Fluoro-bicyclo[1.1.1]pentanes

After more than 20 years of trials, a practical scalable approach to fluoro-bicyclo[1.1.1]pentanes (19F-BCPs) has been developed. Physico-chemical properties of fluoro-bicyclo[1.1.1]pentanes have been studied, and the core was incorporated into the structure of the anti-inflammatory drug Flurbiprofen instead of the fluorophenyl ring

Three-component synthesis of C2F5-substituted pyrazoles from C2F5CH2NH2·HCl, NaNO2 and electron-deficient alkynes

A one-pot reaction between C2F5CH2NH2·HCl, NaNO2 and electron-deficient alkynes gives C2F5-substituted pyrazoles in excellent yields. The transformation smoothly proceeds in dichloromethane/water, tolerates the presence of air, and requires no purification of products by column chromatography. Mechanistically, C2F5CH2NH2·HCl and NaNO2 react first in water to generate C2F5CHN2, that participates in a [3 + 2] cycloaddition with electron-deficient alkynes in dichloromethane

Water-soluble Bioisosteres of the ortho-substituted Phenyl Ring

Water-soluble analogues of the ortho-substituted phenyl ring were developed. Replacement of the phenyl ring in bioactive compounds with 2 oxabicyclo[2.1.1]hexanes in many cases improved solubility, reduced lipophilicity, enhanced metabolic stability, and most importantly – retained bioactivity

Unexpected isomerization of oxetane-carboxylic acids

We unexpectedly discovered that popular oxetane-carboxylic acids are intrinsically unstable. They easily isomerize into lactones under storage at rt, or under slight heating. Chemists should keep in mind the high instability of these common molecules, as this could dramatically affect the reaction yields and lead to negative results (especially in those reactions that require heating)

Modular Synthesis of Cyclic β-Difluoroamines

Fluorine-containing saturated nitrogen heterocycles are very attractive structures in medicinal and biological chemistry because fluorine can be used to tune conformation as well as key properties such as basicity and bioavailability. At present cyclic fluorinated amines are accessed using hazardous reagents such as DAST or by lengthy synthesis routes. Here we report a modular two-step synthesis of cyclic β-fluoroalkyl amines using a photoredox-catalysed cyclisation/hydrogen atom transfer reaction of bromodifluoroethylamines

1,2-Disubstituted Bicyclo[2.1.1]hexanes as Bioisosteres of the ortho-substituted Benzene

1,2-Disubstitued bicyclo[2.1.1]hexanes have been designed, synthesized, and validated as a new generation of saturated bioisosteres of ortho-substituted benzenes. Incorporation of the bicyclo[2.1.1]hexane core into the structure of agrochemicals Boskalid (BASF), Bixafen (Bayer CS), and Fluxapyroxad (BASF) gave saturated analogs that exhibited a high antifungal activity