Porter 1 Radical Addition Reactions

A decade ago, radical reactions were thought to be of little use in synthesis due to lack of selectivity. Much progress has recently been made in this domain, and it has even become possible to control the stereoselectivity in many radical reactions [1469]. Curran, Giese, Porter and their coworkers initiated the study of asymmetric radical addition reactions by introducing chiral residues either on the radical precursor or on the alkene. 

In 1995, Porter et al. [34] reported the first excellent results for free radical addition to an electron-deficient alkene by use of chiral zinc complexes. Reaction of the oxa-zolidinone 9 with tert-butyl iodide and allyltributylstannane 30 in the presence of Zn(OTf)2 and a chiral bis(oxazoline) ligand 12 gave the adduct 44 in 92 % yield with 90 % ee (Sch. 18). The chiral bis(oxazoline) complexes derived from ZnCl2 or Mg(OTf)2 gave racemic products. In this reaction, lower allyltin/alkene ratios gave substantially more telomeric products, and a [3 + 2] adduct 45 of the oxazolidinone 9 and the allylstannane 30 was obtained at temperatures above 0 °C. 

Within the past decade, diastereosolective radical reactions have become feasible and the factors contolling selectivity defined. Chiral auxiliaries for radical reactions have been recently developed in analogy to those developed for carban-ion chemistry in the 1970s and 1980s. The first example of stoichiometric use of a chiral ligand for enantioselective radical additions was recently reported by Porter and coworkers [59,60,61]. Reaction of the amide 14 with allyltrimethyl-silane at -78 °C, initiated by triethylborane, in the presence of 1 equiv. each of zinc triflate and the chiral bidentate ligand 15, provided the allylated product in a yield up to 88% and ee of 90%, Eq. (18). The presumed intermediate is the a-keto radical complexed to the chiral Lewis acid. 

Another application of asymmetric radical additions, proposed by Giese, Porter and coworkers [276, 334, 1475], is the addition of c-CgHji or ferf-Bu radicals to chiral acrylamides 7.124 (R = H) and 7.125 (R = H) followed by trapping of the initial radical adduct by an acceptor such as a thiopyridone or allyltribu-tylstannane. These reactions are carried out between -35 and + 80°C, and they are highly diastereoselective (Figure 7.78). The adduct radicals are trapped on the least hindered face of the conformation in which A(l,3) strain and dipolar interactions are minimized [454],... 

The addition of peroxyl radicals to double bonds is generally not very fast, and even with p-carotene the rate constant is less than 106 dm3 mol 1 s 1 (Mortensen and Skibsted 1998). Nevertheless, peroxyl radicals of multi-unsaturated compounds have been reported to undergo chain-like peroxidation if the C-C double bonds are suitably disposed [cf. reaction (20) Porter et al. 1980,1981]. 

Scheme 3 shows the effect of Lewis acid on atom transfer reactions. Since Lewis acid complexation can increase the electron-withdrawing nature of a group involved in a complex, it should also increase the rate of addition of alkenes onto a-carbonyl radicals. Both our group [7] and Porter s group [8] have improved the scope of... 

Besides the addition of halogens and hydrohalogens across the double bond just covered, there are many other reagents that will react similarly with unsaturated polymers by free radical, ionic, or radical-ion mechanisms. Of prime importance is the addition of ethylene derivatives to polydienes. One of the earliest reactions of natural rubber to be studied in detail was the combination with maleic anhydride (Cunneen and Porter, 1965). Depending on the reaction conditions and the presence or absence of free radical initiators, one or more of four basic reactions may take place, with the products shown (the arrows indicate where the addition has taken place and the new bonds formed). 

Wu JH, Radinov R, Porter NA. Enantioselective free radical carbon-carbon bond forming reactions chiral Lewis acid promoted acyclic additions. J. Am. Chem. Soc. 1995 117 (44) 11029-11030. 

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