Pd-mediated fluorination

Sanford and co-workers have reported on a Pd-mediated fluorination of 8-methylquinolines using Pd(OAc)2 in the presence of PhI(OPiv)2 as... 

Seheme 15.55 Solvent effects in the Pd-mediated fluorination of aryl triflates. 

Scheme 15.56 Pd-mediated fluorination of aiyl triflates in flow.

As noted, one of the key issues with developing a Pd-mediated fluorination process is the difficulty associated with the reductive elimination step. In 2006, Sanford reported on a pyridine directed C-H activation strategy by reacting a palladium(ii) complex which forms a cyclic metallated intermediate this then reacts with an electrophilic fluoride to yield the aromatic fluorine (Scheme 15.75). °... 

Yu developed a similar method of Pd-mediated directed electrophilic fluorination of C-H bonds using iV-benzyl triflimide derivatives. Key to the success of Yu s chemistry is the use of 2,4,6-trimethylpyridinium fluoride as the triflate salt, which was identified through a screen of fluorinating agents. 

Scheme 15.75 Sanford s Pd-mediated p Tidine directed fluorination.

Scheme 15.78 Pd-mediated O-methyl oxime ethers directed fluorination.

Another system, a mixture of Pd(OAc)2 and IPr HC1, can mediate this reaction in the presence of a fluorine source [121]. The use of TBAF is essential for this reaction as it can act as a base, deprotonating the imidazolium salt, as a fluorous medium for tin extraction and as a fluorinating agent. In fact, the in situ formation of a hypervalent organnostannate speeds up the trans-metallation step and therefore eases the coupling reaction. Unfortunately, the reaction is limited to aryl bromides and activated aryl chlorides, on the other hand vinylstannates can also be used as coupling partners (Scheme 14). 

C-H-Oleflnation. Pd(II)-mediated aromatic C(sp2)-H olefi-nation occurs via a tandem reaction with tosylamide as directing group and bond formation partner (eq 12). The reaction tolerates different substituents at the phenyl ring such as methyl, methoxy, bromine, fluorine, trifluoromethyl and biphenyl with yields from 64% to 87%. Further, instead of CO Bu aliphatic esters as well as carbonyl, carboxamide, halogens, and aryl substitutents are suitable substrates. ... 

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