title: Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications.
abstract: (1H-Benzo[d][1,2,3]triazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzo[d][1,2,3]triazol-1-yl 4-methylbenzenesulfonate (Bt-OTs), and 3H-[1,2,3]triazolo[4,5-b]pyridine-3-yl 4-methylbenzenesulfonate (At-OTs) are classically utilized in peptide synthesis for amide-bond formation. However, a previously undescribed reaction of these compounds with alcohols in the presence of a base, leads to 1-alkoxy-1H-benzo- (Bt-OR) and 7-azabenzotriazoles (At-OR). Although BOP undergoes reactions with alcohols to furnish 1-alkoxy-1H-benzotriazoles, Bt-OTs proved to be superior. Both, primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From (31)P{(1)H}, [(18)O]-labeling, and other chemical experiments, phosphonium and tosylate derivatives of alcohols seem to be intermediates. These then react with BtO(-) and AtO(-) produced in situ. In order to demonstrate broader utility, this novel reaction has been used to prepare a series of acyclic nucleoside-like compounds. Because BtO(-) is a nucleofuge, several Bt-OCH2Ar substrates have been evaluated in nucleophilic substitution reactions. Finally, the possible formation of Pd π-allyl complexes by departure of BtO(-) has been queried. Thus, alpha-allylation of three cyclic ketones was evaluated with 1-(cinnamyloxy)-1H-benzo[d][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis.
authors.affiliation: Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA.
authors.forename: Mahesh K
authors.initials: MK
authors.lastname: Lakshman
authors.affiliation: Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Singh
authors.affiliation: Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA.
authors.forename: Raghu Ram
authors.initials: RR
authors.lastname: Chamala
authors.affiliation: Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA.
authors.forename: Vijayender R
authors.initials: VR
authors.lastname: Yedulla
authors.affiliation: Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA.
authors.forename: Domenick
authors.initials: D
authors.lastname: Wagner
authors.affiliation: Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Leung
authors.affiliation: Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA.
authors.forename: Lijia
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA.
authors.forename: Asha
authors.initials: A
authors.lastname: Matin
authors.affiliation: Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA.
authors.forename: Sadia
authors.initials: S
authors.lastname: Ahmad
keywords: alkoxy; azabenzotriazole; benzotriazole; peptide-coupling; phosphonium