Radical Cyclization by Ipso Substitution of the Methoxy Group:  Considerable Effect of HMPA on Samarium-Mediated Cyclization

Abstract

Alkyl radicals generated by treatment of thiocarbamates of conformationally favorable 3-alkyl-3-arylpropan-1-ols with tris(trimethylsilyl)silane and AIBN efficiently undergo intramolecular ipso substitution of the methoxy group, yielding the corresponding cyclized products. In contrast, either conformationally favorable or flexible 1-arylalkan-3- or 4-ones easily cyclize into five- or six-membered condensed rings by treatment with SmI(2) via ketyl radical intermediates. The addition of HMPA as cosolvent dramatically changes the cyclization mode of the SmI(2)-induced reaction, and the para-cyclization products are exclusively formed. This "HMPA effect" can be rationalized by the strong chelating ability of HMPA with the samarium atom.

Samarium Diiodide Mediated Ketyl–Aryl Coupling Reactions – Influence of Substituents and Trapping Experiments

“…Tanaka et al also studied substrates with two or more substituents, in particular the combination of alkoxycarbonyl substituents and methoxy groups. [30] They could demonstrate that in the absence of HMPA the coordination of samarium(II) diiodide to o-methoxy groups has a strong influence on the reaction outcome, mainly leading to ipsosubstitutions. In the presence of the strong ligand HMPA the interaction of Sm II with the oxygen containing substituents should be less important.…”

Construction of pyrrolophenanthridinone scaffolds mediated by samarium(II) diiodide and access to natural product synthesis

“…Previously, we reported that the ketyl radical ipso substitution reaction of an aromatic methoxy group is effectively promoted by SmI 2 without HMPA to afford cyclized products. 17 Thus, we examined the reaction of 7h with LiBr instead of HMPA or without an additive. Unexpectedly, the yield of the ipso-substituted product was decreased or null compared with that when HMPA was used (entries 12 and 13 vs entry 11).…”

Development of Useful Reactions Involving Tandem Cyclizations Based on the Novel Reactivities of Allenic Compounds

“…Although space restriction does not permit a detailed description, our group developed some other interesting novel reactions such as (1) stereoselective synthesis of 1,3-amino alcohols via allenylindium reagents using 2-ethynylaziridines as chiral carbon nucleophiles, 143,144) (2) samarium(II)-mediated radical cyclization onto an aromatic group, [174][175][176][177][178] (3) synthesis and isomerization of vinylaziridines and their application to the stereoselective synthesis of (E)-alkene dipeptide isosteres. [64][65][66][67]179,180) The author hopes the presented reactions based on the novel reactivities of allenes will facilitate further development of allene chemistry [181][182][183] and application to synthesis of pharmacologically important compounds from this class of compounds.…”