Aryl isothiocyanates 4+2 cycloaddition reactions

Cycloaddition of 2-nitrosopyridine 48 with nitrile oxides can give either di-A -oxides such as 49 or 3-mono-A -oxides such as 50 (93JHC287). In general, greater electron withdrawing character in the aromatic substituent appears to favor formation of the di-A -oxides. Sulfur ylides such as compound 51 are obtained from aryl isothiocyanates and l-amino-2-methylthiopyridinium iodides (84JCS(P1)1891) nitrogen ylides can be obtained from a similar reaction (86H(24)3363). 

A successful method for preparing 1,3-thiazetidines is the cycloaddition of carbodiimides with isocyanates. The cycloadduct 151 was derived by the interaction of carbodiimide 152 and tosyl isothiocyanate . Reaction of 152 with methyl or phenyl isothiocyanate preferentially leads to iminotriazine-thiones. Cycloaddition between aryl isothiocyanates and dicyclohexylcar-bodiimide produced 153. ... 

A cycloreversion mechanism is suggested for the transformation of the nonisolable cycloadduct 90 to the aldehyde 91 and isothiocyanate 92 <1996BCJ719> and for the spiro-1,4,2-oxathiazole intermediates 94 to the dioxothiazoline 95 and the aryl isothiocyanate 92 <2001MOL510>. Both cycloadducts are obtained by cycloaddition reactions of nitrile oxides 88 to thiocarbonyl compounds (Scheme 12). 

A representative 1,3-dipolar cycloaddition process occurs with yV-aryl-C-(trifiuoromethyl)-nitrilimines, generated from the corresponding hydrazonoyl bromides, c.g. 4. under basic conditions. which can react with dimethyl fumarate and maleate,bicyclic olefins. and dipolarophiles containing cumulative double bonds. With sodium isocyanates as the dipolarophilc the cycloaddition reaction occurs across the C = N bond, while with potassium isothiocyanate it occurs through the C = S bond. ... 

Reaction of l-benzyl-4-acetylimino-l,2,4-triazolium (493) with aryl isothiocyanates in benzene yields a mixture of 1,3-cycloaddition product (494) and 1,5-disubstituted triazole (495). However, in DMF, mainly the... 

With aryl isothiocyanates, 4-XCgH4NCS, (X = H, Me, OMe or NO2), complex 25a reacted in the familiar way by cycloaddition of the C=S bond and isocyanide insertion to form the bicyclo[2.2.2] adducts 32. The structure of 32, X = H, has been determined by X-ray crystallography. In the presence of a second equivalent of isocyanide, the bicyclo[3.2.2] products 33, resulting from a second isocyanide insertion, could be isolated. This reaction is cleanly thermally... 

Cycloaddition and cyclization routes were used to access certain 1,3-diazines. The 4+2 cycloaddition reaction of 4-(N-allyl-N-aryl)amino-l,3-diaza-l,3-butadienes with vinyl-, isopropenyl-, and chloroketene led to pyrimidinone-fused pyrimidinones <97T13841>. Cis-cyclopenta[d]pyrimidines were derived from cis-2-amino-l-cyclopentanecarboxylates by cyclization with KOCN and KSCN <97JHC1211>. 2-Thioxopyrido[3, 2 4,5]thieno[3,2-r/]pyrimidin-4(3//)-ones 19 were prepared by cyclocondensation of 2-carbethoxy-3-amino-4-phenyl-6-substituted-thieno[2,3-/)]pyridines and isothiocyanates <97JHC937>. Thiazolyl-benzimidazoles derived from 2-cyanomethyl-l//-benzimidazole and 2,3-dihydrothiazole-2-(3//)-thiones were cyclized to the corresponding thiazolo[4,5-r/]pyrimidines <97PHA346>. Reductive cyclization of 6-cyanomethyl-5-nitropyrimidines afforded 7-alkyl-5//-pyrrolo[3,2-r/]pyrimidines and 6-amino-7,7-dialkyl-7//-pyrrolo[3,2-rf]pyrimidines <97T391>. 7-Methyl-5-alkyl-2-vinyl-pyrazolo[3,4-r/]pyrimidine-4,6(5//,7//)-diones arose from cyclization and alkylation of... 

The cycloaddition reaction of the ynamine 38 with an aryl isothiocyanate affords the 2H-thietamine 39 in high yield when the ynamine is stable <01SL361>. Thietanylureas are available from thietanyl 3-isocyanate <00MI565>. 

Tetra(ethylthio)allene, (EtS)2C=C=C(SEt)2, undergoes a cycloaddition reaction with ArSOa NCO or with an aryl isothiocyanate. However, though allenes are not directly comparable with ethylenes in many respects, further studies are likely to clarify the structural requirements for tetra-thioethylenes to show minimal electrophilic and dienophilic reactivity. 

Isothiocyanates can also be used, however in such cases the competition with the common [2 + 2] cycloaddition must be considered. Reaction with N-aryl isothiocyanates at ambient temperature helps the [2 + 2] cycloaddition being favored affording the 4-thioxo-2-azetidinones (thioxo-jd-lac-tams) in satisfactory yields with high enantioselectivities, whereas reaction... 

Azabutadienes have been shownto react in a [4 + 2]cycloaddition across the C=S of aryl isothiocyanates, to give a new synthesis of imino-2,3-dihydro-1,3-thiazines (302). Cyclization does not occur if the steric requirements of are too large. The new ring system (303) has been formed by reaction of cyclic thioureas with 2-chloro-3-cyanopyridine. 

Carbenes can also participate in [1+2+2] cycloaddition reactions, in these reaction, ionic intermediates are formed, which can be intercepted by a second molecule of the isothiocyanate. For example, dimethoxycarbene, formed in the thermolysis of 1,2,3,4-tetrachloro-7,7-dimethoxy-5-phenylbicyclo[2.2.1]hepta-2,5-diene 11, reacts with excess aryl isothiocyanate to give the [1+2+2] cycloadducts 12. The initial reaction of dimethoxycarbene with the aryl isothiocyanate generates a 1,3-dipole, which undergoes a [3+2] cycloaddition reaction with the second equivalent of the aryl isothiocyanate... 

A stepwise cycloaddition reaction of thioisomiinchenones with aryl isothiocyanates results in the thionation of the mesoionic compound in good yield ... 

Also, A-(arylsulfonyl)aziridines 97 react with isothiocyanates to give the [3+2] cycloadducts 98. In this reaction the isothiocyanate undergoes reaction across its C=S bond . In contrast, substituted A-(arenesulfonyl)aziridines, in the presence of sodium iodide as the catalyst, undergo [3+2] cycloaddition reactions with aryl isothiocyanate across their C=N... 

Cyclic aldo- and ketonitrones react similarly with phenyl isothiocyanateHowever, substituted phenyl isothiocyanates react with 5,5-dimethyl-l-pyrroline-l-oxide to give cycloadducts derived from addition across the C=N bond as well as the C=S bond of the isothiocyanates. The C=S cycloadducts are unstable and undergo further transformations . The [3+2] cycloaddition reaction of 3,3,5,5-tetramethylpyrroline-l-oxide with aryl- and phenylcarbonyl isocyanates also occurs exclusively by addition across the C=S bond . ... 

In the [2+2] cycloaddition reactions of isothiocyanates to diazo compounds iminoth-iadiazolines are formed, which rearrange into 5-substituted 1,2,3-thiadiazoles 136. This is the von Pechmann synthesis of 1,2,3-thiadiazoles. The reaction is general and some examples are listed in Table 3.14. The reactivity of the isothiocyanates increases with the electrophilicity of the carbon of the isothiocyanate group, which is enhanced by electron withdrawing groups, i.e. R = aryl < EtOCO < PhCO. 

The [3+2] cycloaddition reaction of l,3,4-oxadiazol-2-ylhydrazones 164 with aryl isothiocyanates affords 1,3,4-thiadiazolines 165. ... 

Further examples of multifunctional isothiocyanates include aryl for-mamidinoyl-isothiocyanates RiNC(=NR )NCS, which may be isomerized into 3H-quinazoline-4-thiones and which undergo well-known amine addition and cycloaddition reactions associated with simpler isothiocyanates ° and sulphonyl isothiocyanates, for which 1,3-dipolar cycloaddition to alkyl azides has been demonstrated,thermolysis of the resulting thiatriazolines giving sulphonyl carbodi-imides ArS02N=O=NR. 

Cycloaddition of phenyl isothiocyanate (296) to pyridinium salts (295) produced imidazo[l,2-a]pyridine-2(3i/)-thiones (297) (77MI41001). Reaction of l-aryl-2-... 

Substituted phenyl isothiocyanates 1 react with (dialkylamino)carbonitriles 2 at 800 MPa to give Af" -aryl-iV, A -dialkylquinazoline-2,4-diamine salts 3 in good to moderate yields. Mechanistically, the reaction probably involves repeated cycloaddition-dectrocyclic ring opening in which carbamimidoyl isothiocyanates are formed as intermediates " (cf. p 57). 

Cycloaddition of phenyl isothiocyanate (296) to pyridinium salts (295) produced imidazo[l,2-a]pyridine-2(3//)-thiones (297) (77Ml4looi). Reaction of l-aryl-2-chloropyridin-6-ones with mono-A/ -substituted ethylenediamines provided dihy-droimidazo[l,2-a]pyridin-5-ones (79CPB1207). Another procedure involves the polyphos-phoric acid cyclization of 2-(2-hydroxyethyl)aminopyridines (76AJC1039). Treatment of certain /3-aminoacrylic esters (298) with benzenediazonium fluoroborate (299) resulted in... 

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