Simaan and Biali
4
. The mixture was
respectively), barriers of 13.9, 14.9, and 17.6 kcal mol-1
were calculated by means of the Gutowsky-Holm18 and
were added 0.4 g (10.5 mmol) of NaBH
stirred at rt under an inert atmosphere for 3 h. After the
mixture was quenched with water and extracted with CHCl
the organic phase was evaporated and the residue precipitated
from a mixture of CHCl /MeOH yielding 70 mg of crude 13.
The product was further purified by chromatography (silica,
eluent 3:1 CHCl /hexane) yielding 45 mg of 13 (11%): mp 238
3
,
Eyring equations. The barrier of 14 is lower than the one
-
1
19
3
of 1 (15.7 kcal mol in CDCl ), but increasing the bulk
3
of the substituent raises the barrier significantly.
3
1
Con clu sion s
°C dec; H NMR (400.133 MHz, CDCl ) δ 7.40 (d, 2H), 7.17 (d,
3
2
2
2
J
H), 6.53 (d, J HF ) 48.3 Hz, 2H), 6.00 (ddd, J
.6 Hz, J ) 5.6 Hz, 2H), 5.66 (m, 2H), 4.58 (ddd, J
) 5.9 Hz, J ) 12.6 Hz, 2H), 3.49 (d, J ) 15.7 Hz, 2H), 3.33
1
) 1.9 Hz, J
2
)
Reaction of the spirodiene calixarene derivative 9 with
alkyl cuprates affords in stereoselective fashion p-tert-
butylcalix[4]arene derivatives with trans-alkyl substit-
uents on opposite methylene bridges. These derivatives
are not available by the fragment condensation method,
and the spirodiene route provides a facile synthetic entry
into this family of systems.
3
1
) 2.0 Hz,
2
3
(d, J ) 15.6 Hz, 2H), 2.39 (d, J ) 12.6 Hz, 2H), 1.36 (s, 18H),
0.97 (s, 18H); 13C NMR (100.133 MHz, CDCl
, rt) δ 151.5 (J )
.3 Hz), 147.0 (J ) 5.6 Hz), 143.7, 141.2 (J ) 11.6 Hz), 125.4,
25.1 (J ) 8.8 Hz), 121.4 (J ) 25.4 Hz), 120.7, 119.5 (J ) 9.9
3
6
1
Hz), 87.8, 84.5 (J ) 172.4 Hz), 74.5, 41.6, 34.6, 34.2, 31.8, 28.3;
•
-
CI MS (-DCI) m/z 684.2 (M ).
,11,17,23-Tetr a -ter t-bu tyl-25,26,27,28-tetr a h yd r oxy-2,-
4-d im eth ylca lix[4]a r en e (Tr a n s Isom er , 14). Into 50 mL
5
Exp er im en ta l Section
1
of dry THF at 0 °C were added under an inert atmosphere 3.5
mL of a 3 M MeMgBr solution in diethyl ether (10.5 mmol)
and 0.34 g of CuCN (3.8 mmol). The mixture was stirred until
a clear solution was obtained. After addition of 1 g of 9 (1.25
mmol), the mixture was stirred for 2 h, and during this time
it was allowed to reach rt. After quenching with water and
P r ep a r a tion of 1. p-tert-Butylcalix[4]arene (1) was pre-
pared by a minor modification of the procedure of Gutsche and
2
0
Iqbal. A 50 g portion of p-tert-butylphenol was mixed with
.7 g of NaOH and 35 mL of a 32% formaldehyde solution.
0
The mixture was rapidly heated with a heating mantle with
stirring under nitrogen until a solid yellow-green mass was
obtained. At this point, the heating was immediately discon-
tinued, 800 mL diphenyl ether was added, and the reaction
continued according to the procedure of Gutsche and Iqbal.
Using this slightly modified procedure, we repeatedly obtained
yields of 40-42 g (74-77%) of 1 (prior to recrystallization),
which are somewhat higher than the 61% yield reported in
ref 20 for the crude product.
extraction of the aqueous phase with CH
organic phases were evaporated and the residue was recrystal-
lized from CHCl /EtOH yielding 0.5 g (59%) 14. Alternatively,
2 2
Cl , the combined
3
the compound could be purified by recrystallization from
1
pyridine: mp 252 °C (from pyridine); H NMR (400.133 MHz,
CDCl , 240 K) δ 10.56 (br s, 4H), 7.15 (br s, 2H), 7.13 (br s,
3
2H), 7.00 (br s, 2H), 6.99 (br s, 2H), 4.73 (q, J ) 6.9 Hz, 1H),
4.22 (d, J ) 13.8 Hz, 2H), 4.10 (q, J ) 7.7 Hz, 1H), 3.53 (d, J
) 13.9 Hz, 2H), 1.94 (d, J ) 7.6 Hz, 3H), 1.71 (d, J ) 6.8 Hz,
3H), 1.20 (s, 18H), 1.18 (s, 18H) ppm; 13C NMR (100.133 MHz,
Rea ction of Sp ir od ien e 9 w ith Tetr a bu tyla m m on iu m
8
a
F lu or id e. Spirodiene 9 (0.3 g, 0.37 mmol) was dissolved in
0 mL of CH Cl , and to the solution was added 1 g of
5
2
2
tetrabutylammonium fluoride hydrate. After 3 h reflux, the
solution was washed with water several times, and the organic
CDCl
3
, 230 K), δ 147.4, 145.8, 144.2, 143.7, 131.9, 130.4, 128.6,
127.2, 127.0, 126.2, 125.1, 121.4, 48.1, 34.1, 33.9, 32.2, 31.3,
-
•
phase was dried (MgSO
4
) and evaporated. The residue was
31.2, 29.4, 18.3, 16.6; CI MS (-DCI) m/z 676.4 (M ).
,11,17,23-Tetr a -ter t-bu tyl-25,26,27,28-tetr a h yd r oxy-2,-
4-d ieth ylca lix[4]a r en e (Tr a n s Isom er , 15). EtMgBr was
prepared by reacting 3 mL of EtBr (0.04 mol) and Mg (0.95 g,
.04 mmol) in 20 mL of dry THF. A 5 mL portion of the
recrystallized from CHCl
3
/MeOH yielding 0.15 g (59%) 11: mp
5
1
2
78-280 °C dec; H NMR (400.133 MHz, CDCl
3
, rt) δ 7.41 (br
1
s, 2H, Ar-H), 7.19 (br s, 2H, Ar-H), 6.90 (t, J ) 2.6 Hz, 2H,
2
CdC-H), 6.60 (d, J HF ) 46.2 Hz, 2H, CHF), 5.96 (t, J ) 1.7
0
Hz, 2H, CdC-H), 3.79 (d, J ) 15.5 Hz, 2H, CH ), 3.07 (d, J )
2
resulting solution of the Grignard reagent (10 mmol) was
added to 50 mL of dry THF at 0 °C under an inert atmosphere
followed by 0.34 g of CuCN (3.8 mmol). After a homogeneous
solution was obtained, 9 (1 g, 1.25 mmol) was added, and the
stirring was continued for 3 h until the mixture reached rt.
1
5.5 Hz, 2H, CH
2
), 1.36 (s, 18H, t-Bu), 1.03 (s, 18H, t-Bu); 13
, rt) δ 193.4, 150.4 (d, J ) 6.6 Hz),
44.8 (d, J ) 2.8 Hz), 144.0, 140.6 (d, J ) 4.7 Hz), 134.1 (d, J
C
NMR (100.133 MHz, CDCl
1
3
)
16.4 Hz), 129.2 (d, J ) 2.6 Hz), 126.2 (d, J ) 2.4 Hz), 122.1
(
d, J ) 26.0 Hz), 121.0, 118.8 (d, J ) 10.0 Hz), 82.6 (d, J )
After quenching with water, extraction with CH
evaporation of the organic phase, the residue was recrystal-
lized from CHCl /MeOH yielding 0.2 g (23%) 15: mp 250 °C;
H NMR (400.133 MHz, CDCl , 240 K) δ 7.11 (d, J ) 2.1 Hz,
H), 7.08 (d, J ) 2.0 Hz, 2H), 6.98 (d, J ) 2.0 Hz, 2H), 6.95 (d,
J ) 2.1 Hz, 2H), 4.37 (t, J ) 7.8 Hz, 1H), 4.20 (d, J ) 13.9 Hz,
H), 3.74 (t, J ) 8.5 Hz, 1H), 3.50 (d, J ) 14.0 Hz, 2H), 2.42
q, J ) 7.6 Hz, 2H), 2.20 (q, J ) 7.4 Hz, 2H), 1.19 (s, 18H),
.16 (s, 18H), 0.92 (overlapping t, 6H); 13C NMR (100.133 MHz,
CDCl , 230 K) δ 147.1, 146.3, 144.2, 143.6, 130.9, 129.2, 128.3,
27.9, 126.9, 126.1, 124.9, 121.6, 56.6, 37.2, 34.0, 33.9, 32.3,
2 2
Cl , and
1
6
74.1 Hz), 82.4, 37.4, 34.6, 34.3, 31.8, 28.3; CI MS (-DCI) m/z
•
-
80.3 (M ).
3
Rea ction of Sp ir od ien e 9 w ith Tetr a bu tyla m m on iu m
1
3
Ch lor id e. Spirodiene 9 (0.2 g, 0.37 mmol) was dissolved in
0 mL of CH Cl , and to the solution was added 4 g of
2
5
2
2
tetrabutylammonium chloride hydrate. After reflux overnight,
the solution was washed with water several times, and the
2
(
1
organic phase was dried (MgSO
4
) and evaporated. The product
1
2 was separated from the starting material 9 by chromatog-
3
2 2
raphy (silica, eluent: 2:1 CH Cl /hexane) and further recrys-
1
3
tallized from CHCl
3
/MeOH yielding 50 mg (28%) 12: mp 252
•-
1.3, 31.2, 24.9, 23.2, 13.8, 12.7; CI MS (-DCI) m/z 704.5 (M ).
,11,17,23-Tetr a -ter t-bu tyl-25,26,27,28-tetr a h yd r oxy-2,-
4-d i(2-p r op yl)ca lix[4]a r en e (Tr a n s Isom er , 16). To 50 mL
1
°
C dec; H NMR (400.133 MHz, CDCl , rt) δ 7.64 (br s, 2H),
3
5
7
2
1
.20 (br s, 2H), 6.87 (d, J ) 2.4 Hz), 6.20 (s, 2H), 5.91 (d, J )
.3 Hz), 3.84 (d, J ) 15.5 Hz, 2H), 3.08 (d, J ) 15.5 Hz, 2H),
1
.38 (s, 18H), 1.03 (s, 18H); 1 C NMR (100.133 MHz, CDCl
3
of dry THF were added under an inert atmosphere at 0 °C
3
,
1
0
0.5 mL of a 2 M solution of i-PrMgCl in ether (21 mmol) and
.34 g of CuCN (3.8 mmol). The mixture was stirred until a
rt) δ 192.9, 150.9, 145.9, 144.2, 141.4, 136.9, 128.4, 126.2,
1
21.9, 121.6, 121.1, 82.7, 50.0, 37.2, 34.7, 34.4, 31.8, 28.3; CI
+
homogeneous solution was obtained, and then 9 (1 g, 1.25
mmol) was added. The mixture was stirred for 4 h, and during
this period it was allowed to reach rt. After quenching with
water, the aqueous phase was extracted with chloroform and
MS (+DCI) m/z 713.3 (MH ).
4
Rea ction of 11 w ith Na BH . A 0.4 g (0.6 mmol) portion of
1
1 was dissolved in 50 mL of dry THF, and to the mixture
the organic phase was dried (MgSO
4
) and evaporated. The
/MeOH yielding 0.2 g
(22%) 16: mp 286 °C; H NMR (400.133 MHz, CDCl , rt) δ
(18) Gutowsky, H. S.; Holm, C. H. J . Chem. Phys. 1956, 25, 1228.
(19) Gutsche, C. D.; Bauer, L. J . J . Am. Chem. Soc. 1985, 107, 6052.
(20) Gutsche, C. D.; Iqbal, M. Org. Synth. 1989, 68, 234.
residue was recrystallized from CHCl
3
1
3
3
638 J . Org. Chem., Vol. 68, No. 9, 2003