Catalytic Enantioselective Intermolecular [5 + 2] Dipolar Cycloadditions of a 3-Hydroxy-4-pyrone-Derived Oxidopyrylium Ylide

Abstract

The first catalytic enantioselective [5+2] dipolar cycloaddition of a 3-hydroxy-4-pyrone-derived oxidopyrylium ylide is described. These studies leveraged the recently recognized ability of oxidopyrylium dimers to serve as the source of ylide, which was found to be key to increasing yields and achieving enantiomeric excesses up to 99%. General reaction conditions were identified for an array of α,β-unsaturated aldehyde dipolarophiles. Reaction products possess four stereocenters, and subsequent reduction introduced a fifth contiguous stereocenter with total stereocontrol.

Diastereoselective Synthesis of 2‐(1,3‐Dioxolanes‐4‐yl)‐4H‐pyran‐4‐ones from 2‐Diazo‐3,5‐dioxo‐6‐ynoates (sulfones) and Aldehydes Based on Tandem Cyclization‐Cycloaddition Strategy

“…γ‐Pyranone unit as a key structural motif exists in large numbers of drug molecules, natural products and synthetic biological molecules (Figure ) In addition, this type of compound has been widely used in organic synthesis . 1,3‐Dioxolanes also possess biological activity, and has been employed as inhibitors (Figure ) .…”

Catalytic Enantioselective Reactions with (Benzo)Pyrylium Salts

“…More recently, an alternative approach for the chiral amino-catalyzed enantioselective [5+2]-dipolar cycloaddition of oxidopyrylium ylides with cinnamaldehydes was reported by Brenner-Moyer and coworkers (Scheme 25). [39] They employed oxidopyrylium dimers as the ylide precursors for the asymmetric cycloaddition reaction with electron-poor dipolarophiles accessible through iminium catalysis using the Jorgensen-Hayashi pyrrolidine catalyst. The oxidopyrylium ylide dimer reactant enabled the use of substoichiometric quantities of both TfOH as strong acid and N,N-diisopropylaniline (DIPEA) as a base, which was critical to attain the best yields, selectivities and reaction times.…”

Oxidopyrylium [5+2] cycloaddition chemistry: Historical perspective and recent advances (2008–2018)

“…In collaboration with the Brenner-Moyer lab, our group also helped developed the first catalytic asymmetric oxidopyrylium cycloaddition of the 3-hydroxy-4-pyrone class (Scheme 33). 53 This was promoted by chiral iminium activation of β-substituted enals. In these studies, it was found that the conjugate acid of N,N-diisopropylaniline was necessary for the reaction to proceed, likely by facilitating iminium formation.…”