Triphenylphosphine-mediated halogenations

Triphenylphosphine is a versatile reagent in organic synthesis. In addition to the applications discussed above, it is also used in a number of halogenation protocols for converting alcohols to alkyl halides. The Appel reaction, shown below for a primary alcohol, is used to prepare both alkyl chlorides and bromides  

The first step of the reaction involves PPh3 attacking a halogen atom in CX4 to form a phosphonium cation. The fact that a halogen atom of CX4 acts as the electrophilic center rather than the carbon may seem odd, but it s a reflection of both the nucleophilicity of phosphoms in triphenylphosphine and the sterically hindered nature of the carbon in CX4 

The trihalomethide anion then picks up a proton from the alcohol  

The trihalomethane (also called haloform) thus formed doesn t play any further role in the mechanism but the alkoxide ion produced reacts with the phosphonium ion to form a pentavalent, pentacoordinate phosphorus intermediate, which falls apart to the alkyl halide 

Formation of triphenylphosphine oxide, once again, is a key driving force for the reaction. 

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Pyridones can also be converted to 2-chloropyridines by exchanging the carbonyl functionality using phosphoroxychloride (POCI3) [72]. A combination of N-halosuccinimides and triphenylphosphine has also been applied to introduce halogens in this position [73]. The carbonyl functionality in 2-pyridones makes these systems reactive towards nucleophiles as well, which add in 1,4-reactions with displacement of halides [74]. The use of transition metal mediated couplings like Heck, and Suzuki have also been successfully applied on halogenated 2-pyridones (d. Scheme 10) [36,75]. 

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