Aldehyde group, directing effect

The NAD+-dependent alcohol dehydrogenase from horse liver contains one catalytically essential zinc ion at each of its two active sites. An essential feature of the enzymic catalysis appears to involve direct coordination of the enzyme-bound zinc by the carbonyl and hydroxyl groups of the aldehyde and alcohol substrates. Polarization of the carbonyl group by the metal ion should assist nucleophilic attack by hydride ion. A number of studies have confirmed this view. Zinc(II) catalyzes the reduction of l,10-phenanthroline-2-carbaldehyde by lV-propyl-l,4-dihy-dronicotinamide in acetonitrile,526 and provides an interesting model reaction for alcohol dehydrogenase (Scheme 45). The model reaction proceeds by direct hydrogen transfer and is absolutely dependent on the presence of zinc(II). The zinc(II) ion also catalyzes the reduction of 2- and 4-pyridinecarbaldehyde by Et4N BH4-.526 The zinc complex of the 2-aldehyde is reduced at least 7 x 105 times faster than the free aldehyde, whereas the zinc complex of the 4-aldehyde is reduced only 102 times faster than the free aldehyde. A direct interaction of zinc(II) with the carbonyl function is clearly required for marked catalytic effects to be observed. 

Kinetic resolution can be accomplished by addition of allyl boronates to aldehyde groups adjacent to the tricarbonyliron fragment [59]. For the synthesis of ikaruga-mycin, Roush and Wada developed an impressive asymmetric crotylboration of a prochiral meso complex using a chiral diisopropyl tartrate-derived crotylborane (Scheme 1.25) [60]. In the course of this synthesis, the stereo-directing effect of the tricarbonyliron fragment has been exploited twice to introduce stereospedfically a crotyl and a vinyl fragment. 

We can, in a qualitative way, combine the directing effects of two or more substituents. In some cases the substituents both direct to the same positions, as in the syntheses of bromoxynil and ioxynil, contact herbicides especially used in spring cereals to control weeds resistant to other weedkillers. They are both synthesized from p-hydroxybenzaldehyde by halogenation. The aldehyde directs meta and the OH group directs ortho so they both direct to the same position. The aldehyde is deactivating but the OH is activating. 

When looking at any compound where competition is an issue it is sensible to consider electronic effects first and then steric effects. For electronic effects, in general, any activating effects are more important than deactivating ones. For example, the aldehyde below has three groups—two methoxy groups that direct ortho and para and an aldehyde that directs meta. 

A new method for the ortho hydroxylation of aromatic aldehydes via orrho-lithiated arcnnatic aminoal-koxides has recently been reported by Einhom et al Fonnation of the aminoalkoxide serves two purposes. Firstly, the aldehyde group is protected and, secondly, the aminoalkoxide directs lithiation to the ortho position. Oxidation of the lithio species was effected by either MoOPH or molecular oxygen, albeit in poor yield. Alternatively, a two-step, one-pot condensation of the lithio intermediate with tributyl borate followed by oxidation with hydrogen peroxide gave the ortho-hydroxy aldehydes (24) in slightly better yields (Scheme 9). 

Because of carbonium ion generation, aromatic aldehydes and ketones can usually be reduced more easily than the corresponding aliphatic compounds. However, a modified Clemmensen reduction is an effective method to reduce isolated aliphatic carbonyl groups directly to methylene groups, and typical examples are shown in equations (4)-(6)." ... 

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