Aliphatic Carbonyls

Paal-Knorr synthesis, 4, 118, 329 Pariser-Parr-Pople approach, 4, 157 PE spectroscopy, 4, 24, 188-189 photoaddition reactions with aliphatic aldehydes and ketones, 4, 232 photochemical reactions, 4, 67, 201-205 with aliphatic carbonyl compounds, 4, 268 with dimethyl acetylenedicarboxylate, 4, 268 Piloty synthesis, 4, 345 Piloty-Robinson synthesis, 4, 110-111 polymers, 273-274, 295, 301, 302 applications, 4, 376 polymethylation, 4, 224 N-protected, 4, 238 palladation, 4, 83 protonation, 4, 46, 47, 206 pyridazine synthesis from, 3, 52 pyridine complexes NMR, 4, 165... 

The irradiation is usually carried out with light of the near UV region, in order to activate only ihc n n transition of the carbonyl function," thus generating excited carbonyl species. Depending on the substrate, it can be a singlet or triplet excited state. With aromatic carbonyl compounds, the reactive species are usually in a Ti-state, while with aliphatic carbonyl compounds the reactive species are in a Si-state. An excited carbonyl species reacts with a ground state alkene molecule to form an exciplex, from which in turn diradical species can be formed—e.g. 4 and 5 in the following example ... 

Aldehydes and ketones are similar in their response to hydrogenation catalysis, and an ordering of catalyst activities usually applies to both functions. But the difference between aliphatic and aromatic carbonyls is marked, and preferred catalysts differ. In hydrogenation of aliphatic carbonyls, hydrogenolysis seldom occurs, unless special structural features are present, but with aryl carbonyls either reduction to the alcohol or loss of the hydroxy group can be achieved at will. 

A variety of catalysts including copper, nickel, cobalt, and the platinum metals group have been used successfully in carbonyl reduction. Palladium, an excellent catalyst for hydrogenation of aromatic carbonyls is relatively ineffective for aliphatic carbonyls this latter group has a low strength of adsorption on palladium relative to other metals (72,91). Nonetheless, palladium can be used very well with aliphatic carbonyls with sufficient patience, as illustrated by the difficult-to-reduce vinylogous amide I to 2 (9). 

Ruthenium is excellent for hydrogenation of aliphatic carbonyl compounds (92), and it, as well as nickel, is used industrially for conversion of glucose to sorbitol (14,15,29,75,100). Nickel usually requires vigorous conditions unless large amounts of catalyst are used (11,20,27,37,60), or the catalyst is very active, such as W-6 Raney nickel (6). Copper chromite is always used at elevated temperatures and pressures and may be useful if aromatic-ring saturation is to be avoided. Rhodium has given excellent results under mild conditions when other catalysts have failed (4,5,66). It is useful in reduction of aliphatic carbonyls in molecules susceptible to hydrogenolysis. 

Hydrogenolysis of aliphatic carbonyls usually does not occur readily unless certain types of structures prevail (78), but hydrogenolysis of an aromatic carbonyl will occur easily, mostly via an intermediate benzyl alcohol. 

Imines are easily reduced and rarely accumulate (62,83). Hydroxylamines are reduced relatively slowly and can be obtained in good yield platinum in acidic media appears to be the preferred system (6,27,54,58,65). Best yields are obtained from oximes of aliphatic carbonyls aromatic oximes give amines. 

Macrocyclic coordination compounds formed bv condensation of metal amine complexes with aliphatic carbonyl compounds. N. F. Curtis, Coord. Chem. Rev., 1968, 3, 3-47 (78). 

As is the case with aryl carbonyls previously studied, aliphatic carbonyls add to olefins to form oxetanes. The picture in this case is far more complicated, however, primarily due to the increased importance of singlet state carbonyl addition to the olefin. In Chapter 1 we saw that in an n->v ... 

Further examples of oxetane formation from aliphatic carbonyls are as follows 1106,184-129 ... 

In the reactions of aliphatic carbonyl compounds with conjugated olefins a very clear distinction of mechanism is possible after comparing calculations with experimental results. Examples are shown in Eqs. 45 112,113) and 46. 114> After n-n excitation of the aldehyde the domi-... 

Termination is principally via radical coupling forming hexabutylditin, or to a lesser degree via the coupling of ketyl radicals. In the case of the mr ketones a different mechanism is proposed. The rate of abstraction of H from the tributyltinhydride by benzylic radicals is slower than the corresponding abstraction by alkyl radicals. Since the rate at which the tributyltin radical will add to aromatic carbonyls is similar to the addition rate to aliphatic carbonyls, the dominant radical species for the tttt systems is the ketyl radical. The primary termination process involves the coupling of the predominant radical species resulting in pinacol formation. 

There is insufficient information on the stereochemistry of the experimentally less simple hydrodimerization of aliphatic carbonyl compounds in a protic... 

We have found a new (/ )-hydroxynitrile lyase from Japanese apricot (P. mume). The new enzyme accepts a broad array of substrates, ranging from aromatic, heteroaromatic, bicyclic to aliphatic carbonyl compounds, and yields the corresponding cyanohydrins with excellent enantioselection. 

Also in the (R)-class of Hnls, although of more limited application, is the (R)-mandelonitrile lyase from Phlebodium aureum [35] which catalyses the addition to some aromatic and heterocyclic carbonyls but only poorly to aliphatic carbonyls. 

Radical additions to alkenes and aromatic systems are well known reactions. The trapping in this manner of radicals obtained by reduction of the aliphatic carbonyl function has proved to be a versatile electrochemical route for the formation of carbon-carbon bonds. Such reactions are most frequently carried out in protic solvents so that the reactive species is a o-radical formed by protonation of the carbonyl radical-anion. Tlie cyclization step must be fast in order to compete with further reduction of the radical to a carbanion at the electrode surface followed by protonation. Cyclization can be favoured and further reduction disfavoured by a... 

The rate of intersystem crossing is just as important as its efficiency. Obviously, if the rate of intersystem crossing is faster than that of diffusion in solution (usually on the order of 1010 sec"1), bimolecular reactions of the excited singlet are precluded. Unfortunately, the intersystem crossing rates are available for only a few carbonyl compounds.11,12 It is known that the rate of intersystem crossing for aliphatic carbonyl compounds (e.g., acetone) is slow (4-20 x 107 sec-1)30 in comparison to that for aromatic carbonyl compounds. Thus, aliphatic (and perhaps some aromatic) carbonyl compounds have an opportunity to react in the excited singlet state. 

Aliphatic carbonyl compounds, such as diacetyl, which has a butter-like odour, also may contribute to the aromas derived from the MaiUard reaction, and many of the Strecker aldehydes also have characteristic aromas (Table 12.1). 

Diimide (N2H2, see p. 779) reduces aromatic aldehydes289 and ketones, but aliphatic carbonyl compounds react very poorly.290... 

In Table 3 the consequences of effects (i)-(vi) are listed systematically for heterocycles, and compared with the similar effect found in the corresponding aliphatic carbonyl compound. 

Alcohols, amines, and thiols add readily to the electrophilic carbon of the carbonyl group to form hemiacetals, carbinolamines, hemiketals, and hemimercaptals. An example is the formation of ring structures of sugars (Eq. 4-1). Water can also add to carbonyl groups and most aliphatic carbonyl compounds... 

The simplest vapor phase reaction of aliphatic carbonyl compounds in their triplet states is cleavage into acyl and alkyl radicals. The acyl radicals, especially at high temperatures, eventually decar-bonylate. 

Cyclization reactions with aliphatic carbonyl compounds other than acetone are, in general, difficult and extremely slow. The reactant mixtures are often allowed to stand for weeks at room temperature and then refluxed in order to obtain appreciable amounts of the products. 

Fluorination ot carbon adjacent to heteroatoms invariably increases lipophilt-city, as does fluorination of double bonds (Table 10), but ot-fluorination of aliphatic carbonyl groups is an exception a-Fluoroketones or aldehydes that form stable... 

Many aliphatic carbonyl compounds show the same dissociation reaction, even acetone (Figure 4.33b). When the carbonyl group is separated from the benzene ring by a suitable substituent such as O, the dissociation takes a different course, as shown in Figure 4.33(c). The resonance stabilization of the phenoxyl radical is much greater than that of the aliphatic radical R, so that splitting of the O-CO bond is favoured. 

The reason for the difference in stereochemistry is that, as quenching studies show, the reactive state of the aromatic carbonyls (which undergo ISC rapidly) is T1 but in aliphatic carbonyls it is The intermediate formed from acetaldehyde and m-2-butene, then, is the singlet biradical 34, whereas the intermediate from benzaldehyde and w-2-butene is the triplet biradical 35. That the stereo-... 

These two methods of activation are complementary. The Lewis-acid (pull) procedure is most efficient for aliphatic carbonyls and the Lewis-base (push) protocol for the aromatic ones. It is noteworthy that TBAF, which often contains residual water, does not inhibit the reaction. 

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