Diesters reduction

The aromatic diester reduction takes place in two steps ... 

A particularly useful transformation of 330a exploits the combination of lithium aluminum hydride and aluminum chloride to execute both diester reduction and reductive cleavage of the benzylidene protecting group to furnish triol 348, which can be converted in modest yields to the acetonide, (3iS)-3-0-benzyl-l,2-0-isopropylidene-L-threitol (349). Catalytic debenzy-lation of 349 generates (3 S)-l,2-0-isopropylidene-L-threitol (350), which is converted to the relatively inaccessible (i )-l,2-0-isopropylideneglycerol (351) [124] (Scheme 78). 

Another viable method for the synthesis of L-foUc acid (1) starts from 6-formylpterin (23). The diester of L-glutamic acid (24) is condensed with 6-formylpterin (23). Reduction of the Schiff base with sodium borohydride is followed by hydrolysis to yield L-foUc acid (37). 

Anhydrides are reduced with relative ease. McAlees and McCrindle 20) established the following increasing order of difficulty for various carbonyls acid chlorides > aldehydes, ketones > anhydrides > esters > carboxylic acids > amides. Reduction may proceed by 1,2-addilion of hydrogen or by cleavage of an oxygen-carbonyl bond. If 1,2-addition to the carbonyl occurs, as in the presence of strong protic acids over palladium, 1,1-diesters are formed by acylation 26). 

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). 

Two preparations of diesters of phosphonous acid have been reported, - One of these, which claims to be the first preparation of these derivatives, involves the reaction of ammonium hypophosphite with triaikylsilylamines to give bis(trialkylsilyl) esters (127) in excellent yield. These compounds are extremely reactive, e.g. they are spontaneously inflammable in air. Dialkyl phosphonites (128) have also been prepared by the reduction of... 

This approaeh allows the Ml synthesis of the modified DIOP ligands (Scheme 21.6). Three new hgands were synthesized with 15-20% global yield (6 steps) according to a similar route as described for DIOP synthesis (11). After chemical reduction of the diester to the diol, the mesylated compounds were isolated. Their treatment with diphenylphosphine previously reacted with n-BuLi to yield LiPPh2 gave the expected ligands with 49-55% isolated yield. 

Another important reductive coupling is the conversion of esters to a-hydroxyketones (acyloin condensation).267 This reaction is usually carried out with sodium metal in an inert solvent. Good results have also been obtained for sodium metal dispersed on solid supports.268 Diesters undergo intramolecular reactions and this is also an important method for the preparation of medium and large carbocyclic rings. 

Scheme 7.11 shows the product structures resulting from the dithionite reduction of a simplified version of WV-15. The symmetric sulfite diester was extracted from the reaction mixture with methylene chloride. The isolation and characterization of the sulfite diester confirmed that this species can form in dithionite reductive activation reactions and provided the chemical shift for the 10a-13C center of a mitosene sulfite ester (49.37 ppm). The aqueous fraction of the reaction contained the mitosene sulfonate and trace amounts of Bunte salt, based on their 13C chemical shifts. 

Preparation of the quaternary anticholinergic agent benzilonium bromide (47) is begun by conjugate addition of ethylamine to methylacrylate, giving aminoester 42. Alkylation of 42 with methyl bromo-acetate leads to diester 43, which is transformed into pyrrolidone 44 by Dieckmann cyclization, followed by decarboxylation. Reduction of 44 by lithium aluminum hydride leads to the corresponding amino-alcohol (45). Transesterification of alcohol 45 with methyl benzilate leads to 46. Benzilonium bromide (47) is obtained by alkylation of ester 46 with ethyl bromide. 2... 

Treatment of the diester 211 (E = CC Et) with lithium IV-benzyltrimethylsilylamide, followed by aqueous acid, yields the cyclopentane derivative 212, the product of an intramolecular Michael addition (equation 104)110. 1-Methylindane is produced in moderate yield by the electrochemical reduction of o-bromo-(3-butenyl)benzene (equation 105)111. 

Additionally, it was found that the double reductive alkylation of the 2,5-diester 66 could be achieved under Birch conditions (Li/NH3) to produce the 3-pyrroline 67. On the basis of a mechanistic postulate that such reductions do not involve transfer of a proton from ammonia, the authors discovered that the same reduction could be performed in THF (no ammonia) with lithium metal and catalytic amounts of naphthalene as an electron shuttle, thereby making this reaction more practicable on a large scale <00TL1327>. 

Lactam 299 was prepared from tryptamine and cyano diester 298 by reductive alkylation in about 12% yield. Phosphorus oxychloride cyclization of 299, followed by catalytic reduction, resulted in the corresponding trans disubstituted indolo[2,3-a]quinolizine 300. After transesterification, formylation and methyla-tion were carried out in two subsequent steps with ethyl formate in the presence of triphenylmethylsodium and with an excess of diazomethane to supply ( )-dihydrocorynantheine (163). 

The stereoselective total synthesis of both ( )-corynantheidine (61) (170,171) (alio stereoisomer) and ( )-dihydrocorynantheine (172) (normal stereoisomer) has been elaborated by Szdntay and co-workers. The key intermediate leading to both alkaloids was the alio cyanoacetic ester derivative 315, which was obtained from the previously prepared ketone 312 (173) by the Knoevenagel condensation accompanied by complete epimerization at C-20 and by subsequent stereoselective sodium borohydride reduction. ( )-Corynantheidine was prepared by modification of the cyanoacetate side chain esterification furnished diester 316, which underwent selective lithium aluminum hydride reduction. The resulting sodium enolate of the a-formyl ester was finally methylated to racemic corynantheidine (171). 

Hirsutine (58), the pseudo isomer of corynantheidine and dihydrocory-nantheine, has been elegantly synthesized by Wenkert and his collaborators (161). The reaction of keto diester290 with Meerwein s reagent, followed by hydrogenation, resulted in pseudo-type diester 321, which on reduction and methylation gave ( )-hirsutine (161). 

In 1969, Szantay and co-workers published a linear synthesis of (+)-yohimbine and (—)-P-yohimbine (75) in full detail (220). Tetracyclic key intermediate 400, obtained from 3,4-dihydro-p-carboline and a properly substituted a,p-unsatu-rated ketone (173), was treated with a proper phosphonoacetic acid derivative to give unsaturated nitrile 401 or unsaturated ester 402. Catalytic reduction of the latter resulted almost exclusively in 404 with normal stereo arrangement, while reduction of 401 supplied a mixture of normal and epialloindolo[2,3-a] quinolizines 403 and 405, respectively. Dieckmann ring closure of diester 404 gave 18a-methoxycarbonylyohimbone (407) as the thermodynamically favored... 

Tetracyclic keto ester 467, prepared earlier (253), was treated with the anion of diethyl methoxycarbonylmethylphosphonate in dimethylformamide. The reaction supplied the unsaturated ester 492, which was catalytically hydrogenated to diester 493. Dieckmann condensation of 493 yielded two nonenolizable keto esters (494 and 495), which could be separated by fractional crystallization. Sodium borohydride reduction of 18a-methoxyyohimbinone (494) gave two alcohols (496 and 497) in a ratio of about 10 1 at the same time, reduction of 180-methoxyyohimbinone (495) furnished another two stereoisomeric alcohols (498 and 499) in approximately equal amounts. Demethylation of the four stereoisomers (496-499) resulted in the corresponding 18-hydroxyyohimbines (500-503)... 

The chloroester and the diester are formed through Cl - Pd - CC Me addition to the double bond followed by reductive elimination (Scheme 10, path a) or further methoxycarbonylation (Scheme 10, path b). 

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