Unusual mechanisms in Claisen rearrangements: an ionic fragmentation leading to a meta-selective rearrangement.

A mechanistic investigation of the acid-catalysed redox-neutral oxoarylation reaction of ynamides using electrospray ionisation mass-spectrometry (ESI-MS) and quantum chemical calculations (DFT and MP2) is presented. This study reveals the diversity of pathways and products available from an otherwise deceptively simple-looking, classical transformation: fragmentation, an unusual meta-arylation and competing α-carbonyl cation pathways are some of the alternatives unveiled by ESI-MS and mechanistic experiments. Detailed calculations explain the observed trends and rationalise the results.

Metal-Free meta-Selective Alkyne Oxyarylation with Pyridine N-Oxides: Rapid Assembly of Metyrapone Analogues.

An efficient metal-free oxyarylation of electron-poor alkynes with pyridine N-oxides has been developed. This transformation affords meta-substituted pyridines analogous to the drug metyrapone in high regioselectivities. Density functional theory (DFT) calculations provided important insight into the mechanism. Evaluation of the inhibitory properties revealed the most active CYP11B1 inhibitor of these derivatives, with two-digit nanomolar inhibitory activity akin to that of metyrapone.

Chemo- and Stereoselective Transition-Metal-Free Amination of Amides with Azides.

The synthesis of α-amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we present a stereoselective α-amination of amides employing simple azides that proceeds under mild conditions with release of nitrogen gas. The amide is used as the limiting reagent, and through simple variation of the azide pattern, various differently substituted aminated products can be obtained. The reaction is fully chemoselective for amides even in the presence of esters or ketones and lends itself to preparation of optically enriched products.

A Unified Strategy to Plakortin Pentalenes: Total Syntheses of (±)-Gracilioethers E and F.

A unified route to oxygenated Plakortin pentalenes is described. Along with the previously disclosed total synthesis of hippolachnin A, the potential of this scheme is demonstrated by the first total synthesis of gracilioether E, as well as the total synthesis of gracilioether F. Key features of the unified synthetic strategy include the concise construction of common key intermediate 1 and a topological-strategy guided functionalization of a highly substituted cyclobutene providing efficient access to the core skeletons.

Divergent ynamide reactivity in the presence of azides - an experimental and computational study.

An unusually divergent reactivity of ynamides in the presence of azides is reported. This new keteniminium-based methodology, which only requires triflic acid as promoter, facilitates access to ß-enaminoamides and biologically important oxazolidine-2,4-diones in a highly selective, divergent manner that is fully controllable by the present azide. A mechanistic rationale for these divergent reaction pathways is delineated and supported by extensive density functional theory analyses, as well as selected mechanistic experiments.

Strong Bonds Made Weak: Towards the General Utility of Amides as Synthetic Modules.

Breaking good: The amide bond is widely recognized as the strongest bond among the carboxylic acid derivatives. Therefore, the potential of amides to serve as synthetic building blocks has remained mostly untapped thus far. This Highlight describes a recent breakthrough that enables the catalytic conversion of amides into esters for the first time.

Total synthesis of (±)-hippolachnin†A.

The first total synthesis of the marine polyketide (±)-hippolachnin A has been achieved in nine linear steps and an overall yield of 9%. Rapid access to the oxacyclobutapentalene core structure was secured by strategic application of an ene cyclization.