Synthesis of Alkyl Fluorides by Silver‐Catalyzed Radical Decarboxylative Fluorination of Cesium Oxalates

Abstract

A combination of silver nitrate (AgNO3) catalyst and Selectfluor® was found to perform radical deoxyfluorination of cesium oxalates derived from corresponding alcohols. The reaction tolerates a wide range of functional groups and provides preferentially access to tertiary alkyl fluorides.

Direct Deoxyfluorination of Alcohols with KF as the Fluorine Source

“…The product was isolated by column chromatography [100:1 (v/v) petrol ether/ethyl acetate] as a white solid (41.4 mg, 53%): mp 101–103 °C; 1 H NMR (400 MHz, CDCl 3 ) δ 4.80 (d, J = 48.8 Hz, 2H), 4.58–4.34 (m, 1H), 2.01–1.93 (m, 3H), 1.92–1.85 (m, 2H), 1.82–1.77 (m, 2H), 1.74–0.93 (m, 72H), 0.90 (d, J = 6.5 Hz, 6H), 0.87–0.85 (m, 10H), 0.83 (s, 3H), 0.78 (s, 4H), 0.65 (s, 6H); 13 C­{ 1 H} NMR (101 MHz, CDCl 3 ) δ 92.9 (d, J = 171.8 Hz), 89.6 (d, J = 165.6 Hz), 56.4 (dd, J = 19.3, 4.9 Hz), 54.3 (d, J = 2.1 Hz), 54.1, 44.2 (d, J = 9.8 Hz), 42.6 (d, J = 1.7 Hz), 40.0, 39.5 (d, J = 15.9 Hz), 36.5–36.1 (m), 35.9–35.6 (m), 35.5, 35.2 (d, J = 16.7 Hz), 34.1, 33.9, 32.4, 32.0 (d, J = 10.9 Hz), 28.5 (dd, J = 28.6, 16.5 Hz), 28.0, 27.2, 27.0, 24.2 (d, J = 3.7 Hz), 23.8, 22.8, 22.6, 21.3, 20.8, 18.7, 12.2 (d, J = 17.0 Hz), 11.2; 19 F NMR (376 MHz, CDCl 3 ) δ 5g -3β, −167.55 (d, J = 49.7 Hz), 5g -3α, −180.07 to −181.65 (m). Spectroscopic data were in agreement with the literature values …”

Total Synthesis of Rameswaralide Utilizing a Pharmacophore-Directed Retrosynthetic Strategy

“…Overman and MacMillan commonly employed methyl oxalates as intermediates for Cs-oxalate salt generation, enabled by selective hydrolysis of the more accessible ester . While methyl, benzyl, and p -nitrobenzyl oxalates were prepared from alcohol 40 , none of the oxalate esters led to sufficiently selective hydrolysis, returning quantities of starting alcohol 40 (not shown, see the Supporting Information for details, pp. 16–18).…”

Catalytic alkene skeletal modification for the construction of fluorinated tertiary stereocenters

“…On the other hand, catalytic fluorination of alkenes, allylic electrophiles, and C–H bonds with nucleophilic fluoride sources represents in general an efficient option considering the availability of fluoride sources. 5,6…”