Synthesis of Heterocycles through Transition‐Metal‐Catalyzed Isomerization Reactions

Abstract

Metal-catalyzed isomerization of N- and O-allylic systems is emerging as an effective method to form synthetically useful iminium and oxocarbenium intermediates. In the presence of tethered nucleophiles, several recent examples illuminate this approach as a powerful strategy for the synthesis of structurally complex and diverse heterocycles. In this Concept article, we attempt to cover this area of research through a selection of recent versatile examples.

Crown Ether Base: Highly Active, Regioselective and Reusable Catalytic Systems for Double Bond Migration in Allylic Compounds

“…This reaction has also been used for the unmasking allylic protecting groups ,. Additionally, double bond migration is a key step of two‐ or multistep strategies, such as isomerizations: ‐Claisen rearrangements, ‐RCM, −1,3‐dipolar cycloaddition and other tandem reactions and cascades . As the catalysts of the double bond migration metals on supports (e. g., Pd / C , Rh / C ), Brønsted or Lewis acids (e. g., HClO 4 , H 2 SO 4 , zeolites), transition metal complexes ( Ti , Zr , V , Cr , Mo , Fe , Ru , Os , Co , Rh , Ir , Ni , Pd , Pt ) and various organic and inorganic bases which have been used up till now.…”

Tandem Long Distance Chain-Walking/Cyclization via RuH2(CO)(PPh3)3/Brønsted Acid Catalysis: Entry to Aromatic Oxazaheterocycles

“…The method allows for the isomerization of an N -allylamide into a reactive imine which subsequently undergoes a Brønsted acid catalyzed Friedel–Crafts type C–C bond forming reaction under relay catalysis. Following this pioneering work, this methodology was successfully applied in the synthesis of nitrogenated heterocycles by intramolecular trapping of the electrophilic iminium ion intermediate (X = N) with C and O nucleophiles (Scheme , eq 1). , More recently, the process has also been extended to generate the less stable oxocarbenium ions (X = O), starting in this case from the corresponding allyl ethers …”

Novel Hybrid Prins/Aza‐Prins Oxocarbenium/N‐Acyliminium Cascade: Expedient Access to Complex Indolizidines

“…In the context of ever‐growing environmental concerns that stimulate the need for improved reaction sequences and synthetic strategies, we thus imagined to shorten and improve flexibility of our initial methodology by combining in a one‐pot event the Mannich–Prins cyclisation cascade with the catalytic isomerization of the readily available N ‐allyl N,O‐acetals (Scheme ) . Besides saving time, waste and cost, this would also establish an innovative chemical bi‐catalytic development . The efficient catalytic isomerization of N ‐allyl imides including the pillar phthalimide and succinimide representatives is well documented in the literature, and it was also exploited for the initial construction route of our aminal substrates (see Scheme ).…”

“…[12,24] Besides saving time, waste and cost, this would also establish an innovative chemical bi-catalytic development. [29] The efficient catalytic isomerization of N-allyl imides including the pillar phthalimide and succinimide representatives is well documented in the literature, [28] and it wasa lso exploited for the initial construction route of our aminal substrates (see Scheme 3). RuHCl(CO)(PPh 3 ) 3 has proven particularly effective in enabling such transformations.…”