Lewis acid-mediated radical reaction

Curran, D. R Porter, N. A. Giese, B. Stereochemistry of Radical Reactions, VCH, Weinheim, 1995. For an excellent recent review on Lewis acid mediated radical rcaclions see Rcnaud, R Gerster, M. Angew. Chem., Int. Ed. Engl. 1998, 37, 2562-2579. 

Similar to the addition of secondary phosphine-borane complexes to alkynes described in Scheme 6.137, the same hydrophosphination agents can also be added to alkenes under broadly similar reaction conditions, leading to alkylarylphosphines (Scheme 6.138) [274], Again, the expected anti-Markovnikov addition products were obtained exclusively. In some cases, the additions also proceeded at room temperature, but required much longer reaction times (2 days). Treatment of the phosphine-borane complexes with a chiral alkene such as (-)-/ -pinene led to chiral cyclohexene derivatives through a radical-initiated ring-opening mechanism. In related work, Ackerman and coworkers described microwave-assisted Lewis acid-mediated inter-molecular hydroamination reactions of norbornene [275]. 

A potential method for the preparation of novel amino acids via the highly selective addition of radicals to the glyoxylic oxime derivative of Oppolzer s camphor sultam (88) has been reported.181 Both Lewis acid and non-Lewis acid-mediated reaction conditions for the addition of alkyl radicals generated from alkyl iodides and Et3B/Bu3SnH were examined. A new chiral auxiliary based upon (R,R)-2,5-diphenylpyiTolidine has been used in the addition of phenylthiyl radicals to unsaturated methacrylamides. The selectivity was found to be better than that reported for the structurally related 2,5-dimethylpyrrolidine derivative.182... 

In one of the earliest reports on enantioselective radical reactions, chiral Lewis acid mediated conjugate addition followed by enantioselective H-atom transfer a to a carbonyl was reported by Sato and co-workers (Scheme 3) [22], The single point binding chiral aluminum complex presumably coordinates to the carbonyl oxygen of the lactone as shown in 10. The strong Lewis acidity of the aluminum complex activates the substrate 7 to nucleophilic conjugate addition, which is followed by an enantioselective H-atom transfer from BuaSnH in a chiral environment provided by BINOL ligand in 8. Only 28% ee was observed for product 9. 

An enantioselective reduction of an a-iodolactone under radical conditions has been reported [95CC481]. Treatment of 207 with tin hydride, magnesium(II) iodide and in the presence of a chiral amine gave the 8-lactone 208 in good yield and moderate enantioselectivity. This is one of the first examples of chiral Lewis acid mediated enantioselective radical reactions. 

The formation of a quaternary carbon center by the radical-mediated allylation of an a-iodolactone was examined for substrate 341 by Murakata, Jono, and Hos-hino [71]. Lewis acids for this reaction were prepared from a bis-sulfonamide and tri-methylaluminum in dichloromethane. Other aluminum compounds were employed in the preparation of the catalyst but all resulted in similar or lower asymmetric induction. The Lewis acid was complexed with the lactone and then the allylation procedure in Sch. 44 was performed. It was found that superior asymmetric induction could be achieved if the Lewis acid was prepared from the ligand with two equivalents of trimethylaluminum. It was also interesting that some turnover could be achieved, as indicated by the data obtained from use of 50 mol % catalyst. 

Although copper reagents, hahdes and triflates, are widely used in atom-transfer polymerization reactions (ATRP) [63], these processes do not fall under the category of Lewis acid-mediated reactions. Sherrington and co-workers have shown that a vinyl monomer coordinated to a chiral copper Lewis acid (122) undergoes stereoselective polymerization (Sch. 29) [64]. A chiral block-copolymer 124 was prepared under radical conditions. 

Metal-mediated and metal-catalyzed reactions require a transition metal. However, certain transition-metal complexes (e.g., TiCU, FeCl3) act only as Lewis acids in organic reactions, and others (TiCl3, Sml2) act as one-electron reducing agents like Na and Li reactions promoted by these compounds are classified in polar acidic, pericyclic, or free-radical classes. 

Sibi and Ji reported that acyl radicals, generated from acyl bromides, can participate in Lewis acid-mediated diastereoselective radical addition reactions (Scheme 4-26) [49]. Using triethylborane/02 as a radical initiator, the reaction was conducted at -78 °C. 

Lewis Acid-Mediated Diastereoselective Radical Reactions... 

One of the more commonly used organotin reagents in both free-radical reactions and Lewis acid-mediated reactions is allyltributyltin [3, 7]. This reagent permits the construction of new carbon-carbon bonds from free radical precursors such as alkyl halides however, reactions with a-ketocydopropanes were poorly understood. Tin(IV) enolates generated from a-ketocyclopropane 44 and allyltributyltin undergo both radical allylation and electrophilic quench as shown in Scheme 11, forming O-stannyl ketyl 45 with allyltributyltin and subsequent scission of the cyclopropane... 

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