Acid anhydrides, cyclic, reduction

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

Acyclic acid anhydrides are reduced to produce primary alcohols using NaBH4 and its many deriva-tives.2 - In most cases, the reaction gives both the primary alcohol and the carboxylate salt (1 1). Whilst such monoreduction may be desirable in cyclic anhydride chemistry (vide infra), it is inefficient when acyclic anhydrides are reduced. Thus, B2H6 or LAH reductions are the preferred synthetic methods. The reductions of mixed anhydrides, for example carboxylic/diphenylphosphoric or carboxylic/car-bonic anhydrides, produce the primary alcohol from the acyl component. ... 

Haworth phenanthrene synthesis. Acylation of aromatic compounds with aliphatic dibasic acid anhydrides to (i-aroylpropionic acids, reduction of the carbonyl group according to Clemmensen or Wolff-Kishner procedures, cyclization of the y-arylbutyric acid with 85% sulfuric acid, and conversion of the cyclic ketone to polycyclic hydroaromatic and subsequently to aromatic compounds. 

Reduction of cyclic anhydrides. Although acid anhydrides are reduced to only a slight extent by sodium borohydride, cyclic anhydrides are reduced to 8- and y-lactones in 51-97% yield. Hydride attack occurs principally at the carbonyl group adjacent to the more highly substituted carbon atom.7... 

Hydrolysis of the ester functions of dimethyl 2,2-bis(4-methoxyphenyl)-277-naphtho[l,2-6]pyran-5,6-dicarboxylate and cyclisation of the resulting dicarboxylic acid yields the cyclic anhydride 51. Reduction affords a mixture of two isomeric furano-fused naphthopyrans. Treatment of the anhydride with primary amines provides a route to the corresponding pyrrole derivatives. Both types of hetero-fused naphthopyrans show a red shift relative to the starting naphthopyran diester and reduced half-lives <01 WOP32661>. 

The carbonylation of nickelacycles proceeds readily at room temperature to give the corresponding cyclic anhydride by reductive elimination. For example, nickelacycle 44, prepared by oxidative addition of the corresponding cyclic anhydride and decarbonylation, regenerates the starting material after treatment with carbon monoxide (Scheme 12). Acid hydrolysis of the reaction mixtures allows the formation of dicar-boxylic acids, as illustrated for nickelacycles 30,45, and 46 (Scheme 12). 

More generally, reduction of cyclic anhydrides such as phthalic anhydride (benzene-1,2-dicarboxylic acid anhydride) with zinc (Zn) in ethanoic acid (acetic acid, CH3CO2H) results in the formation of cyclic esters (lactones) (Scheme 9.114). As shown, the zinc (Zn) metal is oxidized (to zinc oxide [Zn02]), while the... 

The classic method for controlling stereochemistry is to perform reactions on cyclic substrates. A rather lengthy but nonetheless efficient example in the prostaglandin field uses bicyclic structures for this purpose. Bisacetic acid derivative S is available in five steps from Diels-Alder reaction of trans-piperylene and maleic anhydride followed by side-chain homologation. Bromolactonization locks the molecule as bicyclic intermediate Esterification, reductive dehalogen-... 

Reduction of Cyclic Anhydrides to Lactones and Acid Derivatives to Alcohols... 

One exception to the use of primary phosphines is in the reported syntheses of the catASium M dass of ligands 20 [46-49]. In one report, reaction of the cyclic sulfate with P(TMS)3 yields the TMS-protected secondary phospholane, which could then be reacted with the appropriate 1,2-dichloro spedes [46]. An alternative procedure to the same intermediate involves preparation of 1-phenyl-phospholane via the bismesylate, subsequent lithium-induced P-Ph deavage, and quenching with TMSC1 [49]. The ligand based on 2,3-dichloromaleic anhydride (20a originally referred to as MalPHOS [46]) has been shown to be effective for the chiral reduction of a- and /1-deliydroarnino acid derivatives and itaconate derivatives. 

Reductions of anhydrides of monocarboxylic acids to alcohols are very rare but can be accomplished by complex hydrides [55, 99]. More frequent are reductions of cyclic anhydrides of dicarboxylic acids, which give lactones. Such reductions were carried out by catalytic hydrogenation, by complex hydrides and by metals. 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

The cyclohexene 121, which was readily accessible from the Diels-Alder reaction of methyl hexa-3,5-dienoate and 3,4-methylenedioxy-(3-nitrostyrene (108), served as the starting point for another formal total synthesis of ( )-lycorine (1) (Scheme 11) (113). In the event dissolving metal reduction of 121 with zinc followed by reduction of the intermediate cyclic hydroxamic acid with lithium diethoxyaluminum hydride provided the secondary amine 122. Transformation of 122 to the tetracyclic lactam 123 was achieved by sequential treatment with ethyl chloroformate and Bischler-Napieralski cyclization of the resulting carbamate with phosphorus oxychloride. Since attempts to effect cleanly the direct allylic oxidation of 123 to provide an intermediate suitable for subsequent elaboration to ( )-lycorine (1) were unsuccessful, a stepwise protocol was devised. Namely, addition of phenylselenyl bromide to 123 in acetic acid followed by hydrolysis of the intermediate acetates gave a mixture of two hydroxy se-lenides. Oxidative elimination of phenylselenous acid from the minor product afforded the allylic alcohol 124, whereas the major hydroxy selenide was resistant to oxidation and elimination. When 124 was treated with a small amount of acetic anhydride and sulfuric acid in acetic acid, the main product was the rearranged acetate 67, which had been previously converted to ( )-lycorine (108). 

Cyclic orthoesters derived from gem-diols offer a further route to alkenes. As part of a three-step conversion, they may be ring opened with hydrobromic acid to give O-acyl bromodeoxy compounds that undergo reductive elimination with copper-zinc. In this way, unsaturated nucleosides have been made by way of mixed 2y3,-bromo-2y3,-deoxy-3,/2, carboxyl-ates.174 A more direct route to alkenes from cyclic orthoesters involves heating in acetic anhydride together with zirconium oxide.175... 

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