Highly Chemoselective gem‐Difluoropropargylation of Aliphatic Alcohols

Abstract

Despite the potential of α‐fluoroethers in medicinal chemistry, their synthetic methods, especially etherification of aliphatic alcohols, have been limited. Herein, we developed two‐ and three‐step gem‐difluoropropargylation of aliphatic alcohols including amino acid derivatives and naturally occurring bioactive molecules. Highly chemoselective etherification proceeded by using the gem‐difluoropropargyl bromide dicobalt complex in the presence of silver triflate and triethylamine. Decomplexation of dicobalt complexes was achieved by using cerium ammonium nitrate or N,N,N′‐trimethylethylenediamine. The thus obtained gem‐difluoropropargyl ethers were converted to various α‐difluoroethers which are expected to be useful for medicinal chemistry.

Deuteration of terminal alkynes realizes simultaneous live cell Raman imaging of similar alkyne-tagged biomolecules

“…The calculated CuC vibrational frequency of 1-hexyne is red-shifted by 148 cm −1 upon deuteration (from 2120 cm −1 to 1972 cm −1 ). This value is much larger than those observed in the replacement of the alkyne carbons with 13 C (e.g., 48 cm −1 for mono- 13 C-alkyne and 77 cm −1 for di- 13 Calkyne). 12 Herein, we demonstrate the potential of D-alkynes as Raman tags for live cell Raman imaging.…”

“…Alkynes can be introduced without affecting the biological activities of small molecules and can be selectively detected using a Raman microscope with the technique referred to as alkyne-tag Raman imaging (ATRI). 2,7 Since ATRI was first established by Sodeoka et al in 2011, various alkyne tags (e.g., diynes, 3,8-11 13 C-labeled alkynes, 12 and gem-difluoroalkynes 13 ) have been developed to observe biomolecules.…”

DMSO‐Assisted K3PO4‐Catalyzed Cooperative Metal‐Free, Base‐Free Etherification of Chloroheteroarenes at Low Temperature

“…C, H and N analyses were carried out locally using Elementar Vario Micro Select (15153041). 1 H (400 MHz) and 13 C (100 MHz) NMR spectra were recorded on Bruker Avance 400 spectrometer. 1 H (500 MHz) and 13 C (125 MHz) NMR spectra were recorded on Bruker Avance 500 spectrometer.…”

“…We further envisaged the possibility of testing the developed reaction conditions for promoting regio or chemoselective etherification. [12,13] Amino alcohols are useful reagents commonly employed as chiral reagents in synthesis present us with a chemoselective challenge of two similarly reactive functionalities of -OH and -NH 2 that could both undergo reactions with chloroheteroarenes (S N Ar) to give competing CÀ O & CÀ N products. We believed that the cooperative effect exhibited by DMSO/K 3 PO 4 would help promote etherification over amination (10 a-b, Part A, Scheme 3).…”

Synthetic Access to gem-Difluoropropargyl Vinyl Ethers and Their Application to Propargyl Claisen Rearrangement

“…In the past few decades, there have been reports of various fluoroalkylation reagents of oxygen atoms, i.e. phenols, ketones, and alcohols (Scheme a). However, despite the ubiquity of oxygen atoms, there are fewer methods for their fluoroalkylation than for the fluoroalkylation of carbon atoms.…”