Ketone functionality introduction

Enolizalion of conjugated or /3,y-unsatiirated enones and dienones in O-deiiterated solvents facilitates the introduction of deuterium labels into positions as far as three and five carbon atoms away from a given ketone function. Exchange of the activated hydrogens in androst-4-en-3-one (12) provides a good illustration of the potential of this method. Saturation of the double bond (section V) in the deuterated enone (13) followed by back exchange of the a-deuteriums (section II-B) proves to be an excellent method for the preparation of 6,6-d2-5a-androstan-3-one (15). ... 

The A -6-ketone functionality in polyhydroxy cholestanes is common to all the insect moulting hormones of the ecdysone type. Therefore, there has recently been considerable interest in the introduction of A -double bonds into 6-ketones. The different approaches that follow illustrate the utility of isomerization, rearrangement, and blocking groups. 

Instead of reducing the ketone function, a lithium organic reagent, e.g. phenyllithium, can be added followed by an acid-catalyzed elimination of water to give product 3.85 This procedure allows the introduction of various substituents. By this method 3-[2-(dimethylamino)ethoxy]-... 

Introduction of oxygen a to a ketone function can also be carried out via the silyl enol ether. Lead tetraacetate gives the a-acetoxy ketone.219... 

Introduction of a 3-ketone function or a 3a-OFI group enhances androgenic activity. A hydroxyl group... 

A method for introduction of the ring D side chain was then investigated, starting with the tetracycle 69. Although the ketone functionality in the D ring could serve to introduce the alkyl group in the a-position, the stereochemical outcome and efficiency of this alkylation was doubtful and would require subsequent removal of a very hindered ketone. It was decided to remove Ae D ring... 

The non-stereospecific introduction of bromine a to the ketone function was achieved following reaction of pristinamycin 11 with bromine in the presence of triethylamine (Scheme 17). 

Certain functionalised esters combine the virtues of acyl protection (ease of introduction, electronic deactivation, lability to base) with the ability to be deprotected under specialised conditions that leave other esters unaffected. Of these, the only example that has seen reasonably widespread application is the levulinate (Lev) derivative which, in chemistry that parallels the cleavage of ClAc derivatives with soft nucleophiles, are cleavable by conversion of the comparitively reactive ketone functionality into a nucleophilic entity that can cyclise onto the ester carbonyl releasing the protected hydroxyl. The example in Figure 2.45 shows that the acetates survive unscathed in Lev deprotection with hydrazine so that only the 2-OH is released [63]. 

The cyclopropyl group serves not only as the latent angular methyl group but also allows direct methylation of the ketone for introduction of the gem dimethyl function. 

In general bromination of 20-ketones is directed to the introduction of functionality at C-21. However, on occasion 17-bromo compounds are required for dehydrobromination to A -20-ketones, although these are generally obtained in other ways. Kinetic enolization of a 20-ketone gives the A °-enol, whereas the thermodynamic product is the A kjsomer. An interesting enolate trapping reaction has been used recently to prepare 16-methyl-A -20-ketones ... 

The introduction of the l/, 2j5-methylene function into cortical hormones is best carried out by starting with the A -3)S-aIcohols (7) which are prepared by lithium aluminum hydride or lithium tri-t-butoxyaluminum hydride reduction of the corresponding A -3-ketones. 

---