Rotational Isomers of <i>N</i>-Methyl-<i>N</i>-arylacetamides and Their Derived Enolates: Implications for Asymmetric Hartwig Oxindole Cyclizations

Mandel, Jérémie; Pan, Xiaohong; Hay, E. Ben; Geib, Steven J.; Wilcox, Craig S.; Curran, Dennis P.

doi:10.1021/jo400385t

Cited by 14 publications

(9 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A negative correlation between δ CO and the rotational barriers was also observed (Figure b). Those results are consistent with the idea that pyramidalization of the nitrogen atom significantly affects the N–Ar bond rotation . Therefore, the atropostability of chiral anilides is governed by both steric and electronic effects …”

Section: Resultssupporting

confidence: 91%

Enantioselective Synthesis of Atropisomeric Anilides via Pd(II)-Catalyzed Asymmetric C–H Olefination

et al. 2020

View full text Add to dashboard Cite

Atropisomeric anilides have received tremendous attention as a novel class of chiral compounds possessing restricted rotation around an N-aryl chiral axis. However, in sharp contrast to the well-studied synthesis of biaryl atropisomers, the catalytic asymmetric synthesis of chiral anilides remains a daunting challenge, largely due to the higher degree of rotational freedom compared to their biaryl counterparts. Here we describe a highly efficient catalytic asymmetric synthesis of atropisomeric anilides via Pd(II)-catalyzed atroposelective C−H olefination using readily available L-pyroglutamic acid as a chiral ligand. A broad range of atropisomeric anilides were prepared in high yields (up to 99% yield) and excellent stereoinduction (up to >99% ee) under mild conditions. Experimental studies indicated that the atropostability of those anilide atropisomers toward racemization relies on both steric and electronic effects. Experimental and computational studies were conducted to elucidate the reaction mechanism and rate-determining step. DFT calculations revealed that the amino acid ligand distortion is responsible for the enantioselectivity in the C−H bond activation step. The potent applications of the anilide atropisomers as a new type of chiral ligand in Rh(III)-catalyzed asymmetric conjugate addition and Lewis base catalysts in enantioselective allylation of aldehydes have been demonstrated. This strategy could provide a straightforward route to access atropisomeric anilides, one of the most challenging types of axially chiral compounds.

show abstract

Section: Resultssupporting

confidence: 91%

Enantioselective Synthesis of Atropisomeric Anilides via Pd(II)-Catalyzed Asymmetric C–H Olefination

et al. 2020

View full text Add to dashboard Cite

show abstract

“…17 This amide is a 70/30 mixtures of diastereomers according to 1 H NMR analysis. These must be the E-rotamers of the two possible diastereomers created by the stereocenter and the N–Ar axis.…”

Section: Resultsmentioning

confidence: 99%

“…Related diastereomers with higher N–Ar rotation barriers have been separated and shown to give the same products on radical cyclization. 17a So separation is pointless because the two diastereomers of 24 will give the same radical and hence the same result on radical cyclization.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Radical Cyclizations of Cyclic Ene Sulfonamides Occur with β-Elimination of Sulfonyl Radicals to Form Polycyclic Imines

et al. 2013

Self Cite

View full text Add to dashboard Cite

Radical cyclizations of cyclic ene sulfonamides provide stable bicyclic and tricyclic aldimines and ketimines in good yields. Depending on the structure of the precursor, the cyclizations occur to provide fused and spirocyclic imines with five-, six-, and seven-membered rings. The initial radical cyclization produces an α-sulfonamidoyl radical that undergoes elimination to form the imine and a phenylsulfonyl radical. In a related method, 3,4-dihydroquinolines can also be produced by radical translocation reactions of N-(2-iodophenylsulfonyl)tetrahydroisoquinolines. In either case, very stable sulfonamides are cleaved to form imines (rather than amines) under mild reductive conditions.

show abstract

“…The N-Ar rotation barrier of a 2-phenylacetamide analog was reduced from 31 kcal mol −1 in the precursor to 17 kcal mol −1 in the enolate. This dramatic barrier reduction has implications of both N-Ar and amide C-N rotations [8].…”

Section: Introductionmentioning

confidence: 99%

Understanding Chemistry and Unique NMR Characters of Novel Amide and Ester Leflunomide Analogues

et al. 2017

View full text Add to dashboard Cite

A series of diverse substituted 5-methyl-isoxazole-4-carboxylic acid amides, imide and esters in which the benzene ring is mono or disubstituted was prepared. Spectroscopic and conformational examination was investigated and a new insight involving steric interference and interesting downfield deviation due to additional diamagnetic anisotropic effect of the amidic carbonyl group and the methine protons in 2,6-diisopropyl-aryl derivative (2) as conformationaly restricted analogues Leflunomide was discussed. Individual substituent electronic effects through π resonance of p-substituents and most stable conformation of compound (2) are discussed.

show abstract

Rotational Isomers of N-Methyl-N-arylacetamides and Their Derived Enolates: Implications for Asymmetric Hartwig Oxindole Cyclizations

Cited by 14 publications

References 57 publications

Enantioselective Synthesis of Atropisomeric Anilides via Pd(II)-Catalyzed Asymmetric C–H Olefination

Enantioselective Synthesis of Atropisomeric Anilides via Pd(II)-Catalyzed Asymmetric C–H Olefination

Radical Cyclizations of Cyclic Ene Sulfonamides Occur with β-Elimination of Sulfonyl Radicals to Form Polycyclic Imines

Understanding Chemistry and Unique NMR Characters of Novel Amide and Ester Leflunomide Analogues

Contact Info

Product

Resources

About