Stereoselective [2+2]-Cycloadditions of chiral allenic ketones and alkenes: Applications towards the synthesis of benzocyclobutenes and endiandric acids

Guo, Renyu; Witherspoon, Brittany P.; Brown, M. Kevin

doi:10.1016/j.tet.2022.132932

Cited by 3 publications

(4 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was readily accomplished by oxidation of the cycloadducts (e.g., 5.17) with 5.18 . 40 Another congener of the aforementioned ladderane phospholipids is [3]-ladderanol, which contains a bicyclo[4.2.0]octane core. 3 The synthesis commenced with preparation of bicyclic enone 6.2 from β,γ-alkynyl ketone 6.1 on gram scale with control of diastereoselectivity and enantioselectivity (Scheme 6A).…”

Section: Chiral Allenic Ketonesmentioning

confidence: 99%

See 1 more Smart Citation

Lewis Acid-Promoted [2 + 2] Cycloadditions of Allenes and Ketenes: Versatile Methods for Natural Product Synthesis

Guo

Brown

2023

Acc. Chem. Res.

Self Cite

View full text Add to dashboard Cite

Conspectus Cycloaddition reactions are an effective method to quickly build molecular complexity. As predicted by the Woodward–Hoffmann rules, concerted cycloadditions with alkenes allow for the constructions of all possible stereoisomers of product by use of either the Z or E geometry. While this feature of cycloadditions is widely used in, for example, [4 + 2] cycloadditions, translation to [2 + 2] cycloadditions is challenging because of the often stepwise and therefore stereoconvergent nature of these processes. Over the past decade, our lab has explored Lewis acid-promoted [2 + 2] cycloadditions of electron-deficient allenes or ketenes with alkenes. The concerted, asynchronous cycloadditions allow for the synthesis of various cyclobutanes with control of stereochemistry. Our lab developed the first examples of Lewis acid-promoted ketene–alkene [2 + 2] cycloadditions. Compared with traditional thermal conditions, Lewis acid-promoted conditions have several advantages, such as increased reactivity, increased yield, improved diastereoselectivity, and, for certain cases, inverse diastereoselectivity. Detailed mechanistic studies revealed that the diastereoselectivity was controlled by the size of the substituent and the barrier of a deconjugation event. However, these reactions required the use of stoichiometric amounts of EtAlCl2 because of the product inhibition, which led us to investigate catalytic enantioselective [2 + 2] cycloadditions of allenoates with alkenes. Through the use of chiral oxazaborolidines, a broad range of cyclobutanes can be prepared with the control of enantioselectivity. Mechanistic experiments, including 2D-labled alkenes and Hammett analysis, illuminate likely transition state models for the cycloadditions. Additional studies led to the development of Lewis acid-catalyzed intramolecular stereoselective [2 + 2] cycloadditions of chiral allenic ketones/esters with alkenes. The methods we developed have been instrumental in the synthesis of several families of natural products. Specifically, one key lactone motif in (±)-gracilioether F was constructed by a ketene–alkene [2 + 2] cycloaddition and subsequent regioselective Baeyer–Villiger oxidation sequence. Enantioselective allenoate–alkene [2 + 2] cycloadditions allowed for the synthesis of (−)-hebelophyllene E. Another attempt of applying this method in the synthesis of (+)-[5]-ladderanoic acid failed to deliver the desired cyclobutane because of an unexpected rearrangement. The key cyclobutane was later assembled by a stepwise carboboration/Zweifel olefination process. Finally, the stereoselective [2 + 2] cycloadditions of allenic ketones and alkenes was applied in the syntheses of (−)-[3]-ladderanol, (+)-hippolide J, and (−)-cajanusine.

show abstract

Section: Chiral Allenic Ketonesmentioning

confidence: 99%

“…One direct application of the method was in the synthesis of benzocylobutenes (e.g., 5.19 ) (Scheme E). This was readily accomplished by oxidation of the cycloadducts (e.g., 5.17 ) with 5.18 …”

Section: Stereoselective [2 + 2] Cycloadditions Of Chiral Allenic Ket...mentioning

confidence: 99%

Lewis Acid-Promoted [2 + 2] Cycloadditions of Allenes and Ketenes: Versatile Methods for Natural Product Synthesis

Guo

Brown

2023

Acc. Chem. Res.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Isolable fused polycycles incorporating the 6–4 ring junction have been synthesized from a chirality transfer [2+2] cycloaddition using enantioenriched alkenyl allenones 107 (Scheme 21). [78,79] Compounds 107 have been generated in the reaction media from the isomerization of the corresponding alkynes 106 in the presence of optically pure urea catalyst 109 . Further [2+2] cycloaddition promoted by Bi(OTf) 3 has allowed the synthesis of a family of bicycles 108 tolerating both aryl and sterically hindered alkyl substituents.…”

Section: Synthetic Utilitymentioning

confidence: 99%

“…Adducts 108 have been employed for the enantioselective synthesis of ent ‐[3]‐ladderanol ( 110 ) (Scheme 21). [78,79] …”

Section: Synthetic Utilitymentioning

confidence: 99%

Highlighting the Rich Chemistry of the Allenone Moiety

Almendros

Alonso

2023

Adv Synth Catal

View full text Add to dashboard Cite

Conjugated and non-conjugated allenones appear as recurring motifs in organic synthesis, natural products and mechanistic investigations showing unique properties and applications. The ability of allenones to build cycles has provided a direct access to strained systems, medium-sized rings, arenes, heterocycles and complex polycycles. In addition, allenones have served as models in mechanistic investigations and catalysis. The critic compilation herein presented will provide an exhaustive overview of the synthetic possibilities allenones may offer, which certainly will inspire our community in their search of more efficient synthetic methodologies, preparation of biological and pharmaceutical targets, and improve our knowledge in theoretical organic chemistry. Great part of this review will discuss synthetic aspects, catalysis innovation and mechanistic insights of the chemical transformations implying the allenone motif. In addition, many examples on total synthesis and pharmacologically active compounds will be described. We hope that this overview will be attractive to the organic chemistry, synthetic chemistry, catalysis, theoretical chemistry, natural products and medicinal chemistry communities. 3.5. Synthesis of Spirocycles and Bridged Structures 3.6. Open-Chain Structures from Allenones 3.7. Allenones in Total Synthesis 4.

show abstract