title: Dechalcogenative allylic selenosulfide and disulfide rearrangements: complementary methods for the formation of allylic sulfides in the absence of electrophiles. Scope, limitations, and application to the functionalization of unprotected peptides in aqueous media.
abstract: Primary allylic selenosulfates (seleno Bunte salts) and selenocyanates transfer the allylic selenide moiety to thiols giving primary allylic selenosulfides, which undergo rearrangement in the presence of PPh3 with the loss of selenium to give allylically rearranged allyl alkyl sulfides. This rearrangement may be conducted with prenyl-type selenosulfides to give isoprenyl alkyl sulfides. Alkyl secondary and tertiary allylic disulfides, formed by sulfide transfer from allylic heteroaryl disulfides to thiols, undergo desulfurative allylic rearrangement on treatment with PPh3 in methanolic acetonitrile at room temperature. With nerolidyl alkyl disulfides this rearrangement provides an electrophile-free method for the introduction of the farnesyl chain onto thiols. Both rearrangements are compatible with the full range of functionality found in the proteinogenic amino acids, and it is demonstrated that the desulfurative rearrangement functions in aqueous media, enabling the derivatization of unprotected peptides. It is also demonstrated that the allylic disulfide rearrangement can be induced in the absence of phosphine at room temperature by treatment with piperidine, or simply by refluxing in methanol. Under these latter conditions the reaction is also applicable to allyl aryl disulfides, providing allylically rearranged allyl aryl sulfides in good yields.
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607-7061, USA. dcrich@chem.wayne.edu
authors.forename: David
authors.initials: D
authors.lastname: Crich
authors.forename: Venkataramanan
authors.initials: V
authors.lastname: Krishnamurthy
authors.forename: Franck
authors.initials: F
authors.lastname: Brebion
authors.forename: Maheswaran
authors.initials: M
authors.lastname: Karatholuvhu
authors.forename: Venkataraman
authors.initials: V
authors.lastname: Subramanian
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Hutton
mesh_terms: D000498:Allyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry*; D016566:Organoselenium Compounds / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000498:Allyl Compounds; D004220:Disulfides; D016566:Organoselenium Compounds; D010455:Peptides; D010720:Phosphines; D013438:Sulfhydryl Compounds; D013440:Sulfides