Synthons acyl cation

The corresponding disconnection is of the newly formed C-C bond 8a. The synthons are the acyl cation and a nucleophilic carbon species that might be a metal derivative RM (chapter 13) but will generally be an enolate in the next 10 chapters. And that is how carbonyl compounds are nucleophilic. 

Methoxy(trimethylsilyl)methane and methoxybis(trimethylsilyl)niethane have been proposed as new synthons for the formyl anion and the methoxycarbonyl anion, respectively after alkylation, C-Si cleavage is achieved by anodic oxidation. Similar electrochemical oxidative cleavage of acylsilanes reveals their potential as acyl cation synthons. Anodic oxidation of N-silylmethyl carbamates in methanol produces f -methoxymethyl carbamates in high yield. 

The acyl cation 2a or acylium ion 2b is a familiar intermediate in the Friedel-Crafts reaction. It is easy to make (acid chloride + Lewis acid 1) and it can be observed by NMR as it expresses the natural reactivity pattern of the acyl group. The acyl anion by contrast has umpolung or reverse polarity.1 One might imagine making it from an aldehyde by deprotonation 3 and that it would be trigonal 4a or possibly an oxy-carbene 4b. Such species are (probably) unknown and their rarity as well as their potential in synthesis has led to many synthetic equivalents for this elusive synthon. The acyl anion, the d1 synthon, is the parent of all synthons with umpolung2 and should perhaps have been treated before the homoenolates dealt with in the previous chapter. 

Interconversion a results in logical synthons, alkoxy anion TM 5.4a and acyl cation TM 5.4b. The reagent for anionic synthon is a-hydroxy ketone, available by a-bromination of ketone followed by hydrolysis of halogen. Now we observe that disconnection b offers a more simple solution. Since the reagent for TM 5.4c is a-haloketone, this intermediate can be directly acylated by carboxylate anions to TM 5.4. The complete synthetic proposal for TM 5.4 is presented in Scheme 5.12. Synthesis of enantiomerically pure a-alkylcarboxylic acids is discussed in Sect. 3.6.3. 

Usually, the a-pyranic addition products (3) cannot be isolated because they isomerize immediately in a thermally allowed electrocyclic process affording acyclic dienones (4), which in many cases react further. Therefore, pyrylium salts 2A react with most nucleophiles as if they had the electronic structure 2B, and thus the pyrylium cation behaves as a useful synthon, namely the last vinylog in the series of acyl halides (Cj synthon) - p-halovinyl ketones (C3 synthon) - pyrylium (C5 synthon) [50, 51],... 

The corresponding reactions are mostly ionic involving nucleophilic displacement by SnI, Sn2 or carbonyl substitution with amines, alcohols and thiols on carbon electrophiles. The normal polarity of the disconnection 1 will be a cationic carbon synthon 2 and an anionic heteroatom synthon 3 represented by acyl or alkyl halides 4 as electrophiles and amines, alcohol or thiols 5 as nucleophiles. 

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