10160
C. De Risi et al. / Tetrahedron 57 *2001) 10155±10161
3H, OCH3), 4.33 .q, J6.9 Hz, 2H, OCH2CH3), 4.95 .q,
J6.4 Hz, 1H, CH3CHO), 5.12 and 5.14 .AB system,
J12.2 Hz, 2H, OCH2Ph), 7.35 .m, 5H, Ph), 9.47 .br, 1H,
NH). 13C NMR: d 25.30 .q, J116.4 Hz, SiCH3), 25.19 .q,
J116.4 Hz, SiCH3), 13.81 .q, J126.3 Hz, OCH2CH3),
17.86 .s, C.CH3)3), 22.70 .q, J129.6 Hz, CH3CHO),
25.64 .q, J124.4 Hz, t-Bu), 51.92 .q, J146.3 Hz,
OCH3), 61.97 .t, J147.0 Hz, OCH2CH3), 67.77 .t, J
146.7 Hz, OCH2Ph), 68.32 .d, J146.8 Hz, CH3CHO),
113.52 .s, C-3), 128.14 .d, J159.3 Hz, Ph), 128.36 .d,
J159.3 Hz, Ph), 128.48 .d, J159.3 Hz, Ph), 135.25 .s,
Ph), 140.47 .s, C-2), 151.51 .s, NHCOO), 163.60 .s,
COO), 165.75 .s, COO). Found: C, 59.37; H, 7.65; N,
3.03. C23H35NO7Si requires C, 59.33; H, 7.58; N, 3.01.
CH3CHO and OCH2CH3). 13C NMR: d 25.54 .q, J
117.7 Hz, SiCH3), 24.51.q, J117.7 Hz, SiCH3), 13.89
.q, J118.8 Hz, OCH2CH3), 17.56 .s, C.CH3)3), 20.97 .q,
J124.4 Hz, CH3CHO), 25.39 .q, J129.6 Hz, t-Bu), 51.13
.q, J145.9 Hz, OCH3), 53.54 .d, J139.2 Hz, CH), 55.76
.d, J133.4 Hz, CH), 60.85 .t, J146.8 Hz, OCH2CH3),
67.49 .d, J144.4 Hz, CH3CHO), 172.15 .s, COO),
174.23 .s, COO). Found: C, 54.10; H, 9.43; N, 4.30.
C15H31NO5Si requires C, 54.02; H, 9.37; N, 4.20.
1
5b: IR .®lm): 3393, 1740, 1609 cm21. H NMR: d 0.09 .s,
3H, SiCH3), 0.10 .s, 3H, SiCH3), 0.86 .s, 9H, t-Bu), 1.20±
1.32 .m, 6H, CH3CHO and OCH2CH3), 1.79 .br, 2H, NH2),
2.90 .dd, 1H, J7.9, 3.8 Hz, CHCO2CH3), 3.66 .s, 3H,
OCH3), 3.92 .d, J3.8 Hz, 1H, CHNH2), 4.10±4.40 .m,
3H, CH3CHO and OCH2CH3). 13C NMR: d 24.90 .q, J
122.4 Hz, SiCH3), 24.17 .q, J117.6 Hz, SiCH3), 14.24 .q,
J126.1 Hz, OCH2CH3), 17.99 .s, C.CH3)3), 22.37 .q, J
124.7 Hz, CH3CHO), 25.84 .q, J124.2 Hz, t-Bu), 51.64 .q,
J146.2 Hz, OCH3), 53.10 .d, J139.4 Hz, CH), 56.19 .d,
J131.3 Hz, CH), 61.23 .t, J146.8 Hz, OCH2CH3), 66.59
.d, J143.1 Hz, CH3CHO), 172.09 .s, COO), 174.66 .s,
COO). Found: C, 54.09; H, 9.44; N, 4.28. C15H31NO5Si
requires C, 54.02; H, 9.37; N, 4.20.
4.3.3. ꢀ^)-Methyl 2-amino-3-methoxycarbonyl-4-tert-
A
butyldimethylsilyloxy-pentanoate ꢀ4a) and ꢀ5a).
solution of 3a .300 mg, 0.66 mmol) in ethanol .10 ml)
was hydrogenated in a Parr apparatus in the presence of
Ni±Raney W-2 as the catalyst for 8 h. The suspension
was ®ltered through celite and the solvent evaporated
under reduced pressure to give the mixture of 4a and 5a
.136 mg, 65%) as a yellow oil. IR .®lm): 3395, 1743,
1
1606 cm21. H NMR: the isomers 4a and 5a are present in
9:1ratio; 4a shows resonances at: d 0.02 .s, 3H, SiCH3),
0.06 .s, 3H, SiCH3), 0.85 .s, 9H, t-Bu), 1.26 .d, J6.1Hz,
3H, CH3CHO), 1.72 .br, 2H, NH2), 2.91.dd, J7.9, 4.9 Hz,
1H, CHCO2CH3), 3.66 .s, 3H, OCH3), 3.71.m, H1,
CHNH2), 3.72 .s, 3H, OCH3); 5a shows resonances at: d
0.02 .s, 3H, SiCH3), 0.06 .s, 3H, SiCH3), 0.85 .s, 9H, t-Bu),
1.26 .d, J6.1Hz, 3H, CH3CHO), 1.72 .br, 2H, NH2), 2.72
.dd, J7.9, 3.8 Hz, 1H, CHCO2CH3), 3.66 .s, 3H, OCH3),
3.72 .s, 3H, OCH3), 3.92 .d, J3.8 Hz, 1H, CHNH2), 4.3 .q,
4.4. General procedure for the synthesis of the 2-azeti-
dinones ꢀ6) and ꢀ7)
A cooled .08C) solution of the appropriate b-aminoester 4 or
5 .1mmol) in dry CH 2Cl2 .5 ml) was treated with triethyl-
amine .1.1 mmol) and trimethylchlorosilane .1.1 mmol).
The resulting solution was stirred at the same temperature
for 30 min, then tert-butylmagnesium chloride .2 M in
diethyl ether, 6.6 mmol) was added and stirring was con-
tinued at room temperature until completion .12 h). Water
.10 ml) was added and the precipitated magnesium salts
were ®ltered through celite. The phases were separated,
the aqueous phase was extracted with CH2Cl2 .3£10 ml)
and the combined organic extracts were dried and evapo-
rated. The crude residue thus obtained was puri®ed by ¯ash-
chromatography .eluent EtOAc±light petroleum 1:3).
J6.1Hz, 1H, CH CHO). 13C NMR resonances for 4a: d
3
25.37 .q, J117.6 Hz, SiCH3), 24.31.q, J117.6 Hz,
SiCH3), 17.75 .s, C.CH3)3), 21.13 .q, J125.3 Hz,
CH3CHO), 25.55 .q, J126.0 Hz, t-Bu), 51.53 .q, J
146.1 Hz, OCH3), 52.15 .q, J146.4 Hz, OCH3), 53.65 .d,
J139.7 Hz, CH), 56.05 .d, J132.6 Hz, CH), 67.55 .d,
J203.4 Hz, CH), 172.34 .s, COO), 174.94 .s, COO) and
for 5a: d 25.37 .q, J117.6 Hz, SiCH3), 24.31.q, J
117.6 Hz, SiCH3), 14.07 .s, C.CH3)3), 22.29 .q, J
125.3 Hz, CH3CHO), 25.67 .q, J126.0 Hz, t-Bu), 51.53
.q, J146.1 Hz, OCH3), 52.15 .q, J146.4 Hz, OCH3),
53.65 .d, J139.7 Hz, CH), 56.05 .d, J132.6 Hz, CH),
66.36 .d, J203.4 Hz, CH), 172.30 .s, COO), 174.90 .s,
COO).
4.4.1.
ꢀ^)-3-[ꢀ1-tert-Butyldimethylsilyloxy)-ethyl]-4-
methoxycarbonyl-azetidin-2-one ꢀ6a). This compound
was obtained from the mixture of 4a and 5a by using the
afore-mentioned general procedure as a yellowish oil. IR
1
.®lm): 3285, 1778, 1743 cm21. H NMR: d 0.09 .s, 6H,
Si.CH3)2), 0.89 .s, 9H, t-Bu), 1.34 .d, J6.4 Hz, 3H,
CH3CHO), 3.34 .br, 1H, CHCONH), 3.77 .s, 3H, OCH3),
4.09 .d, J2.7 Hz, 1H, CHNH), 4.15±4.30 .m, 1H, CHOSi),
6.40 .br, 1H, NH). 13C NMR: d 25.01.q, J117.6 Hz,
SiCH3), 24.13 .q, J117.9 Hz, SiCH3), 18.04 .s,
C.CH3)3), 20.76 .q, J125.5 Hz, CH3CHO), 25.73 .q, J
124.8 Hz, t-Bu), 50.03 .d, J152.3 Hz, CH), 52.52 .q, J
146.9 Hz, OCH3), 64.06 .d, J136.9 Hz, CH), 64.99 .d, J
140.9 Hz, CH), 167.21 .s, NHCOO), 171.98 .s, COO).
Found: C, 54.40; H, 8.82; N, 4.88. C13H25NO4Si requires
C, 54.32; H, 8.77; N, 4.87.
4.3.4. ꢀ^)-Ethyl 2-amino-3-methoxycarbonyl-4-tert-
A
butyldimethylsilyloxy-pentanoate ꢀ4b) and ꢀ5b).
solution of 3b .1g, 2.15 mmol) in ethanol .30 ml) was
hydrogenated in a Parr apparatus in the presence of
Ni±Raney W-2 as the catalyst for 8 h. The suspension
was ®ltered through celite and the solvent evaporated
under reduced pressure. The residue was puri®ed by ¯ash-
chromatography .eluent EtOAc±light petroleum 1:3) to
give 4b .450 mg, 63%) and 5b .50 mg, 7%) as yellow oils.
1
4b: IR .®lm): 3393, 1740, 1606 cm21. H NMR: d 0.02 .s,
3H, SiCH3), 0.06 .s, 3H, SiCH3), 0.85 .s, 9H, t-Bu), 1.20±
1.40 .m, 6H, CH3CHO and OCH2CH3), 1.85 .br, 2H, NH2),
2.90 .dd, J7.9, 4.9 Hz, 1H, CHCO2CH3), 3.63±3.68 .m,
1H, CHNH2), 3.72 .s, 3H, OCH3), 4.10±4.40 .m, 3H,
4.4.2.
ꢀ^)-3-[ꢀ1-tert-Butyldimethylsilyloxy)-ethyl]-4-
ethoxycarbonyl-azetidin-2-one ꢀ6b). This compound was
obtained from 4b by using the afore-mentioned general
procedure as a yellowish oil, yield 75%. IR .®lm): 3306,