Full text of DOI:10.1016/S0040-4020(00)00773-0

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 8473±8480
Hydroboration and Suzuki±Miyaura Coupling Reactions with the
Electronically Modulated Variant of an Ynamine: The Synthesis
of (E)-b-Arylenamides
*
Bernhard Witulski, Nicole Buschmann and Uwe Bergstr aÈ ûer
Fachbereich Chemie, Universit aÈ t Kaiserslautern, Erwin Schr oÈ dinger Straûe, D-67663 Kaiserslautern, Germany
Received 7 August 2000; accepted 29 August 2000
AbstractÐThe ®rst hydroboration of an 1-alkynylamideÐthe electronically modulated variant of an ynamineÐis described. This hydro-
boration in combination with a Suzuki±Miyaura cross-coupling reaction with aryl bromides or aryl iodides allows a ¯exible synthesis of (E)-
0
b-arylenamides and 3-(2 -amidovinyl)indoles with high degree of molecular diversity. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
subsequent cross-coupling reaction with organic halides
provided access to stereode®ned b-arylvinyl sulphides.
8
The sequence of a chemo- and regioselective monohydro-
boration of alkynes followed by a palladium-catalysed
cross-coupling reaction with aryl or vinyl halides
However, neither a hydroboration nor the use of 1-alkynyl-
amines 1 (ynamines) in Suzuki±Miyaura cross-coupling
reactions has been reported so far. This lack of attention is
presumably attributed to the electron richness of the
ynamine carbon±carbon triple bond, that is responsible for
the extraordinary reactivity and extreme sensitivity towards
hydrolysis of these otherwise attractive building blocks for
(
¯
Suzuki±Miyaura coupling) provides a highly ef®cient and
exible access to vinyl aryls or conjugated dienes via the
1
formation of a new carbon±carbon bond. The usefulness of
this method for the synthesis of natural products and drug
related targets arises from the fact that many functional
groups are tolerated by this two step procedure, and that
9
organic chemistry.
cross-couplings proceed without the loss of a prede®ned
stereochemistry.
alkynes have been subjected to the Suzuki±Miyaura cross-
coupling protocol, only a few reports appeared using
synthetically pro®table alkynes bearing a heteroatom
adjacent to the carbon±carbon triple bond.
2
Although numerous functionalised
Recently we described a practicable synthesis for N-func-
tionalised 1-alkynylamides (ynamides) of type 2 and 3, a
new set of electronically tuneable alkynes whose protecting
groups (PG) serve both in masking the amine functionality
and in tuning the electron density, and hence the reactivity,
1
0
of the adjacent carbon±carbon triple bond (Scheme 1).
Monohydroborations of 1-halogeno-1-alkynes proceeded
regio- and stereoselectively to give the corresponding (Z)-
These electronically modulated variants of ynamines have
been used by us in intramolecular Pauson±Khand reactions
for the construct of proline derivatives, as well as in
3
-halogeno-1-alkenyl boranes, that have been used for the
11
1
synthesis of (Z)-1-halogeno-1-alkenes, 1,1-dihalogeno-1-
4
rhodium- and ruthenium-catalysed crossed alkyne cyclo-
trimerisations for the chemo- and regioselective synthesis
5
6
alkenes, and (Z)-1-alkenylboronic esters Ðeach one
being a versatile building block for transition metal
catalysed cross-coupling reactions. The direct hydrobora-
tion of 1-alkoxy-1-alkynes with catecholborane afforded
1
2
of highly substituted indolines. Given our interest in the
chemistry and reactivity of N-functionalised 1-alkynyl-
amides, we considered their application as building blocks
in Suzuki±Miyaura cross-coupling reactions for the forma-
tion of stereode®ned (E)-b-arylenamides. b-Arylenamides
are important structural features of a wide variety of organic
molecules with signi®cance to organic synthesis and
medicinal chemistry, and they can be found as a structural
motif in natural products like tuberine, erbstatin and asper-
2-alkoxyvinyl boronic esters that were coupled with aryl
halides to the corresponding b-arylvinyl ethers with reten-
7
tion of con®guration of the ole®nic component. Similarly,
the catalytic hydroboration of 1-alkylthio-1-alkynes and the
1
3
gillamide. b-Arylenamides have been prepared by a
number of different methods and mostly multistep pro-
Keywords: ynamines; hydroboration; catalysis; palladium; 1-alkynyl-
amides; cross-coupling reaction.
1
4
cedures were employed. However, two metal assisted
*
3
Corresponding author. Tel.: 149-631-205-2032; fax: 149-631-205-
921; e-mail: witulski@rhrk.uni-kl.de
couplings for the formation of b-arylenamides were
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00773-0

8
474
B. Witulski et al. / Tetrahedron 56 (2000) 8473±8480
Scheme 1.
reported including the direct vinylic substitution of
b-arylvinyl bromides by phthalimides and the Heck
arylation of N-vinyloxyazolone.
The direct hydroboration of 7 with catecholborane (8) gave
only the monohydroboration product 9 with E-con®guration
1
5,16
1
as indicated by a doublet at dˆ8.05 (Jˆ16.55 Hz) in the H
NMR spectra recorded in CDCl . However, the isolation of
3
Herein we report the ®rst introduction of an enamide group
into arenes based on a Suzuki±Miyaura cross-coupling
protocol using an ynamide as a CHvCH±N(PG) building
vinylborane 9 turned out to be less favourable for the
anticipated cross-coupling reactions due to its instability
and dif®culties of storage and puri®cation. Therefore, a
one-¯ask procedure was envisaged.
2
block.
The optimum conditions for carrying out the cross-coupling
reactions in a two-step one-¯ask procedure along Scheme 3
started with the hydroboration of alkyne 7 with catechol-
borane (8) (1±1.5 equiv.) in THF at 708C as described
above. The in situ formed organoborane complex 9
(1.5 equiv.) was then coupled at 70±808C with an aryl
iodide or aryl bromide after addition of a catalytic amount
of Pd(PPh3)4 (10 mol%) and freshly powdered NaOH
(3 equiv.). Cross-coupling reactions could also be achieved
when an aqueous 3 M NaOH solution was used as base,
however in some cases the yields were lower and side
Results and Discussion
The synthesis of ynamide 7 needed for the hydroboration
and cross-coupling studies relied on our recently developed
approach to N-functionalised 1-alkynylamides via the direct
1
0,17
N-ethynylation with alkynyliodonium salts (Scheme 2).
Ynamide 6 was obtained in gram quantities in 75% yield
after adding 5 to the lithium salt of the amide 4 in toluene at
room temperature. Following its isolation, a desilylation
with TBAF in wet THF resulted in the desired 1-alkynyl-
amide 7 in 96% yield. Unlike its N,N-dialkyl-substituted
analogues, ynamide 7 is easy to handle, withstands aqueous
work-up procedures as well as chromatographic puri®cation
on silica gel. This atypical stability towards hydrolysis
strongly indicates that 7 is an electron de®cient variant of
an ynamine.
products resulting from
dominant.
a
protodeboration became
Electron de®cient as well as electron rich aryl iodides were
ef®ciently coupled using this protocol in overall yields of
61±80% (Table 1). In all cases the cross-coupling reactions
proceeded with the retention of con®guration of the inter-
mediate vinylborane 9 giving exclusively the corresponding
(E)-b-arylenamides 11a±d. Suzuki±Miyaura cross-
couplings were less ef®cient for the aryl bromides 10c and
10e, however they still could be accomplished in moderate
to good yields (Table 1, entry 3 and 5).
Hydroboration of 7 with catecholborane (8) (1±1.5 equiv.)
in THF at 708C for 2 h proceeded chemo- and regio-
selectively to the (E)-vinylborane 9. The completion of
the reaction was con®rmed by observing the disappearance
of alkyne 7 by TLC and the stereochemical outcome of the
reaction was examined by the isolation of 9 via bulb to bulb
Finally we applied this cross-coupling protocol to the
0
2
3
1
18
distillation (225±2608C, 10 Torr) and H NMR analysis.
synthesis of 3-(2 -amidovinyl)indoles 15, compounds of
Scheme 2. Reagents and conditions: (i) nBuLi (1.1 equiv.), toluene, 08C, then addition of 5 (1.2 equiv.); (ii) TBAF, wet THF, 08C, 20 min.
Scheme 3. Reagents and conditions: (i) catecholborane (8) (1.5 equiv.), THF, 708C, 2 h; (ii) aryl halogenide (XˆBr, I), NaOHsolid (3 equiv.); Pd(PPh
3 4
)
(
10 mol%), 808C, 4 h, sealed tube.

B. Witulski et al. / Tetrahedron 56 (2000) 8473±8480
Table 1. Aminoethenylation of arenes according to Scheme 3
8475
2
Scheme 4. Reagents and conditions: (i) I
2
, KOH, DMF, 208C, 0.45 h (100%); (ii) R ˆBoc: Boc
2
O, Et
3
N, DMAP (10 mol%), CH
2
Cl , 208C, 0.5 h, (88±98%);
2
2
2
R ˆSO Tol: TosCl, NaOH, CH
Cl
2 2
, 208C, 5 h, (60±80%); (iii) 7 and catecholborane (8), THF, 708C, 2 h, then addition of 14, NaOHsolid (3 equiv.), Pd(PPh
3
)
4
(
10 mol%), 708C, 10±40 h, sealed tube, (58±84%).
synthetic and medicinal interest since they possess the struc-
tural feature of dehydrotryptamin, serotonin and bufotenin.
Furthermore 3-(2 -amidovinyl)indoles 15 might be useful as
4p-electron components in Diels±Alder reactions for the
19
formation of carbazoles.
more pronounced electron-withdrawing character of the
N-tosyl group enhanced the rate of reaction for the oxidative
addition of the palladium catalyst into the indoyl±iodine
bond and therefore favouring the overall catalytic process.
0
Suitable crystals for X-ray diffraction studies were
obtained from indole 15d after crystallisation from CHCl /
pentane at 2208C. The indole ring of 15d is approximately
planar (mean deviation from best planeˆ1.6 pm). The
3
-Iodoindoles 14 were obtained by direct iodination of the
3
2
0
indoles 12a and 12b followed by protecting the N-1 position
at the indole nucleus. N-protection was necessary to allow
the anticipated cross-coupling reactions (Scheme 4). The
products 15a±d were obtained in yields of 58±84% after
isolation and puri®cation with column chromatography
following the above described one ¯ask procedure of the
Suzuki±Miyaura cross-coupling reaction (Table 2). Again
in all cases the desired 3-vinylindoles 15 were received with
complete retention of the con®guration of the stereo-
chemistry of the initial vinyl borane complex 9. Notably,
cross-coupling reactions with the N-tosylated 3-iodoindoles
0
Table 2. Aminoethenylation of 3-iodo-1H-indoles 14 to 3-(2 -amido-
vinyl)indoles 15 (all reactions were carried out in sealed Schlenk tubes
using 1.5 equiv. of 9 with respect to the amount of 7, 10 mol%
3 4
Pd(PPh ) , and 3 equiv. of solid NaOH)
1
2
R
Entry
14
R
Conditions
15
Yield (%)
1
2
3
4
14a
14b
H
H
Boc
THF, 708C, 40 h 15a
58
71
74
84
SO
2
Tol THF, 708C, 20 h 15b
THF, 708C, 26 h 15c
14c OMe Boc
14d OMe SO
14b and 14d were faster than those having a N-Boc protect-
ing group at the indole nucleus (14a and 14c). Obviously the
2
Tol THF, 708C, 10 h 15d

8
476
B. Witulski et al. / Tetrahedron 56 (2000) 8473±8480
2
0
Figure 1. Molecular structure of 15d. Selected bond lengths (pm) and angles (8): N1±C2 141.5(3), C2±C3 135.3(4), C3±C31 145.8(4), C31±C32 130.0(3),
C32±N2 141.3(3) N2±C41 146.6(3); N1±C2±C3 109.7(3), C2±C3±C3a 107.1(2), C2±C3±C31 130.5(3), C3±C31±C32 127.2(3), C31±C32±N2 125.5(3),
C32±N2±C41 118.2(2).
conformation of the diene unit C2vC3±C31vC32 is s-cis-
synclinal with a torsional angle of 232.18, the bond length
of the central C3±C31 bond has the typical butadiene value
of 145.8(4) pm. The bond angles C2±C3±C31 (130.58) and
C3±C31±C32 (127.28) are relatively large. The methylene
group of the benzyl substituent at N2 is nearly coplanar with
the alkene unit, the torsional angle C41±N2±C32±C31
being 23.98. The bond length N2±C32 [141.3(3) pm] are
in a comparable region with the endocyclic indole nitrogen/
carbon atom bond lengths (see Fig. 1).
Spectra were recorded as thin ®lms or in KBr pellets.
NMR spectra were recorded in CDCl as solvent on Bruker
3
AMX 400 and Bruker AC 200 spectrometers with either
TMS or solvent as internal reference; J-values are given
in Hz with an accuracy of ^0.2. Assignments were
supported by DEPT spectra. Elemental analyses were
carried out on a Perkin±Elmer elemental analyser EA 240
and on a Perkin±Elmer 2400 CHN elemental analyser. Mass
spectra were recorded under EI conditions on a Finnigan
MAT 90 spectrometer. The syntheses of the 3-iodo-1H-
indoles 13a±b and 14a±d were carried out in analogy to
2
3
published methods.
Conclusion
N-Benzyl-N-trimethylsilanylethynyl-4-methylbenzene-
sulphonamide (6). N-benzyl-4-methylbenzenesulphon-
amide (4) (1.51 g, 5.78 mmol) was dissolved in toluene
(50 mL) and nBuLi (4.1 mL, 1.6 M in hexane) was added
at 08C via syringe. After 20 min, the alkynyliodonium salt 5
(3.12 g, 6.92 mmol) was added to the reaction mixture in
small portions and thereafter stirred overnight at room
temperature. The reaction mixture was ®ltered through a
plug of silica gel and the crude product puri®ed by chroma-
In summary, by taking advantage of the electronic de®cient
properties of 1-alkynylamide 7 the ®rst hydroboration of an
ynamine became possible. The combination of hydrobora-
tion and Suzuki±Miyaura cross-coupling reaction in a one
¯
molecular diversity to (E)-b-arylenamides 11 and to the
ask procedure afforded a convenient access with high
0
corresponding 3-(2 -amidovinyl)indoles 15, compounds
with potent interest in synthetic and medicinal chemistry.
Applications of this strategy in more elaborated syntheses of
indole alkaloids are part of our current research programs.
tography (SiO
ynamide 6 (1.55 g, 75%) as a colourless solid, mp 58±608C.
, hexanes:diethyl etherˆ9:1 (v/v)) yielding
2
1
H NMR (400 MHz): dˆ7.72 (d, Jˆ8.3 Hz, 2H), 7.3 (m,
1
H), 4.47 (s, 2H), 2.43 (s, 3H), 0.08 (s, 9H); C NMR
3
7
Experimental
(100 MHz): dˆ144.5 (s), 134.6 (s), 134.3 (s), 129.5 (d),
28.9 (d), 128.3 (d), 128.2 (d), 127.8 (d), 95.3 (s), 73.9
(s), 55.4 (t), 21.6 (q), 0.1 (q); IR (KBr): nˆ3062, 3013,
109, 1597, 1496, 1363, 1374, 1253, 1188, 1176, 1090,
1049, 946 cm ; MS (EI), m/z (%): 357 (M , 10), 202 (6),
155 (16), 149 (9), 91 (100), 73 (10); Anal. Calcd. for
1
General procedures
2
2
1
1
Reactions requiring anhydrous conditions were performed
using ¯ame-dried glassware and conducted under an
atmosphere of nitrogen. Anhydrous solvents were prepared
in accordance with standard protocols. Compounds were
puri®ed by chromatography on silica gel 60 (63±230
mesh). Melting points were measured on a B uÈ chi melting-
point apparatus and are uncorrected. IR spectra were
recorded on a Perkin±Elmer FT-IR spectrometer 16PC.
C H23NO SSi (357.542): C, 63.83; H, 6.48; N, 3.92.
19 2
Found: C, 63.45, H, 6.45, N, 3.83.
N-Benzyl-N-ethynyl-4-methylbenzenesulphonamide (7).
Ynamide 6 (552 mg, 1.54 mmol) was dissolved in oxygen
free wet THF (50 mL) and treated at 08C with TBAF (2 mL

B. Witulski et al. / Tetrahedron 56 (2000) 8473±8480
8477
of a 1 M solution in THF). The progress of the desilylation
was followed by TLC and after 10 min diethyl ether and
brine were added. The organic phase was separated, dried
C, 71.08; H, 5.72; N, 3.45. Found: C, 70.82, H, 5.44, N,
3.38.
with MgSO and after evaporation of the solvent the crude
4
N-Benzyl-N-[(E)-2-(4-methoxyphenyl)ethenyl]-4-methyl-
benzenesulphonamide (11b). Prepared according to the
general procedure using 7 (73 mg, 0.26 mmol), 8
product was puri®ed by column chromatography (SiO2,
hexanes:diethyl etherˆ9:1) yielding ynamide 7 (423 mg,
1
6%) as a colourless solid, mp 95±968C. H NMR
9
(0.38 mL of a 1 M solution in THF) and additional THF
(2 mL). Thereafter NaOH (21 mg, 0.51 mmol), Pd(PPh3)4
(20 mg, 0.02 mmol), 4-iodoanisole (10b) (40 mg,
0.17 mmol) and THF (3 mL) were added. The crude product
was chromatographed on silica gel (hexanes:diethyl
etherˆ95:5 (v/v)) to afford 11b (41 mg, 61%) as colourless
(
7
200 MHz): dˆ7.82 (d, Jˆ8.4 Hz, 2H), 7.32±7.40 (m,
1
3
H), 4.55 (s, 2H), 2.74 (s, 1H), 2.51 (s, 3H); C NMR
(
1
100 MHz): dˆ144.7 (s), 134.6 (s), 134.2 (s); 129.7 (d),
28.6 (d), 128.5 (d), 128.3 (d), 127.7 (d), 76.2 (s), 59.7
(
2
1
d), 55.2 (t), 21.6 (q); IR (KBr): nˆ3277, 3062, 2928,
134, 1596, 1495, 1452, 1431, 1359, 1189, 1171, 1088,
048, 931 cm ; MS (EI), m/z (%): 285 (M , 10), 155
solid; mp 119±1208C; R 0.37 (hexanes:ethyl acetateˆ8:2
f
2
1
1
1
(v/v)). H NMR (400 MHz): dˆ7.69±7.71 (m, 2H), 7.23±
(
(
5
35), 130 (14), 91 (100); Anal. Calcd. for C H NO S
1
285.36): C, 67.35; H, 5.30; N, 4.91. Found: C, 67.48, H,
.16, N, 4.83.
7.33 (m, 8H), 7.09±7.11 (m, 2H), 6.76±6.79 (m, 2H), 5.62
(d, Jˆ14.6 Hz, 1H), 4.61 (s, 2H), 3.76 (s, 3H), 2.41 (s, 3H);
6
15
2
1
3
C NMR (100 MHz): dˆ158.4 (s), 143.9 (s), 135.9 (s),
135.4 (s), 129.9 (d), 128.8 (s), 128.6 (d), 127.4 (d), 127.0
(d), 126.9 (d), 126.5 (d), 124.9 (d), 114.0 (d), 112.2 (d), 55.3
tert-Butyl 5-bromo-1H-indole-1-carboxylate (10e). 5-
Bromoindole (1.00 g, 5.10 mmol) was dissolved in
(q), 49.5 (t), 21.5 (q); IR (neat): nˆ3033, 2925, 1644, 1608,
2
1
1512, 1454, 1356, 1249, 1163, 1091, 1031, 943, 807 cm ;
CH Cl
2
(100 mL) and thereafter Boc O (1.34 g,
2
2
1
MS (EI), m/z (%): 393 (M , 21), 238 (38), 121 (6), 91 (100);
6.15 mmol) and DMAP (124 mg, 1.02 mmol) were added.
The mixture was stirred at room temperature overnight. The
solvent was evaporated and the crude product was chroma-
Anal. Calcd. for C H NO S (393.50): C, 70.20; H, 5.89; N,
2
3.56. Found: C, 69.96, H, 5.67, N, 3.45.
3
23
3
tographed over silica gel (SiO , hexanes:diethyl etherˆ8:2
2
(
v/v)) to afford 10e (1.37 g, 91%) as colourless solid, mp
H
N-[(E)-2-(1,3-Benzodioxol-5-yl)ethenyl)-N-benzyl-4-
methylbenzenesulphonamide (11c). From 4-bromo-1,2-
methylenedioxybenzene (10c): Prepared according to the
1
5
5±578C, R 0.76 (hexanes:diethyl etherˆ8:2 (v/v).
f
NMR (400 MHz): dˆ8.01 (d, Jˆ8.8 Hz, 1H), 7.68 (d,
Jˆ1.9 Hz, 1H), 7.58 (d, Jˆ3.7 Hz, 1H), 7.40 (dd,
Jˆ8.8 Hz, Jˆ1.9 Hz, 1H), 6.50 (d, Jˆ3.7 Hz, 1H), 1.66
general procedure using
7 (61 mg, 0.21 mmol), 8
(0.32 mL of a 1 M solution in THF) and THF (2 mL). There-
after NaOH (17 mg, 0.42 mmol), Pd(PPh3)4 (16 mg,
0.01 mmol), 4-bromo-1,2-methylenedioxybenzene (10c)
(0.017 mL, 0.14 mmol) and additional THF (3 mL) were
added. The crude product was chromatographed on silica
gel (hexanes:diethyl etherˆ95:5 (v/v)) to afford 11c (32 mg,
56%) as colourless solid.
1
3
(
s, 9H); C NMR (100 MHz): dˆ149.8 (s), 134.3 (s),
1
32.7 (d), 127.4 (d), 123.9 (d), 117.0 (d), 116.4 (s), 106.9
1
d), 84.5 (s), 28.6 (q); MS (EI), m/z (%): 295 (M , 94), 238
100), 224 (75), 196 (96).
(
(
N-[(E)-2-(4-Acetylphenyl)ethenyl]-N-benzyl-4-methyl-
benzenesulphonamide (11a). General procedure:
Ynamide 7 (63 mg, 0.22 mmol) was introduced into a
Schlenk tube with screw cap and THF (2 mL) was added.
Under nitrogen atmosphere catechol borane (8) (0.33 mL of
a 1 M solution in THF) was introduced via syringe and the
sealed tube kept at 70±808C for 2 h. Thereafter, NaOH
From 4-iodo-1,2-methylenedioxybenzene (10d): Prepared
according to the general procedure using 7 (70 mg,
0.24 mmol), 8 (0.37 mL of a 1 M solution in THF) and
THF (2 mL). Thereafter NaOH (20 mg, 0.49 mmol),
Pd(PPh ) (19 mg, 0.02 mmol), 4-iodo-1,2-methylenedioxy-
3
4
(
4
17.6 mg, 0.44 mmol), Pd(PPh3)4 (17 mg, 0.02 mmol),
-iodoacetophenone (10a) (37 mg, 0.15 mmol) and addi-
benzene (10d) (40 mg, 0.16 mmol) and additional THF
(3 mL) were added. The crude product was chromato-
graphed on silica gel (hexanes:diethyl etherˆ95:5 (v/v)) to
tional THF (3 mL) were added and the mixture kept for
additional 4 h at 808C. After cooling diethyl ether (20 mL)
and NaOH (3N, 20 mL) were added and the mixture washed
with brine. The organics were dried with MgSO4 and
concentrated. The crude product was chromatographed on
silica gel (hexanes:diethyl etherˆ95:5 (v/v)) to afford 11a
afford 11c (50 mg, 75%) as colourless solid; mp 163±
1
1648C; Rf 0.32 (hexanes:ethyl acetateˆ8:2 (v/v)).
H
NMR (400 MHz): dˆ7.70 (d, Jˆ8.4 Hz, 2H), 7.21±7.31
(m, 8H), 6.73 (d, Jˆ1.5 Hz, 1H), 6.66 (d, Jˆ8.0 Hz, 1H),
6.56 (dd, Jˆ8.0 Hz, Jˆ1.5 Hz, 1H), 5.89 (s, 2H), 5.58 (d,
1
3
(
(
49 mg, 80%) as colourless solid; mp 154±1558C; R 0.21
hexanes:ethyl acetateˆ8:2 (v/v)). H NMR (400 MHz):
Jˆ14.4 Hz, 1H), 4.60 (s, 2H), 2.42 (s, 3H); C NMR
(100 MHz): dˆ148.0 (s), 146.3 (s), 144.0 (s), 135.9 (s),
135.3 (s), 130.5 (d), 129.9 (d), 128.6 (d), 127.5 (d), 127.0
(d), 126.8 (d), 125.3 (d), 119.7 (d), 112.3 (d), 108.3 (d),
105.0 (d), 101.0 (t), 49.5 (t), 21.5 (q); IR (neat): nˆ2919,
1644, 1504, 1492, 1446, 1352, 1252, 1164, 1090, 1038, 812,
f
1
dˆ7.82 (d, Jˆ8.5 Hz, 2H), 7.72 (d, Jˆ8.0 Hz, 2H), 7.64
(
d, Jˆ14.6 Hz, 1H), 7.22±7.32 (m, 9H), 5.64 (d,
Jˆ14.5 Hz, 1H), 4.67 (s, 2H), 2.54 (s, 3H), 2.42 (s, 3H);
1
3
C NMR (100 MHz): dˆ197.3 (s), 144.3 (s), 141.4 (s),
2
1
1
1
(
(
35.7 (s), 134.9 (s), 134.8 (s), 130.0 (d), 129.0 (d), 128.8
768, 737 cm ; MS (EI), m/z (%): 407 (M , 26), 332 (33),
252 (19), 222 (19), 91 (100), 77 (20), 32 (90); Anal. Calcd.
for C H NO S (407.49): C, 67.79; H, 5.19; N, 3.44.
d), 128.7 (d), 127.6 (d), 127.0 (d), 126.7 (d), 125.2
d), 110.3 (d), 49.4 (t), 26.4 (q), 21.5 (q); IR (neat): n:
2
3
21
4
3
1
4
034, 1677, 1638, 1599, 1495, 1360, 1325, 1270, 1181,
Found: C, 67.44, H, 5.31, N, 3.44.
2
165, 1090, 1047, 944, 872 cm ; MS (EI), m/z (%):
1
1
05 (M , 59), 277 (9), 262 (15), 224 (16), 208 (11), 106
tert-Butyl 5-((E)-2-{benzyl-[4-methylphenyl)sulphonyl]-
amino}-ethenyl)-1H-indole-1-carboxylate (11d). Prepared
(
36), 91 (100); Anal. Calcd. for C H NO S (405.51):
24 23 3

8
478
B. Witulski et al. / Tetrahedron 56 (2000) 8473±8480
1
according to the general procedure using 7 (62 mg,
.22 mmol), 8 (0.32 mL of a 1 M solution in THF) and
THF (2 mL). Thereafter NaOH (17 mg, 0.43 mmol),
pentane mp 238±1398C. H NMR (400 MHz): dˆ7.96 (d,
0
Jˆ8.7 Hz, 1H), 7.78 (d, Jˆ8.7 Hz, 2H), 7.70 (s, 1H), 7.22±
1
3
7.39 (m, 5H), 2.34 (s, 3H); C NMR (100 MHz): dˆ145.3
(s), 134.9 (s), 134.3 (s), 132.4 (s), 130.0 (d), 129.7 (d), 126.9
(d), 125.6 (d), 123.9 (d), 122.0 (d), 113.4 (d), 84.3 (s), 66.8
Pd(PPh ) (17 mg, 0.015 mmol), 10e (43 mg, 0.15 mmol)
3
4
and additional THF (3 mL) were added. The crude product
was chromatographed on silica gel (hexanes:diethyl
etherˆ95:5 (v/v)) to afford 11d (55 mg, 75%) as colourless
1
(s), 21.6 (q); MS (EI), m/z (%): 396 (M , 100), 242 (78), 155
(25), 115 (26), 91 (37); Anal. Calcd. for C H INO S
(397.23): C, 45.35; H, 3.04; N, 3.53. Found: C, 45.35, H,
2.81, N, 3.41.
1
5
12
2
solid; mp 164±1668C; R 0.6 (hexanes:ethyl acetateˆ8:2
f
1
(
7
v/v)). H NMR (400 MHz): dˆ7.98 (d, Jˆ8.0 Hz, 1H),
.73 (d, Jˆ8.0 Hz, 2H), 7.53 (d, Jˆ3.8 Hz, 1H), 7.45 (d,
Jˆ14.6 Hz, 1H), 7.22±7.36 (m, 8H), 7.15 (dd, Jˆ8.7 Hz,
tert-Butyl 3-iodo-5-methoxy-1H-indole-1-carboxylate (14c)
and 3-iodo-5-methoxy-1-[(4-methylphenyl)sulphonyl]-
1H-indole (14d). 14c was prepared according to the
above procedure using 3-iodo-5-methoxy-1H-indole (13b)
Jˆ1.6 Hz, 1H), 6.46 (d, Jˆ3.8 Hz, 1H), 5.76 (d, Jˆ14.6 Hz,
1
H), 4.65 (s, 2H), 2.41 (s, 3H), 1.65 (s, 9H); C NMR
3
1
(
1
(
100 MHz): dˆ150.0 (s), 144.3 (s), 136.4 (s), 135.9 (s),
31.3 (s), 130.3 (d), 129.1 (s), 129.06 (d), 127.9 (d), 127.6
s), 127.4 (d), 127.3 (d), 126.1 (d), 122.3 (d), 118.1 (d),
(917 mg, 3.36 mmol), Boc O (879 mg, 4.02 mmol) and
2
DMAP (82 mg, 0.67 mmol). Chromatography over silica
gel (SiO , hexanes:diethyl etherˆ6:1(v/v) produced the
1
2
1
15.6 (d), 113.2 (d), 107.5 (d), 84.1 (s), 50.0 (t), 28.6 (q),
2.0 (q); IR (neat): nˆ3303, 2979, 1731, 1643, 1470, 1369,
2
1
desired product 14c (1.23 g, 98%); mp 112±1138C. H
2
258, 1227, 1164, 1132, 1087, 1025, 938, 734 cm ; MS
1
NMR (400 MHz): dˆ8.03 (d, Jˆ9.0 Hz, 1H), 7.71 (s,
1
(
(
(
EI), m/z (%): 502 (M , 7), 402 (23), 291 (22), 247 (44), 156
25), 106 (19), 91 (100); Anal. Calcd. for C H N O S
502.63): C, 69.30; H, 6.02; N, 5.57. Found: C, 68.99, H,
.60, N, 5.41.
1H), 6.99 (dd, Jˆ9.0 Hz, Jˆ2.5 Hz, 1H), 6.86 (d,
1
3
Jˆ2.5 Hz, 1H), 3.92 (s, 3H), 1.68 (s, 9H); C NMR
(100 MHz): dˆ156.5 (s), 148.6 (s), 133.0 (s), 130.6 (d),
116.0 (d), 114.5 (d), 103.7 (d), 84.1 (s), 65.1 (s), 55.7 (d),
2
9
30
2
4
5
2
8.1 (q).
tert-Butyl 3-iodo-1H-indole-1-carboxylate (14a) and 3-
iodo-1-[(4-methylphenyl)sulphonyl]-1H-indole (14b). A
solution of I (4.39 g, 17.28 mmol) in DMF (30 mL) was
14d was prepared according to the above procedure using
5-methoxy-1H-indole (12b) (942 mg, 6.40 mmol), I2
(1.64 g, 6.48 mmol) and KOH (661 mg, 11.77 mmol) giving
3-iodo-5-methoxy-1H-indole (13b) (1.53 g, 87%). The
obtained crude product was immediately tosylated by
using 3-iodo-5-methoxy-1H-indole (13b) (716 mg,
2.62 mmol), 4-methylbenzenesulphonyl chloride (750 mg,
3.93 mmol) and NaOH (126 mg, 3.15 mmol) in CH Cl .
2
dropped into
7.07 mmol) and KOH (2.39 g, 42.7 mmol) in DMF
30 mL) at room temperature and stirred for 0.45 h. The
a solution of 1H-indole (12a) (2 g,
1
(
reaction mixture was poured into ice and water (400 mL)
containing ammonia (0.5%) and sodium metabisulphite
(
0.1%). The white precipitate was ®ltered and washed
with cold water. The obtained 3-iodo-1H-indole (13a)
4.15 g, 100%) was used without further puri®cation.
2
2
After column chromatography (SiO2, hexanes:ethyl
acetateˆ8:2 (v/v)) and crystallisation from CH Cl 14d
(
2
2
(
660 mg, 60%) was obtained as colourless solid, mp 174±
1
3-Iodo-1H-indole (13a) (1.57 g, 6.46 mmol) was dissolved
in CH Cl (150 mL) and treated with Boc O (1.57 g,
1758C, R 0.46 (hexanes:ethyl acetateˆ8:2 (v/v)), H NMR
f
(400 MHz) dˆ7.87 (d, Jˆ9.0 Hz, 1H), 7.77 (d, Jˆ8.4 Hz,
2H), 7.67 (s, 1H), 7.25 (d, Jˆ9.0 Hz, Jˆ2.5 Hz, 1H), 6.80
2
2
2
7
0
.17 mmol), triethylamine (2.7 mL), and DMAP (79.8 mg,
.65 mmol) and was stirred at room temperature for 0.5 h.
1
3
(d, Jˆ2.5 Hz, 1H), 3.87 (s, 3H), 2.37 (s, 3H); C NMR
(100 MHz): dˆ157.5 (s), 146.6 (s), 135.3 (s), 133.9 (s),
130.8 (d), 130.4 (d), 129.3 (s), 127.3 (d), 115.6 (d), 114.9
(d), 104.3 (d), 67.3 (s), 56.1 (q), 22.0 (q).
The solution was then washed twice with sodium metabi-
sulphite (5%), dried with MgSO and concentrated. Chro-
4
matography over silica gel (SiO2, hexanes:diethyl
etherˆ8:2 (v/v)) followed by crystallisation from pentane
1
gave 14a (1.94 g, 88%) as colourless solid, mp 36±408C. H
tert-Butyl 3-((E)-2-{benzyl-[(4-methylphenyl)sulphonyl]-
amino}ethenyl)-1H-indole-1-carboxylate (15a). Prepared
according to the general procedure using 7 (154 mg,
0.54 mmol), 8 (0.54 mL of a 1 M solution in THF) and
THF (2 mL). Thereafter NaOH (43 mg, 1.08 mmol),
Pd(PPh ) (42 mg, 0.036 mmol), 14a (124 mg, 0.36 mmol)
NMR (400 MHz): dˆ8.13 (d, Jˆ8.1 Hz, 1H), 7.73 (s, 1H),
1
3
.29±7.43 (m, 3H), 1.68 (s, 9H); C NMR (100 MHz):
7
dˆ148.7 (s), 134.9 (s), 132.1 (s), 130.1 (d), 125.3 (d),
1
23.3 (d), 121.5 (d), 115.1 (d), 65.4 (s), 28.14 (q); MS
1
EI), m/z (%): 343 (M , 69), 287 (100), 270 (13), 243
(
(
(
3
4
98), 116 (28), 57 (98); Anal. Calcd. for C H INO
2
343.16): C, 45.50; H, 4.11; N, 4.08. Found: C, 45.37, H,
.66, N, 3.96.
and additional THF (5 mL) were added. The crude product
was chromatographed on silica gel (hexanes:diethyl
etherˆ19:1 (v/v)) to afford 15a (104 mg, 58%) as colourless
1
3
14
3
solid; mp 129±1318C; R 0.46 (hexanes:ethyl acetateˆ8:2
f
1
To a solution of 3-iodo-1H-indole (13a) (4.15 g, 17.07
mmol) in CH Cl (50 mL) was added NaOH (819 mg,
(v/v)). H NMR (400 MHz): dˆ8.12 (d, Jˆ7.9 Hz, 1H),
7.74 (d, Jˆ8.1 Hz, 2H), 7.49±7.55 (m, 2H), 7.42 (s, 1H),
7.21±7.37 (m, 9H), 5.73 (d, Jˆ14.8 Hz, 1H), 4.67 (s, 2H),
2
2
2
(
5
0.46 mmol) and 4-methylbenzenesulphonyl chloride
3.96 g, 20.77 mmol) and stirred at room temperature for
h. The solution was washed with brine, dried with
MgSO and concentrated. Chromatography over silica gel
1
3
2.41 (s, 3H), 1.64 (s, 9H); C NMR (100 MHz): dˆ149.5
(s), 144.1 (s), 135.8 (s), 135.7 (s), 135.3 (s), 130.0 (d), 128.7
(d), 128.6 (s), 127.6 (d), 127.0 (d), 126.9 (d), 126.6 (d),
124.6 (d), 122.8 (d), 121.7 (d), 119.4 (d), 117.1 (s), 115.4
(d), 103.8 (d), 83.8 (s), 49.4 (t), 28.2 (q), 21.6 (q); IR (neat):
nˆ3033, 2972, 2926, 1728, 1648, 1451, 1355, 1308, 1254,
4
(
desired product 14b. An analytical pure sample (2.69 g,
SiO , hexanes:diethyl etherˆ6:1 (v/v)) produced the
2
40%) was obtained after crystallisation from CH Cl /
2 2

B. Witulski et al. / Tetrahedron 56 (2000) 8473±8480
8479
2
208, 1163, 1100, 1055, 1020, 946, 840, 814, 766 cm ; MS
1
1
(
and THF (2 mL). Thereafter NaOH (37 mg, 0.91 mmol),
Pd(PPh ) (42 mg, 0.036 mmol), 14d (130 mg, 0.30 mmol)
1
EI), m/z (%): 502 (M , 5), 291 (21), 247 (20), 134 (32), 118
3
4
(22), 106 (22), 91 (100), 65 (27); Anal. Calcd. for
C H N O S (502.63): C, 69.30; H, 6.02; N, 5.57. Found:
C, 68.91, H, 6.03, N, 5.43.
and additional THF (5 mL) were added. The crude product
was chromatographed on silica gel (hexanes:diethyl
etherˆ19:1 (v/v)) to afford 15d (149 mg, 84%) as colourless
2
9
30
2
4
solid; mp 173±1748C; R 0.27 (hexanes:ethyl acetateˆ8:2
f
1
1-(4-Methylphenyl)sulphonyl-3-((E)-2-{benzyl[4-methyl-
(v/v)). H NMR (400 MHz): dˆ7.83 (d, Jˆ8.9 Hz, 1H),
phenyl)sulphonyl]amino}ethenyl)-1H-indole (15b). Prepared
according to the general procedure using 7 (64 mg,
0.22 mmol), 8 (0.27 mL of a 1 M solution in THF) and
THF (2 mL). Thereafter NaOH (18 mg, 0.45 mmol),
7.74 (d, Jˆ8.5 Hz, 2H), 7.69 (d, Jˆ8.5 Hz, 2H), 7.43 (d,
Jˆ14.6 Hz, 1H), 7.16±7.36 (m, 10H), 6.89 (dd, Jˆ8.9 Hz,
Jˆ2.3 Hz, 1H), 6.76 (d, Jˆ2.3 Hz, 1H), 5.59 (d, Jˆ14.6 Hz,
1
3
1H), 4.66 (s, 2H), 3.77 (s, 3H), 2.42 (s, 3H), 2.31 (s, 3H); C
NMR (100 MHz): dˆ156.4 (s), 144.8 (s), 144.2 (s), 135.8
(s), 135.3 (s), 135.0 (s), 130.1 (s), 130.0 (d), 129.9 (s), 129.8
(d), 128.7 (d), 127.6 (d), 127.3 (d), 127.0 (d), 126.9 (d),
126.7 (d), 122.2 (d), 119.1 (s), 114.6 (d), 113.7 (d), 102.4
(d), 102.3 (d), 55.6 (q), 49.5 (t), 21.54 (q), 21.50 (q); IR
(neat): nˆ2924, 1651, 1597, 1495, 1473, 1454, 1363, 1214,
Pd(PPh ) (21 mg, 0.018 mmol), 14b (59 mg, 0.15 mmol)
3
4
and additional THF (3 mL) were added. The crude product
was chromatographed on silica gel (hexanes:diethyl
etherˆ19:1 (v/v)) to afford 15b (59 mg, 71%) as colourless
solid; mp 170±1718C; R 0.31 (hexanes:ethyl acetateˆ8:2
f
1
(
7
v/v)). H NMR (400 MHz): dˆ7.95 (d, Jˆ8.1 Hz, 1H),
2
1
.74 (m, 2H), 7.73 (m, 2H), 7.52 (d, Jˆ14.7 Hz, 1H), 7.44
1166, 1122, 1090, 1038, 980, 944, 813 cm ; MS (EI), m/z
1
(
1
d, Jˆ7.4 Hz, 1H), 7.18±7.38 (m, 12H), 5.66 (d, Jˆ14.7 Hz,
(%): 586 (M , 9), 431 (15), 407 (10), 276 (36), 183 (13),
144 (15), 91 (100), 77 (11); Anal. Calcd. for C H N O S
5 2
1
H), 4.66 (s, 2H), 2.42 (s, 3H), 2.32 (s, 3H); C NMR
3
3
2
30
2
(
1
(
1
100 MHz): dˆ144.9 (s), 144.2 (s), 135.8 (s), 135.3 (s),
35.2 (s), 135.1 (s), 130.0 (d), 129.9 (d), 128.9 (s), 128.7
d), 127.6 (d), 127.4 (d), 127.0 (d), 126.9 (d), 126.8 (d),
24.9 (d), 123.4 (d), 121.7 (d), 119.9 (d), 119.0 (s), 113.7
d), 102.6 (d), 49.5 (t), 21.53 (q), 21.51 (q); IR (neat):
nˆ3064, 2922, 1648, 1597, 1445, 1364, 1317, 1291,
(586.73): C, 65.51; H, 5.15; N, 4.77. Found: C, 65.49, H,
5.23, N, 4.67.
(
Acknowledgements
2
1
1
166, 1125, 1090, 1045, 978, 943, 837 cm ; MS (EI),
This work was supported by the Deutsche Forschungs-
gemeinschaft (Wi-1696). We thank J oÈ rg Steinbach for
recording the mass spectra, Birgit Dusch and Tatjana
Schaible for performing several elemental analyses, and
Professor Dr Manfred Regitz for the support of our work.
1
m/z (%): 556 (M , 56), 401 (93), 246 (76), 155 (22), 91
100), 44 (19); Anal. Calcd. for C H N O S (556.70):
(
3
1
28
2
4 2
C, 66.88; H, 5.07; N, 5.03. Found: C, 66.56, H, 4.91, N,
.90.
4
tert-Butyl 3-((E)-2-{benzyl-[(4-methylphenyl)sulphonyl]-
amino}ethenyl)-5-methoxy-1H-indole-1-carboxylate (15c).
Prepared according to the general procedure using 7
References
(
132 mg, 0.46 mmol), 8 (0.56 mL of a 1 M solution in
THF) and THF (2 mL). Thereafter NaOH (37 mg,
.93 mmol), Pd(PPh3)4 (43 mg, 0.037 mmol), 14c
115 mg, 0.31 mmol) and additional THF (5 mL) were
1. (a) Suzuki, A. J. Organomet. Chem. 1999, 576, 147. (b) Suzuki,
A. In Metal-catalyzed Cross-coupling Reactions; Diederich, F.,
Stang, P. J., Eds.; Wiley-VCH: New York, 1998. (c) Miyaura,
N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. For the hydroboration
of alkynes, see: (d) Brown, H. C. Organic Syntheses via Boranes;
Wiley: New York, 1975. (e) Brown, H. C.; Gupta, S. K. J. Am.
Chem. Soc. 1971, 93, 1816. (f) Brown, H. C.; Gupta, S. K. J. Am.
Chem. Soc. 1972, 94, 4370. (g) Lane, C. F.; Kabalka, G. W.
Tetrahedron 1976, 32, 981.
0
(
added. The crude product was chromatographed on silica
gel (hexanes:diethyl etherˆ19:1 (v/v)) to afford 15c
(
0
122 mg, 74%) as colourless solid; mp 132±1348C; R
f
1
.37 (hexanes:ethyl acetateˆ8:2 (v/v)).
H
NMR
(
400 MHz): dˆ7.74 (d, Jˆ8.4 Hz, 2H), 7.47 (d,
Jˆ14.6 Hz, 1H), 7.25±7.41 (m, 9H), 6.90 (dd, Jˆ8.9 Hz,
Jˆ2.4 Hz, 1H), 6.87 (d, Jˆ2.4 Hz, 1H), 5.69 (d, Jˆ14.6 Hz,
2. For representative examples of Suzuki±Miyaura cross-coupling
reaction in the synthesis of natural products see: (a) Alvarez, R.; de
Lera, A. R. Tetrahedron: Asymmetry 1998, 9, 3065. (b) White,
J. D.; Kim, T.-S.; Nambu, M. J. Am. Chem. Soc. 1995, 117,
5612. (c) Cassani, G.; Massardo, P.; Piccardi, P. Tetrahedron
Lett. 1983, 24, 2513. (d) Nicolaou, K. C.; Sorensen, E. J. Classics
in Total Synthesis; VCH: Weinheim, 1996.
1
H), 4.68 (s, 2H), 3.82 (s, 3H), 2.42 (s, 3H), 1.63 (s, 9H); C
3
1
NMR (100 MHz): dˆ155.9 (s), 149.5 (s), 144.1 (s), 135.9
(
(
1
4
1
1
s), 135.4 (s), 130.3 (s), 130.0 (d), 129.5 (s), 128.7 (d), 127.5
d), 126.99 (d), 126.95 (d), 126.5 (d), 122.1 (d), 116.9 (s),
16.0 (d), 113.0 (d), 103.7 (d), 102.2 (d), 83.6 (s), 55.7 (q),
9.5 (t), 28.2 (q), 21.6 (q); IR (neat): nˆ2979, 2927, 1728,
652, 1478, 1452, 1390, 1369, 1349, 1338, 1318, 1304,
3. (a) Kamabuchi, A.; Moriya, T.; Miyaura, N.; Suzuki, A. Synth.
Commun. 1993, 23, 2851. (b) Brown, H. C.; Ravindran, N.;
Kulkarni, S. U. J. Org. Chem. 1980, 45, 384. (c) Brown, H. C.;
Campbell, J. B., Jr. J. Org. Chem. 1980, 45, 389. (d) Brown, H. C.;
Bhat, N. G.; Somayaji, V. Organometallics 1983, 2, 1311.
4. (a) Brown, H. C.; Blue, C. D.; Nelson, D. J.; Bhat, N. G. J. Org.
Chem. 1989, 54, 6064. (b) Zweifel, G.; Arzoumanian, H. J. Am.
Chem. Soc. 1967, 89, 5086.
2
1
273, 1212, 1161, 1092, 1018, 946, 836 cm ; MS (EI),
1
m/z (%): 533 (M , 38), 448 (35), 447 (100), 445 (36), 357
46), 356 (39), 343 (81), 342 (40), 329 (35), 328 (45); Anal.
Calcd. for C H N O S (532.66): C, 67.65; H, 6.06; N,
(
3
0
32
2
5
5
.26. Found: C, 67.60, H, 6.07, N, 5.14.
1-(4-Methylphenyl)sulphonyl-3-((E)-2-{benzyl[4-methyl-
phenyl)sulphonyl]amino}ethenyl)-5-methoxy-1H-indole
5. (a) Zweifel, G.; Lewis, W.; On, H. P. J. Am. Chem. Soc. 1979,
101, 5101. (b) Fisher, R. P.; On, H. P.; Snow, J. T.; Zweifel, G.
Synthesis 1982, 127. (c) Masuda, Y.; Suyama, T.; Murata, M.;
Watanabe, S. J. Chem. Soc., Perkin Trans. 1 1995, 2955.
(
15d). Prepared according to the general procedure using 7
130 mg, 0.46 mmol), 8 (0.55 mL of a 1 M solution in THF)
(

8
480
B. Witulski et al. / Tetrahedron 56 (2000) 8473±8480
6
. (a) Brown, H. C.; Subrahmanyam, C.; Hamaoka, T.; Ravindran,
K.; Watanabe, H.; Kitahara, T. Synlett 2000, 397. (f) Brettle, R.;
Mosedale, A. J. J. Chem. Soc., Perkin Trans. 1 1988, 2185.
(g) Laso, N. M.; Quiclet-Sire, B.; Zard, S. Z. Tetrahedron Lett.
1996, 37, 1605. (h) Meuzelaar, G.; Blom, A.; Maat, L.; Sheldon,
R. A. Eur. J. Org. Chem. 1999, 519.
N.; Bowman, D. H.; Misumi, S.; Unni, M. K.; Somayaji, V.; Bhat,
N. G. J. Org. Chem. 1989, 54, 6068. (b) Brown, H. C.; Imai, T.
Organometallics 1984, 3, 1392. (c) Campbell, J. B., Jr.; Molander,
G. A. J. Organomet. Chem. 1978, 156, 71. (d) Brown, H. C.;
Somayaji, V. Synthesis 1984, 919.
15. Busacca, C. A.; Johnson, R. E.; Swestock, J. J. Org. Chem.
1993, 58, 3299.
7
. (a) Hegedus, L. S.; Toro, J. L.; Miles, W. H.; Harrington, P. J.
J. Org. Chem. 1987, 52, 3319. (b) Satoh, M.; Miyaura, N.; Suzuki,
A. Synthesis 1987, 373. (c) Miyaura, N.; Maeda, K.; Suginome, H.;
Suzuki, A. J. Org. Chem. 1982, 47, 2117.
16. Ogawa, T.; Kiji, T.; Hayami, K.; Suzuki, H. Chem. Lett. 1991,
1443.
17. For the preparation of 5 and the discussion of the chemistry of
alkynyliodonium salts, see: (a) Stang, P. J. In Modern Acetylene
Chemistry; Stang, P. J., Diederich, F., Eds.; VCH: Weinheim,
1995. (b) Stang, P. J.; Zhdankin, V. V. Chem. Rev. 1996, 96, 1123.
18. The hydroboration of the electron rich (N-methyl, N-phenyl)-
1-alkynylamine failed under these conditions and gave only tarry
decomposition products.
8
. (a) Gridnev, I. D.; Miyaura, N.; Suzuki, A. J. Org. Chem. 1993,
8, 5351. (b) Gridnev, I. D.; Miyaura, N.; Suzuki, A.
5
Organometallics, 1993, 12, 589; the direct hydroboration of
-thio-1-alkynes is less regioselective and preferentially places
1
the boron alpha to sulphur leading to regioisomeric analogues of
the catalysed version: (c) Hoshi, M.; Masuda, Y.; Arase, A. Bull.
Chem. Soc. Jpn. 1990, 63, 447. (d) Gerard, J.; Bietlot, E.; Hevesi,
L. Tetrahedron Lett. 1998, 39, 8735.
19. (a) Pindur, U.; Otto, C. Tetrahedron 1992, 48, 3515.
(b) Pindur, U. Heterocycles 1988, 27, 1253. (c) Schlecht, M. F.;
Giadinoto, S. Heterocycles 1987, 25, 485. (d) Akg uÈ n, E.; Pindur,
U. J. Heterocyclic Chem. 1985, 22, 585.
9
. For reviews discussing the chemistry of ynamines, see:
a) Himbert, G. In Methoden Org. Chem. (Houben-Weyl), 1993,
(
Vol. E15, p 3267. (b) Collard-Motte, J.; Janousek, Z. Top. Curr.
Chem. 1986, 130, 89. (c) Pitacco, G.; Valentin, E. In The Chemistry
of Amino, Nitroso and Nitro Compounds and their Derivatives,
Supplement F, Part 1; Patai, S., Ed.; Wiley: New York, 1982,
p 624. (d) Ficini, J. Tetrahedron 1976, 32, 1449.
20. Crystal data for 15d: STOE Imaging Plate Diffraction
System, graphite monochromator, Mo
K
a
radiation (lˆ
Ê
0.71073 A), cell determination and re®nement by STOE
programmes Ver. 2.75, structure solution by direct methods
2
1
22
(SHELXS-86) and structure re®nement by SHELXL-93,
hydrogen atoms were included in the re®nement using riding
10. Witulski, B.; Stengel, T. Angew. Chem. 1998, 110, 495;
Angew. Chem. Int. Ed. 1998, 37, 489.
2
1
models. C H N O S ; Mˆ586.70 g mol
; triclinic; space
group P1 (No. 2); lattice constants aˆ9.999(2), bˆ12.089(2),
3
2
30
2
5 2
1
1. Witulski, B.; G oÈ ûmann, M. Chem. Commun. 1999, 1879.
2. (a) Witulski, B.; Stengel, T. Angew. Chem. 1999, 111, 2521;
Ê
1
cˆ13.208(3) A, aˆ88.19(3), bˆ87.94(3), gˆ68.49(3)8, Vˆ
3
3
21
Ê
Angew. Chem. Int. Ed. 1999, 38, 2426. (b) Witulski, B.; Stengel,
T.; Fern a ndez-Hern a ndez, J. M. Chem. Commun. 2000 (in press);
for other recent examples on ynamide cycloadditions, see:
1484.1(5) A ; Zˆ2;
D
ˆ1.313 Mg/m ; mˆ2.23 cm
;
Tˆ
cal.
3
293(2) K; crystal size 0.80£0.35£0.20 mm ; 2.19#Q#26.208.
14688 re¯ections collected, 5429 independent re¯ections
2
1
2
2
o
2
(c) Rainier, J. D.; Imbriglio, E. Org. Lett. 1999, 1, 2037.
(d) Hsung, R. P.; Zi®csak, C. A.; Wie, L.-L.; Douglas, C. J.;
(Rint.ˆ0.0433); 373 parameters; w ˆ[s (F )1 (0.0452P) ] and
2
o
2
c
1
2
Pˆ[(F )12F ]/3; R ˆ0.0387, wR ˆ0.0933 for 2529 re¯ections
2
2
Xiong, H.; Mulder, J. A. Org. Lett. 1999, 1, 1237.
3. (a) Toske, S. G.; Jensen, P. R.; Kauffman, C. A.; Fenical, W.
with I.2s(I) and R ˆ0.0760, wR ˆ0.1102 for all data; residual
2
3
23
1
electron density 264 e nm
and 2230 e nm , SˆGOF (on
2
Tetrahedron 1998, 54, 13459. (b) Umezawa, H.; Imoto, M.; Sawa,
T.; Isshiki, K.; Matsuda, N.; Uchida, T.; Inuma, H.; Hamada, M.;
Takeuchi, T. J. Antibiot. 1986, 39, 170. (c) Nakamura, H.; Iitaka,
Y.; Imoto, M.; Isshiki, K.; Naganawa, H.; Takeuchi, T.; Umezawa,
H. J. Antibiot. 1986, 39, 314. (d) Okuma, K.; Anzai, K.; Suzuki, S.
J. Antibiot. 1962, 15A, 115.
F )ˆ1.206. Crystallographic data of 15d were deposited with the
Cambridge Crystallographic Data Centre. CCDC reference
number: 148382.
21. Sheldrick, G. M. SHELXS-86, Program for Crystal Structure
Solution, University of G oÈ ttingen, 1990.
22. Sheldrick, G. M. SHELXL-93, Program for Crystal Structure
Re®nement, University of G oÈ ttingen, 1993.
1
4. (a) Ziegenbein, W.; Franke, W. Chem. Ber. 1957, 90, 2291.
b) Harada, T.; Ohno, T.; Kobayashi, S.; Mukaiyama, T. Synthesis
991, 1216. (c) Brettle, R.; Shibib, S. M.; Wheeler, K. J. J. Chem.
(
23. (a) Ottoni, O.; Cruz, R.; Alves, R. Tetrahedron 1998, 54,
13915. (b) Kelly, T. A.; McNeil, D. W.; Rose, J. M.; David, E.;
Shih, C.-K.; Grob, P. M. J. Med. Chem. 1997, 40, 2430. (c) Bocchi,
V.; Palla, G. Synthesis 1982, 1096.
1
Soc., Perkin Trans. 1 1985, 831. (d) Redeker, U.; Engel, N.;
Steglich, W. Tetrahedron Lett. 1981, 22, 4263. (e) Kuramochi,