The Asymmetric Hetero‐Diels–Alder Reaction in the Syntheses of Biologically Relevant Compounds

Abstract

The hetero-Diels-Alder reaction is one of the most powerful transformations in the chemistry toolbox for the synthesis of aza- and oxa-heterocycles embodying multiple stereogenic centers. However, as compared to other cycloadditions, in particular the dipolar cycloadditions and the Diels-Alder reaction, the hetero-Diels-Alder reaction has been much less explored and exploited in organic synthesis. Nevertheless, this powerful transformation has opened up efficient and creative routes to biologically relevant small molecules and different natural products which contain six-membered oxygen or nitrogen ring systems. Recent developments in this field, in particular in the establishment of enantioselectively catalyzed hetero-Diels-Alder cycloadditions steered by a plethora of different catalysts and the application of the resulting small molecules in chemical biology and medicinal chemistry research, are highlighted in this Minireview.

Asymmetric Photocatalysis by Intramolecular Hydrogen‐Atom Transfer in Photoexcited Catalyst–Substrate Complex

“…Forpractical reasons,itisworth noting that this new asymmetric photoreaction can be scaled up.On ascale of 4.5 mmol (1.08 g), the reaction 1d!2d afforded an improved yield of 90 %with aslightly increased enantiomeric excess of 99 %a nd the rhodium catalyst was reisolated in 86 %yield by capture with an auxiliary ligand in aprocedure reported recently. [9,10] An intersystem crossing to the singlet-state ketene IV sets the stage for an intramolecular asymmetric hetero-Diels-Alder reaction [11] to form the rhodium bound cyclopropane product VI.P roduct release and recoordination of new substrate then initiates anew catalytic cycle. The catalytic cycle starts with the rhodium catalyst binding to the N-acyl pyrazole substrate in ab identate fashion (int.…”

Catalytic Enantioselective Assembly of Homoallylic Alcohols from Dienes, Aryldiazonium Salts, and Aldehydes

“…Notably,t he successful multicomponent reaction of unsaturated aldehydes proceeded with excellent results (entries 5a nd 6). More significantly,a liphatic aldehydes performed well in the reaction (entries [7][8][9][10][11][12]. In particular, the introduction of different functionalities to the aliphatic aldehydes was nicely accommodated and yielded multiply functionalized chiral homoallylic alcohols with excellent selectivities (entries 9-12).…”

“…[12] Very recently,T oste and co-workers showed that the chiral ion pair 2' ' (Scheme 2), generated from am etathesis reaction of the insoluble aryldiazonium salt 2 and chiral phosphate salt by phase transfer (CAPT), [11] was able to undergo oxidative addition with the palladium(0) A species to give the chiral aryl palladium(II) phosphate B. [13] We and others previously found that the aryl palladium(II) species could undergo migratory insertion of a1 ,3-diene to generate a p-allyl palladium intermediate.…”

Hetero-Diels–Alder reactions of hetaryl thiochalcones with acetylenic dienophiles

“…In that case, the asymmetric version is of special importance [3]. The most frequently reported hetero-Diels-Alder reactions belong to the so-called aza-or oxa-types with the C=N or C=O units in the diene or dienophile.…”