Direct Addition of Grignard Reagents to Aliphatic Carboxylic Acids Enabled by Bulky turbo-Organomagnesium Anilides.

Invited for the cover of this issue is the group of Abraham Mendoza at Stockholm University. The image depicts a Grignard reagent "turbo-charged" with a magnesium anilide additive. Read the full text of the article at 10.1002/chem.202104053.

Direct Addition of Grignard Reagents to Aliphatic Carboxylic Acids Enabled by Bulky turbo-Organomagnesium Anilides.

The synthesis of ketones through addition of organometallic reagents to aliphatic carboxylic acids is a straightforward strategy that is limited to organolithium reagents. More desirable Grignard reagents can be activated and controlled with a bulky aniline-derived turbo-Hauser base. This operationally simple procedure allows the straightforward preparation of a variety of aliphatic and perfluoroalkyl ketones alike from functionalized alkyl, aryl and heteroaryl Grignard reagents.

Computational and Experimental Study of Turbo-Organomagnesium Amide Reagents: Cubane Aggregates as Reactive Intermediates in Pummerer Coupling.

The dynamic equilibria of organomagnesium reagents are known to be very complex, and the relative reactivity of their components is poorly understood. Herein, a combination of DFT calculations and kinetic experiments is employed to investigate the detailed reaction mechanism of the Pummerer coupling between sulfoxides and turbo-organomagnesium amides. Among the various aggregates studied, unprecedented heterometallic open cubane structures are demonstrated to yield favorable barriers through a concerted anion-anion coupling/ S-O cleavage step. Beyond a structural curiosity, these results introduce open cubane organometallics as key reactive intermediates in turbo-organomagnesium amide mixtures.

Decarboxylative Alkyl Coupling Promoted by NADH and Blue Light.

Photoexcited dihydronicotinamides like NADH and analogues have been found to generate alkyl radicals upon reductive decarboxylation of redox-active esters without auxiliary photocatalysts. This principle allowed aliphatic photocoupling between redox-active carboxylate derivatives and electron-poor olefins, displaying surprising water and air-tolerance and unusually high coupling rates in dilute conditions. The orthogonality of the reaction in the presence of other carboxylic acids and its utility in the functionalization of DNA is presented, notably using visible light in combination with NADH, the ubiquitous reductant of life.

Hypervalent iodine(iii) fluorinations of alkenes and diazo compounds: new opportunities in fluorination chemistry.

The fluorination of organic molecules is a rapidly evolving and exciting field in synthesis, which still poses huge challenges despite the advances made in the past decades. Hypervalent iodine(iii) reagents, which have already proven their versatility as synthetic tools in organic chemistry, are currently on the rise in fluorination chemistry. With their ability to break new mechanistic grounds, they grant access to completely new reactivities and thus also to novel fluorinated structural scaffolds. This review aims to provide an overview of the achievements made in the iodine(iii) mediated fluorinations of aliphatic Csp2-carbon atoms with special focus on the opportunities provided by this exciting class of hypervalent substances.

Iodine(III)-catalyzed rearrangements of imides: a versatile route to α,α-dialkylated α-hydroxy carboxylamides.

A tertiary hydroxy group α to a carboxyl moiety comprises a key structural motif in many bioactive substances. With the herein presented metal-free rearrangement of imides triggered by hypervalent λ(3)-iodane, an easy and selective way to gain access to such a compound class, namely α,α-disubstituted-α-hydroxy carboxylamides, was established. Their additional methylene bromide side chain constitutes a useful handle for rapid diversification, as demonstrated by a series of further functionalizations. Moreover, the in situ formation of an iodine(III) species under the reaction conditions was proven. Our findings clearly corroborate that hypervalent λ(3)-benziodoxolones are involved in these organocatalytic reactions.

Structure of a putative fluorinated natural product from Streptomyces sp. TC1.

Fluorine-containing natural products are extremely rare. The recent report on the isolation and biological activity of the bacterial secondary metabolite 3-(3,5-di-tert-butyl-4-fluorophenyl)propionic acid was thus highly remarkable. The compound contained the first aromatic fluorine substituent known to date in any natural product. The promise to discover an enzyme capable of aromatic fluorination in the producing strain Streptomyces sp. TC1 prompted our immediate interest. A close inspection of the originally reported analytical data of the fluoro metabolite revealed inconsistencies that triggered us to validate the reported structure. The results of these efforts are presented in this communication.

Halocarbocyclization versus dihalogenation: substituent directed iodine(III) catalyzed halogenations.

The nucleophilicity of the substituents in iodobenzene pre-catalysts have a huge impact on product selectivity in iodine(III) triggered halogenations, steering the reactivity from solely carbocyclizations towards dihalogenations. Utilizing this catalyst-dependent reactivity a diastereo- and chemoselective dihalogenation method was established allowing the conversion of structurally and electronically diverse unsaturated compounds in excellent yields.

Transition-metal-free synthesis of benzimidazoles mediated by KOH/DMSO.

Benzimidazoles are prepared by intramolecular N-arylations of amidines mediated by potassium hydroxide in DMSO at 120 °C. In this manner, diversely substituted products have been obtained in moderate to very good yields.