3-Sulfolenes preparation

Sulfolane (tetramethylenesulfone) [126-33-0] M 120.2, m 28.5 , b 153-154 /18mm, 285 /760mm, d 1.263, n 1.4820. Prepared commercially by Diels-Alder reaction of 1,3-butadiene and sulfur dioxide, followed by Raney nickel hydrogenation. The principle impurities are water, 3-sulfolene, 2-sulfolene and 2-isopropyl sulfolanyl ether. It is dried by passage through a column of molecular sieves. Distd... 

Ethylene disulfonyl-1,3-butadiene (43) is an example of an outer-ring diene with a non-aromatic six-membered heterocyclic ring containing sulfur. It is prepared by thermolysis of sulfolenes in the presence of a basic catalyst. It is very reactive [43] and even though it is electron-deficient, it readily reacted with both electron-rich and electron-poor dienophiles (Equation 2.15). 

The thiophene ring system can be utilized as a synthetic scaffold for the preparation of nonthiophene materials as the sulfur moiety can be removed by reduction (desulfurization) or extrusion (loss of SO2). The extrusion of sulfur dioxide from 3-sulfolenes (2,5-dihydrothiophene 1,1-dioxides) give dienes (butadienes or o-quinodimethanes) that can be utilized to prepare six-membered rings by cycloaddition chemistry. For example, thermolysis of 3-sulfolene 120 provided tricyclic pyrazole 122 via an intramolecular cycloaddition of the o-quinodimethane 121 that results by extrusion of sulfur dioxide <00JOC5760>. Syntheses of 3-sulfolenes 123 and 124 <00S507> have recently been reported. 

A considerable number of processes have been described for the preparation of the two simplest dendralenes however, most of them are rather means of formation than efficient preparative methods. As Scheme 2 shows for [3]dendralene 7, thermal methods of preparation predominate (1,2-eliminations and periyclic processes) however, these methods do not always start from readily accessible precursors [5], The most effective procedure - which can hence be employed in subsequent reactivity studies (see below) - consists in the cheletropic decomposition of 11 carried out by Cadogan and Gosney et al. [6] although the preparation of the sulfolene derivative also requires several steps. 

Sulfolenes are versatile 1,3-diene synthons (transformed by refluxing pyridine) which are useful as key intermediates in many natural product syntheses637,638 or as natural products in their own right639. Alkylation of anions of 3-sulfolene has allowed for the introduction of a wide range of substituents in the 2- and 5-positions640. Alkylation of sulfolenes with a,[Pg.738]

Few examples of functionalization on the benzene ring of benzisothiazole have been reported (see Section 4.05.7.2). Studies on the reactivity of unsaturated chains in cycloaddition reactions have been reported (see Section 4.05.7.3). The high reactivity of 4-vinylisothiazolin-3-one A-oxides in Diels-Alder cycloadditions, both as diene and dienophile, is illustrated by their tendency to dimerize. 5-Vinylisothiazole A,A-dioxides react at the vinyl function with different 1,3-dipoles. Isothiazolo-3-sulfolenes 265 give an o-quinodimethane which can be trapped with a dienophile. Different isothiazole derivatives substituted with a carbon chain functionalized with heteroatoms have been prepared as ligands for the formation of complexes. 3-Oxocamphorsulfonimide reacts with the anion of alkynes and several studies on the reactivity of the products with electrophiles are reported. 

Five membered ring sulfones (thiolene-1, 1-dioxides, sulfolenes or dihydrothiophene-1, 1-dioxides) can be obtained by peracid oxidation of tetrahydrothiophene. The extrusion of sulfure dioxide from dihydrothiophene-1,1 dioxides or sulfolenes like (178) has been much studied as it provides a synthetic route to dienes, e.g. butadiene (152) (Scheme 70). The reverse reaction provides a method of synthesis of sulfolene (178) from butadiene (152) and sulfur dioxide. Thiolene dioxides or sulfolenes can be generally prepared by addition of sulfur dioxide to conjugated dienes for example, 1,4-dimethylbutadiene (179) in the presence of sulfure dioxide, triethylamine and formic acid affords 2,5-dimethylsulfolene (180) (Scheme 71). 

Source of butadiene (2, 390, ref. 2). The preparation of diethyl rrcms-AMetra-hydrophthalate by the reaction of 3-sulfolene with diethyl fumarate has been published.1... 

In the dithiin series, 2,3-(ethylenedisulfonyl)-1,3-butadiene (156) may be prepared readily by thermolysis of its stable 3-sulfolene precursor (155) in the presence of pyridine. The disulfone (156) is a very reactive diene and, although electron-deficient, readily reacts with both electron-rich and electron-poor dienophiles to afford the cycloadducts (157) <92CB499>. 

For multistep syntheses that include a Diels-Alder reaction, corresponding 1,3-dienes are necessary. They can be prepared by the method described. In many cases, the 1,3-diene is not isolated, but the Diels-Alder reaction is carried out with 3-sulfolene and dienophile in boiling xylene. 

Chloro-4-fluorothiophene-1,1-dioxide 234, a new synthetically useful fluoro-diene was prepared from commercially available 3-sulfolene. This compound reacts with different types of dienophiles acetylenes, alkenes, furans quinine, and antracene giving the 3-fluoro-4-chloro-substituted arenes or cyclic chlorofluorodienes. " ... 

Chou and co-workers ° investigated 4,6-dihydro-2-substimted-thieno[3,4-d] oxazole 5,5-dioxides 758 both experimentally and theoretically. The authors were initially disappointed to find that 4-bromo-3-sulfolanone 757 did not react with formamide or acetamide to yield 754 or 758 (R = CH3) (Scheme 1.208). This synthetic approach had been successful for preparing 2-substituted thiazolo-3-sulfolenes 759. ... 

The extrusion of SO2 from heteroaromatic-fused 3-sulfolenes has been successfully used as a general strategy for the synthesis of a variety of o-quinodimethane derivatives [137]. This synthetic approach is quite attractive due to the relative ease with which the sulfolenes are prepared, as well as the stability of these versatile precursors. Under thermal conditions (150°C), indolo-3-sulfolenes 417a-b readily produce the quinodimethane intermediates 418a-b, which then undergo Diels-Alder cycloaddition reactions with A-phenylmaleimide (220) to produce the [4-1-21-cycloadducts 419a-b in good yields (Scheme 95) [138]. 

Ko C-W, Chou T-s (1998) Preparation and reactions of benzofurano-, indolo-, and benzothieno-3-sulfolenes. J Org Chem 63 4645 653... 

PREPARATION OF SUBSTITUTED 3-SULFOLENES AND THEIR USE AS PRECURSORS FOR DIELS-ALDER DIENES... 

This review will concentrate on ways in which functionality can be assembled around the sulfolene nucleus, to provide useful masked diene precursors for Diels-Alder reactions. We therefore make only brief mention of ways in which SO2 has been added to dienes. Such reactions are used mainly to prepare simple sulfolenes, or to mask existing dienes [113]. 

Dihydrothiophenes are very easily oxidized to sulfolenes by a variety of oxidizing agents. Accordingly, a common approach to sulfolenes is to construct a substituted dihydrothiophene first, then oxidize it. The synthesis of dihydrothiophenes has been reviewed [11]. As the approaches to sulfolenes are very wide ranging, we illustrate general strategies which are frequently employed to provide common basic types of sulfolene unit. We also exemplify the preparation of commonly used sulfolene ring systems. 

Michael additions of a-mercaptoacetates to a,P-unsaturated systems, followed by Diekmann or aldol-type cyclization, provide access to hydrothiophenes, such as (1), which are useful precursors for a variety of sulfolenes. Scheme 6.2 [27,115]. The ester group of ketoester (la) can be manipulated to provide a range of substituents. The ketone group can then be reduced to an alcohol, and after this has been eliminated, the resultant dihydropyran can be oxidized to a 3-sulfolene. 3-Cyano-3-sulfolene (4) is of general utility and can be efficiently prepared by this strategy from intermediate cyanoketone (lb) [9,10]. Other sulfolenes can be prepared by analogous methods. 

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