Isocyanates, cycloaddition with

The 27T-electrons of the carbon-nitrogen double bond of 1-azirines can participate in thermal symmetry-allowed [4 + 2] cycloadditions with a variety of substrates such as cyclo-pentadienones, isobenzofurans, triazines and tetrazines 71AHC(13)45). Cycloadditions also occur with heterocumulenes such as ketenes, ketenimines, isocyanates and carbon disulfide. It is also possible for the 27r-electrons of 1-azirines to participate in ene reactions 73HCA1351). 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

Substituted azocine systems are much more stable than the parent compound, and 2-methoxy derivatives have been intensively examined. Starting from cyclohexa-1,4-diene (3), a [2 + 2] cycloaddition with chlorosulfonyl isocyanate, followed by removal of the chlorosulfonyl group, leads to the /3-lactam 4, which can be transformed by O-methylation with Meerwein s salt into the corresponding imidate. Monobromination with A-bromosuccinimide and subsequent treatment with base results in a methoxyazabicyclo[4.2.0]octatriene derivative, which spontaneously isomerizes to 2-methoxyazocine (5).13,14... 

The intermolecular dimerization of nitrile oxides has been described as a procedure to prepare Fx with identical substituent both in the 3 and 4 position (Fig. 3). This procedure is a [3 -F 2] cycloaddition where one molecule of nitrile oxide acts as 1,3-dipole and the other as dipolarophile [24-26]. Yu et al. has studied this procedure in terms of theoretical calculus [27,28]. Rearrangement of isocyanates competes with the bimolecular dimerization, with the former becoming dominant at elevated temperatures. 

In contrast to a simple [2 + 2] cycloaddition with a nitrile, 21 undergoes an interesting reaction with an isocyanate involving multiple cleavage and recoupling of bonds to give a five-membered ring compound (Eq. 22).76... 

The pyrido[l,2-tf][l,3,5]triazine-2,4(3//)-dione derivative 89 was obtained in a cycloaddition reaction of diphenyl-methyl isocyanate 90 with 2-pyridyl isocyanate 91 derived from the corresponding acyl azide via Curtius rearrangement <2002ARK438>. Compound 89 was also synthesized by the reaction of diphenylacetyl chloride 118 and picolinyl azide 116a in the presence of triethylamine (Scheme 11) <2002ARK438>. ... 

Thermally induced intra-intermolecular criss-cross cycloaddition of nonsymmetrical azines 363 in the presence of phenyl isocyanate provides the corresponding products of the mixed criss-cross cycloaddition 364 (Scheme 55) <2002TL6431>. Two different reaction mechanisms, intra-intermolecular and inter-intramolecular, of the mixed criss-cross cycloaddition with opposite sequence of reaction steps are possible. Quantum chemistry calculations suggest the intra-intermolecular mechanism as the most probable mechanism of this reaction <2004CCC231>. 

Heptafluoro-4-(trifluoromethyl)-2,3-pentanedione undergoes cycloaddition with phosphorus isocyanate 237 to give a spirocyclic dioxaphospholene 35 (Equation 54) <1997PS419>. 

The Mukaiyama-Hoshino reaction between a nitroalkane and phenyl isocyanate generates a nitrile oxide, and this method has been used in the synthesis of 1,2,4-oxadiazoles as discussed in CHEC-II(1996) <1996CHEC-II(4)179>. In a more recent advance, nitroethane undergoes ultrasound-mediated cycloaddition with trichloroacetonitrile to give the extremely useful (see Equation 11) 5-trichloromethyl-l,2,4-oxadiazole 228 (Equation 45) <1995TL4471>. 

Chalcogenation of a divalent germanium compound with styrene sulfide has been examined as an alternative route to the first free germanethione Tbt(Tip)Ge = S 165142 (Scheme 32) and later on allowed the synthesis of new base-stabilized germanethiones 187 and 188156 [Eq. (37)]. Phenyl isocyanate also may serve as a sulfur source leading to 165, which was evidenced by electronic spectroscopy and underwent a subsequent [2 + 2] cycloaddition with phenyl isocyanate157 (Scheme 36). 

Upon reaction of A -vinyliminophosphoranes (109) with aromatic isocyanates, vinylcarbodiimides (110) are formed, as shown in Scheme 47. Divi-nylcarbodiimides (111) can be obtained as side products (88CB271). With isonitriles the vinylcarbodiimides also afford pyrroles (112) via [4 + 1]-cycloaddition. Divinylcarbodiimide can also react via [4 -l- l]-cycloaddition with an isonitrile, whereupon an electrocyclic step of the initial diaza-1,3,5-trienes (113) follows. Finally, the pyrrolo[2,3-e]pyrazine 114 is obtained (88CB271). 

The cycloadditions of thioacyl isocyanates proceeded with exo and cis selectivity. 

Besides removal of alkyl-based groups located at the N-2 of a pyridazin-3(27/)-one also real reactions in the side chain appeared. Pyridazinium ylides, obtained via deprotonation of iV-alkylpyridazinium salts, have been reacted with phenyl isocyanates and benzenediazonium salts <2002MI287, 1997T4411>. As discussed in Section 8.01.5.7.2 1,3-dipolar cycloaddition with ethyl acrylate and ethyl propiolate were also studied. 

In all cases, the initial addition to generate 520 was diastereospecific, that is, the isocyanate always adds to 519 from the face opposite to the 4-ethyl substituent of the oxazoline. In the cases wherein 521 was isolated (Entries 17-20 from Table 8.33), the stereochemistry of the two additional chiral centers from the secondary [2 + 2] cycloaddition was controlled by the chiral center formed during the initial reaction, that is, the isocyanate reacts with 520 from the opposite face of the neighboring Ri group. For Ri = H, R2 = Me, 519 reacted with an arylisocyanate (R3 = Ar) to give tricyclic adducts 521a and 521b as a 1.7 1 mixture of diaster-eomers (Entries 18-20). For Rj = Ph, R2 = Me, 519 reacted with phenylisocyanate... 

The other diazines can also undergo cycloaddition with ynamines an example of a pyridazine addition is shown in equation (94) (72TL1517), and of an addition to a pyrazine in equation (95) (72LA(761)39). Pyrazinediones react with the electron-deficient acetylenedicar-boxylic ester, with subsequent expulsion of isocyanic acid, as shown in equation (96) (73JCS(P1)404). 

Amidines formed by condensation of 4-aminouracils with dimethylformamide dimethyl acetal are effective dienophiles, and form pyrimido[4,5-rflpyrimidines by [4-I-2] cycloaddition with isocyanates, isothiocyanates (Equation 83) <2005TL1433> and imines (Equation 84), A similar process has also been reported, using a nitrone as the dienophile (Equation 85) <2006BMCL3537>. 

The 1,3-dipolar nitrone character of dibenz[c,e]azepine N-oxide (161) is apparent in its cycloadditions with phenyl isocyanate, JV-phenylmaleimide (74ZN(B)425> and JV-sulfinylaryl-sulfonamides (ArS02NS0) (81TL2141). 

A synthesis of the monoterpene alkaloid ( )-actinidine has been accomplished through the intramolecular cycloaddition of a substituted pyrimidine (81JCS(P1)1909). Condensation of the diester (756) with formamidine provided the pyrimidine precursor (757) which when heated at its melting point (203 °C) underwent cycloaddition with elimination of isocyanic acid to produce the pyridone (758). Conversion of the pyridone into the chloropyridine was effected with phosphoryl chloride. The chlorine atom was then removed by hydrogenoly-sis over palladium on charcoal to afford the racemic alkaloid (759 Scheme 175). 

Aryl isocyanates undergo a novel cycloaddition with A-benzylidenealuminum amides (173) via a series of dipolar intermediates to yield the triazines (174 Scheme 106) (78LA1111). 

Woodward s synthesis, 4, 416-419 Chlorophyll b, 4, 382 Chlorophyll c, 4, 382 Chlorophyll d, 4, 382 Chlorophylls, 4, 378 biosynthesis reviews, 1, 99 structure, 4, 370 substituents reactions, 4, 402 Chloroporphyrin e6, 4, 404 Chloroprothixene pharmacology, 3, 942 Chloropyramine as antihistamine, 1, 177 Chloropyrifos synthesis, 2, 201 Chloropyrifos-ethyl as insecticide, 2, 516 Chloropyrifos-methyl as insecticide, 2, 516 Chloroquine, 1, 145 adsorption on nucleic acids, 1, 179 as antimalarial, 1, 173, 2, 517 Chloroquine, hydroxy-as antimalarial, 2, 517 Chlorosulfonyl isocyanate cycloaddition reactions with alkenes, azetidin-2-ones from, 7, 261 reactions... 

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