[2 + 1 + 1] Assembly of spiro β-lactams by Rh()-catalyzed reaction of diazocarbonyl compounds with azirines/isoxazoles

• Published in: Organic & biomolecular chemistry Vol. 17; no. 28; pp. 6821 - 683
• Main Authors: Golubev, Artem A, Smetanin, Ilia A, Agafonova, Anastasiya V, Rostovskii, Nikolai V, Khlebnikov, Alexander F, Starova, Galina L, Novikov, Mikhail S
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 17.07.2019; Royal Society of Chemistry
• Subjects: Acids; Bromine; Catalysis; Chemical reactions; Chemistry; Chemistry, Organic; Cross coupling; Crystallography; Cycloaddition; Dienes; Hydrogen storage; Intermediates; Physical Sciences; Rhodium; Science & Technology; β-Lactam antibiotics; INSERTION; KETENES; IMINES; ESTERS; DIAZOKETONES; DIAZO-COMPOUNDS; COPPER; CYCLOADDITION REACTION; RHODIUM CARBENOIDS; CARBENOID FUNCTIONALIZATION
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c9ob01301f

A domino synthesis of dispiro-fused N -vinyl β-lactams from diazo-Meldrum's acid and 2 H -azirines or 5-alkoxyisoxazoles via the "2-azabuta-1,3-diene formation/Staudinger ketene-imine cycloaddition" sequence is described. The Rh 2 (Piv) 4 -catalyzed formation of the 2-azabuta-1,3-diene intermediates in the first stage of the reaction sequence proceeds via addition of the rhodium carbenoid to the azirines/isoxazoles and provides the first example of the generation of iminium-type ylides from diazo-Meldrum's acid. This methodology was extended to monospiro-β-lactams, which were synthesized in two steps using acyclic α-diazocarbonyl compounds in the stage of the formation of 2-azabuta-1,3-dienes. The method allows for the rapid assemblage of the carbon part of the azetidin-2-one system from diazo compounds only and affords spiro- and dispiro-β-lactams in moderate yields. A bromine atom in the 2-bromoalkenyl moiety of the synthesized β-lactams can be easily substituted by hydrogen under catalytic hydrogenation conditions or by 2-pyridyl-substituent via the Stille cross-coupling reaction. The Rh( ii )-catalyzed assembly of the carbon skeleton of N -vinyl-substituted spiro β-lactams from diazocarbonyl compounds is described.