The chemoselective cyclisation of unsymmetrical γ-diketones to cyclopentenones by directed aldol reaction using a magnesium chelate

The feasibility of synthesising disubstituted cyclopent-2-enones chemoselectively from unsymmetrical γ-diketones, using an aldol reaction directed by magnesium chelation, has been studied. Treatment of 3,3-dimethylhexane-2,5-dione 15 with aqueous sodium hydroxide (0.5 mol dm–3) gives a mixture of 3,5,5-trimethyl-12 and 3,4,4-trimethylcyclopent-2-enone 14 in an isomer ratio of 2.2 : 1. Insertion of an α-methoxycarbonyl grouping as a control element allows formation of a magnesium chelate 17 when treated with magnesium methoxide, and the major product is then mainly the undehydrated aldol 21. This, when treated with aqueous sodium hydroxide (0.5 mol dm–3) to dehydrate, hydrolyse and decarboxylate, gives the 3,5,5-trimethyl- and 3,4,4-trimethylcyclopent-2-enones in a nearly chemospecific ratio of 1 : 49. When 3-methoxycarbonyl-4,4-dimethylhexane-2,5-dione 16 is treated with aqueous sodium hydroxide (0.5 mol dm–3), omitting the magnesium methoxide treatment, the corresponding ratio of cyclopentenones was still an interesting 1 : 7.3. Treatment with sodium methoxide in methanol gives, by contrast, γ-lactone 27.Treatment of undecane-4,7-dione 34 with aqueous sodium hydroxide (0.5 mol dm–3) at reflux gives 2,3-dipropylcyclopent-2-enone 36 and 3-butyl-2-ethylcyclopent-2-enones 35 in a ratio of almost 1 : 1. Treatment of 6-methoxycarbonylundecane-4,7-dione 33 with magnesium methoxide in methanol gives undehydrated aldol which when treated with aqueous sodium hydroxide gives the dipropylcyclopent-2-enone 36 and 3-butyl-2-ethylcyclopent-2-enones 35 in 9 : 1 ratio. Conversely, the 5-methoxycarbonyldione 32 gives a corresponding ratio of 36 to 35 of 1 : 9. The best ratios attained, 1 : 15 for 36 and 35 from 32 and 20 : 1 for 36 and 35 from 33, were when magnesium methoxide in refluxing benzene or toluene were employed. There is still a strong chemoselective effect when the magnesium treatment is omitted.Preliminary examination of the corresponding cyclohex-2-enone systems gave poorer chemoselectivities when either procedure was employed. 6-Methoxycarbonyldodecane-5,9-dione 52 gave 2,3-dipropyl-54 and 3-butyl-2-ethyl-cyclohex-2-enone 55 in a ratio of ∼4 : 1 whilst the 5-methoxycarbonyldodecane-4,8-dione 53 gave a 1: ∼4 ratio.