B(C₆F₅)₃-catalyzed synthesis of benzylic azides

<p>B(C₆F₅)₃ was found to catalyze the reaction between trimethylsilyl azide and benzylic acetates. Secondary and tertiary benzylic acetates were competent substrates in this reaction providing the azide products in moderate to high yields. Mechanistic experiments are consistent with the possible formation of a Lewis acid-base pair between the B(C₆F₅)₃ and trimethylsilyl azide.</p

Chemoselective Benzylation of Aldehydes Using Lewis Base Activated Boronate Nucleophiles

A benzylation of aldehydes using primary and secondary benzylboronic acid pinacol esters is reported. Activation of the boronic ester with <i>s</i>-butyllithium rendered it nucleophilic toward aldehydes. The activated nucleophile chemoselectively transfers the benzyl group over the <i>sec</i>-butyl group, providing excellent yields of the benzylated products. ¹¹B NMR experiments were performed to study the mechanism of this transformation

Total Synthesis of (−)-Vindoline and (+)-4-<i>epi</i>-Vindoline Based on a 1,3,4-Oxadiazole Tandem Intramolecular [4 + 2]/[3 + 2] Cycloaddition Cascade Initiated by an Allene Dienophile

It is reported that an allene dienophile can initiate a tandem intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of 1,3,4-oxadiazoles, that the intermediate cross-conjugated 1,3-dipole (a carbonyl ylide) can participate in an ensuing [3 + 2] dipolar cycloaddition in a remarkably effective manner, and that the reaction can be implemented to provide the core pentacyclic ring system of vindoline. Its discovery improves a previous total synthesis of (−)-vindoline and was used in a total synthesis of (+)-4-<i>epi</i>-vindoline and (+)-4-<i>epi</i>-vinblastine that additionally enlists an alternative series of late-stage transformations

Iron(III)/NaBH₄-Mediated Additions to Unactivated Alkenes: Synthesis of Novel 20′-Vinblastine Analogues

An Fe(III)/NaBH₄-mediated reaction for the functionalization of unactivated alkenes is described defining the alkene substrate scope, establishing the exclusive Markovnikov addition, exploring a range of free radical traps, examining the Fe(III) salt and initiating hydride source, introducing H₂O–cosolvent mixtures, and exploring catalytic variants. Its use led to the preparation of a novel, potent, and previously inaccessible C20′-vinblastine analogue

Iron(III)/NaBH₄-Mediated Additions to Unactivated Alkenes: Synthesis of Novel 20′-Vinblastine Analogues

An Fe(III)/NaBH₄-mediated reaction for the functionalization of unactivated alkenes is described defining the alkene substrate scope, establishing the exclusive Markovnikov addition, exploring a range of free radical traps, examining the Fe(III) salt and initiating hydride source, introducing H₂O–cosolvent mixtures, and exploring catalytic variants. Its use led to the preparation of a novel, potent, and previously inaccessible C20′-vinblastine analogue

A Remarkable Series of Vinblastine Analogues Displaying Enhanced Activity and an Unprecedented Tubulin Binding Steric Tolerance: C20′ Urea Derivatives

A systematic series of previously inaccessible key C20′ urea and thiourea derivatives of vinblastine were prepared from 20′-aminovinblastine that was made accessible through a unique Fe­(III)/NaBH₄-mediated alkene functionalization reaction of anhydrovinblastine. Their examination defined key structural features of the urea-based analogues that contribute to their properties and provided derivatives that match or exceed the potency of vinblastine by as much as 10-fold in cell-based functional assays, which is directly related to their relative tubulin binding affinity. In contrast to expectations based on apparent steric constraints of the tubulin binding site surrounding the vinblastine C20′ center depicted in an X-ray cocrystal structure, remarkably large C20′ urea derivatives are accommodated