Catalytic Asymmetric Prins Bicyclization for the endo‐Selective Formation of 2,6‐dioxabicyclo[2.2.2]octanes

Abstract

A new Lewis acid-catalyzed endo-selective Prins bicyclization of γ,δ-unsaturated aldehydes or ketones with a broad range of aldehydes to dioxabicyclo[2.2.2]octanes is disclosed. When using a chiral BINOL-derived N-triflylphosphoramide (NTPA) as catalyst and glyoxylate esters as substrates, the cross-dimerization afford functionalized bicyclic acetals with excellent diastereo- and enantioselectivities.

N-Triflylphosphoramides: highly acidic catalysts for asymmetric transformations

“…To finish this section, we include a reaction reported by the groups of Wang and Goeke. 151 Although the reaction does not strictly involves an oxy-carbenium ion in the enantiodetermining step, it serves as a suitable example to bridge to the next section, which accounts for aldol reactions.…”

The Catalytic Asymmetric Intermolecular Prins Reaction

“…Because it embodies a double bond functionalization and a carbon–carbon bond formation in a single step, 6 the Prins reaction remains a key transformation in synthesis, providing direct access to products with common motifs in fragrances and bioactive molecules. 7 Nevertheless, the possibility of side reactions (carbonyl-ene, 8 carbonyl-olefin metathesis, 9 and/or olefin polymerization, among others) can complicate the panorama. For these reasons, designing an efficient, catalytic variant of this reaction, surmounting the challenging control of product selectivity, is extremely desirable.…”

“…The fate of this reactive species depends on the reaction conditions, leading to products such as unsaturated alcohols, 1,3-diols, and/or derivatives thereof (Figure A). Because it embodies a double bond functionalization and a carbon–carbon bond formation in a single step, the Prins reaction remains a key transformation in synthesis, providing direct access to products with common motifs in fragrances and bioactive molecules . Nevertheless, the possibility of side reactions (carbonyl-ene, carbonyl-olefin metathesis, and/or olefin polymerization, among others) can complicate the panorama.…”

Direct Formation of Oxocarbenium Ions under Weakly Acidic Conditions: Catalytic Enantioselective Oxa-Pictet–Spengler Reactions

“…Nevertheless, a number of creative approaches have been reported, the majority of which rely on the formation of oxocarbenium ions from acetals or enol ethers . Oxidative methods are also known. , Most catalytic enantioselective transformations reported to date feature cyclic and relatively stable pyrylium- or (iso)­chroman-type oxocarbenium ions. Direct condensation of an alcohol with an aldehyde has only rarely been applied in the context of asymmetric catalysis .…”