Claisen Rearrangement Triggered by Brønsted Acid Catalyzed Alkyne Alkoxylation

Over the past two decades, catalytic alkyne alkoxylation-initiated Claisen rearrangement has proven to be a practical and powerful strategy for the rapid assembly of a diverse range of structurally complex molecules. The rapid development of Claisen rearrangements triggered by transition-metal-catalyzed alkyne alkoxylation has shown great potential in the formation of carbon–carbon bonds in an atom-economic and mild way. However, metal-free alkyne alkoxylation-triggered Claisen rearrangement has seldom been exploited. Recently, Brønsted acids such as HNTf2 and HOTf have been shown to be powerful activators that promote catalytic alkyne alkoxylation/Claisen rearrangement, leading to the concise and flexible synthesis of valuable compounds with high efficiency and atom economy. Recent advances on the Brønsted acid catalyzed alkyne alkoxylation/Claisen rearrangement are introduced in this Account, in which both intramolecular and intermolecular tandem reactions are discussed.

Zinc Chloride Catalyzed Amino Claisen Rearrangement of 1-N-Allylindolines: An Expedient Protocol for the Synthesis of Functionalized 7-Allylindolines

Abstract7-Allylindolines are valuable synthons for designing biologically active molecular libraries. Lewis acid catalyzed amino-Claisen rearrangement provides a one pot synthetic entry to these heteroarenes. In this context, Zinc chloride (ZnCl2)–N,N-dimethylformamide system efficiently catalyzed amino-Claisen rearrangements of 1-N-allylindolines to 7-allylindolines. The rearrangement is influenced by stereoelectronic effects of substituents present in 1-N-allylindolines. The substrates containing electron donating functionalities underwent rearrangement at lower temperature than substrates with electron withdrawing functional groups. The regioselectivity of the process is governed by the substitution pattern on allyl moiety in 1-N-allylindoline as well as ZnCl2 catalyst loading in the reaction system.

Peptide Modifications: Versatile Tools in Peptide and Natural Product Syntheses

Peptide modifications via C–C bond formation have emerged as valuable tools for the preparation and alteration of non-proteinogenic amino acids and the corresponding peptides. Modification of glycine subunits in peptides allows for the incorporation of unusual side chains, often in a highly stereoselective manner, orchestrated by the chiral peptide backbone. Moreover, modifications of peptides are not limited to the peptidic backbone. Many side-chain modifications, not only by variation of existing functional groups, but also by C–H functionalization, have been developed over the past decade. This account highlights the synthetic contributions made by our group and others to the field of peptide modifications and their application in natural product syntheses.1 Introduction2 Peptide Backbone Modifications via Peptide Enolates2.1 Chelate Enolate Claisen Rearrangements2.2 Allylic Alkylations2.3 Miscellaneous Modifications3 Side-Chain Modifications3.1 C–H Activation3.1.1 Functionalization via Csp3–H Bond Activation3.2.2 Functionalization via Csp2–H Bond Activation3.2 On Peptide Tryptophan Syntheses4 Conclusion