Construction of α-Phosphonolactams via Rhodium(II)-Catalyzed Intramolecular C-H Insertion Reactions.

The Rh(II)-catalyzed intramolecular CH insertion reactions of N,N-dialkyl-α-diazo-α-(diethylphosphono)acetamides 2a,f–j in CHCl3 or ClCH2CH2Cl were found to give monocyclic and bicyclic α-phosphono-β-lactams, 3a and 3f–j, in 43–67% yields via regiospecific α-CH insertion of the N-alkyl groups. Similar treatment of N-benzyl-N-isopropyl-α-diazo-α-(diethylphosphono)acetamide (2b) and the corresponding N-isobutyl-N-methylacetamide 2d in ClCH2CH2Cl afforded mixtures of β-lactams 3b (35%) and and 3b′ (16%), β-lactam 3d (47%), and γ-lactam 4d (10%), respectively, each of which is formed by the competitive CH insertion reaction between benzylic and isopropyl α-CH bonds and between methyl α-CH and methine β-CH bonds, respectively. For the formation of β-lactams, the selectivity in the rhodium-mediated CH insertion in ClCH2CH2Cl follows the order methyl > methine > benzylic α-CH bond on N-substituents. The N,N-dibutyl-α-diazo homologue 2c and Nα[α-diazo-α-(diethylphosphono)acetyl]-2-methylindoline (2k) exclusively produced γ-lactams 4c (67%) and 4k (81%) via insertion into the methylene β-CH and methyl β-CH bonds. tert-Butyl N-[α-diazo-α-(dibenzylphosphono)acetyl]-piperidine-2-carboxylate (2m) on similar treatment, followed by deprotection of the benzyl ester afforded the 7-phosphono carbacepham 6 in 32% overall yield. Similar Rh(II)-catalyzed cyclization of N-methyl-N[4-benzyloxy-α-(diethylphosphono)-phenyl(diethyl-phosphono)methyl]-α-diazo-acetamide (2n) led to 1-[4′-benzylphenyl(diethylphosphono)methyl] -3-(diethyl-phosphono)azetidin-2-one (3n) in 78% yicld. The phosphono group at C-7 of 3f was converted into the acetylamino group via a four-step reaction. Application of chiral rhodium(II) carboxylates 12a–c to the insertion reactions of 2b,c produced α-phosphono-β-and γ-lactams, 3b and 4c, in 6–24% ee and 25–29% ee, respectively.