4- Oxopentanoate esters

Oxopentanoate (Levulinate) Ester ROCOCH2CH2COCH3, LevOR Formation... 

The synthesis of 4-alkyl-y-butyrolactones 13 and 5-alkyl-<5-valerolactones 14 can be achieved in high enantiomeric excess by alkylation of ethyl 4-oxobutanoate and ethyl 5-oxopentanoate (11, n = 2, 3). The addition of diethylzinc, as well as dimethylzinc, leads to hydroxy esters 12 in high optical purity. When methyl esters instead of ethyl esters are used as substrates, the enantioselectivity of the addition reaction is somewhat lower. Alkaline hydrolysis of the hydroxy esters 12, followed by spontaneous cyclization upon acidification, leads to the corresponding y-butyro- and -valerolactones32. 

Methyl 4,4-dimethyl-3-oxopentanoate Pentanoic acid, 4,4-dimethyl-3-oxo-, methyl ester (9) (55107-14-7)... 

The procedure is very easy to reproduce and the asymmetric reduction may be applied to a wide range of aromatic ketones and keto esters such as ethyl 3-oxopentanoate. 

No metalation is required for the / -fluorination of a-oxo esters.150 Ethyl 3-methyl-2-oxo-butanoate and 3-methyl-2-oxopentanoic acid give the corresponding /f-fluoro derivatives 30 a and 30 b, respectively, in quantitative yield on reaction with A-fluorobis(trifluoromethylsul-fonyl)amine (Id). 3-Fluoro-2-oxobutanoic acid (30c) is exclusively formed by treating 2-oxobutanoic acid with an equimolar amount of reagent Id.150... 

For esters with only one a-hydrogen, such as ethyl 2-methyl propanoate (ethyl isobutyrate), a more powerful base (e.g. sodium triphenylmethide, Ph3CeNa ) is required to affect the condensation reaction [the forced Claisen ester condensation, e.g. the synthesis of ethyl 2,2,4-trimethyl-3-oxopentanoate (ethyl iso-butyrylisobutyrate), Expt 5.176]. In this case the reaction sequence is completed in the step corresponding to (ii) above since the /1-keto ester (24) has no a-hydro-gen for step (iii), and the powerful base is required to force the equilibrium (i) to the right. 

One preparative procedure for achieving this reaction involves the acylation of the magnesium enolate of diethyl malonate with an acid chloride in benzene solution (cf. Expt 5.96), and the resulting aclymalonic ester is then heated to 200 °C with an arylsulphonic acid to effect the decarbethoxylation step. An illustrative example is the preparation of ethyl 3-oxopentanoate (ethyl propionyl-acetate, Expt 5.177). 

In the absence of monomer, GTP catalysts are destroyed by the initiator. A one to one molar mixture of bifluoride and MTS, for example produces methyl isobuterate, trimethylsilylfluoride, trimethylsilylmethoxide, methyl 2,2,4-trimethyl-3-oxopentanoate, and other oligomers [19, 26]. Seebach has shown that ester enolates generate ketenes at room temperature [27] (Scheme 16). These reactions support the dissociative mechanism wherein... 

Let s try a synthesis. Suppose the target is ethyl 2-methyl-3-oxo-2-propylpentanoate. The presence of the /3-ketoester functionality suggests employing an alkylation reaction and/or an ester condensation. In one potential pathway, the propyl group can be attached by alkylation of a simpler /3-ketoester. Further retrosynthetic analysis suggests that the new target (ethyl 2-methyl-3-oxopentanoate) can be prepared from ethyl propanoate by a Claisen ester condensation. 

Reduction of octyl 3-oxopentanoate with baker s yeast furnishes octyl (S)-3-hydroxypentanoate of 97% e.e. After transesterification to the corresponding methyl ester 18, it can be purified as its 3,5-dinitrobenzoate to give (S)-18 of 100% e.e. (21). 

The (S)-enzyme (relative molecular mass 48000 -50000) reduced 3-oxoacid esters, 4-oxo and 5-oxoacids and esters enantioselectively to (S)-hydroxy compounds. The K -values for ethyl 3-oxobutanoate, ethyl 3-oxohexanoate, 4-oxopentanoic acid and 5-oxohexanoic acid were determined as 0.9 mM, 5.3 mM, 17.1 mM and 13.1 mM, respectively. 

SYNS ETHYLKETOVALERATE ETHYL 4-KETOVALERATE ETHYL LAEVULINATE ETHYL LEVULATE ETHYL 4-OXOPENTANOATE ETHYL 4-OXOVALERATE LEVULINIC ACID, ETHYL ESTER... 

C6H10O3 3-methyl-4-oxopentanoic acid 6628-79-1 17.00 1.0932 1 8174 C6H11N04 L-glutamic acid 5-methyl ester 1499-55-4 25.00 1.1410 2... 

There are a number of variations of the condensation reaction of acid derivatives. The reaction between a cyclic ketone having a pendant alkynyl ester unit and tetra-butylammonium fluoride leads to cyclization to a bicyclic alcohol with an exocyclic allene moiety. A chain-extension reaction culminates in acyl addition of an ester enolate. The reaction of a p-keto ester, such as methyl 3-oxobutanote and EtZnCH2k leads to chain extension via a carbenoid-like insertion reaction (p. 803), which reacts with an aldehyde in a second step to give a methyl 3-oxopentanoate derivative with a —CH(OH)R group at C-2 relative to the ester carbonyl. ... 

Ethyl levulinate (4-oxopentanoic acid ethyl ester)... 

---