Recent Advances on the Photoinduced Radical Nucleophilic Substitution Reactions

MARÍA E. BUDÉN; SANDRA E. MARTÍN; ROBERTO A. ROSSI

Handbook of Organic Photochemistry and Photobiology

CRC Press

Lugar: London; Año: 2012; p. 347 - 366

Nucleophilic substitution is feasible through processes that involve electron transfer(ET) steps. In these reactions a compound bearing an adequate leaving group is substituted atthe ipso position by a nucleophile. Several reviews have been published on the subject inrelation to the mechanism and to the synthetic applications of the process which has become one of the common methodologies in modern synthesis. In this review we will describe themost recent advances in photostimulated SRN1 reactions. With this aim in mind, we expect tocover recent SRN1 substitutions, with an emphasis on the scope of the process in terms ofsynthetic capability and target applications. The critical review illustrates the mechanisticconsiderations required for planning synthetic applications and a wide range of syntheticprotocols.The SRN1 reaction, which stands for Unimolecular Radical Nucleophilic Substitution,is a chain process that involves radicals and radical anions as intermediates. Severalnucleophiles can be used for SRN1 reactions such as carbanions and heteroatom anionsresulting in the formation of new C-C or C-heteroatom bonds in good yields. An exception tothis is the reaction of aromatic alkoxides with aromatic substrates. In these cases C-O bondformation is not observed; instead C-C bond formation is achieved instead. For example, theunsubstituted phenoxide ions have been reported to react with ArX to afford the ortho- (ca.40%) and para- (ca. 20%) C-C coupled products.1 On the other hand, alcoxide ions afford theO-alkylation products with aliphatic substrates with EWG at thealfa carbon.There is a theoretical study (DFT/B3LYP level) on the reaction of aromatic alcoxideions with phenyl and 4-nitrobenzyl radicals with the aim of interpreting the factors thatcontrol the regiochemical outcome of these reactions. While FMO predicts the experimentalregioselectivity of phenyl radicals with good accuracy, it fails in the nitrobenzyl case.A similar behavior is observed with nitrogen nucleophiles (anions from aromaticamines, pyrrole, diazoles and triazoles) in reactions with aromatic substrates, no C-N isobserved, but C-C bond is formed. On the other hand, with nitrogen nucleophiles N-alkylationproducts are formed with aliphatic substrates with EWG at the alfa carbon.Anions derived from tin, phosphorus, arsenic, antimony, sulfur, selenium andtellurium react through the heteroatom to form a new C-heteroatom bond by this mechanism.