title: Intra- and intermolecular alkylation of N,O-acetals and π-activated alcohols catalyzed by in situ generated acid.
abstract: Intramolecular and intermolecular alkylations of carbocation precursors of limited ionization ability, principally N,O-acetals, without the use of an exogenous reagent have been developed. The reactions are carried out in 1,1,2,2-tetrachloroethane (TCE) and take advantage of the ability of this solvent to continuously release small amounts of HCl by thermolytic elimination. A study of the reaction led to several improved protocols such as (1) preheated TCE, (2) microwave-assisted reactions, and (3) flow or sealed-tube conditions, which allow significant reaction rate enhancements and made possible some challenging reactions such as the α-amidoalkylation of ketones. Studies using flow chemistry confirmed not only that very low concentrations of HCl generated from the solvent were responsible for the reactivity but also that TCE had additional beneficial properties in comparison to other chlorinated solvents such as dichloroethane. The method can easily be extended to the alkylation using proelectrophiles such as π-activated alcohols, which are normally unreactive toward HCl catalysis. This work represents the first successful use of HCl, the simplest strong Brønsted acid, as an efficient alkylation catalyst.
authors.affiliation: Unité de Recherche en Chimie Organique et Macromoléculaire, Faculté des Sciences et Techniques de l' Université du Havre , EA 3221, FR CNRS 3038, 25 rue Philippe Lebon, BP 540, 76058 Le Havre cedex, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Hamon
authors.forename: Niall
authors.initials: N
authors.lastname: Dickinson
authors.forename: Alice
authors.initials: A
authors.lastname: Devineau
authors.forename: David
authors.initials: D
authors.lastname: Bolien
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Tranchant
authors.forename: Catherine
authors.initials: C
authors.lastname: Taillier
authors.forename: Ivan
authors.initials: I
authors.lastname: Jabin
authors.forename: David C
authors.initials: DC
authors.lastname: Harrowven
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whitby
authors.forename: A
authors.initials: A
authors.lastname: Ganesan
authors.forename: Vincent
authors.initials: V
authors.lastname: Dalla
mesh_terms: D000080:Acetals / Q000737:chemistry*; D000438:Alcohols / Q000737:chemistry*; D000478:Alkylation; D002384:Catalysis; D004980:Ethane / Q000031:analogs & derivatives* / Q000737:chemistry; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry*; D007202:Indicators and Reagents / Q000737:chemistry; D008872:Microwaves; D015394:Molecular Structure; D012997:Solvents / Q000737:chemistry
chemical_list: D000080:Acetals; D000438:Alcohols; D006843:Hydrocarbons, Chlorinated; D007202:Indicators and Reagents; D012997:Solvents; C015530:1,1,2,2-tetrachloroethane; D004980:Ethane