Metal-Catalyzed Trifluoromethylation

It has recently been reported that rhodium catalysts (Rh Cl(PPh3)3) are able to mediate the addition of trifluoromethyl iodide, in the presence of Et2Zn, onto the position of 

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Direct metal-catalyzed trifluoromethylation of (hetero)arenes 13ASC617. 

As a ligand in a transition-metal-catalyzed trifluoromethylation, A,A -dimethylethylenediamine can also be employed (Scheme 26.7), but in this case, a stoichiometric amount of AgF is required because of its cooperative effect of silver, as shown in Scheme 26.8. This reaction does not proceed when KF is employed instead of AgF. Additionally, even when NaOt-Bu is not used, 41% of the desired coupling product can be given. 

Transition-metal-catalyzed trifluoromethylation using a 5-(trifluoromethyl)dibenzo-thiophenium salt reagent has been published (Scheme 26.23). 

To make the transformation even more useful, different carbon electrophiles should be connected sequentially in a stepwise manner. For this purpose, a transition-metal-catalyzed cross-coupling reaction opened the way. As shown in Scheme 22, cinnamyl chloride is treated with bis(iodozincio)methane (3) in the presence of palladium catalyst with various phosphine ligands. Phosphine ligands, having an electron-withdrawing group, such as tris[3,5-bis(trifluoromethyl)phenyl]phosphine and tris(2-furanyl)phosphine, show excellent results47. 

Pyridyldimethylsilane 24 is a reagent for the metal-catalyzed hydrosilylation of alkynes and alkenes <2004EROS1>. 4-(Trifluoromethyl)pyridine 25 has been used as a building block in heterocycle synthesis <2005EROS1>. 

Pang, W., Zhu, S., Jiang, H. and Zhu, S. (2006) Transition metal-catalyzed formation of CF3-substituted P-unsaturated alkene and the synthesis of a-trifluoromethyl-substituted P-amino ester. Tetrahedron, 62, 11760-11765. 

Transition metal-catalyzed Csp -monofluoro-, difluoro-, perfluorome-thylation and trifluoromethyl thiolation 13BJ02476. 

Transition metal-catalyzed arene trifluoromethylation 12CJO1380. 

Ye Y, Sanford MS (2012) Merging visible-light photocatalysis and transition-metal catalysis in the copper-catalyzed trifluoromethylation of boronic acids with CF3I. J Am Chem Soc 134 9034-9037... 

Almost at the same time, Backvall et al. demonstrated that PSL and metal-catalyzed DKR can also be applied to other primary alcohols bearing an unfunctionalized stereo-genic center in the (3-position. The chosen substrates were racemic 2-arylpropan-l-ols (rac-10 is included, as an example, in Scheme 57.4), which are precursors of the nonsteroidal anti-inflammatory 2-arylpropionic acids (profens). DKR processes were performed in toluene at 80 C, with catalyst la, Amano PS-D 1 lipase, and 4-nitrophenyl 3-[4-(trifluoromethyl)phenyl]propanoate as the acyl donor. In this case, the metal catalyst is also indirectly involved in the racemization of the primary alcohol. Initially, metal-catalyzed dehydrogenation of the alcohol takes place, with the resulting aldehyde undergoing enoUzation, which can be facilitated by the elevated temperature. 

Usually the reaction requires an excess of zinc metal, a few hours in refluxing toluene, and can eventually be catalyzed with small amounts of zinc salts. A modification of this method, employing dimethyl zinc instead of zinc metal, has been used to prepare a stable complex of bis(trifluoromethyl)zinc with pyridine (eqnation 10). 

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