Diisobutylaluminum hydride lactones

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

The most widely used reagent for partial reduction of esters and lactones at the present time is diisobutylaluminum hydride (DiBAlH).83 By use of a controlled amount of the reagent at low temperature, partial reduction can be reliably achieved. The selectivity results from the relative stability of the hemiacetal intermediate that is formed. The aldehyde is not liberated until the hydrolytic workup and is therefore not... 

MISCELLANEOUS BENZOHETEROCYCLES Partial reduction of lactone 166 (using for example diisobutylaluminum hydride in the cold) affords lactol 167. Condensation with nitromethane leads to the corresponding alkylated tetrahydrobenzopyran 170. The sequence probably starts by aldol reaction of the hydroxylactone form of the lactol (168) with nitrome thane to give the vinyl nitro intermediate 169 ... 

Diisobutylaluminum hydride was also employed (153) for the reduction of 2,6-dideoxy-3-C-methyl-D-arabmo-hexono-1,4-lactone (121) to an antibiotic component, the branched-chain sugar evermicose (2,6-dideoxy-3-C-methyl-D-nrabmo-hexose, 122). The L-enantiomer of 122 (olivomycose, 125a), L-amicetose 125b, and 2,6-dideoxy-3-C-methyl-L-n Zw-hexose (l-... 

Reduction of lactones leads to cyclic bemiacetals of aldehydes. With a stoichiometric amount of lithium aluminum hydride in tetrahydrofuran at —10° to —15° and using the inverse technique, y-valerolactone was converted in 58% yield to 2-hydroxy-5-methyl tetrahydrofuran, and a-methyl-5-caprolac-tone in 64.5-84% yield to 3,6-dimethyl-2-hydroxytetrahydropyran [1028]. Also diisobutylaluminum hydride in tetrahydrofuran solutions at subzero temperatures afforded high yields of lactols from lactones [7024]. 

A more useful way of reducing esters to ethers is a two-step procedure applied to the reduction of lactones to cyclic ethers. First the lactone is treated with diisobutylaluminum hydride in toluene at —78°, and the product - a lactol - is subjected to the action of triethylsilane and boron trifluoride etherate at —20° to —70°. y-Phenyl-y-butyrolactone was thus transformed to 2-phenyltetrahydrofuran in 75% yield, and 5-lactone of 3-methyl-5-phenyl-5-hydroxy-2-pentenoic acid to 4-methyl-2-phenyl-2,3-dihydropyran in 72% yield [1034]. 

Many examples of natural furans are recorded as having been prepared from five-membered heterocycles such as 2(5H)-furanones (butenolides), which are reduced to furans with diisobutylaluminum hydride. The facile elimination of selenoxides derived from a-phenylseleneyl-y-lactones with formation of endocyclic a,/3-unsaturated butenolides is reported (75JOC542) as a useful route to 2,4- and 2,3,4-substituted furans via their corresponding butenolides. The mixture of dihydrofurans obtained from the tosylhydrazone of tetrahydro-2-furanone (Scheme 88) was oxidized to furans by 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (66CJC1083). 

R,4R)-Pentanediol, 237 Sulfur compounds ra-Chloroperbenzoic acid, 76 Unsaturated lactones Diisobutylaluminum hydride, 115... 

Based on the precedented reduction of 2//-dihydropyrones,86 the combination of Lewis acid and hydride source exemplified by Et3SiH/BF3 seemed ideally suited to our needs (Scheme 9). While (+)-artemisinin 1 could not be reduced directly to 10-deoxoartemisinin 108 with Et3SiH/BF3, dihydroartemisinin (175, R = H) was smoothly converted at low temperature to desired tetrahydropyran 108 in 96% yield. Further, this method was insensitive to scale being readily accomplished on the gram or milligram level. It was also found that small scale reductions could be more conveniently conducted utilizing diisobutylaluminum hydride in place of sodium borohydride. As applied to the problematical case, it was found that lactone 125 could be reduced to lactol and thence 115 as outlined in Scheme 3 in excellent yield. Furthermore, the yield for the conversion of lactone 45 into 9-butyl-10-deoxoartemisinin 112 could be similarly improved from 58 to 90%. 

To a solution of 0.50 g of (-)-3a,5a-dihydroxy-2p-[(3RS)-3-hydroxy-3-methyl-trans-octenyl]cyclopentane-la-acetic acid - lactone 3-benzoate in 15 ml of tetrahydrofuran at -78°C under nitrogen was added 10 ml of 10% diisobutylaluminum hydride in toluene. After a gas evolution was ceased, the reaction was quenched by addition of 10 ml of saturated aqueous ammonium chloride. The resulting mixture was stirred at room temperature, filtered through Celite, and extracted with ethyl acetate. Extract was evaporated to give 0.48 g of (-)-3a,5a-dihydroxy-2p-[3-(RS)-3-hydroxy-3-methyl-trans-octenyl]cyclopentane-l-a-acetaldehyde y-lactol 3-benzoate as an oil. 

Reduction of lactones to lactols with diisobutylaluminum hydride has become an important, high-yielding reaction in the wake of many syntheses of prostaglandins. First introduced in this role in 1969, ° DIB AH can give 98% yields of lactols from y-lactones by reaction at -60 C for 20 min in toluene. ... 

Reduction has been reported for other hydride reagents, such as diisobutylaluminum hydride aluminum hydride and 9-BBN-H. a,p-Unsaturated lactones are also reduced by DIBAL-H to the corresponding lactols in high yields. ... 

Diisobutylaluminum hydride (DIBAL) is a reliable reagent for the reduction of lactone 29 to the corresponding lactol 67. This is due to the formation of stable tetrahedral intermediate 66, which prevents further reduction (via hydroxyaldehyde 68 to the diol) and decomposes during aqueous workup to provide the desired lactol 67. 

Whitesell s synthesis of ( )-sarracenin [( )-495] (Vol. 4, p. 501, Ref. 314) has been published in full." It is worthwhile noting certain difficulties reported at the end of the synthesis involving the apparently simple steps shown in Scheme 48. Partial reduction of the lactone function in 496 with diisobutylaluminum hydride requires two equivalents, the first of which is taken up by complexation with the carbomethoxy group. Even with this problem solved, the yield of sarracenin [( )-495] from 496 was only 15%, and it is impossible to see where the loss was because of the instability of the intermediate compounds.Because both epimers of 497 were available in an earlier step toward 496, Whitesell also synthesized the as yet unnatural episarracenin with an epimeric 8-methyl group. 

Construction of the suitably substituted geranic acid for making the furan ring has been effected too. For example, Poulter et al. have prepared the substituted geranate 865 by reaction of 4-methyl-3-pentenylcopper with the acetylenic ester 866. The ester 865 then underwent cyclization in the presence of acid to the lactone 867, related to scobinolide (161), and the action of acid on the lactol produced from 867 with diisobutylaluminum hydride gave perillene (849). The lactone 867 has also been prepared by a slightly different method the C9 alcohol 868 was made (in poor yield) from isobutenol and prenyl chloride with butyllithium. The extra carbon atom was introduced by the action of sodium cyanide on the epoxide of 868, and hydrolysis of the cyano group followed by dehydration yielded the lactone 867. The dimethylthioacetal of 867 has been used to synthesize perillene (849). This thioacetal was made from the suitably substituted ketene thioacetal 869 and dimethylsulfonium methylide. Thus the ketene thioacetal 870 (readily prepared from acetone, carbon disulfide, and sodium amylate, followed by methylation °) can be prenylated with lithium... 

Substituted Claisen substrate 1 containing an oxygen at C-5 rearranges to an intermediate 1,4-dicarbonyl compound, which undergoes facile lactonization to give 2. Lactone 2 is transformed to cyclopentenone 3 by reduction with diisobutylaluminum hydride and subsequent treatment with a mild base87. 

A four-step synthesis for racemic acid 6 was accomplished starting with the cyclic lactone oxacyclotridecan-2-one, which was a-methylated with lithium diisopropylamide (LDA) and methyl iodide, as shown in Fig. (6). Reduction of 3-methyloxacyclotridecan-2-one with diisobutylaluminum hydride (DIBAL) in toluene at -78°C afforded... 

Reduction of a,p-unsaturated y-lactones to furanes (1,262). Pelletier et al. have developed a general method for conversion of 2(5H)-furanones (1) into substituted furanes (4). The method involves cycloaddition of diazoalkanes, diazo esters, and diazoketones, followed by decomposition to alkylated 2(5H)-furanones (3). The final step involves reduction with diisobutylaluminum hydride. 

---