Cyclohexenones, from 1,5-diketones

I, 5-dicarbonyl compounds and their interesting and varied chemistry, e.g., the formation of cyclohexenones from aldol condensation of the products. As an extension of the de Mayo reaction (the photocycloaddition of enolated /i-diketones to double bonds) enol esters, enol ethers, vinylogous esters and amides, and dioxinone have been employed as the enone components. Some intermolecular examples have already been discussed in Section 1.6.1.4.2.1.6. (cf. Table 4, entries 2 and 3) and some intramolecular systems are collected in Table 5, entries 10,... 

Cyclohexenone ring from diketones Azeotropic water entrainment... 

Although problems of regiochemistry are inherent, the aldol condensation of diketones has found vide application. Typical examples are syntheses of cyclopentenones and cyclohexenones from 1,4- and 1,5-diketones, respectively. The concept is illustrated by a synthesis of jasmone 12 (Eq. (12)) [28] and of the homosteroid derivative 13, the latter arising under thermodynamic control in a Robinson annelation reaction (Eq. (13)) [29]. 

Cyclohexenone ring from diketones with ester hydrolysis or decarbalkoxylation... 

The first step of the Robinson annulation is simply a Michael reaction. An enamine or an enolate ion from a jS-keto ester or /3-diketone effects a conjugate addition to an a-,/3-unsaturated ketone, yielding a 1,5-diketone. But as we saw in Section 23.6,1,5-diketones undergo intramolecular aldol condensation to yield cyclohexenones when treated with base. Thus, the final product contains a six-membered ring, and an annulation has been accomplished. An example occurs during the commercial synthesis of the steroid hormone estrone (figure 23.9). 

Cyclohexenone is reduced either by sodium amalgam [138] or electrochemically in acetonitrile containing tetrabutylammonium fluoroborate [139] and affords mainly the tail-to-tail diketonic hydrodimer. Some 10-26% of the head-to-tail hydrodimer has been detected in the mixture of products from reduction at a mercury cathode in aqueous ethanol under both acidic and basic conditions [140]. Substituents on the 3- and 4-positions, as in XXXIII, cause formation of some head-to-tail XXXV and head-to-head hydrodimers XXXVI (see Table 9). The product ratios depended on the concentration of water in acetonitrile used as solvent. Other work discussed later indicates that the presence of metal ions that can coordinate with alkoxy groups also changes these product ratios. 

Diketones and their aldol-derived cyclohexenones are obtained from alkylation of l-benzyl-2,6-di-cyanopiperidine followed by hydrolysis. - This dicyano analog of (47) provides a new method for the synthesis of rra/u-2-mediyl-6-ui ecylpiperidine (solenopsin), a-propylpiperidine (coniine) and other 2,6- alkylpiperidine alkaloid. 

Silyl enol ethers need Lewis acid catalysis for efficient Michael reactions, such as the more substituted (and conjugated) isomer 110 forming a 1,5-diketone 111 from cyclohexenone in good yield.39 This product 111 is a mixture of diastereoisomers as have been many of the products in this chapter. We have also seen some reactions giving single diastereoisomers but without explanation. It is high time that we addressed the question of stereoselectivity and this is the subject of the next chapter. 

Intermolecular de Mayo reactions are efficient for cyclic 1,3-diketones such as dimedone (5,5-dimethyl-l,3-cyclohexanedione)96,103,104 and acyclic systems such as acetylacetone93-95. Unsymmetrical acyclic /l-diketones, such as 1-phenyl-1,3-butanedione98 can enolize in two directions, however, reaction normally occurs preferentially from a single enol form. Examples of alkene photocycloaddition to trapped ends of /(-dicarbonyl compounds (e.g., 2,2-dimethyl-3(2/f)-furanone and 2,2.6-trimethyl-4/f-l,3-dioxin-4-one) are given in Table 1 (entries 26, 27) and Table 2 (entry 35) 10°. If the enol is stabilized by derivatization (e.g., acetylated dimedone 3-acetoxy-5,5-dimethyl-2-cyclohexenone), the primary cyclobutane photoproducts can be isolated96. 

Perchloric acidlL-phenylalanine 2-Cyclohexenone ring from 1,5-diketones Asym. induction... 

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