7944
B. Jiang, H. Tian / Tetrahedron Letters 48 (2007) 7942–7945
4. (a) Kozawa, Y.; Mori, M. Tetrahedron. Lett. 2001, 42,
OTBS
H
OTBS
H
4869–4873; (b) Kozawa, Y.; Mori, M. J. Org. Soc. 2003,
68, 8068–8074; (c) Alcaide, B.; Polanco, C.; Sierra, M. A.
J. Org. Soc. 1998, 63, 6786–6796.
5% PtCl2
toluene, 80 oC
N
R1
NH
5. (a) Mishida, M.; Shibasaki, M.; Ikegami, M. Tetrahedron
Lett. 1981, 22, 4819–4822; (b) Shibasaki, M.; Nishida, A.;
Ikegami, S. J. Chem. Soc. Chem. Commun. 1982, 22, 1324–
1325.
6. (a) Prasad, J. S.; Liebeskind, L. S. Tetrahedron. Lett. 1988,
29, 4253–4256; (b) Prasad, J. S.; Liebeskind, L. S.
Tetrahedron Lett. 1988, 29, 4257–4260.
O
O
3
R1
6
R1
Yield recovered S.M.
a
50%
42%
55%
H ( )
13%
Ph (h) 30%
CO2Et (i) 9%
7. Haruta, J.-I.; Nishi, K.; Kikuchi, K.; Matsuda, S.;
Tamura, Y.; Kita, Y. Chem. Pharm. Bull. 1989, 37,
2338–2343.
Figure 2. Cyclization of 4-propargyl-2-azetidinone derivatives pro-
moted by PtCl2.
8. Ziegler, C. B., Jr.; Curran, W. V.; Feigelson, G. B.; Bitha,
P.; Fabio, P.; Strohmeyer, T.; Short, K.; Lin, Y.-I.
Tetrahedron 1994, 50, 12085–12096.
9. For a review about additions of organometallic reagents
to C=N Bonds see: Bloch, R. Chem. Rev. 1998, 98, 1407–
1438.
of 4-allenyl-2-azetidinone 4a to 5 mol% PtCl2 in toluene
produced the bicyclic b-lactam product 5a in 69% yield
(Table 2, entry 1), while 4-(10-methylallenyl)-2-azetidi-
none 4b gave the desired product 5b in 89% yield (Table
2, entry 2).6a When the reaction was carried out with
other azetidinones, the allene part bearing alkyl or aryl
group10 gave good yields of cyclization products (Table
2, entries 3–8). However, the 2-azetidinones allene with
CO2Et, BnOCH2, and AcOCH2 substituents gave poor
yields and most of the starting materials were recovered
(entries 9–11).
10. Lee, P. H.; Kim, H.; Lee, K.; Kim, M.; Noh, K.; Kim, H.;
Seomoon, D. Angew. Chem. Int. Ed. 2005, 44, 1840–1843.
11. Typical procedure for zinc-mediated reaction: A two-
necked schlenk tube with a condenser was charged with 1
(100 mg) and zinc powder (102 mg, pre-treatment accord-
ing to Purification of Laboratory Chemicals, fifth edition,
Butterworth–Heinemann, 2003) under Ar. Then, THF
(3 mL) and propargyl bromide (3 equiv) were added
successively via a cannula at rt. The mixture was kept on
a pre-heated oil bath and stirred under refluxed condition
or 45 ꢁC as indicated in Table 1 before it was allowed to
cool to rt. After quenched by saturated NH4Cl solution
(4 mL), the mixture was extracted with EtOAc (4 mL·3).
The combined organic layers were dried over anhydrous
Na2SO4 and concentrated in vacuo to give a residue that
was further purified by column chromatography on silica
(EA:PE = 1:4–1:6). Characterization data for representa-
tive compounds are shown as follows:
When 4-propargyl-2-azetidinone (3a) was treated with
5 mol% of PtCl2 at 80 ꢁC, the cyclization product 6a
with the unsaturated bond shifted to C1–C2 position
was obtained in 13% yield (Fig. 2). The phenyl analog
3h gave 6h in slightly better yield under the same condi-
tion. Substrate 3i also gave 6i in 9% yield, which was
close to the carbapenem. Unfortunately, screening vari-
ous platinum compounds and additives did not improve
the yield.
Compound 4b: FTIR (KBr) 3144, 3091, 2954, 2928, 2904,
2857, 1962, 1759, 1714 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 5.76 (br s, 1H), 4.72–4.65 (m, 2H), 4.16–4.08 (m, 1H),
4.00 (d, J = 2.1 Hz, 1H), 2.89–2.85 (m, 1H) 1.64 (dd,
J=3.0, 3.3 Hz, 3H), 1.13 (d, J = 6.3 Hz, 6H), ꢀ0.02 (s,
6H); 13C NMR (75 MHz, CDCl3) d 205.4, 168.4, 109.6,
98.3, 76.2, 65.1, 64.2, 51.3, 25.6, 22.5, 17.4, 14.5, ꢀ4.5,
ꢀ5.1; HRMS (MALDI) calcd for C15H27NO2SiNa+
304.1703, found 304.1716.
In summary, a convenient synthetic method for 4-alle-
nyl-2-azetidinone and 4-propargyl-2-azetidinone deriva-
tives has been established via Zn-mediated reactions. We
have also demonstrated that PtCl2 catalyzes intramole-
cular amidation of those products to afford carbapenem
skeletons.
Compound 3i: FTIR (KBr) 3216, 2958, 2933, 2887, 2858,
2236, 1756, 1719 cmꢀ1 1H NMR (300 MHz, CDCl3) d
;
Acknowledgements
5.92 (br s, 1H), 4.22 (q, J = 6.6 Hz, 3H), 3.95–3.89 (m,
1H), 2.94–2.90 (m, 1H), 2.71–2.66 (m, 2H), 1.30 (t,
J = 6.6 Hz, 3H), 1.22 (d, J = 6.6 Hz, 3H), 0.86 (s, 9H),
0.06 (s, 6H); 13C NMR (75 MHz, CDCl3) d 167.5, 153.1,
83.8, 74.9, 64.7, 64.1, 61.9, 47.8, 25.5, 24.7, 22.4, 17.7, 13.8,
ꢀ4.4, ꢀ5.2; HRMS (MALDI) calcd for C17H29NO4SiNa+
362.1758, found 362.1766.
We gratefully acknowledge Shanghai Byelen Chemical
Co., Ltd. for the gift of 4-acetoxy-2-azetidinone and
the National Natural Foundation of China for financial
support.
12. (a) Nishida, A.; Shibasaki, M.; Ikegami, S. Chem. Pharm.
Bull. 1986, 34, 1434–1446; (b) Shibasaki, M.; Nishida, A.;
Ikegami, S. Tetrahedron Lett. 1982, 23, 2875–2878.
References and notes
13. The 1a, 1b-isomers of 3m, 3n were unseparated by column
chromatography or recrystallization and the configuration
of 1-methyl was assigned as the following methods: (a)
comparing the 1H NMR spectrograms of 3l and sono-
gashira coupling product of iodobenzene and (3S,4R)-
4-((S)-but-3-yn-2-yl)-3-((R)-1-(tert-butyldimethylsilyloxy)-
ethyl)azetidin-2-one (7) prepared according to Ref. 7; (b)
deprotecting the Bn group of 3m with DDQ to the known
free OH compound (Ref. 4b); (c) the pure 1b-isomer of 3n
was prepared from 7 by protecting NH with TBS, treating
1. For a review see Sunagawa, M.; Sasaki, A. Heterocycle
2001, 54, 1.
2. (a) Manhas, M. S.; Wagle, D. R.; Chiang, J.; Bose, A. K.
Hererocycles 1988, 27, 1755; (b) Georg, G. I. The Organic
chemistry of b-Lactam; VCH: New York, 1992; (c) BerKs,
A. H. Tetrahedron 1996, 52, 331–375.
3. (a) Alcaide, B.; Almendros, P. Chem. Soc. Rev. 2001, 30,
226–240; (b) Palomo, C.; Aizpurua, J. M.; Ganboa, I.;
Oiarbide, M. Synlett. 2001, 1813–1826.