Ring-opening/spirocyclization

This method has also been incorporated into an inverse electron demand-HDA/ ring-opening/spirocyclization cascade [189] for the synthesis of bis(benzannulated) 5,5-spiroacetals (Scheme 92). 

The epimerization likely occurs through an enamine retro-aAAol reaction after formation of the initial cyclized product (92) (Scheme 6.16) [47]. First, a ring opening of 92 forms the enamine-aldehyde (93a). Rotation about the C-C a-bond in 93a provides intermediate 93b in which enamine addition to the aldehyde to reclose the ring would give 93c. After protonation of the enolate, 91 would result with an overall epimerization of the spirocyclic carbon. In addition to the 2D NMR data, we also planned a complement of experiments to support the epimerization assignment. 

The reaction of [H2C(SiMe3)2C]2Si 180 with cyclopropylmethyl chloride proceeds via ring opening and formation of product 192 containing a spirocyclic Si atom, whose formation can be attributed to a radical-reaction pathway... 

Cycloadditions with other symmetrical acetylenes were carried out by using thiocarbonyl (5)-methylide (69) (159). Interestingly, no reaction was observed when acetylene dicarboxamide was used. The reaction of 69 with cyclooctyne resulted in the formation of cycloadduct 103 (Scheme 5.38). Interestingly, the spirocyclic 2,5-dihydrothiophenes of type 103 or 104 undergo acid-catalyzed ring opening upon treatment with silica gel or trifluoroacetic acid to give thiophenes 105 and 106, respectively. 

The silver(I)-mediated electrocyclic ring opening of halocyclopropanes has been used to induce extensive skeletal rearrangements in gcm-dibromospiropentanes, providing rapid construction of naphthalenes and/or indenes (Scheme4.21 ).34 A variety of Lewis acids, Brpnsted acids, and solvent effects were carefully examined before optimal conditions were identified. It was found that subjection of spirocycle 60 to silver acetate in trifluoroacetic acid afforded rearrangement products 61 and 62 in moderate to good yields. The proposed mechanism of the reaction is illustrated in Scheme 4.21. 

An unusual 4-exo-trig cyclization accompanied by a later rearrangement was observed with aryl enolether 13 (Scheme 6) [48], The benzoxetane 14, which is formed in the initial cyclization step, undergoes ring-opening to form the phenoxy radical 15. 5-Endo cyclization of 15 and reduction of the resulting benzylic radical leads to the spirocycle 16. Diverse polycyclic products have also recently been obtained by intramolecular aryl radical cyclizations to tetrahydropyridines [49]. 

Fused heterocyclic tertiary enaminones were later reported to similarly give the corresponding isoxazoles and pyrazoles188 (equation 131). The products of the Anand reaction would be the result of nucleophilic attack at the a-carbon of the enaminone followed by spirocyclization and ring opening. His observations are in clear contrast to the results of Dannhardt and coworkers who have recently189 used the closely related... 

The analogous thiirenium ion derived from l,5-dithia-cyclonon-7-yne 32 could not be isolated but instead the spirocyclic compound 33 was obtained (Scheme 3). The reactions were proposed to proceed through an intermediate a-thiocarbonyl-stabilized carbene analogous to the ring opening of oxirenes (Scheme 4) <2002JA8316>. 

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