LETTER
Perhydrooxazinones from 2-Aza-3-trimethylsilyloxy-1,3-butadiene
1737
(3) For Review see: Panunzio, M.; Zarantonello, P. Org. Process
Res. Dev. 1998, 2, 49.
(t, 1H, J=7.95), 7.43 (s, 5H), 6.48 (s, 1H), 5.40 (s, 1H), 3.13
(d, 1H, J=16.64), 2.91 (d, 1H, J=16.64), 1.65 (s, 3H); 13
C
(4) Bacchi, S.; Bongini, A.; Panunzio, M.; Villa, M. Synlett 1998,
843.
NMR 168.37, 145.45, 137.25, 131.53, 130.08, 129.01, 126.73,
124.00, 120.82, 81.31, 77.07, 41.62, 32.14; 6d (cis Me-H2):
m.p.=145.7 °C; 1H NMR 8.34 (t, 1H, J=2.08), 8.15 (m, 1H),
7.78 (m, 1H), 7.50 (m, 6H), 6.55 (s, 1H), 6.05 (s, 1H), 2.94 (d,
1H, J=16.35), 2.82 (d, 1H, J=16.35), 1.80 (s, 3H); 13C NMR
167.96, 148.08, 137.46, 130.36, 129.93, 129.51, 128.96,
126.82, 122.42, 119.64, 80.60, 76.13, 43.61, 26.07; 5e (trans
Me-H2): m.p.= 190-2°C; 1H NMR 8.27 (d, 2H, J=8.75), 7.63
(d, 2H, J=8.75), 7.44 (s, 5H), 6,32 (s, 1H), 5.39 (s, 1H), 3.12
(5) (a) Bandini, E.; Martelli, G.; Spunta, G.; Bongini, A.;
Panunzio, M. Tetrahedron Lett. 1996, 37, 4409. (b) Bandini,
E.; Martelli, G.; Spunta, G.; Panunzio, M. Synlett 1996, 1017.
(6) (a) Bandini, E.; Martelli, G.; Spunta, G.; Bongini, A.;
Panunzio, M.; Piersanti, G. Tetrahedron: Asymm. 1997, 8,
3717. (b) Bongini, A.; Panunzio, M.; Bandini, E.; Martelli, G.;
Spunta, G. J. Org. Chem. 1997, 62, 8911. (c) Panunzio, M.;
Villa, M.; Missio, A.; Rossi, T.; Seneci, P. Tetrahedron Lett.
1998, 39, 6585.
(d, 1H, J=16.68), 2.92 (d, 1H, J=16.68), 1.66 (s, 3H); 13
C
NMR 168.32, 150.30, 147.76, 137.25, 130.11, 129.05, 126.72,
126.68, 124.21, 81.41, 77.25, 41.76, 32.01; 6e (cis Me-H2):
m.p. =204-6 °C; 1H NMR 8.20 (d, 2H, J=8.70), 7.62 (d, 2H,
J=8.70), 7.35 (m, 5H), 6.68 (s, 1H), 6.02 (s, 1H), 2.90 (d, 1H,
J=16.60), 2.79 (d, 1H, J=16.60), 1.76 (s, 3H); 13C NMR
167.79, 152.88, 147.27, 137.54, 130.07, 129.05, 126.85,
125.32, 123.76, 84.64, 77.03, 43.57, 26.06; 5f (trans Me-H2):
m.p.=84-86°C; 1H NMR 7.75 (m, 3H), 7.60 (m, 2H), 7.35 (s,
5H), 7.15 (m, 2H), 6.10 (s, 1H), 5.13 (s, 1H), 3.90 (s, 3H), 3.25
(d, 1H, J=17.10), 2.85 (d, 1H, J=17.10), 1.68 (s, 3H);13C NMR
168.99, 158.33, 138.10, 136.68, 136.64, 134.18, 129.83,
129.70, 128.80, 128.45, 127.84, 126.85, 124.81, 124.30,
119.23, 105.69, 81.10, 77.50, 55.34, 41.18, 31.74; 6f (cis Me-
H2): m.p.= 130-2°C; 1H NMR 7.80- 7.10 (m, 11H), 6.43 (s,
(7) Bandini, E.; Martelli, G.; Spunta, G.; Bongini, A.; Panunzio,
M.; Piersanti, G. Tetrahedron:Asymm. 1999, 10, 1445.
(8) Synthesis of Perhydro-oxazin-4-ones: General procedure
To a solution of LiHMDSA (1 ml of 1M solution in THF) at
0°C benzaldehyde or (S)-triisopropylsilyloxy lactaldehyde
(1mmol) in heptane (5 ml) was added. The reaction mixture
was allowed to reach r.t. spontaneously while the stirring was
continued for 1h. TMSCl (1.1 mmol) was added in one portion
at 0°C and the reaction mixture further stirred for 1 h. A white
precipitate formed. The solution was cooled at 0°C and NEt3
(2 mmol) was added in one portion. The acetyl chloride 3 (1
mmol) was added dropwise. Stirring was maintained for 1/2 h
at 0°C and 1/2 h at r.t. while a new copious precipitate
appeared. The precipitate was filtered under argon, the solvent
removed in vacuo and to the resulting oily residue CH2Cl2 (10
ml) was added and the solution cooled at -78°C. Ketone 4 in
CH2Cl2 (2 ml) was added followed by BF3 Et2O (1.1 mmol) in
CH2Cl2 (5 ml). The solution was stirred overnight while the
temperature was allowed to reach r.t.. The mixture was poured
into 5% NaHCO3 aqueous solution and extracted with CH2Cl2
. The organic layers were dried and the solvent removed in
vacuo. Flash chromatography of the residue (CH2Cl2 /acetone
9/1) yielded pure isolated perhydro-oxazin-4-ones.
1H), 6.10 (s, 1H), 3.90 (s, 3H), 2.93 (s, 2H), 1.82 (s, 3H); 13
C
NMR 168.67, 157.92, 141.00, 138.25, 133.78, 129.81, 129.75,
128.85, 127.15, 126.96, 123.17, 122.62, 119.06, 105.60,
80.66, 76.67, 53.31, 43.94, 25.82; 5g: m.p. =118-20°C; 1H
NMR 7.40 (m, 5H), 6.90 (s, 1H), 5.75 (s, 1H), 2.68 (d, 1H, J=
16.90), 2.37 (d, 1H, J= 16.90), 2.15 (m, 1H), 2.05-1.50 (m,
7H); 13C NMR 169.54, 138.42, 129.46, 128.67, 126.72, 83.91,
80.68, 41.25, 39.92, 34.02, 23.83, 22.80; 5h: m.p.=136-8°C;
1H NMR 7.40 (m, 5H), 6.90 (s, 1H), 2.32 (s, 2H), 2.00 (m,
2H), 1.50 (m, 8H); 13C NMR 169.49, 138.44, 128.99, 128.34,
126.45, 79.11, 73.79, 42.17, 38.24, 32.16, 25.12, 21.47, 21.31;
5i: m.p.=124-6 °C; 1H NMR 7.40 (m, 5H), 6.45 (s, 1H), 5.74
(s, 1H), 2.40 (s, 2H), 2.05-1.35 (m, 12H); 13C NMR 169.78,
138.43, 129.55, 128.80, 126.74, 79.88, 78.36, 43.25, 42.33,
36.02, 29.45, 29.33, 21.77, 21.61; 11a: 1H NMR 6.35 (s, 1H),
4.47 (d, 1H, J= 6.84), 3.78 (quintet, 1H, J= 6.16), 2.30 (m,
(9) All compounds, identified as pure isolated compound, gave
analytical data (I.R., 1H and 13C NMR, MS and E.A.)
consistent with the assigned structures and literature data. The
configuration of each isomer has been determined by means of
NOE experiments. Selected data as follows: (1H NMR: 200
MHz, CDCl3, ppm ; 13C NMR 50 MHz, CDCl3, ppm). 3: 1H
NMR 8.42 (s, 1H), 7.85 (m, 2H), 7.42 (m, 3H), 4.68 (s, 1H),
4.30 (s, 1H), 0.30 (s, 9H); 13C NMR 156.83, 156.44, 135.93,
131.08, 128.94, 128.57, 91.64, -0.13. 5a: m.p.=98-100°C; 1H
NMR 7.36 (m, 5H), 7.10 (s, 1H), 5.72 (s, 1H), 2.44 (d, 1H,
2H), 1.30 (s, 6H), 1.25 (d, 3H, J=6.06), 1.08 (s, 21H); 13
C
NMR 168.56, 82.04, 72.33, 71.09, 43.32, 29.41, 23.77, 19.15,
17.82, 12.33. 12a: 1H NMR 6.15 (s, 1H), 4.90 (d, 1H, J= 3.40),
4.00 (dq, 1H, J= 3.40, 6.12), 2.30 (m, 2H), 1.32 (s, 3H), 1.30
(s, 3H), 1.12 (d, 3H, J= 6.12), 1.04 (s, 21H); 13C NMR 168.76,
79.98, 72.33, 69.10, 43.24, 29.41, 23.20, 17.72, 15.45, 11.93.
11b: 1H NMR 6.32 (s, 1H), 4.36 (d, 1H, J= 6.82), 3.75
(quintet, 1H, J= 6.16), 2.22 (s, 2H), 1.90- 1.30 (m, 10H), 1.23
(d, 3H, J= 6.16), 1.00 (s, 21H); 13C NMR 169.06, 81.47, 73.60,
71.69, 43.02, 38.39, 31.91, 21.64, 21.56, 21.53, 19.68, 18.10,
12.62. 12b: 1H NMR 6.12 (s, 1H), 4.88 (d, 1H, J= 3.20), 4.02
(dq, 1H, J=3.20 6.16), 2.28 (s, 2H), 1.90 (m, 1H), 1.70- 1.20
(m, 9H), 1.13 (d, 3H, J= 6.16), 1.04 (s, 21H); 13C NMR
169.06, 79.33, 73.60, 69.35, 42.73, 38.31, 31.75, 25.39, 21.51,
17.97, 15.68, 12.19. 14a: m.p.=160-2°C; [a]2D0=+38.75
(c=0.96 CHCl3); 1H NMR 7.40 (m, 5H), 6.40 (s, 1H), 5.83 (d,
1H, J= 3.66), 3.25 (d, 1H, J= 14.94), 2.15 (m, 2H), 1.80 (m,
3H), 1.50 (m, 2H), 1.10-0.75 (m, 12H); 13C NMR 172.14,
137.90, 129.41, 128.83, 126.41, 81.33, 78.17, 49.74, 49.68,
41.08, 34.90, 27.75, 26.24, 23.74, 22.18, 21.27, 17.66; 14b:
m.p.= 174-6°C; [a]2D0=-64.37 (c= 0.32 CHCl3); 1H NMR 7.40
(m, 5H), 6.10 (s, 1H), 5.71 (d, 1H, J=1.96), 2.79 (d, 1H,
J=16.78), 2.12 (m, 3H), 1.70 (m, 2H), 1.55 (m, 3H), 1.20-0.80
(m, 11H); 13C NMR 171.07, 138.15, 129.46, 128.86, 126.50,
J=16.8), 2.28 (d, 1H, J=16.8) 1.38 (s, 3H), 1.30 (s, 3H); 13
C
NMR 169.38, 138.29, 129.40, 128.61, 126.72, 80.26, 73.12,
43.22, 29.28, 24.22; 5b (trans Me-H2): m.p.=176-8°C; 1H
NMR 7.40 (m, 10H), 6.70 (s, 1H), 5.25 (s, 1H), 3.11 (d, 1H,
J=16.85), 2.76 (d, 1H, J=16.85), 1.60 (s, 3H); 13C NMR
168.89, 141.71, 137.80, 129.29, 128.57, 128.44, 127.79,
126.54, 125.54, 80.61, 77.04, 40.85, 31.73; 6b (cis Me-H2):
m.p.= 156-8°C; 1H NMR 7.40 (m, 10H), 6.36 (s, 1H), 6.00 (s,
1H), 2.80 (s, 2H), 1.73 (s, 3H); 13C NMR 168.70, 146.00,
138.23, 129.70, 128.86, 128.42, 127.34, 126.87, 124.12,
80.46, 76.46, 43.87, 25.77; 5c (trans Me-H2): m.p.=103-5°C;
1H NMR 7.42 (m, 5H), 6.10 (s, 1H), 5.73 (s, 1H), 2.48 (s, 2H),
1.88 (sextet, 1H, J=7.38), 1.65 (sextet, 1H, J=7.38), 1.30 (s,
3H), 1.00 (t, 3H, J=7.38; 13C NMR 169.73, 138.20, 129.73,
128.91, 126.77, 80.33, 75.83, 42.57, 30.18, 26.38, 7.81; 6c
(cis Me-H2) m.p.=82-4°C; 1H NMR 7.42 (m, 5H), 6.35 (s,
1H), 5.80 (s, 1H), 2.53 (d, 1H, J=16.75), 2.30 (d, 1H, J=16.75),
1.65 (q, 2H, J=7.45), 1.39 (s, 3H), 0.96 (t, 3H, J=7.45); 13
C
NMR 169.59, 138.42, 129.61, 128.81, 126.74, 80.20, 75.50,
41.63, 35.37, 22.38, 7.63; 5d (trans Me-H2): m.p.=184-6°C;
1H NMR 8.34 (t, 1H, J=2.02), 8.20 (m, 1H), 7.76 (m, 1H), 7.60
Synlett 1999, No. 11, 1735–1738 ISSN 0936-5214 © Thieme Stuttgart · New York