Strychnine transannular Diels-Alder reaction

Fused carbazoles related to pyrido[4,3-6]carbazole alkaloids were prepared by a Diels-Alder route, and a 3-aza bioisostere of the antitumor alkaloid olivacine was synthesized <02CPB1479>. Indoloid [3.3]cyclophane 40a gave the pentacyclic indoloid 41a upon heating <02OL127>. This led to a concise formal total synthesis of ( )-strychnine in 12 facile steps from tryptamine when a similar transannular inverse-electron-demand Diels-Alder reaction of indoloid [3.3]cyclophane 40b gave 41b <02AG(E)3261>. 

In a concise formal total synthesis of strychnine, the cyclophane 108 was prepared in 65% yield by applying the hydroboration-intramolecular coupling method to 107 under high dilution conditions, and converted to the pentacycle 109 by transannular inverse-electron-demand Diels-Alder reaction [88]. 

An interesting transannular Diels-Alder/retro-Diels-Alder reaction cascade was employed in a formal total synthesis of ( )-strychnine by Bodwell and Li (Scheme 20.5). ° The reaction cascade involved a transannular inverse-electron-demand Diels-Alder (lEDDA) reaction of cyclophane 12 to form 13, which spontaneously expelled a molecule of nitrogen by the retro-Diels-Alder reaction to give 14 in quantitative yield. This led to a formal total synthesis of strychnine after 14 was converted into a common... 

SCHEME 20.5. The transannular Diels-Alder/retro-Diels-Alder reaction cascade in the synthesis of ( )-strychnine. 

---