Reduction of the Ester Groups

Perhaps the most reported reactions of these polymers are reductions of the functional groups. Among them is the reaction with lithium aluminum hydride to reduce the ester groups. The success, however, depends upon the reaction medium. Poly(methyl methacrylate) is reduced to poly(methal-lyl alcohol) in ether solvents  

The results, however, are inconclusive, because combustion analyses fail to match the theoretical composition for poly(methallyl alcohol). It is impossible to teU to what extent the reduction takes place. Inconclusive results are also obtained in similar reductions of poly(methyl acrylate) in mixtures of tetrahydrofiuan and benzene. When a product of such reduction is acetylated with acetic anhydride in pyridine as follows  

Even after hydrolysis in water, treatment with hot m-cresol, and extracted with hydrochloric acid to remove the suspended inorganic materials, the product is still only soluble in pyridine and m-cresol. 

The problem is apparently due to some residual aluminum that is hard to remove. If, however, the reduction is carried out in a iV-methylmorpholine solution, followed by addition of potassium tartrate, a pure product can be isolated. A -Methylmorpholine is a good solvent for reductions of various macromolecules with metal hydrides.In addition, the solvent permits the use of strong NaOH solutions to hydrolyze the addition complexes that form. Other polymers that can be reduced in it are those bearing nitrile, amide, imide, lactam, and oxime pendant groups. Reduction of polymethacrylonitrile, however, yields a product with only 70% of primary amine groups. Complete reductions of pendant carbonyl groups with LiAlH4 in solvents other than A -methyl-morpholine, however, were reported. Thus, a copolymer of methyl vinyl ketone with styrene was fully reduced in tetrahydrofuran.  

Reductions with metal hydrides are often preliminary steps for additional reactions. For instance, a product of UAIH4 reduction of syndiotactic poly(methyl methacrylate) can be reacted with succinic anhydride and then converted to an amide  

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Reduction of the ester group in (31) requires protection of the ketone the double bond wanders during this step but returns to conjugation in (27). 

The crucial cyclization of 129 was accomplished by oxidation with pyri-dinium chlorochromate (PCC) and acetylation, providing two cyclohexane derivatives (130 and 131) in the ratio of 10 1. Thermal decarboxylation of 130 resulted in formation of the cyclohexene derivative 132, with concomitant elimination. Reduction of the ester group with diisobutylaluminum hydride converted 132 into 133. Hydroboration-oxidation of 133 gave the carba-sugar derivative 134 as a single product. 

The above two consecutive transformations provide straightforward access from propargyl alcohols to cyclopropene derivatives with an a- or /1-hydroxy group. This simple method is complementary to the access to 3-hydroxymethylcyclopropenes, via Rh2(OAc)4 catalyzed addition of diazoacetate to alkynes followed by reduction of the ester group, a route that is restricted to the access of primary cyclopropenyl alcohols [57], and is an alternative to the use of 2,2-dibromo-l-chlorocyclopropane via cyclopropenyl Uthium. 

The anion radical species formed by the electroreduction of aliphatic esters show interesting reactivities, and the reduction of olefinic esters gives bicyclic products with high regio- and stereoselectivity. The electroreduction of the ester in the presence of chlorotrimethylsilane affords a tricyclic product (Scheme 21) [35, 40]. The mechanism of this cyclization reaction seems to be the addition of anion radical species, formed by the reduction of the ester group, to the carbon-carbon double bond. 

Bromination to 4 and substitution of the bromine by an amine gives 5. Sodium borohydride reduction of the ketone to an alcohol 6 is followed by a resolution with (-)-di-/ -toluoyltartaric acid and reduction of the ester group with lithium aluminum hydride to give diol 7. Catalytic debenzylation gives albuterol, sometimes called salbutamol. 

An alternative access to murrayanine (9) was developed starting from the mukonine precursor 609. The reduction of the ester group of 609 using diisobutylaluminum hydride (DIBAL) afforded the benzylic alcohol 611. In a one-pot reaction, using very active manganese dioxide, 611 was transformed to murrayanine (9) (574) (Scheme 5.36). 

TrihydroxyheIiotridane-6,7-0-acetonide (351) was synthesized using the same method (67) (Scheme 9.67). When refluxed in benzene, the azide 348 afforded the diastereomeric vinyl aziridines 349 in 44% yield. On FVP of vinyl azrridine (349) followed by catalytic reduction and subsequent LiAUTj reduction of the ester group, trihydroxyheliotridane-6,7-0-acetonide (351) was formed in 34% yield. 

The alcohol 10 introduced at step j was prepared following a literature procedure from ethyl-2-(piperidin- 4-yl)acetate after N-Boc protection and selective reduction of the ester group using lithium aluminum hydride (Villalobos et al., 1994) (reaction scheme b). 

The enantioselective synthesis of a somewhat more complex renin inhibitor starts with the reduction of the ester group in the chiral amino-ester (19-1) by means of diisobutyl aluminum hydride in the cold. The aldehyde product (19-2) is then reacted with prior isolation with the ylide from phosphonium salt (19-3) and a strong base... 

Treatment of the dichloromethyl derivative 472 with sodium cyanide gave290 an almost quantitative yield of the epimeric nitriles (480, 481). The mixture could not he separated by chromatographic methods, but differences in reactivity of the stereoisomers towards methanolic hydrogen chloride allowed isolation of only one ester, namely, 482 the trails cyanide underwent ready conversion into the methyl ester, whereas the cis compound gave a rather complicated mixture of products, with amide 483 being identified as the major component. Reduction of the ester group in 482, followed hydrolysis of the dichloromethyl group, afforded DL-t/ireo-DL- Y/o-octose, characterized as the heptaacetate, and identified as threo-ido-octito by comparison with an authentic sample. 

So step 1 is protection of other hydroxy groups, step 2 is a normal Moffatt-Pfitzner oxidation, and step 3 is a Wittig reaction. The tertiary butyl ester is used to provide steric hindrance in step 4 to any approach of borohydride to the carbonyl group when an ethyl ester was used, some reduction of the ester grouping was found. 

Mercapto-4-amino-5-carbethoxypyrimidine has been converted to 2-methylmercapto-4-amino-5-hydroxymethylpyrimi-dine,6 an antimetabolite possessing antitumor activity,7 by methylation of the mercapto group followed by reduction of the ester group to a hydroxymethyl group with lithium aluminum hydride.6... 

Reduction of y-amino-a, -unsaturated esters These substrates when com-plexed with BF3 etherate can be reduced selectively to y-amino esters with only slight reduction of the ester group (equation I). 

Reduction of the ester group to give secondary alcohol 54 and sub sequent protection with /e/t-butyldimethylsilyl chloride leads to si-lyl ether 55 Oxidative cleavage of the cyclopropyl ring in this system proceeds through a radical mechanism and results in ben/oate ester 56. Basic ester hydrolysis gives piimar> alcohol 16... 

Reaction of ( )-diethyl tartrate (2) with benznldehyde leads to acetal 14 The second reaction accomplishes reduction of the ester groups to primary alcohols. Simultaneously, with the aid of a Lewis acid, the acetal is reductively cleaved to leave a benzyl protecting group 5... 

The first step is reduction of the ester group to give primary alcohol 33, which is subsequently protected as the fcrr-butyldiphenylsi-lyl ether 34 The benzylidene acetal is selectively cleaved with Lewis-acid activation under reductive conditions to generate protected secondary alcohol 8... 

Step 2 Reductive cleavage of the acetal and reduction of the ester groups. 

Step 2a Utilization of 1 eq of diisobutylaluminum hydride (DIBAL-H) ensures reduction of the ester group stops to the corresponding aldehyde. 

By reduction of the ester groups with lithium aluminum hydride the corresponding tetraalcohol was obtained which was converted to the tetrabromide 46 by treatment with phosphorus tribromide. Debromination with zinc in the presence of maleic anhydride (MA) furnished the bis anhydride 47, which, after esterification and aromatization, provided the... 

A selective reduction of the carboethoxy group in the 1,3-dithiolane 490 with NaBH4 in ethanol or in a mixture of ether/MeOH provided the alcohol 491 in quantitative yield (Equation 58). A selective reduction of the ester group to formyl was also possible <2000TL5653>. 

Step 2. Reductive cleavage of the acetal and reduction of the ester groups Step 3. Selective transacetalization of the 1,3-diol with benzaldehyde dimethyl acetal... 

Since the reduction of (136) by sodium borohydride in deuteriomethanol resulted in the incorporation (at C-16) of only one deuterium atom the possibility of inversion at C-20 during the reduction is excluded. The oxindole analogue (136) of dihydro-mancunine must therefore also belong to the pseudo series, and C-20 retains its configuration in its formation from dihydrosecologanin. A third representative of the pseudo series is obtained by milder reduction of (136), which avoids both reduction of the ester group and inversion at C-3/C-7, and affords both C-16 epimers of the hydroxy-ester (141). ... 

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