Lewis acid carbonyl group

If water acts as a nucleophile and adds to the Lewis acid carbonyl group, there is a choice to be made. In principle, water could add to either the carbon or the oxygen of the carbonyl group (Rg. 16.20). 

As mentioned in the New Concepts section, there is a single, central reaction in this chapter, the addition of a nucleophile to the Lewis acid carbonyl group. The details of the mechanism vary, depending on whether the reaction is acid-catalyzed, base-catalyzed, reversible, or irreversible. Here are some general examples. 

The Lewis basic carbonyl group forms a complex with the empty p orbital of the Lewis acidic borane. Hydride transfer is then possible from anionic boron to electrophilic carbon. The resulting tetrahedral intermediate collapses to an iminium ion that is reduced again by the borane. 

A Lewis basic carbonyl group can be activated by coordination with a metal-centered Lewis acid, with profound reactivity and stereochemical consequences. In the context of asymmetric synthesis many Lewis acid-mediated reactions are known to proceed with better stereoselectivity than their non-catalyzed counterparts—very recently a variety of chiral Lewis acids have been shown to be remarkably efficient... 

These points prompt a few words of caution regarding the results discussed in this section and some comments on theoretical results in general. In particular, besides considerations of the size and effect of basis sets, one needs to examine the energy dependence on electron correlation. For donor-acceptor complexes, such as Lewis acid-carbonyls, electron correlation seems to be crucial. It is also instructive to consider the dipole moments of various structures in theoretical studies. Assumption of a gas phase environment may overestimate destabilization due to a large dipole, as dipoles can often be stabilized quite effectively in solution. At times the interpretation of theoretical results are the source of trouble and confusion. Thus two different groups propound apparently conflicting and opposite views on the effect of Lewis acids on the carbonyl dipole. 

The 13C NMR study clearly reveals that acetophenone largely shifts to the downfield when in association with BF3, while no shift is observed in trifluoroacetophenone under the same conditions. This fact suggests that no association of the markedly weak Lewis basic carbonyl group of 27 with Lewis acid is observed under the NMR analysis conditions. The nonfluorinated carbonyl group associates strongly with Lewis acid to enhance the electrophilic reactivity, while the corresponding fluorinated one does not (Scheme 1.19) [ 8]. 

Lewis add-base interactions are very common in chemistry and are often rather subtle. You are about to meet, in the next chapter, an important way of making C-C bonds by adding organometallics to carbonyl compounds, and in many of these reactions there is an interaction at some point between a Lewis acidic metal cation and a Lewis basic carbonyl group. 

The proposed Si-face stereoinduction model involves stabilization of the Lewis acid-carbonyl complex with a formyl iZ-bond to the BINOL ether oxygen (l l complex of ethyl glyoxal 90). Replacement of the formyl hydrogen with an alkyl group provided little of the expected product with the bisindolyl alkylated side adduct (91) predominating and minimal stereocontrol for the associated adduct (not shown in scheme, 10% ee). 

Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

Finally, if there could be a way in which in water selective ri Jt-coordination to the carbonyl group of an a,P-imsatLirated ketone can be achieved, this would be a breakthrough, since it would subject monodentate reactants to catalysis by hard Lewis acids ". ... 

The rate of the Lewis-acid catalysed Diels-Alder reaction in water has been compared to that in other solvents. The results demonstrate that the expected beneficial effect of water on the Lewis-acid catalysed reaction is indeed present. However, the water-induced acceleration of the Lewis-add catalysed reaction is not as pronounced as the corresponding effect on the uncatalysed reaction. The two effects that underlie the beneficial influence of water on the uncatalysed Diels-Alder reaction, enforced hydrophobic interactions and enhanced hydrogen bonding of water to the carbonyl moiety of 1 in the activated complex, are likely to be diminished in the Lewis-acid catalysed process. Upon coordination of the Lewis-acid catalyst to the carbonyl group of the dienophile, the catalyst takes over from the hydrogen bonds an important part of the activating influence. Also the influence of enforced hydrophobic interactions is expected to be significantly reduced in the Lewis-acid catalysed Diels-Alder reaction. Obviously, the presence of the hydrophilic Lewis-acid diminished the nonpolar character of 1 in the initial state. 

A regioselective aldol condensation described by Biichi succeeds for sterical reasons (G. Biichi, 1968). If one treats the diaidehyde given below with acid, both possible enols are probably formed in a reversible reaaion. Only compound A, however, is found as a product, since in B the interaction between the enol and ester groups which are in the same plane hinders the cyclization. BOchi used acid catalysis instead of the usual base catalysis. This is often advisable, when sterical hindrance may be important. It works, because the addition of a proton or a Lewis acid to a carbonyl oxygen acidifies the neighbouring CH-bonds. 

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