Chiral cyclohexanone

F E R R I E R Chiral cyclohexanone synthesis Transtormatlon o< unsaturated glycosides into cyclohexanone derivatives by heating in aqueous acetone with mercury (II) salts... 

Reductive hydrolysis of anilines, which may occur as an unwanted side reaction when anilines are reduced in aqueous media, can be turned to synthetic advantage. Reductive cleavage is facilitated by substitution on the nitrogen and by acidic media. Palladium is the preferred catalyst (33), Reductive hydrolysis of substituted anilines carrying chiral N-substituents gives chiral cyclohexanones (34),... 

A very effective method for removal of the chiral auxiliary from cyclohexenones 34 involves treatment with I2 in THF-H2O to give the iodolactones 35 (Scheme 9). These highly functionalized chiral cyclohexanones have figured prominently in the asymmetric synthesis of natural products e.g. Scheme 15. Furthermore, selective cleavage of the cyclohexanone ring in 35... 

Although reasonable asymmetric induction has been observed in the alkylation of a chiral cyclohexanone enamine, it was noted1 in 1977 that in order to obtain higher induction in this type of reaction. Clearly what is needed is an amine with a C2 axis of symmetry . (+ )-trans-... 

The copper-catalyzed conjugate addition of methyl magnesium iodide to cyclohexenone and trapping the enolate as its trimethylsilyl enol ether, followed by a trityl hexachloro-antinomate-catalyzed Mukaiyama reaction, is apphed to / -(—jcarvone. C-2, C-3 functionalized chiral cyclohexanones are converted into their a-cyano ketones, which are submitted to Robinson annulation with methyl vinyl ketone. Highly functionalized chiral decalones are obtained that can be used as starting compounds in the total synthesis of enantiomerically pure clerodanes (equation 70). 

To reach chiral cyclohexanones, we have found that the bicyclic lactam 10, derived from 5-oxohexanoic acid and the commercially available amino diol, gave excellent results. A number of examples were obtained (Table I).8... 

Hydrogenation of A, Af-dimethylaniline in dilute aqueous HCl produces cyclohexanone and cyclohexanol (90% yield). Reductive hydrolysis of anilines that are properly substituted with a chiral ligand on the nitrogen atom affords chiral cyclohexanones with 30% optical yield ... 

Hanessian and Beaudoin [310] have performed the diastereoselective condensation of lithiated phosphonamides 1.74 with prochiral or chiral cyclohexanones. Each enantiomer of the nonracemic alkene product is prepared from the appropriate reagent (Figure 6.34). Denmark and Chen studied similar reactions of oxazaphosphorinanes 1.96 (R = Ph, SPh) [356], These reactions are performed in a two-step fashion, and olefin formation requires activation with PhjCOTf in the presence of 2,6-hrtidine. 

Butadiene telomerizes with chiral cyclohexanone-derived enamines under substrate control with (5)-2-(methoxymethyl)pyrrolidine (SMP) or its a,a-dimethyl analog as chiral auxiliary12. After removal of the auxiliary by hydrolysis, 2-[( )-2,7-octadienyl]cyclohexanone (6) is obtained in 57 % yield with 72 % ee (R = H) or in 60 % yield with 92 % ee (R = CH3). Cyclopen-tanones, cycloheptanones and cyclooctanones can be similarly converted. 

They developed a flow system in which ethylene was introduced into the stream by a needle valve. After introduction of the gas the tubing was wrapped around a medium pressure Hg arc lamp (Schemed 9A). Using this flow system they converted chiral cyclohexanone 50 to cyclobutane 51 and observed a 10-fold increase in rate with quantitative conversion to the desired cyclobutane after 1 minute (Scheme 9B). 

Following similar iminium activation strategies using prolinol-derived organocatalysts, highly functionalized chiral cyclohexanone derivatives [192], dihydropyranone compounds [193], and polysubstituted cyclopentanones [194] have been also synthesized. 

Chiral cyclohexanones obtained by the Ferrier carbocyclization reaction are useful precursors for the synthesis of cyclitols and aminocyclitols, some of which are found in clinically important aminoglycoside antibiotics. Additionally, highly substituted cyclohexenones, prepared by the Ferrier carbocyclization followed by (3-elimination, can undergo various further transformations, also making these compounds potential chiral building blocks for the preparation of structurally complex compounds having cyclohexane unit(s). This section provides an overview of the reported synthetic strategies toward various types of natural products based on utilization of the Ferrier carbocyclization reaction. 

Conformational effects on mesomorphism and twisting ability of chiral cyclohexanones in mesophases have been studied by Kutulya et al by the use of the semiempirical AMI and PM3 methods and by analysis of proton-proton couplings. 

At present, chiral Pt(II) complexes represent the most efficient catalytic system in terms of activity and enantioselectivity for poorly reactive meso and chiral cyclohexanones, with important improvements observed when working in water, as reported in the following sections. 

Fig. 12 Synthesis of chiral cyclohexanone bearing a terminal alkyne and chiral cycloheptanone by copper-NHC-catalysed ECA of Grignard reagents to cyclic enynones by Alexalds [84]...

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