Thiocarbonyl ylides cycloaddition

An attempted synthesis of biotin using thiocarbonyl ylide cycloaddition was carried out (131,133,134). The crucial step involves the formation of the tetrahydrothiophene ring by [3 + 2] cycloaddition of a properly substituted thiocarbonyl ylide with a maleic or fumaric acid derivative (Scheme 5.27). As precursors of the thiocarbonyl ylides, compounds 25a, 72, and 73 were used. Further conversion of cycloadducts 74 into biotin (75) required several additional steps including a Curtius rearrangement to replace the carboxylic groups at C(3) and C(4) by amino moieties. 

In a related study, the spiro thiadiazoline 212, formed by reaction of 208 with CHzNz, reacts with methyl pymvate or its trifluoro analogue to give oxathiolane products 213 resulting from thiocarbonyl ylide cycloaddition (Equation 74) <1996HCA1537>. Reaction of fluorobenzoquinone with chloromethanesulfmic acid affords the benzoxathiole A,A-dioxide 214 (Equation 75) <1996AP361>. 

Huisgen s experimental evaluation of the thiocarbonyl ylide cycloadditions allows an understanding of the dichotomy of answers to the question concerted or two-... 

Another interesting example of a photochemi-cally induced domino process is the combination of the photocyclization of aryl vinyl sulfides with an intramolecular addition as described by Dittami et al. [901 as intermediate a thiocarbonyl ylide can be assumed. The domino-Norrish I-Knoevenagel-allyl-silane cyclization developed by us allows the efficient stereoselective formation of 1,2-trans-subsituted five- and six-membered carbocycles.1911 A photochemical cycloaddition of enamino-aldehydes and enamino-ketones with the intermediate formation of an iminium salt followed by addition to allylsilanes gives access to novel bicyclic heterocy-des. New examples of photochemically induced... 

When thiocarbonyl derivatives are treated with an excess of electrophilic carbene complex, alkenes are usually obtained [1333-1336], The reaction is believed to proceed by the mechanism sketched in Figure 4.18, closely related to the thiocarbonyl olefination reaction developed by Eschenmoser [1337], Few examples have been reported in which stable thiiranes could be isolated [1338], The intermediate thiocarbonyl ylides can also undergo reactions similar to those of carhonyl ylides, e.g. 1,3-dipolar cycloadditions or 1,3-oxathiole formation [1338], Illustrative examples of these reactions are given in Table 4.22. 

When planning reactions of thiocarbonyl compounds with electrophilic carbene complexes it should be taken into aceount that thiocarbonyl compounds can undergo uncatalyzed 1,3-dipolar cycloaddition with acceptor-substituted diazomethanes to yield 1,3,4-thiadiazoles. These can either be stable or eliminate nitrogen to yield thiiranes or other products similar to those resulting from thiocarbonyl ylides [1338]. 

Some years later, the first stable thiocarbonyl ylides 9 and 10 were prepared by the reaction of thiourea with cyano-substituted oxiranes (19,20) or by addition of Rh-di(tosyl)carbenoid to benzo-l,2-dithiole-3-thione (21), respectively. Enhanced stability and the low reactivity of 9 and 10, which enables their isolation in crystalline form, results from the push-pull substitution at the two termini [cf. also (22)]. Another class of stable thiocarbonyl ylides that are also able to afford [3 + 2]-cycloaddition products are the mesoionic 1,3-dithiole-4-ones of type 11 (23,24). 

Like other 1,3-dipolar species, thiocarbonyl ylides are able to enter intramolecular as well as intermolecular cycloaddition reactions. In this chapter, selected examples of both types will be illustrated. 

As is the case with other 1,3-dipoles, thiocarbonyl ylides undergo [3 + 2]-cycloaddition reactions producing five-membered sulfur heterocycles [cf. (8)]. These ylides belong to the class of electron-rich 1,3-dipoles (89) and, according... 

Numerous examples involving the preparation of tetrahydrothiophenes via [3 + 2] cycloaddition of thiocarbonyl ylides with electron-poor alkenes have been reported. Thiobenzophenone (5)-methylide (16), generated from 2,5-dihydro-1,3,4-thiadiazole (15) and analogous compounds, react with maleic anhydride, N-substituted maleic imide, maleates, fumarates, and fumaronitrile at —45°C (28,91,93,98,128,129). Similar reactions with adamantanethione (5)-methylide (52) and 2,2,4,4-tetramethyl-3-thioxocyclobutanone (5)-methylide (69) occur at ca. +45°C and, generally, the products of type 70 were obtained in high yield (36,94,97,130) (Scheme 5.25). Reaction with ( )- and (Z)-configured dipolaro-philes stereospecifically afford trans and cis configured adducts. 

An attractive approach toward the preparation of polycyclic systems containing a thiophene ring involves the intramolecular [3 - - 2] cycloaddition of thiocarbonyl ylides. A number of representative examples were reported using mesoionic compounds. Gotthardt et al. (151) used l,3-dithiolium-4-olates such as 89 bearing an olefinic side chain. Upon heating to 120 °C in xylene, the polycyclic tetrahy-drothiophene 90 was formed (Scheme 5.33). 

It is also worthy to note that the intramolecular [3 + 2] cycloaddition of thiocarbonyl ylides occurs easily with nonactivated C=C bonds, whereas the corresponding intermolecular process does not occur. 

An intramolecular cycloaddition reaction was also used in the synthesis of the annelated tetrahydrothiophene (97), starting from l,3-oxathiolan-5-one (96) (131) (Scheme 5.36). Thiocarbonyl ylide formation occurred by thermal extrusion of CO2 at 250 °C, yielding 97 in 62% yield. 

Intramolecular [3- -2]-cycloadditions of thiocarbonyl ylides with nonactivated acetylenes have also been described. Most representative examples involved the use of mesoionic substrates. The initially formed polycyclic adducts of type 110 undergo spontaneous elimination of phenyl isocyanate (24,62,151). A typical example leading to compound 111 is shown in Scheme 5.40. 

For preparative purposes, the reaction of thiocarbonyl ylides with carbonyl compounds can be considered as an alternative method for the synthesis of 1,3-oxathiolanes. Aromatic aldehydes, chloral, glyoxalates, mesoxalates, pyruvates as well as their 3,3,3-trifluoro analogues are good intercepting reagents for thioketone (5)-methylides (36,111,130,163). All of these [3 + 2] cycloadditions occur in a regioselective manner to produce products of type 123 and 124. 

Other examples of functionalized thiocarbonyl ylides that have been generated by the desilylation method are those bearing an imino group (49) (see Scheme 5.7). These ylides readily undergo [3 + 2] cycloaddition with aromatic aldehydes to afford l,3-thioxolane-2-imines of type 24 (X = RiN). The reaction with ketones is sluggish, however, and the cycloadducts are obtained in very low yield. 

Only a few examples of the [3 + 2] cycloaddition of thiocarbonyl ylides with C=N compounds have been reported so far. By comparison with aldehydes, imines are poor dipolarophiles. For example, Al-benzylidene methylamine and adamanta-nethione (5)-methylide (52) produce 1,3-thiazolidine (129) in only 13% yield (163). An alternative and efficient approach to 1,3-thiazohdines involves the [3 + 2] cycloaddition of azomethine ylides with thiocarbonyl compounds [cf. (169)]. 

Nitrogen-containing heteroaromatic compounds react with (chloromethyl)[(tri-methylsilyl)methyl] sulfide in the presence of CsF to afford fused 1,3-thiazolidines of type 130. These compounds are the result of a formal [3 + 2] cycloaddition of the parent thiocarbonyl ylide la across the C=N bond (170). In these cases, the formation of the five-membered cycloadduct is believed to occur in two steps via an intermediate onium ion. 

Reactions of thiocarbonyl ylides with nitriles are scarce. Simple nitriles do not undergo bimolecular cycloaddition (171). There is, however, a single example of an intramolecular case that was reported by Potts and Dery (24c,62). By analogy to the intramolecular cycloaddition with acetylenic dipolarophiles (Scheme 5.40), the primary product derived from the reaction of a thiocarbonyl ylide with a nitrile group undergoes a subsequent elimination of phenylisocyanate to give the fused 1,3-thiazole (131). 

The following types of dipolarophiles have been used successfully to synthesize five-membered heterocycles containing three heteroatoms by [3 + 2]-cycloaddition of thiocarbonyl ylides azo compounds, nitroso compounds, sulfur dioxide, and Al-sulfiny-lamines. As was reported by Huisgen and co-workers (91), azodicarboxylates were noted to be superior dipolarophiles in reactions with thiocarbonyl ylides. Differently substituted l,3,4-thiadiazolidine-3,4-dicarboxylates of type 132 have been prepared using aromatic and aliphatic thioketone (5)-methylides (172). Bicyclic products (133) were also obtained using A-phenyl l,2,4-triazoline-3,5-dione (173,174). 

A-Sulfinylamines (R—N=S=0) are known to function as reactive dienophiles and dipolarophiles, and some examples of [3 + 2] cycloaddition with thiocarbonyl ylides have been reported (176). For example, the reaction of thiobenzophenone (5)-methylide (16) with both A-phenyl and N-tosylsulfinylamines occurs regiose-lectively to give 1,3,4-dithiazolidine 3-oxides (135). In the case of thiocarbonyl ylide 69, reaction with N-phenyl sulfinylamine selectively afforded the analogous product 136 (R = Ph). However, the corresponding reaction with Al-tosyl sulfinylamine resulted in a mixture of the N,S-adduct (136) (R =Tos) and the 0,S-adduct 137. Formation of a mixture of products is compatible with a stepwise reaction via a zwitterionic intermediate. 

Karlsson and Hogberg (291,292) applied the thiocarbonyl ylide 175 in a diastereoselective 1,3-dipolar cycloaddition with 165. The thiocarbonyl yhde was generated in situ by an elimination reaction. The reaction with 165 gave 176 (R = Bu, BnO, Ph) with selectivities of up to 64—80% de. Furthermore, the cycloaddition of a chiral galactose-derived nitrile imine with 165 has been reported (104). 

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