Preparation of Fluorinated Tetrahydropyrans and Piperidines using a New Nucleophilic Fluorination Reagent DMPU/HF

Abstract

DMPU/HF (HF content 65 wt %/wt) is an ideal nucleophilic fluorination reagent for the diastereoselective synthesis of substituted 4-fluorotetrahydropyrans and 4-fluoropiperidines via a fluoro-Prins reaction. When compared to classical nucleophilic fluorination reagents like pyridine/HF, DMPU/HF gives both higher yields and better diastereoselectivity.

Multifaceted ion exchange resin-supported hydrogen fluoride: a path to flow hydrofluorination

“…30,31 However, there are only few reports on the fluoro-Prins reaction for the synthesis of fluorinated tetrahydropyrans. [32][33][34][35] Moreover, most of the reported syntheses of fluorinated tetrahydropyrans suffer from either low yields or, especially, low diastereoselectivity. With our ion exchange resin supported-HF reagent, we obtained fluorinated tetrahydropyrans with high diastereoselectivities and in good yields.…”

HF Fluorination for the Synthesis of Alkyl Fluorides

“…Hammond reagent, DMPU-HF (65% wt/wt; 1:11.9 mol ratio), has been used in the Prins reactions of homoallylic alcohols or N-tosyl-homoallylic amines with aldehydes to give the corresponding 4-fluorotetrahydropyrans and 4fluoropiperidines in high yields (yields of 56-92% for tetrahydropyrans and 42-100% for piperidines) and with high diastereoselectivity (cis/trans = >17-22:1 to for tetrahydropyrans and >2-10:1 for piperidines) (Fig. 9) [13].…”

Bromofluorination of unsaturated compounds using DMPU/HF as a fluorinating reagent

“…We also demonstrated the synthetic utility and effectiveness of DMPU/HF in some nucleophilic fluorination reactions: the gold-catalyzed hydrofluorination of alkynes [13], fluoro-Prins cyclization reactions [14] and ring-opening fluorination of aziridines [15]. DMPU/HF exhibited high reactivity and selectivity compared with the other aforementioned HF-based reagents.…”