Heteroatoms with acyl groups

Fig. 6.15. Carboxylic acid activation with DCC. [1,3] means the intramolecular substitution of the oxygen atom 01 by the N atom "3" via a cyclic four-membered tetrahedral intermediate. From the point of view of the heteroatoms, this SN reaction corresponds to a migration of the acyl group R-C=0 from the oxygen to the nitrogen. (Examples for amino acid activations in the form of the pentafluorophenyl ester C or the benzotriazolyl ester D are given in Figure 6.32 (oligopeptide synthesis) and Figure 6.31 (dipeptide synthesis), respectively.

As discussed above, dialkylamino carbene complexes result in the formation of indenes due to the increased donor ability of the nitrogen compared to the oxygen heteroatom. The formation of benzannulation products is favored, however, if the electron density at nitrogen is lowered by substitution with electron-withdrawing acyl groups [33]. The example in Scheme 12 demonstrates the effect. 

In addition to protons, alkyl and acyl groups, silyl groups are sufficiently electropositive to initiate carbocationic polymerizations. Silicon is more electropositive than carbon, and therefore reacts with many nucleophiles, especially those based on oxygen. The resulting silicon-heteroatom bonds are relatively labile trimethylsilyl is thus often referred to as a bulky... 

The major groups of acyclic organic peroxides may be obtained by successively substituting H atoms in H2O2 with alkyl, aryl, acyl, alkoxycarbonyl or heteroatom substituents (Figure 3). A formal O insertion into the 0—0 bond provides polyoxides, i.e. compounds with at least three O atoms in a row. Substituents R have the potential to modify the... 

An unexpected reactivity in the functionalization of 2-acyl-l,3-dithianes has been reported by Mioskowski and co-workers. They found that 2-acyl-l,3-dithianes with no further heteroatom at the acyl side chain react with aldehydes to give 2-acyl-2-hydroxyalkyl-l,3-dithianes, whereas a silyl-protected hydroxy group in the side chain of the 2-acyl-l,3-dithiane led to formation of the aldol product at the opposite site of the carbonyl group. Acyl chlorides always react with 2-acyl-l,3-dithianes to give the enol esters (Scheme 81) <2003TL213>. 

The most important reactions of alkyl substituents a and y to the ring heteroatom are those which proceed via base-catalyzed deprotonation. Treatment of 2- and 4-alkyl heterocycles with strong bases such as sodamide and liquid ammonia, alkyllithiums, LDA, etc., results in an essentially quantitative deprotonation and formation of the corresponding carbanions. These then react normally with a wide range of electrophiles such as alkyl halides and tosylates, acyl halides, carbon dioxide, aldehydes, ketones, formal-dehyde/dimethylamine, etc., to give the expected condensation products. Typical examples of these transformations are shown in Scheme 17. Deprotonation of alkyl groups by the use of either aqueous or alcoholic bases can also be readily demonstrated by NMR spectroscopy, and while the amount of deprotonation under these conditions is normally very small, under the appropriate conditions condensations with electrophiles proceed normally (Scheme 18). 

For the purposes of this review, we include probe molecules that can be either directly adsorbed or formed in situ. Examples of the latter case are carbenium ions and related electrophilic species. We will also consider several important heteroatom-substituted carbenium ions and heteroatom analogs of carbenium ions. Acylium ions are the intermediates in Friedel-Crafts acylation reactions (96). The most simple, stable acylium ion is the acetylium ion, 1, and others are formally derived by replacing the methyl group with other R groups. Oxonium ions, formed by alkylation of an ether, resemble carbenium ions but are in fact onium ions in terms of their structures. Their stabilization requires strongly acidic media, and like carbenium ions, oxonium ions have been proposed as intermediates in a... 

We start with acid derivatives since we almost always choose to disconnect the bond between the heteroatom and the carbonyl group. So we make esters 11 and amides 13 from acid (acyl) chlorides 12 and alcohols or amines. 

In chapter 10 we compared C-C disconnections with related two-group C-X disconnections, mainly at the alcohol oxidation level. In this chapter we deal more fully with carbonyl compounds, chiefly aldehydes and ketones, by two related disconnections. We start by comparing the acylation of heteroatoms by acid derivatives such as esters (a 1,1-diX disconnection 1 that can also be described as a one-group C-X disconnection) with the acylation of carbon nucleophiles and move on to compare the 1,2-diX disconnection 3 with the alkylation of enolates 6. Here we have reversed the polarity. We mention regioselectivity—a theme we shall develop in chapter 14. 

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