Evolution of a Unified, Stereodivergent Approach to the Synthesis of Communesin F and Perophoramidine

Abstract

Expedient synthetic approaches to the highly functionalized polycyclic alkaloids communesin F and perophoramidine are described using a unified approach featuring a key decarboxylative allylic alkylation to access a crucial and highly congested 3,3-disubstituted oxindole. Described are two distinct, stereoselective alkylations that produce structures in divergent diastereomeric series possessing the critical vicinal all-carbon quaternary centers needed for each synthesis. Synthetic studies toward these challenging core structures have revealed a number of unanticipated modes of reactivity inherent to these complex alkaloid scaffolds. Additionally, several novel and interesting intermediates en route to the target natural products, such as an intriguing propellane hexacyclic oxindole encountered in the communesin F sequence, are disclosed. Indeed, such unanticipated structures may prove to be convenient strategic intermediates in future syntheses.

Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations

“…The Stoltz group has utilized this strategy for the syntheses of communesin F 82 and perophoramidine. 83 …”

Convergent and Biomimetic Enantioselective Total Synthesis of (−)-Communesin F

“…This exquisite structural complexity coupled with an array of interesting biological properties has prompted investigations directed towards the chemical synthesis of these alkaloids, 2 culminating in innovative solutions for the total synthesis of (±)-communesin F ( 1 ) by Qin, 3 Weinreb, 4 and Funk, 5 in addition to a formal synthesis by Stoltz. 6 To date, Ma’s total synthesis of (−)-communesin F ( 1 ) 7 remains the only enantioselective solution for this archetypical alkaloid. As an outgrowth of our investigations in the area of calycanthaceous alkaloids, 8,9 we sought to develop a unified and convergent approach to the communesin alkaloids.…”

Arylacetic Acids in Organic Synthesis

“…Among them, we mainly discussed about reactions triggered by six kinds of pathways: (1) acid as the directing group; (2) decarboxylation; (3) deprotonation; (4) nucleophilic methylenes; (5) nucleophilic acids; (6) electrophilic acids. Especially, nucleophilic methylenes, Friedel‐Crafts reaction, nucleophilic acids and electrophilic acids have been used in total synthesis of (−)‐pauciflorol F, moxaverine, (−)‐6‐O‐desmethylantofine and (+)‐6‐O‐desmethylantofine, derivate of salvianolic acid B, communesin F and perophoramidine, (+)‐O‐methylthalibrine, sparstolonin B, lennoxamine, chilenine, fumaridine, 8‐Oxypseudoplamatine, 2‐O‐methyloxyfagaronine, (S)‐equol, xiamenmycin A and (±)‐glabridin . However, challenges still existed: (1) C−N and C−X (X=F, Cl, Br, I) bond may be constructed simultaneously during one procedure by the aid of decarboxylation and formation of radicals; (2) Decarboxylative cross coupling or tandem applications with boron reagent, diazonium salt, 1,3‐dicarbonyls were anticipated; (3) The ketones from reactions of arylacetic acids with aryl acids may function as useful intermediates in tandem reactions and show their significances in construction of diverse heterocycles.…”