Synthesis of Biologically Active Compounds Based on the Regio- and Stereo-Controlled Radical Cyclizations

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1. Radical cyclization of ω-haloalkenes having a sulfur atom or a nitrile group at the terminus of their alkenic bond was found to undergo in an exo manner exclusively. A mechanistic rationalization for the results was proposed and the methods were applied to the syntheses of the key intermediates for (±)-ipalbidine and (±)-physostigmine.2. Stereoselective synthesis of (3R^*, 3aS^*, 7aS^*)-3-aryloctahydroindol-2-ones using 5-exo radical cyclization was developed and the method was applied to a formal synthesis of (±)-pancracine.3. Formation of 6-endo cyclization products by radical reaction of N-vinylic 2-iodobenzamides was found to proceed through a consecutive 5-exo aryl radical cyclization and neophyl rearrangement.4. In the course of the study on the radical cyclization of N-(ο-bromobenzyl) enamides, we found a first example of the formation of 6-endo cyclization product onto alkene having no substituent on the alkenic bond. We also found that the enamides having two phenylthio groups at the terminus or the N-vinylic bond underwent radical cyclization in a 5-exo manner exclusively. The latter method was applied to the synthesis of a model compound of mappicine ketone, an anti-herpesvirus compound.5. The use of an iodine atom is recognized to give a better result than does that of a chlorine atom in the radical reactions of halogeno compounds. We found, surprisingly, that in the 5-endo cyclization of α-halo amides, the use of a chlorine atom gave the cyclization products in high yields, whereas that of an iodine atom gave only a limited amount of the expected cyclization product.6. Mu(OAc)_3/Cu(OAc)_2-mediated oxidative radical cyclization of α-(methylthio) amides was developed and the method was applied to a concise construction of an erythrinane skeleton.