An investigation into domino-Heck reactions of N-acylamino-substituted tricyclic imides: Synthesis of new prospective pharmaceuticals

Article abstract of DOI:10.1002/hlca.200790244

Heck and domino-Heck reactions of unsaturated N-acylamino-substituted tricyclic imides with aryl(heteroaryl) iodides and phenyl- or (trimethylsilyl)acetylene were either carried out in the presence of formate or phenyl- and (trimethylsilyl)acetylene, respectively. The C-C coupling reactions appeared to be completely diastereoselective, giving the corresponding N-acylamino-5-exo-aryl (heteroaryl)- (5a-c, 6a,b), N-(benzoylamino)-5-exo- phenyl-6-exo-[(trimethylsilyl)ethynyl]- (5d), or 5-exo-(4-chlorophenyl)-N-(2,2- dimethylpropanoylamino)-6-exo-(phenylethynyl)bicyclo[2.2.1]heptane-2-endo, 3-endo-dicarboximide (6c) (Schemes 3 and 4).

Full text of DOI:10.1002/hlca.200790244

2380
Helvetica Chimica Acta – Vol. 90 (2007)
An Investigation into Domino-Heck Reactions of N-Acylamino-Substituted
Tricyclic Imides: Synthesis of New Prospective Pharmaceuticals
by Emine Bagdatlia), Nüket Öcal*a), and Dieter E. Kaufmannb)
a) Yildiz Technical University, Faculty of Art and Sciences, Department of Chemistry,
Davutpasa Campus, TR-34210 Istanbul (phone: þ 90(212)4491750; e-mail: nocal@yildiz.edu.tr)
b) Clausthal University of Technology, Institute of Organic Chemistry, Leibnizstr. 6,
D-38678 Clausthal-Zellerfeld
Heck and domino-Heck reactions of unsaturated N-acylamino-substituted tricyclic imides with
aryl(heteroaryl) iodides and phenyl-or (trimethylsilyl)acetylene were either carried out in the presence
of formate or phenyl-and (trimethylsilyl)acetylene, respectively. The C ÀC coupling reactions appeared
to be completely diastereoselective, giving the corresponding N-acylamino-5-exo-aryl (heteroaryl)- (5a –
c, 6a,b), N-(benzoylamino)-5-exo-phenyl-6-exo-[(trimethylsilyl)ethynyl]- (5d), or 5-exo-(4-chlorophen-
yl)-N-(2,2-dimethylpropanoylamino)-6-exo-(phenylethynyl)bicyclo[2.2.1]heptane-2-endo,3-endo-dicar-
boximide (6c) (Schemes 3 and 4).
Introduction. – In the last decade, organopalladium-catalyzed CÀC bond-
formation has become one of the most efficient approaches in the synthesis of organic
molecules. The Heck reaction, in particular, is widely used as an important method to
build biologically active compounds in synthetic chemistry and the pharmaceutical
industry [1][2]. As an extension of the Heck reaction, Pd-catalyzed hydroarylation of
alkynes and alkenes continues to attract research interest in simple coupling processes
and cyclization reactions. The research in the field of domino reactions also is attracting
considerable attention in synthetic organic chemistry since it enables the rapid
assembly of complex molecules in one-pot processes [3][4].
Kaufmann and co-workers have carried out new examples of Heck reactions using
bicyclic systems aiming at the synthesis of new biologically active compounds [5 – 7].
Preparations of epibatidine analogues with bi-and tricyclic skeletons in a single
synthetic operation via reductive Heck and additional domino-Heck reactions have
recently been reported by us [8]. In the present work, we focused on reductive Heck
reactions of the polyfunctionalized tricyclic molecules 3 and 4 with a strained C¼C
bond and an acylamino-imide or hydrazide group.
Organic derivatives of substituted hydrazines are extensively used in medicine as
pharmacological agents exhibiting tuberculocidal, anticancer, radioprotection, anti-
depressant, psychotherapeutic, and other kinds of biological activities [9]. Kasꢀyan and
co-workers indicated that, in contrast, the hydrazinolysis product of dicarboxyclic acid
anhydrides and derivatives of the bicyclo[2.2.1]hept-5-ene-2-endo,3-endo-dicarboxylic
acids are poorly studied [10]. Furthermore, the synthesis of imide derivatives is
important, because such compounds exhibit a wide range of pharmacological effects
[11][12].
ꢀ 2007 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 90 (2007)
2381
Results and Discussion. – Our synthesis started with the Diels – Alder reaction of
cyclopentadiene and maleic anhydride. Hydrazinolysis of anhydride 1 was carried out
with hydrazine hydrate in EtOH for 5 h to give bicyclic aminoimide 2 by a known
procedure [13] (Scheme 1).
Scheme 1
Aminoimide 2 reacted with benzoyl chloride in pyridine as base to afford N-
(benzoylamino)bicyclo[2.2.1]hept-5-ene-2-endo,3-endo-dicarboximide (3)1) [14]. The
same reaction occurred with 2,2-dimethylpropanoyl chloride to give N-[(2,2-dimethyl-
propanoyl)amino]bicyclo[2.2.1]hept-5-ene-2-endo,3-endo-dicarboximide (4)1) as a new
compound (Scheme 2).
Scheme 2
The presence of a strained C¼C bond in the N-substituted aminoimides 3 and 4
provided the possibility for carrying out Heck reactions with aryl(heteroaryl) iodides,
in the presence of triphenylarsine (AsPh3) as a ligand and palladium(II) acetate [15].
Treatment of 3 with iodobenzene, 1-chloro-4-iodobenzene, or 2-chloro-5-iodopyridine
under reductive Heck conditions gave the new compounds 5a – c as 5-exo products after
chromatographic separation (Scheme 3).
1
)
Trivial atom numbering (syn/anti relative to the imide); for systematic names, see Exper. Part.

2382
Helvetica Chimica Acta – Vol. 90 (2007)
Scheme 31)
We also synthesized 6a and 6b as new 5-exo compounds from 4 with 1-chloro-4-
iodobenzene or 2-chloro-5-iodopyridine, respectively, under the same conditions
(Scheme 4). The use of (trimethylsilyl)acetylene with 1-iodobenzene and of phenyl-
acetylene with 1-chloro-4-iodobenzene under domino-Heck conditions provided the
alkynylated tricyclic systems 5d and 6c, respectively. The configuration of the new
1
1
compounds was inferred from their H-NMR and H,1H-COSY data. Due to the
symmetry of 3 and 4, after column chromatographic separation, we obtained single
diastereoisomers, only. Not surprisingly, the attachments of the phenyl or silylethynyl
group took place exclusively from the exo-side of the tricyclic alkene moieties of 3 and
4. The structures of 5d and 6c were also assigned by their 1H,1H-COSYand HSQC data
in CDCl3.
Scheme 4

Helvetica Chimica Acta – Vol. 90 (2007)
2383
In conclusion, the [Pd(OAc)2]-catalyzed hydroarylation of the easily accessible
tricyclic unsaturated N-(acylamino)-imides 3 and 4, in the presence of AsPh3 as a
ligand, proved to be a stereoselective, versatile and high-yield approach for the
synthesis of the aryl and heteroaryl derivatives of imides. Domino-Heck sequential
CÀC couplings with aryl or heteroaryl halides were shown to be feasible in the
presence of (trimetylsilyl)acetylene or phenylacetylene.
We gratefully acknowledge financial support of this work by the Yildiz Technical University
Scientific Research Projects Coordination Department (Project No. 26-01-02-04).
Experimental Part
1. General. All reactions were conducted under N2 and carried out in a Schlenk system. Column
chromatography (CC): silica gel 60. TLC: silica gel precoated (0.2 mm layer) aluminium sheets (Merck).
M.p.: Gallenkamp-melting-point apparatus; uncorrected. IR Spectra: Perkin-Elmer FT-IR spectrometer;
KBr pellets; in cmÀ1. NMR Spectra: Bruker Digital-FT-NMR-Avance (400 MHz) and Varian Inova
(500 MHz) spectrometers; CDCl3 solns.; d in ppm rel. to SiMe4 as internal standard, J in Hz. MS: Varian
Saturn 2100T/GC3900 GC/MS spectrometer; FAB ionization; in m/z (rel. %).
2. Heck Reactions of Compounds 3 and 4: General Procedure. A soln. of [Pd(OAc)2] (5.6 mg,
0.025 mmol) and AsPh3 (33.7 mg, 0.11 mmol) in anh. DMF (3 ml) was stirred under N2 at 658 for 15 min.
Then, 3 or 4 (1 mmol), Et3N (488 ml, 3.5 mmol), the appropriate aryl or heteroaryl iodide (1.5 mmol),
and HCOOH (138 mg, 3 mmol) were added. The mixture was stirred for 8 – 24 h. After cooling to r.t.,
AcOEt and brine were added, and the org. layer was dried (MgSO4), the solvent evaporated, and the
residue purified by CC.
3. Domino-Heck Reactions of Compounds 3 and 4: General Procedure. [Pd(OAc)2] (5.6 mg,
25 mmol) and AsPh3 (55 mmol) were dissolved in dry DMF (3 ml), and the soln. was stirred at 408 for
15 min. Then, 3 or 4 (1 mmol), the aryl compound (1.5 mmol), Et3N (488 ml, 3.50 mmol), and
(trimethylsilyl)ethyne or phenylethyne (3 mmol) were added rapidly in one portion. The mixture was
kept at the same temp. for 24 h. After cooling to r.t., brine (50 ml) was added, the mixture extracted with
AcOEt and dried (MgSO4), the solvent evaporated, and the residue purified by CC.
4. rel-[(3aR,4S,7R,7aS)-1,3,3a,4,7,7a-Hexahydro-1,3-dioxo-4,7-methano-2H-isoindol-2-yl]benz-
amide (3) was prepared according to [14] in 85% yield. White crystals. M.p. 104 – 1068.
N-(Benzoylamino)-5-exo-phenylbicyclo[2.2.1]heptane-2-endo,3-endo-dicarboximide (¼ rel-N-
[(3aR,4S,5S,7R,7aS)-Octahydro-1,3-dioxo-5-phenyl-4,7-methano-2H-isoindol-2-yl]benzamide; 5a). CC
(AcOEt/hexane 2 :1): 5a (90%). White crystals. M.p. 119 – 1218. IR: 3274, 3059, 2971, 1785, 1731, 1692,
1189. 1H-NMR (400 MHz): 1.59 (d, J ¼ 10.6, HantiÀC(7)); 1.66 – 1.80 (m, HsynÀC(7)); 1.90 – 1.98 (m,
CH2(6)); 2.98 (d, J ¼ 10.0, HÀC(1), HÀC(4)); 3.22 – 3.27 (m, HÀC(2), HÀC(3), HendoÀC(5)); 7.20 –
7.35 (m, 5 arom. H); 7.42 (t, J ¼ 7.4, 2 arom. H); 7.54 (t, J ¼ 7.4, 1 arom. H); 7.85 (d, J ¼ 8.4, 2 arom.H);
8.68 (br. s, NH). 13C-NMR (100 MHz): 32.61 (CH2); 39.29 (CH2); 39.94; 41.64; 45.91; 46.53; 47.15; 126.12;
127.16; 127.73; 128.46; 128.71; 130.49 (q); 132.83; 152.68 (q); 165.24 (C¼O); 175.03 (C¼O); 175.33
.
(C¼O). MS: 360 (11.8, Mþ ), 255 (8.2, [M À COPh]þ), 191 (25.5, [M þ 1 À C13H14]þ), 119 (11.8,
NCOPhþ), 105 (56.4, COPhþ), 77 (16.4, Phþ), 57 (100, NNHCOþ).
N-(Benzoylamino)-5-exo-(4-chlorophenyl)bicyclo[2.2.1]heptane-2-endo,3-endo-dicarboximide
(¼ rel-N-[(3aR,4S,5S,7R,7aS)-5-(4-Chlorophenyl)-octahydro-1,3-dioxo-4,7-methano-2H-isoindol-2-yl]-
benzamide; 5b). CC (AcOEt/hexane 2 :1): 5b (83%). White crystals. M.p. 122 – 1248. IR: 3263, 3060,
2970, 1786, 1730, 1692, 1189. 1H-NMR (400 MHz): 1.63 (d, J ¼ 10.6, HantiÀC(7)); 1.68 – 1.72 (m,
HsynÀC(7)); 1.83 – 1.89 (m, HexoÀC(6)); 1.93 (d, J ¼ 10.6, HendoÀC(6)); 2.95 (d, J ¼ 5.2, HÀC(1)); 2.99
(br. s, HÀC(4)); 3.22 – 3.31 (m, HÀC(2), HÀC(3), HendoÀC(5)); 7.19 (d, J ¼ 8.4, 2 arom. H); 7.27 – 7.30
(m, 2 arom. H); 7.45 (t, J ¼ 7.6, 2 arom. H); 7.58 (t, J ¼ 7.2, 1 arom. H); 7.87 (d, J ¼ 8.4, 2 arom. H); 8.44
(br. s, NH). 13C-NMR (100 MHz): 32.91 (CH2); 39.30 (CH2); 39.95; 41.10; 45.78; 46.42; 47.08; 127.73;
128.51; 128.79; 130.53 (q); 131.82 (q); 132.96; 143.32 (q); 165.38 (C¼O); 174.82 (C¼O); 174.96 (C¼O).

2384
Helvetica Chimica Acta – Vol. 90 (2007)
.
MS: 394 (11.8, Mþ ), 359 (0.9, [M À Cl]þ), 289 (5.5, [M À COPh]þ), 274 (0.9, [M À NHCOPh]þ), 178
(3.6, C11H11Clþ), 138 (5.9, C8H7Clþ), 105 (100, COPhþ), 77 (30, Phþ).
N-(Benzoylamino)-5-exo-(6-Chloropyridin-3-yl)bicyclo[2.2.1]heptane-2-endo,3-endo-dicarboxi-
mide (¼ rel-N-[(3aR,4S,5S,7R,7aS)-5-(6-Chloropyridin-3-yl)-octahydro-1,3-dioxo-4,7-methano-2H-iso-
indol-2-yl]benzamide; 5c). CC (AcOEt/hexane 5 :1): 5c (68%). Yellow crystals. M.p. 90 – 938. IR:
3263, 3054, 2971, 1783, 1730, 1690, 1186. 1H-NMR (500 MHz): 1.63 (d, J ¼ 11.0, HantiÀC(7)); 1.72 – 1.78
(m, HsynÀC(7), HexoÀC(6)); 1.85 (d, J ¼ 11.0, HendoÀC(6)); 2.95 (d, J ¼ 5.2, HÀC(1)); 2.98 (br. s,
HÀC(4)); 3.21 – 3.31 (m, HÀC(2), HÀC(3), HendoÀC(5)); 7.25 (d, J ¼ 8.4, 2 arom. H); 7.43 – 7.59 (m, 3
arom. H); 7.89 (d, J ¼ 7.2, 2 arom. H); 8.22 (s, 1 arom. H); 8.83 (br. s, NH). 13C-NMR (125 MHz): 32.94
(CH2); 38.95; 39.36 (CH2); 39.98; 45.25; 46.22; 46.97; 124.01; 127.80; 128.81; 130.53 (q); 133.01; 139.28
.
(q); 148.25; 149.13 (q); 165.69 (C¼O); 174.60 (C¼O); 174.62 (C¼O). MS: 395 (31.8, Mþ ), 179 (11.8,
C10H10ClNþ), 105 (100, COPhþ), 77 (51.8, Phþ).
N-(Benzoylamino)-5-exo-phenyl-6-exo-[(trimethylsilyl)ethynyl]bicyclo[2.2.1]heptane-2-endo,3-en-
do-dicarboximide (¼ rel-N-{(3aR,4S,5R,6S,7R,7aS)-Octahydro-1,3-dioxo-5-phenyl-6-[2-(trimethylsilyl)-
ethynyl]-4,7-methano-2H-isoindol-2-yl}benzamide; 5d). CC (AcOEt/hexane 2 :1): 5d (76%). Light
yellow crystals. M.p. 124 – 1278. IR: 3297, 3063, 2958, 2176, 1789, 1728, 1693, 1190. 1H-NMR (500 MHz):
0.24 (s, Me3Si); 1.93 (d, J ¼ 10.7, HantiÀC(7)); 2.66 (d, J ¼ 10.3, HsynÀC(7)); 3.18 (d, J ¼ 4.9, HÀC(4));
3.32 (d, J ¼ 3.9, HÀC(1)); 3.39 – 3.46 (m, HÀC(2), HÀC(3), HendoÀC(5)); 3.51 (br. s, HendoÀC(6));
7.32 – 7.44 (m, 5 arom. H); 7.57 (t, J ¼ 7.8, 2 arom. H); 7.70 (t, J ¼ 8.8, 1 arom. H); 7.99 (d, J ¼ 7.3, 2 arom.
H); 8.61 (br. s, NH). 13C-NMR (125 MHz): À 0.03 (Me); 38.89 (CH2); 40.46; 44.15; 46.10; 46.22; 46.89;
47.78; 89.92, 106.60 (CꢀC); 126.55; 128.10; 128.14; 128.71; 129.06; 129.17; 130.77; 133.16 (q); 141.70 (q);
.
165.62 (C¼O); 174.85 (C¼O); 174.91 (C¼O). MS: 456 (4.5, Mþ ), 441 (20.9, [M À Me]þ), 383 (1.8,
[M À SiMe3]þ), 322 (4.5, [M À NNHCOPh]þ), 120 (0.9, NHCOPhþ), 105 (100, COPhþ), 77 (31.8, Phþ),
73 (18.2, Me3Siþ).
5. N-[(2,2-Dimethylpropanoyl)amino]bicyclo[2.2.1]hept-5-ene-2-endo,3-endo-dicarboximide (¼ rel-
N-[(3aR,4S,7R,7aS)-1,3,3a,4,7,7a-Hexahydro-1,3-dioxo-4,7-methano-2H-isoindol-2-yl]-2,2-dimethylpro-
panamide; 4). N-Aminobicyclo[2.2.1]hept-5-ene-2-endo,3-endo-dicarboximide (2; 600 mg, 3.3 mmol),
which was prepared according to [10], and 2,2-dimethylpropanoyl chloride (411 mg, 3.3 mmol) were
stirred in pyridine (5 ml) at r.t. for 4 h. After TLC control, the pyridine was removed i.v. The residue was
purified by CC (AcOEt/hexane 1:1): 4 (90%). White crystals. M.p. 253 – 2558. IR: 3251, 3071, 2980, 1785,
1724, 1669, 1201. 1H-NMR (500 MHz): 1.30 (s, 3 Me); 1.55 (d, J ¼ 8.8, HsynÀC(7)); 1.76 (d, J ¼ 9.8,
HantiÀC(7)); 3.33 (br. s, HÀC(1), HÀC(4)); 3.44 (br. s, HÀC(2), HÀC(3)); 6.19 (s, HÀC(5), HÀC(6));
7.31 (br. s, NH). 13C-NMR (125 MHz): 26.26 (Me); 37.53 (CH2); 43.29; 43.92; 50.81 (q); 133.78; 172.82
.
(C¼O); 175.30 (C¼O). MS: 262 (4.5, Mþ ), 247 (0.9, [M À Me]þ), 197 (11.8, [M þ 1 À C5H6]þ), 178
(63.6, [M þ 1 À COCMe3]þ), 114 (49.1, NNHCOCMe3þ), 92 (5.5, C7H8þ ), 57 (100, Me3Cþ).
5-exo-(4-Chlorophenyl)-N-[(2,2-dimethylpropanoyl)amino]bicyclo[2.2.1]heptane-2-endo,3-endo-di-
carboximide (¼ rel-N-[(3aR,4S,5S,7R,7aS)-5-(4-Chlorophenyl)-octahydro-1,3-dioxo-4,7-methano-2H-
isoindol-2-yl]-2,2-dimethylpropanamide; 6a). CC (AcOEt/hexane 5 :1): 6a (86%). Yellow crystals.
1
M.p. 92 – 958. IR: 3316, 3049, 2971, 1786, 1729, 1695, 1191. H-NMR (400 MHz): 1.33 (s, 3 Me); 1.56 (d,
J ¼ 11.2, HantiÀC(7)); 1.63 (s, HsynÀC(7)); 1.76 – 1.87 (m, CH2(6)); 2.8 (d, J ¼ 5.6, HÀC(1)); 2.93 (br. s,
HÀC(4)); 3.14 – 3.25 (m, HÀC(2), HÀC(3), HendoÀC(5)); 7.13 (d, J ¼ 8.4, 2 arom. H); 7.23 (d, J ¼ 8.6, 2
arom. H); 7.43 (br. s, NH). 13C-NMR (100 MHz): 27.35 (Me); 32.63 (CH2); 38.62 (q); 39.23 (CH2); 39.84;
41.06; 45.79; 46.38; 46.95; 128.42; 128.56; 129.87 (q); 131.74 (q); 174.51 (C¼O); 174.61 (C¼O); 174.64
.
(C¼O). MS: 374 (20.9, Mþ ), 290 (18.2, [M þ 1 À COCMe3]þ), 274 (5.5, [M À NHCOCMe3]þ), 178 (21.8,
C11H11Clþ), 138 (11.8, C8H7Clþ), 114 (13.6, NNHCOCMeþ3 ), 85 (14.5, COCMe3þ), 57 (100, Me3Cþ).
5-exo-(6-Chloropridin-3-yl)-N-[(2,2-dimethylpropanoyl)amino]bicyclo[2.2.1]heptane-2-endo,3-en-
do-dicarboximide (¼ rel-N-[(3aR,4S,5S,7R,7aS)-5-(6-Chloropyridin-3-yl)-octahydro-1,3-dioxo-4,7-
methano-2H-isoindol-2-yl]-2,2-dimethylpropanamide; 6b). CC (AcOEt): 6b (62%). White crystals.
M.p. 238 – 2408. IR (KBr): 3263, 3086, 2975, 1786, 1732, 1699, 1194. 1H-NMR (400 MHz): 1.37 (s, 3 Me);
1.66 (d, J ¼ 11.6, HantiÀC(7)); 1.74 (s, HsynÀC(7)); 1.77 – 1.83 (m, HexoÀC(6)); 1.89 (d, J ¼ 12.0,
HendoÀC(6)); 2.94 (d, J ¼ 4.4, HÀC(1)); 3.02 (br. s, HÀC(4)); 3.21 – 3.32 (m, HÀC(2), HÀC(3),
HendoÀC(5)); 7.27 (d, J ¼ 8.4, 1 arom. H); 7.51 – 7.53 (dd, J ¼ 2.5, 10.8, 1 arom. H); 7.62 (br. s, NH); 8.28
(d, J ¼ 2.4, 1 arom. H). 13C-NMR (100 MHz): 27.34 (Me); 32.68 (CH2); 38.61 (q); 38.93; 39.30 (CH2);

Helvetica Chimica Acta – Vol. 90 (2007)
2385
39.90; 45.35; 46.17; 46.86; 123.91; 138.02; 139.21 (q); 148.38; 149.18 (q); 174.28 (C¼O); 174.37 (C¼O);
.
176.77 (C¼O). MS: 375 (96.4, Mþ ), 291 (35.5, [M þ 1 À COCMe3]þ), 205 (6.4, C12H12ClNþ), 179 (31.8,
C10H10ClNþ), 139 (8.2, C7H6ClNþ), 85 (7.3, COCMe3þ), 57 (92.7, Me3Cþ).
5-exo-(4-Chlorophenyl)-N-[(2,2-dimethylpropanoyl)amino]-6-exo-(phenylethynyl)bicyclo[2.2.1]-
heptane-2-endo,3-endo-dicarboximide (¼ rel-N-[(3aR,4S,5R,6S,7R,7aS)-5-(4-Chlorophenyl)-octahydro-
1,3-dioxo-6-(2-phenylethynyl)-4,7-methano-2H-isoindol-2-yl]-2,2-dimethylpropanamide; 6c). CC
(AcOEt/hexane 2 :1): 6c (68%). Light yellow crystals. M.p. 116 – 1198. IR: 3345, 3060, 2973, 2225,
1
1787, 1733, 1699, 1192. H-NMR (500 MHz): 1.36 (s, 3 Me); 1.79 (d, J ¼ 10.7, HantiÀC(7)); 2.48 (d, J ¼
10.3, HsynÀC(7)); 3.09 (d, J ¼ 3.9, HÀC(4)); 3.14 (d, J ¼ 3.9, HÀC(1)); 3.26 – 3.28 (m, HÀC(2),
HÀC(3)); 3.51 (d, J ¼ 7.3, HendoÀC(6)); 3.58 (br. s, HendoÀC(5)); 6.84 (d, J ¼ 7.3, 2 arom. H); 7.13 – 7.20
(m, 5 arom. H); 7.27 (d, J ¼ 7.3, 2 arom. H); 7.41 (br. s, NH). 13C-NMR (125 MHz): 26.33 (Me); 37.10
(CH2); 37.60 (q); 39.07; 42.60; 44.34; 44.65; 45.41; 46.26; 84.77, 88.65 (CꢀC); 122.21; 126.59; 126.88;
127.00; 128.68; 130.21 (q); 130.92; 133.77 (q); 139.15 (q); 172.84 (C¼O); 172.93 (C¼O); 175.64 (C¼O).
.
MS: 474 (9.1, Mþ ), 389 (14.5, [M À COCMe3]þ), 374 (2.7, [M À NHCOCMeþ3 ]), 304 (2.7, C21H17Clþ),
278 (23.6, C19H15Clþ), 238 (7.3, C16H11Clþ), 114 (4.5, NNHCOCMe3þ), 57 (59.1, CMeþ3 ).
REFERENCES
[1] D. Mitchell, H. Yu, Curr. Opin. Drug Discov. Dev. 2003, 6, 876.
[2] Z.-L. Wei, C. George, A. P. Kozikowski, Tetrahedron Lett. 2003, 44, 3847.
[3] E. Negishi, A. de Meijere, ꢁ Handbook of Organopalladium Chemistry for Organic Synthesisꢂ,
Wiley-Interscience, New York, 2002, p. 1133.
[4] A. V. Cheprakov, I. P. Beletskaya, Chem. Rev. 2000, 100, 3009.
[5] J. Storsberg, M.-L. Yao, N. ꢃcal, A. de Meijere, A. E. W. Adam, D. E. Kaufmann, Chem. Commun.
2005, 5665.
[6] J. C. Namyslo, D. E. Kaufmann, Chem. Ber./Recl. 1997, 130, 1327.
[7] F. Stuhlmann, D. E. Kaufmann, J. Prakt. Chem. 1999, 341, 455.
[8] C. Yolacan, E. Bagdatli, N. ꢃcal, D. E. Kaufmann, Molecules 2006, 11, 603.
[9] O. V. Krishchik, I. N. Tarabara, A. O. Kasꢂyan, S. V. Shishkina, O. V. Shishkin, A. K. Isaev, L. I.
Kasꢂyan, Russ. J. Org. Chem. 2004, 40, 114.
[10] L. I. Kasꢂyan, I. N. Tarabara, Y. S. Bondarenko, S. V. Shishkina, O. V. Shishkin, V. I. Musatov, Russ. J.
Org. Chem. 2005, 41, 1122.
[11] S. R. T. Prado, V. C. Filho, F. Campos-Buzzi, R. Correa, S. M. C. S. Cadena, M. B. M. Oliveria, Z.
Naturforsch., C 2004, 59, 663.
[12] A. D. Andricopula, L. A. Müller, V. C. Filho, G. S. Cani, J. F. Roos, R. Correa, A. R. S. Santos, R. J.
Nunes, R. A. Yunes, Farmaco 2000, 55, 319.
[13] I. N. Tarabara, A. O. Kasꢂyan, O. V. Krishchik, S. V. Shishkina, O. V. Shishkin, L. I. Kasꢂyan, Russ. J.
Org. Chem. 2002, 38, 1299.
[14] S. M. Verma, C. K. Rao, Tetrahedron 1972, 28, 5029.
[15] J. C. Namyslo, D. E. Kaufmann, Synlett 1999, 114.
Received July 9, 2007