Free radicals in synthesis. Clean reagents affording oxidative or reductive termination

Neurotoxic organotin reagents currently play a key role in radical chemistr y. As a result, this is an important area for development of new clean repl acement reactions. The pharmaceutical industry in particular has had to avo id use of radical methodology for the formation of carbon-carbon bonds for this reason. With the current dawn in green chemistry, a host of new clean radical methods is beginning to flourish. Our aim has been to develop new n ontoxic methodology for carbon-carbon bond formation by radical chemistry, which would provide either reductive termination (giving a hydrogen atom to the ultimate radical, as happens with tributyltin hydride), or oxidative f unctionalization, installing a useful polar group at the site of the ultima te radical. Two methods for effecting radical reactions in an environmental ly friendly way are presented: (i) The tetrathiafulvalene (TTF)-mediated ra dical-polar crossover reaction converts arenediazonium salts to aryl radica ls, which have sufficient lifetime to cyclize onto alkenes-the resulting al kyl radicals couple with TTF+. to afford sulfonium salts which, in turn, un dergo solvolysis to alcohols, ethers or amides. The method provides the key step in a synthesis of (+/-)-aspidospermidine. (ii) Hypophosphite salts an d hypophosphorous acid, on the other hand, form C-C bonds with reductive te rmination. These economical reagents afford radicals efficiently, starting from aryl iodides, alkyl bromides, and alkyl iodides, and give very easy se paration of products from by-products.