Rhodium(II)-Catalyzed Cyclization of Amido Diazo Carbonyl Compounds

Abstract

A series of acyclic diazo ketoamides were prepared from N-benzoyl-N-alkylaminopropanoic acids and were treated with a catalytic amount of rhodium(II) acetate. The resultant carbenoids underwent facile cyclization onto the neighboring amide carbonyl oxygen atom to generate seven-membered carbonyl ylide dipoles. Subsequent collapse of the dipoles with charge dissipation produce bicyclic epoxides which undergo further reorganization to give substituted 5-hydroxydihydropyridones in good yield. Depending on the nature of the substituent groups, it was possible to trap some of the initially formed carbonyl ylide dipoles with a reactive dipolarophile such as DMAD. In other cases, cyclization of the dipole to the epoxide is much faster than bimolecular trapping. A related cyclization/rearrangement sequence occurred when diazo ketoamides derived from the cyclic pyrrolidone and piperidone ring systems were subjected to catalytic quantities of Rh(II) acetate. With these systems, exclusive O-cyclization of the amido group onto the carbenoid center occurs to generate a seven-ring carbonyl ylide dipole. Starting materials are easily prepared, and the cascade sequence proceeds in good yield and does not require special precautions. The overall procedure represents an efficient one-pot approach toward the synthesis of various indolizidine and quinolizidine ring systems.

Insight into Transannular Cyclization Reactions To Synthesize Azabicyclo[X.Y.Z]alkanone Amino Acid Derivatives from 8-, 9-, and 10-Membered Macrocyclic Dipeptide Lactams

“…Although electrophile-induced intramolecular cyclization reactions may proceed by formation of a dihalide that is subsequently displaced by the lactam to form the ring, cyclizations of macrocycles ( Z )- 11a , ( Z )- 11e , and ( Z )- 10d are presumed to proceed by way of iodonium-like intermediates based on their stereochemical outcomes . The ambidentate nucleophilic nature of the amide group has been observed to give imidates in iodocyclizations of simpler olefins, , and such O -selectivity has been explained on the basis of hard–soft acid–base theory considering the iodine–olefin π-complex to be a hard electrophile. , However, transannular attack of oxygen would result in an anti-Bredt bridgehead heterocycle, which may be relatively disfavored due to ring strain. Given the choices between placing iodide on the nonlactam ring, forming a strained N -acylazetidine or forming the anti-Bredt imidate, the latter product 5 was favored.…”

Tandem Cyclization‐Cycloaddition Reactions of Rhodium Generated Carbenoids from α‐Diazo Carbonyl Compounds.

“…The Rh(II)-catalyzed reaction of the amido diazo ketoester 261 was found to cleanly afford the rearranged indolizidone 264 via the intermediates 262 and 263 (Scheme 80). 116 Seven-membered ring carbonyl ylides derived from phthalimides can also participate in these tandem cyclizationcycloaddition reactions, the Rh 2 (OAc) 4 -catalyzed reaction of 1-diazo-4-phthalimidobutanone (265) proceeding quite smoothly with DMAD and NPM. 116 When N-phenylmaleimide was used as the trapping agent, the cycloadduct 266 (45%) was obtained as the major product (Scheme 81), along with 267.…”

An unprecedented benzannulation of oxindoles with enalcarbenoids: a regioselective approach to functionalized carbazoles

“…Electrophilic diacceptor rhodium enalcarbenoid 6 derived from diazoenal 1 reacts with oxindole 2 to form an unstable strained spiro-epoxide 8 via zwitterion 7. 13 Rapid epoxide opening in 8 followed by aromatization leads to the formal sp 2 C-O insertion product g-hydroxyenal 4. Brønsted acid catalyzed E/Z enal isomerization of 4 through an intramolecular oxa-Michael addition via 10-12 results in the Z-enal 13.…”