Homobenzylic ether cleavage

This work and related studies provided the basis for the stereoelectronic model for homobenzylic ether cleavage in Fig. 3.1. This model includes overlap of the benzylic carbon-carbon bond with the SOMO of the aromatic ring (structure 13), thereby stabilizing the benzylic radical upon cleavage. Additionally, overlap of a heteroatom lone pair and the benzylic o orbital was shown to be necessary for cleavage (structure 14). 

Arnold s demonstration" that oxocarbenium ion intermediates can be formed through homobenzylic ether radical cation fragmentation reactions shows that mild oxidizing conditions can be used to prepare important reactive intermediates. Scheme 3.2 illustrates a critical observation in the development of an explanatory model that allows for the application of radical cation fragmentation reactions in complex molecule synthesis. In Arnold s seminal work, cleavage of the benzylic carbon-carbon bond in substrate 1 is promoted by 1,4-dicyanobenzene (DCB) with photoirradiation by a medium-pressure mercury vapor lamp. With methanol as the solvent, the resulting products were diphenylmethane (2) and formaldehyde dimethyl acetal (3). 

Several of the reactivity patterns that were observed in the development of the oxidative carbon-carbon bond forming reactions were evident in the ETIC reaction of compound 56 (Scheme 3.19). Two homobenzylic ethers that potentially could fragment are present in this substrate. Cleavage in the presence of CAN was observed exclusively at the site that contains the geminal methyl groups, however, resulting in the formation of tetrahydropyran 57. This cyclization, which was used in the synthesis of a subunit of the cytotoxin apicularen demonstrated that fragmentations can be... 

Floreancig [42] has described a new solid-phase linker system cleaved by oxidative electron transfer. The cleavage process is based on the oxidative fragmentation of homobenzylic ethers. Acetal 230, immobilized on a soluble oligonorbornene scaffold prepared by ROMP polymerization, was efficiently... 

This project arose from a desire to find a tmique application for some methodological work that my group had developed on oxidative carbocation formation. This process (Scheme 1) showed that oxocarbenium and acyliminium ions could be formed from oxidative cleavage reactions of homobenzylic ethers and amides, respectively. Cychzation reactions ensued when a nucleophilic group was incorporated into the cationic fragment. 

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