Cadman, MLF; Crombie, L; Freeman, S; Mistry, J
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 ⼠4:1 whilst the 5-methoxycarbonyldodecane-4,8-dione 53 save a 1 : ⼠4 ratio.