DIBALH,

Enantiopure (7 )-3-alkylpiperidines (38, R = Me, Et) were obtained when perhydropyrido[2,l-Z)][l,3]benzoxazin-9-ones (37, R = H, Me) were treated first with an excess of AIH3, then with PCC, followed by a 2.5 N solution of KOH (99TL2421). Treatment of optically active perhydropyr-ido[2,l-Z)][l,3]benzoxazines 39 and 40 with LAH in the presence of AICI3 and DIBALH (if R = COOEt) yielded 3-substituted piperidines 41 (00TA2809). 

Carboxylic esters have been reduced to aldehydes with DIBALH at — 70°C, with... 

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]. 

Cyclization of substituted phenylacetylene sequences afforded functionalized macrocycles that were amenable to subsequent manipulation. For example, transesterification of 42 with octanol in the presence of 18-crown-6 ether and potassium carbonate gave the corresponding ester in 85% yield (Scheme 13). The ester functionalities could be reduced by DIBALH to give the hydroxymethyl-substituted macrocycle (43) in 61 % yield. The low yield of this particular transformation is attributed to mechanical losses during purification, due to the highly polar nature of the product. Macrocycle 43 could then be treated with alkyl bromides to give a group of benzyl ether derivatized PAMs. 

Alkyl derivatives of boron and alane can function as reducing reagents in a similar fashion. Two reagents of this type, disiamylborane and diisobutylaluminum hydride (DiBAlH) are included in Table 5.3. The latter is an especially useful reagent. 

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. 

The electrophilicity of alane is the basis for its selective reaction with the amide group. Alane is also useful for reducing azetidinones to azetidines. Most nucleophilic hydride reducing agents lead to ring-opened products. DiBAlH, A1H2C1, and A1HC12 can also reduce azetinones to azetidines.100... 

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... 

Ketosulfoxides are subject to chelation control when reduced by DiBAlH in the presence of ZnCl2.141 This allows the use of chirality of the sulfoxide group to control the stereochemistry at the ketone carbonyl. 

A related method was applied in the course of synthesis of a precursor of a macrolide antibiotic, protomycinolide IV. The migrating group was an a-trimethylsilylalkenyl group.68 In this procedure, the DiBAlH first reduces the ketone and then, after rearrangement, reduces the aldehyde to a primary alcohol. 

Entry 8 involves a migration initiated by epoxide ring opening. This reaction involves migration of a vinyl substituent. Entry 9 is a stereospecific migration of the aryl group. The DiBAlH both promotes the rearrangement and reduces the product aldehyde. 

PhCH20 OTBDMS I CO9C9H1 4 eq DiBAlH PhCHgO OTBDMS I ch2oh... 

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