Phosphine‐Catalyzed β,γ‐Umpolung Domino Reaction of Allenic Esters: Facile Synthesis of Tetrahydrobenzofuranones Bearing a Chiral Tetrasubstituted Stereogenic Carbon Center

Abstract

An enantio-, diastereo-, regio-, and chemoselective phosphine-catalyzed β,γ-umpolung domino reaction of allenic esters with dienones has been developed for the first time. The designed sequence, involving oxy-Michael and Rauhut-Currier reactions, produced highly functionalized tetrahydrobenzofuranones, bearing a chiral tetrasubstituted stereogenic center, in up to 96 % ee.

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

“…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.…”

Bio‐inspired Domino oxa‐Michael/Diels–Alder/oxa‐Michael Dimerization of para‐Quinols

“…para-Quinols (1; Scheme 1) are ideal in this regard, since they are readily available through oxidation of commonplace phenols and they feature an abundance of electrophilic and nucleophilic sites. [4] One of the most complex examples of am ultiple-bond-forming reaction involving pquinols comes from the CarreÇo laboratory,w here they demonstrated that [(p-tolylsulfinyl)methyl]-p-quinol can participate in as pectacular,a lbeit unique,q uadruple domino reaction sequence to form ap entacyclic trimer (Scheme 1b). [3] Many domino reaction sequences have been reported that involve initial addition of the p-quinol alcohol onto an electrophile with subsequent 5-exo-trig cyclization to generate anew fused five-membered ring (Scheme 1a).…”

“…[3] Many domino reaction sequences have been reported that involve initial addition of the p-quinol alcohol onto an electrophile with subsequent 5-exo-trig cyclization to generate anew fused five-membered ring (Scheme 1a). [4] One of the most complex examples of am ultiple-bond-forming reaction involving pquinols comes from the CarreÇo laboratory,w here they demonstrated that [(p-tolylsulfinyl)methyl]-p-quinol can participate in as pectacular,a lbeit unique,q uadruple domino reaction sequence to form ap entacyclic trimer (Scheme 1b). [5] In our own laboratory,wehave achieved ashort biomimetic synthesis of the natural products (AE)-incarviditone and (AE)-incarvilleatone through dimerization of (AE)-rengyolone, a p-quinol-derived natural product (Scheme 1c).…”

X‐ray Structure Analysis of N‐Containing Nucleophilic Compounds by the Crystalline Sponge Method

“…This demonstrates that the CS method is now ap racticalt ool for drug-discoveryr esearch in pharmaceuticali ndustries.Crystalline sponge (CS) methods are emerging technologiesi n X-ray crystallography facilitatingt he crystal structure determination of non-crystalline (or hard-to-crystallize)c ompounds, withoutt raditional crystallization, on am icrogram scale. [1][2][3][4][5][6] The method uses the porous complex [(ZnI 2 ) 3 ·(tpt) 2 ·x(solvent)] n (1a;t pt = 2,4,6-tris(4-pyridyl)-1,3,5-triazine) [7] as aC St hat can absorb small-to-medium-sized organic molecules,o rient them uniformly in their pores, and make them observable by conventional single crystal X-ray crystallography. Since our earlier publications, the CS method has attracted considerable interest from pharmaceutical industries because they often have situations to urgently determine the structure of trace amountso fc ompounds,s uch as metabolites or impurities derived from their drugs of interest.…”