Desymmetric Michael reactions cyclohexadienones

A strategy for the desymmetrization of cyclohexadienones via asymmetric aza-Michael reaction using cinchonine-derived thiourea 52 was developed by You s group (Scheme 11.33) [113]. A series of highly enantioenriched bicyclic pyrrolidine and morpholine derivatives were obtained in excellent yields and enantioselectivities. 

Desymmetrization of cyclohexadienones bearing a bisphenylsulfonyl methylene group (164) via asymmetric Michael reaction catalysed by the cinchonine-derived urea (166a) has been reported to afford cyclization products (165) with <91% eeP ... 

You and coworkers developed a desymmetrization protocol based on an intramolecular oxo-Michael reaction, using as catalyst the phosphoric acid derivative 121 [110]. Cyclohexadienones 120 were transformed into the corresponding bicyclic systems 122 with high yields and enantioselectivities. Remarkably, the 4-substituent in the cyclohexadienone has a great influence on the enantioselective outcome of the reaction. Bulkier substituents at the 4-position lead to lower reaction rates and enantioselectivities (Scheme 33.35). This desymmetrization reaction was used as a key reaction for the efficient synthesis of the natural products cleroindicins C,... 

Recently, an oxidative dearomatization of substituted phenols followed by a desymmetrizing asymmetric intramolecular Michael addition catalyzed by the pro-linol derivative 27 has been described towards the synthesis of highly functionalized polycyclic molecules with excellent enantioselectivities [40]. As shown in Scheme 2.15, the reaction starts with an oxidation of the phenol moiety to the corresponding mera-cyclohexadienones employing PhlCOAc), mild oxidant that does not react with the aldehyde nor with the catalyst. In the presence of different nucleophiles such as, methanol, cyanide, or fluoride, intermediates 26 are formed, which suffer intramolecular Michael addition of the aldehyde moiety to afford the desired chiral products 28 with excellent diastereo- and enantioselectivities. 

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