Thermolytic cyclization

A hydrazine or substituted hydrazine in lieu of the amino group on the pyrimidine precursor is also an effective species. In what may be described as a Fischer indole-type reaction, 2-amino-6-hydrazino-4(3//)-oxopyrimidine 129 undergoes thermolytic cyclization when heated with compounds 130 (Scheme 12). The resultant product 131 is obtained in modest yield <1996H(43)323, B-2002MI439>. 

Provided a suitable acid methylene group, e.g., the cyanomethyl group, may be introduced conveniently in the heterocyclic nucleus, the benzannelation by condensation with a vinamidinium salt (7), followed by thermolytic cyclization, offers... 

One-bond formation by thermolytic cyclization of 4-(tetrazol-2-yl)pyrimidines (Scheme 4). 

Spiro-isoxazoline 57 (Scheme 16) undergoes thermolytic rearrangement followed immediately by cyclization of the intermediate enaminone to bicyclic 58 (89J(P1)1253). Imine 59 when heated gives iminium salt 60, hence providing a new and efficient route to parent substance 2 (03T3099). 

Brown et al. [36] attempted to approach pentalene (2) by a thermolytic ring-contraction-cyclization of 3-ethenylbenzyne 41, which, in turn, was generated by flash vacuum thermolysis of 3-ethenylphthalic anhydride 40. Indeed, the pentalene dimer 43 ( 50%) was formed along with phenylacetylene 44 ( 50%) in 80% overall yield (Scheme 6). The failure to detect monomeric pentalene (2) is in accord with the observation of de Mayo et al. that 1-methylpentalene (37) dimerizes above —140 °C [29]. The formation of phenylacetylene 44 was unexpected, and it is as yet unclear as to whether it arises by migration of two hydrogens in the aryne 41 or the intermediate carbene 42, or whether it is a secondary product formed from pentalene (2). 

Other classes of heterocycles undergo thermolytic fragmentation to give imido-nitrenes, as typified by the thermolysis of 1,5-diphenyltetrazole 41, the intermediates 42 can either cyclize on to an aromatic ring to form benzimidazoles 43 or undergo a Wolff-type rearrangement to carbodiimides 44 (Scheme 7). Thermal decomposition of 2-acyltetrazoles... 

Cyclic vinyloxiranes were opened with r-butyldimethylsilyl cyanide to yield isonitriles, as shown in equation (50). °° The opening of vinyloxiranes like (142) with TMS-I, TMS-I/TiCU and Smh was attempted in an effort to provide a topographical option for the [2 + 3] dihydrofuran annulation. While the 2,5-substitution pattern inherent in (143) is furnished through thermolytic rearrangements, the 2,3-isomer would result from an 5n2 opening of (142) to allylic iodide (154), which would cyclize to 2,3-function-... 

A prototype for the new cyclization reaction is the Ziegler-Hafner synthesis of azulene (J)4 by heating the fulvenoid decapentaene (/). Woodward28 was the first to argue that a thermal, electrocyclic [rr 10 s] ring-closure could be involved in this thermolytic process. Of course it seems likely that the nonisolable intermediate (2) may be formed by an intramolecular electrophilic attack of atom 10 to the electron-rich position 1 in compound (1). Indeed a distinction between the two different reaction modes is mechanistically irrelevant in this case. But only its interpretation as an electrocyclic process allows the generalization to [ir 6 s] cyclizations too. 

The relative ease of the cyclization step from A to C may also be linked to the nucleophilic or coordinative ability of the heteroatom bound to the metal. The reaction of 7 with diphenylacetylene (Ph2C2) leads to the seven-membered derivatives 68 and 69 after prior isolation of the monoinsertion product 24, treatment with a silver salt, followed by the usual thermolytic conditions. This is another rare example of an intramolecular formation of a C-S bond within the coordination sphere of a transition metal and a novel, albeit limited to one alkyne, route to the rare family of dibenzo[bd] thiepins. With the closely related 8, which differs from 7 only by the tertiary amine unit in the metallacyclic framework instead of a thioether function, a carbocyclic product 71 is obtained (see under carbocycle reactions, next section). The formation of the seven-membered S-heterocycles is attributed to the good coordinative ability of the thioether group in 7. The S-atom remains close to the vinylic carbon function before the cyclization. With the poorly coordinating, readily displaced amine function in 8, the N-atom is detached from the metal and ultimately affords a spirocyclic product (see Scheme 18). 

It is believable that the pyrazoline, 4 or 5, undergoes thermolytic decomposition and gives the diradical 6 first. Then, the diradical formed a bond quickly to give the cyclopropane 1 This could be a reversible reaction between the diradical 6 and the cyclized product 7. 

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