Alcohol - ketone interconversions

In this chapter, we have examined the use of cells and enzymes to chemically transform lipids. We have had to be selective and have predominantly focused attention on the transformation of sterols and steroids. We first explained why these compounds were commercially important and why they only occur in low concentrations in natural systems. We pointed out that a very large number of reaction types are possible, but those which have found greatest use include stereospedfic hydroxylations, alcohol/ketone interconversion, hydrolysis, conjugation and isomerisation. 

Scheme 17 Mechanism of alcohol-ketone interconversion coupled with the hydrogen evolution step." ...

The interconversion of alcohols to ketones is a common biochemical reaction. The introduction of hydroxyl groups into toe steroid nucleus and side chain creates a variety of secondary alcohols. Some of these, especially at positions 3, 7, 11 and 17 are frequently oxidised to ketones. 

Isomerization has been observed with many a,j3-unsaturated carboxylic acids such as w-cinnamic 10), angelic, maleic, and itaconic acids (94). The possibility of catalyzing the interconversion of, for example, 2-ethyl-butadiene and 3-methylpenta-l,3-diene has not apparently been explored. The cobalt cyanide hydride will also catalyze the isomerization of epoxides to ketones (even terminal epoxides give ketones, not aldehydes) as well as their reduction to alcohols. Since the yield of ketone increases with pH, it was suggested that reduction involved reaction with the hydride [Co" (CN)jH] and isomerization reaction with [Co (CN)j] 103). A related reaction is the decomposition of 2-bromoethanol to acetaldehyde... 

A series of 2-substituted cyclohexanones was studied over a wide range of temperature in an attempt to optimize the diastereoselectivity of diisobutylaluminium phenoxides in the reduction of ketones.161 Hydride transfer dominates at high temperature, but a Meerwein-Ponndorf-Verley-type interconversion of the aluminium alcoholate intermediates (via the reactant ketone) is an important factor in diastereoselection at low temperature. 

Since the hemiketals of cyclopropanone are in equilibrium with the parent ketone, they may be interconverted by standing in the presence of the appropriate alcohol. 4> However, in the cases of cyclopropanone ethyl and methyl hemiketals, dissociation to the ketone is slow and hemi-ketal interconversion requires about two weeks at room temperature for completion. 4>... 

WeVe talked at length about the interconversions of acid derivatives, explaining the mechanism of attack of nucleophiles such as ROH, H20, and NH3 on acyl chlorides, acid anhydrides, esters, acids, and amines, with or without acid or base present. We shall now go on to talk about substitution reactions of acid derivatives that take us out of this closed company of compounds and allow us to make compounds containing functional groups at other oxidation levels such as ketones and alcohols. 

B. Functional Groups — Preparation, reactions, and interconversions of alkanes, alkenes, alkynes, dienes, alkyl halides, alcohols, ethers, epoxides, sulfides, thiols, aromatic compounds, aldehydes, ketones, carboxylic acids and their derivatives, amines... 

Metab. studies with the cis- and trans- form in the rat suggest that interconversion occurs via oxidation to ketone and reduction back to alcohol ( 2). 

Such successive half-reactions are not properly self-consistent, and a tally of such combinations could be made and used mechanically to discard certain sequences from a derived set if a criterion of true self-consistency is desired 5>. On the other hand many of the refunctionalization steps in the actual s mtheses surveyed 24,31) are of exactly this kind, i.e., derivatization of alcohols to mesylates, acetates, etc., ketone-ketal protective interconversions, ester-acid interconversions, etc. Thus, although the self-consistency criterion was applied for reasons of efficiency and does strongly reduce the tree, the fact that the original definition of Z is broad allows a generous amount of implicit refunctionalization in practice. Furthermore, it should be possible to tabulate which of the pairs of successive half-reactions require it and which do not so that its exclusion can be a matter of choice. 

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