Sulphonates, coupling reactions

The photoextrusion of sulphur dioxide to form cyclophanes or other novel aromatic molecules has been reviewed and studied by Givens208-210, while the photodecomposition of aromatic sulphones to form products of radical coupling reactions has recently also received attention211. 

The ratio ARH/ARj (monoalkylation/dialkylation) should depend principally on the electrophilic capability of RX. Thus it has been shown that in the case of t-butyl halides (due to the chemical and electrochemical stability of t-butyl free radical) the yield of mono alkylation is often good. Naturally, aryl sulphones may also be employed in the role of RX-type compounds. Indeed, the t-butylation of pyrene can be performed when reduced cathodically in the presence of CgHjSOjBu-t. Other alkylation reactions are also possible with sulphones possessing an ArS02 moiety bound to a tertiary carbon. In contrast, coupling reactions via redox catalysis do not occur in a good yield with primary and secondary sulphones. This is probably due to the disappearance of the mediator anion radical due to proton transfer from the acidic sulphone. 

Fig. 3.127. Representative coupling reaction between PNBD and the sodium salt of 2-naphtol-6-sul-phonic acid to yield the 6-sulphonate-2-naphtol-l-azo-p-nitrobenzene azo dye. Reprinted with permission from C. Bravo-Diaz et al. [177],...

Pyrrole anion is unreactive in liquid ammonia under irradiation with PhBr or 1-chloro-naphthalene. However, the reactions of aryl chlorides (p-chlorobenzonitrile, 3- and 4-chloropyridines and 4-chlorodiphenyl sulphone) with 2,5-dimethylpyrrole anion under electrochemical inducement in the presence of a redox mediator gave the C3-substituted product in moderate yields (35-40%) (equation 120)225. The rate constant of the coupling reaction between this nucleophile and aryl radicals is about 5-8 x 109 M"1 s 1 determined by electrochemical methods225. 

In the same way, the coupling reaction of acyl chlorides and organotins is particularly efficient and general . This represents an alternative to the carbonylative three-component coupling reaction, and gives access to various aldehydes, ketones and a, fi-unsaturated ketones. A similar reaction is feasible with chloroformates, carbamoyl chlorides and snlphonyl chlorides, giving respectively a, -unsaturated esters, amides and sulphones . ... 

The important property of these compounds is that they will couple with aromatic amines and hydroxy derivatives to form highly coloured products which, when rendered soluble by sulphonation, give rise to a great range of dyestuffs known as the azo dyes. A simple example of a coupling reaction is shown in the following equations ... 

Isoprosopinine A and B (223a,b) were synthesized via a coupling reaction of a bromoalkyl piperidine with sulphone anions to extend the side chain. Removal of the sulphone groups with sodium amalgam, and further deprotection gave 223a,b [500]. 

The sulphone coupling which was applied for the first time to the synthesis of vitamin A (29) by Julia [41] has frequently been used for the preparation of retinoids and carotenoids [42]. In this reaction a carbon-carbon double bond is produced by alkylation of the a-carbanion of a sulphone 36 by a halogen derivative 37 to give 38, followed by a base-promoted elimination to give the desired alkene 39 (Scheme 9). 

A prominent example of the application of the sulphone coupling is the synthesis of (3,p-carotene (2) by the reaction of the Ci3-sulphone 40 with the dichloride 41 to give 15,15 -didehydro-p,p-carotene, which was transformed to p,p-carotene (2) (Scheme 10). 

Illustrated in the second example (Scheme 3) is the synthesis of zeaxanthin (119), a symmetrical carotenoid which can also be prepared by an analogous strategy employing the Julia sulphone coupling method instead of the Wittig reaction [3, 4]. 

For the synthesis of some symmetrical carotenoids, p,p-carotene (3), another strategy based on the dimerization of a C2o-intermediate (2 x C20 = C40), has been used [7-9]. Since the yields of such coupling reactions via the corresponding phosphoranes, sulphones or aldehydes with Ti as a reagent) have not been very high, this approach is only efficient if the C2o-building blocks, like, for example vitamin A, are readily available and inexpensive (Scheme 5). 

Recently the application of sulphone coupling was reported for the preparation of lycopene (31) [6]. Geranyldiethylamine (21) was converted into geranylsulphone (22) by reaction with ethyl chloroformate and sodium chlorophenylsulphate. Treatment of 22 with BuLi, crocetin-dialdehyde (536), acetic anhydride and base led to the C4o-disulphone 23 with a di-cis configuration. Reduction with disodium dithionite gave (all- )-lycopene (31) (Scheme 5). 

The first example of dihalocarbene insertion into a saturated C—H bond of an organometallic complex has been reported using a phase-transfer catalyst The first example of phase-transfer catalysts for electrophilic substitution involved an azo-coupling reaction in water-dichloromethane using sodium 4-dodecylbenzene-sulphonate giving a rate acceleration of ca. 200-fold. ... 

Conant and Peterson123 made the first kinetic study of the coupling of diazonium ions with aromatics, and measured the rates of reaction of diazotised aniline and its 2-MeO, 4-Me, 4-Br and 4-S03H derivatives with the sodium salts of 4-hydroxybenzenesulphonic acid, 2-naphthol-3,6-disulphonic acid, 1-naphthol-3,8-disulphonic acid, and l-naphthol-4-sulphonic acid. The reaction was second-order, viz. 

Trost published a desulphonylation procedure for aryl alkyl sulphones using an excess of sodium amalgam in buffered ethanol126 (equation 52). Trost claimed that this is superior to earlier reactions using sodium amalgam in ethanol because of a couple of factors the use of the acid phosphate buffer to prevent formation of significant amounts of sodium methoxide is particularly important, since this can cause isomerizations in base-sensitive substrates, and the temperature should be kept low, but optimized for each substrate. 

---