Thioaldehyde Diels-Alder reaction

Heteroatom Diels-Alder reaction of thioketones and thioaldehydes... 

Hetero Diels-Alder reactions of 114 with thioaldehydes and thioketones were also reported to give the syn addition products exclusively [64]. 

On transforming the cyclopentenone 1431 into the trimethylsilyloxy diene 1432 the ensuing Diels-Alder cyclization gives rise to 69% tricychc compound 1433 [10] (Scheme 9.8). For Diels-Alder-reactions of thioaldehydes, selenoaldehydes, or unsaturated nitroso compounds with cyclopentadiene, see the reactions of 602 to 603 and of 605 to 606 in Scheme 5.48 and of 1092 to 1093 in Scheme 7.43. For Diels-Alder-reactions of silyloxyazadienes such as 510 with maleic anhydride to give 511, see Scheme 5.29. 

The regiochemistry of the Diels-Alder reaction of a thioaldehyde depends on the nature of the substituent directly linked to the sp2-carbon atom [175]. 

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

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. 

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. 

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). 

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. 

The groups of Kirby224,340 and of Revesz477 have studied the Diels-Alder reactions of thebaine 134 with ethyl thioxoacetate (equation 140) and other thioaldehydes, thus preparing several opiate antagonists. 

Photolysis of diene (377) affords heterocycle (30) (36% yield) via the thioaldehyde (378) which undergoes an intramolecular hetero-Diels-Alder reaction <88JOC2220>. 

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... 

In a more recent study, Koizumi et al. employed terpene derivatives as chiral auxiliaries attached to thioaldehydes [405], but these heterodienophiles gave only moderate diastereoselectivities in reactions with cyclopentadiene. Mazzan-ti et al. have investigated the hetero Diels-Alder reaction of thioketones bearing an asymmetric silicon atom directly attached to the thiocarbonyl moiety which induced diastereoselectivities up to 50% de [406]. 

Due to the high reactivity and high sensitivity of thioaldehydes, Lewis acid catalysis has not been applied to thia Diels-Alder reactions. However, Heim-garten et al. clearly demonstrated the suitability of Lewis acids to make less reactive thiocarbonyl compounds, e. g. thiazole thiones, react as heterodieno-philes in hetero Diels-Alder reactions [412]. 

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). 

Thiophene 1-oxides have been shown to undergo syn-n-face see 110 selective Diels-Alder reactions. The oxide was shown to preferentially undergo Diels-Alder reaction with a variety of thioaldehydes, thioketones <03TL5159> and dienophiles <03JA8255>, through the w-n-face to give 111-117. 

Baldwin and Lopez used fragmentation of thiosulfinate (17) to furnish transient thioaldehyde (18), which was trapped by intramolecular Diels-Alder reaction to yield bicyclic compounds (19) and (20) in equal amounts (82CC1029 83T1487). 

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]. 

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. 

Thioaldehydes 1 exhibit high endo selectivity in the hetero-Diels-Alder reaction with cyclopen-tadiene (2), but only moderate facial selectivity. In the case of aldehyde Id, bearing a free hydroxy group, inversion of the asymmetric induction is observed63. 

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. 

This transformation undoubtedly occurs via a retro-Diels-Alder reaction of 10 to give a thioaldehyde. 

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. 

Diels-Alder reactions of a variety of other thioaldehydes have been... 

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