Chemoselective, Substrate‐directed Fluorination of Functionalized Cyclopentane β‐Amino Acids

Abstract

This work describes a substrate-directed fluorination of some highly functionalized cyclopentane derivatives. The cyclic products incorporating CH F or CHF moieties in their structure have been synthesized from diexo- or diendo-norbornene β-amino acids following a stereocontrolled strategy. The synthetic study was based on an oxidative transformation of the ring carbon-carbon double bond of the norbornene β-amino acids, followed by transformation of the resulted "all cis" and "trans" diformyl intermediates by fluorination with "chemodifferentiation".

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

“…As the fluorination of the five-membered diol stereoisomers (±)- 1 and (±)- 4 proved to be highly substrate dependent and on the basis of our earlier findings on substrate determinant fluorinations [ 37 ], we next investigated the effect of the nature of the N -protecting group on this reaction. The treatment of N -Cbz-protected dihydroxylated cyclopentane β-amino ester (±)- 6 with Deoxofluor under various conditions provided an unidentifiable mixture of products.…”

Stereocontrolled Synthesis of Functionalized Azaheterocycles from Carbocycles through Oxidative Ring Opening/Reductive Ring Closing Protocols

“…There are two main methodologies in the literature for oxidative ring opening: either through ozonolysis of alkenes or cleavage of vicinal diols. [36][37][38][39][40][41] Both are useful methods to prepare synthetically valuable dialdehydes or diketones. [39] The Upjohn method is a two-step procedure for the cleavage of the CÀ C double bond.…”

Application of nucleophilic fluorinating reagents for the synthesis and transformations of cyclic β-amino acid derivatives

“…It raised the interest in the Institute of Pharmaceutical Chemistry, and a high number of such derivatives were synthesized from unsaturated bicyclic β-lactams. [25][26][27][28][29][30][31][32][33][34] Usually, the first step was regio-and stereo-selective introduction of a hydroxy group followed by either hydroxy-fluorine exchange or oxidation into keto derivatives and subsequent carbonyl→difluoromethylene transformation. [25][26][27][28][29]31,33] A new aziridine ring-opening method with XtalFluor-E was developed too.…”

“…(Cyclic dialdehydes were obtained by oxidative ring opening of bicyclic diols, and showed increased stability compared to their acyclic counterparts, enabling their isolation.) [32] As a result, we decided to synthesize α,β-unsaturated aldehydes from dihydroxylated β-amino acid derivatives and investigate the substrate dependence of their fluorination. Because transformation of cyclopentanediols in this manner would require closure of a strained four-membered ring and compounds with seven-membered ring are expensive, only cyclohexanediols were chosen as starting materials.…”

“…With the help of nucleophilic fluorinating reagents, preparation of a high number of such derivatives was accomplished. [25][26][27][28][29][30][31][32][33][34] The present PhD work focused on the synthesis of various types of fluorinated functionalized cyclic β-amino acid derivatives. The aim of the research was to obtain such compounds through new synthetic pathways starting from selectively epoxidated or dihydroxylated cyclic β-amino acid derivatives, utilizing deoxyfluorinating reagents.…”