Thioketones Diels-Alder reactions

A sequence of two thermal intramolecular cycloadditions has been used to develop a short synthetic approach to tetrahydrothiopyrans [122], The multiple process includes an m m-hetero- and an intramolecular-carbon Diels-Alder reaction. An intramolecular /zctcro-Diels-Alder reaction of divinyl-thioketone 134 afforded a 9 1 mixture of cycloadducts 135 and 136 which then underwent a second intramolecular cycloaddition which syn o H-2)-exo-diastereoselectively led to hexacyclic tetrahydrothiopyrans 137 and 138, respectively (Scheme 2.51). 

Azadienes undergo Diels-Alder reactions to form pyridine, dihydro- and tetrahydropyridine derivatives. N-Vinyl lactim ethers undergo Diels-Alder reactions with a limited set of dienophiles. " Thioketones react with dienes to give Diels-Alder cycloadducts. The carbonyl group of lactams have also been shown to be a dienophile. Certain heterocyclic aromatic rings (among them furans) can also behave as dienes in the Diels-Alder reaction. Some hetero dienes that give the reaction are -C=C-C=0, 0=C-C=0, and N=C-C=N. ... 

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]. 

The cycloadduct of an a,a -dioxo-thioketone with antracene,84 treated at low temperature with the Nysted reagent and TiCl4, transforms a ketone group to the corresponding methylenic group. This product is thermically decomposed via retro Diels-Alder reaction into the unstable a, p-unsaturated-a -oxo derivative (Scheme 10). 

The heterodiene and dienophile behaviours of thioketones have been investigated by Saito in diene-trasmissive112 and transannular113 Diels Alder reactions. 

This chapter deals with [2 + 2]cycloadditions of various chromophors to an olefinic double bond with formation of a four-membered ring, with reactions proceeding as well in an intermolecular as in an intramolecular pattern. Due to the variety of the starting materials available (ketones, enones, olefins, imines, thioketones, etc.. . .), due to the diversity of products obtained, and last but not least, due to the fact that cyclobutanes and oxetanes are not accessible by such a simple one-step transformation in a non-photo-chemical reaction, the [2+2]photocycloaddition has become equivalent to the (thermal) Diels-Alder reaction in importance as for ring construction in organic synthesis. 

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. 

In search for control of absolute stereochemistry, the reaction of thio-chalcones was investigated with unsaturated amides bearing an Evans chiral oxazolidinone [223] and dimenthyl fumarate [224, 225]. For the first time with thiocarbonyl compounds, the efficiency of Lewis acid addition was demonstrated, and reactions could be conducted at room temperature. With EtAlCl2 (Table 4, entry 2) or A1C13 (entry 3), levels of induction up to 92% were attained for the endo isomer. Yb(OTf)3 in DMSO also caused the acceleration of the reaction with chiral acrylamides with p-facial selectivity [226]. This group has also reported [227] an intramolecular hetero Diels-Alder reaction with divinyl thioketones and the double bond of an allyloxy group (Table 4, entry 4). 

In a study of the diene-transmissive Diels-Alder reactions <90BCJ284>, cycloaddition of a substituted 1,4-dihydrothiadiazine and maleic anhydride or A-(p-methoxyphenyl)maleimide gave substituted bicyclo[4.4.0]dec-10-enes (107) in good yield (Equation (59)) <90BCJ284>. The starting thiadiazine is itself a Diels-Alder adduct of an a,(l a, / -unsaturated thioketone and dead. 

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]. 

Such syntheses take advantage of transannular intramolecular hetero Diels-Alder reactions [426], another impressive example is the diene transmissive hetero Diels-Alder reaction of the thioketone 5-14. The diene 5-15 formed by this cycloaddition underwent a second Diels-Alder reaction with N-phenyl-maleimide to yield the fused polycycle 5-16 as single diastereomer (Fig. 5-5) [427]. 

The use of Lewis acids in order to catalyze hetero Diels-Alder reactions of thia-1,3-butadienes is not widespread, but recent investigations stemming from Saito et al. reveal a remarkable acceleration of these transformations in the presence of A1C13 or EtAlCl2 [428]. In a first study concerning asymmetric hetero Diels-Alder reactions of thia-1,3-butadienes, Saito et al. found Lewis acids to have a beneficial effect on the induced diastereoselectivities. Thus, the thioketone 5-17, generated in situ by thermal cycloreversion from its dimer, underwent a completely endo-selective cycloaddition upon treatment with (-)-dimenthyl... 

Hetero-Diels-Alder reactions performed with trifluoromethyl-substituled heterodienes or with trifluoromcthyl-substituted heterodienophiles have resulted in the synthesis of a large number of fluoro-heterocyclic compounds. Ketones, thioketones, imincs, nitriles, and their parent a,/3-unsaturated systems have been studied in cycloaddition reactions. Cycloadditions are regioselec-tive. An interesting aspect is the competition with ene-type reactions, aldol reactions and, depending on the partners, with [2 + 2]-cycloaddition reactions. 

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. 

Non-enolisable thioketones behave as dienophiles in Diels-Alder reactions and are considerably more reactive than the analogous ketones in these reactions. 

With 1,3-dienes like 2,3-dimethylbutadiene (48), sulfines (45) undergo the Diels-Alder reaction to form the [4 + 2] cycloadducts (49) (Scheme 25). In this reaction, sulfines behave similarly to thioketones and certain sulfenes (see Chapter 7, p. 117), although the latter generally show a greater tendency to form [2 + 2] cycloadducts. 

Though thioketones have been used as dienophiles in hetero Diels-Alder reactions (20), only one example has been reported for the use of a thienium cation as a dienophile (21). 

At present it has not been determined unambiguously whether this reaction constitutes an example of direct ,/3-unsaturated thioketone 4ir participation in a [4 + 2] cycloaddition or 2ir thiocarbonyl Diels-Alder reaction with the dienes followed by an undetected [3,3]-sigmatropic rearrangement.7d... 

The stable, monomeric 0-enaminodithioesters, like their thioketone counterparts, have been shown to participate in regiospecific, intermolec-ular Diels-Alder reactions with a range of representative electron-deficient and reactive dienophiles (Scheme 8-1V).19-20 Cinnamic acid thioamides exist in equilibrium with their dimers at room temperature, although to date no reports of their cycloaddition with other dienophiles have been detailed [Eq. (9)].21... 

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. 

Interestingly, no a,/3-unsaturated thiocarbonyl dimer and no products derived from the 27t thiocarbonyl participation in Diels-Alder reactions were observed although the potential, reversible generation of such products could not be ruled out. In contrast, the low temperature dimerization of a,j8-unsaturated thioketones including methyl vinyl thioketone, generated by flash vacuum pyrolysis (FVP), provided 1 derived from the clean, regiospecific Diels-Alder dimerization with 4tt and 2tt thiocarbonyl participation [Eq. (2)].4... 

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