Alkylation of dianions of .beta.-keto esters

Abstract

The dianions from a variety of P-keto esters have been generated using 1 equiv of sodium hydride and 1 equiv of n-butyllithium or methyllithium or 2 equiv of lithium diisopropylamide. The dianions react with a range of alkylating agents to produce y-alkylated products exclusively in good yield. Reaction of these dianions with a,wdihaloalkanes yields cyclic 1 : 1 adducts, cyclic 1 : 2 adducts, or acyclic 1 : 2 adducts, depending on the alkylating agent and the reaction conditions. This method offers ready access to a wide range of compounds which were previously difficult to obtain, ecently we had envisioned the synthesis of a num-(4) J. D. Hagarty, U. S. Patent 3,565,928 (1971); Chem. Absrr., 74, ( 5 ) T. M. Harris and C.

Total Synthesis of Tetranormethyl-calcimycin

“…A dianion solution of methyl acetoacetate (12.5 ml, 116.3 mmol) was prepared with a 60% NaH (5.0 g, 125.1 mmol) and 1.36N n-:-BuLi hexane solution, (92.0 ml, 125.1 mmol) in dry THF (200 ml), according to the literature. 16 ) To the solution was ,added 4-bromo-1-butene (15.0ml, 147.8 mmol) with stirring at O°C under Ar, stirring being continued for 2 hr. AcOH was then added to the mixture to destroy any excess base, and the mixture was concentrated in' vacuo.…”

“…Condensation of 15 with an aminophenol (19)5) was achieved with the help of benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate (BOP)13) to give an amide (16), which was heated with a catalytic amount of pyridinium p-toluenesulfonate 14 ) in dichloroethane to produce the benzoxazole drivative 17 in a reasonable yield. Completion of the synthesis requireddeprotecting the" amino and carboxyl groups.…”

Evolution of a Strategy for the Synthesis of Structurally Complex Batzelladine Alkaloids. Enantioselective Total Synthesis of the Proposed Structure of Batzelladine F and Structural Revision.

“…Thus, addition of the dianion of methyl acetoacetate (50) to iodide 49 proceeded cleanly, delivering 51 in 68% yield. 33 Transesterification of this product with allyl alcohol gave allyl ester 52 in nearly quantitative yield. 34…”

The Development of a Facile Tandem Wolff/Cope Rearrangement for the Synthesis of Fused Carbocyclic Skeletons

“…2 To a cooled solution (-5 °C; salt water-ice bath) of methyl acetoacetate (13.2 mL, 123 mmol) in anhydrous THF (250 mL) under an N 2 atmosphere was added NaH (60% dispersion in oil, 6.4 g, 160 mmol) portionwise over 5 min. The resulting gray suspension was stirred 15 min after which time a clear solution had formed.…”

“…The crude yellow oil was purified by flash chromatography (10:1 hexanes:ethyl acetate eluent) to yield SM2 (9.6 g, 48% yield) as a faint yellow oil: All physical data compares favorably with reported literature data. 2 a-Diazo-b-Keto ester SM3. To a solution of b-keto ester SM2 (1.0 g, 5.1 mmol) in acetonitrile (15 mL) at 23 °C was added triethylamine (1.42 mL, 10.2 mmol) via syringe followed by paraacetamidobenzenesulfonyl azide, pABSA 3 (1.59 g, 6.6 mmol).…”