Radical reactions, chiral metal complexes

Previously, examples of chiral Lewis acid coordination of either the radical or radical acceptor involved coordination to Lewis basic sites, typically oxygen or nitrogen. However, certain transition metals are also capable of coordination to al-kenes and, if complexed to a chiral ligand, can also afford chiral addition products. This has been illustrated in the enantioselective atom transfer additions of alkane and arene-sulfonyl chlorides and bromotrichloromethanes to olefins using chiral ruthenium complexes. These reactions are thought to follow a radical redox chain process detailed in Eq. (20). 

Thus, this first example of stereoselective radical reaction, initiated with the system based on Fe(CO)5, shows opportunities and prospects of using the metal complex initiators for obtaining the stereomerically pure adducts of bromine-containing compounds to vinyl monomers with chiral substituents. 

Very recently, chiral tricarbonylchromium complexes have been introduced as novel chiral auxiliaries for aza Diels-Alder reactions [192, 193]. Using the brominated imine 3-8, Kiindig s group was successful in efficiently generating enantiopure polycyclic compounds such as 3-10 by cycloaddition of 3-8 to l-methoxy-3-trimethylsilyloxy-l,3-butadiene (Danishefsky s diene), subsequent radical cyclisation of the cycloadduct 3-9 and oxidative metal removal from 3-11 (Fig. 3-3). 

Radical reactions have been recognised only recently for the construction of enantiomerically pure compounds (Renaud and Sibi 2001 Zimmerman and Sibi 2006). In addition to substrate- or auxiliary-induced diastereoselective radical reactions, and in addition to the use of chiral Lewis acids, chiral hydrogen atom donors or chiral transition metal complexes, template molecules can be used to generate a chiral environment and induce chirality to the substrate. With the chiral complexing agent 12, enantioselective radical reactions were achieved with enantiomeric excesses up to 99% ee. 

These selected examples show the importance of Lewis acid in diastereoselective radical reactions. Complexation with Lewis acid, in an endocyclic manner or by using extremely bulky metal complexes such as MABR or MAD, reduces the conformational flexibility of intermediate radicals resulting in an improved facial bias. Lewis acid has been shown to effectively enhance facial selectivity by making a temporary ring a to the radical, thus mimicking the exocyclic effect. Radical reactions involving chiral auxiliaries have also benefited from the use of Lewis acid. 

The radical mechanism of OA occurs only for polar substrates. A free radical initiator (I) is made, typically by photolysis or electrochemical means. The initiator reacts with the metal complex to oxidize it by one electron, as shown in Figure 19.10. The species can then react with RX to generate R-. The R- radical undergoes a chain reaction with a second metal complex to make R-M " -X and another R- radical. This continues until chain termination by two R radicals coupling together or by radical trapping. The propagation step in the mechanism competes with isomerization or racemization of R-, so that the product is almost always a racemic mixture of optical isomers when a chiral C atom is used. Unlike the S 2 mechanism, the rate of the reaction is independent of steric bulk on the transition metal. Furthermore, the reaction sequence with respect to 3°>2°> I >CH3 (which maps with the... 

The addition of sulfonyl chlorides to alkenes In the presence of a catalytic amount of dIchlorotris(triphenylphosphIne) ruthenlum(II) affords 1 1 adducts. Under these reaction conditions It Is believed that sulfonyl radicals, which are confined to the coordination sphere of the metal complex, are involved. When the chiral phosphine (—)-DIOP ((2,3-0-isopropylidene)-2,3-dihydroxy-l,4-bis(diphenylphosphino)butane) is used as a ligand, the addition of 4-methoxybenzenesulfonyl chloride to styrene proceeds to provide the (R) isomer in 40% ee (eq 2). ... 

The functionalization of zinc porphyrin complexes has been studied with respect to the variation in properties. The structure and photophysics of octafluorotetraphenylporphyrin zinc complexes were studied.762 Octabromoporphyrin zinc complexes have been synthesized and the effects on the 11 NMR and redox potential of 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetraarylporphyrin were observed.763 The chiral nonplanar porphyrin zinc 3,7,8,12,13,17,18-heptabromo-2-(2-methoxyphenyl)-5,10,15,20-tetraphenylporphyrin was synthesized and characterized.764 X-ray structures for cation radical zinc 5,10,15,20-tetra(2,6-dichlorophenyl)porphyrin and the iodinated product that results from reaction with iodine and silver(I) have been reported.765 Molecular mechanics calculations, X-ray structures, and resonance Raman spectroscopy compared the distortion due to zinc and other metal incorporation into meso dialkyl-substituted porphyrins. Zinc disfavors ruffling over doming with the total amount of nonplanar distortion reduced relative to smaller metals.766 Resonance Raman spectroscopy has also been used to study the lowest-energy triplet state of zinc tetraphenylporphyrin.767... 

Chiral samarium (II) complexes have also been applied towards the hydrodimerization of acrylic acid amides [16]. Such reactions involve the ligand-controlled dimerization of conjugated ketyl radicals in the enantioselective formation of 3,4-tra .y-disubstituted adipamides (Eq. 11). Yields were mainly low, often under 40% and enantiocontrol was modest with selectivities ranging from around 50-85% ee. A nine-membered chelated transition state 37 is used to rationalize the stereoselectivity of the dimerization where the ligand-bound conjugated ketyl radicals are oriented cis to each other on the metal assuming an octahedral geometry. 

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