Heterocycles from sulfones

Formation of fused heterocycles from acetylenic or allenic sulfones and pyrroles or furans as dienes 01T5263. 

Six-inembered heterocyclic fused sulfones produced by annulation of dihydrothiophenes include the quinoxaline sulfone 40 derived from 3-bromo-4-oxotetrahydrothiophene dioxide and 1,2-diaminobenzene <94TI0721>. The difficulty in extrusion of SO2 from this sulfone has already been discussed. We found similar problems in attempts to generate the quinoline... 

As expected, no problems in extrusion of SO2 were encountered with the quinoline 3,4-fused sulfone 45 obtained as shown in Scheme 31. The coumarin o-quinodimethane was also generated from a sulfone 46 produced by annulation of a dihydrothiophene <96T3117>. Clearly a wide range of heterocyclic fused sulfones can be obtained by annulation of a limited number of readily available dihydrothiophenes, the scope only being limited by the imagination of the synthetic chemist. 

Heterocyclics from carbohydrates Ring closure with sulfonic acid esters Dihydro-1,4-thiazine ring... 

By varying the cleavage cocktail, it is also possible to generate very diverse libraries of heterocyclic species upon cleavage from sulfone linkers (Table 1.11, Entries 22-25). Such work has been extensively developed by Kurih , and Ganesan , ... 

Besides heterocyclic synthesis, the sulfone linker unit has also been applied to the preparation of a variety of other substrates. " " " " The diverse cleavage strategies that can be applied to cleave substrates from sulfone linkers make them a versatile multifunctional linker. This together with the simple purification process, compared to solution-phase synthesis, adds to the potential of sulfone chemistry being applied to solid-phase synthesis. 

Reactions of N-heterocyclics with sulfonic acid azides 3-Diazo-2-sulfonyliminoindolines from indoles... 

The protocol consisting of alkylation followed by oxidation and base-induced elimination of sulfones can also be found in the strategy of other solid phase syntheses. Lam et al. for example constructed o ,)S-unsaturated ketones 475, [291] as well as various heterocyclic compounds 469-474 and 476-478 following this route. Scheme 71 gives an overview of possible structures obtainable from sulfone-linked y6-carbonyl compounds 468a,b. 

Without additional reagents 0-Heterocyclics from cyclic sulfones... 

There is a large variety of chloro or fluoro substituted heterocyclic rings which undergo X displacement by cell-0. Vinyl sulfones are usually generated under alkaline conditions from P-sulfatoethjisulfones,... 

Thiophene, which is more stable to acid, is readily sulfonated by shaking with concentrated sulfuric acid at room temperature. Benzene is not reactive under these conditions and this is the basis for the purification of benzene from thiophene contamination. With all three heterocycles, if the a-positions are blocked, then sulfonation occurs at the /3-position. 

The importance of the solvent, in many cases an excess of the quatemizing reagent, in the formation of heterocyclic salts was recognized early. The function of dielectric constants and other more detailed influences on quatemization are dealt with in Section VI, but a consideration of the subject from a preparative standpoint is presented here. Methanol and ethanol are used frequently as solvents, and acetone,chloroform, acetonitrile, nitrobenzene, and dimethyl-formamide have been used successfully. The last two solvents were among those considered by Coleman and Fuoss in their search for a suitable solvent for kinetic experiments both solvents gave rise to side reactions when used for the reaction of pyridine with i-butyl bromide. Their observation with nitrobenzene is unexpected, and no other workers have reported difficulties. However, tetramethylene sulfone, 2,4-dimethylsulfolane, ethylene and propylene carbonates, and salicylaldehyde were satisfactory, giving relatively rapid reactions and clean products. Ethylene dichloride, used quite frequently for Friedel-Crafts reactions, would be expected to be a useful solvent but has only recently been used for quatemization reactions. ... 

The reaction of 3-methoxy-1,2,4-triazine 1-oxide 20 with the carbanion generated from chloromethyl phenyl sulfone proceeds as the vicarious nucleophilic substitution (VNS) of hydrogen (Scheme 1, path B) via addition of the carbanion at position 5 of the heterocycle. Following base-induced elimination of HCl and protonation, 3-methoxy-5-phenylsulfonyl-1,2,4-triazine 4-oxides 65 result (88LA627). 

Colona and coworkers oxidized a variety of alkyl aryl and heterocyclic sulfides to the sulfoxides using t-butyl hydroperoxide and a catalytic amount of a complex (97) derived from a transition metal and the imines of L-amino acids. Of the metals (M = TiO, M0O2, VO, Cu, Co, Fe), titanium gave the highest e.e. (21%), but molybdenum was the most efficient catalyst. The sulfoxides were accompanied by considerable sulfone. ... 

A stereoselective one-pot synthesis of substituted 1,2-thiazetidine 1,1-dioxides (P-sultams) 55 started from heterocyclic pentafluorophenyl (PFP) sulfonates <06OL5513>. 

The first application of microwave irradiation in conjunction with dry media in the generation of nitrile oxide intermediates was reported by Hamelin [29]. In this example, methyl nitroacetate (170) was mixed with a dipolarophile in the presence of catalytic amounts of toluene-p-sulfonic acid (PTSA) (10% weight). Subsequent microwave irradiation led to the formation of the corresponding heterocyclic adducts (Scheme 9.52). Reactions were performed in an open vessel from which water was continuously removed [103], Likewise, irradiation in a domestic oven of a mixture of ethyl chloro(hydroxyimino)acetate (173) and a dipolarophile over alumina led to the same results in only a few minutes (Scheme 9.52) [103]. 

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