Cycloaddition reactions thioaldehydes

Diels-Alder reaction (see also [4+2] Cycloaddition) of thioaldehydes 31 of vinuylsulfonium salts 168... 

Diels-Alder reactions of thioketones are well documented in the literature471, however, since Schaumann published his review1, advances have been recorded in the cycloadditions with thioaldehydes due, mainly, to the development of new synthetic methods (Section III) and techniques (FVT), and therefore the reactions with aldehydes will be highlighted473. 

Cycloaddition reactions of thioaldehydes and sulfines are most probably encountered in plants, as elegantly and soundly shown by the group of Eric Block during their investigation of sulfur products occurring in the Allium species (for a review see [91]). They were able [92, 93] to isolate bicyclic dithioacetal oxides, called zwiebelanes, and also to synthesise them from a thioxosulfine, already described in this review (Sect. 2.6, Scheme 18). An extremely rich stereochemical and analytical study has resulted. 

The behavior of monosubstituted sulfmes is in contrast to that of unsymmetrically disubstituted analogues in the cycloaddition reaction, which occurred with retention of the stereochemistry.44 The deviant result was attributed to a Z to E isomerization of sulfmes during the cycloaddition and to a surprisingly high reactivity of the -thioaldehyde 5-oxides compared with the Z-isomers.43... 

Sulfines, which are thiocaibonyl 5-oxides, have been used many times as heterodienophiles. As with thioaldehydes, the development of this field has been limited more by the availability of these often unstable species rather than by problems with the Diels-Alder chemistry. It should be noted that sulfines can exist as configurationally stable ( )- or (Z)-isomers and this stereochemistry can play a role in the outcome of the cycloaddition reactions. 

Mechanistic studies in this area are essentially nonexistent. Recently, the regiochemistry of some [4 + 2] cycloadditions of thioaldehydes has been rationalized based on FMO theory.2 It is difficult to generalize the resulting stereochemistry of this type of Diels-Alder reaction since systematic studies are lacking and since many structurally diverse kinds of thiocarbonyl dienophiles have been used as 277 components. 

In situ generated thioaldehydes (368) undergo a 1,3-dipolar cycloaddition reaction with pyr-azolidinium ylide (367) to produce bicyclic esters (369) (Equation (55)) <88TL5061>. 

The cycloaddition reaction between l,2-dithiole-3-thiones that are not substituted in the 5-position and acetylene derivatives has been found to give the thioaldehydes (4) as brown solids or pastes. " The products could not be obtained analytically pure, but were characterized spectroscopically. The yields of the thioaldehydes were rather dependent on the... 

The cycloaddition reactions of the reactive a-oxo sulfines 45 with dienes are well investigated and [4+2] cycloadducts 46 are obtained. Benzoyl substituted thioaldehyde -oxides already react with 2,3-dimethyl-l,3-butadiene at —78 °C. 

Thioaldehyde was also used as dienophile affording corresponding dihydro-2H-thiopyrans P. Herczegh, M. Zsely, R. Bognar, S. Laszlo, Cycloaddition reactions leading to carbohydrate derivatives part I. Hetero Diels-Alder reaction of monosaccharide O-thioformates, Tetrahedron Lett. 27 (1986) 1509-1512. 

Synthesis.— The condensation of acetonitrile with ethyl thionoformate by means of butyl-lithium has been reported to yield thioformylacetonitrile (1) after subsequent treatment of the intermediate lithium salt (2) with hydrochloric acid. The thioaldehyde could not be isolated, but it was reasonably stable in solution in the tautomeric enethiol form (3), and was characterized as its stable S-methyl derivative (4). Several new, stable thioaldehydes, (5) and (6), have been synthesized by solvolysis of the VUsmeier salts (7) and (8) with aqueous sodium hydrogen sulphide. Some deuteriated analogues of (6) were similarly prepared from the corresponding salts (9). The thioaldehydes (10) were isolated as amorphous solids from the cycloaddition reaction of l,2-dithiole-3-thione with propiolic acid or its... 

Selenoaldehydes 104, like thioaldehydes, have also been generated in situ from acetals and then directly trapped with dienes, thus offering a useful one-pot procedure for preparing cyclic seleno-compounds [103,104], The construction of a carbon-selenium double bond was achieved by reacting acetal derivatives with dimethylaluminum selenide (Equation 2.30). Cycloadditions of seleno aldehydes occur even at 0 °C. In these reactions, however, the carbon-selenium bond formed by the nucleophilic attack of the electronegative selenium atom in 105 to the aluminum-coordinated acetal carbon, may require a high reaction temperature [103], The cycloaddition with cyclopentadiene preferentially gave the kinetically favorable endo isomer. 

Thioaldehyde S-oxides behave as dienophiles with 1,3-dienes [241]. Cycloaddition involves the carbon-sulfur double bond of the heterocumulene to furnish dihydro-2H-thiapyran S-oxides (Table 6, entry 1). The cis trans product ratio was found to depend upon the initial diene/sulfine ratio. A large excess of diene selectively provided the cis cycloadducts, as a result of a stereospecific reaction of the (Z) sulfine. With a produced proportion of diene, mixtures of cis trans isomers are obtained, with a preference for the cis compound. The Italian authors have demonstrated that the slower reaction allows a (Z) to (E) isomerisation of the sulfines prior to addition. 

The stereoselectivity of hetero Diels-Alder reactions of thioaldehydes and cyclopentadiene has thoroughly been investigated by Vedejs and his coworkers [404]. In general, these cycloadditions proceed only with moderate endo selec-tivities for high endo-selectivities, very bulky thioaldehydes are necessary. This... 

Finally, a thia Diels-Alder reaction representing a less common cycloaddition type in natural product synthesis shall be discussed. Thus, Vedejs et al. have included such a cycloaddition into an elegant strategy aimed at the synthesis of macrocyclic [ll]-cytochalasans such as zygosporin E 7-76 [536-538]. Thus, release of the thioaldehyde 7-73 from its phenacyl sulfide precursor in the presence of the silyloxydiene 7-74 yielded 7-75 as 2 1 mixture with its C20 epimer. Fortunately, equilibration of this mixture raised the ratio up to 10 1. Several subsequent steps yielded the tetracyclic intermediate 7-77 cleavage of its thioether moiety then liberated the 11-membered macrocycle present e.g. in zygosporin E 7-76 (Fig. 7-16). 

Diazo transfer reactions forming triazolo-pyrimidines, 55, 156 to tetramic acids, 57, 176 Diazoacetic ester, cycloaddn to thioaldehyde, 55, 6 Diazoacetic ester, a-lithio-, addition to thio- and seleno-pyrylium ions, 60, 160 Diazoalkanes. trifluoromethyl-, cycloadditions, 60, 30 2-Diazoazoles, cycloadditions, 59, 68-76, 79, 85, 94, 97, 136... 

Several groups have examined the exotendo stereoselectivity of thioaldehyde cycloadditions. 5 f Scheme 23 outlines some of the methods used for in situ generation of thioaldehydes and selected stereochemical results with cyclopentadiene. As can be seen, these reactions generally give a predominance of endo products kinetically. Vedejs has rationalized this outcome as arising from steric factors. 

Another stereochemical aspect of these Diels-Alder reactions which has been studied by the Vedejs group is the facial selectivity in cycloadditions of chiral thioaldehydes. For instance, thioaldehyde (184), generated by the photochemical method, added to cyclopentadiene to give exo adducts (185) and (186) Jong with endo isomers (187) and (188) (Scheme 24). As was the case for achiral thioaldehydes, the endo adducts predominated (-9 1). The facial selectivity obtained can be rationalized via a Felkin-Anh or Comforth model for asymmetric induction. 

Only a few intramolecular thioaldehyde [4 + 2] cycloadditions have been executed to date. Vedejs et al. have looked at systems such as that shown in equation (88).Their photochemical method is useful in effecting intramolecular reactions but stereoselectivity in the process was only moderate. Baldwin and Lopez have described the single intramolecular cycloaddition shown in equation (89) which involves a new thermal method for generating thioaldehydes from alkyl thiosulfinates. ... 

Thiocarbonyl compounds have been employed in Diels-Alder reactions to prepare thiopyranyl systems,1 and generally the carbon-sulfur double bond serves as the 2it dienophile component of the [4 + 2] cycloaddition (Chapter 5). However, there are several reported examples of a,j8-unsaturated thioaldehydes, thioketones, and dithioesters participating as the diene partners of Diels-Alder reactions in which the thiocarbonyl group comprises a component of the 4tt diene system. 

---