Thiyl Radical Reaction Based On Dithiocarbamates And Its Application In The Total Synthesis Of Cyclobrassinin

Chemical reaction involving thiyl radical is an important means to realize the construction of Carbon-Carbon and Carbon-Heteroatom bonds and it has a wide range of applications in organic synthesis, Pharmaceuticals, polymer and many other fields. On one hand, thiol, thiophenol and other thiyl radical precursors could be oxidized by an appropriate oxidizing reagent, which provide an effective radical method to synthesize disulfide compounds. On the other hand, many compounds could be obtained via the radical addition reaction between thiyl radical and alkene, alkyne or other substrate containing unsaturated double bond or triple bond with the advantage of high efficience, mild condition and atom economy which were not easily prepared by other reaction.Bis(1-alkyl/arylimino-l-alkyl/arylthiomethyl) disulfides compounds, containing both the sulfur-sulfur bond and dithiocarbonimidate scaffolds, have certain applications in organic synthesis, biologically active compounds and rubber chemistry. However, the synthetic method of these compounds are scarcely reported. Hence, it is necessary to develop a mild and effective method to synthesize these compounds. Active thiyl radical could be formed under mild condition when N-monosubstituted dithiocarbamates underwent hydrogen abstraction process with dilauroyl peroxide or benzoyl peroxide as radical initiators and hydrogen abstractors. When the substituent of dithiocarbamates at nitrogen atom are aryl groups, the thiyl radicals tend to be electrically neutral due to the conjugation effect of the aromatic rings. The electrically neutral thiyl radicals prefer to dimerize to afford the target disulfide compounds. The current method is a high effective and easily handled way for the preparation of target disulfide compounds under mild conditions. Meanwhile, the mass fragmentation of bis(1-alkyl/arylimino-l-alkyl-/arylthiomethyl) disulfides were also studied with positive ESI-HRMS. The results demonstrated that a molecule of aryl isonitrile was lose during the dissociation of molecular ion.Cyclobrassinin is a natural product of phytoalexin with antibacterial activity. The reported methods for its preparation have been focused on the ion pathways and suffered from the limitation of low yields. Thus, to develop a high efficient method to synthesize the Cyclobrassinin and its analogues is important. Active thiyl radical could be formed when N-(1H-indole-3-methyl)-S-methyl dithiocarbamate or its analogues underwent hydrogen abstraction process with benzoyl peroxide as radical initiator and hydrogen abstractors. The thiyl radical is eletrophilic due to the eletron-withdrawing effect of imine goup. The eletrophilic thiyl radical could attack the 2-position of indole ring to generate the thermodanamically more stabled benzyl tertiary carbon radical followed with the ortho hydrogen elimination reaction to yield Cyclobrassinin and its analogues in moderate yield. As far as we know, it is the first work to synthesize the Cyclobrassinin and its analogue compounds via radical method.