Stereochemistry Friedel-Crafts alkylation

Suga et al. studied the SnCU- or AlCb-catalyzed Friedel-Crafts alkylation of benzene with (R)-(+)-1,2-epoxybutane (27) to investigate the stereochemistry of the ring-opening process. The primary products were (/ )-(-)-(28), with almost 100% optical purity, and (S)-(-)-(29), with 55-56% optical purity (Scheme 7). 

The next step is a simple electrophilic attack by another molecule of formaldehyde on the alkene - in other words a simple Prins reaction 215 - showing the regioselectivity we expect to produce the secondary benzylic cation 216. The second molecule of formaldehyde has added onto the opposite side from the first. The resulting cation is perfectly placed for an intramolecular Friedel-Crafts alkylation 216 of the benzene ring. This is again a stereoselective reaction giving the more stable anti diastereoisomer 214. This sequence involves three successive C-C bondforming reactions and the stereochemistry is simply controlled by the preference for the more stable anti product. 

To disconnect a 1,3-diX compound not at the carbonyl oxidation level we must first alter the oxidation level by FGI, If the TM contains no oxygen substituent, we must produce one by substitution. Japanese chemists wished lo study the stereochemistry of the Friedel-Crafts alkylation and chose to make optically active (43) for this purpose. Disconnection of the ester reveals a 1,3-diX relationship, and adjustment of the oxidation level to the acid (44) takes us back to simple starting materials. 

Friedel-Crafts chemistry at an asymmetric center generally proceeds with racemization, but the use of mesylates or chlorosul-fonates as leaving groups has resulted in alkylations with excellent control of stereochemistry. The reactions proceed with inversion of configuration (eq 3). Cyclopropane derivatives have been used as three-carbon units in acylation reactions (eq 4). In conjunction with triethy Isilane, a net alkylation is possible under acylation conditions (eq 5). These conditions are compatible with halogen atoms present elsewhere in the molecule. Acylation reactions of phenolic compounds with heteroaromatic systems have also been accomplished (eq 6). ... 

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