A general practical approach to hetero(aromatic) and aliphatic P(O)Me 2 -substituted derivatives is elaborated. The key synthetic step was a [Pd]-mediated C−P coupling of (hetero)aryl bromides/iodides with HP(O)Me 2 . The P(O)Me 2 substituent was shown to dramatically increase solubility and decrease lipophilicity of organic compounds. This tactic was used to improve the solubility of the antihypertensive drug prazosin without affecting its biological profile.

Electron-rich N-substituted pyrazoles smoothly reacted with trifluoroacetic anhydride in pyridine to form the corresponding trifluoromethyl ketones in good yields.Fluorinated compounds have played an important role in chemistry: ~20% of all pharmaceuticals and agrochemicals contain at least one fluorine atom. 2,3 This is because the incorporation of fluorine, trifluoromethyl groups, or other fluorinated fragments into organic molecules significantly changes their physicochemical and biological properties. For example, the trifluoromethyl substituent effectively influences the pK a of the neighboring functional groups, the compound lipophilicity, solubility, conformational preferences, and hydrolytic and metabolic stabilities. 4 Therefore, elaboration of practical, robust methods to prepare novel trifluoromethylated building blocks on a large scale from common starting materials is of interest to both academia and industry. 5Recently, our colleagues trifluoroacetylated 1,3-azoles with trifluoroacetic anhydride in pyridine. 6 The formed 2-(trifluoroacetyl)-1,3-azoles were subsequently used to prepare novel drug-like compounds. 7 We wanted to expand this methodology to the pharmacologically relevant pyrazole core. 8 Indeed, 4-trifluoroacetylated pyrazoles have already attracted attention in medicinal projects, agScheme 1 Chemical approaches to 4-(trifluoroacetyl)pyrazoles. 10-15 a Synthon for a tricarbonyl compound.

Direct Noncatalytic Electrophilic Trifluoroacetylation of Electron-Rich Pyrazoles. -(YARMOLIUK, D. V.; ARKHIPOV, V. V.; STAMBIRSKYI, M. V.; DMYTRIV, Y. V.; SHISHKIN, O. V.; TOLMACHEV, A. A.; MYKHAILIUK*, P. K.; Synthesis 46 (2014) 9, 1254-1260, http://dx.doi.org/10.1055/s-0033-1340840 ; Dep. Chem., Taras Shevchenko Natl. Univ., Kiev 01601, Ukraine; Eng.) -H. Hoennerscheid 41-135