In-Promoted Allylations of 2,3-Azetidinediones in Water
J . Org. Chem., Vol. 63, No. 16, 1998 5471
1
Cl2, cm-1) 3400, 1730, 1330, 1260, 1150; H NMR (300 MHz,
2 H), 3.07-2.90 (m, 2 H), 2.51-2.39 (m, 1 H), 1.51 (overlapping
t, J ) 6.5 Hz, 3 H), 1.24 and 1.13 (2d, J ) 6.3 Hz, total 2 H)
(OH not observed); 13C NMR (75 MHz, CDCl3) ppm 173.8,
173.7, 140.0, 139.7, 134.0, 131.2, 129.1, 127.6, 127.5 (2 C),
126.0, 125.7 (2 C), 125.6, 125.5 (2 C), 122.9, 122.6, 122.3, 69.9,
69.8, 53.9, 53.6, 51.8 (2 C), 51.4, 51.2, 47.1, 46.8, 23.6, 23.4,
CDCl3) δ 7.83-7.23 (m, 8 H), 7.04-7.01 (m, 2 H), 6.82 (s, 1
H), 5.58 (s, 1 H), 4.73 (q, J ) 7.0 Hz, 1 H), 4.47 (s, 1 H), 3.86
(s, 1 H), 3.66 (s, 3 H), 3.19 (d, J ) 5.6 Hz, 1 H), 3.01 (d, J )
5.6 Hz, 1 H), 1.17 (d, J ) 7.0 Hz, 3 H) (OH not observed); 13
C
NMR (75 MHz, CDCl3) ppm 167.9, 167.1, 139.5, 138.5, 136.3,
128.7 (2 C), 128.5 (2 C), 127.7 (2 C), 127.6 (2 C), 85.4, 53.7,
52.2, 51.9, 51.3, 50.0, 41.7, 24.0, 17.8; MS m/z (M+) calcd
21.8, 21.7; MS m/z (M+) calcd 301.1678, obsd 301.1672; [R]22
D
+22.0 (c 0.156, C2H5OH).
365.1627, obsd 365.1603; [R]22 +12.0 (c 0.25, C2H5OH).
Submission of a 10 g (74 mmol) sample of the above ester
to the action of 92 mmol of tert-butylmagnesium chloride
according to the above procedure (elution with 75% ethyl
acetate in hexanes) delivered 7.45 g (74%) of the â-lactam as
a diastereomeric mixture: colorless crystals, mp 102-104 °C;
IR (CHCl3, cm-1) 3413, 1732, 1450, 1396, 1265; 1H NMR (300
MHz, CDCl3) δ 8.18-8.13 (m, 1 H), 7.89-7.80 (m, 2 H), 7.60-
7.43 (m, 4 H), 5.73 (q, J ) 6.9 Hz, 1 H), 4.20-3.93 (m, 1 H),
3.22-2.99 (m, 2 H), 2.73-2.67 (m, 1 H), 2.00 (br s, 1 H), 1.76-
1.68 (m, 3 H), 1.29-1.23 (m, 1.5 H), 1.14 (d, J ) 6.3 Hz, 1 H),
1.07 (d, J ) 6.3 Hz, 0.5 H); 13C NMR (75 MHz, CDCl3) ppm
167.6, 133.8, 131.0, 129.0, 128.9, 128.8, 128.63, 128.60, 126.7,
126.6, 125.9, 125.51, 125.46, 125.0, 123.5, 123.0, 65.3, 64.9,
55.6, 55.5, 46.9, 46.8, 39.1, 38.6, 21.2, 21.1, 17.91, 17.88 (other
signals overlapped); MS m/z (M+) calcd 269.1416, obsd 269.1431;
D
For 19b: colorless crystals, mp 135-138 °C; IR (CH2Cl2,
cm-1) 3330, 1730, 1400, 1260; H NMR (300 MHz, CDCl3) δ
1
7.41-7.18 (m, 8 H), 6.83-6.79 (m, 2 H), 6.76 (s, 1 H), 6.55 (s,
1 H), 4.78 (q, J ) 7.0 Hz, 1 H), 4.42 (s, 1 H), 3.65 (s, 3 H), 3.45
(br s, 1 H), 3.23 (d, J ) 5.6 Hz, 1 H), 3.10 (d J ) 5.6 Hz, 1 H),
1.50 (d, J ) 7.0 Hz, 3 H); 13C NMR (75 MHz, CDCl3) ppm 168.0,
167.0, 139.4, 138.6, 129.7 (2 C), 129.6 (2 C), 128.5 (2 C), 128.3,
128.2, 127.6, 127.3, 126.3 (2 C), 85.6, 52.1, 51.7, 50.6, 50.0,
18.2; MS m/z (M+) calcd 365.1627, obsd 365.1629; [R]22D +60.8
(c 0.12, C2H5OH).
For the X-ray crystallographic analysis, see Figure 4.
For 20b: colorless crystals, mp 125-127 °C; IR (CH2Cl2,
cm-1) 3350, 1740, 1270; H NMR (300 MHz, CDCl3) δ 7.42-
1
7.16 (m, 8 H), 7.05-7.02 (m, 2 H), 6.54 (s, 1 H), 5.83 (s, 1 H),
4.68 (q, J ) 7.0 Hz, 1 H), 4.56 (s, 1 H), 4.21 (s, 1 H), 3.68 (s, 3
H), 3.40 (d, J ) 5.8 Hz, 1 H), 3.10 (d, J ) 5.8 Hz, 1 H), 1.14 (d,
J ) 7.0 Hz, 3 H); 13C NMR (75 MHz, CDCl3) ppm 169.0, 167.6,
139.5, 138.1, 137.3, 129.1 (2 C), 128.8, 128.7 (2 C), 128.6 (2
C), 128.5, 127.6, 127.4, 126.7 (2 C), 84.7, 52.2, 51.6, 50.6, 18.0;
[R]22 +10.5 (c 0.134, C2H5OH).
D
Anal. Calcd for C17H19NO2: C, 75.81; H, 7.11. Found: C,
75.88; H, 7.08.
Dehydration of the preceding material (3.82 g, 14.20 mmol)
with methanesulfonyl chloride (1.62 mL, 21.3 mmol), triethyl-
amine (2.11 mL, 21.3 mmol), and DBU (3.18 mL, 21.3 mmol)
in the manner detailed earlier afforded 3.0 g (84%) of the
ethylidene derivative as an E:Z mixture. Olefinic cleavage in
the above intermediate was accomplished with sodium perio-
date (14.8 g, 68.9 mmol) and osmium tetraoxide (25 mg) in
methanol (150 mL) and water (100 mL) to give 4.93 g (74%)
of 24 as a colorless oil: IR (CHCl3, cm-1) 1820, 1780, 1350,
MS m/z (M+) calcd 365.1627, obsd 365.1610; [R]22 -140.1 (c
D
0.23, C2H5OH).
For the X-ray crystallographic analysis, see Figure 5.
For 21b: colorless crystals, mp 140-142 °C; IR (CH2Cl2,
cm-1) 3380, 1730, 1400, 1250, 1140; 1H NMR (300 MHz, CDCl3)
δ 7.37-7.19 (m, 8 H), 6.82-6.79 (m, 2 H), 6.51 (s, 1 H), 5.84
(s, 1 H), 4.77 (q, J ) 7.0 Hz, 1 H), 4.61 (s, 1 H), 4.58 (s, 1 H),
3.67 (s, 3 H), 3.33 (d, J ) 5.8 Hz, 1 H), 3.29 (d, J ) 5.8 Hz, 1
H), 1.49 (d, J ) 7.0 Hz, 3 H); 13C NMR (75 MHz, CDCl3) ppm
169.3, 167.6, 139.3, 138.1, 137.3, 129.1 (2 C), 128.6 (2 C), 127.3
(2 C), 126.4 (2 C), 85.1, 52.2, 50.5, 50.4, 50.3, 18.0; MS m/z
(M+) calcd 365.1627, obsd 365.1638; [R]22D +89.4 (c 0.216, C2H5-
OH).
1
1100; H NMR (300 MHz, CDCl3) δ 8.15 (d, J ) 8.4 Hz, 1 H),
7.89 (t, J ) 7.7 Hz, 1 H), 7.60-7.20 (m, 4 H), 6.15 (q, J ) 6.9
Hz, 1 H), 3.75 (d, J ) 9.9 Hz, 1 H), 3.25 (d, J ) 9.9 Hz, 1 H),
1.95 (d, J ) 6.9 Hz, 3 H); 13C NMR (75 MHz, CDCl3) ppm 192.5,
162.6, 133.9, 133.0, 130.9, 129.5, 129.1, 127.4, 126.3, 125.1,
123.9, 123.4, 56.9, 48.0, 17.3; MS m/z (M+) calcd 239.0946, obsd
Anal. Calcd for C22H23NO4: C, 72.31; H, 6.34. Found: C,
72.12; H, 6.39.
239.0958; [R]22 +19.7 (c 0.152, C2H5OH).
D
Anal. Calcd for C15H13NO2‚1/3H2O: C, 73.45; H, 5.62.
For the X-ray crystallographic analysis, see Figure 6.
C. Rea ction w ith 5a : 63:27 mixture of 22 and 23 in 85%
yield. For 22: colorless oil; IR (CHCl3, cm-1) 3380, 1730, 1216;
1H NMR (300 MHz, CDCl3) δ 7.50-7.25 (m, 10 H), 6.19 (ddd,
J ) 10.7, 8.4, 1.9 Hz, 1 H), 5.32 (s, 1 H), 5.28 (s, 1 H), 4.78 (q,
J ) 7.1 Hz, 1 H), 3.81 (d, J ) 8.2 Hz, 1 H), 3.33 (d, J ) 5.6 Hz,
1 H), 3.00 (d, J ) 5.6 Hz, 1 H), 1.31 (d, J ) 7.0 Hz, 3 H) (OH
not observed); 13C NMR (75 MHz, CDCl3) ppm 168.5, 137.9,
136.7, 135.4, 131.2, 129.2, 128.72, 128.69, 128.6, 127.7, 127.4,
126.7, 126.5, 119.3, 84.8, 63.7, 54.5, 51.4, 49.5, 18.1; MS m/z
Found: C, 73.87; H, 5.64.
Gen er a l P r oced u r e for Ad d ition s In volvin g 24.
A
suspension of the bromide (0.31 mmol) and indium powder (40
mg, 0.34 mmol) in water (5 mL) was stirred vigorously for 1
h, treated with a solution of 24 (50 mg, 0.21 mmol) in THF (5
mL), and continuously agitated for 12 h prior to dilution with
ethyl acetate and the usual workup.
A. Reaction with 4a : 66:27:7 mixture of 25a , 26a , and 27a
(or 28a ) in 72% yield. For 25a : colorless oil; IR (neat, cm-1
)
3380, 1728, 1274; 1H NMR (300 MHz, CDCl3) δ 8.18-7.25 (m,
7 H), 6.29 (s, 1 H), 5.92 (s, 1 H), 5.72 (q, J ) 6.9 Hz, 1 H), 3.95
(s, 1 H), 3.74 (s, 3 H), 3.19 (d, J ) 5.6 Hz, 1 H), 2.64 (d, J )
5.6 Hz, 1 H), 1.74 (d, J ) 6.9 Hz, 3 H), 1.34 (d, J ) 7.1 Hz, 3
H) (OH not observed); 13C NMR (75 MHz, CDCl3) ppm 168.6,
140.9, 134.7, 133.8, 131.0, 128.8, 128.0, 126.9, 125.9, 124.9,
123.6, 122.9, 100.2, 98.7, 84.9, 52.4, 51.4, 46.9, 39.7, 17.9, 14.9;
(M+ + H) calcd 308.1573, obsd 308.1653; [R]22 -45.2 (c 0.20,
D
C2H5OH).
For 23: colorless crystals, mp 128-129 °C; IR (CH2Cl2, cm-1
)
3358, 1730; 1H NMR (300 MHz, CDCl3) δ 7.42-7.01 (series of
m, 10 H), 6.16-6.03 (m, 1 H), 5.19 (d, J ) 8.0 Hz, 1 H), 5.30
(s, 1 H), (s, 1 H), 4.84 (q, J ) 7.0 Hz, 1 H), 3.74 (d, J ) 7.7 Hz,
1 H), 3.22 (d, J ) 5.5 Hz, 1 H), 3.19 (d, J ) 5.5 Hz, 1 H), 2.75
(s, 1 H), 1.52 (d, J ) 7.0 Hz, 3 H); 13C NMR (75 MHz, CDCl3)
ppm 168.6, 139.7, 137.9, 135.3, 129.2, 128.7 (2 C), 128.6 (2 C),
128.5, 127.5, 127.4, 126.6, 119.2, 85.0, 54.5, 50.6, 49.4, 30.9,
18.1; MS m/z (M+) calcd 307.1572, obsd 307.1535; [R]22D -44.4
(c 0.25, C2H5OH).
MS m/z (M+) calcd 353.1627, obsd 353.1650; [R]22 +40.6 (c
D
0.17, C2H5OH).
For 26a : colorless crystals, mp 109-110 °C; IR (CHCl3,
cm-1) 3379, 1728, 1273; 1H NMR (300 MHz, CDCl3) δ 8.15 (d,
J ) 8.4 Hz, 1 H), 7.90-7.80 (m, 1 H), 7.61-7.45 (m, 5 H), 6.04
(s, 1 H), 5.79 (q, J ) 6.9 Hz, 1 H), 5.38 (s, 1 H), 4.53 (br s, 1
H), 3.65 (s, 3 H), 3.06 (d, J ) 5.5 Hz, 1 H), 2.75 (q, J ) 7.2 Hz,
1 H), 2.58 (d, J ) 5.5 Hz, 1 H), 1.75 (d, J ) 6.9 Hz, 3 H), 1.15
(d, J ) 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3) ppm 168.7,
168.5, 140.8, 134.7, 133.9, 131.0, 128.9, 128.7, 128.3, 126.7,
125.9, 125.1, 123.7, 123.1, 85.0, 52.4, 50.9, 46.2, 41.1, 17.5, 14.5;
1-[(1R)-1-(Naph th yl)eth yl]-2,3-azetidin edion e (24). Stir-
ring of 13 (12.03 g, 92.5 mmol) with (R)-R-(1-naphthyl)-
ethylamine (15.85 g, 92.15 mmol) in dry methanol (200 mL)
under N2 for 2 h with workup as above (elution with 50% ethyl
acetate in hexanes) gave 25.6 g (92%) of the 1,4-adduct as a
mixture of diastereomers: IR (CH2Cl2, cm-1) 3250, 1730, 1100;
1H NMR (300 MHz, CDCl3) δ 8.13 (t, J ) 8.3 Hz, 1 H), 7.86 (d,
J ) 7.4 Hz, 1 H), 7.75 (d, J ) 7.4 Hz, 1 H), 7.60-7.25 (m, 4
H), 4.63 (overlapping q, J ) 6.6 Hz, 1 H), 4.25 (overlapping q,
J ) 6.3 Hz, 1 H), 3.70 and 3.67 (2s, total 3 H), 3.78-3.61 (m,
MS m/z (M+) calcd 353.1627, obsd 353.1650; [R]22 -180.8 (c
D
0.12, C2H5OH).
Anal. Calcd for C21H23NO4: C, 71.37 H, 6.56. Found: C,
71.36; H, 6.65.
For the X-ray crystallographic analysis, see Figure 7.