ASYMMETRIC-SYNTHESIS OF BETA-LACTAMS VIA THE ZINC-MEDIATED GLYCINE ESTER ENOLATE IMINE CONDENSATION REACTION USING ALPHA-AMINO ESTERS AS THE CHIRAL AUXILIARY
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VANMAANEN, HL
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机构:UNIV UTRECHT,DEBYE RES INST,DEPT MET MEDIATED SYNTH,3584 CH UTRECHT,NETHERLANDS
VANMAANEN, HL
KLEIJN, H
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机构:UNIV UTRECHT,DEBYE RES INST,DEPT MET MEDIATED SYNTH,3584 CH UTRECHT,NETHERLANDS
KLEIJN, H
JASTRZEBSKI, JTBH
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机构:UNIV UTRECHT,DEBYE RES INST,DEPT MET MEDIATED SYNTH,3584 CH UTRECHT,NETHERLANDS
JASTRZEBSKI, JTBH
VERWEIJ, J
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机构:UNIV UTRECHT,DEBYE RES INST,DEPT MET MEDIATED SYNTH,3584 CH UTRECHT,NETHERLANDS
VERWEIJ, J
KIEBOOM, APG
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机构:UNIV UTRECHT,DEBYE RES INST,DEPT MET MEDIATED SYNTH,3584 CH UTRECHT,NETHERLANDS
KIEBOOM, APG
VANKOTEN, G
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机构:UNIV UTRECHT,DEBYE RES INST,DEPT MET MEDIATED SYNTH,3584 CH UTRECHT,NETHERLANDS
VANKOTEN, G
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[1] UNIV UTRECHT,DEBYE RES INST,DEPT MET MEDIATED SYNTH,3584 CH UTRECHT,NETHERLANDS
[2] GIST BROCADES,RES & DEV,2600 MA DELFT,NETHERLANDS
Imine esters of glycine, (R)-phenylglycine, (R)-(1,4-cyclohexadienyl)glycine and (S)-valine have been employed in the ester enolate-imine condensation via double activation with ZnCl2. The reaction of the chlorozinc enolate (1b) of ethyl (2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentyl)acetate with (R)-methyl N-benzylidene-2-phenylglycinate (2a) afforded the trans-beta-lactam 3a in 79% yield with excellent asymmetric induction (de >97%). Other imine esters also afforded trans-beta-lactams diastereoselectively, albeit in lower conversions (37-70%). Methyl (S)-2-[N-[3-(trimethylsilyl)-2-propyn-1-ylidene]amino]-3-methylbutanoate (2e) afforded a mixture of four diastereoisomers (68% conversion). The products were isolated as 3-phthalimido beta-lactams 5b-e and as 3-[(methoxycarbonyl)amino]-beta-lactam 6b. The reactivity of the zinc enolates and the diastereoselectivity of the reactions are discussed in terms of the coordination of the imine esters to ZnCl2 (template effect) and the stability and aggregation equilibria of the zinc enolates.