Thiocarbonyl compounds, Diels-Alder

Although almost all kinds of thiocarbonyl compounds are good dienophiles, synthetic applications derived from the Diels-Alder adducts of thioketones, thionesters and dithioesters remain rather rare and focused on specific targets, as in the preparation of a fragment of the antibiotic erythronolide from the cycloadduct formed regioselectively from 2-methyl-l,3-pentadiene and an a-oxodithioester, a particularly efficient dienophile [524]. 

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). 

Thiocarbonyl compounds are excellent reaction partners in all types of cycloadditions, especially 1,3-dipolar (Section IV.E.3) and Diels-Alder reactions (Section IV.E.4). They have been frequently used in the trapping of unstable thiocarbonyl derivatives1. 

The last years have seen a great development of the hetero Diels-Alder reactions of thiocarbonyl compounds, due to their rather high reactivity, as reported by many groups, including those of Kirby, Bonini, Capozzi, DeglTnnocenti, Vallde, Okazaki, Koizumi, Saito and Huisgen. A simple orbital frontier treatment allows comparison of the reactivity of C=S vs C=0 [119]. 

Table 2. Hetero Diels-Alder reactions of thiocarbonyl compounds as dienophiles...

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). 

The first volume begins with a comprehensive review by Prof. Jose Luis Garcia Ruano and Dr. Belen Cid de la Plata of asymmetric cycloaddition mediated by sulfoxides, including dipolar and other processes in addition to Diels-Alder chemistry. It is followed by a discussion of the synthetic uses of thiocarbonyl compounds by Prof. Patrick Metzner. 

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]. 

Thiocarbonyl compounds of all kinds are excellent heterodienophiles. There has not been much systematic study of this class of reaction but it seems that such cycloadditions are generally regio-selective. One difference between carbonyl and thiocarbonyl Diels-Alder reactions is that the dihydro-thiopyran adducts from the latter dienophiles often undergo cycloreversion. The slow development of this field is peifaaps mainly due more to lack of methods for generating certain thiocarbonyl compounds than with difficulties in effecting cycloadditions. 

A number of thiocaibonyl compounds in the carboxylic acid oxidation state have been utilized in Diels-Alder reactions, but no systematic study in this area has been done. Some of the various structural types of thiocarbonyls which are reactive dienophiles are indicated in equations (90), (91) and (92).16s Reactions of this class show good to moderate regioselectivity, but relatively little is loiown with regard to stereoselectivity. Additional examples can be found in earlier reviews. ... 

Hexafluoropropane-2-thionc (9) is an exceedingly active dienophile in Diels Alder reactions, forming adducts with butadiene, furan, anthracene, and even styrene, all under very mild conditions. Other thiocarbonyl compounds are also very active dienophiles (see Table 9).64... 

The Diels- Alder reaction has been used to prepare unsaturated ring systems in this series. A common example is the dimerization of a) -unsaturated thiocarbonyl compounds (Equation (49)) <86JA7045>. These thiocarbonyl compounds are commonly unstable at room temperature, but can be generated in situ in a number of ways . 

The excellent dienophilic character shown by thiocarbonyl compounds in inverse-electron demand Diels-Alder cycloadditions has been utilized in the synthesis of 1,3,4-thiadiazines (Scheme 41)... 

The Diels-Alder reaction of a-nitrosostyrenes (147) with various thiocarbonyl compounds (148) has provided a high-yielding synthesis of the previously unknown 1,5,2-oxathiazine ring system (30a-c) (Equation (31)) <85TL2131, 87JCS(P1)2647>. a subsequent synthesis of this ring system employed essentially the same method except that the diene was the nitrosoethylene derivative (149) (Equation... 

One report has described the use of thiocarbonyl compounds as the he-terodienophile 2tt component of a Diels-Alder reaction with vinylnitroso compounds.80... 

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