7344 J . Org. Chem., Vol. 61, No. 21, 1996
Lin et al.
portion. To this mixture at 0 °C was added dropwise a solution
of 0.155 mL (1.26 mmol) of pivaloyl chloride in 50 mL of
anhydrous CH3CN. The mixture was stirred at 0 °C for 2 h,
warmed to 25 °C for 45 min, and filtered through Celite. The
filtrate was concentrated in vacuo giving a residue which was
carefully washed with petroleum ether/ether (3:1) to afford 837
mg (97%) of a foam comprised of a 1:1 E,Z mixture of iminium
salt 13: UV max (CH3CN) 284 nm (ꢀ 26 000); 1H NMR -0.25,
-0.07 (S, 9 H), 0.81 and 0.84 (ABq, J ) 5.5 Hz), 1.41 and 1.48
(ABq, J ) 12.5 Hz, 2 H), 1.02 (s, 9 H), 2.54-2.74 (m, 2 H),
3.27-3.86 (m, 6 H), 3.82 and 4.12 (ABq, J ) 17.3 Hz, 1H),
3.87 and 4.24 (ABq, J ) 17.9 Hz, 1H) 4.20 and 5.00 (ABq, J )
15.5 Hz, 1H), 4.74 and 5.15 (ABq, J ) 15.7 Hz, 1H), 4.29 and
4.38 (ABq, J ) 12.3 Hz, 1H), 4.39 and 4.43 (ABq, J ) 12.2 Hz,
1H), 4.61 and 4.85, 4.81 and 4.88 (s, 2 H), 5.78 and 5.87 (ABq,
J ) 1.2 Hz, 1H), 5.90 and 5.95 (ABq, J ) 1.1 Hz, 1H), 6.63
and 6.75, 6.69 and 6.81 (s, 2 H), 7.00 (d, J ) 6.4 Hz), 7.10-
7.39 (m, 9 H); 13C NMR -1.8, -1.6, 24.3, 24.4, 26.2, 30.3, 31.7,
32.1, 33.3, 39.7, 56.2, 57.3, 58.7, 59.5, 69.7, 69.7, 72.7, 73.0,
101.3, 108.0, 110.8, 108.9, 109.2, 109.7, 109.9, 121.2, 122.4,
122.5, 127.1, 127.3, 127.5, 127.6, 127.7, 128.2, 128.3, 128.5,
129.0, 129.1, 129.5, 131.4, 131.7, 131.9, 132.4, 137.8, 137.9,
138.0, 138.3, 146.1, 146.4, 148.8, 148.9, 172.3, 172.4, 187.4,
187.4, 187.9; IR (CHCl3) 1785, 1565, 1500; MS, m/ z (relative
intensity) 651 (M - HClO4, 0.03), 568 (28), 496 (63), 476 (12),
459 (40), 404 (39), 387 (100), 368 (23), 332 (32), 296 (58), 254
(33), 242 (28), 227 (26), 214 (22), 185 (10); HRMS, m/ z
651.3374 (C40H49SiNO5 requires 651.3380).
Ir r a d ia tion of Im in iu m P er ch lor a te 13. F or m a tion of
1-Aza -1-b en zyl-6-[2′-(2-(b en zyloxy)et h yl)-4′,5′-(m et h yl-
en ed ioxy)p h en yl]-3-m et h ylid en e-7-(p iva loyloxy)sp ir o-
[4.4]n on -6-en e (14). A nitrogen-purged 3.4 × 10-3 M solution
of iminium salt 13 in CH3CN (837 mg, 1.11 mmol in 336 mL)
was irradiated with Corex-filtered light for 12 h at which time
the absorbance at 284 nm was 47% of the initial value.
Saturated aqueous NaHCO3 (4 mL) was added, and the
resulting mixture was concentrated in vacuo to give a residue
which was dissolved in CH2Cl2 and washed with water. The
organic layer was dried and concentrated in vacuo to yield a
residue which was subjected to F-20 alumina column chro-
matography giving 297 mg (46%) of spirocyclic amine 14
(elution with 90:10 hexanes/ethyl acetate) and 251 mg (40%)
of enaminone 12 (elution with ethyl acetate). 14: UV max
(CH3CN) 291 (ꢀ 5100); 1H NMR 1.00 (s, 9 H), 1.65 (d of
apparent t, J ) 13.7, 9.7, 8.3 Hz, 1 H), 2.08 (d, J ) 15.3 Hz, 1
H), 2.32-2.46 (m, 3 H), 2.71-2.79 (m, 2 H, H-8), 2.80-2.91
(m, 2 H), 3.25 (d, J ) 13.7 Hz, 1 H), 3.46 (d, J ) 14.3 Hz, 1 H),
3.54 (dt, J ) 9.2, 6.2 Hz), 3.61 (dt, J ) 9.2, 6.1 Hz, 1 H), 4.51
(d, J ) 13.7 Hz, 1 H), 4.54 (ABq, J ) 12.1 Hz, 2 H), 4.71, 4.73
(s, 2 H), 5.88, 5.89 (ABq, J ) 1.4 Hz, 2 H), 6.75 (s, 1 H), 6.77
(s, H), 7.17-7.41 (m, 10 H); 13C NMR (CD3CN) 27.1, 27.2, 31.0,
34.4, 39.5, 45.1, 52.5, 55.7, 71.6, 73.3, 77.6, 102.2, 105.7, 110.0,
110.9, 126.4, 127.4, 127.7, 128.5, 128.6, 129.0, 129.4, 133.0 (C-
2′), 140.1, 141.0, 146.3, 147.4, 148.0, 152.3, 176.7; IR (CHCl3)
1740, 1685 (w), 1500; MS, m/ z (relative intensity) 579 (M, 4),
494 (7), 488 (5), 386 (4), 372 (2), 238 (3), 198 (4), 184 (29), 149
(3), 129 (4), 115 (3), 106 (4), 91 (100), 85 (5), 57 (67); HRMS,
m/ z 579.3009 (C37H41NO5 requires 579.2985).
3.51 (dt, J ) 9.0, 6.4 Hz, 1 H), 3.60 (dt, J ) 9.0, 5.9 Hz, 1 H),
4.50, 4.53 (ABq, J ) 12.7 Hz, 2 H), 4.66 (d, J ) 13.5 Hz, 1 H),
5.87, 5.89 (ABq, J ) 1.4 Hz, 2 H), 6.78 (s, 1 H), 6.82 (s, 1 H),
7.20-7.34 (m, 10 H); 13C NMR 26.5, 26.7, 30.2, 33.3, 38.6, 49.9,
51.6, 57.7, 70.7, 72.9, 74.7, 100.9, 108.9, 110.2, 124.1, 125.3,
126.9, 127.5, 127.6, 128.1, 128.3, 128.4, 131.5, 138.2, 138.3,
145.6, 147.2, 151.7, 175.6, 212.6; IR (CHCl3) 2950, 2925,2860,
1745,1680 (w); MS, m/ z (relative intensity) 581 (M, 24), 496
(6), 406 (6), 242 (7), 200 (6), 186 (6), 120 (43), 91 (100), 57
(73);HRMS, m/ z 581.2780 (C36H39NO2 requires 581.2777).
1-Aza -1-ben zyl-6-[2′-(2-(ben zyloxy)eth yl)-4′,5′-(m eth yl-
en ed ioxy)p h en yl]-7-(p iva loyloxy)sp ir o[4.4]n on -6-en -3-
on e Dith iok eta l (17). To a solution of 119 mg (0.204 mmol)
of ketone 16 in 1.85 mL (22.0 mmol) of 1,2-ethanedithiol at
-15 to -20 °C was added dropwise 0.215 mL (1.75 mmol) of
BF3‚OEt2. The resulting mixture was stirred at -15 to -20
°C for 8.5 h, poured into cold saturated aqueous NaHCO3, and
extracted with ether. The ethereal extracts were dried and
concentrated in vacuo to yield a residue which was subjected
to Florisil column chromatography (90:10 hexanes/ethyl ac-
etate) to afford 97 mg (72%) of thioketal 17: 1H NMR 0.97 (s,
9 H), 1.80 (ddd, J ) 13.6, 9.5, 8.3 Hz, 1 H), 2.23 (d, J ) 13.9
Hz, 1 H), 2.32-2.39 (m, 1 H), 2.46 (d, J ) 13.9 Hz, 1 H), 2.48-
2.57 (m, 1 H), 2.69-2.76 (m, 2 H), 2.79-2.89 (m, 2 H), 2.83 (d,
J ) 10.2 Hz, 1 H), 2.98-3.03 (m, 1 H), 3.14-3.20 (m, 2 H),
3.30 (d, J ) 10.2 Hz, 1 H), 3.34 (d, J ) 13.9 Hz, 1 H), 3.52 (dt,
J ) 9.2, 6.1 Hz, 1 H), 3.61 (dt, J ) 9.2, 5.9 Hz, 1 H), 4.47 (d,
J ) 13.9 Hz, 1 H), 4.51, 4.55 (ABq, J ) 12.1 Hz, 2 H), 5.86,
5.92 (ABq, J ) 1.5 Hz, 2 H), 6.74 (s, 1 H), 6.83 (s, 1 H), 7.18-
7.44 (m, 10 H); 13C NMR (CD3CN) 27.1, 29.0, 31.1, 34.4, 39.5,
40.7, 40.9, 50.9, 55.7, 65.7, 68.4, 71.5, 73.3, 77.6, 102.2, 109.9,
111.2, 126.3, 127.2, 127.7, 128.5, 129.0, 129.4, 133.1, 140.1,
140.8, 146.3, 148.0, 152.5, 176.7; IR (CHCl3) 1735; MS, m/ z
(relative intensity) 657 (M, 100), 572 (44), 566 (31), 556 (24),
550 (11), 538 (36), 537 (35), 453 (21), 345 (22), 262 (70), 223
(33), 185 (23), 120 (40); HRMS, m/ z 657.2605 (C38H43NO5S2
requires 657.2583).
1-Aza -1-ben zyl-6-[2′-(2-(ben zyloxy)eth yl)-4′,5′-(m eth yl-
en edioxy)ph en yl]-7-(pivaloyloxy)spir o[4.4.]n on -6-en e (18).
Raney nickel (Aldrich) (5.6 g of a 50% slurry in pH 10 water)
was sequentially repetitively washed with 50 mL portions of
water and THF, suspended in 50 mL of THF, and added as a
slurry to 188 mg (0.286 mmol) of thioketal 17. The mixture
was stirred for 2.5 h at 25 °C and filtered through Celite. The
filtrate was concentrated in vacuo to yield a residue which was
subjected to F-20 alumina column chromatography (hexanes
to 95:5 hexanes/ethyl acetate) to afford 105 mg (65%) of
spirocyclic amine 18. Crystallization from hexanes-ethyl
acetate gave pure 18, mp 114-115 °C: UV max (CH3CN) 290
1
nm (ꢀ 4000); H NMR 0.97 (s, 9 H), 1.45-1.74 (m, 5 H), 2.23
(dt, J ) 9.1, 6.9 Hz), 2.32-2.36 (m, 1 H), 2.36 (dd, J ) 16.5,
8.5 Hz, 1 H), 2.73 (p, J ) 8.3 Hz, 1 H), 2.76-2.91 (m, 3 H),
3.25 (d, J ) 13.6 Hz), 3.55 (dt, J ) 9.2, 6.2 Hz, 1 H), 3.26 (dt,
J ) 9.2, 6.2 Hz, 1 H), 4.44 (d, J ) 13.6 Hz), 4.52, 4.55 (ABq, J
) 12.1 Hz, 2 H), 5.86, 5.90 (ABq, J ) 1.5 Hz, 2 H), 6.75 (s, 1
H), 6.77 (s, 1 H), 7.16-7.40 (m, 10 H); 13C NMR 20.9, 26.8,
27.1, 30.1, 33.4, 36.9, 38.7, 49.6, 52.1, 71.1, 72.9, 76.2, 100.7,
108.7, 110.5, 125.8, 126.4, 127.1, 127.5, 127.6, 128.2, 128.3
128.4, 131.2, 138.5, 140.4, 145.3, 146.8, 150.3, 175.8; IR
(CHCl3) 1735, 1680; MS, m/ z (relative intensity) 567 (M, 15),
482 (36), 476 (30), 466 (52), 432 (8), 374 (21), 186 (23), 173
(52), 149 (40), 120 (100); HRMS, m/ z 567.3006 (C36H41NO5
requires 567.2985). Anal. Calcd for C36H41NO5: C, 76.16; H,
7.28; N, 2.47. Found: C, 75.80; H, 7.26; N, 2.41.
1-Aza -1-ben zyl-6-[2′-(2-(ben zyloxy)eth yl)-4′,5′-(m eth yl-
en ed ioxy)p h en yl]-7-(p iva loyloxy)sp ir o[4.4]n on -6-en -3-
on e (16). To a solution of 297 mg (0.512 mmol) of spirocyclic
amine 14 in 90 mL of methanol at -78 °C was added 0.050
mL of 70% aqueous HClO4 (0.58 mmol). After the solution
was stirred for 30 min, 32 mL of a -78 °C O3-saturated CH2-
Cl2 solution (1.2 mmol of O3) was added. The mixture was
maintained at -78 °C for 30 min, quenched sequentially with
2 mL of dimethyl sulfide and 2 mL of saturated aqueous
NaHCO3, warmed to 25 °C, poured into cold water, and
extracted with CHCl3. The organic extracts were dried and
concentrated in vacuo to yield a residue which was subjected
to Florisil column chromatography (90:10 hexanes/ethyl ac-
etate) to afford 187 mg (63%) of ketone 16: 1H NMR 0.99 (s,
9 H), 1.74 (d of apparent t, J ) 13.8, 9.7, 8.4 Hz, 1 H), 2.09 (d,
J ) 17.4 Hz, 1 H), 2.43 (d, J ) 17.4 Hz, 1 H), 2.43-2.51 (m, 2
H), 2.67-2.74 (m, 1 H), 2.72 (d, J ) 17.8 Hz, 1 H), 2.79-2.87
(m, 2 H), 3.23 (d J ) 17.8 Hz, 1 H), 3.36 (d, J ) 13.5 Hz, 1 H),
1-Aza-6-[2′-(2-h ydr oxyeth yl)-4′,5′-(m eth ylen edioxy)ph e-
n yl]-7-(p iva loyloxy)sp ir o[4.4]n on -6-en e (19). To a solution
of 79 mg (0.14 mmol) of 18 in 14 mL of anhydrous methanol
were added 80 mg of 10% Pd/C and 4.8 mL of a freshly
prepared 0.25 M solution of anhydrous ammonium formate
(1.2 mmol) in anhydrous methanol. The resulting mixture was
stirred at reflux for 25 min, cooled to 0 °C, and filtered through
Celite. The collected solids were washed with ethyl acetate,
and the resulting filtrate was extracted with cold saturated
aqueous NaHCO3. The aqueous layer was extracted with CH2-
Cl2, and the organic layers were combined, dried, and concen-
trated in vacuo to give 19 which was not purified further: 1H