Regioselectivity nucleophilic substitution

Regioselective nucleophilic substitution at the 5 position is proved to occur when 1-hydroxytryptophan and -tryptamine derivatives are treated with 85% HCOOH (99H1157). Truly amazing is the fact that only substrates carrying a C—C—N structure in the side chain at the 3 position can undergo this regioselective substitution. 

Y= CHjCHjNHCOOMe, CH2CH2NHAC, CH2CH(NHAo)COOMe Regioselective Nucleophilic Substitution at the 5-Position... 

The earlier reported palladium-catalyzed, regioselective nucleophilic substitution reaction of 1-halo-l-vinylcyclopropanes 10 to give alkylidenecyclopropanes can also be extended to stabilized carbanion nucleophiles. Use of a BINAP-modified catalyst leads to asymmetric induction with up to 47% ee. Again no ring opening of cyclopropanes was observed. 

A direct synthesis of trisubstituted isothiazole 1,1-dioxides, which are difficult to prepare by other methods, has been achieved by treatment of a substituted meth-anesulfonamide with diethyl oxalate in ethanol. Thus, the disodium salt of 3,4-dihydroxy-5-(ethoxycarbonyl)isothiazole 1,1-dioxide (42) is obtained in high yield when 41 is treated with diethyl oxalate in the presence of sodium ethoxide at room temperature (equation 24)35. Regioselective nucleophilic substitution of 3,4-dichloro- and 4-chloro-3-ethoxy-5-(ethoxycarbonyl)isothiazole 1,1-dioxide, prepared from 42, oxalyl chloride and ethanol occurs at the C-3 and C-4 positions with alcohol, amines and iV-(trimethylsilyl) amines. 

The A,-type cation radical intermediates are fiiequently proposed for the nucleophilic substitution reactions of aryl-substituted cyclopropane cation radicals. Rao and Hixson were the first to report the unusual regioselective nucleophilic substitution of 4. The more highly substituted C-2 of 4 is regioselectively attacked by methanol and reduction of the resulting radical 5 followed by protonation gives... 

Fig. 5.11. Regioselective nucleophilic substitution reactions of [S(Cl)=NPCl2=NPCl2] ...

---