Functional group addition carbonyl compounds

Different groups reported in 2007 on the use of C9 amino cinchona alkaloids as catalysts for the stereoselective functionalization of branched carbonyl compounds. Connon and coworkers demonstrated that the C9 amino derivative of epidihydro-quinine (40) and epidihydroquinidine (41) were effective catalysts for the conjugate addition of aldehydes and (cyclic) ketones to nitroalkenes via enamine catalysis [99] (Scheme 6.46). The catalysts with the same configuration at C9 as in the natural cinchona alkaloid gave poor results, in line with the results obtained for... 

The carbonyl substrate 3 to be reacted with the organozinc compound 2 can be an aldehyde or ketone that may contain additional functional groups. With a vinylogous halo ester—i.e. a y-halocrotyl ester—the corresponding y-crotylzinc derivative is formed. 

With respect to the carbonyl substrate, a variety of additional functional groups is tolerated, e.g. ester, ether, halogen. With compounds that contain an ester as well as a keto or aldehyde function, the latter usually reacts preferentially. Due to its mild reaction conditions the Wittig reaction is an important method for the synthesis of sensitive alkenes, as for example highly unsaturated compounds like the carotinoid 17 shown above. 

By the end of this chapter, we will have seen all the common functional groups. Of those groups, amines and carbonyl compounds are the most abundant and have the richest chemistry. In addition to the proteins and nucleic acids already mentioned, the majority of pharmaceutical agents contain amine functional groups, and many of the common coenzymes necessary for biological catalysis are amines. 

Carbinolamine (Section 19.8) A molecule that contains the R2C(OH)NH2 functional group. Carbinolamines are produced as intermediates during the nucleophilic addition of amines to carbonyl compounds. 

Azirines (three-membered cyclic imines) are related to aziridines by a single redox step, and these reagents can therefore function as precursors to aziridines by way of addition reactions. The addition of carbon nucleophiles has been known for some time [52], but has recently undergone a renaissance, attracting the interest of several research groups. The cyclization of 2-(0-tosyl)oximino carbonyl compounds - the Neber reaction [53] - is the oldest known azirine synthesis, and asymmetric variants have been reported. Zwanenburg et ah, for example, prepared nonracemic chiral azirines from oximes of 3-ketoesters, using cinchona alkaloids as catalysts (Scheme 4.37) [54]. 

Since aromatic substitutions, aliphatic substitutions, additions and conjugate additions to carbonyl compounds, cycloadditions, and ring expansion reactions catalyzed by Fe salts have recently been summarized [17], this section will focus on reactions in which iron salts produce a critical activation on unsaturated functional groups provided by the Lewis-acid character of these salts. 

Compounds in which a carbonyl or other nucleophilic functional group is close to a carbenoid carbon can react to give ylide intermediate.221 One example is the formation of carbonyl ylides that go on to react by 1,3-dipolar addition. Both intramolecular and intermolecular cycloadditions have been observed. 

We have intentionally selected example reactions (Figs. 29-33) that would not usually be immediately obvious to a chemist. The examples chosen have all been concerned with rearrangements of various types, since their courses are frequently difficult to predict. It remains to emphasize that the reactivity functions contained in EROS perform perfectly well with other types of reaction. This is true, for example, with reactions that a chemist could derive directly from an analysis of the functional groups in a molecule. Thus, EROS predicts addition reactions to carbonyl compounds, nucleophilic substitutions, and condensation reactions, to name just a few examples. In all these reaction types, the possibility of assigning a quantitative estimate to the reactivity at the various sites via the reactivity functions is of particular merit. It... 

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