Tandem Radical Cyclisation Reactions for the Construction of Pseudocopsinine and Aspidosperma alkaloid models

“…1 H NMR (600 MHz, CDCl 3 ) δ 7.72 (dt, J = 8.0, 0.7 Hz, 1H), 7.38−7.29 (m, 5H), 7.22−7.15 (m, 2H), 7.03 (td, J = 7.5, 1.1 Hz, 1H), 5.41 (dd, J = 17.9, 10.9 Hz, 1H), 5.35 (d, J = 12.3 Hz, 1H), 5.12 (d, J = 12. 3 ). (−)-22.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…Related to the Aspidosperma alkaloids but containing an additional C20–C2 bond, the unique hexacyclic system of 1 features an unusual central strained bicyclo[2.2.1]heptane core and six contiguous stereocenters, of which three are quaternary and two are adjacent to one another. Prior synthetic efforts toward 1 are limited to the model studies of Penkett and Parsons , and semisyntheses of the related natural products tuboxenin and vindolinine (Δ 6,7 - 1 ) by Levy . The latter employed a sodium-mediated radical cyclization of 20-iodotabersonine to effect C20–C2 bond formation without control of the relative stereochemistry, resulting in a mixture of all four possible C20/C3 diastereomers in a low combined yield of ca.…”

Section: Introductionmentioning

confidence: 99%

Divergent Total Syntheses of (−)-Pseudocopsinine and (−)-Minovincinine

2020

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Herein, the first total syntheses of (−)-pseudocopsinine (1) and (−)-minovincine (3) from a common intermediate 8 are detailed, enlisting late-stage, hydrogen atom transfer (HAT)-mediated free radical bond formations (C20–C2 and C20–OH, respectively) that are unique to their core or structure. The approach to 1 features an Fe-mediated HAT reaction of the intermediate olefin 2, effecting a transannular C20–C2 free radical cyclization of a challenging substrate with formation of a strained [2.2.1] ring system and reaction of a poor acceptor tetrasubstituted alkene with a hindered secondary free radical to form a bond and quaternary center adjacent to another quaternary center. Central to the assemblage of their underlying Aspidosperma skeleton is a powerful [4 + 2]/[3 + 2] cycloaddition cascade of 1,3,4-oxadiazole 9, which affords the stereochemically rich and highly functionalized pentacyclic intermediate 8 as a single diastereomer in one step. The work extends the divergent total synthesis of four to now six different natural product alkaloid classes by distinguishing late stage key strategic bond formations within the underlying Aspidosperma core from the common intermediate 8. Together, the work represents use of strategic bond analysis combined with the strategy of divergent synthesis to access six different natural product classes from a single intermediate.

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“…5 Parsons has also reported a conceptually different approach to the Aspidosperma skeleton using aryl radicals. 6 We now wish to disclose a new route to the ABCE-tetracycle using a novel tandem radical route to create the C-and E-rings.…”

mentioning

confidence: 99%