Heck Reaction in Diols and Cascade Formation of Cyclic Ketals

Abstract

The regioselective Heck arylation of butyl vinyl ether in alcohols is utilized for the formation of a variety of cyclic ketals. When carried out in ethylene glycol, propane-1,2-diol, or propane-1,3-diol, the palladium-catalyzed arylation afforded dioxolanes or dioxanes directly. With diols such as glycerol, 3-chloropropane-1,2-diol, and 2-methylpropane-1,3-diol, isolation of the Heck adducts and the use of an acid catalyst for the ketalization were necessary; an efficient phosphoric acid was identified. The procedure presented provides a new pathway for the synthesis of cyclic ketals, particularly those that are functionalized.

MSTFA as an Effective TMS Source for the TMSOTf-Catalzyed Synthesis of Cyclic Acetals

“…Cyclic acetals can often be derived from chiral or functionalized diols as found in the synthesis of natural products and bioactive molecules and in asymmetric induction methods. , As illustrated in Scheme , when chiral and hindered diols were used, the acetals ( 5a – 5c ) were obtained in 85–91% yield without the use of the precious diols in large excess or as a solvent . Due to the electron-withdrawing effect from the gem-difluorides, we speculated that 2,2-difluoropropane-1,3-diol should be less reactive.…”

“…In the context of multistep synthesis of organic compounds with multiple functional groups, cyclic acetals are one of the most well-established and frequently used protective strategies for the carbonyl groups. − Moreover, cyclic acetals are used as chiral auxiliaries, present in several bioactive molecules (Figure ), and find wide applications in industrial manufacturing such as fuel additives, surfactants, and flavors . To date, enormous efforts have been dedicated to the development of an efficient system to produce acetals.…”