Exercising Regiocontrol in Palladium-Catalyzed Asymmetric Prenylations and Geranylation: Unifying Strategy toward Flustramines A and B

Abstract

Palladium-catalyzed asymmetric prenylation of oxindoles to selectively afford either the prenyl or the reverse prenyl product has been demonstrated. Control of regioselectivity in this transformation is governed by choice of ligand, solvent, and halide additive. The resulting prenylated and reverse prenylated products have been transformed into ent-flustramides and ent-flustramines A and B. Additionally, control in regio- and diastereoselectivity has been obtained using π-geranylpalladium complexes.

Metal catalyzed allylic alkylation: its development in the Trost laboratories

“…49,79 Interestingly, with 3,3-disubstituted allylating agents, the regioselectivity can be controlled to direct C-C bond formation to the disubstituted terminus of the π-allyl unit (eq 79). 80 This regioselectivity derives from attack of the nucleophile at the more electrophilic terminus of the allyl unit combined with using the naphtho linker which favors the olefin – Pd(0) coordination in the initial alkylated product to the one possessing the least substituted olefin because of its lower LUMO energy allowing increased back-bonding from the low valent metal. The amazing aspect of this type of alkylation is the facility with which two adjacent quaternary stereocenters evolve from each partner in the allylic alkylation in high ee and de.…”

Formal synthesis of (−)-flustramine B and its absolute configuration assignment by vibrational circular dichroism exciton chirality

“…The spectroscopic data of 11 were consistent with those reported. 19 4.5. Preparation of 2-(6-bromo-1,3-bis(3-methylbut-2-enyl)-2-oxoindolin-3-yl)acetic acid 12…”

Spirooxindoles as novel 3D-fragment scaffolds: Synthesis and screening against CYP121 from M. tuberculosis

“…18 A number of the substituted 3-alkylidene-2-oxindoles dienophiles were reduced with NaBH 4 to produce the corresponding 2-oxoindolines 10a-f and 13c, which are themselves interesting fragment scaffolds that were not represented in our fragment library. 19 These reduced intermediates allowed investigation of the inherent binding properties of the oxindoline scaffold. The reaction with NaBH 4 was rapid (1-2 min) in converting the highly coloured 3-alkylidene-2-oxindoles to a clear solution and resulted in product yields of 28-89%, Scheme 1.…”