Ylide compounds thiocarbonyl ylides

Organometallic betaines of type I can be considered as the closest structural analogs of carbon betaines of the (+ )P-C-C-X( ) type (IV), which were regarded for a long time as possible intermediates in classical reactions of carbonyl and thiocarbonyl compounds with phosphorus ylides (Wittig and Corey-Chaykovsky reactions and related processes,5,6 Scheme 1). Vedejs and coworkers7,8 proved unambiguously that oxapho-sphetanes (III) are true intermediates in the reactions of nonstabilized phosphorus ylides with carbonyl compounds. The formation of oxabetaines (+)p-c-c-o(-> was detected only in the form of their adducts with lithium salts.9,10... 

Reactions of Phosphorus Ylides with Carbon Disulfide, Stable Thiocarbonyl Compounds, and Thiosilanones... 

The spectral parameters of 15a and other silicon-organophosphorus betaines described henceforth in Section 2.2.2 allowed us to show reliably that the reaction of phosphorus ylides with thiocarbonyl compounds, unlike the classical Wittig reaction, occurs through the intermediate formation of betaines (17)11 (Scheme 9). Erker and coworkers performed a more detailed... 

As mentioned above (see Scheme 1), three main directions of the decomposition of intermediates that formed are possible when phosphorus and arsenic ylides react with compounds bearing C=X bonds 5,6,19,63,64,88 (i) elimination of R3E15=X to form olefins (Wittig type reaction) (ii) retro-Wittig type decomposition and (iii) elimination of R3E15 and formation of three-membered cycles (Corey-Chaykovsky type reaction). According to the data of Erker and coworkers,12,13,51 under kinetic control, the reaction of phosphorus ylides with thiocarbonyl compounds also affords phosphines and thiiranes, whose further transformations lead to olefins and R3PS under thermodynamic control. 

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]. 

The dipolar structure 1 describes the chemical behavior of thiocarbonyl ylides best, although other mesomeric forms have been used for the representation of the electronic structure of these dipoles. The parent compound, thioformaldehyde (5)-methylide (1), was studied by means of spectroscopic and theoretical methods (2-5), which showed that the molecule possesses a bent allyl-type structure (6). According to theoretical calculations, structures lA and IB have the largest contribution (31.5% each) in the representation of the electronic structure, whereas 1C, which reflects the 1,3-dipolar character, has only a 4.2% contribution (5). 

In comparison with other 1,3-dipoles that have been extensively explored in organic synthesis (7), sulfur-centered 1,3-dipoles (1-4) are rather uncommon species. However, within the last two decades, remarkable progress has been made regarding both methods of generation and synthetic applications. In particular, thiocarbonyl ylides (1) were established as key intermediates useful for the preparation of sulfur-containing heterocyclic compounds. General methods for the preparation of thiocarbonyl ylides and their chemical reactivity have been reviewed (8-11). 

Historically, the first reactions involving thiocarbonyl ylides involve the preparation of thiiranes and 1,3-dithiolanes from diazomethane and thiocarbonyl compounds reported early in the last century by Staudinger and co-workers (12,13). Similar reactions have been smdied by Schonberg and co-workers (14—16) during the 1960s, but neither was the reaction mechanism understood nor have thiocarbonyl ylides been recognized as key intermediates. [For some remarks to this subject see (8) and (10) in (17).]... 

As mentioned earlier, the first example of the generation of a thiocarbonyl ylide by deprotonation of a thioxonium salt was reported by Knott (18) and is presented in Scheme 5.1. This method is frequently used since the starting materials 32 are easily available via alkylation of C=S functionalized compounds such as thioke-tones, thioamides, thiourea derivatives, and dithioesters (Scheme 5.11). 

Typically, thioxonium salts (32) are stable compounds, and the deprotonation is performed at low temperatures. This method has been used to synthesize reactive thiocarbonyl yhdes as well as stable and isolable ones (56-60). Arduengo and Burgess (3) prepared differently substituted thiocarbonyl ylides from thiourea derivatives, and in the case of 33, the structure has been established by X-ray crystallography. 

Acidic compounds of type R—XH, which are able to protonate thiocarbonyl ylides, also undergo 1,3-addition leading to products of S,S-, S,0-, or 5,A-acetal type (Scheme 5.20). Thiophenols and thiols add smoothly to thiocarbonyl ylides generated from 2,5-dihydro-l,3,4-thiadiazoles (36,38,86,98,99). Thiocamphor, which exists in solution in equilibrium with its enethiol form, undergoes a similar reaction with adamantanethione (5)-methylide (52) to give dithioacetal 53 (40) (Scheme 5.21). Formation of analogous products was observed with some thiocarbonyl functionalized NH-heterocycles (100). 

As mentioned on pages 317 and 324, the 1,3-dipolar electrocycUzation of thiocarbonyl ylides leads to thiirane derivatives, which represents an excellent method for the preparation of those three-membered rings. Typically, thiiranes are isolated as the final products, but in some instances they are produced as intermediate compounds which spontaneously desulfurize to give alkenes [twofold extrusion (47,48)]. 

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 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. 

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). 

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. 

Based on a series of kinetic studies, Huisgen et al. (91-93) established that thiocarbonyl compounds, especially aromatic thioketones, function as very active dipolarophiles (superdipolarophiles) toward thiocarbonyl ylides. In fact, the trapping reaction of thiocarbonyl ylides with thiocarbonyl compounds represents an excellent method for the preparation of 1,3-dithiolanes. 

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. 

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. 

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). 

Nitroso compounds are seldom used as dipolarophiles for trapping reactions with thiocarbonyl ylides. However, Sheradsky and Itzhak (175) did report one example where nitrosobenzene reacts with a thioisomiinchnone to give 134 as the major product. 

Cyclization of a thiocarbonyl ylide with the C=C-bond of an aromatic ring was observed in the reaction of aryl biphenyl-2-yl ketones with di(tosyl)diazomethane in the presence of Rh2(OAc)4 (189). In the case where the aryl ring contains a 4-methoxy group, benzo[c]thiophene (164) was the only product formed. In contrast, when the aryl ring consists of a 2,4,6-trimethylphenyl group, compounds 165 and 166 were produced. It would seem that after 1,5-dipolar electrocyclization of the intermediate thiocarbonyl ylide occurs, aromatization then takes place by elimination of toluenesulfinic acid or methyl toluenesulfinate. 

Like many other 1,3-dipoles (e.g., nitrile ylides, imines, and oxides) (7), thiocarbonyl ylides undergo head-to-head dimerization to give sterically crowded 1,4-dithianes. The first reported example involves the formation of 2,2,3,3-tetraphenyl-l,4-dithiane (18) from thiobenzophenone (5)-methylide (16) (17,28) (cf. Scheme 5.3). Other (5)-methylides are known to form analogous 1,4-dithianes (e.g., thiofluorenone (5)-methylide yields 172) (17). The (5)-methylides of 4,4-dimethyl-2-phenyl-l,3-thiazole-5(4//)-thione (105) and methyl dithiobenzoate (60,104) dimerize to give compounds 173 and 174, respectively. 

When thiocarbonyl and ot-diazocarbonyl compounds are combined, acyl-substituted thiocarbonyl ylides 158 are generated from a nonisolable 3-acyl-1,2,4-thiadiazoline 157 (Scheme 8.36). In addition to giving acylthiiranes 159 and 1,3-dithiolanes 160, dipoles 158 can also 1,5-cyclize to produce 1,3-oxathioles 161. Acyl-thiocarbonyl ylides derived from diazoketones [e.g., HC(0)C(N2)R, R = Ph, f-Bu (219,220) 2-diazocyclohexanone (221)] produce 1,3-oxathioles [e.g., 162 (220), Scheme 8.36], while those derived from diazoesters (218,222,223) lead to thiiranes by 1,3-cyclization. Ylides derived from a-diazocarboxamides form 1,3-oxathioles (e.g., 163) and thiiranes (e.g., 159, R = f-Bu, R = NMePh, R = R" = Ph), depending on the nature of the substituents (220). A related 1,5-cyclization of an aminomethyl-thiocarbonyl ylide formed from dimethyl 3-anilino-2-diazobutanedioate was also reported (224). 

Thiocarbonyl Ylide from Catalytic Reaction of ot-Diazocarbonyl Compounds 167... 

Similar to ethers and carbonyl compounds, sulfides or thiocarbonyl groups interact with metal carbene to generate the corresponding ylides. These ylides undergo similar subsequent reactions as their oxygen counterparts (Figure 4). 

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