Diastereofacial Selectivity in Azomethine Ylide Cycloadditions
J . Org. Chem., Vol. 62, No. 3, 1997 497
1/2 SiCH2CHCH2) 5.04 (dd, 1 H, J 1 ) 9.6 Hz, J 2 ) 5.7 Hz,
Hz, COCHCH2), 3.66 (d, 1 H, J ) 6.9 Hz, COCHCHCH2), 3.15
(m, 1 H, COCHCHCH2), 2.58 (s, 3 H, NMe), 2.34 (ddd, 1 H, J 1
) 13.8 Hz, J 2 ) 10.8 Hz, J 3 ) 7.2 Hz, 1/2 COCHCH2), 1.9 (m,
1 H, COCHCH2), 1.9 (m, 1 H, 1/2 COCHCHCH2), 1.65 (dd, 1
H, J 1 ) 16.2 Hz, J 2 ) 9.9 Hz, 1/2 COCHCHCH2); 13C NMR
(75 MHz, CDCl3) δ 175.0, 172.2, 136.7, 135.9, 134.9, 134.6,
134.3, 130.2, 129.9, 128.4, 128.1, 127.4, 127.0, 72.5, 66.8, 61.0,
54.4, 36.6, 35.1, 33.2, 13.7; IR (CHCl3) 3020 (s), 1730 (s), 1680
(s), 1420 (s), 1200 (br), 1110 (s), 690 (s) cm-1; MS (EI) m/z,
469 (5%, [M + H]+), 468 (20%, [M]+), 427 (8%, [M - C3H5]+);
HRMS m/z calcd for C28H28N2O3Si [M]+ 468.1869, obsd 468.1865.
Cycloa d d u ct 24b: yield 49% (62% based on recovered SM),
ds ) 10/1; mp 129-131 °C (hexanes); Rf 0.24 in 3:1 hexanes/
PhCH), 4.84-4.42 (m, 2 H, SiCH2CHCH2), 4.41 (dd, 1 H, J 1
J 2 ) 9.6 Hz, 1/2 PhCHCH2), 3.96 (dd, 1 H, J 1 ) 9.6 Hz, J 2
)
)
5.7 Hz, 1/2 PhCHCH2), 2.71(s, 2 H, N(COCH)2), 2.37 (s, 3 H,
NMe), 1.53 (d, 2 H, J ) 7.8Hz, SiCH2), 0.02 (s, 6H, SiMe2); 13
C
NMR (75MHz, CDCl3) δ 172.0 (CO), 133.7, 128.3, 127.9, 127.7
(Ar), 113.5, 60.9, 56.6, 45.1, 41.4, 24.1, -2.8; IR (CH2Cl2) 3040
(s), 2980 (s),1720 (s), 1410 (s), 1350 (m), 1180 (m), 1080 (m),
1020 (m), 890 (m); MS (EI) m/z 344 (<1%, [M]+), 329 (<1%,
[M - CH3]+), 303 (100%, [M - C3H5]+); HRMS m/z calcd for
C18H24N2O3Si [M]+ 344.1556, obsd 344.1506.
Gen er a l P h otolysis P r oced u r e. The starting aziridine
was dissolved in spectrophotometric grade MeCN (0.01 M) and
transferred to a quartz reaction vessel, and isoprene (2 or 3
drops) was added. The resulting solution was degassed (freeze-
thaw method) three times and then irradiated in a Rayonet
photochemical reactor (3000 Å for 14, 2537 Å for 19, 21, and
23a /b) until the reaction was judged to be complete by TLC.
The solvent was removed to provide the crude product mixture
which was purified by flash chromatography over silica gel.
Diastereomer ratios were determined from the 1H NMR
spectra of unresolved mixtures.
1
EtOAc; H NMR (300 MHz, CDCl3) δ 7.25 (m, 5 H, Ph), 5.9
(dd, 1 H, J 1 ) 11.1 Hz, J 2 ) 5.7 Hz, PhCH), 4.60 (dd, 1 H, J 1
) J 2 ) 11.1 Hz, 1/2 PhCHCH2), 4.08 (dd, 1 H, J 1 ) 11.1 Hz, J 2
) 5.2 Hz, 1/2 PhCHCH2), 3.82 (d, 1 H, J ) 7.8 Hz, COCHCH2),
3.47 (d, 1 H, J ) 7.2 Hz, COCHCHCH2), 3.0 (m, 1 H,
COCHCHCH2), 2.59 (s, 4 H, NMe and 1/2 COCHCH2), 1.88
(dd, 1 H, J 1 ) 13.5 Hz, J 2 ) 5.4 Hz, 1/2 COCHCH2), 1.15 (m,
1 H, 1/2 COCHCHCH2), 1.86 (m, 1 H, 1/2 COCHCHCH2), 0.86
(dd, 1 H, J 1 ) 15.6 Hz, J 2 ) 9.9 Hz, 1/2 COCHCHCH2), 0.15
(s, 3 H, Me), 0.06 (s, 3 H, Me); 13C NMR (75 MHz, CDCl3) δ
174.9, 171.9, 136.6, 128.2, 127.1, 126.8, 72.2, 66.6, 60.1, 54.2,
36.4, 35.5, 33.3, 17.3, 1.8, -1.6; IR (CHCl3) 3040 (s), 1710 (s),
1680 (s), 1420 (s), 1110 (s), 630 (s) cm-1; MS (EI) m/z, 345
(1.6%, [M + H]+), 344 (4%, [M]+), 343 (8%, [M - H]+), 316
(2.7%, [M - CO]+), 303 (100%, [M - C3H5]+), 286 (<1%, [M -
SiMe2]+); HRMS m/z calcd for C18H24N2O3Si [M]+ 344.1556,
obsd 344.1554.
Cor r ela tion Exp er im en t for 16. To a solution of 16 (54
mg, 0.1 mmol) in MeOH (1 mL plus a minimum amount of
CH2Cl2) was added 3 drops of concd HCl. The clear solution
was stirred at rt overnight. TLC analysis (20:1 CH2Cl2/MeOH)
indicated (intermediate) glycolate ester formation so the
solution was warmed to 60 °C and stirred for a further 48 h
when TLC analysis then revealed that the reaction was
essentially complete. The mixture was quenched with satu-
rated NaHCO3 solution and extracted with EtOAc The organic
layers were dried over MgSO4 and filtered, and the solvent
was removed to give the crude alcohol which was purified by
flash chromatography (30:1 CH2Cl2/MeOH) to deliver the pure
Cycloa d d u ct 16: 46% yield (72% based on recovered SM),
1
ds ) 12/1; Rf 0.32 in 2:1 hexanes/EtOAc; H NMR (300 MHz,
CDCl3) δ 7.6-7.1 (m, 15 H, Ph), 5.8 (dd, 1 H, J 1 ) 9.6 Hz, J 2
) 6.0 Hz, PhCH), 4.88 (dd, 1 H, J 1 ) J 2 ) 9.6 Hz, 1/2
PhCHCH2), 4.4 (m, 1 H, 1/2 OCH2CH2O), 4.11 (m, 3 H,
OCH2CH2O and 1/2 PhCHCH2), 4.04 (d, 1 H, J ) 6.4 Hz,
NCOCHCHCO2), 3.92 (m, 1 H, 1/2 OCH2CH2), 3.66 (d, 1 H, J
) 7.8 Hz, NCOCHCH2), 3.48 (ddd, 1 H, J 1 ) 10.8 Hz, J 2 ) J 3
) 6.4 Hz, NCOCHCHCO2), 2.52 (m, 1 H, 1/2 NCOCHCH2),
2.4 (m, 1 H, 1/2 NCOCHCH2), 2.32 (s, 3 H, NMe); 13C NMR
(75 MHz, CDCl3) δ 173.4, 170.8, 169.4(CO), 136.9, 134.6, 131.7,
130.5, 128.2, 128.1, 127.9, 127.7, 127.5(Ar), 68.9, 66.8, 66.3,
62.4, 61.9, 56.5, 46.1, 35.9, 29.5, 29.4; IR (CH2Cl2) 3040 (s),
2975 (s),1735 (s), 1680 (s), 1410 (s), 1340 (m), 1120 (w), 890
(s) cm-1; MS (EI) m/z, 542 (26.4%, [M]+), 514 (41.7%, [M -
CO]+), 466 (11.8%, [M - Ph + H]+), 465 (100%, [M - Ph]+),
423 (77%), 297 (54.7%), 108 (100%); HRMS m/z calcd for
C30H30N2O4Si [M]+ 542.1873, obsd 542.1873.
Cycloa d d u ct 20: 60% yield, ds ) 2.5/1; Rf 0.47 in 3:1
hexanes/EtOAc; 1H NMR (300 MHz, CDCl3) δ 7.2 (m, 5 H, Ph),
5.9 (m, 1 H, PhCH), 5.07 (dd, J 1 ) J 2 )10.2 Hz, 1/2 PhCHCH2),
4.12 (m, 1 H, 1/2 SiOCH2), 3.9 (m, 1 H, 1/2 SiOCH2), 3.79 (d,
1 H, J ) 7.5 Hz, NCOCHCH), 3.6 (d, 1 H, J ) 6.9 Hz,
NCOCHCH2), 2.92 (m, 1 H, 1/2 NCOCHCH2), 2.46 (s, 3 H,
NMe), 2.02 (dd, J 1 ) 13.5 Hz, J 2 ) 5.1 Hz, 1/2 NCOCHCH2),
1.0 (m, 27 H, 4 × C3H7); IR (CHCl3) 3010 (s), 2950 (s), 2860
(s), 1730 (s), 1680 (s), 1510 (m), 1180 (br), 1100 (s), 960 (s)
cm-1; MS (EI) m/z, 503 (12.5%, [M - C3H7]+), 475 (21.6%, [M
- SiC3H7]+), 443 (4%), 281 (11.6%, [M - 163]; HRMS m/z calcd
for C25H39N2O5Si[M - SiC3H7]+ 475.2628, obsd 475.2627.
Cycloa d d u ct 22: 72% isolated yield (79% based on recov-
ered SM), ds ) 5/1; mp 223-224 °C (from hexanes/ EtOAc);
methyl ester alcohol (18 mg, 54% yield) as a viscous oil.
A
solution of this alcohol (10 mg, 0.03 mmol), diisopropylethyl-
amine (0.05 mL, 0.3 mmol), and methoxymethyl (MOM)
chloride (0.007 mL, 0.09 mmol) was stirred at rt overnight.
The reaction mixture was partitioned between water and CH2-
Cl2, the combined organic layers were dried over MgSO4 and
filtered, and the solvent was removed to give the crude product.
Purification by flash chromatography (20:1 CH2Cl2/MeOH)
gave the pure MOM ether methyl ester 17 (10 mg, 88%) as a
colorless oil. Rf 0.38 in 20:1 CH2Cl2/MeOH; 1H NMR (300
MHz, CDCl3) δ 7.25 (m, 5 H, Ph), 5.85 (dd, 1 H, J 1 ) 8.0 Hz,
J 2 ) 5.5 Hz, PhCH), 4.60 (d, 1 H, J ) 7.5 Hz, 1/2 OCH2O),
1
4.58 (d, 1 H, J ) 7.5 Hz, 1/2 OCH2O), 4.36 (dd, 1 H, J 1 ) J 2
)
Rf 0.47 in 1:1 hexanes/EtOAc; H NMR (300 MHz, CDCl3) δ
8.0 Hz, 1/2 OCH2Ph), 4.16 (dd, 1 H, J 1 ) 8.0 Hz, J 2 ) 5.5 Hz,
OCH2Ph), 3.92 (d, 1 H, J ) 5.5 Hz, NCOCHCHCO2Me), 3.74
(d, 1 H, J ) 6.1 Hz, NCOCHCH2), 3.66 (d, 1 H, J ) 7.8 Hz,
NCOCHCHCO2Me), 3.44 (ddd, 1 H, J 1 ) 9.4 Hz, J 2 ) 5.5 Hz,
J 3 ) 4.4 Hz, CHCO2Me), 3.31 (s, 3 H, OMe), 3.28 (s, 3 H, CO2-
Me), 2.5 (m, 1 H, 1/2 CH2CHCO2Me), 2.46 (s, 3 H, NMe), 2.30
(dd, 1 H, J 1 ) 14.0 Hz, J 2 ) 5.5 Hz, 1/2 CH2CHCO2Me); 13C
NMR (75 MHz, CDCl3) δ 173.3, 170.0, 128.4, 128.0, 127.7,
127.5, 96.1, 68.8, 65.9, 65.3, 53.2, 53.1, 45.2, 35.48, 29.9, 29.5;
IR (CHCl3) 3010 (s), 1740 (s), 1680 (s), 1410 (s), 1340 (m), 1120
(w), 890 (s) cm-1; MS (EI) m/z, 377 (2.6%, [M + H]+), 376
(15.8%, [M]+), 375 (44%, [M - H]+), 317 (26.4%, [M - CO2-
Me]+), 315 (15%, [M - OCH2OMe]+), 273 (100%); HRMS m/z
calcd for C19H24N2O6 [M]+ 376.1634, obsd 376.1634.
Cycloa d d u ct 22 f La cton e 25. A 5/1 mixture of silaketal
22 and d ia -22 (40 mg, 0.08 mmol) was dissolved in a cooled
solution of HF/CH3CN (1:9 v/v) and stirred at 0 °C for 10 min
when TLC analysis (17:1 CHCl3/MeOH) revealed that the
reaction was complete. The mixture was quenched with
saturated sodium bicarbonate solution and the resulting
suspension extracted with EtOAc. The combined organic
7.66-7.17 (m, 15 H, Ph), 6.13 (dd, 1 H, J 1 ) 10.2 Hz, J 2 ) 2.7
Hz, PhCH), 4.88 (dd, 1 H, J 1 ) J 2 ) 10.2 Hz, 1/2 PhCH2), 4.28
(dd, 1 H, J 1 ) 10.2 Hz, J 2 ) 2.7 Hz, 1/2 PhCH2), 3.96 (d, 1 H,
J
) 11.4 Hz, 1/2 SiOCH2), 3.87 (d, 1 H, J ) 4.2 Hz,
NCOCHCHCH2), 3.79 (m, 1 H, 1/2 SiOCH2), 3.54 (d, 1 H, J )
6.6 Hz, NCOCHCH2), 2.78 (m, 1 H, NCOCHCHCH2), 2.43 (s,
3 H, NMe), 2.35 (m, 2 H, NCOCHCH2); 13C NMR (75 MHz,
CDCl3) δ 172.9, 172.6 (CO), 136.9, 134.8, 134.6, 131.8, 130.9,
130.4, 128.5, 128.3, 128.1, 127.9, 127.7, 127.3 (Ar CH), 68,7,
67.2, 63.1, 60.6, 55.6, 41.7, 35.2, 28.8; IR (CHCl3) 3140 (m),
3060 (m), 2985 (m), 1675 (s), 1420 (m), 1340 (m), 1120 (s), 690
(s) cm-1; MS (EI) m/z, 485 (12.1%, [M + H]+), 484 (42.1%, [M]+),
483 (12.7%, [M - H]+) 456 (34.8%, [M - CO]+), 407 (100%, [M
- Ph]+), 365 (94.1%), 82 (100%), 77 (8%, [Ph]+); HRMS m/z
calcd for C28H28N2O4Si [M]+ 484.1818, obsd 484.1812.
Cycloa d d u ct 24a : 64% yield (71% with recovered SM), ds
) 16/1; mp 199-200 °C (from hexanes/EtOAc); Rf 0.36 in 1:1
hexanes/EtOAc; 1H NMR (300 MHz, CDCl3) δ 7.2-7.2 (m, 15
H, Ph), 6.13 (dd, 1 H, J 1 ) 11.1 Hz, J 2 ) 5.7 Hz, PhCH), 4.82
(dd, 1 H, J 1 ) J 2 ) 11.1 Hz, 1/2 PhCHCH2), 4.25 (dd, 1 H, J 1
) 11.1 Hz, J 2 ) 5.2 Hz, 1/2 PhCHCH2), 3.80 (d, 1 H, J ) 7.2