Sulphone coupling

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]. 

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). 

Can be coupled in the 4-position with dia-zotized bases to give a series of azo dyestuffs more usually it is first sulphonated to give a valuable series of intermediates for solubilized azo dyestuffs. The nitro-l-naphthols are themselves dyestuffs, e.g. 2,4-dinitro-l-naph-thol ( naphtol yellow ). 

I-Naphthylamine readily diazotizes and couples to aromatic hydroxylic or basic compounds. It was thus used as a first component in a number of important monoazo dyes, but its use has been severely curtailed because of its potent carcinogenicity. It sulphonates to give naphthionic acid (l-naphthylamine-4-sul-phonic acid). 

If aminoazobenzene is sulphonated with fuming sulphuric acid, and the product again diazotised and coupled w ith /3-naplilhol, Bicbrich scarlet is formed. 

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. 

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. 

These results were significantly improved by the same authors using the well-defined pre-catalyst 16 (PEPPSl-lPr), that is able to promote the coupling of alkyl halides, aryl halides or alkyl sulphonates with alkylzinc chlorides or bromides [83,84]. 

This synthetic sequence for an olefin synthesis has been further developed by Kocienski who has shown that eliminative desulphonylations carried out on / -acyloxysulphones are remarkably stereoselective for the synthesis of trans-disubstituted-olefins. The method has wide applicability in that a-lithio phenyl sulphones are readily generated, and are readily coupled to aldehydes or ketones, to give j8-hydroxysulphones. The hydroxyl function of these is then esterified and the synthesis is completed by the reductive elimination with sodium amalgam. Kocienski has prepared two reviews that summarize his syntheses of a range of natural products - one of which is diumycinoP obtained... 

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