Catalyst-Controlled Annulations of Strained Cyclic Allenes with π-Allylpalladium Complexes

Abstract

Strained cyclic allenes are a class of in situ-generated fleeting intermediates that, despite being discovered more than 50 years ago, has received significantly less attention from the synthetic community compared to related strained intermediates. Examples of trapping strained cyclic allenes that involve transition metal catalysis are especially rare. We report the first annulations of highly reactive cyclic allenes with in situ-generated π-allylpalladium species. By varying the ligand employed, either of two isomeric polycyclic scaffolds can be obtained with high selectivity. The products are heterocyclic and sp 3 -rich and bear two or three new stereocenters. This study should encourage the further development of fragment couplings that rely on transition metal catalysis and strained cyclic allenes for the rapid assembly of complex scaffolds.

Cyclic Allene Approach to the Manzamine Alkaloid Keramaphidin B

“…Strained cyclic allenes provide new tools for the rapid generation of highly complex sp 3 -rich scaffolds under mild reaction conditions. Although they were experimentally discovered over 50 years ago, − they have recently emerged as valuable synthetic building blocks. ,− Most relevant to the studies described herein, it has been demonstrated that azacyclic allenes ( 2 ) serve as competent dienophiles in strain-promoted Diels–Alder cycloadditions due to their appreciable strain energy of ∼27 kcal/mol . Generally, studies have focused on the use of electron-rich dienes, but in the context of our total synthesis studies, we found that regioselectivity of the cycloaddition with respect to the olefins of the cyclic allene can be modulated by using relatively electron-deficient pyrones.…”

Asymmetric cascades of the π-allyl complex: a journey from transition-metal catalysis to metallaphotocatalysis

“…The developed method included the reaction of the allene precursor 30f with cyclic carbamates 29a in the presence of 5 mol% of Pd(PPh 3 ) 4 and CsF for the synthesis of the corresponding tetrahydroquinoline motifs 30g in good yield and excellent diastereoselectivity (Scheme 30). 57 Interestingly, the alternation of Pd(PPh 3 ) 4 with the dppf Pd G3 catalyst led to the indolines 30h in good yield. The proposed mechanism included the initial generation of π-allylpalladium complex Int-30i , which upon ligand-controlled regioselective migration with allene Int-30j led to the formation of new π-allylpalladium complex Int-30k-l .…”

4-Vinylbenzodioxinones as a new type of precursor for palladium-catalyzed (4+3) cycloaddition of azomethine imines

“…The precursors for the formation of π-allylpalladium zwitterionic intermediates play a critical role in the cycloaddition reactions, affecting the reactivity, cycloaddition types and structure of the cycloadducts. A variety of precursors with diverse structures have been reported, such as vinyl lactones, 7 methylidene lactones, 8 vinyl cyclic carbamates, 9 methylidene cyclic carbamates, 10 vinyl cyclic carbonates, 11 methylidene cyclic carbonates, 12 vinyl lactams 13 and acyclic carbonates. 14 Among them, cyclic carbamates 9,10 and cyclic carbonates 11,12 are usually used for the synthesis of functionalized azaheterocycles and oxa-heterocycles (Scheme 1a).…”

“…A variety of precursors with diverse structures have been reported, such as vinyl lactones, 7 methylidene lactones, 8 vinyl cyclic carbamates, 9 methylidene cyclic carbamates, 10 vinyl cyclic carbonates, 11 methylidene cyclic carbonates, 12 vinyl lactams 13 and acyclic carbonates. 14 Among them, cyclic carbamates 9,10 and cyclic carbonates 11,12 are usually used for the synthesis of functionalized azaheterocycles and oxa-heterocycles (Scheme 1a). Although several types of cyclic carbonates such as allenyl cyclic carbonates, vinyl cyclic carbonates and methylidene cyclic carbonates have been reported, to the best of our knowledge, the benzo-fused cyclic carbonates have never been developed for the generation of an oxygen-containing π-allylpalladium precursor.…”