Organocatalyzed [4+2] Annulation of All‐Carbon Tetrasubstituted Alkenes with Allenoates: Synthesis of Highly Functionalized 2H‐ and 4H‐Pyran Derivatives.

Abstract

A stereoselective [4 + 2] annulation of acyclic all-carbon tetrasubstituted alkenes with allenoates was described. The reaction with DABCO proceeded smoothly leading to the formation of highly functionalized 4H-pyran derivatives in good yields. We have also reported first b-ICD-catalyzed [4 + 2] annulation affording functionalized enantioenriched 2H-pyran derivatives bearing a chiral all-carbon quaternary center.[a] T.Scheme 1. Lewis base (LB)-catalyzed reactions of allenoates with electrophiles (E).Scheme 2. Tertiary amine-catalyzed annulation of allenoates with electrophiles.

Organocatalytic Synthesis of Highly Functionalized Heterocycles by Enantioselective aza-Morita–Baylis–Hillman-Type Domino Reactions

“…α-Substituted α,β-unsaturated carbonyl compounds can be readily accessed by the Rauhut-Currier (RC) reaction, also called the vinylogous MBH reaction, through the coupling of two different α,β-unsaturated enones wherein one acts as a latent enolate. 85) As part of our research into the development of enantioselective domino reactions, [41][42][43][44][45][46][47][48][49][50][51][52][86][87][88][89][90] we became interested in designing sequences to address optically active α-methylidene-γ-lactams. We envisioned that the amidation of 28 with 27, followed by the BA-LB-catalyzed carbon-carbon bond-forming reaction of intermediary 29, would result in the generation of α-methylidene-γ-lactams 30 in high yield with high enantiocontrols (Chart 13).…”

“…Based on the pioneering efforts of Cristau 99) (stoichiometric process), Trost 100) (catalytic process for alkynes), Lu 101 (for allenes) and Zhang 102) (enantioselective version), there has been increasing interest in γ-umpolung additions of various nucleophiles to electrondeficient allenes and alkynes. 103) As part of our research into chiral LB catalysis, [41][42][43][44][45][46][47][48][49][50][51][52] we became interested in designing new sequences to approach important structures via nucleophilic attack to the γ-position of allenoates. Before the elimination of the LB catalyst, if the zwitterionic intermediate C would react with electrophiles, the result may be a formal dual umpolung coupling (Chart 18).…”

“…This review article describes our recent research on the development of organocatalyzed domino reactions initiated by enantioselective MBH-type processes. [41][42][43][44][45][46][47][48][49][50][51][52] 41,42) Isoindoline skeletons are standard structures in a variety of natural products and pharmaceuticals, such as nuevamine 53) and pagoclone, 54) as well as their functionalized derivatives. 55) As such, these materials show a range of biological potencies involving anti-leukemic, anxiolytic, anti-tumoral, and potent endothelin A receptor antagonist activities.…”