Reactions of acyl anion equivalents derived from cyanohydrins, protected cyanohydrins and α-dialkylaminonitriles

Structural characterization of Group 4 transition metal halide bis- Arduengo carbene complexes MCl4L2: X-ray crystal structure analyses and DFT calculations

The cyanide-ion-catalyzed dimerization of aromatic and heterocyclic aldehydes to α-hydroxy ketones, also known as the benzoin condensation, is one of the oldest reactions in organic chemistry. A key intermediate in this reversible reaction is a nitrile-stabilized carbanion. In 1973 it was shown that these carbanions add irreversibly to α,β-unsaturated ketones, esters, and nitriles to give 1,4-diketones, 4-ketocarboxylic esters, and 4-ketocarbonitriles, respectively. The reaction succeeds only in aprotic solvents, preferably dimethylformamide. Benzoins and aldehydes can be used interchangeably as starting materials since they are in rapid equilibrium. Cyanide ion catalysis fails with aliphatic aldehydes because they resinify under the strongly basic conditions. Vitamin B1 (thiamine) has long been known to convert aliphatic aldehydes into acyloins in buffered aqueous solution. The catalytic effect of vitamin B1 is due to the presence of a thiazolium cation. Thiazolium salts in general as well as other azolium salts also catalyze the formation of acyloins. The optimum conditions for thiazolium salt catalysis have been worked out. It was shown subsequently that thiazolium salts, in combination with bases, also catalyze the addition of aliphatic, aromatic, and heterocyclic aldehydes to α,β-unsaturated carbonyl compounds. The 1,4-diketones, 4-ketocarboxylic esters, and 4-ketocarbonitriles are usually formed in good to excellent yields. Cyanide ion and thiazolium salt catalysis thus complement each other.



This chapter covers the literature of the catalyzed nucleophilic addition of aldehydes to electrophilic double bonds up to 1988. The reaction has been reviewed previously.


Keywords:

catalysts;
nucleophilic addition;
aldehydes;
mechanism;
1,4-diketones;
acceptors;
4-ketonitriles;
4,7-diketonitriles;
4-ketocarboxylic esters;
triketo compounds;
polyketo compounds;
experimental procedures;
divinyl sulfone;
nitriles;
Michael acceptors;
unsaturated esters;
lactones;
unsaturated acids;
electrophilic double bond;
scope;
limitations;
experimental procedures

The Catalyzed Nucleophilic Addition of Aldehydes to Electrophilic Double Bonds

The alkaloidal venom components of two species of thief ants,Solenopsis (Diplorhoptrum) species AA andS. (Diplorhoptrum)conjurata have been found to contain (5Z,9Z)-3-hexyl-5-methylindolizidine and a mixture of (5Z,9Z)-3-ethyl-5-methylindolizidine andcis-2-methyl-6-nonyl-piperidine,trans-2-methyl-6-nonylpiperidine,cis-2-methyl-6-undecylpiperidine, and hexadecanoic acid.Monomorium pharaonis was similarly investigated and found to contain the indolizidine and pyrrolidines previously described (Ritter et al., 1977b). Both indolizidines were synthesized along with their stereoisomers and separated by preparative gas chromatography. Spectral studies revealed the stereochemistry to be 5Z,9Z in both cases. The stereochemistry of 2-butyl-5-pentylpyrrolidine inM. phaeronis has also been established. Biosynthetic relationships are discussed.

(5Z,9Z)-3-alkyl-5-methylindolizidines fromSolenopsis (Diplorhoptrum) species.

The disclosure relates to pyridazine derivatives of formula (I), wherein the variables are as defined in the specification. These pyridazine derivative compounds are useful as 11beta-hydroxysteroid dehydrogenases inhibitors (11beta-HSD1 inhibitors), and are suitable for treating disorders associated with the enzyme 11beta-hydroxysteroid dehydrogenase1 such as diabetes Type II, obesity, eating disorders, dyslipidemiae and hypertension.

Pyridazine derivatives as 11beta-hydroxysteroid dehydrogenase type 1 inhibitors

Thiazoliumsalz-katalysierte Additionen von Aldehyden an die Vinylketone 4–6, 47 fuhren zu 1,4-Diketoketalen 7–13, 1,4,8,-Triketonen 14–23 und 1,4,9-Triketonen 48–51. Die Vinylketone entstehen durch Pyrolyse aus den Norbornenderivaten 1–3, 46, die durch metallorganische Synthesen dargestellt werden. Die 1,4,8-Triketone reagieren mit Hydrazin zu 5,6,7,8-Tetrahydrocinnolinen 24–32. Die cyclisierende Aldolreaktion fuhrt bei den 1,4-Diketoketalen zu Cyclopentenonderivaten 33–36, bei den 1,4,8-Triketonen zu Cyclohexenonderivaten 37–43.



Addition of Aldehydes to Activated Double Bonds, XXXII. Syntheses and Reactions of 1,4-Dioxo Ketals, 1,4,8-Triketones, and 1,4,9-Triketones.



Thiazolium salt catalyzed additions of aldehydes to the vinyl ketones 4–6, 47 lead to 1,4-dioxo ketals 7–13 1,4,8,-triketones 14–23, and 1,4,9-triketones 48–51. The vinylketones are obtained by pyrolysis of the norbornene derivatives 1–3, 46, which were synthesized by metal organic reactions. The 1,4,8-triketones react with hydrazine to give 5,6,7,8-tetrahydrocinnolines 24–32. The aldol reaction of the 1,4-dioxo ketals leads to cyclopentenone derivatives 33–36, the reaction of 1,4,8-triketones to cyclohexenone derivatives 37–43.

Alfred Mertens

Papers

Addition von Aldehyden an aktivierte Doppelbindungen, XXXII. Synthesen und Reaktionen von 1,4-Diketoketalen, 1,4,8-Triketonen und 1,4,9-Triketonen

Addition von Aldehyden an aktivierte Doppelbindungen, XXX. Synthese von unsymmetrischen γ‐Polyketonen, 4,7,10‐Triketoestern und 4,7,10‐Triketonitrilen