Lithiated three-membered heterocycles as chiral nucleophiles in the enantioselective synthesis of 1-oxaspiro[2,3]hexanes

Cocco, Andrea; Rubanu, Maria Grazia; Sechi, Maria Laura; Frongia, Angelo; Mastrorilli, Pietro; Degennaro, Leonardo; Colella, Marco; Luisi, Renzo; Secci, Francesco

doi:10.1039/d0ob00771d

“…The cis-stereoisomer underwent Payne rearrangement under basic conditions, leading to the desired 1-azaspiro[2,3]hexane (338) (Scheme 59). 94 Aziridines were also reported to be useful catalysts. 95 Rachwalski and co-workers described an asymmetric Morita-Baylis-Hillman reaction of methyl vinyl ketone and methyl acrylate (339) with various aromatic aldehydes (340) using chiral aziridine-phosphines (341) as chiral catalysts (Scheme 60).…”

Section: Organic and Biomolecular Chemistry Reviewmentioning

confidence: 99%

“…The cis -stereoisomer underwent Payne rearrangement under basic conditions, leading to the desired 1-azaspiro[2,3]hexane ( 338 ) (Scheme 59). 94…”

Section: Aziridines As Reaction Intermediates and Catalystsmentioning

confidence: 99%

Recent advances in the accessibility, synthetic utility, and biological applications of aziridines

Dank

¹

,

Ielo

²

2023

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“…[5] Moreover these three-dimensional motifs provide a gateway beyond the flat (twodimensional) structures that have long dominated small molecule screening libraries. [6] 1-Oxaspiro [2.3]hexanes 1 are commonly obtained from cyclobutanones, either by reaction with a carbenoid (e.g., sulfur ylides), [1,7] or via olefination and subsequent epoxidation [1,8] of the resulting methylene cyclobutane. [9] However, for the introduction of different functional groups onto the cyclobutane ring, these strategies require this functionality to be pre-installed in the cyclobutanone starting material.…”

Section: Introductionmentioning

confidence: 99%

Strain‐Release Driven Epoxidation and Aziridination of Bicyclo[1.1.0]butanes via Palladium Catalyzed σ‐Bond Nucleopalladation

Wölfl

¹

,

Winter

²

,

Li

³

et al. 2023

Angewandte Chemie

1

0

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The development of preparative methods for the synthesis of four-membered carbocycles is gaining increasing importance due to the widespread utility of cyclic compounds in medicinal chemistry. Herein, we report the development of a new methodology for the production of spirocyclic epoxides and aziridines containing a cyclobutane motif. In a two-step one-pot process, a bicyclo[1.1.0]butyl sulfoxide is lithiated and added to a ketone, aldehyde or imine, and the resulting intermediate is cross-coupled with an aryl triflate through CÀ C σ-bond alkoxy-or aminopalladation with concomitant epoxide or aziridine formation. After careful optimization, a remarkably efficient reaction was conceived that tolerated a broad variety of both aromatic and aliphatic substrates. Lastly, through several high yielding ring-opening reactions, we demonstrated the excellent applicability of the products as modular building blocks for the introduction of threedimensional structures into target molecules.

show abstract

Strain‐Release Driven Epoxidation and Aziridination of Bicyclo[1.1.0]butanes via Palladium Catalyzed σ‐Bond Nucleopalladation

Wölfl

¹

,

Winter

²

,

Li

³

et al. 2023

View full text Add to dashboard Cite

The development of preparative methods for the synthesis of four-membered carbocycles is gaining increasing importance due to the widespread utility of cyclic compounds in medicinal chemistry. Herein, we report the development of a new methodology for the production of spirocyclic epoxides and aziridines containing a cyclobutane motif. In a two-step one-pot process, a bicyclo[1.1.0]butyl sulfoxide is lithiated and added to a ketone, aldehyde or imine, and the resulting intermediate is cross-coupled with an aryl triflate through CÀ C σ-bond alkoxy-or aminopalladation with concomitant epoxide or aziridine formation. After careful optimization, a remarkably efficient reaction was conceived that tolerated a broad variety of both aromatic and aliphatic substrates. Lastly, through several high yielding ring-opening reactions, we demonstrated the excellent applicability of the products as modular building blocks for the introduction of threedimensional structures into target molecules.

show abstract

Lithiated three-membered heterocycles as chiral nucleophiles in the enantioselective synthesis of 1-oxaspiro[2,3]hexanes

Abstract: The reaction between configurably stable -lithiated oxiranes (and aziridines) and 3-substituted cyclobutanones allows to obtain enantiomerically enriched cyclobutanols (er > 98:2). These adducts, subjected to base-mediated Payne rearrangement lead to...

Cited by 4 publications

References 55 publications

Recent advances in the accessibility, synthetic utility, and biological applications of aziridines

Recent advances in the accessibility, synthetic utility, and biological applications of aziridines

Strain‐Release Driven Epoxidation and Aziridination of Bicyclo[1.1.0]butanes via Palladium Catalyzed σ‐Bond Nucleopalladation

Strain‐Release Driven Epoxidation and Aziridination of Bicyclo[1.1.0]butanes via Palladium Catalyzed σ‐Bond Nucleopalladation

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