Construction of α‐phosphonolactams via rhodium (II)‐catalyzed intramolecular C-H insertion reactions

Abstract
The Rh(II)‐catalyzed intramolecular CH 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‐CH 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 CH insertion reaction between benzylic and isopropyl α‐CH bonds and between methyl α‐CH and methine β‐CH bonds, respectively. For the formation of β‐lactams, the selectivity in the rhodium‐mediated CH insertion in ClCH2CH2Cl follows the order methyl > methine > benzylic α‐CH 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‐CH and methyl β‐CH 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.

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