Tosyl cyanide

Type G syntheses are typified by the 1,3-dipolar cycloaddition reactions of nitrile sulfides with nitriles. Nitrile sulfides are reactive 1,3-dipoles and they are prepared as intermediates by the thermolysis of 5-substituted-l,3,4-oxathiazol-2-ones 102. The use of nitriles as dipolarophiles has resulted in a general method for the synthesis of 3,5-disubstituted-l,2,4-thiadiazoles 103 (Scheme 11). The thermolysis is performed at 190°C with an excess of the nitrile. The yields are moderate, but are satisfactory when aromatic nitrile sulfides interact with electrophilic nitriles. A common side reaction results from the decomposition of the nitrile sulfide to give a nitrile and sulfur. This nitrile then reacts with the nitrile sulfide to yield symmetrical 1,2,4-thiadiazoles <2004HOU277>. Excellent yields have been obtained when tosyl cyanide has been used as the acceptor molecule <1993JHC357>. 

The addition of tosyl cyanide to cyclopentadiene leads to intermediate formation of radical 27, which then is trapped by tosyl cyanide by cyano group transfer. The trans-... 

In contrast, the 5-phenyliminothiatriazoline (323) reacts as a masked 1,3-dipole with a variety of electrophilic nitriles. Tosyl cyanide and ethyl cyanoformate both react with (323) in refluxing chloroform to give initially (324) which then isomerizes to (325) as the reaction proceeds (Scheme 71) <91JHC333>. When the solvent is changed to acetone the reaction with the nitriles proceeds faster due to the formation of the adduct (326) which is capable of undergoing cycloaddition/elimination reactions at 20 °C. Trichloroacetonitrile does not react with (323) in chloroform solution in acetone,... 

The 1,3-dipolar cycloaddition reaction of nitrile sulfides with nitriles yields 3,5-disubstituted 1,2,4-thiadiazoles of unequivocal structure. This method has received considerable attention in recent years. Electron deficient nitriles such as tosyl cyanide afford high yields of 5-tosyl derivatives (341) (Equation (53) see also Scheme 61) <93JHC357). 

Few preparations of nitriles have been performed on insoluble supports (Table 13.19). Aromatic and heteroaromatic nitriles have been prepared on solid phase from the corresponding iodoarenes by metallation followed by reaction with tosyl cyanide (Entry 1, Table 13.19). Moreover, the reaction of chloromethyl polystyrene with NaCN has been used to prepare support-bound benzyl cyanide (Entry 2, Table 13.19). Cleavage with simultaneous formation of nitriles can be achieved by treating polystyrene-bound sulfonylhydrazones with KCN (Entry 3, Table 13.19) or by cleaving amides from a Rink or Sieber linker with TFA anhydride (Entry 10, Table 3.38 [262]). Support-bound benzaldehydes have been converted into 3-aryl-2-propenenitriles by means of a Horner-Emmons reaction with (Et0)2P(0)CH2CN [263]. 

Normally tosyl cyanide reacts with the functionalized zinc reagents, such as 44, to provide the expected nitrile 45 (0°C to 25 °C, 2 h). However, the benzylic zinc reagent 46 and the corresponding copper-zinc reagent 47 react with tosyl cyanide differently. Whilst the zinc reagent furnishes the SE2 substitution product 48 (functionalization at the ortho position of the phenyl ring), the zinc-copper compound leads to the direct (SE2) substitution product 49 (Scheme 1.14).51... 

Similar reaction conditions allowed the preparation of a-branched nitriles (Fig. 83). When mono-, di-, and trisubstituted olefins 355 bearing functionalities, such as esters, aldehydes, ketones, amides, or alcohols, were reacted with tosyl cyanide 356 and phenylsilane in the presence of 1 mol% of the (salen)Co catalysts 357a or 357b the corresponding nitriles 358 were isolated in 55-99% yield (entry 21) [402]. Although no mechanistic evidence was provided, the reaction may be assumed to proceed similarly as the hydroazidation. 

An unsaturated bicyclic lactam, 2-azabicyclo[2.2.1]hept-5-en-3-one (77), which was synthesized by the Diels-Alder reaction of tosyl cyanide with cyclopentadiene... 

The cyanide ion is an ambident nucleophile (it can react via N or via C) and isocyanides (also called isonitiiles, R—N=C) may be side products. If the preparation of isocyanides is desired, they can be made the main products by the use of reagents with more covalent metal-carbon bonds, such as silver or copper(I) cyanide (p. 515). However, the use on an excess of LiCN in acetoneATHF gave the nitrile as the major product. Tosyl cyanide (T0ISO2CN) has been used in some cases. 

In 1974, Jagt and Van Leusen (74JOC564) found that sulfonyl cyanides are good dienophiles. At room temperature, tosyl cyanide (67) dissolved in cyclopentadiene 68 is converted into 3-tosyl-2-azabicyclo [2.2.1 ]hepta-2,5-diene (69) (95%). This is the first example of the formation of a primary Diels-Alder cycloadduct of a nitrile. Adduct 69 was hydrolyzed with acetic acid and water to the lactam 70. Daluge and Vince (73JOC2311) used 70 to synthesize puromycin analog 76 (Scheme 9). Lactam 70 was hydrolyzed to the cis-amino... 

A very reactive and selective carbon electrophile such as tosyl cyanide (TosCN) [41] reacts with various organozinc halides affording polyfunctional nitriles in good yields (Scheme 9-12 see Section 9.6.1) [42]. 

Cases in which allyl radicals display sufficient reactivity to participate successfully in radical chain reactions include the addition of bromotrichloromethane to butadiene the reaction of cyclopentadiene with tosyl cyanide, the addition of thiols , stannanes " and hydrogen halides . All these reactions follow the simple two-step radical chain mechanism depicted in Scheme 1, and the low reactivity of the intermediate allyl radicals can be compensated by using the trapping agent in excess or even as the solvent. In chain reactions with three or more chain-carrying radicals, this compensation is not possible anymore, because the concentration of the reaction partners has to be chosen such that the selectivity requirements for all intermediate radicals are satisfied. Complex radical chain reactions with polyenes as one of the reactants are therefore not known. 

The application of functionally substituted organozincs allows for the construction of carbon-carbon bonds while circumventing tedious protection-deprotection strategies, as exemplified below.Note that tosyl cyanide reacts with alkenyl or arylzinc reagents to provide a,(3-unsaturated alkenyl or aromatic nitriles, respectively. 

Other heterodienophiles include diethyl azodicarboxylate, tosyl cyanide and phosphaalkynes. Barrelene, benzobarrelene and 2,3-naphthobarrelene react at 100-110 °C (sealed tube) with diethyl azodicarboxylate to give as the main product the corresponding homo-Diels-Alder adduct 27. ... 

Three products were obtained in the reaction of norbornadiene with tosyl cyanide, including the homo-Diels-Alder adduct 29 which could not be isolated, due to its facile hydrolysis to 30. ... 

Boger and Corbett have also recently described a convenient modification of the original Hudson methodology [20]. Their procedure is based upon the known [21] propensity of methanesulfonyl- and toluenesulfonyl cyanide to rearrange to the corresponding sulfinyl cyanate (cf. 8, Scheme 4). Thus, treatment of an oxime with commercially available tosyl cyanide (7) generates 8 in situ, which leads to the O-sulfinylated oxime 9 and then to the N-tosyl imine. This methodology avoids the use of reactive, often unstable sulfinyl chlorides. 

Table 6-1 contains some typical examples of these cycloadditions. A clever total synthesis of an unusual isonitrile fungal metabolite has been achieved using the bicyclic adduct prepared from tosyl cyanide and cyclo-pentadiene (Scheme 6-I).6... 

Various functional groups could also be introduced to unactivated afkenes by excess NaBH4 and Pehi 182-184 jq BIrL, and iron complexes coordinated by appropriate ligands mediated the Markovnikov olefin addition of radical traps such as sodium azide, potassium thiocyanate, air (O2), iV-acetylsulfanilyl chloride, potassium cyanate, tosyl cyanide, and TEMPO (eq 43). Ely-drofluorination of unactivated alkenes were also realized by this system with Selectfiuor . ... 

Two new stereospecific syntheses of vinyl nitriles are reported. One involves the treatment of vinyl cuprates with cyanogen chloride (benzenesulphonyl cyanide or p-tosyl cyanide) in THF to give the vinyl nitriles in good yield (Scheme 16). The other synthesis comprises the conversion of vinyl halides into nitriles by direct... 

A soln. of startg. 2-aza-1,3-diene and tosyl cyanide in benzene stirred at 20° for 30 min, and the mixture treated with methanol 6-tosyl-4(3//)-pyrimidinone. Y 93%. F.e. and with CI3CCN in place of TsCN, also prepn. of startg. dienes, s. P. Bayard et al.. Tetrahedron Letters 29, 3799-802 (1988). 

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