd, 1H, 3J3,4 = 3.1 Hz, 3J4,5 = 5.9 Hz, H-4fuc), 4.08−
4.03 (m, 2H, H-6a/bgal), 4.00 (pseudo-t, 1H , 3J 2,3 = 3J3,4 = 3.3 Hz, H-
3
7.39−7.37 (m, 3H), 7.33 (br s, 1H, NH), 3.06 (d, 3H, JCH ,NH = 4.9
3
Hz) ppm.
(1Z,3E)-3-[Iodo(phenyl)methylidene]-N-methyl-2-benzofur-
an-1(3H)-imine (13a). Purification by flash chromatography (eluent
petroleum ether/EtOAc, 7:1) afforded the product (220 mg, 72%) as
light yellow crystals with spectral properties identical to those reported
previously: mp 126.5−129.3 °C (lit.3 mp 122.0−125.0 °C); 1H NMR,
COSY, NOESY (600 MHz, CDCl3) δ = 8.82 (d, 1H, 3J4,5 = 7.9 Hz, H-
3fuc), 3.89 (dd, 1H, J = 2.0 Hz, J2,3 = 3.4 Hz, H-2fuc), 3.02−2.98
3
3
1,2
(m, 1H, H-5gal), 2.14, 2.08, 1.97, 1.79 (4 × s, 4 × 3H, CH3acetyl), 1.64
3
(d, 3H, J5,6 = 6.8 Hz, H-6fuc) ppm; 13C NMR, HSQC, HMBC (101
3
MHz, CDCl3) δ = 170.4, 170.2, 169.9, 169.3 (4 × COacetyl), 153.5
(C-1), 149.2 (C-3),145.0 (C-6) 139.9 (C-3a), 139.1, 138.4, 137.1 (3 ×
CqPh), 132.2 (C-7a), 128.9, 128.8, 128.6, 128.3, 128.0, 127.9, 127.8,
127.5, 127.1 (CPh), 127.2 (C-5) 125.5 (C-4), 119.9 (C-7), 87.8 (C-I),
86.0 (C-1gal), 78.0 (C-2fuc), 75.6 (C-3fuc), 74.6 (C-4fuc), 73.4 (CH2Ph),
73.3 (CH2Ph), 72.0 (CH2Ph), 71.9 (C-5gal), 71.8 (C-5fuc), 70.9 (C-
3gal), 70.3 (C-2gal), 67.3 (C-4gal), 64.4 (C-1fuc), 61.8 (C-6gal), 20.9, 20.8,
20.7, 20.6 (4 × s, 4 × 3H, CH3acetyl), 13.8 (C-6fuc) ppm; 15N HMBC
(600/61 MHz, CDCl3) δ = 220.2 (CN), 363.7 (NO2) ppm; IR
(ATR) ν (cm −1) = 1747, 1710, 1615, 1216, 747; ESI-HRMS m/z
4), 7.85 (d, 1H, J6,7 = 7.6 Hz, H-7), 7.64−7.62 (m, 3H, H-5, 2 × o-
Ph), 7.54 (td, 1H, 3J5,6 = 3J6,7 = 7.6 Hz, 4J4,6 = 0.5 Hz, H-6), 7.40−7.37
3
(m, 2H, 2 × m-Ph), 7.28 (t, 1H, Jm,p = 7.4 Hz, p-Ph), 3.16 (s, 3H,
CH3) ppm; 13C NMR, HSQC, HMBC (151 MHz, CDCl3) δ = 154.6
(C-1), 147.2 (C-3), 140.6 (C-1Ph), 135.9 (C-3a), 131.8 (C-7a), 131.2
(C-5), 130.6 (C-6), 130.2 (C-2Ph), 128.3 (C-4Ph), 127.9 (C-3Ph), 124.9
(C-4), 122.9 (C-7), 73.4 (C-I), 35.1 (CH3) ppm; 15N HMBC (600/61
MHz) δ = 209.7 ppm; IR (ATR) ν (cm−1) = 1708, 1613, 1020, 759;
ESI-HRMS m/z calcd for C16H13INO 362.0042, found 362.0056.
(1Z)-4-Iodo-N-methyl-3-phenyl-1H-isochromen-1-imine
(13b).3 Purification by flash chromatography (eluent petroleum ether/
EtOAc, 7:1) afforded the product (26.0 mg, 8%) as a yellow solid.
calcd for C50H51IN O16Na 1085.2181, found 1085.2220.
2
N-Phenyl-2-(phenylethynyl)benzamide (9). Recrystallization
from ethyl acetate gave 3.22 g (69%) of the product as colorless
crystals with spectral properties identical to those previously reported:
mp 154.4−156.6 °C (lit.39 mp 151.0−153.0 °C); 1H NMR (400 MHz,
CDCl3) δ = 9.21 (br s, 1H, NH), 8.16−8.13 (m, 1H), 7.68−7.64 (m,
3H), 7.52−7.47 (m, 4H), 7.41−7.32 (m, 5H), 7.14 (t, 1H, J = 7.4 Hz).
(1Z,3E)-3-[Iodo(phenyl)methylidene]-N-phenyl-2-benzofur-
an-1(3H)-imine (11a). Purification by flash chromatography (eluent
petroleum ether/EtOAc, 30:1) afforded 1.19 g (54%) of the product as
yellow crystals with spectral properties identical to those previously
reported (additionally, we assigned the 13C shift of 75.1 ppm to the
quaternary carbon connected to the double bond, originally reported
−
Crystals suitable for X-ray formed with I3 as the counterion: 1H
NMR, COSY, NOESY (600 MHz, CDCl3) δ = 8.12 (d, 1H, 3J8,7 = 8.9
Hz, H-8), 7.69−7.68 (m, 3H, H-5, 2 × o-Ph), 7.56 (t, 1H, 3J5,6 = 3J6,7
8.9 Hz, H-6), 7.49−7.45 (m, 3H, 2 × m-Ph, p-Ph), 7.40 (t, 1H, 3J6,7
=
=
3J7,8 = 8.9 Hz, H-7), 3.17 (s, 3H, CH3) ppm; 13C NMR, HSQC,
HMBC (151 MHz, CDCl3) δ = 153.4 (C-3), 150.8 (C-1), 136.2 (C-
1Ph), 133.9 (C-4a), 132.4 (C-6), 131.2 (C-5), 129.9 (C-4Ph), 129.9 (C-
2Ph), 129.1 (C-7), 128.2 (C-3Ph), 126.3 (C-8), 123.9 (C-8a), 75.5 (C-
I), 33.8 (CH3) ppm; 15N HMBC (600/61 MHz) δ = 282.6 ppm; IR
(ATR) ν (cm−1) = 1662, 1602, 1078, 754.
2-(Cyclohex-1-en-1-ylethynyl)-N-phenylbenzamide (14). Pu-
rification by HPLC (eluent isocratic MeCN/H2O, 95:5) afforded the
product (189 mg, 41%) as yellow crystals with spectral properties
identical to those previously reported: mp 97.0−98.3 °C (lit.3 mp
3
1
as missing): mp 96.0−97.0 °C (lit. mp 97.0−99.0 °C); H NMR,
COSY (600 MHz, CDCl3) δ = 8.89 (d, 1H, 3J4,5 = 7.8 Hz, H-4), 8.08
3
3
3
(d, 1H, J6,7 = 7.7 Hz, H-7), 7.73 (t, 1H, J4,5 = J5,6 = 7.8 Hz, H-5),
7.68−7.62 (m, 3H, H-6, 2 × o-Ph), 7.40−7.38 (m, 4H, 2 × m-Ph, 2 ×
1
99.0−100.0 °C); H NMR (400 MHz, CDCl3) δ = 9.33 (br s, 1H,
F
dx.doi.org/10.1021/jo3017378 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
NH), 8.17−8.14 (m, 1H), 7.69−7.67 (m, 2H), 7.55−7.52 (m, 1H),
7.47−7.42 (m, 2H), 7.39−7.35 (m, 2H), 7.16−7.12 (m, 1H), 6.29−
6.28 (m, 1H), 2.21−2.14 (m, 4H), 1.70−1.58 (m, 4H) ppm.
(4) Robin, S.; Rousseau, G. Tetrahedron 1998, 54, 13681.
(5) Hashmi, A. S. K.; Hutchings Graham, J. Angew. Chem., Int. Ed.
2006, 45, 7896.
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́
Cuenca, A. B. Org. Lett. 2010, 12, 1900.
(1Z,3E)-3-[Cyclohex-1-en-1-yl(iodo)methylidene]-N-phenyl-
2-benzofuran-1(3H)-imine (15a). Purification by HPLC (eluent
MeCN/H2O, 90:10, to 100% MeCN) afforded the product (32.5 mg,
16%) as a yellow oil with spectral properties identical to those
previously reported:3 1H NMR, COSY, NOESY (600 MHz, CDCl3) δ
= 7.97−7.95 (m, 1H, H-7), 7.79−7.77 (m, 1H, H-4), 7.67−7.65 (m,
2H), 7.51−7.49 (m, 2H, H-5, H-6), 7.42−7.39 (m, 2H, m-Ph) 7.19 (t,
1H, 3Jm,p = 7.3 Hz, p-Ph), 6.11−6.10 (m, 1H, H-2CyH), 2.33−2.26 (m,
2H, H-6CyH), 2.18−2.17 (m, 2H, H-3CyH), 1.86−1.82 (m, 2H, H-
(7) Mehta, S.; Waldo, J. P.; Larock, R. C. J. Org. Chem. 2009, 74,
1141.
(8) Chen, D.; Song, G.; Jia, A.; Li, X. J. Org. Chem. 2011, 76, 8488.
(9) Jithunsa, M.; Ueda, M.; Miyata, O. Org. Lett. 2011, 13, 518.
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77, 1572.
5
CyH), 1.75−1.71 (m, 2H, H-4CyH) ppm; 13C NMR, HSQC, HMBC
(151 MHz, CDCl3) δ = 152.2 (C-1), 149.6 (C-3), 144.9 (C-1Anil),
(12) Zhao, P.; Chen, D.; Song, G.; Han, K.; Li, X. J. Org. Chem. 2011,
77, 1579.
136.7 (C-1CyH), 133.8 (C-3a), 132.7 (C-7a), 132.1 (C-5), 130.7 (C-
2
CyH), 129.8 (C-6), 128.9 (C-3Anil), 125.4 (C-4Anil), 125.2 (C-2Anil);
(13) Khan, M. W.; Kundu, N. G. Synlett 1997, 12, 1435.
(14) Larock, R. C.; Yum, E. K.; Refvik, M. D. J. Org. Chem. 1998, 63,
7652.
(15) Hiroya, K.; Itoh, S.; Sakamoto, T. J. Org. Chem. 2004, 69, 1126.
(16) Sakai, N.; Annaka, K.; Fujita, A.; Sato, A.; Konakahara, T. J. Org.
Chem. 2008, 73, 4160.
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2009, 121, 8396.
(18) Bian, M.; Yao, W.; Ding, H.; Ma, C. J. Org. Chem. 2010, 75, 269.
(19) Parvatkar, P. T.; Parameswaran, P. S.; Tilve, S. G. Chem.Eur. J.
2012, 18, 5460.
124.0 (C-7), 122.5 (C-4), 81.7 (C-I), 27.9 (C-6CyH), 25.9 (C-3CyH),
22.7 (C-5CyH), 21.9 (C-4CyH) ppm; 15N HMBC (600/61 MHz) δ =
226.5 ppm; IR (ATR) ν (cm−1) = 1687, 1651, 1006, 749; ESI-HRMS
m/z calcd for C21H19INO 428.0511, found 428.0505.
(1Z)-3-(Cyclohex-1-en-1-yl)-4-iodo-N-phenyl-1H-isochro-
men-1-imine (15b). Purification by HPLC (eluent MeCN/H2O,
90:10, to 100% MeCN) afforded the product (115 mg, 53%) as a
yellow oil with spectral properties identical to those previously
reported:3 1H NMR, COSY, NOESY (600 MHz, CDCl3) δ = 8.33
(dd, 1H, 3J7,8 = 7.9 Hz, 4J6,8 = 0.8 Hz, H-8), 7.66 (d, 1H, 3J5,6 = 7.9 Hz,
H-5), 7.58 (td, 1H, 3J5,6 = 3J6,7 = 7.9 Hz, 4J6,8 = 0.8 Hz, H-6), 7.43 (td,
1H, 3J6,7 = 3J7,8 = 7.9 Hz, 4J5,7 = 0.5 Hz, H-7), 7.37−7.35 (m, 2H, 2 ×
(20) K. Banerjee, A.; S. Laya, M.; V. Cabrera, E. Curr. Org. Chem.
2011, 15, 1058.
(21) Wiebe, C.; Schlemmer, C.; Weck, S.; Opatz, T. Chem. Commun.
3
m-Ph), 7.21−7.20 (m, 2H, 2 × o-Ph), 7.11 (t, 1H, Jm,p = 7.4 Hz, p-
Ph), 6.16−6.15 (m, 1H, H-1CyH), 2.20−2.18 (m, 2H, H-3CyH), 2.17−
2.16 (m, 2H, H-6CyH), 1.71−1.67 (m, 2H, H-5CyH), 1.65−1.61 (m, 2H,
H-4CyH) ppm; 13C NMR, HSQC, HMBC (151 MHz, CDCl3) δ =
155.6 (C-3), 148.9 (C-1), 146.1 (C-1Anil), 135.2 (C-2CyH), 134.9 (C-
4a), 133.7 (C-1CyH), 132.9 (C-6), 131.3 (C-5), 128.7 (C-7), 128.6 (C-
2011, 47, 9212.
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4467.
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1456.
3
Anil), 127.4 (C-8), 123.8(C-4Anil), 123.7 (C-8a), 122.9 (C-2Anil), 73.9
(C-I), 26.4 (C-3CyH), 25.0 (C-6CyH), 22.3 (C-5CyH), 21.6 (C-4CyH
)
ppm; 15N HMBC (600/61 MHz) δ = 229.1 ppm; IR (ATR) ν (cm−1)
= 1652, 1591, 1025, 755; ESI-HRMS m/z calcd for C21H19INO
428.0511, found 428.0497.
(29) Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys.
1980, 72, 650.
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ASSOCIATED CONTENT
* Supporting Information
General methods, spectra for all compounds, final energies and
coordinates from DFT calculations, and crystallographic
information files (CIFs) of 8, 11a, 11b, 13a, and 13b. This
material is available free of charge via the Internet at http://
pubs.acs.org.
■
S
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AUTHOR INFORMATION
Corresponding Author
*E-mail: opatz@uni-mainz.de (T.O.); straub@oci.uni-
heidelberg.de (B.F.S.).
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We thank Dr. J. C. Liermann (University of Mainz) for NMR
spectroscopy and Prof. Paul Margaretha (University of
Hamburg) for helpful discussions. This work was supported
by the German Federal Ministry for Education and Research
(T.O., Grant 0315139).
NOTE ADDED IN PROOF
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After the submission of our manuscript, a related paper was
submitted by Larock and coworkers. Mehta, S.; Yao, T.; Larock,
R. C. J. Org. Chem. doi:10.1021/jo301958q.
REFERENCES
(1) Yao, T.; Larock, R. C. J. Org. Chem. 2003, 68, 5936.
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Tetrahedron Lett. 2004, 45, 2063.
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(3) Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70, 1432.
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