Confronting the Challenging Asymmetric Addition of Vinyl Arene Pronucleophiles into Ketones: Ligand-Controlled Regiodivergent Processes Through a Dearomatized Allyl-Cu Species DOI Creative Commons
Yuyang Dong, Alexander W. Schuppe, Binh Khanh

et al.

Published: Nov. 19, 2021

The selective reductive coupling of vinyl arenes and ketones represents a versatile approach for the rapid construction enantiomerically enriched tertiary alcohols. Herein, we demonstrate CuH-catalyzed regiodivergent ketones, in which selectivity is controlled by ancillary ligand. This leverages an situ generated benzyl- or dearomatized allyl-Cu intermediate, yielding either exocyclic addition products, respectively. method exhibits excellent regio-, diastereo- enantioselectivity, tolerates range common functional groups heterocycles. Computational studies suggest that regio- enantioselectivity are ligand, while diastereoselectivity enforced steric interactions between alkyl-Cu intermediate ketone substrates six-membered cyclic transition state.

Language: Английский

Diastereoselective Indole-Dearomative Cope Rearrangements by Compounding Minor Driving Forces. DOI Creative Commons

Subhadip De,

Breanna Tomiczek,

Yinuo Yang

et al.

Published: Jan. 10, 2022

Reported herein is the discovery of a diastereoselective indole-dearomative Cope rearrangement. A suite minor driving forces (substrate destabilizing effects; product stabilizing effects) are what promote this otherwise unfavorable dearomatization reaction. These include following that work in concert to overcome penalty for dearomatization: (i.) steric congestion starting material, (ii.) alkylidene malononitrile and stilbene conjugation events product, (iii.) an unexpected intramolecular p–p* stack on side equilibrium. The key substrates rapidly assembled from alkylidenemalononitriles indole-phenylmethanol derivatives resulting many successful examples (high yields diastereoselectivity). products structurally complex bearing vicinal stereocenters generated by dearomative They also contain variety functional groups interconversion architectures. On line, described proof-of-concept strategies achieving enantioselectivity conversion valuable functionalized small drug-like molecules.

Language: Английский

Citations

1
Carbodefluorination via a carbene-initiated rearrangement strategy DOI Creative Commons
Linxuan Li, Xinyu Zhang, Yongquan Ning

et al.

Published: March 1, 2022

The C–F bond cleavage and C–C formation (i.e., carbodefluorination) of readily accessible (per)fluoroalkyl groups constitutes an atom-economical efficient route to partially fluorinated compounds. However, the selective mono-carbodefluorination trifluoromethyl (CF3) remains a formidable challenge, due notorious inertness risk over-defluorination arising from strength decrease as defluorination proceeds. Herein, we report carbene-initiated rearrangement strategy for carbodefluorination fluoroalkyl ketones with β,γ-unsaturated alcohols. reaction starts silver carbene ketone N-triftosylhydrazone, followed by nucleophilic addition alcohol form key oxonium ylide intermediate, which triggers HF elimination through Claisen in situ generated difluorovinyl ether. This method described here is versatile enables conversion into skeletally functionally diverse α-mono- α,α-difluoro-γ,δ-unsaturated ketones. mechanism origin chemoselectivity were established experimental computational approaches. Collectively, current integrates successive on single molecule entity intramolecular cascade process, thereby offering significant advances over existing stepwise strategies term selectivity, efficiency, functional group tolerance, etc.

Language: Английский

Citations

1
Confronting the Challenging Asymmetric Addition of Vinyl Arene Pronucleophiles into Ketones: Ligand-Controlled Regiodivergent Processes Through a Dearomatized Allyl-Cu Species DOI Creative Commons
Yuyang Dong, Alexander W. Schuppe, Binh Khanh

et al.

Published: Nov. 30, 2021

The selective reductive coupling of vinyl arenes and ketones represents a versatile approach for the rapid construction enantiomerically enriched tertiary alcohols. Herein, we demonstrate CuH-catalyzed regiodivergent ketones, in which selectivity is controlled by ancillary ligand. This leverages an situ generated benzyl- or dearomatized allyl-Cu intermediate, yielding either exocyclic addition products, respectively. method exhibits excellent regio-, diastereo- enantioselectivity, tolerates range common functional groups heterocycles. Computational studies suggest that regio- enantioselectivity are ligand, while diastereoselectivity enforced steric interactions between alkyl-Cu intermediate ketone substrates six-membered cyclic transition state.

Language: Английский

Citations

0
Confronting the Challenging Asymmetric Addition of Vinyl Arene Pronucleophiles into Ketones: Ligand-Controlled Regiodivergent Processes Through a Dearomatized Allyl-Cu Species DOI Creative Commons
Yuyang Dong, Alexander W. Schuppe, Binh Khanh

et al.

Published: Nov. 19, 2021

The selective reductive coupling of vinyl arenes and ketones represents a versatile approach for the rapid construction enantiomerically enriched tertiary alcohols. Herein, we demonstrate CuH-catalyzed regiodivergent ketones, in which selectivity is controlled by ancillary ligand. This leverages an situ generated benzyl- or dearomatized allyl-Cu intermediate, yielding either exocyclic addition products, respectively. method exhibits excellent regio-, diastereo- enantioselectivity, tolerates range common functional groups heterocycles. Computational studies suggest that regio- enantioselectivity are ligand, while diastereoselectivity enforced steric interactions between alkyl-Cu intermediate ketone substrates six-membered cyclic transition state.

Language: Английский

Citations

0