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

Abstract

Neurotoxic organotin reagents currently play a key role in radical chemistry. As a result, this is an important area for development of new clean replacement reactions. The pharmaceutical industry in particular has had to avoid 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 nontoxic 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 functionalization, installing a useful polar group at the site of the ultimate radical. Two methods for effecting radical reactions in an environmentally friendly way are presented: (i) The tetrathiafulvalene (TTF)-mediated radicalpolar crossover reaction converts arenediazonium salts to aryl radicals, which have sufficient lifetime to cyclize onto alkenes-the resulting alkyl radicals couple with TTF +• to afford sulfonium salts which, in turn, undergo solvolysis to alcohols, ethers or amides. The method provides the key step in a synthesis of (±)-aspidospermidine. (ii) Hypophosphite salts and hypophosphorous acid, on the other hand, form C-C bonds with reductive termination. These economical reagents afford radicals efficiently, starting from aryl iodides, alkyl bromides, and alkyl iodides, and give very easy separation of products from by-products.

Summary of Existing Models of the Ni‐P Coating Electroless Deposition Process

“…The phosphorus‐centered radical [HPO 2 − ]• was detected in these studies. There is much work presenting reactions, in which hypophosphites, including sodium hypophosphite, act as a radical‐chain carrier . There are also data indicating that the first coating layer on the substrates having aluminum or iron appears via the exchange reaction : …”

Green chemistry: the emergence of a transformative framework

“…. Tributyltin hydride, a known neurotoxin, can be replaced by a hypophosphite salt in reductive termination of free-radical reactions (125). Organotin antifoulants (e.g.…”

N,2,3,4‐Tetrasubstituted Pyrrolidines through Tandem Lithium Amide Conjugate Addition/Radical Cyclization/Oxygenation Reactions

“…Exclusive 2,3-trans and up to 6:1 3,4-cis/trans diastereoselectivities were achieved in the targeted tetrasubstituted pyrrolidines. tive generation of multiple types of reactive intermediates, such as carbanions, radicals, or carbocations, at will, [11] thus overcoming potential reactivity pitfalls. [12] Such polar-radical or radicalpolar crossover reactions have found a number of applications in natural product synthesis.…”

“…Single‐electron transfer (SET) is the key to the interconversion of radical and polar intermediates by overall oxidative, reductive, or redox‐neutral pathways . It also enables the consecutive generation of multiple types of reactive intermediates, such as carbanions, radicals, or carbocations, at will, thus overcoming potential reactivity pitfalls . Such polar–radical or radical–polar crossover reactions have found a number of applications in natural product synthesis …”

“…entries 1-4, 6, and[10][11]. The lithium amide derived from prenylamine 2b reacted less selectively in the polar conjugate addition with 1d, 1f or ethyl (E)-4-{[(tert-butyl)dimethylsilyl]oxy}but-2-enoate; this translated into low yields of pyrrolidines 6 and 7, and the formation of inseparable side products (not shown).…”