Reduction DIBALH

Chiral tricyclic fused pyrrolidines 29a-c and piperidines 29d-g have been synthesized starting from L-serine, L-threonine, and L-cysteine taking advantage of the INOC strategy (Scheme 4) [19]. L-Serine (23 a) and L-threonine (23 b) were protected as stable oxazolidin-2-ones 24a and 24b, respectively. Analogously, L-cysteine 23 c was converted to thiazolidin-2-one 24 c. Subsequent N-allylation or homoallylation, DIBALH reduction, and oximation afforded the ene-oximes, 27a-g. Conversion of ene-oximes 27a-g to the desired key intermediates, nitrile oxides 28 a-g, provided the isoxazolines 29 a-g. While fused pyrrolidines 29a-c were formed in poor yield (due to dimerization of nitrile oxides) and with moderate stereoselectivity (as a mixture of cis (major) and trans (minor) isomers), corresponding piperidines 29d-g were formed in good yield and excellent stereoselectivity (as exclusively trans isomers, see Table 3). 

In an alternative approach, the isomeric unsaturated pyrrolidine or piperidine aldoximes 245 a and 245b were prepared and subjected to lOOC reaction affording 246a and 246b, respectively (Eq. 28). Esterification of 240 followed by N-tert-BOC protection and DIBALH reduction provided aldehyde 244 (X = 0) which was subjected to Wittig olefination. Introduction of a two carbon aldoxime chain on N in 244 (X = CH2) was carried out by alkylation with Et a-bromoacetate after deprotection of the N atom in 244. Reduction and oxima-tion led to 245. 

A more general route to 4-acetoxy-l,3-dioxanes utilizes the reductive acylation of l,3-dioxane-4-ones [46] (Scheme 21). l,3-Dioxane-4-ones 126 are prepared from the corresponding -hydroxy carboxylic acids. Low temperature reduction with DIBALH generates a diisobutylaluminum hemiacetal (127) which undergoes acylation in situ with AC2O in the presence of pyridine and DMAP. This method allows for the preparation of a wide range of 4-acetoxy-l,3-dioxanes, without the problem of a-epimerization. This method also represents a general approach to acylic a-acetoxy ethers, which are themselves useful synthetic intermediates [47,48]. 

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... 

A-methoxy-A-methyl amides.87 LiAlH4 and DiBAlH have both been used as the hydride donor. The partial reduction is again the result of the stability of the initial reduction product. The A-methoxy substituent leads to a chelated structure that is stable until acid hydrolysis occurs during workup. 

Combined use of Co(acac)2 and DiBAlH also gives selective reduction for a,(3-unsaturated ketones, esters, and amides.112 Another reagent combination that selectively reduces the carbon-carbon double bond is Wilkinson s catalyst and triethylsilane. The initial product is the enol silyl ether.113... 

In a similar procedure, through diisobutylaluminium hydride (DIBALH)-reduction of nitrile into imine and condensation with A-benzylhydroxylamine, C-(l-fluorovinyl) nitrones were synthesized (Scheme 2.30, Table 2.4) (228). 

Purine nucleosides of type 1.4 (1177) were prepared by the reductive cleavage at the anomeric position of the ribofuranosyl moiety of 1176 with diisobutylaluminium hydride (DIBALH). The reductive ring opening was explained by the initial formation of a Lewis complex (93TL4835). 

Catalytic hydrogenation of triple bonds and the reaction with DIBALH usually give the cis olefin. Most of the other methods of triple-bond reduction lead to the more thermodynamically stable trans olefin. However, this is not the case with the method involving hydrolysis of boranes or with the reductions with activated zinc, hydrazine, or NHjOSOyH, which also give the cis products. 

LiAIH(OEt)3,345 DIBALH,346 and NaAIH4.347 The metal hydride method is useful for aliphatic and aromatic nitriles. Reduction to the aldehyde has also been accomplished by treatment of the nitrile with sodium hypophosphate and Raney nickel in aqueous acetic acid-pyridine or formic acid,348 and with zinc and a Cob(I)alamin catalyst in aqueous acetic... 

The aluminoxy acetal intermediates in ester reduction using DIBALH can be trapped with either TMSOTf93 or TMS imidazole94 to give monosilyl acetals (equation 21). 

Claisen-Ireland rearrangement of 239 followed by DIBALH reduction gives a mixture of syn and anti isomers 240 (equation 194)34-347. In a similar manner, orthoester Claisen rearrangements of 241 give stereoselectively the corresponding chiral allylsilanes 242 (equation 195)348. 

The successful conversion of 65 into mniopetal E (5) was eventually achieved as shown in Scheme 12. The DIBALH reduction of 65 at -78... 

The synthesis of substrates 88-96 for the IMDA reaction is depicted in Schemes 14 and 15. Treatment of 74 with I2, PPh3, and imidazole [91] provided iodide 75. The substitution of the iodo group in 75 by an anion generated from 2-methylpropionitrile [56-60] provided a hepta-nitrile derivative 76 in 95% yield. Then the secondary hydroxyl group in 76 was protected as an MOM ether to provide 77. Reduction of 77 with DIBALH followed by acidic hydrolysis gave aldehyde 78. The Horner-Emmons reaction of 78 with triethyl 4-phosphonocrotonate in the presence of LiOHH20 and molecular sieves 4A powder [68]... 

Numerous other metal hydride reagents have been developed to accomplish a variety of specialized reductions. The only other one that will be discussed here is di-isobutylaluminum hydride, i-Bu2A1H or DIBALH ... 

Epoxidation of endocyclic enol ether 37 with dimethyl dioxirane (DMDO) followed by one-pot reduction with DIBALH produced a 10 1 mixtrrre of alcohols, in which the major isomer possessed... 

From halides. Halides are easily converted into selenides. Since halides are also suitable radical precursors, this transformation is usually done when side reactions of halides with nucleophiles can occur. An example of this type is reported in Eq. (1). The bromide 5 was converted into a phenyl selenide, which could stand DIBALH reduction and imine formation. Tin mediated cyclization of 6 afforded the cyclopentylamine 7 in 72% yield [5]. 

The reductive acetylation of esters and lactones can be accomplished by treatment of the ester with a two-fold excess of DIBALH at -78°C followed by trapping of the resulting aluminum hemiacetal intermediate with acetic anhydride in the presence of pyridine and DMAP at low temperature. This transformation has been successfully applied to a wide range of esters and lactones, including sterically-... 

Reduction of A -(aminocarbonyl)-a-amino esters 1134 and A -(aminothiocarbonyl)-a-amino esters 1135 with DIBALH affords 4-hydroxyimidazolidin-2-ones 1136 and 4-hydroxyimidazolidine-2-thiones 1137, respectively. These substances eliminate a water molecule upon acidic work-up to give imidazol-2-ones 1138 and imidazole-2-thiones 1139 (Scheme 276) <1997SL521>. 

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