Radical Carboazidation:  Expedient Assembly of the Core Structure of Various Alkaloid Families

Abstract

A procedure for one-pot intermolecular radical addition of 2-iodoesters to terminal alkenes followed by azidation of the radical adduct has been developed. This sequential reaction represents an alkene carboazidation process. Its efficacy is demonstrated by the two-step preparation of various lactams such as pyrrolidinones, pyrrolizidinones, and indolizidinones. An easy access to spirolactams bearing an amino-substituted quaternary carbon center is also described. These compounds are important building blocks for the synthesis of numerous alkaloids such as, for instance, FR901483.

3‐Pyridinesulfonyl Azide: A Useful Reagent for Radical Azidation

“…The products 1 and 2 were obtained in 80 and 75% yield, respectively (Table 1, entries 1 and 4) by using standard reaction conditions where 3 mol % of the initiator, di-tert-butyl hyponitrite (DTBHN), were added every 2 hours (Method A). [3,4] These results are very similar to those obtained with benzenesulfonyl azide (entries 2 and 5, 79% and 74%). Interestingly, when 9 mol % of initiator were added in one portion at the beginning (Method B), the reaction time was significantly reduced from 6 hours to 90 minutes.…”

“…This result compares favorably (shorter reaction time, higher yield) with the reaction involving benzenesulfonyl azide according to Method A (80% in 10 h). [3,4] ð3Þ…”

Boron: A key element in radical reactions

“…Therefore, it has to be used in stoichiometric amount. Recently, we have developed a radical carboazidation [9][10][11][12] reaction that has found numerous applications for alkaloid synthesis [13][14][15]. The chain process requires the transformation of an arylsulfonyl radical into an alkyl radical.…”

Radical azidation reactions and their application in the synthesis of alkaloids

“…This threecomponent sequence represents a formal carboazidation of alkenes (Scheme 2) [12,13]. When followed by a reduction/lactamization sequence, this reaction gives direct access to pyrrolizidinones and indolizidinones.…”