Phase Lygo-Corey

In 1997 the Corey [1] and Lygo [2] groups disclosed the use of N-(anthracenyl)methyl-modified Cinchona alkaloids (e.g., 1) as catalysts in phase transfer alkylations, which afforded remarkable enantiomeric excesses of up to 99%. During the ensuing years, these groups have expanded the scope and limitations of these catalysts, as summarized below. 

A similar approach was reported by Lygo and co-workers who applied comparable anthracenylmethyl-based ammonium salts of type 26 in combination with 50% aqueous potassium hydroxide as a basic system at room temperature [26, 27a], Under these conditions the required O-alkylation at the alkaloid catalyst s hydroxyl group occurs in situ. The enantioselective alkylation reactions proceeded with somewhat lower enantioselectivity (up to 91% ee) compared with the results obtained with the Corey catalyst 25. The overall yields of esters of type 27 (obtained after imine hydrolysis) were in the range 40 to 86% [26]. A selected example is shown in Scheme 3.7. Because the pseudo-enantiomeric catalyst pairs 25 and 26 led to opposite enantiomers with comparable enantioselectivity, this procedure enables convenient access to both enantiomers. Recently, the Lygo group reported an in situ-preparation of the alkaloid-based phase transfer catalyst [27b] as well as the application of a new, highly effective phase-transfer catalyst derived from a-methyl-naphthylamine, which was found by screening of a catalyst library [27c],... 

In an attempt to develop a PEG-supported version of a chiral phase-transfer catalyst the Cinchona alkaloid-derived ammonium salt 15 used by Corey and Lygo in the stereoselective alkylation of amino acid precursors was immobilized on a modified PEG similar to that used in the case of 13. The behaviour of the catalyst obtained 16, however, fell short of the expectations (Danelli et al. 2003). Indeed, while this catalyst (10 mol%) showed good catalytic activity promoting the benzy-lation of the benzophenone imine derived from tert-butyl glycinate in 92% yield (solid CsOH, DCM, -78 to 23 °C, 22 h), the observed ee was only 30%. Even if this was increased to 64% by maintaining the reac-... 

Lygo and Corey groups and introduced a new era of asymmetric phase-transfer catalysis (Scheme 16.5). 

In 2000, Zhang and Corey extended the utility of Lygo s eatalyst 8n to the asymmetrie Miehael addition of acetophenone to 4-metho3grchalcone under mild phase-transfer conditions and proposed a mechanism predicting the configuration of the chiral-adduct." Two different views of the three-dimensional arrangements of 4-methoxychalcone, the enolate of acetophenone, and catalyst 8n are shown in Scheme 16.17. 

Corey et al. [20] developed the catalyst 12c, which showed superior results to Lygo s catalysts in the same reaction at very low temperature. They provided a general idea in the cinchona-based phase-transfer catalyst design the quaternary... 

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