Dianion formation, acetoacetate

Acylation of the dianion of ethyl acetoacetate by an ester is a useful addition to this area of pyranone synthesis. In this reaction and in the formation of the trianions of 2,4,6-triketones the use of lithium diisopropylamide as the base is valuable (76JA7733). The triketo acid from the trianion cyclizes in mineral acids to the pyran-4-one, but in acetic anhydride the pyran-2-one is formed (Scheme 101) (71JA2506). 

The scope of the strategy was then extended in spectacular fashion (Scheme 6). The mixture of 19 and 20 was transformed into the corresponding aldehydes 26 through reduction/oxidation of the ester groups. Treatment with the dianion derived from ethyl acetoacetate then led to hydroxyketones 27. Chelation-controlled, syn-selective reduction [9] of this mixture followed by menthonide formation gave 28 as four diaste-... 

Hydroxyhomophthalates. Complete details are available for construction of benzene rings by condensation of 1, as the dianion equivalent of methyl acetoacetate, with various 1,3-dicarbonyl equivalents.1 The reaction has been extended to condensation of 1 with a 1,3,5-tricarbonyl unit to form 3-hydroxyhomophthalates. Thus when 1 (2 equivalents) is treated with trimethyl orthoformate (1 equivalent) in the presence of TiCl4, dimethyl 3-hydroxy-homophthalate (2) is formed in 68% yield. The reaction is believed to involve formation of the 1,3,5-tricarbonyl equivalent a, which then condenses with 1 to form 2. 

The rate of the Carroll rearrangement has been increased by formation of a dianion on treatment of allylic acetoacetates with two equivalents of lithium diisopropylamide in tetrahy-drofuran at — 78 CC followed by heating to reflux l0°. With one equivalent of base no reaction occurs. 

Trost and co-workers have reported the coupling of 7-methyloct-Z-2-en-l-yl bromide with the dianion of methyl acetoacetate to give (168) (R=Hi) (186). The diazoderivative (168) (R=Na) was thermolyzed in the presence of copper powder to give the cyclopropane (169). Ring cleavage of the cyclopropyl ring using lithiiun dimethyl cuprate resulted in stereospecific formation of the cholesterol side chain where the relative orientation of the ultimate C-17 and C-20 positions in (170) is the same as that of the natural product. 

---