Carbenes indolizidine

Members of the tetracyclic dibenzopyrrocoline alkaloid family can be prepared by the intramolecular ring closure of l-(o-halobcnzyl)-tetrahydroisoquinoline derivatives. (3.38.)47 The analogous transformation of dihydroisoquinolines (3.39.) proceeds probably through the isomeric enamine form obtained by the tautomeric shift of the double bond 48 The palladium-carbene catalyst system applied in these reactions was also effective in the preparation of indoline, indolizidine and pyrrolizidine derivatives 49... 

Nickel-catalyzed cyclization of a 1,3-diene side chain of the substituted pyrrolidones yields a precursor to the indolizidine alkaloid (—)-elaeokanine C (Equation 86) <1997TL3931>. Other metal-catalyzed reactions include the Rh-induced in situ carbene generation and subsequent cyclization onto the heteroatom to yield piperidines <1997T16565, 1997JOC67>. Pauson-Khand cyclizations have also been used (Equation 87) <1997T6611>. 

Surprisingly, the indolizidine aziridine 39 was synthesized in 88% yield, but was found to be an uncatalyzed reaction, providing the product upon diazo-transfer at 0°C to oxime 37. Two plausible mechanisms are invoked for this carbene reaction sequence (1) a carbenoid insertion process or (2) collapse of the azomethine ylide formed upon addition of the diazoamide. The uncatalyzed process is likely due to a dipolar cycloaddition of the diazo and pendent oxime. 

The Ag- or Pd-mediated intramolecular cyclization of urethanes onto allylic substituents is used in the synthesis of piperidine alkaloids <97JOC776, 97CL221>. Similarly, the tungsten-mediated cyclization of urethanes on alkynes via the metal vinylidene carbene has been reported <97TL7687>. Ni-catalyzed intramolecular cyclization of a 1,3-diene side chain of 5 8 onto an aldehyde affords a precursor to the indolizidine alkaloid (-)-elaeokanine C <97TL3931>. 

Basic treatment of pyridines bearing an enyne substituent has been shown to generate an indolizidine carbene in a singlet ground state. This carbene can be... 

The unusual reactivity of NSBVs 6-1 was further demonstrated by their reaction with diazo compounds (Scheme 6.5). The reaction chemistry of diazo compounds as carbene precursors has been well developed and reviewed [40, 41]. However, transition metal or Lewis acid-catalyzed cycUzadon of diazo compounds with normal aziridines is very rare [42—44]. There are few examples including copper-catalyzed coupling of 2-acylaziridines or 2-vinylaziridines with diazo compoimds, giving bicyclic aziridines, indolizidines, or seven-membered lactams as products. 

---