Lithium carboxylates, reaction with

This procedure illustrates a new method for the preparation of 6-alkyl-a,g-unsaturated esters by coupling lithium dialkylcuprates with enol phosphates of g-keto esters. The procedure for the preparation of methyl 2-oxocyclohexanecarboxylate described in Part A Is based on one reported by Ruest, Blouin, and Deslongcharaps. Methyl 2-methyl-l-cyc1ohexene-l-carboxylate has been prepared by esterification of the corresponding acid with dlazomethane - and by reaction of methyl 2-chloro-l-cyclohexene-l-carboxyl ate with lithium dimethylcuprate. -... 

Alpha hydrogen atoms of carbonyl compounds are weakly acidic and can be removed by strong bases, such as lithium diisopropylamide (LDA), to yield nucleophilic enolate ions. The most important reaction of enolate ions is their Sn2 alkylation with alkyl halides. The malonic ester synthesis converts an alkyl halide into a carboxylic acid with the addition of two carbon atoms. Similarly, the acetoacetic ester synthesis converts an alkyl halide into a methyl ketone. In addition, many carbonyl compounds, including ketones, esters, and nitriles, can be directly alkylated by treatment with LDA and an alkyl halide. 

Lithium aluminum hydride, reaction with aldehydes, 610 reaction with carboxylic acids. 611-612... 

The next major obstacle is the successful deprotection of the fully protected palytoxin carboxylic acid. With 42 protected functional groups and eight different protecting devices, this task is by no means trivial. After much experimentation, the following sequence and conditions proved successful in liberating palytoxin carboxylic acid 32 from its progenitor 31 (see Scheme 10) (a) treatment with excess 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) in ie/t-butanol/methylene chloride/phosphate buffer pH 7.0 (1 8 1) under sonication conditions, followed by peracetylation (for convenience of isolation) (b) exposure to perchloric acid in aqueous tetrahydrofuran for eight days (c) reaction with dilute lithium hydroxide in H20-MeOH-THF (1 2 8) (d) treatment with tetra-n-butylammonium fluoride (TBAF) in tetrahydrofuran first, and then in THF-DMF and (e) exposure to dilute acetic acid in water (1 350) at 22 °C. The overall yield for the deprotection sequence (31 —>32) is ca. 35 %. 

Eq. (3), with lithium diisopropylamide (LDA) to a lithiospecies and in its subsequent reaction with C02 affording via the corresponding 4-carboxylic acid its ethyl ester 59. In the alternative version perchlorate 48e is electro-chemically reduced in acetonitrile to an anionic species that was converted either to a 3 1 mixture of isomers 56 (R = f-Bu) and 60 or to 4//-thiopyran 56 (R = PhCH2) with f-BuI or PhCH2Br, respectively (90ACS524). The kinetics of the benzylation procedure was followed by cyclic voltammetry [88ACS(B)269]. 

The procedure described here illustrates the preparation of mixed lithium arylhetero(alkyl)cuprate reagents and their reactions with carboxylic acid chlorides,4 These mixed cuprate reagents also react with a,a -dibromoketones,12 primary alkyl halides,4 and a,/3-unsaturated ketones,4 with selective transfer of only the alkyl group. 

A variation of this transfonnation reacts the acid with hthium naphthalenide in the presence of 1-chlorobutane. The product is the ketone. A related reaction treats the lithium carboxylate with lithium metal and the alkyl halide, with sonication, to give the ketone. ... 

In this section primarily reductions of aldehydes, ketones, and esters with sodium, lithium, and potassium in the presence of TCS 14 are discussed closely related reductions with metals such as Zn, Mg, Mn, Sm, Ti, etc., in the presence of TCS 14 are described in Section 13.2. Treatment of ethyl isobutyrate with sodium in the presence of TCS 14 in toluene affords the O-silylated Riihlmann-acyloin-condensation product 1915, which can be readily desilylated to the free acyloin 1916 [119]. Further reactions of methyl or ethyl 1,2- or 1,4-dicarboxylates are discussed elsewhere [120-122]. The same reaction with trimethylsilyl isobutyrate affords the C,0-silylated alcohol 1917, in 72% yield, which is desilylated to 1918 [123] (Scheme 12.34). Likewise, reduction of the diesters 1919 affords the cyclized O-silylated acyloin products 1920 in high yields, which give on saponification the acyloins 1921 [119]. Whereas electroreduction on a Mg-electrode in the presence of MesSiCl 14 converts esters such as ethyl cyclohexane-carboxylate via 1922 and subsequent saponification into acyloins such as 1923 [124], electroreduction of esters such as ethyl cyclohexylcarboxylate using a Mg-electrode without Me3SiCl 14 yields 1,2-ketones such as 1924 [125] (Scheme 12.34). 

Conversions of carboxylic acids to ketones are typically performed in stepwise fashion6 via intermediates such as acid chlorides,7 anhydrides,8 thioesters,9 or N-alkoxy amides,10 or by the direct reaction of carboxylic adds with lithium reagents.11 In this latter method trimethylsifyl chloride has been shown to be an effective reagent for trapping the tetrahedral alkoxide intermediates and for quenching excess organolithium reagent. 

Reactions with Carboxylic Acid Esters Alkyl nitrones can be metallized upon treatment with phenyl lithium in ether solution. The Li-derivatives react with carboxylic acid esters to give 3-oxo nitrones (305)- the analogs of 3-diketones and j3-keto esters (545). With the help of the 13C NMR method it has been found that 3-oxo nitrones (305) exist as an equilibrium mixture... 

Besides their application in asymmetric alkylation, sultams can also be used as good chiral auxiliaries for asymmetric aldol reactions, and a / -product can be obtained with good selectivity. As can be seen in Scheme 3-14, reaction of the propionates derived from chiral auxiliary R -OH with LICA in THF affords the lithium enolates. Subsequent reaction with TBSC1 furnishes the 0-silyl ketene acetals 31, 33, and 35 with good yields.31 Upon reaction with TiCU complexes of an aldehyde, product /i-hydroxy carboxylates 32, 34, and 36 are obtained with high diastereoselectivity and good yield. Products from direct aldol reaction of the lithium enolate without conversion to the corresponding silyl ethers show no stereoselectivity.32... 

When the reaction with substituted benzaldehydes is conducted in the presence of ammonia, the a-amino carboxylic acids are formed [11], The corresponding reaction involving bromoform is less effective and, for optimum yields, the addition of lithium chloride, which enhances the activity of the carbonyl group, is required. In its absence, the overall yields are halved. The reaction of dichlorocarbene with ketones or aryl aldehydes in the presence of secondary amines produces a-aminoacetamides [12, 13] (see Section 7.6). 

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