Carbonyl groups hardness

Carbonyl or cyano groups, of proven value in Diels-Alder reactions and 1,3-dipolar cycloadditions, are unsuitable for anionic cycloadditions owing to the pronounced nucleophilic and basic character of the anionic reagents. Instead of cycloaddition nucleophilic attack of these groups or deprotonation of the substrates would occur. This means that aromatic residues are indispensible which are practically unremovable after the cycloaddition and, unlike the carbonyl group, hardly unsuitable for subsequent synthetic steps. 

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 ". ... 

Pt-catalyzed hydration of various aliphatic and aromatic alkynes under phase transfer conditions in (CH2C1)2/H20 in the presence of Aliquat 336 led to either a Markovnikov product, mixtures of two ketones, or ketones with the carbonyl group positioned away from the bulky side.72 In the absence of the phase transfer reagent, Aliquat 336, hardly any reaction took place. Recently, a hydrophobic, low-loading and alkylated polystyrene-supported sulfonic acid (LL-ALPS-SO3H) has also been developed for the hydration of terminal alkynes in pure water, leading to ketones as the product.73 Under microwave irradiation, the hydration of terminal arylalkynes was reported to proceed in superheated water (200°C) without any catalysts.74... 

While main group metals and early transition metals are hard Lewis acids favoring coordination of carbonyl groups, gold, one of the late transition metals, is classified as a soft metal that activates 7r-electron systems like olefins and... 

As for pyrones. the nature of the nucleophile (hard or soft) determines whether reactions occur at the carbonyl group or at the atom of the enone system. Electrophiles attack in I he benzene ring. 

Pyrones and thiopyrones react very readily with a variety of nucleophiles, but here the situation is complicated not only by the carbonyl group, but by the fact that these compounds show elements of both aromatic and aliphatic character. Pyran-2-one (9) can in principle react with nucleophiles at the 2-, 4- or 6-position and examples of each type of reaction are known. There is an approximate correlation with the hard and soft acid and base hypothesis, in that hard nucleophiles such as HO generally react at the 2-position while soft nucleophiles such as hydride ion generally react at the 6-position. Reactions at the 4-and 6-positions can, of course, be rationalized mechanistically simply as examples of conjugate addition. A similar situation obtains with pyran-4-ones (10), where reaction can in principle occur at the 2- or 4-position. Hard nucleophiles generally react at the 2-position,... 

It is appropriate at this point to summarize the tendency of various nucleophiles to add to the carbonyl group. In general, the strong bases (organometallics, hydrides, negative ions) are most effective among the neutral nucleophiles, the soft ones, for example the sulfur bases, tend to be more effective in addition than the hard ones, for example the oxygen bases. 

Enolate ions, which are usually strong nucleophiles, are more important in preparative applications than are the enols. In additions to carbonyl groups, the carbon end, rather than the oxygen end, attacks but in SA,2 substitutions on alkyl halides, significant amounts of O-alkylation occur. The more acidic compounds, such as those with the j3-dicarbonyl structure, yield enolates with the greater tendency toward O-alkylation. Protic solvents and small cations favor C-alkylation, because the harder oxygen base of the enolate coordinates more strongly than does the carbon with these hard Lewis acids.147... 

This reaction is widely utilised in organic synthesis, when carbonyl groups may be protected as the thioacetals or thioketals. Unlike acetals or ketals, the thio compounds do not undergo acid catalysed hydration, and may be used in acidic reaction conditions. The metal-directed hydrolysis is rationalised in terms of the soft-soft interaction of the sulfur with the metal cation, in contrast to the hard-soft interaction with a proton. Hydrolysis is readily achieved on treatment with aqueous mercury(n) or silver(i) salts. Once again, the... 

It was shown on the basis of IR spectral data that the soft mercury chloride is coordinated on the chromium atom and the indicated hard acids are connected with N or O (R = OH) donor centers [457], This conclusion required x-ray diffraction proof, since a coordination (of the type 754) on the oxygen atom of the carbonyl group is not excluded due to the presence of the C = 0 fragment [91,450,451],... 

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