Enantioselective Synthesis of Cyclic, Quaternary Oxonitriles

Güneş, Yakup; Polat, M. Fatih; Şahin, Ertan; Fleming, Fraser F.; Altundaş, Ramazan

doi:10.1021/jo1011202

Cited by 8 publications

(5 citation statements)

References 58 publications

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“…Treating the enantiopure allylic alcohols 6i – 6m with NaH and 15‐crown‐5 gave the respective alkoxyalkenenitriles, which were then thermolyzed to give the corresponding oxonitriles (Table 2). Allylic alcohols 6i , 6j , and 6k 5 gave the allyl ketones in good yields (Table 2, entries 1–3). The determination of the enantiopurity of 8i – 8k by GC or HPLC proved difficult 15.…”

Section: Resultsmentioning

confidence: 98%

“…The high efficiency and excellent predictability of the Claisen rearrangement has proved to be exceptionally well suited for the installation of quaternary centers in oxonitriles (Scheme ) 3. Detailed studies with five‐membered‐ring α‐ketonitriles identified CCl 4 /Ph 3 P as an ideal combination of reagents for converting oxonitrile 1 into chloroalkenecarbonitriles 2 ,4 which react with alkoxides in an addition–rearrangement protocol ( 2 → 3 → 4 ) 5…”

Section: Introductionmentioning

confidence: 99%

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Enantioselective Installation of Quaternary Centers in Cyclic Oxonitriles

et al. 2015

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Quaternary centers are rapidly and selectively installed in a series of seven‐membered and bridged cyclic oxonitriles through conjugate addition of an alkoxide to chloroalkenenitriles, followed by a Claisen rearrangement. Using this strategy, the stereogenic information of the carbinol in secondary allylic alcohols is transferred to the newly generated quaternary center. Experimentally, the sequence rapidly gives alkyl cyanocycloheptanones and bicycloalkanonecarbonitriles in good yield and with high selectivity, in a single synthetic operation.

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Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Enantioselective Installation of Quaternary Centers in Cyclic Oxonitriles

et al. 2015

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“…However, difficulties in the preparation of the latter as well as its commercial availability led us to undertake a different synthetic route entiling the preparation of ethyl carboxylate intermediate 43 and its successive transformation into carboxamide derivative 45 . In particular, cycloheptanone was reacted with DMF and POCl 3 to give intermediate 41 [ 43 ] that was used for the preparation of compound 42 [ 44 ] by reaction with hydroxylamine hydrochloride in N -methyl-2-pyrrolidinone (NMP). Intermediate 42 was then reacted with ethyl thioglycolate in presence of K 2 CO 3 in a MeOH/THF mixture, to give compound 43 [ 45 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis and characterization of 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide-based compounds targeting the PA-PB1 interface of influenza A virus polymerase

Massari

Bertagnin

Pismataro

et al. 2021

European Journal of Medicinal Chemistry

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Influenza viruses (Flu) are responsible for seasonal epidemics causing high rates of morbidity, which can dramatically increase during severe pandemic outbreaks. Antiviral drugs are an indispensable weapon to treat infected people and reduce the impact on human health, nevertheless anti-Flu armamentarium still remains inadequate. In search for new anti-Flu drugs, our group has focused on viral RNA-dependent RNA polymerase (RdRP) developing disruptors of PA-PB1 subunits interface with the best compounds characterized by cycloheptathiophene-3-carboxamide and 1,2,4-triazolo[1,5- a ]pyrimidine-2-carboxamide scaffolds. By merging these moieties, two very interesting hybrid compounds were recently identified, starting from which, in this paper, a series of analogues were designed and synthesized. In particular, a thorough exploration of the cycloheptathiophene-3-carboxamide moiety led to acquire important SAR insight and identify new active compounds showing both the ability to inhibit PA-PB1 interaction and viral replication in the micromolar range and at non-toxic concentrations. For few compounds, the ability to efficiently inhibit PA-PB1 subunits interaction did not translate into anti-Flu activity. Chemical/physical properties were investigated for a couple of compounds suggesting that the low solubility of compound 14 , due to a strong crystal lattice, may have impaired its antiviral activity. Finally, computational studies performed on compound 23 , in which the phenyl ring suitably replaced the cycloheptathiophene, suggested that, in addition to hydrophobic interactions, H-bonds enhanced its binding within the PA C cavity.

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“…Chiral allylic alcohols are important natural products [ 11 ] and the key intermediates for many stereospecific reactions, such as Claisen rearrangement [ 20 ], epoxidation [ 21 ], and S N 2′ displacement with organometallic regents [ 22 ]. However, the reports concerning oxazaborolidine catalysis for the reduction of α,β-enones are very limited, probably due to the occurrence of a side reaction, i.e., hydroboration.…”

Section: Asymmetric Reduction Of αβ-Enonesmentioning

confidence: 99%

Practical Enantioselective Reduction of Ketones Using Oxazaborolidine Catalysts Generated In Situ from Chiral Lactam Alcohols

Kawanami

Yanagita

2018

Molecules

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Oxazaborolidine catalyst (CBS catalyst) has been extensively used for catalytic borane reduction with a predictable absolute stereochemistry and high enantioselectivity. However, the use of isolated CBS catalyst sometimes has the drawback of low reproducibility due to the aging of the CBS catalyst during storage. Therefore, we investigated a more reliable and practical method for the reduction of a variety of ketones including challenging substrates, primary aliphatic ketones, α,β-enones, and trifluoromethyl ketones. This review surveys the developments in borane reduction using oxazaborolidine catalysts generated in situ from chiral lactam alcohols and borane.

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Enantioselective Synthesis of Cyclic, Quaternary Oxonitriles

Cited by 8 publications

References 58 publications

Enantioselective Installation of Quaternary Centers in Cyclic Oxonitriles

Enantioselective Installation of Quaternary Centers in Cyclic Oxonitriles

Synthesis and characterization of 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide-based compounds targeting the PA-PB1 interface of influenza A virus polymerase

Practical Enantioselective Reduction of Ketones Using Oxazaborolidine Catalysts Generated In Situ from Chiral Lactam Alcohols

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