Ethyl 2-methyl-3-oxopentanoate

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. 

Ethoxide Ethyl 2-methyl-3-oxopentanoate (stronger acid p Tj 11)... 

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. 

The required nitroalkane was synthesised from ethyl levulinate (ethyl 4-oxopentanoate) by formation of ethyl 4-oxopent-2-enoate by bromination/dehydrobromination, reduction with sodium borohydride in methanol to give initially ethyl 4-hydroxypent-2-enoate in 82% yield and Michael addition of methyl nitromethane (in 70% yield) from which 2-methoxy-5-methyl-4-... 

ANSWER (b) Ethyl 3-oxopentanoate can be alkylated twice, first Avith methyl iodide and then Avith ethyl iodide. Hydrolysis and decarboxylation give the desired product. 

Other novel diazo compounds that have been subjected to 1,3-dipolar cycloaddition with activated alkenes, and that give unusually functionalized pyrazolines (Scheme 8.7), include l-diazo-3-trimethylsilylpropan-2-one (20) (49), 2-diazo-methyl-4(57/)-furanones (21) (50), methyl 2-diazo-5-methylanilino-5-oxopentano-ate (22) (51), 2-(acylamino)-2-diazoacetates (23) (51), ethyl 2-diazo-4,4,4-trichloro-3-(ethoxycarbonylamino)butyrate (24) (52), and diazopropyne (53). 

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. 

Ethyl 2-methyl-3-oxo-2-propylpentanoate Ethyl 2-methyI-3-oxopentanoate... 

Form Supplied in colorless oil commercially available. Analysis of Reagent Purity optical rotation NMR spectroscopy. Preparative Methods the preparation of (5, 5)-ethyl-DuPHOS is based on (3R,61 )-octane-3,6-diol as an enantiomerically pure starting compound. The latter is synthesized by a three-step procedure starting from methyl 3-oxopentanoate, which is transformed to methyl (l )-3-hydroxypentanoate (99% ee) by enantioselective hydrogenation with a Ru-(R)-BINAP catalyst, followed by hydrolysis to the hydroxy acid. The subsequent electrochemical Kolbe coupling reaction leads to (3R,6R)-octane-3,6-diol in a protocol that can be scaled up to multigram quantities (eq 1). ... 

C6H10O3 2-methyl-4-oxopentanoic acid 6641-83-4 459.55 40.012 2 7993 C6H11Br02 ethyl 2-bromobutanoate 533-68-6 450.15 39.116 ... 

C7H1203 methyl 3-methyl-4-oxopentanoate 25234-83-7 473.15 41.310 1,2 11601 C7H13CI02 ethyl 2-chloro-3-methylbutanoate 91913-99-4 452.15 39.306 1,2... 

C8H1403 ethyl 4-methyl-3-oxopentanoate 7152-15-0 446.15 38.735 1,2 14751 C8H15CI 1 -chloro-4-ethyl-3-hexene 82507-04-8 446.15 38.822 ... 

A useful sabinene (767) synthesis has been described by Rousseau and Slougui. The keto ester 768 (R = O) was prepared conventionally from ethyl 4-methyl-3-oxopentanoate and converted to the methylene compound 768 (R = CH2) by a Wittig reaction. The trimethylsilylketene acetal 769 was then treated with bromoform and diethylzinc in pentane, yielding 70% of the ester 765 (R =... 

Longer chained 2-oxo alkanoates, as well as 4-methyl-2-oxopentanoates, behave in a similar manner (Table 4). e.g., ethyl 4-methyl-2-oxopentanoate gives ethyl (S )-2-hydroxy-4-methylpentanoate with 75% ee upon reduction with Alpine-Borane29. 

This breakthrough comes from a vague notion that the isopropyl group of methyl 4-methyl-3-oxopentanoate may even be a little too large and the ethyl group of methyl 3-oxopentanoate may be a little too small. Hence we decided to test a cyclopropyl group, which has a size between that of the isopropyl and ethyl groups (eq. 2). 

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