Thioaldehyde cycloaddition

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. 

Vedejs - Intramolecular thioaldehyde cycloaddition shows only moderate stereoselectivity [88JOC2220]... 

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. 

Density functional and semiempirical AMI molecular orbital calculations have been used to investigate substituent effects on site selectivity in heterocumulene-hetero-diene4 + 2-cycloadditions between ketene imines and acroleins.The new and novel heterocumulenes a, /3-unsaturated thioaldehyde S -oxides (97) behave as both diene... 

Heteroatomic dipolarophiles are competent in the dipolar cycloaddition of nitronates. The in situ generated thioaldehydes and thioketones react with sUyl nitronate 120 to afford the 1,4,2-oxathiazolidine in good yield (Table 2.36) (113-116). 

The high reactivity of the C=S bond toward diazo dipoles was also helpful in the characterization of thiopivaldehyde, a monomeric thioaldehyde persistent in inert organic solvents for 16 h at 20 °C. This thioaldehyde underwent ready cycloaddition with ethyl diazoacetate (210). Similarly, the diazocumulene 9-(diazomethylene)fluorene could be generated by diazotization of 9-(aminomethy-lene) fluorene and was trapped by the cycloaddition with thiobenzophenone (211). 

Thioaldehyde oxides are reported to be one of the lachrymatory agents in onions and are speculated to dimerize via an initial [4+2] cycloaddition to a five-membered ring that rearranges to a 1,2-dithietane dioxide. The latter has also been isolated from extracts of onions (80JA2490) and is reported to be the only characterized derivative of a 1,2-dithietane (Scheme 121). 

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

Thioaldehydes Thioaldehydes can be generated from a-silyl disulfides (1) by treatment with CsF in THF at 25° or with Bu4NF in THF at 0°. The thioaldehyde is identified by cycloaddition to cyclopentadiene. 

Optically active a-alkoxycarbonylthioaldehydes were prepared from the corresponding a-dichloroacetates by treatment with bis(tributyltin)sulfide and tetrabutylammonium fluoride309 8-arylmenthols were used as chiral auxiliaries and the thioaldehydes underwent asymmetric hetero-Diels-Alder cycloaddition (equation 48). 

Organosilicon compounds have also been reacted with thiocarbonyl ylides to afford a variety of heterocycles468,469 and in Section III.F.5 we pointed out the 1,3-dipolar cycloaddition between in situ generated thioaldehydes and a pyrazolidinium ylide to produce a nuclear analogue of pyrazolidinone antibacterial agents332. Moreover, Vedejs has applied the dipolar cycloaddition between a thione, generated from a Norrish-type II fragmenta-... 

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. 

Partially and perfluorinated thioketones and thioaldehyde were stabilized as anthracene adducts (70). The adducts (70) were prepared in moderate yield from the corresponding carbonyl compounds with P4S10 or Lawesson s reagent in the presence of anthracene under toluene reflux. The generated thiocarbonyl compounds are not accessible in bulk due to their tendency towards polymerization. By thermolysis of the anthracene adducts (70) in the presence of C,N-bis(triisopropylsilyl)nitrilimine (NI), 1,3,4-thiadiazole derivatives (71) were obtained. Also, 1,3-dipolar cycloaddition with bis(trimethylstannyl)diazomethane (BTSD) to give consecutive products (72) from a 1,2-metallotropic migration of primary adducts was discussed. [95LA95]... 

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. 

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 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). 

Thioaldehyde 5-oxides were subjected to 1,4-cycloaddition with a variety of... 

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... 

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... 

Nakayama and co-workers have shown that 3, 4-di-/er/-butylthiophene 1-oxide can serve as trapping agents for unstable thioaldehydes and thioketones. Benzothiophenium salts 118 have been shown to undergo [4+2] cycloaddition with a number of dienes to give compounds of type 119<03JOC731>. 

Alkenyl-4,4-dimethyl-l,3-oxathianes are synthetic equivalents of the highly reactive a,p-unsaturated thioaldehyde system. As such, they react with alkenes in a tandem cationic [4 -l-2] polar cycloaddition - elimination sequence to yield 3,4-dihydro-2//-thiopyrans (Scheme 33) <03T1859>. 

Thioaldehydes have been used as heterodienophiles in cycloadditions (Diels-Alder or 1,3-dipolar) mainly in connection with attempts to show the formation of the transient thioaldehydes by trapping in situ. During... 

Until recently, few reliable methods were available for preparation of thioaldehydes, which are usually very unstable, and little had been done with these species as dienophiles. However, this problem has now been remedied and there has been considerable interest in using thioaldehydes in [4 + 2] cycloadditions. ... 

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 Their photochemical method is useful... 

---