The Acylation of β-Keto Ester Dianions

Abstract

A method for the successful acylation of the dianion of simple β-keto esters to yield β,δ-diketo esters has been developed. The dianion of methyl acetoacetate also reacts with the monoanion of methyl acetoacetate to give a triketo ester which cyclizes to methyl orsellinate. These dianions also add to nitriles to give 5-amino-3-keto-4-pentenoates which may in some cases cyclize to 4-hydroxypyridones.

Chemoenzymatic synthesis of the chiral side-chain of statins: application of an alcohol dehydrogenase catalysed ketone reduction on a large scale

“…Large amounts of unreacted tert-butyl acetoacetate were found in the crude products of these reactions. These results are in accordance with the findings of Huckin and Weiler[23,24]. Presumably, the a-chloro substituent of methyl chloroacetate 14 can stabilise the primary tetrahedral addition intermediate which prevents the harmful liberation of the newly formed keto group prior to hydrolytic work-up.…”

“…Diketo esters like 10 are sensitive towards acids, bases, traces of heavy metal ions, and thermal stress which makes their isolation difficult. We decided to investigate the Cacylation of in situ generated b-keto ester bisenolates, a method introduced by Huckin and Weiler [23,24]. Yamaguchi and co-workers describe the preparation of methyl 6-chloro-3,5-dioxohexanoate by C-acylation of the Na,Libisenolate of methylacetoacetate with methyl chloroacetate (14) in the presence of boron trifluoride [25].…”

Synthesis of 4-Alkyl- and 4-(ω-Chloroalkyl)-3-hydroxy-5-alkylidenebuten­olides Based On Cyclizations of 4-Alkyl- and 4-(ω-Chloroalkyl)-1,3-bis(tri­methylsilyloxy)buta-1,3-dienes with Oxalyl Chloride

“…The syntheses of compounds 2b-h, [9][10][11][12][13][14] 3a and 4a, 2c and (2Z)-ethyl 2-[3-ethyl-4-hydroxy-5-oxofuran-2(5H)-ylidene]acetate (5a) 3b have been reported previously. 3b…”

“…Ethyl 3-Oxoheptanoate (2b) 9 Ethyl acetoacetate (6.30 mL, 50.0 mmol), i-Pr 2 NH (17.5 mL, 125.0 mmol), n-BuLi (15%, n-hexane; 78.5 mL, 125.0 mmol), and 1-iodopropane (1a; 10.20 g, 60.0 mmol) in THF (300 mL) gave 2b after chromatography (hexane-EtOAc, 100:1→5:1) as a slightly yellowish oil (7.70 g, 93%; 11% enol form). Ethyl 3-Oxodecanoate (2d) 11 Ethyl acetoacetate (6.3 mL, 50.0 mmol), i-Pr 2 NH (17.5 mL, 125.0 mmol), n-BuLi (15%, n-hexane; 78.5 mL, 125.0 mmol), and 1-iodohexane (1c; 12.7 g, 60.0 mmol) in THF (300 mL) gave 2d after chromatography (n-hexane-EtOAc, 100:1→5:1) as a slightly yellowish oil ( (4), 169 (10), 143 (33), 130 (100), 114 (13), 97 (17), 85 (22).…”

Synthesis of 3,3-Dimethylenedithio-5-oxyaldehydes

“…Although limited work has been reported on 1-3 the preparation of 3,s-dioxopentanoic esters, a literature survey reveals that this system is synthetically difficult owing to its unstability . An approach affording a potential ethyl 3,5-dioxopentanoic ester, in which the reactivity of the aldehyde group is 4 protected as a dithiane', is know. In order to extend the synthetic utility of such potential f3-ketoaldehydes, we became interested in the preparation of similar systems having a protected ketone group instead of the aldehyde group.…”