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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
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Parameterization of Arynophiles: Experimental Investigations towards a Quantitative Understanding of Aryne Trapping Reactions
Abstract Arynes are highly reactive intermediates that may be used strategically in synthesis by trapping with arynophilic reagents. However, ‘arynophilicity’ of such reagents is almost completely anecdotal and predicting which ones will be efficient traps is often challenging. Here, we describe a systematic study to parameterize the arynophilicity of a wide range of reagents known to trap arynes. A relative reactivity scale, based on one-pot competition experiments, is presented by using furan as a reference arynophile and 3-chlorobenzyne as a the aryne. More than 15 arynophiles that react in pericyclic reactions, nucleophilic addition, and σ-bond insertion reactions are parameterized with arynophilicity (A) values, and multiple aryne precursors are applicable.
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- PAR ID:
- 10343351
- Date Published:
- Journal Name:
- Synthesis
- ISSN:
- 0039-7881
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1055/a-1845-3066
