<i>N</i>-Nitromethylphthalimide. A formyl anion equivalent

Cowherd, Frank G.; Doria, Marie-Carmen; Galeazzi, E.; Muchowski, Joseph M.

doi:10.1139/v77-405

Cited by 13 publications

(6 citation statements)

References 2 publications

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“…In this context, we have found that N-nitromethylphthalimide, which can be easily prepared from commercially available starting materials in a very simple way, [11] constitutes an excellent hydroxymetanimidoyl anion equivalent to be used as a Michael donor in enantioselective conjugate addition reactions with a,b-unsaturated aldehydes under iminium activation (see Scheme 1). [12] On one hand, N-nitromethylphthalimide is an acidic compound, which can participate as pronucleophile under the neutral or slightly basic reaction conditions associated to iminium catalysis, [13] therefore allowing the use of a chiral secondary amine catalyst to achieve enantiocontrol.…”

Section: In Memory Of Our Colleague and Friend Rafael Suaumentioning

confidence: 99%

Organocatalytic Enantioselective Formal Conjugate Addition of a Hydroxymoyl Anion to α,β‐Unsaturated Aldehydes

Alonso

Reyes

Carrillo

et al. 2011

Chemistry A European J

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In memory of our colleague and friend Rafael SuauThe conjugate addition reaction is a fundamental transformation in organic chemistry. The wide variety of reagents amenable to participate as Michael donors or acceptors makes this reaction extremely versatile, allowing the preparation of many different classes of highly functionalized compounds in a very easy and reliable way. Moreover, the conjugate addition reaction also occurs very often with the concomitant generation of one or more stereocenters and, in this context, intense research has focused on the development of catalytic enantioselective approaches for carrying out this important reaction in a stereocontrolled way.[1] Although most of the methodologies reported to date involve the use of transition-metal catalysts, several organocatalytic enantioselective variants of the conjugate addition reaction have been developed in the last few years;[2] many of which have performed excellently with regard to chemical efficiency and stereocontrol. On the other hand, many research groups have also directed their attention to finding novel reactivity patterns applied to the conjugate addition reaction by using umpoled reagents, [3] which have expanded the array of compounds which can be used as Michael donors or acceptors, to further increase the scope of this methodology. In particular, the enantioselective conjugate addition of acyl or formyl anions to a,b-unsaturated carbonyl compounds or related derivatives entails a particular interest because this transformation allows the preparation of 1,4-dicarbonyl compounds, which are classically much more difficult to access by standard C À C bond forming reactions than the corresponding 1,3-or 1,5-dicarbonyl compounds.[4] However, despite the enormous potential of the oxime moiety and the key role played by this functional group in plenty of organic reactions, the development of umpoled reagents that behave as hydroxymoyl anion equivalents remains unexploited.In fact, even for the related case of the conjugate addition of acyl/formyl anion equivalents, enantioselective versions for this particular transformation under metal-free conditions are very scarce (see Scheme 1). For example, the Stetter reaction using N-heterocyclic carbenes (NHC) as catalysts can be an extremely effective approach for the formal enantioselective conjugate addition of acyl anions, [5] but it is ineffective when trying to use formaldehyde as the Michael donor.For the particular case of the conjugate addition of a formyl anion equivalent, there is only one single example related to an enantioselective organocatalytic version; this involves the use of N,N-dialkylhydrazones as Michael donors, which undergo conjugate addition to b,g-unsaturated a-ketoesters under chiral Brønsted-acid catalysis to give moderate levels of enantioselection.[6] Another relevant example involves oxazol-5A C H T U N G T R E N N U N G (2 H)-ones as aryloyl anion equivalents in the conjugate addition to enoylphosphonates, [7] which also relies on Brønsted-acid catalysis. In...

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Section: In Memory Of Our Colleague and Friend Rafael Suaumentioning

confidence: 99%

Organocatalytic Enantioselective Formal Conjugate Addition of a Hydroxymoyl Anion to α,β‐Unsaturated Aldehydes

Alonso

Reyes

Carrillo

et al. 2011

Chemistry A European J

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“…In our initial synthesis of target compounds 1 − 3 , the lipophilic side chain was introduced on the cyclohexane ring via the coupling of the mixed homocuprates,11a 18 and 23 , with 2-cyclohexen-1-one (Scheme ). A subsequent route involved the use of the Wadsworth−Horner−Emmons reaction between the ylide of a β-ketophosphonate 11b-d ( 26 or 27 ) and cyclohexanecarboxaldehyde 29 (Scheme ).…”

Section: Chemistrymentioning

confidence: 99%

“…Further reduction 15a of the methyl ester using DIBAL-H in toluene at −78 °C afforded the protected 3-oxocyclohexane carboxyaldehyde 29 . This aldehyde could be isolated and characterized but not stored more than several hours 11e. For this reason the reduction of the ester 28 had to be performed concomitantly to the formation of the ylide of the appropriate β-ketophosphonate ( 26 or 27 ) using sodium hydride in THF at −40 °C.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Structure−Activity Relationships of New 1,3-Disubstituted Cyclohexanes as Structurally Rigid Leukotriene B₄ Receptor Antagonists

et al. 1999

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A series of 1-hydroxy-3-¿3-hydroxy-7-phenyl-1-hepten-1-yl cyclohexane acetic acid derivatives was designed based on postulated active conformation of leukotriene B(4) (LTB(4)) and evaluated as human cell surface LTB(4) receptor (BLTR) antagonists. Binding was determined through ¿(3)HLTB(4) displacement from human neutrophils and receptor antagonistic assays by in vitro measurements of inhibition of leukocyte chemotaxis induced by LTB(4). On the basis of these assays, a structure-affinity relationship was investigated. Optimization of the acid chain length and omega-substitution of a phenyl group on the lipophilic tail were shown to be critical for binding activity. These modifications led to the discovery of compounds with submicromolar potency and selective BLTR antagonism. The most potent compound 3balpha (IC(50) = 250 nM) was found to significantly inhibit oedema formation in a topical model of phorbolester-induced inflammation. Substantial improvement of in vitro potency was achieved by modification of the carboxylic acid function leading to the identification of the N,N-dimethylamide series. Compound 5balpha, free of agonist activity, displayed higher potency in receptor binding with an IC(50) of 40 nM. These results support the hypothesis that the spatial relationship between the carboxylic acid and allylic hydroxyl functions is crucial for high binding affinity with BLTR.

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“…IR: 2240,1702. 5-(2-Cyano-I-cyclooclen-1-yloxy)pentanoate (1 1) and Ethyl 5-(I-Cyano-2-oxocyclooc-fyLy[)pentanoate (12). A mixture of 1 (4.53 g, 30 mmol), ethyl 5-bromopentanoate (13; 12.54 g, 60 mmol), Bu,NOH (15.5 g, 60 mmol, 40% aq.…”

Section: Rearrangementmentioning

confidence: 99%

“…layer washed with H,O until neutral and dried. Workup and chromatography as described in Method A gave 4 (870 mg, 59.4%), cJ [12].…”

Section: Derivatives Of 2-oxocyclododecane-1-carbonitrile (2) 21 Mmentioning

confidence: 99%

Studies on the Carbon Zip Reaction of 2‐Oxocycloalkane‐1‐carbonitriles

Süße

Hájíček

Hesse

1985

Helvetica Chimica Acta

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As a part of continuing interest in the zip reaction, we present the results on a carbon ring-enlargement reaction of activated ketones with a CN group as a charge stabilizer. Two series of (l-cyano-2-oxocy-cloalky1)alkanoates were prepared from 8and 12-membered cyano-ketones 1 and 2, respectively, namely the propanoates 3 and 4, the butanoates 6 , s and 9 as well as the pentanoates 12 and 15. While treatment with t-BuOK of the former two homologous esters resulted in both ring enlargement and competitive transesterification, the pentanoates 12 and 15 afforded mostly the diastereoisomeric mixtures of bicyclic alcohols 2Oa-c and 31a,b, respectively, which remained intact on further exposure to base. It was shown thatapart from the base used (C-BuOK us. Li(i-Pr),Nthe distribution of products was greatly influenced by the ring size of substrates. This is further illustrated by treatment of ketones 34 and 35 with t-BuOK. While the former rearranged smoothly to diketone 36, no reaction at all took place with the latter. The behavior of the substrates is discussed in terms of steric and energetic reasons.

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N-Nitromethylphthalimide. A formyl anion equivalent

Cited by 13 publications

References 2 publications

Organocatalytic Enantioselective Formal Conjugate Addition of a Hydroxymoyl Anion to α,β‐Unsaturated Aldehydes

Organocatalytic Enantioselective Formal Conjugate Addition of a Hydroxymoyl Anion to α,β‐Unsaturated Aldehydes

Synthesis and Structure−Activity Relationships of New 1,3-Disubstituted Cyclohexanes as Structurally Rigid Leukotriene B₄ Receptor Antagonists

Studies on the Carbon Zip Reaction of 2‐Oxocycloalkane‐1‐carbonitriles

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N-Nitromethylphthalimide. A formyl anion equivalent

Cited by 13 publications

References 2 publications

Organocatalytic Enantioselective Formal Conjugate Addition of a Hydroxymoyl Anion to α,β‐Unsaturated Aldehydes

Organocatalytic Enantioselective Formal Conjugate Addition of a Hydroxymoyl Anion to α,β‐Unsaturated Aldehydes

Synthesis and Structure−Activity Relationships of New 1,3-Disubstituted Cyclohexanes as Structurally Rigid Leukotriene B4 Receptor Antagonists

Studies on the Carbon Zip Reaction of 2‐Oxocycloalkane‐1‐carbonitriles

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Synthesis and Structure−Activity Relationships of New 1,3-Disubstituted Cyclohexanes as Structurally Rigid Leukotriene B₄ Receptor Antagonists