Borohydride, sodium 1,2-reduction with conjugated

On the other hand, 4-alkoxycarbonyl- and 4-aminocarbonyl-substituted isoxazoles 6 undergo unusual conjugate reduction with sodium borohydride and sodium... 

Hapten molecules containing aldehyde residues may be crosslinked to carrier molecules by use of reductive animation (Chapter 3, Section 4). At alkaline pH values, the aldehyde groups form intermediate Schiff bases with available amine groups on the carrier. Reduction of the resultant Schiff bases with sodium cyanoborohydride or sodium borohydride creates a stable conjugate held together by secondary amine bonds. 

A difference in the reactivities and selectivities between tetra-n-butylammonium borohydride and sodium borohydride in the reduction of conjugated ketones is well illustrated with A1-9 2-octalone (Scheme 11.3) [17], Reduction with the sodium salt in tetrahydrofuran is relatively slow and produces the allylic alcohol (1) and the saturated alcohol (2) in a 1.2 1 ratio whereas, in contrast, tetra-n-butylammonium borohydride produces the non-conjugated alcohol (3) (50%) and the saturated alcohol (2) (47%), with minor amounts of the ketone (4), and the allylic alcohol (1) [16]. It has been proposed that (3) results from an initial unprecedented formation of a dienolate anion and its subsequent reduction. 

Reductions with sodium amalgam are fairly mild. Only easily reducible groups and conjugated double bonds are affected. With the availability of sodium borohydride the use of sodium amalgam is dwindling even in the field of saccharides, where sodium amalgam has been widely used for reduction of aldonic acids to aldoses. 

Complex hydrides can be used for the selective reduction of the carbonyl group although some of them, especially lithium aluminum hydride, may reduce the a, -conjugated double bond as well. Crotonaldehyde was converted to crotyl alcohol by reduction with lithium aluminum hydride [55], magnesium aluminum hydride [577], lithium borohydride [750], sodium boro-hydride [751], sodium trimethoxyborohydride [99], diphenylstarmane [114] and 9-borabicyclo[3,3,l]nonane [764]. A dependable way to convert a, -un-saturated aldehydes to unsaturated alcohols is the Meerwein-Ponndorf reduction [765]. 

The CD fragment 1s synthesized starting with resolved bicyclic acid 129. Sequential catalytic hydrogenation and reduction with sodium borohydride leads to the reduced hydroxy acid 1. The carboxylic acid function is then converted to the methyl ketone by treatment with methyl-lithium and the alcohol is converted to the mesylate. Elimination of the latter group with base leads to the conjugated olefin 133. Catalytic reduction followed by equilibration of the ketone in base leads to the saturated methyl ketone 134. Treatment of that intermediate with peracid leads to scission of the ketone by Bayer Villiger reaction to afford acetate 135. The t-butyl protecting... 

Selective reductions This complex borohydride is particularly useful for selective 1,2-reduction of acyclic a,/ -cnones and of conjugated cyclohexenones to allylic alcohols. However, the 1,2-selectivity is less marked with conjugated cyclopentenones. The reagent reduces unhindered cyclic ketones to the more stable (equatorial) alcohols with stereoselectivity greater than that of sodium borohydride. 

Table 8 Reduction of Conjugated Carbonyl Tosylhydrazones with Sodium Borohydride in Acetic Acid...

The empirical formula is C15H21ON and the IR- and NMR-spectra supplied evidence of a furan ring, a imTis-quinolizidine system, and a double bond conjugated with furan. On reduction with sodium borohydride dehydrodeoxynupharidine gave the dihydro derivative, C15H23ON, which was identical with ( —)-deoxynupharidine hence the problem of its structure was reduced to that of the position of the double bond. 

The stereoselectivity of the hydride reduction of conjugated cyclohexenones has also been subjected to close examination from both experimental and theoretical viewpoints. Much of the work has involved polycyclic systems, e.g.. steroids which have little conformational flexibility and in which axial and equatorial directions of approach can be clearly defined. With small" hydride donors, these substrates show an even clearer preference for axial attack than the corresponding cyclohexanones. For examples involving reductions with lithium aluminum hydride and sodium borohydride, see Table 10. 3/(-Acetylcholest-5-en-7-one and cholest-2-en-l-one are notable in that the analogous saturated substrates are attacked from the equatorial direction115 l16. The reduction of 17/i-hydroxy-4-androsten-3-one (testosterone) to 4-androstene-3/1,17/j-diol with d.r. 90 10 can be compared with the sodium borohydride reduction of 17/i-hy-droxyandrostan-3-one (dihydrotestosterone) to androstane-3/ ,17/ -diol with d.r. 81 19 (see p 4030). 

Dextran was oxidized with sodium periodate to the corresponding polyaldehyde and daunomycin was coupled with a part of the aldehydes via its amino sugar. This complex was further bound to the lysines of the antibody. This conjugate can either be used directly or stabilized by further reduction with sodium borohydride. 

Cyclopropanecarboxylic esters have been prepared, in 75—86 % yield, by intramolecular alkylation of 4-chloroalkyl esters, using phase-transfer catalysis. Monoalkylation of nitro-alkenes by acrylic esters occurs in a controlled manner if a two-phase system is used, to give products of Michael addition in 45—65 % yield for five examples. An interesting variant on this reaction involves the generation of the a-nitro-carbanion by conjugate reduction of a nitroalkene with sodium borohydride followed by its conjugate addition to methyl acrylate yields of 62—95% are reported for five cases (Scheme 39). ... 

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