Isocyanic acid cycloaddition

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). 

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). 

RHF methodology, used to investigate the cycloaddition reaction of isocyanic acid with methylenimine, confirmed a two-step mechanism via a cis intermediate for the equimolar reaction.22 The 2 + 2-cycloaddition of chlorosulfonyl and trichloroacetyl... 

An ab initio study of the 2 + 2-cycloadditions of allene to isocyanic acid and ketene to vinylimine found the reactions to be concerted and mostly asynchronous.28,29 The diastereoselective 2 + 2-cycloaddition of dichloroketene with a chiral enol ether (26) produced the cyclobutanone (27), which leads to a key intermediate (28) in (g) the total synthesis of the natural alkaloid (-)-Swainsonine (29) (Scheme 8).30 The... 

Dobrowolski and co-workers reported calculations of the thermodynamic stability of the products derived from cycloaddition of vinylimine and ketene and of isocyanic acid and allene using MP2, density functional theory (DFT) (B3PW91), and Hartree-Fock (HF) methods with the 6-311+- -G basis set. Fourteen different structures were calculated for these cycloaddition reactions and the values of the free Gibbs energy showed that only 4- and 3-methylene-/3-lactams could be formed in considerable amount. 

Cycloaddition reactions of thioketene and isocyanic acid forming four-membered ring products have been studied by means of the ab initio RHF/6-31G method. The two alternative reactions are concerted but nonsynchronous, taking place through twisted or planar four-membered cyclic transition states. The activation barriers were calculated to be... 

In contrast to the difficulty in producing cyclobutadiene by the simple [2 + 2] cycloaddition of alkynes, the addition of 1,3-dipolar species across the carbon-carbon triple bond of alkynes is quite facile. Thus, in addition to the fourth example of Table 6.9 showing that alkyl azides can add across the triple bond, reactions such as that of ethyne (acetylene, H-C=C-H) with isocyanic acid (fulminic acid. 

Isocyanates are Hquids or soHds which are highly reactive and undergo addition reactions across the C=N double bond of the NCO group. Reactions with alcohols, carboxyUc acids, and amines have been widely exploited ia developiag a variety of commercial products. Cycloaddition reactions involving both the C=N and the C=0 double bond of the NCO group have been extensively studied and used for product development (1 9). 

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 e, 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... 

Enamines of cyclic ketones do not form cycloaddition products, but give the mono- or dicarboxanilides (110,111). Thus the enamine (113) on reaction with 1 equivalent of phenyl isocyanate gave 160. Treatment of 113 with 2 equivalents, or 160 with 1 equivalent, of phenyl isocyanate gave the 2,6-disubstituted product (161). Mild acid hydrolysis of 160 and 161 produced the corresponding cyclohexanone(2-mono- and 2,5-di)carbox-anilides (110). 

Several syntheses of annulated uracils of biological value were recently reported. The key reaction was a microwave-assisted one-pot [4 -i- 2] cycloaddition of oxazino[4,5-d]-, pyrano-[2,3-d]-, pyrido[2,3-dj- and pyrimido[4,5-djpyrimidines, in the sohd state [134] and under solvent-free conditions [135]. The synthetic approach was based on the reaction of NJ -di-methyl-5-formylbarbituric acid 208 with maleimide in the sohd state for 5 min under microwave irradiation at 120 °C to give the pyrano[2,3-d]pyrimi-dine derivative 209 in 90% yield (Scheme 76). The reaction of 208 with phenyl isocyanate under microwave irradiation in the absence of solvent... 

An intramolecular cycloaddition of the tetradecatrienyl nitroethyl ether 263 was used in the synthesis of the 14-membered bicyclic precursor 265 of crassin acetate 266, a cembrane lactone possessing antibiotic and antineoplastic activity (332). Nitro compound 263 was obtained from farnesyl acetate (262) in several steps and was then treated with phenyl isocyanate and triethylamine to give the tricyclic isoxazoline 264 (Scheme 6.98). Conversion to ketone 265 was accomplished by hydrogenation of the cycloadduct with Raney Ni and boric acid followed by acetylation (332). In this case, the isoxazoline derived from a 3-butenyl nitroethyl ether moiety served to produce a 3-methylenetetrahydropyran moiety (332). 

Shibasaki and co-workers used an intramolecular nitrile oxide cycloaddition to prepare the skeleton of phorbol (272) (Scheme 6.99), a tumor promoter that activates protein kinase C (PKC) (333). Nitroalkene 268 was elaborated in several steps from (+)-3-carene (267) and was subjected to cycloaddition by means of -chlorophenyl isocyanate-triethylamine to give cycloadduct 269 in 88% yield. Reductive hydrolysis employing Raney Ni and boric acid afforded hydroxyketone 270, that was subsequently used for the construction of the optically active derivative 271, which contains the phorbol skeleton (333). 

The cycloaddition chemistry of pyridones (695) is quite analogous to that of the a-pyrones (79CC1091). Pyridones will react under high pressure conditions with acetylenedicarboxylic acid esters to furnish cycloadducts (696) which when heated expel a molecule of an isocyanate to yield substituted aromatics (697 Scheme 163). 

A 1,4-dipolar cycloaddition between tetrahydropyrido[l,2-a]pyrimidi-none 114 (R = Me) and 4-methyl-l, 2,4-triazoline-3,5-dione 666gave stable adduct 667 in acetonitrile or in acetic acid at room temperature for 1 hour (Scheme 44) (85CB4567). When ethyl cyanoformate was used as dienophile in boiling toluene for 20 hours, ethyl 3-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[ 1,2-a]pyrimidine-2-carboxylate 669 was obtained (86CB1445). Pyrido[l,2-a]pyrimidine-2-carboxylate 669 was formed from the initial adduct 668 by elimination of phenyl isocyanate. Reaction of tetrahydropyr-ido[l,2-a]pyrimidinone 114 (R = Me) with l-(diethylamino)-l-propyne in... 

The Lewis acid-catalysed 3 + 2-cycloaddition of aziridine-2-carboxylates with isocyanates proceeds regio- and stereo-specifically to produce enantiomerically pure 4-substituted imidazolin-2-ones in high yields.33 The reaction of ethyl 7-iodo-2-heptynoate (27), 2-arylaziridines (28), and K2C03 produces polysubstituted indolizidines (30) via an S /formal 3 + 2-cycloaddition (29) process (Scheme 8).34... 

---