Synergistic Organoboron/Palladium Catalysis for Regioselective N-Allylations of Azoles with Allylic Alcohols

Abstract

A method for regioselective palladium-catalyzed allylic alkylation of ambident nitrogen heterocycles, employing simple allylic alcohols as electrophile precursors, is described. An organoboron co-catalyst serves both to activate the azole-type nucleophile toward selective N-functionalization and to accelerate the formation of a π-allylpalladium complex from the allylic alcohol. The method can be applied to various heterocycle types, including 1,2,3-and 1,2,4-triazoles, tetrazoles, pyrazoles, and purines, and can be extended to substituted allylic alcohol partners.

Boronic Acid-Catalyzed Regio- and Stereoselective N-Glycosylations of Purines and Other Azole Heterocycles: Access to Nucleoside Analogues

“…Recent research from our group has shown that arylboronic acid or diarylboronic acid catalysts can be used to achieve regioselective N -functionalizations of azoles with a variety of partners, including epoxides, α,β-unsaturated carbonyl compounds, and allylic alcohols (Scheme ). , In each case, it was proposed that the organoboron catalyst activated both the azole nucleophile (via B–N coordination) and the electrophile. Considering that the method enabled functionalizations of purine derivatives, along with other azole nucleophiles that could serve as nucleobase analogues, we aimed to develop an N -glycosylation method based on this activation mode.…”

Synergistic Organoboron/Palladium Cocatalyzed Dehydrative Couplings of Azoles with Allylic Alcohols: A Combined Experimental and Computational Mechanistic Investigation

“…By employing allylic alcohols as the electrophiles in the presence of a palladium bis­(phosphine) cocatalyst, regioselective dehydrative N-allylations of various azoles were achieved (Scheme ). − Control experiments showed that the organoboron catalyst has a significant effect on both reaction rate and N-allylation regioselectivity, suggesting that it plays a role both in activating the allylic alcohol electrophile, in cooperation with the Xantphos­(Pd) complex, and the azole nucleophile. , The allylation method has been extended to other NH-pronucleophiles, including pyridones and sulfoximines …”

Intermolecular Aza-Wacker Coupling of Alkenes with Azoles by Photo-Aerobic Selenium-π-Acid Multicatalysis

“… 1 Due to the industrial significance of this heterocycle class, substantial efforts were invested into method development and strategical concepts for their bespoke and diversified syntheses. 2 In this context, 3 electrophilic allylations of azoles were shown to offer an expedited avenue toward valorized building blocks and synthetic intermediates for established pharmaceuticals, drug leads, and agrochemicals. 4 The direct redox-coupling of 1,2-di- or higher substituted alkenes to azoles without any prefunctionalization 5 of either reactant provides a streamlined, highly redox economic 6 avenue to customized target structures.…”