Synthesis of α-CF₃ Amides via Palladium-Catalyzed Carbonylation of 2-Bromo-3,3,3-trifluoropropene

Abstract

Amide compounds are important organic compounds, which play an important role in biomedical chemistry, materials science, life science, and other fields. The synthesis of α-CF 3 amides, especially compounds containing 3-(trifluoromethyl)-1,3,4,5-tetrahydro-2H-benzo [b][1,4]diazepine-2-one, has long been a challenge due to the tensile properties and instability of the rings. Here, we report an example of palladium-catalyzed carbonylation of CF 3 -containing olefin to form α-CF 3 acrylamide. By controlling the ligands, we can get different amide compounds as products. This method has good substrate adaptability and functional group tolerance.

Copper-Catalyzed Synthesis of 4-CF3-1,2,3-Triazoles: An Efficient and Facile Approach via Click Reaction

“…Our continuing interest in the chemistry of 1,2,3-triazoles [ 63 , 64 , 65 , 66 , 67 ] and the importance of trifluoromethyl-substituted 1,2,3-triazoles encouraged us to evaluate the possibility of performing click reactions of 3,3,3-trifluoropropyne (TFP) with aryl- and alkyl-azides under mild and practical conditions. In contemplating possible methods to carry out these click reactions, we recognized that 2-bromo-3,3,3-trifluoropropylene (BTP) is a commercially available reagent [ 68 , 69 , 70 , 71 , 72 ], and that its [3+2]-cycloaddition reactions have been employed to produce CF 3 -substituted pyrazoles [ 73 , 74 , 75 , 76 ], -isoxazoles [ 77 ] and -pyrroles [ 78 ]. Particularly informative are the observations that BTP can be readily transformed to TFP by treatment with bases [ 79 , 80 , 81 , 82 , 83 ] like i -Pr 2 NLi and 1,8-diazabicyclo[5.4.0]undec-7-ene DBU, and that compared to gaseous TFP, BTP is an inflammable, storage-stable and easily handled liquid.…”

Synthesis of Secondary Trifluoromethylated Alkyl Bromides with Further Conversion to Boronic Esters and Alcohols

“…We have developed an alternative synthesis of secondary trifluoromethylated alkyl bromides via a catalyst‐free decarboxylative process, which is initiated and promoted by the photochemical activity of an in situ generated electron‐donor‐acceptor (EDA) complex involving a redox ester and a Hantzsch ester. In this protocol, commercially available 2‐bromo‐3,3,3‐trifluoropropene (BTP) [33–35] serves as a radical acceptor for the first time (Scheme 2b) [36] . In addition to carboxylic acids, amines can also be used as radical precursors through a deaminative process when transformed to Katritzky salts [37–46] .…”

Access to Amides and Lactams via Pyridotriazole as a Transformable Directing Group

“…Amide and lactam scaffolds are a class of substantial motifs frequently found in pharmaceuticals and naturally occurring molecules like imatinib, lenalidomide, and elmenol H. − A wide range of approaches to constructing such indispensable amide bonds have been developed, ranging from conventional acylation of amines mediated by amide coupling agents , to modern strategies such as catalytic direct amidation , or visible light irradiation. , Among these studies, transition-metal-catalyzed C–H activation stands out as a simpler synthetic route for direct amidation of unactivated C–H bonds. − Many transition-metal-catalyzed C–H functionalization methods require directing groups (DGs), − especially transformable DGs, to enhance the regioselectivity and practicality. − By the DG-assisted C–H activation strategy, selectively installing nitrogen-based functional groups (FGs) into molecules via the direct addition of C–H bonds to unsaturated polar C–N π-bonds represents the most powerful and economical method for rapid amide and lactam synthesis. − We envisioned isocyanates to be particularly useful. As useful carbon synthons in organic synthesis, isocyanates have been extensively implemented in the construction of C–C bond formation for forging amides. − Hence, employing isocyanates as FGs would be a more straightforward approach to the synthesis of amides.…”

“…Amide and lactam scaffolds are a class of substantial motifs frequently found in pharmaceuticals and naturally occurring molecules like imatinib, lenalidomide, and elmenol H. 1−3 A wide range of approaches to constructing such indispensable amide bonds have been developed, ranging from conventional acylation of amines mediated by amide coupling agents 4,5 to modern strategies such as catalytic direct amidation 6,7 or visible light irradiation. 8,9 Among these studies, transitionmetal-catalyzed C−H activation stands out as a simpler synthetic route for direct amidation of unactivated C−H bonds.…”