Activity carbonylation, relationship

It is widely accepted that the carbonyl reactivity toward nucleophiles increases in the order aldehyde>ketone>ester>amide [6]. This reactivity order is simply based on the extent to which each carbonyl carbon is sterically and electronically activated. However, reactivities might change when these carbonyl substrates are subjected to a Lewis acid. It is generally assumed that the coordination capability of the carbonyl oxygen to Lewis acids is the means by which Lewis acids activate carbonyl substrates. Thus, in some re.spects, the reaction rate parallels the Lewis basicity of the carbonyls. Furthermore, the reactivity of a carbonyl substrate depends on the reaction type as well as the Lewis acid employed. Special care must be taken in assessing the relationship between the relative reaction rate, the relative Lewis basicity, and the inherent carbonyl reactivity of each substrate. It is instructive to take a look at the following example (Schemes 2-2 and 2-3 Fig. 2-1). 

Exploratory research on structure activity relationships in the meperidine series revealed the interesting fact that the oxygen atom and carbonyl group of this molecule could often be interchanged. That is, the so-called "reversed meperidine" (C) still exhibits analgesic activity in experimental animals. (Note that, except for the interchange, the rest of the molecule is unchanged.)... 

Ni catalysts for olefin polymerization incorporating a-iminocarboxamide ligands are activated by the formation of borane-carbonyl adducts (153).542 Structure/reactivity relationships are similar to Brookhart s dimine catalysts. 

Another noncatalytic step proposed by King et al. (18) in iron carbonyl/base catalysis of the WGSR involves the formation of formate ion however, we recently observed that formate formation appears to have little importance in the related rhodium catalysis of hydrohydroxymethylation. We plan to perform studies of the CO + KOH and C02 + KOH reactions independent of catalysis to more fully appreciate the relationship of these reactions to solution pH and thus the catalytic activity. 

This annulation process was of considerable value in early approaches to steroid synthesis. The structural relationship of the bicyclic product obtained here to the male sex hormone testosterone is immediately apparent. Further, the non-conjugated carbonyl is now activating the adjacent carbon that subsequently features in building up the third ring system. 

Manabe, S., Nishino, C. and Matsushita, K. (1985). Studies on relationship between activity and electron density on carbonyl oxygen in sex pheromone mimics of the American cockroach, part XI. Journal of Chemical Ecology 11 1275-1287. 

N-propinylazoles of the BAY d 9603 type have a close structural relationship to the tritylazoles. They have a wide range of activity, particularly effective against mould fungi. Starting material here is the readily available diphenyl-propinol obtained by ethinyla-tion of benzophenone. The method for the conversion of this carbinol into the corresponding N-substituted imidazole is the reaction with carbonyl or thionyl-bis-imidazole, or preferably with the tris-imidazolide of phosphoric acid in a polar solvent. All other alkylation methods in which carbocations occur as intermediates completely fail. 

The triester 70 was needed to study pericyclic reactions with electron-rich (a) and electron poor (b) alkenes.12 The a, 3-unsaturated carbonyl disconnection reveals an enolisable ester 72 (X is some activating group such as CCbR) and a very electrophilic keto-diester 71. The synthesis of the allyl ester 72 is all right but the tricarbonyl compound 71 with two 1,2-diCO relationships, is a challenge. 

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