Carbonyl groups, 40. addition paths

The addition paths of two separated MeMgCl molecules to the carbonyl group of chiral a-alkoxy carbonyl compounds, which are shown in Schemes 8 and 9 and in Figure 11 in Section IV, were traced. However, in these models, one MeMgCl molecule bridges two oxygen atoms and acts merely as a catalyst. Instead, the Schlenck dimer (MeMgCl)2 should be considered for the carbonyl reactant coordination. 

Strong evidence for the reaction path of the addition of a nucleophile to a carbonyl group comes from the X-ray structure of the naphthalene amino ketone 122 (85). In most 1,8-disubstituted naphthalenes, both substituents are splayed outward (cf. 123). In 122, the C-CO bond is splayed outward, but the C-N bond leans inward (cf. 124). This brings the nitrogen into a more favorable position for attack than is possible in the undistorted molecule. Similar observations were made with the amino ester (122,... 

We have already discussed in Chapter 2 that nucleophilic addition to a carbonyl group is controlled by stereoelectronic effects. Both X-ray data and theoretical calculations indicate a clearly defined path (cf. p.32) for the attack of a nucleophile on a carbonyl group. Baldwin (1) has also used a vector analysis approach to predict the stereochemistry of the addition products. 

To determine which oxygen of 4-butanolide becomes labeled with 180, trace the path of 180-labeled water (O = lsO) as it undergoes nucleophilic addition to the carbonyl group to form the tetrahedral intermediate. 

The mechanism of the indenone synthesis (Scheme 3) seems to involve (1) oxidative addition of the aryl iodide to Pd(0) (2) arylpalladium coordination to the alkyne and subsequent insertion of the alkyne to form a vinylpalladium intermediate (8), (3) then either the vinylic palladium intermediate adds to the carbonyl group and subsequently undergoes a /3-hydride elimination (path A) or the alde-hydic C-H bond may oxidatively add to the palladium to produce an organopalla-dium(IV) intermediate (six-membered ring palladacycle) which subsequently undergoes rapid reductive elimination of the indenone and palladium (path B). The actual mode of ring closure of the vinylic palladium intermediate to the inde-... 

The reactivity of the carbonyl group in a,/3-unsaturated dialdoses was studied in more detail. The interaction with phenylhydrazine and its derivatives led to different results. 3-0-Benzyl-l,2-0-cyclo-hexyl idene-5,6-dideoxy-a-D-xyZo-hept-5-e nodialdo-l,4-furanose (56) gave57 a (2,4-dinitrophenyl)hydrazone. Action of (2,4-dinitrophenyl)-hydrazine on derivatives 67 led18 to complex mixtures. In the case of the acetylated derivatives (66), as well as of branched-chain derivatives (69), the interaction with (2,4-dinitrophenyl)hydrazine resulted in the formation of the expected hydrazones (Refs. 24 and 51, respectively). The interaction with phenylhydrazine was, however, proved to proceed by two paths in this case. Only the nitro derivatives (66, R = p-nitrophenyl) and (69, R = p-nitrophenyl) were shown24,51 to form the expected hydrazones. The phenyl derivative 66 (D-galacto, R = Ph) and p-methoxyphenyl derivative 69 (R = p-MeOC8H4) afforded substituted pyrazolines (74) (Ref. 24) and (75) (Ref. 51), respectively, as a result of subsequent intramolecular addition of a... 

In addition to the reaction between the no orbital of the carbonyl group and the orbital, another conceivable reaction path for hydrogen abstraction is based on an interaction between the tco and the orbital. This is referred to as a perpendicular attack. 

Addition to the Carbonyl Group — The internal, cyclic hemiacetal formation is one of the illustrations of such addition. The H2N-X nucleophiles, with X being NH2 (hydrazine), NHAr (arylhydrazines), OH (hydroxylamine), NHCONH2 (semi-carbazide), NHCSNH2 (thiosemicarbazide), or alkyl (primary amine), produce hydrazones, arylhydrazones, oximes, semicarbazones, thiosemicarbazones, and alkyl imines (Schiff bases), respectively, following the following path 5.4 + 5.15 — 5.16 ->. .. -> 5.21. 

The correlation coefficients between the individual RDF descriptors and the ASD (Figure 5.15) show no signihcant difference between the compounds 7-14 because of the high diversity in the data set. In addition, the compounds 2 and 3 as well as compounds 19 and 20 are indicated as similar within the data set. One major difference between the compounds 6-14 (ethyl ester) and 15 (methyl ester) is only indicated by the bond-path RDF descriptor that reacts sensitively to the additional carbonyl group of compound 15. 

It is possible to predict the preferred stereochemical path of nucleophilic addition if one face of a carbonyl group is significantly more hindered to the approach of the reagent than the other. When no clear distinction between the two faces is evident, other, more subtle effects, which are stiU incompletely understood, come into play. 

In the reactions that are known to follow path a (equation 86), the transition metal is electron-rich or low-valent. A recent report describes the reverse addition of a M-Si bond to a carbonyl group by an early transition-metal silyl (path b, equation 86). The d° silyl... 

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