Michael addition stereoselectivity enhancement

Michael additions of ketone enolates. The stereochemistry of Michael additions of lithium enolates of ketones to a,(3-enones is controlled by the geometry of the enolate. Addition of (Z)-enolates results in anti-products with high diaster-eoselectivity, which is not changed by addition of HMPT. Reaction of (E)-enolates is less stereoselective but tends to favor syn-selectivity, which can be enhanced by addition of HMPT. 

Pore engineering of COFs is an important aspect to explore their applicability towards a wide field of uses. A covalently linked porphyrin-COF catalyst has been synthesized using imine groups by attaching organoca-talytic sites onto the pore walls of the synthesized COF (Figure 9.3). Such a kind of surface activation provides enhanced activity in the stereoselective asymmetric Michael addition reaction. Recyclability and continuous catalytic ability are the key features of this COF catalyst. 

The synthesis is initiated by the organocatalyzed cascade that activates a,p-unsaturated aldehyde 8 with the formation of an iminium ion (Scheme 14.2). In this way, the imidazolidinone catalyst allows hydride transfer from the Hantzsch dihydropyridine 9 onto the highly activated conjugated alkene 11, which creates the nucleophilic enamine intermediate 12. Because of the chirality of the organocatalyst, stereoselective Michael addition (97% ee) to the adjacent enone occurs, with minor preference for the cis diastereomer (2 1 dr). Fortunately, this undesired diastereomer slowly epimerizes to the required trans isomer, which produces (-l-)-ricciocarpin A when treated with samarium triisopropoxide. Besides the Cannizzaro-like redox disproportionation, which allows the lactone producing Evans-Tihchenko reaction to occur, samarium(III) also enhances the epimerization to the trans isomer and therefore produces the desired isomer in high selectivity. 

These naturally occurring products were targeted by Hayashi and coworkers in 2013 in a similar manner using a Michael/Henry reaction cascade, employing prolinol 17 to effect the highly stereoselective Michael addition at room temperature [13], Subsequent base (DtPEA) addition enhances the slow Henry reaction to completion in high selectivity. Finally, phosphonate 36 initiates a Horner-Wadsworth-Eimnons (HWE) reaction in the same pot to yield the intermediate 37 (76 17 7 dr) (Scheme 14.5). 

A dramatic enhancement of stereoselectivity has been observed when using as a solvent for the Michael addition of / -dicarbonyls to nitroalkenes, catalysed by (325). Thus, in toluene, the reaction afforded the product with 5 1 dr and 46% ee, whereas in CsFg these figures were improved to 24 1 dr and 90% ee. DFT calculations were employed to rationalize the origin of this effeet. ... 

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