- Leveraging the n→π* Interaction in Alkene Isomerization by Selective Energy Transfer Catalysis
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Examples of geometric alkene isomerization in nature are often limited to the net exergonic direction (ΔG°0) comparatively under-represented. Inspired by the expansiveness of the maleate to fumarate (Z→E) isomerization in biochemistry, we investigated the inverse E→Z variant to validate nO→πC=O* interactions as a driving force for contra-thermodynamic isomerization. A general protocol involving selective energy transfer catalysis with inexpensive thioxanthone as a sensitizer (λmax=402 nm) is disclosed. Whilst in the enzymatic process nO→πC=O* interactions commonly manifest themselves in the substrate, these same interactions are shown to underpin directionality in the antipodal reaction by shortening the product alkene chromophore. The process was validated with diverse fumarate derivatives (>30 examples, up to Z:E>99:1), including the first examples of tetrasubstituted alkenes, and the involvement of nO→πC=O* interactions was confirmed by X-ray crystallography.
- Brüss, Linda,Daniliuc, Constantin G.,Gilmour, Ryan,McLaughlin, Calum,Molloy, John J.,Nevesely, Tomá?
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supporting information
(2021/11/30)
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- Discovery and Optimization of 7-Alkylidenyltetrahydroindazole-Based Acylsulfonamide EP3 Antagonists
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A novel series of 7-alkylidenyltetrahydroindazole-based acylsulfonamides were discovered as potent EP3 antagonists. The initial lead compound 7 exhibited potent in vitro EP3 inhibitory activity and good selectivity against other EP receptors. In addition,
- Zhu, Bin,Zhang, Xuqing,Guo, Lili,Rankin, Matthew,Bakaj, Ivona,Ho, George,Lee, Seunghun P.,Norquay, Lisa,Macielag, Mark
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supporting information
p. 111 - 117
(2021/12/17)
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- TEMPO-Enabled Electrochemical Enantioselective Oxidative Coupling of Secondary Acyclic Amines with Ketones
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An electrochemical asymmetric coupling of secondary acyclic amines with ketones via a Shono-type oxidation has been described, affording the corresponding amino acid derivatives with good to excellent diastereoselectivity and enantioselectivity. The addition of an N-oxyl radical as a redox mediator could selectively oxidize the substrate rather than the product, although their oxidation potential difference is subtle (about 13 mV). This electrochemical transformation proceeds in the absence of stoichiometric additives, including metals, oxidants, and electrolytes, which gives it good functional group compatibility. Mechanistic studies suggest that proton-mediated racemization of the product is prevented by the reduction of protons at the cathode.
- Gao, Jun-Qing,Gao, Pei-Sen,He, Zeng,Ma, Cong,Mei, Tian-Sheng,Wang, Xiu,Wang, Zhen-Hua,Xu, Xue-Tao
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supporting information
p. 15599 - 15605
(2021/10/02)
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- ACYLSUFONAMIDE COMPOUNDS USEFUL AS EP3 RECEPTOR ANTAGONISTS
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The present invention is directed to acylsulfonamide derivatives of formula (I), pharmaceutical compositions containing them and their use as antagonists of the EP3 receptor, for the treatment of, for example, impaired oral glucose tolerance, elevated fasting glucose, Type II Diabetes Mellitus, Syndrome X (also known as Metabolic Syndrome) and related disorders and complications thereof.
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Page/Page column 94
(2020/01/31)
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- Photoredox-Catalyzed Isomerization of Highly Substituted Allylic Alcohols by C?H Bond Activation
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Photoredox-catalyzed isomerization of γ-carbonyl-substituted allylic alcohols to their corresponding carbonyl compounds was achieved for the first time by C?H bond activation. This catalytic redox-neutral process resulted in the synthesis of 1,4-dicarbonyl compounds. Notably, allylic alcohols bearing tetrasubstituted olefins can also be transformed into their corresponding carbonyl compounds. Density functional theory calculations show that the carbonyl group at the γ-position of allylic alcohols are beneficial to the formation of their corresponding allylic alcohol radicals with high vertical electron affinity, which contributes to the completion of the photoredox catalytic cycle.
- Guo, Kai,Huang, Jun,Li, Anding,Li, Yuanhe,Yang, Zhen,Zhang, Zhongchao
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supporting information
p. 11660 - 11668
(2020/05/25)
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- Fe(III)-Catalyzed Diastereoselective Friedel-Crafts Alkylation-Hemiketalization-Lactonization Cascade for the Synthesis of Polycyclic Bridged 2-Chromanol Lactones
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An unprecedented Fe(III)-catalyzed Friedel-Crafts alkylation-hemiketalization-lactonization cascade of electron-rich hydroxy arenes and distinctively functionalized unsaturated 4-keto esters is developed for the construction of polycyclic bridged 2-chroma
- Borade, Balasaheb R.,Nomula, Rajesh,Gonnade, Rajesh G.,Kontham, Ravindar
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supporting information
p. 2629 - 2633
(2019/04/17)
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- Biocatalytic access to nonracemic γ-oxo esters: Via stereoselective reduction using ene-reductases
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The asymmetric bioreduction of α,β-unsaturated γ-keto esters using ene-reductases from the Old Yellow Enzyme family proceeds with excellent stereoselectivity and high conversion levels, covering a broad range of acyclic and cyclic derivatives. Various strategies were employed to provide access to both enantiomers, which are versatile precursors of bioactive molecules. The regioselectivity of hydride addition on di-activated alkenes was elucidated by isotopic labeling experiments and showed strong preference for the keto moiety as activating/binding group as opposed to the ester. Finally, chemoenzymatic synthesis of (R)-2-(2-oxocyclohexyl)acetic acid was achieved in high ee on a preparative scale combining enzymatic reduction followed by ester hydrogenolysis.
- Turrini, Nikolaus G.,Cioc, Rǎzvan C.,Van Der Niet, Daan J. H.,Ruijter, Eelco,Orru, Romano V. A.,Hall, Mélanie,Faber, Kurt
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supporting information
p. 511 - 518
(2017/08/14)
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- Microwave-assisted regioselective olefinations of cyclic mono- and di-ketones with a stabilized phosphorus ylide
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A number of cyclic mono- and di-ketones underwent regioselective olefination with (carbethoxyethylidene)triphenylphospharane under controlled microwave heating. The Wittig reaction of 4-substituted cyclohexanones or 1,2- and 1,4-cyclohexanediones with the ylide at 190 °C for 20 min in MeCN afforded the exocyclic olefins in >94:6 isomer ratios. On the other hand, the same reactions carried out at 230 °C for 20 min in the presence of 20 mol % DBU furnished the endocyclic olefins in >83:17 isomer ratios. The base-mediated isomerization of the exocyclic olefins into the endocyclic isomers was primarily driven by thermodynamic stability of the products and the effect of ring structures on deconjugation was examined.
- Wu, Jinlong,Li, Dan,Wu, Huafeng,Sun, Lijie,Dai, Wei-Min
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p. 4643 - 4650
(2007/10/03)
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- Divergent enantioselective synthesis of (-)-galanthamine and (-)-morphine
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An efficient divergent synthetic strategy for the synthesis of the opiate and amaryllidaceae alkaloids emerges by employing a Pd-catalyzed asymmetric allylic alkylation (AAA) to set the stereochemistry. Three generations of syntheses of galanthamine are discussed in detail with particular focus on the scope of the palladium-catalyzed AAA reactions and intramolecular Heck reactions. The pivotal tricyclic intermediate is available in six steps from 2-bromovanillin and the monoester of methyl 6-hydroxycyclohexene-1-carboxylate. This intermediate requires only two steps to convert to (-)-galanthamine. Using a Heck vinylation, we found that the fourth ring of codeine/morphine could be formed. The final ring formation involves a novel visible light-promoted hydroamination. Thus, six steps are required to convert the pivotal tricyclic intermediate into codeine, which has been demethylated in high yield to morphine.
- Trost, Barry M.,Tang, Weiping,Toste, F. Dean
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p. 14785 - 14803
(2007/10/03)
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- SYNTHESES DE CYCLOHEXENONES α-SUBSTITUEES VIA LA THERMOLYSE DE CETOSULFOXYDES TERTIAIRES
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The sulfenylation-dehydrosulfenylation method, combined with carbon-carbon bond forming reactions, has been applied to the synthesis of some α-functionalized cyclohexenones 3.Hence, the sodium anion of the 2-methylthiocyclohexanone in THF reacts with primary, allyl and benzyl halides as well as with Michael acceptors to lead to the tertiary ketosulfides 1a-j.Further oxidation by NaIO4 and thermolysis in boiling toluene of the resulting sulfoxides 2 have been performed.The scope and limitations of this strategy are also discussed. Key Words: α-functionalized cyclohexenones; tertiary ketosulfides and ketosulfoxides; sulfenylation and deshydrosulfenylation; thermolysis.
- Barillier, Daniel,Benhida, Rachid,Vazeux, Michel
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