Product isolation reduction with complex hydrides

The domain of hydrides and complex hydrides is reduction of carbonyl functions (in aldehydes, ketones, acids and acid derivatives). With the exception of boranes, which add across carbon-carbon multiple bonds and afford, after hydrolysis, hydrogenated products, isolated carbon-carbon double bonds resist reduction with hydrides and complex hydrides. However, a conjugated double bond may be reduced by some hydrides, as well as a triple bond to the double bond (p. 44). Reductions of other functions vary with the hydride reagents. Examples of applications of hydrides are shown in Procedures 14-24 (pp. 207-210). 

Treatment of an ethereal solution of 4-oxo-dihydro-l,3-diaza-anthracene (108) with lithium aluminum hydride reportedly resulted in the reduction of only the 1,2-carbon-nitrogen double bond with 4-oxo-l,2,3,4-tetrahydro-l,3-diazaanthracene (109) being the only product isolated.134 Apparently conditions were not sufficiently vigorous for the further reduction of the tautomeric form of 109, or possibly the formation of a complex with the aluminohydride pre-... 

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. ... 

It was found [99JCS(PI )3713] that, in all cases, the formation of the deiodinated products 38 and 39 was accompanied by formation of the diynes 40 which were isolated in 60-90% yield. The authors believed that the mechanism of deiodination may be represented as an interaction ofbis(triphenylphosphine)phenylethynyl-palladium(II) hydride with the 4-iodopyrazole, giving rise to the bisftriphenylphos-phine)phenylethynyl palladium(II) iodide complex which, due to the reductive elimination of 1 -iodoalkyne and subsequent addition of alk-1 -yne, converts into the initial palladium complex. Furthermore, the interaction of 1-iodoalkynes with the initial alkyne in the presence of Cul and EtsN (the Cadiot-Chodkiewicz reaction) results in the formation of the observed disubstituted butadiynes 40 (Scheme 51). 

Although estrone and estradiol (26) have both been isolated from human urine, it has recently been shown that it is the latter that is the active compound that binds to the so-called estrogen receptor protein. Reduction of estrone with any of a large number of reducing agents (for example, any of the complex metal hydrides) leads cleanly to estradiol. This high degree of stereoselectivity to afford the product of attack at the alpha side of the molecule is characteristic of many reactions of steroids. 

The oxidative addition of silanes (with silicon-hydrogen bonds) to coordinatively unsaturated metal complexes is one of the most elegant methods for the formation of metal-silicon bonds. Under this heading normally reactions are considered which yield stable silyl metal hydrides. However, in some cases the oxidative addition is accompanied by a subsequent reductive elimination of, e.g., hydrogen, and only the products of the elimination step can be isolated. Such reactions are considered in this section as well. 

An asymmetric variant of this reaction was developed using chiral Pd complex 111 with either silanes or disiloxanes [66-68]. Both relative and absolute stereochemistries were controlled in this system and good yields (60-85%) were obtained after oxidation (Eq. 18). Formation of the silane-containing product was inhibited by the presence of water due to competitive formation of the palladium hydrides and silanols [68]. The use of disiloxanes as reductants, however, provided expedient oxidation to the alcohol products without decreasing the isolated yields enantioselectivity was 5-15% lower in this more robust system [66]. Benzhydryldimethylsilane proved to be a good compromise between high yield and facile oxidation [66]. Palladium com-... 

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... 

Nishinaga and co-workers isolated a series of stable cobalt(III)-alkyl peroxide complexes such as (170) and (171) in high yields from the reaction of the pentacoordinated Co"-Schiff base complex with the corresponding phenol and 02 in CH2C12. Complex (170 R=Bu ) has been characterized by an X-ray structure. These alkyl peroxide complexes presumably result from the homolytic addition of the superoxo complex Co111—02 to the phenoxide radical obtained by hydrogen abstraction from the phenolic substrate by the CoUI-superoxo complex. The quinone product results from / -hydride elimination from the alkyl peroxide complex (172)561,56,565,566 The quinol (169) produced by equation (245) has been shown to result from the reduction of the CoIU-alkyl peroxide complex (170) by the solvent alcohol which is transformed into the corresponding carbonyl compound (equation 248).561... 

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