Lactams asymmetric hydroformylation

The asymmetric hydroformylation of //-substituted 4-vinyl (3-lactams, catalyzed by rhodium(I) complexes, leading to l-(3-methylcarbapenem precursors (VI, Fig. 16) has been reported [285]. 

The production of 10-methylcarbapenem (184), which has antibacterial activities and enhanced chemical and metabolic stability, has been reported by asymmetric hydroformylation of 4-vinyl-0-lactams 185 catalyzed by Rh-BINAPHOS complexes (Scheme 12.75). Under optimized conditions, the observed regioselectivity was 55/45 (b/1), enantioselectivity was 93/7 (1860 18600 at 95% conversion, and S/C = 1000.233... 

Alper and co-workers improved the asymmetric hydroformylation of vinyl P-lactams. The substitution of a Zwitterionic rhodium catalyst (187) and CS, S )-BDPP (188) in the asymmetric hydroformylation of 185b produced regioselectivities of >99/1 (b/1) and enantioselectivities of >99/1 (1860 18601) with 70% conversion at 1200 psig syn gas (S/C = 20).234 This transformation has been performed at the kilogram scale.235... 

SCHEME 14.20. Diastereoselective synthesis of 1-p-methylcarbapenem via asymmetric hydroformylation of 4-vinyl-P-lactam. 

FIGURE 14.5. Ligand and pre-catalyst for the asymmetric hydroformylation of 4-vinyl-p-lactams. 

Nozaki K, Li WG, Horiuchi T, Takaya H Saito T, Yoshida A, Matsumura K, Kato Y, Imai T, Miura T, Kumobayashi H. A new StereocontroUed approach to 1 beta-methylcarbapenem asymmetric hydroformylation of 4-vinyl beta-lactams catalyzed by Rh(I) complexes of chiral phosphine-phosphites and phosphine-phosphinites. J. Org. Chem. 1996 61 7658 7659. 

Noonan GM, Cobley CJ, Lebl T, Clarke ML. Asymmetric hydroformylation of an enantiomericaUy pure bicyclic lactam efficient synthesis of functionalised cyclopentylamines. Chem. Eur. J. 2010 16 12788 12791. 

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