Total Synthesis of (+)-seco-C-Oleanane via Stepwise Controlled Radical Cascade Cyclization

Abstract

An asymmetric concise total synthesis of the (+)-seco-C-oleanane 1 was accomplished. The successful route to this natural product involves as the key step a stepwise regio- and stereocontrolled catalytic radical polyene cascade cyclization from preoleanatetraene oxide (16), a process mediated by Cp(2)TiCl. The use of this single-electron-transfer complex permits mild cyclization conditions without using unnecessary prefunctionalizations and stops the process at the bicyclic level. Theoretical data revealed high activation energy for the third ring closure, which would account for the control of the cyclization. This process also led to natural (-)-achilleol B, camelliol A, and (+)-seco-β-amyrin as minor compounds.

Catalytic Radical Domino Reactions in Organic Synthesis

“…In 2012, Barrero, Moral, and coworkers applied a radical/radical/oxidation domino process to the total synthesis of (+)- seco -C-oleanane ( 68A ) (Figure 10). 28 Most notable about this synthesis is that performing this reaction with a substoichiometric amount of Cp 2 TiCl 2 improved the efficiency of the desired 6- endo-trig /6- endo-trig bicyclization process over the use of stoichiometric Ti reductant. The authors propose that this process begins with single electron reduction and ring-opening of epoxide 67 to give tertiary radical 69 .…”

Multi-Bond Forming Processes in Efficient Synthesis

“…[51] Different methods have been pioneered by the likes of Demuth and coworkers [52] and Pattenden and coworkers. [53,54] Oxidative metal-mediated radical polycyclisations [55] have also seen significant application, with notable examples from the groups of Snider, [56] Zoretic, [57] Barrero, [58] and Gonzáles. [59] Historically, asymmetric syntheses by these methods invariably featured chiral substrates.…”

Easy Access to a Cyclic Key Intermediate for the Synthesis of Trisporic Acids and Related Compounds

“…Cp 2 TiCl 2 can be regenerated by means of the 2,4,6-collidine/TMSCl system either from the Cp 2 Ti(IV)Cl(OAc) generated in the -OAc elimination step or from the titanium alkoxide of VIII. It should be pointed out that the Ti(III)-mediated radical cyclization reactions employing substrates without secondary acetate groups at C-4 lead regioselectively to exocyclic double bonds (Scheme 5) [45,[47][48][49][50]. In contrast, in this study it has been proven that it is possible to change selectively the direction of the formation of the olefin by using a suitable leaving group having in mind the affinity for the oxygen of the Ti atom.…”

“…Finally, the acyclic epoxide 8, which also corresponds to the intermediate III of Scheme 1, was cyclized following the Ti(III)-mediated methodology [39,[45][46][47][48][49][50]. In this case catalytic conditions [51] were employed, involving 0.3 equivalents of Ti(III) and 8.0 equivalents of Mn in THF (0.1 M), with 2,4,6-collidine/TMSCl as regenerating system.…”