Ketones functionalised

Figure 4.16. BINAP-Ruthenium hydrogenations of functionalised ketones...

Scheme 9.5 Hydrogenations of p-keto esters and (functionalised) ketones in the presence of a heterogeneous tartaric acid-modified nickel catalyst.

On the other hand, asymmetric aldolisations of functionalised ketones have been studied by Hu e/ ai, using a primary amine of an amino acid introduced into the bispidine framework.In the presence of a weak acidic additive such... 

Scheme 2.36 Aldolisations of functionalised ketones catalysed by bispidine-derived primary amine.

The Rh-catalysed asymmetric hydrosilylation of prochiral ketones has been studied with complexes bearing monodentate or heteroatom functionalised NHC ligands. For example, complexes of the type [RhCl(l,5-cod)(NHC)] and [RhL(l,5-cod)(NHC)][SbFg ], 70, where L = isoquinoline, 3,5-lutidine and NHC are the chiral monodentate ligands 71 (Fig. 2.11). 

NHC-promoted enolate formation from an enal, followed by a desymmetrising aldol event to generate P-lactones and loss of CO, has been exploited by Scheidt and co-workers to generate functionalised cyclopentenes 240 in high ee from enal substrates 238 (Scheme 12.52) [94]. Interestingly, the use of alkyl ketones in this reaction manifold allows the isolation of the p-lactone intermediates with acyclic diketones, P-lactones 239 are formed with the R group anti- to the tertiary alkox-ide, while with cyclic diketones the P-lactone products have the R group with a syn relationship to the alkoxide [95]. 

Scheme 4.13 Additions of functionalised dialkylzinc reagents to ketones with HOCSAC ligand.

This ligand has also been used by the same authors to promote the addition of ZnMe2 to a functionalised a,(3-unsaturated ketone in the asymmetric key step of the first enantioselective synthesis of (-)-frontalin. This synthesis started with the naphthalene-catalysed lithiation of a chlorinated ketal (Scheme 4.15) that, after several transmetalation processes, was trapped by reaction... 

The reduction of nitrobenzene to aniline is a major industrial process at the heart of the production of polyurethanes, and it is also often used as a marker reaction to compare activities of catalysts [1,2], It can be performed over a variety of catalysts and in a variety of solvents. As well as its main use in polymethanes, aniline is used in a wide range of industries such as dyes, agrochemicals, by further reaction and functionalisation. Reductive alkylation is one such way of functionalising aromatic amines [3, 4], The reaction usually takes place between an amine and a ketone, aldehyde or alcohol. However it is possible to reductively alkylate direct from the nitro precursor to the amine and in this way remove a processing step. In this study we examined the reductive alkylation of nitrobenzene and aniline by 1-hexanol. 

The synthesis of both enantiomers of vasicinone has been carried out using almost entirely polymer-supported reagents. The route was based on functionalisation of deoxyvasicinone by a highly selective bromination then via enantioselective reduction of the derived ketone <06SL2609>. 

The Baylis-Hillman reaction of TV-protected 3-substituted 4-formylazetidin-2-ones with methyl vinyl ketone has been used to prepare intermediates from which highly functionalised P-lactams fused to medium rings were obtained by radical, stereocontrolled methods <99CC1913>. 

The retrosynthesis involves the following transformations i) isomerisation of the endocyclic doble bond to the exo position ii) substitution of the terminal methylene group by a more stable carbonyl group (retro-Wittig reaction) iii) nucleophilic retro-Michael addition iv) reductive allylic rearrangement v) dealkylation of tertiary alcohol vi) homolytic cleavage and functionalisation vii) dehydroiodination viii) conversion of ethynyl ketone to carboxylic acid derivative ix) homolytic cleavage and functionalisation x) 3-bromo-debutylation xi) conversion of vinyl trimethylstannane to methyl 2-oxocyclopentanecarboxylate (67). 

Application of this work to a domino process using 51 involves Michael addition of P-ketoesters [91], p-diketones or P-ketosulfones [92] to a,P-unsaturated ketones followed by an intramolecular aldol reaction provides highly functionalised cyclohexanone building blocks with up to four contiguous chiral centres. Gryko has also reported examples of this domino Michael/intramolecular aldol reaction in the coupling of 1,3-diketones and methyl vinyl ketone using L-proUne as catalyst [93],... 

The scope of the Negishi-coupling is not limited to aryl and vinyl halides and sometimes acyl chlorides might also be converted to ketones by this protocol. The 2,3-dihalopyrrole derivative shown in 6.22. was converted into its 2-lithio derivative by selective lithium-halogen exchange at -78 °C. Addition of zinc chloride effected the formation of the appropriate pyrrolylzinc chloride, which was coupled with a functionalised butyroyl chloride in the presence of tetrakis(triphenylphosphino)palladium and furnished the expected 2-acylpyrrole in 61% yield.27... 

The desired spiroacetal 36 was converted to the TBS ether and the terminal alkene moiety was elaborated to the corresponding ethyl ketone in four steps, to provide the fully-functionalised CD-spiroacetal ketone 5, now ready for aldol union with the AB-spiroacetal aldehyde 4. This route was found to be highly scalable, enabling production of multi-gram quantities of the desired C16-C28 fragment 5 with little need to repeat the synthetic sequence. 

Since its discovery in 1953, the reaction has been extensively studied with respect to structural variation in the phosphonium ylide, in the range of functionalised aldehydes and ketones, in the nature of the bases and the polarity of the solvents that may be used, and in the mechanism of the reaction and the factors which influence the ( /Z) ratio. Many thousands of simple and complex syntheses have been effected and the method is widely exploited in research laboratories and in the industrial processes for syntheses in the steroid and carotenoid field. 

In chapters 19 (1,3-diCO) and 21 (1,5-diCO) we were able to use an enol(ate) as the carbon nucleophile when we made our disconnection of a bond between the two carbonyl groups. Now we have moved to the even-numbered relationship 1,2-diCO this is not possible. In the simple cases of a 1,2-diketone 1 or an a-hydroxy-ketone 4, there is only one C-C bond between the functionalised carbons so, while we can use an acid derivative 3 or an aldehyde 5 for one half of the molecule, we are forced to use a synthon of unnatural polarity, the acyl anion 2 for the other half. We shall start this chapter with a look at acyl anion equivalents (d1 reagents) and progress to alternative strategies that avoid rather than solve the problem. 

We used this strategy in chapter 6 under two-group C-X disconnections where bromination of ketones was the usual functionalisation. More relevant here are conversions of carbonyl compounds into 1,2-dicarbonyl compounds by reaction with selenium dioxide SeC>2 or by nitrosation. So acetophenone 57 gives the ketoaldehyde10 58 with SeC>2. These 1,2-dicarbonyl compounds are unstable but the crystalline hydrate 59 is stable and 58 can be reformed on heating. Since aromatic ketones such as 57 would certainly be made by a Friedel-Crafts reaction the disconnection 58a is not between the two carbonyl groups and offers an alternative strategy. 

Metaproterenol 64 is an adrenaline analogue used as a bronchodilator.11 The amine might be inserted by reductive amination on the aldehyde 65 and this might be made by a-functionalisation of the available ketone 66. 

---