Transition metal-free oxidation of activated alcohols to aldehydes and ketones in 1,1,1,3,3,3-hexafluoro-2-propanol

HFIP in Organic Synthesis

“…The Khaksar group reported a protocol for the direct oxidation of benzylic, allylic, and aliphatic alcohols using sodium hypochlorite (NaOCl) in HFIP to afford the corresponding aldehydes and ketones (Scheme ). The oxidation of benzyl alcohol with NaOCl did not occur in TFE or other nonfluorinated solvents such as DCM, ACN, toluene, and ethanol. The authors proposed that the Brønsted acidity of HFIP assists in the ionization of the benzylic alcohol to generate the benzylic carbocation intermediate, which is stabilized by HFIP.…”

Lewis acid free synthesis of 3,4-dihydro-1H-indazolo[1,2-b]phthalazine-1,6,11(2H,13H)-triones promoted by 1,1,1,3,3,3-hexafluoro-2-propanol

“…Reactions in 1,1,1,3,3,3-hexauoro-2-propanol (HFIP) have a facile isolation of the product and can be easily recovered by distillation. [25][26][27] HFIP has been used in organic synthesis because these uorinated alcohols are available on a commercial scale. They can be well dispersed in the reaction mixtures in solvolysis reaction, where the generated cationic intermediates can be trapped by nucleophiles.…”

“…In this process, HFIP with a strong H-bond donor (a ¼ 1.96, pK a ¼ 9.3), high ionizing power (Y OTs ¼ 3.79), and polarity (P s ¼ 11.08) could activate the C]O groups and play a signicant role in increasing the electrophilic character. [25][26][27] Therefore, The formation of products 4a-p can be rationalized by initial formation of heterodiene by standard Knoevenagel condensation of cyclic 1,3-diketones and aromatic aldehydes in the presence of a catalytic amount. Subsequent Michael-type addition of phthalhydrazide to the heterodienes followed by cyclization and dehydration afford the corresponding products 4a-p (Scheme 2).…”