A-Chloro enones

Ceriumflll) chloride heptahydrate. 14,75-77,15,72-73,16,67-68 18,87 20,75 a-Chloro enones. a,p-Epoxy ketones undergo ring opening and dehydration, but changing the solvent system from aq MeOH to MeCN stops the dehydration step. The behavior of 2,3-epoxycyclopentanone differs from that of the cyclohexanone homologue in that the product dehydrates much more readily. 

Interestingly, when the chloro analog was transmetallated and treated with 3-ethoxy cyclohexen-l-one, the expected enone (XI) was not observed, but an enone with a mass of 34 units greater than (XI) was noticed. It also indicated the enone carried the chloro analog. It was presumed that the hetero atoms in the heterocycle present in the starting material (VIII) had performed a directed metallated lithiation providing a different enone bearing the chloro moiety. 

The 1,4-reduction of an enone in the presence of a ketal is shown in Eq. 275.436 The Et3SiH/TFA system reduces the polyfunctional cyclic ,/3-enone in Eq. 276 without affecting the c/-hydroxy carboxyl or a-chloro keto groups.453... 

The Stille coupling of a-iodo enones is sluggish under standard conditions. Significant rate enhancement was observed for the Stille reaction of 2-chloro-5-tributylstannylpyridine and a-iodo enone 76 using triphenylarsine as the soft palladium ligand and Cul as the co-catalyst [63], Oxygenated functionalities did not affect the efficiency of the reaction provided both Ph3As and Cul were added. Additional manipulations of 77 resulted in the synthesis of (+)-epibatidine (78). 

When the 4-position is substituted, Grignard addition occurs at the 2-position, to eventually give a 2,4,6-trisubstituted pyridine via the 6-lithiated species (Scheme 145) (88TL1751). Alternatively, if the 4-substituent is a chloro (88TL1751) or methoxy group (89TL5053), the initial product can be hydrolyzed to an enone rather than being aromatized to a pyridine. 

The facile elimination of -heterosubstituents in ketones allows for the ready construction of a,p-enones. Three different heteroatoms have been employed, chlorine, nitrogen and oxygen. The -chloro enones (products of Friedel-Crafts acylation) suffer Nazarov cyclization under standard conditions. -" Jacquier has prepared a series of -amino enones (31) from Mannich condensations." These substrates undergo cyclization in modest yields under standard conditions (equation 23). Takeda has found that the readily available" tetrahydro-4-pyranones (32) produce 2-cyclopentenone-4-carboxylates upon treatment with TMS-I (equation 24). " It is noteworthy that the putative a-carboalkoxy divinyl ketones have been independently cyclized by Marino using TMS-I. ... 

As in the foregoing systems, a regiochemical ambiguity arises unless the alkene is either symmetrical or highly biased toward Maricovnikov-type addition. Both acid chlorides and bromides can be employed. Aluminum trichloride is the preferred reagent." - Frequently the divinyl ketone or -chloro enone intermediates are isolable as by-products which can be subsequently cyclized. Representative structures are similar to those collected in Scheme 35. 

One synthesis of cyclopentenone [80], requiring a resolution, involved initial ring contraction of phenol when treated with alkaline hypochlorite (49). Resolution of the resulting cis acid [85] was effected with brucine. The desired enantiomer [86] formed the more soluble brucine salt and was thus obtained from the mother liquors of the initial resolution. Oxidative decarboxylation with lead tetracetate, partial dechlorination with chro-mous chloride, and alcohol protection gave chloro enone [87]. Zinc-silver couple (50) dechlorinated [87] to the desired cyclopentenone [80]. 

P-CA/oro-a,p-eiioiies. P-Diketones, particularly cyclic ones, can be converted into p-chloro-a,p-enones by reactions with 1 and LiH as base. Yields are increased substantially by addition of LiCl (2 equiv.). 

With chloroacetyl chloride and aluminum chloride, addition of chloride gave the P-chloro-a-silyl enone in addition to the alkynic ketone. Addition of halide has also been observed in alkynations of 2-alkoxy-1 -trimethylsily lethynes. ... 

Vol 2, p 125) has been reported. In the new process, a-chloro-acryloyIchloride and the fulvene (71) were reacted to give the adduct (72). Hydrolysis of the derived ketone (73) gave the enone... 

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