1661
G. Wagner et al. • Diyne Cyclization in Camphor Derivatives
was separated and the aqueous layer extracted
with dichloromethane (3x50 ml). TTie combined
organic layers were dried (Na2S 0 4), the solvents
were evaporated, and the residue was recrystal-
lized from dichloromethane/hexane (1:1). Yield
3.9 g (90%), m.p. 224-225 0 C; [«]t>2 = -30.0 (c =
1.0 in acetone); [a] ^ = -34.2 (c = 1.0 in ethanol);
m/z'. 431 [M+],
starting material (2.85 vs. 3.23 Ä). The next step in
the reaction should be the annulation of the five-
membered ring, leading to a second interm ediate
13. This cation is indeed another local energy mini-
mum (38.2 kcal/mol more stable). The distance C-
12 - C-13 is typical for a single bond (1.48 A). In
the final cation 14 the positive charge is stabilized
considerably by transfer to the sulfur atom. This is
reflected in an additional decrease of the heat of
formation (64.2 kcal/mol more stable than 12, 26.0
kcal/mol more stable than 13). The stabilization
effect is also reflected in the decrease of the calcu-
lated dipole moments (12: 8.0 D, 13: 8.0 D, 14: 5.1
D). The S-O distance was calculated as 1.69 A
(typical S-O single bond, com pared with the
double bond of 1.42 A to the second oxygen), and
the newly formed C-O bond as 1.41 A(single
bond). Attem pts to localize the transition states
failed, probably due to the high complexity of the
molecules. Energy minima lower than 14 were not
detected. Thus, these calculations support strongly
our conclusions drawn from N M R measurem ents
concerning the structures of the intermediates.
C26H „N O ,S (431.56)
Calcd
C 72.4 H 5.8 N 3.1% ,
Found C 71.9 H 5.9 N 3.1% .
(]aS,3aS, 7R)-7-H ydroxy-l ,8,8-trim ethyl-l a, 7-
bis(phenylethynyl) 1,1a,4,5,6,7-hexahydro-3H-
3a,6-m ethano-2,1-benzisothiazole 2,2-D ioxide (3):
To a solution of 2 (0.30 g, 0.70 mmol) in 3 ml of
dry THF, sodium hydride (60% in mineral oil, 28
mg, 0.70 mmol) was added. A fter stirring for 30
min at room tem perature, dimethyl sulfate (67 /ul,
0.70 mmol) was added, and stirring was continued
for 12 h. A fter workup with dichloromethane/
water, the residue was recrystallized from dichlo-
romethane/hexane (1:1). Yield: 0.30 g (97%), m.p.
166-168° C; [cc]d = -16.9 (c = 0.6 in ethanol); m /
z: 445 [M+],
C27H ,7NO,S (445.59)
Calcd
C 72.8 H6.1 N 3.1% ,
Experimental
Found C 72.5 H 6.0 N 3.2%.
NMR spectra were obtained with a Bruker AM
360 instrument ('H : 360.13 MHz, 13C: 90.56 MHz).
Optical rotations were m easured with a Perkin El-
mer 241 M polarimeter and mass spectra with a
Varian CH5 instrument (El mode, 70 eV).
Semiempirical calculations were perform ed with
P M 3 using the standard param etrization as im ple-
mented in the H y p e r c h e m (release 3 ) and M o p a c
(version 7.0 for DOS) software packages. H y p -
(1aS,3aS, 7R)-7-M ethoxy-1,8,8-trim ethyl-l a, 7-
bis(phenylethynyl)-! ,1a,4,5,6,7-hexahydro-3H -
3a,6-m ethano-2,l-benzisothiazole 2,2-D ioxide (4):
The compound was prepared as described for 3,
except that the amounts of sodium hydride and
dimethyl sulfate were doubled. The crude product
was purified by chromatography (silicagel/dichlo-
rom ethane). R f 0.32, yield: 0.31 g (98%), m.p. 6 2 -
65° C; [a]o = +16.4 (c = 0.9 in ethanol); m/z:
459 [M +\
e r
c
h
e
m
was used for geometry optimizations (Po-
lak-Ribiere algorithm) followed by single-point
calculations and M o p a c for the localization of
transition states.
C^8H 29NO,S (459.61)
Calcd
C 73.2 H 6.4 N 3.1% ,
Found C 73.5 H 6.2 N 3.0% .
Starting materials 2-4
Reaction o f 2 with TiCl4:
(1aS,3aS,7R)-7-H ydroxy-8,8-dim ethyl-la, 7-
(3aS,6aS,9aS)-7-(Z-2-Chloro-2-
phenylm ethylene)-6a-hydroxy-10,10-dimethyl-8-
phenyl-3a,4,5,6,6a, 7-hexahydro-l H,3H-3a,6-
bis(phenylethynyl)-! ,1a,4,5,6,7-hexahydro-3H-
3a,6-m ethano-2,l-benzisothiazole 2,2-D ioxide (2):
To a solution of phenylacetylene (2.6 g, 25 mmol)
in dry diethyl ether (50 ml), 25 mmol of butyl lith-
ium (2.5 M solution in hexane, 10 ml) was added
dropwise at room tem perature. A fter stirring for
30 min the oxoimine 1 (2.3 g, 10 mmol) was added
in five portions over a period of 10 min. The mix-
ture was heated at reflux for 12 h and then hy-
drolyzed with 25 ml of water. The organic layer
methano-indeno[3a,4-c]isothiazole
2,2-D ioxide
(10): To a solution of TiCl4 (55 /d, 0.50 mmol) in
3 ml of dichloromethane, a solution of the sulfon-
amide 2 (0.22 g, 0.50 mmol) in 12 ml of dichloro-
m ethane was added under nitrogen at 0 °C. The
mixture was stirred for 5 h. W ater (10 ml) was
added, and the aqueous layer was extracted with
Unauthenticated
Download Date | 11/18/19 6:18 AM