Oxonium Ylide Rearrangements in Synthesis

Murphy, Graham K.; West, F. G.

doi:10.1002/9781118939901.ch16

Cited by 11 publications

(11 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Onium ylides [1][2][3][4][5] , including sulfur 6a-d , oxonium 7 and ammonium, 8a,b are common intermediates employed in the syntheses of complex molecules. They are typically generated from the reaction of a heteroatom with a metal-supported carbene to furnish reactive zwitterionic intermediates that engage in a diverse set of reaction pathways, including 1,2-Stevens rearrangements, 8b 2,3-sigmatropic rearrangements, 9 and NH insertion reactions (Scheme 1A).…”

Section: Introductionmentioning

confidence: 99%

Tunable aziridinium ylide reactivity: non-covalent interactions enable divergent product outcomes

Nicastri

Zappia

Pratt

et al. 2021

Preprint

View full text Add to dashboard Cite

Methods for rapid preparation of densely functionalized and stereochemically complex N-heterocyclic scaffolds are in demand for exploring potential new bioactive chemical space. This work describes experimental and computational studies to better understand the features of aziridinium ylides as intermediates for the synthesis of highly substituted dehydromorpholines. The development of this chemistry has enabled the extension of aziridinium ylide chemistry to the concomitant formation of both a C–N and a C–O bond in a manner that preserves the stereochemical information embedded in the substrate. The chemistry is tolerant of a wide range of functionalities that can be employed for DNA-encoded library (DEL) synthesis to prepare diverse libraries of heterocycles with potential bioactivity. In addition, we have uncovered several key insights that describe the importance of steric effects, rotational barriers around the C–N bond of the aziridinium ylide, and non-covalent interactions (NCIs) on the ultimate reaction outcome. These critical insights will assist in the further development of this chemistry to generate novel and complex N-heterocycles that will further expand complex amine chemical space.

show abstract

Section: Introductionmentioning

confidence: 99%

Tunable aziridinium ylide reactivity: non-covalent interactions enable divergent product outcomes

Nicastri

Zappia

Pratt

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“… 4 , 5 , 23 − 27 Furthermore, this intramolecular O–C allyl transfer is representative of the broader class of anionic sigmatropic rearrangements. 22 While significant advances have been made toward enantioselective catalysis of rearrangements with related ylides, 5 , 6 , 28 − 32 development of a general, catalytic, enantioselective [2,3]-Wittig rearrangement has lagged. 7 , 8 Accordingly, the transformation has been the subject of intense interest, and during the preparation of this manuscript, two methods for the enantioselective [2,3]-Wittig rearrangement of allyloxyoxindoles were disclosed.…”

Section: Introductionmentioning

confidence: 99%

“…Application of the [2,3]-Wittig rearrangement to the synthesis of hindered homoallylic alcohol fragments in a variety of natural products and pharmaceutical agents stands as a testament to its utility. ,,− Furthermore, this intramolecular O–C allyl transfer is representative of the broader class of anionic sigmatropic rearrangements . While significant advances have been made toward enantioselective catalysis of rearrangements with related ylides, ,,− development of a general, catalytic, enantioselective [2,3]-Wittig rearrangement has lagged. , Accordingly, the transformation has been the subject of intense interest, and during the preparation of this manuscript, two methods for the enantioselective [2,3]-Wittig rearrangement of allyloxyoxindoles were disclosed. , The work described here is complementary in scope to these methods, and we posit that the synergistic ion-binding approach it demonstrates can be extended to enable other anionic sigmatropic rearrangements and related transformations, which have hitherto resisted asymmetric catalysis.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Ion-Binding Catalysis Demonstrated via an Enantioselective, Catalytic [2,3]-Wittig Rearrangement

2016

View full text Add to dashboard Cite

Sigmatropic rearrangements number among the most powerful complexity-building transformations in organic synthesis but have remained largely insensitive to enantioselective catalysis due to the diffuse nature of their transition structures. Here, we describe a synergistic ion-binding strategy for asymmetric catalysis of anionic sigmatropic rearrangements. This approach is demonstrated with the enantioselective [2,3]-Wittig rearrangement of α-allyloxy carbonyl compounds to afford highly enantioenriched homoallylic alcohol products. Chiral thiourea catalysts are shown to engage reactive anions and their countercations through a cooperative set of attractive, noncovalent interactions. Catalyst structure–reactivity–selectivity relationship studies and computational analyses provide insight into catalyst–substrate interactions responsible for enantioinduction and allude to the potential generality of this catalytic strategy.

show abstract

“…Molecular rearrangements are arguably some of the most effective reactions for the generation of new carbon–carbon bonds in the synthesis of complex molecules . In recent years, advances in catalytic onium ylide rearrangements have paved the way for catalyst control of rearrangements that are traditionally unselective. , In this context, catalytic generation of onium ylides from diazocarbonyl compounds has served as a versatile platform for selective rearrangements (Scheme A). Despite many reports of catalytic onium ylide rearrangements of aliphatic systems, , only a few examples of analogous aromatic rearrangements are known which are limited to sulfonium (X = SR) and ammonium (X = NR 2 ) ylides .…”

Section: Introductionmentioning

confidence: 99%

Catalyst-Controlled Regiodivergence in Rearrangements of Indole-Based Onium Ylides

et al. 2021

View full text Add to dashboard Cite

We have developed catalyst-controlled regiodivergent rearrangements of onium-ylides derived from indole substrates. Oxonium ylides formed in situ from substituted indoles selectively undergo [2,3]-and [1,2]-rearrangements in the presence of a rhodium and copper catalyst, respectively. The combined experimental and density functional theory (DFT) computational studies indicate divergent mechanistic pathways involving a metal-free ylide in the rhodium catalyzed reaction favoring [2,3]-rearrangement, and a metal-coordinated ion-pair in the copper catalyzed [1,2]-rearrangement that recombines in the solvent-cage. The application of our methodology was demonstrated in the first total synthesis of the indole alkaloid (±)-sorazolon B, which enabled the stereochemical reassignment of the natural product. Further functional group transformations of the rearrangement products to generate valuable synthetic intermediates were also demonstrated.

show abstract

Oxonium Ylide Rearrangements in Synthesis

Cited by 11 publications

References 51 publications

Tunable aziridinium ylide reactivity: non-covalent interactions enable divergent product outcomes

Tunable aziridinium ylide reactivity: non-covalent interactions enable divergent product outcomes

Synergistic Ion-Binding Catalysis Demonstrated via an Enantioselective, Catalytic [2,3]-Wittig Rearrangement

Catalyst-Controlled Regiodivergence in Rearrangements of Indole-Based Onium Ylides

Contact Info

Product

Resources

About