Dual organocatalysis

With the development of the enantioselective allylic-allylic alkylation of a,a-dicyanoalkenes and MBH carbonates by dual organocatalysis of commercially available modified cinchona alkaloids and (5)-BINOL, Chen and co-workers have delivered an elegant construction of cyclohexene derivatives. The intramolecular Michael reaction of allylic allylic alkylation product 75a could be cyclized to give the desired cyclohexene 76 in the presence of DBU (Scheme 4.25). In the presence of nucleophile BnNH2, allylic compound 75b furnished an imexpected cyclic product 77 rather than the formal double Michael adduct. Interestingly, the reaction of a,a-dicyanoalkene 79 and MBH carbonate 80 under optimized catalytic conditions directly afforded cyclohexene derivatives 81a-c in... 

In 2009, Chen et al. reported the first highly enantioselective allylic-allylic alkylation of a,a-dicyanoalkenes with Morita-Baylis-Hillman carbonates by dual organocatalysis of commercially available modified cinchona alkaloids and S)-BINOL. Excellent stereoselectivities were achieved for a broad range of substrates by using hydroquinidine (anthraquinone-l,4-diyl) diether ((DHQD)2AQN) as the cinchona alkaloid. Indeed, in all the cases studied, only one diastereomer was isolated with both excellent enantioselectivity and yield, as shown in Scheme 5.9. 

Finally, a remarkable four-component tandem Michael-aza-Henry-hemi-aminalisation-dehydration tandem reaction was recently developed by Lin and co-workers on the basis of a dual organocatalysis involving a chiral diaryl prolinol trimethylsilyl ether and a chiral cinchona alkaloid." As shown in Scheme 2.37, the reaction began with the Michael addition of an aldehyde to a nitroalkene catalysed by the L-proline-derived catalyst, giving the corresponding intermediate aldehyde. The latter intermediate... 

Scheme 43.3 Allylic-allylic alkylation of a,a-dicyanoalkenes and Morita-Baylis-Hillman carbonates by dual organocatalysis.

Recently, a dual organocatalysis approach, namely, the combination of the achiral nucleophilic Lewis base catalyst DMAP (23) and the chiral anion-binding thiourea catalyst 27, was applied to the Steglich rearrangement to provide a,a-disubstituted amino acid derivatives 24 in a highly enantioselective fashion (Scheme 43.5) [14]. Notably, replacement of the nucleophilic codiamino acid derivatives with excellent enantiomeric excesses (88-93% ee). 

In 2007, Cordova and coworker [17] first found that amino and heterocyclic carbene catalysis could be combined in one-pot for the direct catalytic conversion of a,P-unsaturated aldehydes into valuable P-functionalized esters in good to high yields with excellent enantioselectivities (Scheme 43.8). The one-pot combination of chiral amine and heterocyclic carbene catalysis opens up the possibility of bio-mimetic asymmetric dual organocatalysis based on carbene catalysis. 

Chiral secondary amines are another important class of privileged functional component in dual organocatalysis that has been widely used in asymmetric catalysis [39]. For example, in 2008, Cordova et al. [40] reported the combinational use of (S)-diphenylprolinol TMS ether (127) and Br0nsted base DABCO (128) as dual organocatalysts to promote the asymmetric domino double Michael addition reaction (nitro-Michael/Michael reaction) of 5-nitropentenoate (125) to a,(i-unsaturated aldehydes (Scheme 43.26), which gave the corresponding nitrogen-,... 

---