Cation-anion synthons

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. 

The [0s(0)2(0H)4] salts are useful synthons for other oxo compounds (Fig. 18-F-4). There are many other oxo species, cationic, anionic, and neutral, some examples being [0s02(en)2]2+, [0s02(0Ac)3] , Os03(NBu(), and Os02(mes) described in Section 18-F-14. 

The retrosynthetic step involving the breaking of bond(s) to form two (or more) synthons is referred to as a disconnection. A synthon is an idealized fragment, usually a cation, anion or radical, resulting from a disconnection. One must select disconnections which correspond to the high yielding reactions. 

If you want to make a diene one obvious place to disconnect is between the two alkenes 1. Though this has a pleasing symmetry, one of the synthons must be a vinyl cation 2 and the other a vinyl anion 3. We have already met stereochemically controlled reagents for the vinyl anion synthon such as vinyl metals 4 (chapter 16) and all we now need is a good reagent for the vinyl cation. That is the subject of this chapter. First we need to examine why you can t just use a vinyl halide and expect to get substitution of the halide ion. 

The reagent for cationic synthon is propionitrile 5 and the reagent for anionic synthon Grignard reagent 4, available from 3-bromopyridine. 

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. 

As presented in Sect. 5.1, an even number of C atoms between oxygen functionalities results in a mismatch of partial charges on the atoms of the central C-C bond. Accordingly, disconnection of the central C-C bond in 1,4-dicarbonyl compounds results in an acceptable anionic synthon and illogical cationic synthon with a positive charge on the a-C atom (Scheme 5.38). 

We have repeatedly introduced acceptable reagents for anionic synthons, while those for cationic synthons are discussed in Sect. 5.2.2. Inversion of polarity on a-C atoms in cationic synthons is achieved by introduction of an o-electron acceptor group, as analyzed in Example 5.4. 

Introduction. The title aUylsilane reagent has been enployed as a conjunctive reagent which is considered to be a synthetic equivalent of a zwitterionic, bifunctional compound possessing a nucleophilic allylic anion synthon and an electrophilic cation synthon in the same molecule (1). 

So far aU our two group disconnections have sensible synthons with anions or cations all stabihsed by functional groups in the right positions. This won t always be the case. Supposing we wanted to make the hydroxy-acid TM 131 we could treat it as an alcohol ... 

More recently, radical additions to fluoroethenes have attracted attention. Eguchi et al. [125] applied the Barton decarboxylation procedure to add a range of alkyl radicals to l,l-dichloro-2,2-difluoroethene. Addition was regioselective and the terminal carbon could be hydrolysed to a carboxyl group with silver(I) mediation (Eq. 39). The fluoroalkene is effectively an equivalent for either difluoroacetyl anion or cation synthons, because the adding radical can be approached from either polarity manifold. 

A. Dondoni and L. Colombo, New formyl anion and cation equivalents, in Advances in the Use of Synthons in Organic Chemistry, Vol. 1, A. Dondoni, ed., JA1 Press, Greenwich, 1993,... 

Directed coupling reactions, where no cross-coupling may occur, requires the reagents derived from the appropriate synthons to be ionically different at the reactive site. The carbon-carbon coupling reaction to form hept-l-ene (Expt 5.8), illustrates the importance of selecting the reactive, and readily available, allyl bromide (cationic site) with butylmagnesium bromide (anionic site) (A), rather than the other alternative (B). 

Glycerol may be derivatized with a variety of compounds to prepare anionic, cationic, or nonionic types of surfactants. This allows numerous compounds to be designed for diverse applications while incorporating glycerol as a key component. This extends the versatility of glycerol in the synthesis of surfactants and demonstrates the general utility of glycerol as a renewable synthon. 

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. 

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