Thermally induced cyclization

Katritzky and co-workers have developed a methodology for the preparation of heterocyclo[h]-fused carbazoles from benzotriazole derivatives (Scheme 26). Using this approach, W,iV -dimethylindolo[3,2-h]carbazole (150) was prepared via a thermally induced cyclization of the benzotriazole-containing precurscM 196 (95JOC3707). 

Marvel et al. described [41] the polymerization of 5,6-dibromocyclohexa-1,3-diene (16) to poly(5,6-dibromo-l,4-cyclohcx-2-ene) 17 followed by a thermally induced, solid state elimination of HBr on the formation of PPP 1. The products, however, display some indications for several types of structural defects (incomplete cyclization, crosslinking). 

The thermally induced Pauson-Khand intramolecular cyclization of 57 leads to tricycHc enones in moderate yields and with variable diastereoselectivities <96T14021>. 

Enaminone 128 (Scheme 33) is obtained, together with an isomeric indo-lizine derivative, by flash vacuum thermolysis of aminomethylene Meldrum s acid derivative through intermediate ketene and delocalized azomethine ylide (85TL833). The thermally induced cyclization of semi-cyclic dienamines to afford, for instance, tricyclic 129 is also believed to start with an azomethine ylide (97JOC7744) the p-chlorophenyl substituent is essential for the reaction. Unstabilized ylide 130, on the other hand, is generated from pipecolinic acid and /1-phenylcinnamaldehyde by the decarboxylation method target base 131 is formed by 1,7-electrocycliza-tion and [l,5]-hydrogen shift (99J(P1)2605). 

The thermally induced cyclization of A -(benzyloxycarbonyl)phenyl ketenimines 415, obtained in a two-step, one-pot procedure from benzyl 2-azidobenzoates 414, led to 2-substituted-4/f-3,l-benzoxazin-4-ones 416 (Scheme 79). The reaction involves the formation of a new carbon-oxygen bond and migration of the benzyl group from the oxygen atom to the terminal carbon atom of the ketenimine fragment <2005S2426>. 

These authors also showed that the indolizidine skeleton can be prepared from cyclopropyl dipolarophiles (Scheme 1.16). The cycloaddition of alkyhdenecyclo-propanes 67 with various nitrones (e.g., 68) afforded the expected isoxazolidine adducts 69 and 70, commonly forming the C(5) substituted adducts 70 (97,105-108) predominantly but not exclusively (109-111). Thermally induced rearrangement of the spirocyclopropyl isoxazolidine adduct 70 afforded the piperidinones 71 (107,108). These authors propose reaction via initial N—O bond homolysis of 70 to diradical 72 followed by ring expansion through relief of the cyclopropyl ring strain forming the carbonyl of a second diradical intermediate 73, which cyclizes to afford the isolated piperidinone 71. 

The carbodiimide 73, obtained by reaction of an iminophosphorane with ethyl isocyanate, underwent a thermally induced cyclization in 1,2-dichlorobenzene at reflux to give the azulene 74 in 42% isolated yield (Scheme 33) <2001JOC6576>. This process was regiospecific since products arising from reaction with the six-membered ring were not observed. 

The cyclization is induced thermally or photochemically. Most cyclizations have a high activation energy barrier and therefore temperatures around 200 °C are needed for the cycloaromatization. The Bergman Cyclizatic n forms a 1,4-benzenediyl diradical - a highly reactive species, that reacts with a H donor to give the corresponding arenes. 

A historic method for 1,2,4-oxathiazolidine synthesis is based on 1,3-cycloaddition reactions, for example, addition of carbonyl compounds across the S-C=N groups of 5-imino-l,2,3,4-thiatriazolines <1996CHEC-II(4)453>. The thermally induced conversion of 677-1,3,5-oxathiazine A-oxides 119 in refluxing benzene results in 1,2,4-oxathiazo-lines 20 in high yields by intramolecular cyclization with extrusion of carboxaldehydes (see Section 6.03.8.2). Oxidative cyclization of A-acylthioureas 114 and iV-acylthiocarbamates 115 by Br2 gives 1,2,4-oxathiazolium hydrobromides 43 and 38, respectively (see Section 6.03.8.1). 

Thermally induced cyclization of the enehydrazine 73, obtained from the sequential treatment of the corresponding arylhydrazine with acetone and TFAA, has been shown to produce the 2,4-disubstituted indole 74 along with the isomeric 2,6-disubstituted system 75. The yields of the products were dependent on the reaction medium however, toluene or chlorobenzene were found to be the solvents of choice, giving 74 as the prevailing product <02H(57)1101>. 

Thermally induced cascade cyclizations under metal-free conditions using epoxyhexene as acid scavenger provided polycyclic furans in high yields <07JOC1395>. 

Thermally induced cyclization of the l-methoxy-3-phenyl-[(2-methoxy)-alkenyljcarbene-chromium complex [= 2,4-dimethoxy-4-phenyl-l-(penta-... 

The thermally generated imminium salts 866 and 868 undergo intramolecular cyclization followed by aromatiza-tion. The former affords 5-methylthieno[3,2-/ ]carbazole 867 and the latter gives the [2,3- ] isomer 869 (Scheme 134) <1995JOC3707>. The thermally induced electrocyclization of enamines 870 affords benzo[ ]thio-phenes 871 or pyrrothienoazepine 872 <1997JOC7744>. 

In order to explain the stereospecificity of the thermally induced cyclization of preisocalamendiol (315) to give dehydroisocalamendiol (316), Terada and Yamamura have carried out molecular mechanics calculations on the ground-state conformers and probable transition states of (315). The computed values of the steric energies of the possible transition states are in good agreement with the observed experimental facts. Other studies related to the conformational aspects of germacrane sesquiterpenoids include an examination of the NOE effects in the isofuranodiene (317), which shows the 1,5-diene system to be in a crossed... 

As in the research work of Vivet et al., new bicyclic sila-heterocycles were synthesized by Handmann et al. <2000ZNB133, 2000JOM19>. Compound rac-164 underwent a thermally induced cyclization reaction to give rac-7-ethoxy-2,2-dimethyl-2,3,5,7a-tetrahydro-177-3a,6,-sila-inden-4-one 9a (Equation 27). The crystal stmcture of 9a and kinetic studies of the cyclization reaction have also been reported. Starting from 3,6-ethoxy-2,5-dihydropyrazine 163, metallation with 1 molar equivalent of -butyllithium and subsequent treatment with 1 molar equivalent of the bis(chloromethyl)silane produced compound 164 in 50% yield. Pleating neat 164 at 120 °C gave the crystalline 9a in almost quantitative yield. 

A series of 2-alkyl(aTyl)thio-3//-quinolin-4-ones 120 were synthesized in a thermally induced cyclization <05OL5281>. Initially, the ketenimine 121 undergoes a [1,5] sigmatropic migration of the alkyl(aryl)thio group to form 122 followed by a 67t-electrocyclic ring closure resulting in the formation of 120, illustrated in Scheme 34. 

Pyridazines in which both nitrogen atoms are at bridgeheads may be obtained in moderate yields by cyclizing an aldehydo phosphonate in the presence of DBU (review [3364]). A thermal method of forming a pyridazine ring gives similar yields. The keto-azo-phosphorane (34.3) undergoes a thermally induced cyclization to produce a 3-substituted cinnoline. 

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