Lithium acid anhydrides

Diacyl peroxides have been reduced with a variety of reduciag agents, eg, lithium aluminum hydride, sulfides, phosphites, phosphines, and haUde ions (187). Hahdes yield carboxyUc acid salts (RO) gives acid anhydrides. With iodide ion and certain trivalent phosphoms compounds, the reductions are sufftcientiy quantitative for analytical purposes. 

Lithium aluminum hydride (LiAlH4) is the most powerful of the hydride reagents. It reduces acid chlorides, esters, lactones, acids, anhydrides, aldehydes, ketones and epoxides to alcohols amides, nitriles, imines and oximes to amines primary and secondary alkyl halides and toluenesulfonates to... 

Note that the diorganocopper reaction occurs only with acid chlorides. Carboxylic acids, esters, acid anhydrides, and amides do not react with lithium diorganocopper reagents. 

Other reagents used for the preparation of lactones from acid anhydrides are lithium borohydride [1019], lithium triethylborohydride (Superhydride ) [1019] and lithium tris sec-butyl)borohydride (L-Selectride ) [1019]. Of the three complex borohydrides the last one is most stereoselective in the reduction of 3-methylphthalic anhydride, 3-methoxyphthalic anhydride, and 1-methoxynaphthalene-2,3-dicarboxylic anhydride. It reduces the less sterically hindered carbonyl group with 85-90% stereoselectivity and is 83-91% yield [1019]. 

In the Mukaiyama aldol additions of trimethyl-(l-phenyl-propenyloxy)-silane to give benzaldehyde and cinnamaldehyde catalyzed by 7 mol% supported scandium catalyst, a 1 1 mixture of diastereomers was obtained. Again, the dendritic catalyst could be recycled easily without any loss in performance. The scandium cross-linked dendritic material appeared to be an efficient catalyst for the Diels-Alder reaction between methyl vinyl ketone and cyclopentadiene. The Diels-Alder adduct was formed in dichloromethane at 0°C in 79% yield with an endo/exo ratio of 85 15. The material was also used as a Friedel-Crafts acylation catalyst (contain-ing7mol% scandium) for the formation of / -methoxyacetophenone (in a 73% yield) from anisole, acetic acid anhydride, and lithium perchlorate at 50°C in nitromethane. 

The C2-symmetrical chiral amine tran.v-(2/ ,6y )-2,6-bis(benzyloxymethyl)piperidine (1), prepared15 from commercially available (S)-2-(benzyloxymethyl)oxirane, has been used in diastereoselective amide alkylations. Thus, the chiral amine of 76% ee is acylated [anhydride or mixed trimethylacetic acid anhydride, 1.2 equivalents of triethylamine and 0.05 equivalents of 4-(dimethylamino)pyridine] and the resulting amide 2 treated with 2.1 equivalents of lithium diisopropylamide at —78 CC to give the enolate. This is then alkylated to give high diastereo-meric ratios (>94 6) of alkylation products 3 in 60-93% yield16. 

Attempts to synthesize C-terminal peptide aldehydes using other reductive techniques are less successful. 24"29 The reduction of a-amino acid esters with sodium amalgam and lithium aluminum hydride reduction of tosylated a-aminoacyldimethylpyrazoles resulted in poor yields. 26,29 The Rosemond reduction of TV-phthaloyl amino acid chlorides is inconvenient because the aldehyde is sensitive to hydrazine hydrate that is used to remove the phthaloyl group. 27 28 jV -Z-Protected a-aminoacylimidazoles, which are reduced to the corresponding aldehydes using lithium aluminum hydride, are extremely moisture sensitive and readily decomposed. 25 The catalytic reduction of mixed carbonic/carboxylic acid anhydrides, prepared from acylated a-amino acids, leads to poor reproducibility and low yields. 24 The major problems associated with these techniques are overreduction, racemization, and poor yields. 

Figure 10.10 The synthesis of 2R-methylbutanoic acid, illustrating the use of a chiral auxiliary. The chiral auxiliary is 2S-hydroxymethyltetrahydropyrrole, which is readily prepared from the naturally occurring amino acid proline. The chiral auxiliary is reacted with propanoic acid anhydride to form the corresponding amide. Treatment of the amide with lithium diisopropyla-mide (LDA) forms the corresponding enolate (I). The reaction almost exclusively forms the Z-isomer of the enolate, in which the OLi units are well separated and possibly have the configuration shown. The approach of the ethyl iodide is sterically hindered from the top (by the OLi units or Hs) and so alkylation from the lower side of the molecule is preferred. Electrophilic addition to the appropriate enolate is a widely used method for producing the enantiomers of a-alkyl substituted carboxylic acids...

Carboxylic acids, acid chlorides, acid anhydrides and esters get reduced to primary alcohols when treated with lithium aluminium hydride (LiAlH) (Fig.M). The reaction involves nucleophilic substitution by a hydride ion to give an intermediate aldehyde. This cannot be isolated since the aldehyde immediately undergoes a nucleophilic addition reaction with another hydride ion (Fig.N). The detailed mechanism is as shown in fig.O. 

Fig.M. Reduction of acid chlorides, acid anhydrides, and esters with lithium aluminium hydride.

For the preparation of 70-72 Koyama etal. (28) employed the 5-3 -(indolyl)-oxazole 88 obtained from ethylindole-3-carboxylate (87) and isocyanomethyl lithium. The oxazole 88 was refluxed in acetic anhydride—acetic acid or propionic anhydride-propionic acid to afford pimprinine (70) and pimprinethine (71) in 13 and 19% yield, respectively. Hydrolysis of these reaction mixtures and that produced with phenylacetic acid anhydride-phenylacetic acid gave high yields (84-92%) of the 3-acylamidoindoles 79-81, which could be smoothly cyclized with phosphorus oxychloride to the natural products 70-72 (28). 

Figure 25.4. Proposed fragmentation pathways of triacylglycerol lithium adducts by ESI-MS3. R = fatty acid. Subscripts after R represent the stereospecific locations. (A) Loss of fatty acid at sn-3, then the loss of oc,p-unsaturated fatty acid at sn-2 (Hsu and Turk, 1999). (B) Loss of fatty acid at sn-3, then the loss of C3H40 from glycerol backbone to form acid anhydride. (C) Loss of fatty acid at sn-2, then the loss of C3H40 from glycerol backbone to form acid anhydride.

In accordance with the method of Garbrecht (144), the lithium salt of lysergic acid is converted in dimethylformamide solution with SO3 to form the mixed lysergic acid sulfuric acid anhydride which reacts with primary or secondary amines to give a good yield of the corresponding lysergic acid amides. 

The basic organometallic reaction cycle for the Rh/I catalyzed carbonylation of methyl acetate is the same as for methanol carbonylation. However some differences arise due to the absence of water in the anhydrous process. As described in Section 4.2.4, the Monsanto acetic acid process employs quite high water concentrations to maintain catalyst stability and activity, since at low water levels the catalyst tends to convert into an inactive Rh(III) form. An alternative strategy, employed in anhydrous methyl acetate carbonylation, is to use iodide salts as promoters/stabilizers. The Eastman process uses a substantial concentration of lithium iodide, whereas a quaternary ammonium iodide is used by BP in their combined acetic acid/anhydride process. The iodide salt is thought to aid catalysis by acting as an alternative source of iodide (in addition to HI) for activation of the methyl acetate substrate (Equation 17) ... 

Reduction of the carbethoxy group to the hydroxymethyl group with lithium aluminum hydride at — 35° and Claisen condensation with ethyl acetate are known to take place with pyridazinecar-boxylic acids. 6-Oxo-l,6-dihydro-2-pyridazinyl aliphatic acids, having the pyridazinonyl residue attached at the a-position of the aliphatic radical, readily undergo decarboxylative acylation with acid anhydrides in the presence of pyridine to form the corresponding 2-alkanones (107). 

Ketone methyknation. The reagent reacts with ketones to yield adducts (2) which can be isolated in excellent yields by aqueous quench, or converted into esters (3) by treatment with n-butyllilhium and then an acylating reagent (acid chloride or acid anhydride). Reduction of the ester (3) with lithium in liquid ammonia affords the... 

Appropriate quenching of a reductively formed lithium enolate with a carboxylic acid anhydride, chloride, methyl chloroformate or diethyl phosphorochloridate yields the corresponding enol esters, enol carbonates or enol phosphates. These derivatives may be transformed into specific alkenes via reductive cleavage of the vinyl oxygen function, as illustrated by the example in Scheme 8. 

The lactam 143 was treated with m-chloroperbenzoic acid, followed by treatment with acid anhydride to yield the aldehyde 144. Catalytic hydrogenation of unsaturated aldehyde 144 gave saturated aldehyde 145, and reduction of 145 with lithium aluminum hydride provided racemic lupinine 4 and racemic epilupinine 139. 

Alkyl and acyl derivatives (28, 30) of 14-aminocodeinones (13, 26) and dihydro-codeinones (20a, 27) are readily prepared acylation is achieved under standard conditions of acid chloride or acid anhydride in the presence of an organic base, while alkylation can be achieved directly with an alkyl halide or by acylation and then lithium aluminium hydride reduction (Scheme 5). In this latter method the 6-keto group is protected as an acetal [8, 9, 18, 19]. For direct alkylation with unactivated alkyl halides, carrying out the reaction in a sealed tube at 120 °C has... 

Lithium aluminum hydride will reduce the following acid anhydride and carboxylic acid to the same alcohol product. 

---