Use of the <i>p</i>‐Tolylsulfinyl Group as a Chiral Inductor in Stereoselective [4+3] Cycloaddition Reactions: Preparation of Enantiopure Polysubstituted 8‐Oxabicyclo[3.2.1]oct‐6‐en‐3‐one Systems Having up to Five Stereocenters

BINOL-based N-trifluoromethanesulfonyl phosphoramides catalyzet he enantioselective (4+ +3) cycloaddition between furans and oxyallyl cations,the latter being generated in situ by oxidation of allenamides.T he chiral organic phosphoramide counteranion is proposed to engage in the activation of the oxyallyl cation intermediate through cooperative hydrogen-bonding and ion-pairing interactions,enabling an efficient chirality transfer that providethe final adducts with high diastereo-and enantioselectivities.R emarkably,t he reaction shows aw ide substrate scope that includes av ariety of substituted allenamides and furans.The construction of seven-membered rings [1] represents am ore challenging task than the preparation of the smaller five-or six-membered analogues owing to their higher ring strain and entropy issues.I np articular,t he 8-oxabicyclo-[3.2.1]octane scaffold (Scheme 1) is ak ey structural motif present in many natural products and synthetic compounds with interesting biological activities. [2] As ac onsequence,t he development of efficient approaches for the stereoselective preparation of such molecular architectures remains atopic of interest. Among the different possibilities,( 4 + +3) cycloadditions are ak ey synthetic method for the stereoselective construction of the cycloheptane core, [3] and especially the ability of allyl cations to undergo cycloadditions with furans [4] has been applied to several successful examples of catalytic and enantioselective versions of this reaction, even though progress in this area dates back af ew years. [5] In most cases, heteroatom-stabilized oxyallyl cations [6] have been used as dienophiles,and almost all processes focused on diastereoselective approaches that relied on the use of inherently chiral substrates [7] or chiral auxiliaries. [8] In fact, only two examples of catalytic and enantioselective (4+ +3) cycloadditions have been reported to date.O ne of these reports made use of the iminium activation approach to activate the oxyallyl cation reagent [9] while the other one relied on aC u II /bis(oxazoline) chiral Lewis acid as the catalyst. [10] In addition, both methods required al arge excess (5-13 equiv) of the diene to provide synthetically useful yields and can only be employed with oxyallyl cations without any substituents at the terminal position. As ar esult, these remarkable pioneering efforts suffered from important limitations in terms of the substrate scope,r estricting the range of architectures that can be obtained. Therefore,alternative versions of this reaction that expand the potential of this approach to the enantioselective synthesis of more elaborated architectures are still missing. In particular,asmentioned, there is no precedent for areaction in which b-substituted oxyallyl cations are used as dipoles in this transformation, which therefore limits this method to cycloheptanone adducts without any substituents at the a'-position with respect to the ketone moiety.In this sense,w eh erein report that chiral BINOL-based Brønsted acids [...

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Enantioselective Oxidative (4+3) Cycloadditions between Allenamides and Furans through Bifunctional Hydrogen‐Bonding/Ion‐Pairing Interactions

Villar

Uria

Martínez

et al. 2017

Angew Chem Int Ed

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BINOL-based N-trifluoromethanesulfonyl phosphoramides catalyze the enantioselective (4+3) cycloaddition between furans and oxyallyl cations, the latter being generated in situ by oxidation of allenamides. The chiral organic phosphoramide counteranion is proposed to engage in the activation of the oxyallyl cation intermediate through cooperative hydrogen-bonding and ion-pairing interactions, enabling an efficient chirality transfer that provide the final adducts with high diastereo- and enantioselectivities. Remarkably, the reaction shows a wide substrate scope that includes a variety of substituted allenamides and furans.

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Use of the p‐Tolylsulfinyl Group as a Chiral Inductor in Stereoselective [4+3] Cycloaddition Reactions: Preparation of Enantiopure Polysubstituted 8‐Oxabicyclo[3.2.1]oct‐6‐en‐3‐one Systems Having up to Five Stereocenters

Cited by 12 publications

References 75 publications

Addition Reactions: Cycloaddition

Addition Reactions: Cycloaddition

Enantioselective Oxidative (4+3) Cycloadditions between Allenamides and Furans through Bifunctional Hydrogen‐Bonding/Ion‐Pairing Interactions

Enantioselective Oxidative (4+3) Cycloadditions between Allenamides and Furans through Bifunctional Hydrogen‐Bonding/Ion‐Pairing Interactions

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