Carvones aldol reaction

A total synthesis of functionalized 8,14-seco steroids with five- and six-membered D rings has been developed (467). The synthesis is based on the transformation of (S)-carvone into a steroidal AB ring moiety with a side chain at C(9), which allows the creation of a nitrile oxide at this position. The nitrile oxides are coupled with cyclic enones or enol derivatives of 1,3-diketones, and reductive cleavage of the obtained cycloadducts give the desired products. The formation of a twelve-membered ring compound has been reported in the cycloaddition of one of the nitrile oxides with cyclopentenone and as the result of an intramolecular ene reaction, followed by retro-aldol reaction. 

Once again, ( )-carvone was chosen as starting material (Scheme 48) (727). Aldol reaction with formaldehyde led to 6-hydroxymethylcarvone. The primary alcohol was protected as silylether 415 to permit addition of (cyanomethyl)lithium. The 5 1 mixture of epimeric tertiary alcohols was separated and the main product, 416, the alcohol generated by axial attack, was protected stereoselectively as bromoether 417 utilizing pyridinium hydrobromide perbromide. To introduce the necessary alkyne, the nitrile was reduced to the aldehyde with diisobutylaluminum hydride and subsequent hydrolysis. Addition of the alkyne led to a 2 1 mixture of... 

Before the introduction of metal-ammonia solutions for the reduction of a,p-unsaturated carbonyl compounds,sodium, sodium amalgam, or zinc in protic media were most commonly employed for this purpose. Some early examples of their use include the conversion of carvone to dihydrocarvone with zinc in acid or alkaline medium, and of cholest-4-en-3-one to cholestanone with sodium in alcohol. These earlier methods are complicated by a variety of side reactions, such as over-reduction, dimerization, skeletal rearrangements, acid- or base-catalyzed isomerizations and aldol condensations, most of which can be significantly minimized by metal-ammonia reduction. 

Alkylation of isovaleramide with 1,3-dichlorobut-2-ene yields (139) after methyl-ation acid-catalysed hydrolysis and internal aldol condensation gives ( )-piperitone. The value of piperitenone and isopiperitenone formation, probably via electrocyclic reaction of the pyrolytic acetic acid-elimination product from A - and A -isomers of (49), cannot be assessed in the absence of reaction yields. (S)-(-)-Pulegone is obtained in good yield from (- )-citronellol by oxidation with pyridinium chlorochromate followed by double-bond isomerization. Low-temperature reduction of ( —)-carvone to ( —)-cz5-carveol (140) and... 

---