Alkyleisen‐ und Alkylcobalt‐Reagenzien, IV<sup>[1]</sup> Aldehydselektive Cyanoalkylierungen mit Cyanoalkyl‐Derivaten von Eisen(II) und anderen Übergangsmetallen

Kauffmann, Thomas; Kieper, Hansjörg; Pieper, Hans

doi:10.1002/cber.19921250422

Cited by 29 publications

(7 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…57,112 An alternative process, the transmetalation of a lithium enolate with chromium trichloride, is not very efficient. 57,113 The nature of the intermediate obtained this way might be considered even more doubtful than that of the Reformatsky intermediates. Lithium enolate / CrCl 3 mixtures show stereoselectivities between those of pure lithium enolates and the chromium(III) enolates of the Reformatsky route.…”

Section: Scheme 2 the Chromium-reformatsky Reactionmentioning

confidence: 99%

Recent Advances in Chromium(II)- and Chromium(III)-Mediated Organic Synthesis

Wessjohann¹,

Scheid²

1999

Synthesis

215

View full text Add to dashboard Cite

Synthetic transformations utilizing chromium(II) or chromium(III) reagents, mainly CÐC-coupling reactions, are discussed. Chromium reagents find increasing application in complex total syntheses where other organometallics are difficult to apply. They are easy to prepare and exhibit extraordinary chemoselectivity and high diastereoselectivity. In this article emphasis is laid on recent results in synthetic procedures, on little known general aspects of (organo)chromium chemistry, and on areas not reviewed before. The most important recent advances include reactions catalytic in chromium ions, anti -selective Reformatsky-type aldol reactions with excellent asymmetric induction, domino radical/carbanion reactions, asymmetric chromium(III) catalyzed epoxide openings and homogeneous alkene polymerization catalysts. Some progress is also made in ligand controlled enantioselective reactions with Cr(II) reagents, but satisfying solutions remain a major challenge in the field.

show abstract

Section: Scheme 2 the Chromium-reformatsky Reactionmentioning

confidence: 99%

Recent Advances in Chromium(II)- and Chromium(III)-Mediated Organic Synthesis

Wessjohann¹,

Scheid²

1999

Synthesis

215

View full text Add to dashboard Cite

show abstract

“…The various metalated phenylacetonitriles were prepared by deprotonation with the appropriate metal amide or organometallic (method A), or by transmetalation of lithiated 1 (method B). Kauffmann has previously described transmetalation of lithiated nitriles to the corresponding Fe(II), Cr(II), Mn(II), Co(II), Ni(II), and Cu(I) derivatives ,, zinc, and aluminum 1 derivatives has also been described.…”

mentioning

confidence: 99%

“…Kauffmann has previously described transmetalation of lithiated nitriles to the corresponding Fe(II), Cr(II), Mn(II), Co(II), Ni(II), and Cu(I) derivatives ,, zinc, and aluminum 1 derivatives has also been described. In the course of our investigations more than 20 metal/oxidation state/ligand combinations were examined.…”

mentioning

confidence: 99%

“…The utility of this reaction would greatly increase if aliphatic nitriles could be shown to react with reliable and high diastereoselectivity. Kauffman reported that lithiated propionitrile and the corresponding Fe(II) derivative underwent addition to benzaldehyde with little selectivity (3:1 and 2:1 respectively, unassigned) . To determine if increasing steric bulk in the nitrile moiety would raise selectivities to a useful level, aldol reactions of lithiated isovaleronitrile 4 and tert -butylacetonitrile 5 were studied in THF at 0.025 M (Table ).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Synthetic Optimization and Structural Limitations of the Nitrile Aldol Reaction

Carlier

et al. 1997

J. Org. Chem.

View full text Add to dashboard Cite

In an effort to further optimize and to define the structural limitations of the nitrile aldol reaction, several studies were undertaken. Lithiated phenylacetonitrile 1 was demonstrated to exhibit diastereoselectivity for addition to benzaldehyde higher than that of other metalated phenylacetonitriles. With a view toward practical lab-scale synthesis of aldols derived from lithiated arylacetonitriles, the effects of reaction concentration and quenching method on isolated yields of the anti-aldols were readdressed. Secondary aldehydes give reasonable recrystallized yields of anti-aldols at reaction concentrations as high as 0.1 M; pivalaldehyde gives good results at concentrations up to 0.3 M. Thirdly, the aldol reaction of lithiated 1 with para-substituted benzaldehydes 6b−g was then studied; increasing electron-withdrawing power of the para substituent was found to cause a marked decrease in diastereoselectivity. Finally, the aldol reactions of two aliphatic nitriles (isovaleronitrile 4 and tert-butylacetonitrile 5) were studied. Suprisingly, aldol diastereoselectivity of aliphatic nitriles is not uniformly anti-selective, and selectivities overall are lower than those afforded by arylacetonitriles.

show abstract

“…Sodium amide, 12) n-butyllithium, [13][14][15] a combination of di-n-butylboryl triflate and diisopropylamine, 16) potassium t-butoxide, 17) and a combination of proazaphosphatrane and magnesium sulfate 18) have been used as condensation reagents for acetonitrile with benzaldehyde. Our attention was drawn to the reaction in the presence of potassium t-butoxide, since it has the following advantages: (1) potassium t-butoxide is readily available from commercial sources, and (2) it does not cause evolution of gas from the reaction mixture.…”

mentioning

confidence: 99%

An Easy Access to 7-Methyl-2-naphthalenecarbonitrile

Koshio¹,

Ishihara²,

Yamada³

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Thromboembolic diseases continue to be a leading cause of morbidity and mortality in the developed world, and the use of anticoagulant drugs is a primary clinical strategy to treat and prevent these diseases. Factor Xa inhibitors have the potential to be superior anticoagulant agents, and thus the search for novel factor Xa inhibitors has emerged as one of the most active areas of current drug discovery.Several potent factor Xa inhibitors containing naphthylamidine moieties have been reported, [1][2][3][4][5] and representative structures of these inhibitors are shown in Fig. 1. These drugs have a common precursor, 7-methyl-2-naphthalenecarbonitrile (1), and several methods have been reported for preparation of this compound.6-10) Earlier syntheses of compound 1 are multi-step procedures 6,8) or require high temperature (flame-heating or heating to 400°C), 7,9) and hence they are impractical and unsuitable for commercial exploitation. More recently, Yokoyama et al. have described the preparation of compound 1 in four steps, in which 2,7-dimethylnaphthalene was used as the starting material. 10) However, 2,7-dimethylnaphthalene is not readily available from commercial sources, and this method also involves a selective transformation of a symmetrical starting material to an asymmetrical target compound. These two problems contribute to decreased synthetic efficacy. Due to the high worldwide market value of factor Xa inhibitors, development of an effective synthetic procedure for the synthesis of the key precursor 1 remains as an important and challenging task. Herein, we present a practical and efficient synthesis of 7-methyl-2-naphthalenecarbonitrile (1) starting from two common, readily available starting materials: m-tolualdehyde (2) and 3-cyanopropionaldehyde dimethyl acetal (3).Teague et al. have reported that condensation of a 3-cyanopropionaldehyde dialkyl acetal with a methoxy-activated aromatic aldehyde, followed by treatment with sulfuric acid, yields a substituted naphthalene product.11) Although this method is limited to activated benzaldehydes such as methoxybenzaldehyde, we adapted it for our target compound using a weakly activated benzaldehyde, m-tolualdehyde (Chart 1). Condensation of 2 with 3 in the presence of LDA (lithium diisopropylamide) gave intermediate alcohol 4, and the crude alcohol was then refluxed in 20% aqueous sulfuric acid to afford compound 1 in 43% yield after chromatographic purification (Chart 1, Entry 1). The more hindered cyclization product, 5-methyl-2-naphthalenecarbonitrile, was not observed.Several different reaction conditions were used in optimizing the reaction for multi-gram preparations, and the results are summarized in Chart 1. Sodium amide, 12) n-butyllithium, 13-15) a combination of di-n-butylboryl triflate and diisopropylamine, 16) potassium t-butoxide, 17) and a combination of proazaphosphatrane and magnesium sulfate 18) have been used as condensation reagents for acetonitrile with benzaldehyde. Our attention was drawn to the reaction in the presence of potassi...

show abstract

Alkyleisen‐ und Alkylcobalt‐Reagenzien, IV^[1] Aldehydselektive Cyanoalkylierungen mit Cyanoalkyl‐Derivaten von Eisen(II) und anderen Übergangsmetallen

Cited by 29 publications

References 21 publications

Recent Advances in Chromium(II)- and Chromium(III)-Mediated Organic Synthesis

Recent Advances in Chromium(II)- and Chromium(III)-Mediated Organic Synthesis

Synthetic Optimization and Structural Limitations of the Nitrile Aldol Reaction

An Easy Access to 7-Methyl-2-naphthalenecarbonitrile

Contact Info

Product

Resources

About

Alkyleisen‐ und Alkylcobalt‐Reagenzien, IV[1] Aldehydselektive Cyanoalkylierungen mit Cyanoalkyl‐Derivaten von Eisen(II) und anderen Übergangsmetallen

Cited by 29 publications

References 21 publications

Recent Advances in Chromium(II)- and Chromium(III)-Mediated Organic Synthesis

Recent Advances in Chromium(II)- and Chromium(III)-Mediated Organic Synthesis

Synthetic Optimization and Structural Limitations of the Nitrile Aldol Reaction

An Easy Access to 7-Methyl-2-naphthalenecarbonitrile

Contact Info

Product

Resources

About

Alkyleisen‐ und Alkylcobalt‐Reagenzien, IV^[1] Aldehydselektive Cyanoalkylierungen mit Cyanoalkyl‐Derivaten von Eisen(II) und anderen Übergangsmetallen