Selective Reduction Between Aldehydes

Selective reduction of ketones.1 This reagent can be used to effect selective reduction of the more hindered of two ketones by DIBAH or dibromoalane. Thus treatment of a 1 1 mixture of two ketones with 1-2 equiv. of 1 results in preferential complexation of the less hindered ketone with 1 reduction of this mixture of free and complexed ketones results in preferential reduction of the free, originally more hindered, ketone. An electronic effect of substituents on a phenyl group can also play a role in the complexation. This method is not effective for discrimination between aldehydes and ketones, because MAD-complexes are easily reduced by hydrides. MAD can also serve as a protecting group for the more reactive carbonyl group of a diketone. The selectivity can be enhanced by use of a more bulky aluminum reagent such as methylaluminum bis(2-f-butyl-6-( 1,1-diethylpropyl)-4-methylphenoxide). 

Neyroz et al. [97] have covalently linked 2NpOH to phos-phatidylethanolamine moiety by the Schiff-base formation between the NH2 of the phospholipid and the aldehyde moiety of 2-hydroxy-1-naphthaldehyde, followed by selective reduction of the imine to obtain a stable secondary amine. This fluorescent phospholipid easily incorporates into DML vesicle membrane and exhibits the typical behavior of ESPT probes. The emission spectrum of this probe inserted in the liposome is similar to that in ethanol medium and is affected by acetate used as a proton acceptor. 

Perhaps the most surprising feature of the sequence is that selective reduction of one aldehyde is possible while the other survives to act as an electrophile in the later aldol cyclisation. The necessity for pre-coordination between the aldehyde and the ester carbonyl group of the alkene acceptor prior to electron transfer to the aldehyde could be responsible for this selectivity.16... 

A comparison of four tri-f-alkoxyaluminum hydrides revealed that lithium tris[(3-ethyl-3-pen-tyl)oxy]aluminum hydride, prepared from LAH and 3-ethyl-3-pentanol, was the most selective for reduction of aldehydes over ketones of all types. Even the less reactive benzaldehyde was reduced in THE at -78 C faster than cyclohexanone (97.7 2.3). A good correlation between the steric demands of the reducing agent and the observed chemoselectivity was observed. 

Chemoselectivity, for example, the differentiation between a ketone and an aldehyde, can in favorable cases be realized by capitalizing on the inherent reactivity of a specific functional group environment. Consider the conversion of 11 to 12 (Scheme 7.18). Traditionally, one tends to apply two short-term protecting groups to achieve the selective reduction of the keto function. 

Extending this technique to the reduction of the dione, L, demonstrated an intramolecular selectivity attributable to conversion of the more reactive C-3 carbonyl to a monoketal intermediate (Gemal and Luche, 1979). This allows the preferential reduction at C-17, and also demonstrates the sharp contrast between aldehyde and ketone ketalization using lanthanide chlorides as catalysts. 

In a subsequent study of reaction parameters, lanthanide ions were found to promote the selective reduction of conjugated aldehydes in the presence of noncon-jugated aldehydes in aqueous ethanol. Erbium trichloride was the preferred catalyst, usually where the solubility of cerium trichloride in solvents such as isopropyl alcohol was unfavorable (Gemal and Luche, 1981b). The authors described the interaction between the lanthanide and the intermediate substrate as a chelating effect . 

A convenient new one-pot procedure for the selective reduction of ketones in the presence of aldehydes (the less usual chemoselectivity) is outlined in Scheme 9. ° The aldehyde is protected as an imine and the ketone is then reduced in situ with a hindred hydride reagent the aldehyde is regenerated on hydrolytic work-up. Conjugated and aromatic aldehydes are protected satisfactorily by this sequence, and moderate discrimination between aliphatic and aromatic aldehydes, with preferential reduction of the aromatic aldehyde, can also be achieved. These authors claim better selectivity than previous methods based on ketalization or hydration of aldehydes with lanthanoid cation catalysts (4,141). 

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