Rapid Entry into Cyclic â-Lactam Arrays
J . Org. Chem., Vol. 63, No. 22, 1998 7903
) -112.0 (c 1.09, CHCl3); IR (film) 1768, 1743 cm-1; 1H NMR
(270 MHz, CDCl3) δ 5.96-5.68 (m, 2H), 5.40 (s, 1H), 5.34-
5.08 (m, 4H), 4.28-4.14 (m, 4H), 4.00 (dd, J ) 6.5, 12.5 Hz,
1H), 3.93-3.88 (m, 1H), 2.94 (dd, J ) 3.0, 16.0 Hz, 1H), 2.52-
2.48 (m, 1H), 2.33-2.28 (m, 1H), 1.31 (t, J ) 7.0 Hz, 3H), 1.21
HRMS (CI) calcd for C10H16NO2 (M + H)+ 182.1181, found (M
+ H)+ 182.1183.
6-(4-Tolu en esu lfon yl)-1,6-d ia za bicyclo[5.2.0]n on -3-en -
9-on e (51): white solid (92%); mp 141 °C; TLC Rf 0.43 (Et2O);
IR (KBr) 1763 cm-1; 1H NMR (270 MHz, CDCl3) δ 7.70 (d, J )
8.0 Hz, 2H), 7.30 (d, J ) 8.0 Hz, 2H), 5.65 (d, J ) 4.0 Hz, 1H),
5.63-5.52 (m, 1H), 5.37-5.28 (m, 1H), 4.32-4.20 (m, 2H),
3.86-3.74 (m, 1H), 3.27 (dd, J ) 4.0, 15.0 Hz, 1H), 3.14-3.03
(m, 1H), 2.78 (dd, J ) 2.0, 15.0 Hz, 1H), 2.43 (s, 3H); 13C NMR
(67.5 MHz, CDCl3) δ 165.3, 144.1, 137.0, 129.8, 128.1, 127.3,
125.6, 64.9, 43.4, 42.2, 39.3, 21.6; MS (CI, NH3) m/z 310 (M +
NH4)+, 293 (M + H)+; HRMS (CI, NH3) calcd for C14H17N2O3S
(M + H)+ 293.0960, found (M + H)+ 293.0964. Anal. Calcd
for C14H16N2O3S: C, 57.32; H, 5.52; N 9.58. Found: C, 57.49;
H, 5.26; N, 9.48.
(d, J ) 6.0 Hz, 3H), 0.88 (s, 9H), 0.09 (s, 3H), 0.05 (s, 3H); 13
C
NMR (67.5 MHz, CDCl3) δ 168.6, 167.1, 133.1, 132.7, 119.2,
118.5, 76.1, 69.5, 65.9, 62.6, 62.0, 53.3, 36.8, 25.9, 23.1, 18.1,
14.1, -4.3, -4.6; MS (CI, NH3) m/z 429 (M + NH4)+, 412 (M +
H)+; HRMS (CI, NH3) calcd for C21H38NO5Si (M + H)+
412.2519, found (M + H)+ 412.2531.
Gen er a l P r oced u r e for th e Rin g-Closin g Meta th esis
of Dien es 28, 29a -d , 31, 32a -b , a n d 39. A solution of
carbene 1 or 3 in CH2Cl2 (6 mL) was added to the correspond-
ing diene (50 mg) (Table 2), stirred for 2 h, and exposed to air.
The dark solution was concentrated and chromatographed.
1-Aza -6-oxa bicyclo[5.2.0]n on -3-en -9-on e (46): colorless
6-Th ia -1-a za bicyclo[5.2.0]n on -3-en -9-on e (52): colorless
oil (79%); TLC Rf 0.33 (3:1 Et2O/hexanes); IR (film) 1754 cm-1
;
oil (84%); TLC Rf 0.33 (Et2O); IR (film) 1756 cm-1; H NMR
1H NMR (250 MHz, CDCl3) δ 6.02-5.90 (m, 1H), 5.61-5.52
(m, 1H), 4.88 (dd, J ) 2.0, 5.0 Hz, 1H), 4.40 (dd, J ) 5.0, 18.0
Hz, 1H), 3.70 (dd, J ) 5.0, 18.0 Hz, 1H), 3.57-3.48 (m, 1H),
3.43 (dd, J ) 5.0, 15.0 Hz, 1H), 3.02 (dd, J ) 2.0, 15.0 Hz,
1H), 2.97 (d, J ) 15.0 Hz, 1H); 13C NMR (62.5 MHz, CDCl3) δ
165.5, 129.8, 127.5, 55.9, 46.0, 41.4, 23.6; MS (CI, NH3) m/z
173 (M + NH4)+, 156 (M + H)+; HRMS (CI, NH3) calcd for
C7H10NOS (M + H)+ 156.0483, found (M + H)+ 156.0494.
1-Aza bicyclo[4.2.0]oct-3-en -8-on e (53): colorless oil (81%);
1
(300 MHz, CDCl3) δ 5.69-5.56 (m, 2H), 5.26 (dd, J ) 1.0, 3.5
Hz, 1H), 4.48-4.33 (m, 2H), 4.23-4.15 (m, 1H), 3.75-3.72 (m,
1H), 3.18-3.11 (m, 1H), 2.91 (d, J ) 15.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 165.3, 128.5, 125.0, 82.6, 65.3, 44.1, 42.1;
MS (CI, NH3) m/z 157 (M + NH4)+; HRMS (CI, NH3) calcd for
C7H13N2O2 (M + NH4)+ 157.0982, found (M + NH4)+ 157.0977.
Anal. Calcd for C7H9NO2: C, 60.42; H, 6.52; N, 10.07.
Found: C, 60.52; H, 6.25; N, 10.35.
1
5-Me t h y l-1-a za -6-o x a b ic y c lo [5.2.0]n o n -3-e n -9-o n e
(47): separable diastereoisomers both as colorless oils (60%
TLC Rf 0.34 (Et2O); IR (film) 1754 cm-1; H NMR (250 MHz,
CDCl3) δ 5.90-5.68 (m, 2H), 4.07 (dd, J ) 4.0, 15.0 Hz, 1H),
3.57-3.42 (m, 2H), 3.21 (ddd, J ) 2.0, 5.0, 15.0 Hz, 1H), 2.56
(dd, J ) 1.0, 15.0 Hz, 1H), 2.52-2.41 (m, 1H), 2.18-2.03 (m,
1H); 13C NMR (62.5 MHz, CDCl3) δ 167.0, 123.8, 122.6, 45.3,
43.1, 38.5, 28.7; MS (CI, NH3) m/z 141 (M + NH4)+, 124 (M +
H)+; HRMS (CI, NH3) calcd for C7H10NO (M + H)+ 124.0762,
found (M + H) 124.0761.
combined yield). 47a : TLC Rf 0.42 (Et2O); IR (film) 1758 cm-1
;
1H NMR (400 MHz, CDCl3) δ 5.56-5.48 (m, 2H), 5.15 (dd, J
) 1.0, 4.0 Hz, 1H), 4.46-4.40 (m, 1H), 4.31 (d, J ) 19.0 Hz,
1H), 3.75 (d, J ) 18.0 Hz, 1H), 3.15 (ddd, J ) 2.5, 3.5, 14.5
Hz, 1H), 2.84 (d, J ) 14.5 Hz, 1H), 1.35 (d, J ) 7.0 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 165.2, 134.1, 123.6, 81.8, 75.3,
45.0, 41.7, 22.2; MS (CI, NH3) m/z 171 (M + NH4)+, 154 (M +
H)+; HRMS (CI, NH3) calcd for C8H12NO2 (M + H)+ 154.0868,
found (M + H)+ 154.0867. 47b: TLC Rf 0.52 (Et2O); IR (film)
1760 cm-1; 1H NMR (400 MHz, CDCl3) δ 5.51 (s, 2H), 5.40 (d,
J ) 3.5 Hz, 1H), 4.75-4.70 (m, 1H), 4.63 (dd, J ) 2.0, 16.5
Hz, 1H), 3.65 (dd, J ) 2.5, 15.5 Hz, 1H), 3.12 (ddd, J ) 1.0,
3.5, 15.5 Hz, 1H), 2.92 (d, J ) 15.0 Hz, 1H), 1.33 (d, J ) 7.0
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 176.4, 134.1, 126.6,
79.9, 64.9, 43.3, 42.5, 21.6; MS (CI, NH3) m/z 171 (M + NH4)+,
154 (M + H)+; HRMS (CI, NH3) calcd for C8H12NO2 (M + H)+
154.0868, found (M + H)+ 154.0868.
1-Azabicyclo[5.2.0]n on -3-en -9-on e (54): colorless oil (83%);
1
TLC Rf 0.28 (Et2O); IR (film) 1745 cm-1; H NMR (270 MHz,
CDCl3) δ 5.80-5.72 (m, 1H), 5.55-5.48 (m, 1H), 4.35 (ddd, J
) 1.0, 5.5, 18.5 Hz, 1H), 3.82-3.76 (m, 1H), 3.57-3.50 (m, 1H),
3.10 (ddd, J ) 1.5, 5.0, 14.5 Hz, 1H), 2.60 (dd, J ) 2.0, 14.5
Hz, 1H), 2.42-2.34 (m, 1H), 2.20-2.07 (m, 2H), 1.76-1.64 (m,
1H); 13C NMR (67.5 MHz, CDCl3) δ 166.2, 130.7, 126.0, 53.2,
42.8, 41.2, 32.9, 24.7; MS (CI, NH3) m/z 138 (M + H)+; HRMS
(CI, NH3) calcd for C8H12NO (M + H)+ 138.0919, found (M +
H)+ 138.0918.
(6R,7S)-(+)-7-[1-(R)-(ter t-Bu tyld im eth ylsilyl)oxyeth yl]-
1-a za bicyclo[4.2.0]oct-3-en -8-on e (55): colorless oil (78%);
TLC Rf 0.34 (1:1 Et2O/hexanes); [R]21D ) +60.0 (c 1.00, CHCl3);
IR (film) 1758, 1748, 1732 cm-1; 1H NMR (250 MHz, CDCl3) δ
5.88-5.64 (m, 2H), 4.17 (m, 1H), 4.06 (dd, J ) 3.0, 18.0 Hz,
1H), 3.54-3.42 (m, 2H), 2.74 (dd, J ) 1.0, 15.0 Hz, 1H), 2.48-
2.34 (m, 1H), 2.22-2.06 (m, 1H), 1.25 (d, J ) 6.0 Hz, 3H), 0.86
(s, 9H), 0.07 (s, 6H); 13C NMR (62.5 MHz, CDCl3) δ 167.2,
124.0, 122.4, 66.9, 65.7, 45.9, 38.1, 28.1, 25.7, 22.8, 17.9, -4.2,
-5.1; MS (CI, NH3) m/z 282 (M + H)+; HRMS (CI, NH3) calcd
for C15H28NO2Si (M + H)+ 282.1889, found (M + H) 282.1871.
1-Meth yl-4-vin yla zetid in -2-on e (58): from 36 following
the general procedure for N-alkylation employing methyl
iodide (method B); colorless oil (0.22 g, 65%); TLC Rf 0.34
(Et2O); IR (film) 1747 cm-1; 1H NMR (270 MHz, CDCl3) δ 5.86-
5.73 (m, 1H), 5.41-5.27 (m, 2H), 3.97-3.91 (m, 1H), 3.17 (ddd,
J ) 0.5, 3.0, 14.5 Hz, 1H), 2.76 (s, 3H), 2.68 (ddd, J ) 1.0, 2.5,
14.5 Hz, 1H); 13C NMR (67.5 MHz, CDCl3) δ 167.1, 136.1,
119.4, 54.8, 44.2, 26.9; MS (CI, NH3) m/z 129 (M + NH4)+, 112
(M + H)+; HRMS (CI, NH3) calcd for C6H13N2O (M + NH4)+
129.1027, found (M + NH4)+ 129.1026.
1-Met h yl-4-(2-p r op en yl)a zet id in -2-on e (59): from 30b
following the general procedure for N-alkylation employing
MeI (method B); colorless oil (63%); TLC Rf 0.24 (Et2O); IR
(film) 1746 cm-1; 1H NMR (270 MHz, CDCl3) δ 5.83-5.71 (m,
1H), 5.20-5.11 (m, 2H), 3.61-3.55 (m, 1H), 2.99 (ddd, J ) 0.5,
5.0, 14.5 Hz, 1H), 2.80 (s, 3H), 2.60 (ddd, J ) 1.0, 2.0, 14.5
Hz, 1H), 2.55-2.25 (m, 2H); 13C NMR (67.5 MHz, CDCl3) δ
167.0, 132.7, 118.4, 51.9, 42.1, 36.8, 27.0; MS (CI, NH3) m/z
143 (M + NH4)+, 126 (M + H)+; HRMS (CI, NH3) calcd for
C7H15N2O (M + NH4)+ 143.1184, found (M + NH4)+ 143.1184.
1-Aza -7-oxa bicyclo[6.2.0]d ec-3-en -10-on e (48): colorless
1
oil (76%); TLC Rf 0.31 (Et2O); IR (film) 1754 cm-1; H NMR
(300 MHz, CDCl3) δ 6.02-5.82 (m, 2H), 4.88 (dd, J ) 2.5, 4.0
Hz, 1H), 4.05-3.97 (m, 1H), 3.86 (dd, J ) 7.0, 14.0 Hz, 1H),
3.55 (dd, J ) 7.5, 14.0 Hz, 1H), 3.59-3.51 (m, 1H), 3.01 (dd, J
) 4.0, 15.0 Hz, 1H), 2.72 (dd, J ) 2.5, 15.0 Hz, 1H), 2.48-2.30
(m, 2H); 13C NMR (75 MHz, CDCl3) δ 165.2, 133.8, 124.9, 82.0,
69.3, 43.0, 35.5, 29.3; MS (CI, NH3) m/z 171 (M + NH4)+, 154
(M + H)+; HRMS (CI, NH3) calcd for C8H15N2O2 (M + NH4)+
171.1134, found (M + NH4)+ 171.1145.
1-Aza -8-oxa bicyclo[7.2.0]u n d ec-3-en -11-on e (49): color-
less oil (23%); TLC Rf 0.31 (Et2O); IR (film) 1761 cm-1; 1H NMR
(400 MHz, CDCl3) δ 5.86 (dt, J ) 7.5, 10.5 Hz, 1H), 5.69 (dt,
J 7) 0.5, 10.5 Hz, 1H), 5.14 (dd, J ) 1.5, 4.0 Hz, 1H), 3.90
(dd, J ) 7.0, 14.5 Hz, 1H), 3.83-3.78 (m, 1H), 3.65 (dd, J )
8.0, 14.5 Hz, 1H), 3.50-3.44 (m, 1H), 2.94 (dd, J ) 4.0, 15.0
Hz, 1H), 2.79 (d, J ) 15.0 Hz, 1H), 2.44-2.26 (m, 2H), 1.71-
1.53 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 165.7, 135.0, 124.3,
83.8, 62.7, 42.8, 36.7, 26.1, 22.4; MS (CI, NH3) m/z 185 (M +
NH4)+, 168 (M + H)+; HRMS (CI, NH3) calcd for C9H14NO2 (M
+ H)+ 168.1025, found (M + H)+ 168.1030.
1-Aza -9-oxa bicyclo[8.2.0]d od ec-3-en -12-on e (50): white
solid (10%); mp 88-89 °C; TLC Rf 0.31 (Et2O); IR (KBr) 1756
cm-1; 1H NMR (400 MHz, CDCl3) δ 5.71 (dt, J ) 4.0, 11.0 Hz,
1H), 5.57-5.51 (m, 1H), 4.94 (d, J ) 3.0 Hz, 1H), 3.94-3.89
(m, 1H), 3.81-3.65 (m, 3H), 2.97 (dd, J ) 2.5, 14.5 Hz, 1H),
2.87-2.77 (m, 1H), 2.66 (dd, J ) 1.5, 14.0 Hz, 1H), 2.11-2.07
(m, 1H), 2.01-1.91 (m, 2H), 1.82-1.74 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 165.8, 138.3, 121.0, 77.9, 69.8, 44.6, 35.8, 26.8,
25.9, 23.5; MS (CI, NH3) m/z 199 (M + NH4)+, 182 (M + H)+;