M. Darabantu et al. / Tetrahedron 56 (2000) 3799±3816
3815
1-Aza-5-hydroxymethyl-3,7-dioxa-8-phenyl-2-spirocyclo-
heptyl-bicyclo[3.3.0]octane, 6d. yellow oil (pentane/
(1C), 41.3 (1C), 37.0 (1C), 36.7 (1C), 36.3 (1C), 32.4 (1C),
30.0 (1C), 29.0 (1C), 28.7 (1C), 19.0 (1C).
AcOEt 2.5:1 v/v); 54. Anal. Calcd for C H NO : C
1
8
25
3
p
p
7
1.26%, H 8.31%, N 4.62%. Found: C 70.99%, H 8.51%,
trans-Di-{(1R ,5S )-1-aza-5-methyl-3,7-dioxabicyclo-
[3.3.0]octa-2-ylidene}-1,4-dispirocyclohexane, l-11a
(50%) and trans-1-{(1R ,5S )-1-aza-5-methyl-3,7-di-
p
p
p
13
N 4.80%. (1S , 8R ,5R )-diastereomer (78%, cis); C NMR
DMSO-d , 100 MHz, d, ppm): 146.4 (1C), 133.1 (2C),
p
p
(
6
0 0 0 0
p
p
1
7
32.1 (2C), 131.9 (1C), 105.5 (1C, C-2), 96.1 (1C, C-8),
9.0 (1C, C-5), 77.9 and 74.8 (2C, C-6, -4), 71.7 (1C, ±
oxabicyclo[3.3.0]octa-2-ylidene}-4-{(1 S ,5 R )-1 -aza-5 -
0
0
0
cyclohexane, u-11a (50%); white crystalline powder; 31;
methyl-3 ,7 -dioxabicyclo[3.3.0]octa-2 -ylidene}-dispiro-
CH OH), 44.0 (1C), 39.6 (1C), 33.9 (1C), 33.7 (1C), 27.2
2
p
1C), 26.7 (1C). (1S ,8S ,5R )-Diastereomer (22%, trans);
H NMR (DMSO-d , 400 MHz, d, ppm and J, Hz, only
6
p
p
(
150-1 and 194-5(Et O, mixture u1l forms); 194-5 (DMSO,
2
1
l-form). Anal. Calcd for C H N O : C 61.91%, H 8.44%,
16 26
2
4
1
N 9.03%. Found: C 62.10%, H 8.11%, N 8.88%. C NMR
3
distinct signals are listed): 7.48±7.28 (5H, m); 5.58 (1H,
s, H-8); 4.90 (1H, t, 5.4, ±OH); 3.92 (1H, d, 8.8, H-6);
(DMSO-d , 100 MHz, d, ppm) l-11a: 96.8 (2C, C-2), 80.3
6
3.84 (1H, d, 9.0, H-6); 3.82 (1H, d, 8.9, H-4); 3.80 (1H, d,
H-4); 3.45 (2H, m, ±CH OH); 2.00±1.39 (8H, m). C NMR
(2C, C-8), 75.3 and 73.0 (4C, C-6, -4), 68.8 (2C, C-5), 34.4
1
3
13
(2C), 28.5 (2C), 23.6 (2C, 2£±CH ). C NMR (CDCl ,
2
3
3
0
81.15 and 81.08 (4C, C-8, -8 ), 76.12, 76.00, 73.82 and
(
DMSO-d , 100 MHz, d, ppm, only distinct signals are
6
100 MHz, d, ppm) l-11a1u-11a: 96.6 (4C, C-2, C-2 ),
0
73.76 (8C, C-6, -6 , -4, -4 ), 69.3 (4C, C-5, -5 ), 34.8
listed): 136.1 (1C), 133.0 (1C), 129.7 (1C), 101.3 (1C, C-
), 79.3 and 77.7 (2C, C-6, -4), 71.0 (1C, ±CH OH). Both
diastereomers were isolated as a single fraction.
0
0
0
8
2
(2C), 34.4 (2C), 29.2 (2C), 29.0 (2C), 23.8 (4C, 4£±CH3).
p
trans-1-{(1R ,5S )-1-Aza-5-ethyl-3,7-dioxabicyclo[3.3.0]-
p
0 0 0 0 0 0
p
p
Typical procedure for the synthesis of the compounds 7
and 11
octa-2-ylidene}-4-{(1 S ,5 R )-1 -aza-5 -ethyl-3 ,7 -dioxa-
0
90%) and trans-di-{(1R ,5S )-1-aza-5-ethyl-3,7-dioxa-
bicyclo[3.3.0]octa-2 -ylidene}-dispirocyclohexane, u-11b
p
p
(
bicyclo[3.3.0]octa-2-ylidene}-1,4-dispirocyclohexane, l-11b
(
1
Di)spiranes 9, 10 as 0.12 M benzene solution (for dispirane
0c, as toluene suspension) were treated with the stoichio-
(10%); white crystalline powder; 33; 148-9(Et O). Anal.
2
metric amount of the corresponding aldehyde (p-TsOH as
catalyst) and re¯uxed in a Dean±Stark trap with stirring and
continuous removal of water. After 8 h TLC monitoring
indicated the starting materials in small traces. After neutra-
lising at room temperature with solid Na CO the reaction
Calcd for C H N O : C 63.88%, H 8.93%, N 8.28%.
4
1
8
30
2
1
Found: C 64.05%, H 8.66%, N 8.55%. C NMR (CDCl ,
3
3
0
(2C, C-8, -8 ), 74.6 and 72.1 (4C, C-6, -6 , -4, -4 ), 73.1 (2C,
75 MHz, d, ppm): u-11b (90%) 96.6 (2C, C-2, -2 ), 81.3
0
0
0
0
C-5, -5 ), 34.4 (2C), 30.4 (2C), 28.8 (2C, 2£±CH CH ), 8.9
2
3
2
3
1
3
mixture was concentrated in vacuo to yield the crude
product which was crystallised from an appropriate solvent
(2C, 2£±CH ). C NMR (CDCl , 75 MHz, d, ppm): l-11b
3
3
0
0
(10%): 96.9 (2C, C-2, -2 ), 82.0 (2C, C-8, -8 ), 75.7 and 72.0
0
0
0
(
7a, 11) or puri®ed by ¯ash chromatography (7b).
(4C, C-6,,-6 ,-4, -4 ), 74.5 (2C, C-5, -5 ), 34.8 (2C), 30.4
2C), 28.6 (2C, 2£±CH CH ), 9.0 (2C, 2£±CH ).
(
2
3
3
Compounds, yields (%), mp (8C, isolation), elemental
analysis and NMR data (if not collected in Table 6) are
listed below.
p
p
trans-Di-{(1R ,5S )-1-aza-5-hydroxymethyl-3,7-dioxabi-
cyclo[3.3.0]octa-2-ylidene}-1,4-dispiro cyclohexane l-11c
p
p
(
50%) and trans-1-{(1R ,5S )-1-aza-5-hydroxymethyl-
p p
p
1S ,5R )-1-Aza-5-hydroxymethyl-r-3-oxa-7-oxa-2-(c-4 -
p
0
0 0 0
3,7-dioxabicyclo[3.3.0]octa-2-ylidene}-4-{(1 S ,5 R )-1 -
(
tertbutylspirocyclohexyl)-bicyclo[3.3.0]octane, 7a-cis
0
0
0
0
aza-5 -hydroxymethyl-3 ,7 -dioxabicyclo[3.3.0]octa-2 -
ylidene}-dispirocyclohexane, u-11c (50%); white crystal-
line powder; 70; 181-2(Et O). Anal. Calcd for C H N O :
p
and (1S ,5R )-1-aza-5-hydroxymethyl-r-3-oxa-7-oxa-2-
p
0
trans. White crystalline powder; 78; 138-9(pentane/Et O
(
t-4 -tertbutilspirocyclohexyl)-bicyclo[3.3.0]octane, 7a-
2
16 26
2
6
C 56.13%, H 7.65%, N 8.18%. Found: C 55.95%, H 8.00%,
2
1
3
4
:1). Anal. Calcd for C H NO : C 66.88%, H 10.10%, N
5
N 8.37%. C NMR (CD OD, 100 MHz, d, ppm) l-11c1
3
1
27
3
0 0
u-11c: 100.5 (4C, C-2, -2 ), 86.1 and 85.0 (4C, C-8, -8 ),
5
.20%. Found: C 67.00%, H 9.94%, N 4.95%. 7a-cis (94%)
C NMR (DMSO-d , 100 MHz, d, ppm): 110.3 (1C, C-2),
1
3
0
0
77.3 and 72.1 (4C, C-5, -5 ), 76.5, 74.6, 74.4 (8C, C-6, -6 ,
6
0
(2C), 32.0 (2C), 31.7 (2C).
9
6
6.5 (1C, C-8), 80.1 (1C, C-5), 72.9 and 70.8 (2C, C-6, -4),
5.5 (1C, ±CH OH), 46.4 (1C, ±CHr), 37.6 (1C), 32.0
-4, 4 ), 68.9 and 67.4 (4C, 4£±CH OH), 38.4 (2C), 38.0
2
2
(
7
1C), 31.0 (1C), 27.5 (1C, ±CH ), 23.9 (1C), 23.7 (1C);
3
1
a-trans (6%) H NMR (DMSO-d , 400 MHz, d, ppm and
6
Preparation of the monospirane 12
J, Hz, only distinct signals are listed): 4.70 (1H, d, 7.0, H-
t), 4.16 (1H, d, 7.0, H-8c), 3.82 (1H, d, 9.8, H-6t), 3.75 (1H,
d, 9.8, H-6c), 3.66 (1H, d, 8.5, H-4t), 3.61 (1H, d, 8.5, H-4c).
8
To 2-amino-2-methylpropane-1,3-diol (7.50 g, 0.071 mol)
in benzene (75 mL), cyclohexanone (8 mL, 7.6 g,
0
.078 mol) and p-TsOH as catalyst were added. The reac-
p
p
p
1S ,5R ,8R )-1-Aza-8-n-hexyl-5-hydroxymethyl-r-3-oxa-
7
(
tion mixture was then re¯uxed in a Dean±Stark trap with
continuous removal of water (about 12 h, TLC monitoring:
benzene/methanol 3:1 v/v, I -bath). The reaction mixture, as
0
tane, 7b-cis. Yellow oil (eluent toluene/acetone 3:1); 55.
-oxa-2-(c-4 -tertbutilspirocyclohexyl)-bicyclo-[3.3.0]oc-
2
Anal. Calcd for C H NO : C 71.34%, H 11.12%, N
1
a solution, was cooled at room temperature, neutralised with
solid Na CO , ®ltered off and concentrated in vacuo to yield
the crude product which was crystallised from excess of
ligroine. The solid was collected, taken with the minimum
amount of THF and the insoluble residue was ®ltered off.
2
39
3
1
3
3.96%. Found: C 70.99%, H 10.94%, N 3.85%. 7b-cis
NMR (DMSO-d , 100 MHz, d, ppm): 102.5 (1C, C-2), 95.9
C
2
3
6
(
(
1C, C-8), 78.5 (1C, C-5), 76.9 and 74.3 (2C, C-6, -4), 72.1
1C, ±CH OH), 45.6 (1C, ±CHr), 42.4 (1C), 41.8 (1C), 41.6
2