Thioaldehydes Diels-Alder adducts

Free intermediate thioaldehydes 598 or 602 and the selenoaldehydes 605 and HMDSO 7 are obtained in THF at 0°C on treatment of aliphatic and aromatic aldehydes with bis(trimethylsilyl)thiane 601 or bis(trimethylsilyl)selenide 604 in the presence of traces of butyllithium, while trapping the sensitive intermediate thio- or selenoaldehydes 602 and 605 with cyclopentadiene or cyclohexadiene to furnish mixtures of endo and exo Diels-Alder adducts such as 603 a and 606 a and 603 b and 603 b [148-150], the exo/endo ratio of which can be controlled [150] (Scheme 5.48). Analogous reaction of ketones such as 2-adamantanone or acetylene ketones with MesSiXSiMes 608 (a. X=S (601) b. X=Se (604)) in the presence of... 

The transient thioaldehydes can also be trapped with dienes giving the corresponding Diels-Alder adducts in good yields. These reactions are carried out in toluene under reflux. Milder conditions (reflux in dichloromethane or benzene) have been reported by Sato and Satoh for a similar transformation which involves cyclic polysulfides instead of elemental sulfur238 (equation 18). The aldehydes obtained were trapped in Diels-Alder reactions. 

As usual, thioaldehydes were trapped in situ as Diels-Alder adducts and the intramolecular version of this strategy using a catalytic amount of butyllithium has also been reported304. 

Retro-Diels-Alder reactions giving thiocarbonyl compounds are favored when simultaneously a comparatively stable diene is formed1. This is the case with anthracene and cyclopentadiene Diels-Alder adducts 81 and 82 which, upon heating, afford a wide array of thioaldehydes and thioketones (equation 84). These adducts are stable at room temperature and have become a convenient way of storing very reactive thiocarbonyl compounds. Cyclopentadiene is the cheapest and most reactive diene for use in Diels-Alder reactions. Also, strain in the bridged cycloadducts facilitates retro-Diels-Alder cleavage224. 

Several accounts of transient thioaldehydes generated from high-energy processes and detected spectroscopically or trapped as Diels-Alder adducts have appeared. Dice and Steer obtained thioformaldehyde from retro [2 + 2]-fragmentation by photolysis, and subsequent trapping afforded (11) (74CJC3518). This is the only report, before the work of Vedejs, that describes intermolecular Diels-Alder trapping of thioaldehydes. However the method is not preparatively useful. 

Kirby and co-workers obtained alkyl thioxoacetate, which was trapped by a diene to give a Diels-Alder adduct, e.g. 30. When this adduct was heated at 110°C in the presence of a new diene, a retro Diels-Alder reaction took place. The thioaldehyde thus generated gave a new adduct, 31. Adduct 30 is, therefore, a thioaldehyde transfer reagent [85JCS(P1)1541]. 

Baldwin and Lopez have formed both aromatic and aliphatic thioaldehydes by pyrolysis of thiosulfinates like 7, and they were able to trap these species as Diels-Alder adducts [Eq. (7)].22... 

Selenocarbonyl compounds have been virtually ignored as hetero-dienophiles. Recently, Krafft and Meinke have found a novel method to generate various selenoaldehydes (Scheme 5-XXII).59 These compounds are reactive dienophiles and can be trapped in situ with cyclopentadiene to give Diels-Alder adducts. As can be seen in the scheme, endo adducts predominate in these cycloadditions. Similar results were found in thioaldehyde additions to cyclopentadiene (cf. Scheme 5-IV). 

In 1988, Vedejs and Fields prepared 3-thiazolines from 5-methoxy-2-methyl-oxazole 249 and a series of thioaldehydes, generated in situ from their cyclopenta-diene adducts. Thus heating 249 and thioaldehyde 250 in a sealed tube at 140°C for 48 h afforded a 95% yield of 251 as a 1 1 mixture of diastereomers (Fig. 3.74). The unactivated oxazole, 5-methyl-2-phenyloxazole was unreactive under the same conditions. A Diels-Alder mechanism was proposed for this reaction but no intermediate Diels-Alder adduct was observed. A nitrile ylide pathway was discounted, since these reactions proceed at room temperature if the thioaldehyde is generated photolytically and oxazoles do not form nitrile ylides under those conditions. Thioformaldehyde, thioacetaldehyde, thiobenzaldehyde, and thioace-tone all successfully underwent similar reactions to provide thiazohnes. 

Thermal cycloreversion of the adducts can be accomplished at a convenient rate when heated in toluene under reflux. If a new diene is present in the reaction mixture, the thioaldehyde thus generated in the retro-Diels-Alder reaction may give a new adduct. Therefore, adducts 81 and 82 act as thioaldehyde or thioketone transfer reagents. These adducts dissociate reversibly on heating, thus ensuring that the concentration of the labile species remains very low. For this reason, polymerization is not a serious problem especially in the case of thioaldehydes224. The transient thiocarbonyl compounds can be trapped not only by dienes but also by 1,3-dipolar cycloadditions332 (equation 85). 

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. 

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