Adamantanethione 5-methylide

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). 

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. 

The reaction of thiocarbonyl ylides with propiolates affords a mixture of regioisomeric cycloadducts. Thus, 2,5-dihydrothiophenes obtained from the reaction of adamantanethione (5)-methylide (52) and methyl propiolate were produced in a 1 1 ratio (95). In the case of ylide 69, the ratio was 1 2 in favor of the sterically less hindered isomer (160). 

The only reported reaction using phenylisocyanate as a trapping agent is one that involves adamantanethione (5)-methylide (52) as the dipole (163). Although a 1 1 adduct was isolated, its spectral data did not fully establish the structure of the... 

Thiocarbonyl ylides are both nucleophilic and basic compounds (40,41,86). For example, adamantanethione (5)-methylide (52) is able to deprotonate its precursor, the corresponding 2,5-dihydro-1,3,4-thiadiazole, and a 1 1 adduct is formed in a multistep reaction (40,86). Thioxonium ion (56) (Scheme 5.22) was proposed as a reactive intermediate. On the other hand, thiofenchone (S)-methylide (48) is not able to deprotonate its precursor but instead undergoes electrocyclization to give a mixture of diastereoisomeric thiiranes (41,87,88). The addition of a trace of acetic acid changes the reaction course remarkably, and instead of an electrocyclization product, the new isomer 51 was isolated (41,87) (Scheme 5.18). The formation of 51 is the result of a Wagner-Meerwein rearrangement of thioxonium ion 49. 

The spiro-l,3,4-thiadiazoline 110 loses Ni at -45 °C to give the short-lived adamantanethione 5-methylide dipole 111. Interception of 111 by various acidic reagents has led to further fuctionalisation of the adamantane ring system, giving thio derivatives <01T145>. 

High-level quantum-chemical calculations on the 3 + 2-cycloadditions of thioformaldehyde 5 -imides, S -methylide, S-oxide, and 5-sulfide have been reviewed. Theoretical studies on the 1,3-dipolar cycloaddition between thioketene 5-oxide and methyleneimine show that this reaction is concerted but non-synchronous. Adamantanethione 5-methylide reacts with thiocarbonyl compounds to produce 1,3-dithiolanes. A density-functional-theory study of the cycloaddition of the sulfine H2CSO predicts the 2 + 3-mechanism having the lowest pathway, with an activation barrier of 12.3kcalmoP. R The thermal and photochemical reactions of fluorenethione 5-oxide (69) with cyclooctyne (70) involves an initial 1,3-dipolar cycloaddition to produce the adduct (71), followed by an efficient sulfur transfer to cyclooctyne to produce the enone (72) and the dithiin (73) (Scheme 26). ° ... 

Diazo Compounds. Diazomethane reacts immediately with 1 dissolved in diethyl ether in a regioselective manner to give 2,5-dihydro- 1,3,4-thiadiazole (17) as a relatively stable sohd. This confound is a superior precursor of the reactive thiocarhony 1 5-methylide (8, eq 9) as it smoothly eliminates nitrogen at 45 °C. In the absence of an appropriate interceptor, thiirane 9 is formed. In the presence of electron-deficient dipolarophiles, diverse five-membered spiro-heterocycles (18) are formed via 1,3-dipolar cycloaddition (eq 9).22.23 Representative examples of dipolarophiles leading to 18 in high yield are DMAD, TV phenyl maleinimide, chloral, dimethyl azodicarboxylate, adamantanethione, as well as 1.21... 

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