Search for: All records

Abstract We describe Pt(II)- and Fe(III)-catalyzed iminocarboxylations of oxime esters conjugated with 1,3-enyne and an ortho-alkynylarene moiety, followed by a spontaneous O→N acyl migration of the enol carboxylate intermediate to generate N-acyl pyrroles and isoindoles. The reaction scope for pyrrole synthesis is general, whereas the formation of isoindoles has a relatively narrow scope because of their instability. 

We developed intramolecular carboxyamidations of alkyne‐tetheredO‐acylhydroxamates followed by either thermally induced spontaneous or 4‐(dimethylamino)pyridine‐catalyzed O→O or O→N acyl group migration. Under iron‐catalyzed conditions, the carboxyamidation products were generated in high yield from bothZ‐alkene and arene‐tethered substrates. DFT calculations indicate that the iron‐catalyzed carboxyamidation proceeds via a stepwise mechanism involving iron‐imidyl radical cyclization followed by intramolecular acyloxy transfer from the iron center to the alkenyl radical center to furnish thecis‐carboxyamidation product. Upon treatment with 4‐(dimethylamino)pyridine, theZ‐alkene‐tethered carboxyamidation products underwent selective O→O acyl migration to generate 2‐acyloxy‐5‐acyl pyrroles. Thermal O→N acyl migration occurs during carboxyamidation if theZ‐alkene linker contains an alkyl or an aryl substituent at the β‐position of the carbonyl group. On the other hand, the arene linker‐containing compounds selectively undergo O→N acyl migration to generateN‐acyl‐3‐acylisoindolinones, and the corresponding O→O acyl migration forming isoindole derivatives was not observed.

 

Substituent-dependent reactivity and selectivity in the intramolecular reactions of arynes tethered with an allene are described. With a 1,3-disubstituted allene moiety, an Alder–ene reaction of an allenic C–H bond is preferred over a [2 + 2] cycloaddition, whereas a [2 + 2] cycloaddition of the terminal π-bond of the allene is preferred with a 1,1-disubstituted allene. With a 1,1,3-trisubstituted allene-tethered aryne, an Alder–ene reaction with an allylic C–H bond is preferred over a [2 + 2] cycloaddition. 

The cycloisomerization of alkyne‐tetheredN‐benzoyloxycarbamates to 2‐(3H)oxazolones is described. Two catalytic systems are tailored for intramolecular 5‐exo‐alkyne carboxyamidation and concomitant alkene isomerization. PtCl₂/CO (5 mol%, toluene, 100 °C) promotes both carboxyamidation and alkene isomerization but has a limited substrate scope. On the other hand, FeCl₃(5 mol%, CH₃CN, 100 °C) promotes carboxyamidation effectively but a cocatalyst is required for the exocyclic alkene isomerization. Thus, a two‐step one‐pot protocol has been developed for a broader reaction scope, which involves FeCl₃‐catalyzed carboxyamidation and base‐induced alkene isomerization. Crossover experiments suggest that these reactions proceed mainly through a mechanism involving acylnitrenoid intermediates rather than carbenoid intermediates.

 

Multicomponent reactions (MCRs) constitute a powerful synthetic tool to generate a large number of small molecules with high atom economy, which thus can efficiently expand the chemical space with molecular diversity and complexity. Aryne-based MCRs offer versatile possibilities to construct functionalized arenes and benzo-fused heterocycles. Because of their electrophilic nature, arynes couple with a broad range of nucleophiles. Thus, a variety of aryne-based MCRs have been developed, the representative of which are summarized in this account. 1 Introduction 2 Aryne-Based Multicomponent Reactions 2.1 Trapping with Isocyanides 2.2 Trapping with Imines 2.3 Trapping with Amines 2.4 Insertion into π-Bonds 2.5 Trapping with Ethers and Thioethers 2.6 Trapping with Carbanions 2.7 Transition-Metal-Catalyzed Approaches 3 Strategies Based on Hexadehydro Diels–Alder Reaction 3.1 Dihalogenation 3.2 Halohydroxylation and Haloacylation 3.3 Amides and Imides 3.4 Quinazolines 3.5 Benzocyclobutene-1,2-diimines and 3H-Indole-3-imines 3.6 Other MCRs of Arynes and Isocyanides 4 Conclusion 

A new [4+2] cycloaddition of allenyne‐alkyne is developed. The reaction is believed to proceed with forming an α,3‐dehydrotoluene intermediate. This species behaves as a σπ‐diradical to react with a hydrogen atom donor, whereas it displays a zwitterionic reactivity toward weak nucleophiles. The efficiency of trapping α,3‐dehydrotoluene depends not only on its substituents but also the trapping agents. Notable features of the reaction are the activating role of the extra alkyne of the 1,3‐diyne that reacts with the allenyne moiety and the opposite mode of trapping with oxygen and nitrogen nucleophiles. Oxygen nucleophiles result in the oxygen‐end incorporation at the benzylic position of the α,3‐dehydrotoluene, whereas with amine nucleophiles the nitrogen‐end is incorporated into the aromatic core. Relying on the allenyne‐alkyne cycloaddition as an enabling strategy, a concise total synthesis of phosphodiesterase‐4 inhibitory selaginpulvilin A is realized.