Sulfur dioxide 4+2 cycloaddition reactions

Few isothiazoles undergo simple cycloaddition reactions. 4-Nitroisothiazoles add to alkynes (see Section 4.17.7.4). With 5-thiones (84) and dimethyl acetylenedicarboxylate, addition to both sulfur atoms leads to 1,3-dithioles (85) (77SST(4)339, 80H(14)785, 81H(16)156, 81H(16)595). Isothiazol-3-one 1-oxide and the corresponding 1,1-dioxide give normal adducts with cyclopentadiene and anthracene (80MI41700), and saccharin forms simple 1 1 or 1 2 adducts with dimethyl acetylenedicarboxylate (72IJC(B)881). 

As formal a, /i-unsaturated sulfones and sulfoxides, respectively, both thiirene dioxides (19) and thiirene oxides (18) should be capable, in principle, of undergoing cycloaddition reactions with either electron-rich olefins or serving as electrophilic dipolarophiles in 2 + 3 cycloadditions. The ultimate products in such cycloadditions are expected to be a consequence of rearrangements of the initially formed cycloadducts, and/or loss of sulfur dioxide (or sulfur monoxide) following the cycloaddition step, depending on the particular reaction conditions. The relative ease of the cycloaddition should provide some indication concerning the extent of the aromaticity in these systems2. 

Since sulfoxides and sulfones are versatile synthetic intermediates, and since in both the thiolene oxide and dioxides the reverse dethionylation" (—SO), and cheletropic extrusion of sulfur dioxide , respectively, readily take place thermally, these cycloadditions are expected to find a useful place in organic synthesis. It should be kept in mind, however, that the retrograde SO-diene reaction and interconversion of the thiolene oxides compete effectively against SO extrusion on heating, and that diene isomerization accompanies the forward reaction (SO -t- diene). 

The reversible reaction between butadiene and sulfur dioxide, which yields sulfolene, has been known for a long time. Such cycloaddition reactions of sulfur dioxide, and of other sulfur oxides, have been reviewed by Block.49... 

The following types of dipolarophiles have been used successfully to synthesize five-membered heterocycles containing three heteroatoms by [3 + 2]-cycloaddition of thiocarbonyl ylides azo compounds, nitroso compounds, sulfur dioxide, and Al-sulfiny-lamines. As was reported by Huisgen and co-workers (91), azodicarboxylates were noted to be superior dipolarophiles in reactions with thiocarbonyl ylides. Differently substituted l,3,4-thiadiazolidine-3,4-dicarboxylates of type 132 have been prepared using aromatic and aliphatic thioketone (5)-methylides (172). Bicyclic products (133) were also obtained using A-phenyl l,2,4-triazoline-3,5-dione (173,174). 

O-Quinodimethanes. A recent simple synthesis of Al") 5(lu)-estratriene-l 7-one (5)2 is based on the fact that on pyrolysis substances such as 1 lose sulfur dioxide with generation of o-quinodimethanes.1 The anion of 1 is generated most satisfactorily with KH (1.1 equivalent) in DMF. at 0°. It can be converted predominately to monoalkylated products, particularly if an excess of the anion is used. Thus reaction of the anion of 1 with 2 results in the diastereoisomers 3 and 4. After deketalization, the corresponding ketones are heated at 210" for 8 hours. The o-quinodimethane (a) is formed and undergoes intramolecular cycloaddition to form 5. 

Exercise 21-24 a. Sulfur dioxide is an angular molecule that can be represented as having a nonbonding electron pair in an sp2 hybrid orbital and one vacant p orbital on sulfur. Use this formulation to derive a thermally allowed transition state for the reversible 1,4-cycloaddition of S02 to 1,3-butadiene (Section 13-3C). b. The three-membered ring sulfone, shown below, is very unstable and rapidly dissociates to S02 and ethene. This process is used for the synthesis of alkenes by the dissociation of cyclic sulfones (Ramberg-Backlund reaction). Determine whether the transition state for the thermally favorable reaction is conrotatory or disrotatory. 

A number of other photochemical 1,4-cycloadditions leading to the formation of heterocyclic systems have been reported, but in general these are less well investigated. The irradiation of o-quinones in the presence of sulfur dioxide affords, often in good yield, the corresponding 1,3,2-dioxathiole or cyclic sulfate 338 [see, for example, Eq. (91)]. Reaction of phenanthraquinone with triphenylphosphine can be achieved photochemically339 or thermally and the product is thought to have the cyclic structure (317). 

Another anomalous cycloaddition is the insertion of a carbene into an alkene. 6-Electron cheletropic reactions (p. 28) are straightforward allowed pericyclic reactions, which we can now classify with the drawings 3.47 for the suprafacial addition of sulfur dioxide to the diene 2.179 and its reverse. Similarly, we can draw 3.48 for the antarafacial addition of sulfur dioxide to the triene 2.180 and its reverse. The new feature here is that one of the orbitals is a lone pair, which is given the letter co to distinguish it from o- and n-bonds, with suprafacial and antarafacial defined by the drawings 3.45 and 3.46, which apply to all sp3 hybrids and p orbitals, filled or unfilled. 

Clearly, there is a fine balance between [2 + 2]- and [4 + 2]-cycloaddition in the reaction of TCNE with vinylindoles. The cycloaddition of 1-methyl-3-vinyl compound and TCNE in benzene gives mainly the [4 + 2]-product, although a small amount of the [2 + 2]-adduct also appeared to be formed. In liquid sulfur dioxide this [4 + 2]-adduct completely isomerized to the [2+ 2]-product. It is probable that in the reaction between diene 205 and TCNE the transition state for [4 + 2]-cycloaddition is destabilized by the steric requirements of the bulky N-benzyl group. 

Scheme 3. The highly-ordered transition state associated with the Diels-Alder reaction has made it a natural target for work in the field of catalytic antibodies [15]. Indeed, Hilvert [15a] has reported recently the first successfully antibody-catalyzed Diels-Alder reaction. Monoclonal antibodies elicited to the boxed hapten 14 provided both acceleration of and multiple turnover of the cycloaddition between tetrachlorothiopene dioxide and IV-ethyl maleimide. The initial adduct decomposes by the chelotropic-extrusion of sulfur dioxide affording the dihydrophthalimide derivative 13...

During the study of the reaction of ketene 65 with imines 66 in sulfur dioxide, substituted thiazolidin-4-one 1,1-dioxides (67) are formed [Eq. (20)], rather than the expected azetidinones.80 This cycloaddition was initially suggested to proceed through a 1,4-dipolar species 68s 8 whereas later, a (3 + 2)-cycloaddition, via a 1,3-dipolar intermediate 69, was demonstrated to support the results better.85 This ketene-sulfur dioxide adduct 69 reacts... 

Cheletropic reactions are a special group of cycloadditions in which the two o bonds are made or broken to the same atom. Thus sulfur dioxide adds to butadiene to give an adduct, for which the sulfur has provided a lone pair to one of the o bonds and has received electrons in the formation of the other. It is an oxidative addition to the sulfur dioxide, changing it from SIV to SVI. The reaction is readily reversible on heating. 

An anomalous cycloaddition is the insertion of a carbene into an alkene. Some cheletropic reactions are straightforwardly allowed pericyclic reactions, which we can illustrate with the drawing 6.127 for the suprafacial addition of sulfur dioxide to a diene, and with the drawing 6.128 for the 8-electron antarafacial addition of sulfur dioxide to a triene. The problem comes with the insertion of a carbene into a double bond, which is well known to be stereospecifically suprafacial on the alkene with singlet electrophilic carbenes [see (Section 4.6.2) page 149]. This is clearly a forbidden pericyclic reaction if it takes place in the sense 6.129. 

Several cases of photochemical reactions, for which the thermal equivalents were forbidden, are shown below. In some cases the reactions simply did not occur thermally, like the [2 +2] and [4 +4] cycloadditions, and the 1,3- and 1,7-suprafacial sigmatropic rearrangements. In others, the photochemical reactions show different stereochemistry, as in the antarafacial cheletropic extrusion of sulfur dioxide, and in the electrocyclic reactions, where the 4-electron processes are now disrotatory and the 6-electron processes conrotatory. In each case,... 

Surveyed in this section are known SOg insertion and desulfination reactions. Kinetic and stereochemical results already discussed in Sections III-V, as well as the cycloaddition processes treated in Section V, have been given a cursory mention for the sake of completeness. The insertion reactions involving bonds other than M—C are omitted. Also excluded are all aspects of the chemistry of metal sulhnate complexes except sulfur dioxide insertion and desulfination. Readers interested in alternative methods of synthesis and in the physical and chemical properties of these and related compounds are referred to a recent review 128). 

The [2 + 2] cycloaddition reaction proceeds via an ionic linear intermediate, which can be intercepted when the reaction is carried out in liquid sulfur dioxide, for example, when diphenylketene is added to a solution of diisopropylcarbodiimide in sulfur dioxide at —78°C. On warming and evaporation of the sulfur dioxide a 90% yield of 1,1-dioxo-... 

Cycloaddition Reactions of Thiocarbonyl S,5-Dioxides and Related Sulfur(VI) Compounds... 

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