Synthesis of N-(2-SF5-ethyl)amines and impact of the SF5 substituent on their basicity and lipophilicity

Chemistry of Pentafluorosulfanyl Derivatives and Related Analogs: From Synthesis to Applications

“…[74b,76] Triflation of alcohol 84 yielded the corresponding triflate 85. [76] The group of Paquin employed the triflate 85 as an electrophilic partner to access a range of N-(2-SF 5 -ethyl)amines 86 via an S N 2 reaction (Scheme 26). Moreover, they evaluated the effect of the adjacent SF 5 group on the basicity and lipophilicity of the corresponding amines.…”

“…The SF 5 -substituted amines showed lower pK aH and log D compared to the trifluoromethyl counterparts. [76] The group of Fokin reacted the methyl SF 5 -acetate 79 with aromatic aldehydes 86 in aldol reactions in presence of Ti(IV) (Scheme 27, A and B). [77] Both transformations are highly diastereoselective yielding mostly trans and syn products when the reaction is executed in non-nucleophilic solvents such as CH 2 Cl 2 (Scheme 27, B).…”

“…Simple base‐mediated hydrolysis of 79 yields the corresponding carboxylic acid 80 , [74c,75] which could be transformed into the acyl chloride 81 or esters 82 – 83 . Furthermore, reduction of the addition intermediate in presence of a hydride source yields the alcohol 84 [74b,76] . Triflation of alcohol 84 yielded the corresponding triflate 85 [76] …”

“…Furthermore, reduction of the addition intermediate in presence of a hydride source yields the alcohol 84 [74b,76] . Triflation of alcohol 84 yielded the corresponding triflate 85 [76] …”

Recent Advances in the Synthesis and Medicinal Chemistry of SF5 and SF4Cl Compounds

“…Scheme 31 Synthesis of N-(2-SF5-ethyl)amines 32 A methodology for performing the reductive amination of aldimines, generated in situ from aliphatic, aromatic, or heteroaromatic aldehydes and aliphatic, aromatic, or heteroaromatic primary/secondary amines, using trichlorosilane in the presence of dimethylformamide as an organocatalyst (≤10 mol %), was published by Kocovsky et al (Scheme 32). 33 Reductive amination of SF5-substituted aromatic aldehydes led to the formation of propargyl amines as potential candidates for further functionalization by click chemistry.…”