New Strategy To Access Enantioenriched Cyclohexadienones: Kinetic Resolution of <i>para</i>-Quinols by Organocatalytic Thiol-Michael Addition Reactions

Tang, Ting; Moon, Nicholas G.; McKay, Lydia; Harned, Andrew M.

doi:10.1021/acsomega.8b01787

Cited by 12 publications

(9 citation statements)

References 87 publications

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“…After screening various catalysts, it was observed that catalyst 93 appeared to be the best which provided Michael addition to para ‐quinol 89 as a single diastereomer 91 and unreacted enantiomer of para ‐quinol 92 (Scheme 11). [48] …”

Section: Asymmetric Synthesismentioning

confidence: 99%

“…After screening various catalysts, it was observed that catalyst 93 appeared to be the best which provided Michael addition to para-quinol 89 as a single diastereomer 91 and unreacted enantiomer of para-quinol 92 (Scheme 11). [48] Tian and co-workers developed a method of kinetic resolution of nonactivated terminal alkene-tethered 2,5-cyclohexadienone 94 with rhodium (III)-catalyst 98. Bis (pinacolato) diboron (B 2 pin 2 ) 95, promoted asymmetric borylative cyclization of compound 94, provided recovered cyclohexadienone 96 and cis-hydrobenzofuranone 97 with excellent yield and enantioselectivity (up to 99 % ee).…”

Section: Through Kinetic Resolutionmentioning

confidence: 99%

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Molecular Complexity from Aromatics: Recent Advances in the Chemistry of paraQuinol and Masked para‐Quinone Monoketal

Chandra

Patel

2020

ChemistrySelect

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Synthesis of complex organic molecules from simple, cheap, and readily available starting materials is one of the most challenging and desirable factors in organic synthesis. In the last two decades, various methods have been developed for the de-aromatization reaction of planar aromatics compounds which lead to reactive intermediates like 2,5-cyclohexadienone ketal and para-quinol having a non-planar framework. Recently, there is an upsurge of interest in the development of the chemistry of these intermediates due to their inherent dual electrophilic and nucleophilic character. The presence of diverse functionality makes them important scaffolds and thus these are intensively utilized for the development of methodologies towards the synthesis of the highly functionalized and diverse chemical framework. These synthons have also been used in the total synthesis of many natural products. Interestingly, these are also adaptable for asymmetric synthesis. This review is a summary of the recent development of methods for 2,5-cyclohexadienone ketal and para-quinol synthesis and their application in natural product synthesis.

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Section: Asymmetric Synthesismentioning

confidence: 99%

Section: Through Kinetic Resolutionmentioning

confidence: 99%

Molecular Complexity from Aromatics: Recent Advances in the Chemistry of paraQuinol and Masked para‐Quinone Monoketal

Chandra

Patel

2020

ChemistrySelect

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“…Reaction rates can be markedly enhanced by substitution at the phenyl moiety: Trifluoromethyl substitution of diphenylthiourea greatly enhances reaction rates and yields. , This enhancement has been primarily ascribed to electronic effects as the electron-withdrawing trifluoromethyl groups increase the acidity of the N–H groups, , enhance π–π interactions, , and enhance the polarity of the ortho-protons of the phenyl ring . Additionally, the choice of the solvent can affect catalytic efficiency . Yet, substitution at the phenyl ring (e.g., trifluoromethyl) and solvents can also affect conformational equilibria and thereby affect catalytic activity. − …”

Section: Introductionmentioning

confidence: 99%

Elucidating Conformation and Hydrogen-Bonding Motifs of Reactive Thiourea Intermediates

et al. 2022

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Substituted diphenylthioureas (DPTUs) are efficient hydrogen-bonding organo-catalysts, and substitution of DPTUs has been shown to greatly affect catalytic activity. Yet, both the conformation of DPTUs in solution and the conformation and hydrogen-bonded motifs within catalytically active intermediates, pertinent to their mode of activation, have remained elusive. By combining linear and ultrafast vibrational spectroscopy with spectroscopic simulations and calculations, we show that different conformational states of thioureas give rise to distinctively different N−H stretching bands in the infrared spectra. In the absence of hydrogen-bond-accepting substrates, we show that vibrational structure and dynamics are highly sensitive to the substitution of DPTUs with CF 3 groups and to the interaction with the solvent environment, allowing for disentangling the different conformational states. In contrast to bare diphenylthiourea (0CF-DPTU), we find the catalytically superior CF 3 -substituted DPTU (4CF-DPTU) to favor the trans−trans conformation in solution, allowing for donating two hydrogen bonds to the reactive substrate. In the presence of a prototypical substrate, DPTUs in trans−trans conformation hydrogen bond to the substrate's C�O group, as evidenced by a red-shift of the N−H vibration. Yet, our time-resolved infrared experiments indicate that only one N−H group forms a strong hydrogen bond to the carbonyl moiety, while thiourea's second N−H group only weakly interacts with the substrate. Our data indicate that hydrogen-bond exchange between these N−H groups occurs on the timescale of a few picoseconds for 0CF-DPTU and is significantly accelerated upon CF 3 substitution. Our results highlight the subtle interplay between conformational equilibria, bonding states, and bonding lifetimes in reactive intermediates in thiourea catalysis, which help rationalize their catalytic activity.

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“…Kinetic resolution as one, which converts racemic dienone into an enantiomerically enriched product and recovered chiral non-racemic cyclohexadienone (Figure 2a). [5] Prochiral dienones are C 2 -symmetric molecules containing enantiotopic faces (ring surfaces) and enantiotopic groups (olefins and carbonyl group) that could provide four possible stereoisomers from conjugate addition reaction (Figure 2b). Enantioselective desymmetrization could generate enantioenriched products containing one or more stereocenters from C 2 -symmetric 2,5cyclohexadienones, which involves the differentiation of enantiotopic faces and groups with designed chiral catalysts or ligands.…”

Section: Introductionmentioning

confidence: 99%

Transition‐Metal Catalyzed Stereoselective Desymmetrization of Prochiral Cyclohexadienones

Munakala

Phanindrudu

Chegondi

2021

The Chemical Record

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The development of transition-metal catalyzed enantioselective and diastereoselective transformations has contributed many advances in the field of synthetic organic chemistry. Particularly, stereoselective desymmetrization of prochiral cyclohexadienones represents a powerful strategy for accessing highly functionalized and stereochemically enriched scaffolds, which are often found in biologically active compounds and natural products. In recent years, several research groups including our group have made a significant progress on transition-metal catalyzed stereoselective desymmetrizations of 2,5-cyclohexadienones. In this account, we will provide an overview of the recent developments in this area employing Pd, Cu, Rh, Au, Ag, Ni, Co, and Mn-catalysts.

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New Strategy To Access Enantioenriched Cyclohexadienones: Kinetic Resolution of para-Quinols by Organocatalytic Thiol-Michael Addition Reactions

Cited by 12 publications

References 87 publications

Molecular Complexity from Aromatics: Recent Advances in the Chemistry of paraQuinol and Masked para‐Quinone Monoketal

Molecular Complexity from Aromatics: Recent Advances in the Chemistry of paraQuinol and Masked para‐Quinone Monoketal

Elucidating Conformation and Hydrogen-Bonding Motifs of Reactive Thiourea Intermediates

Transition‐Metal Catalyzed Stereoselective Desymmetrization of Prochiral Cyclohexadienones

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