Gerasimos A. Rassias

Catalytic Hydrotrifluoromethylation of Unactivated Alkenes

A visible-light-mediated hydrotrifluoromethylation of unactivated alkenes that uses the Umemoto reagent as the CF(3) source and MeOH as the reductant is disclosed. This effective transformation operates at room temperature in the presence of 5 mol % Ru(bpy)(3)Cl(2); the process is characterized by its operational simplicity and functional group tolerance.

Trifluoromethylation of Allylsilanes under Copper Catalysis

Medicinal chemists commonly incorporate a trifluoromethyl group into druglike molecules to enhance binding selectivity, improve metabolic stability and increase lipophilicity. To date, various methods are available for the introduction of the CF3 group onto functionalized arenes and heteroarenes. Numerous catalytic trifluoromethylation reactions of ketones or aldehydes have also been developed, leading to the formation of Csp3–CF3 bonds, including elegant asymmetric variants. The construction of Csp3–CF3 stereogenicity from poorly activated substrates is less common. In this context, the direct selective installation of a CF3 group on an allylic position remains a challenging synthetic problem. Isolated examples of Pd-catalyzed trifluoromethylation of allylstannanes with CF3I [5] and Cu-mediated nucleophilic trifluoromethylation of allyl bromide using the Ruppert–Prakash reagent (CF3SiMe3) are known, [6] giving linear allylic CF3 products. Recently, Buchwald, [7] Wang, and Liu and their co-workers reported that terminal alkenes are amenable to allylic trifluoromethylation under copper catalysis, a reaction also affording linear allylic CF3 products with very good control over E :Z geometry. Access to branched acyclic allylic CF3 products has not been demonstrated, and only two branched cyclic products have been prepared through application of this C H functionalization methodology. To address this synthetic challenge, we reasoned that we could access allylic CF3 products using alkenes temporarily activated with a regiodirecting silyl group. Since our first report in 2003, we have demonstrated that a diverse range of allylic fluorides are accessible upon electrophilic fluorination of allylsilanes under very mild conditions and have found that this reaction is broad in scope and tolerant of various functional groups. The presence of the allylic trimethylsilyl group is essential to increase the nucleophilicity of the proximal alkene and to dictate the regiochemistry of the fluorination. Based on these principles and the availability of various electrophilic trifluoromethylating reagents (e.g., hypervalent iodine reagents I and II, and the sulfonium salts III and IV), we describe herein a copper-catalyzed trifluoromethylation reaction to prepare various branched allylic CF3 products from allylsilanes (Figure 1).

Trifluoromethylation of Allylsilanes under Photoredox Catalysis

A new catalytic method to access allylic secondary CF3 products is described. These reactions use the visible light excited Ru(bpy)3Cl2·6H2O catalyst and the Togni or Umemoto reagent as the CF3 source. The photoredox catalytic manifold delivers enantioenriched allylic trifluoromethylated products not accessible under Cu(I) catalysis.

An organic cation as a silver(I) analogue for the arylation of sp2 and sp3 C–H bonds with iodoarenes

Reactions promoted by stoichiometric amounts of silver salts suffer from high cost, limited availability and raise environmental concerns. This manuscript describes studies leading to the discovery of a general replacement for silver with an inexpensive and convenient organic salt in palladium catalyzed direct C(sp2)–H and C(sp3)–H arylation reactions.

Dihydroisoquinolinium salts: catalysts for asymmetric epoxidation

A range of dihydroisoquinolinium salts has been prepared and tested as asymmetric epoxidation catalysts in an investigation of the reaction mechanism and the factors affecting enantioselectivity in this process.

The reductive cleavage of cyclic aminol ethers to N,N-dialkylaminoderivatives: Modifications to the Eschweiler-Clarke procedure

The reductive cleavage of cyclic aminol ethers to give N-alkylamino- derivatives in very high yields can be achieved using chlorotrimethylsilane in the presence of sodium cyanoborohydride: in the case of cyclic aminol ethers derived from formaldehyde the Eschweiler-Clarke reaction can be carried out in formic acid heated under reflux in the absence of formaldehyde.