Diarylprolinols catalysts

Catalytic asymmetric propargylation has been reviewed (131 references). Aldehydes have been propargylated in up to 99% yield and 92% ee by allenyl-zinc reagents, generated in situ from the action of diethylzinc on iodoallene (or 3-iodopropyne), with a bulky diarylprolinol catalyst. The reaction is conveniently carried out in DCM at low temperature and avoids the use of tin reagents. ... 

In this chapter we will deal with organocatalytic asymmetric transformations using these catalysts, mainly focusing on the significant and major achievements in this area published from 2000 to 2011. However, due to space constraints, this chapter will not cover the great utiHty of diarylprolinol catalysts (category F) for convenience, only references are given [3]. 

By applying nucleophiles with known nucleophiUcities, the electrophiUcity parameters ( ) could be determined by kinetic experiments. Interestingly, in light of the increased steric bulk, the diarylprolinol catalyst-derived iminium ion was found to be 20 times more reactive than the one formed from pyrrohdine [lOj. This increased reactivity is attributed to the electron-withdrawing effect of the aryl substituents. Notably, the intermediate derived from the imidazolidinone-based catalyst showed the highest electrophilicity. 

The ability of the diarylprolinol catalysts to participate in both enamine- and iminium-ion achvations makes them ideal for the sequential addition of nucleophiles and electrophiles through cascade catalysis (Scheme 2.8). Conjugate addition of a nucleophile to the iminium ion forms a transient enamine intermediate 3, which can effectively react with an electrophile in the a-position, forming an a,P-disubstituted adduct. This process commonly proceeds to afford the products in good yields and with high enantio- and diastereoselectivities. If the nucleophile and electrophile are part of the same molecule, cyclic products are obtained. The cascade concept has been widely explored and some illustrative examples are given below [13, 17]. 

The carbanion -type reactivity of dienamine activation can be promoted by a silyl-protected diarylprolinol catalyst in the presence of reactive electrophilic species, such as nitroolefins or diarylmethanols (Scheme 2.10) [20]. Although both direct addition (a-addition) and vinylogous addition (y-addition) are viable reaction pathways, the a-reactivity is the more typical one and usually provides better selectivities due to more effective shielding of the a-position by the aminocatalyst. Interestingly, the a-/y-selectivity of dienamine-mediated carbanion -type addition reactions seems to be strongly influenced by the substitution pattern of the enal reactant For example, it was demonstrated that y,y-disubstituted enals favor the a-addition product while y-functionaUzation is the predominant reaction pathway for y-monosubstituted enals. 

Given the excellent ability of the diarylprolinol catalyst to secure facial discrimination and conformational restriction, high stereoselectivities are often achieved in these reactions. Selective reaction at the proximal double bond of (E,s-trans,E)-4 has, for example, been accomplished, resulting in formal inverse-electron-demand hetero-Diels-Alder reactions [21], Alternatively, several reports have concluded that selective targeting of the distal electron-rich alkene motif of the catalyst-bound intermediate is also viable [22],... 

For selected examples of carbanion -type dienamine activation promoted by silyl-protected diarylprolinol catalysts, see ... 

For selected examples of diene -type dienamine activation promoted by silyl-protected diarylprolinol catalysts, see (a) Bertelsen, S., Marigo, M., Brandes, S., Diner, P., and Jorgensen, K.A. (2005)... 

Fig. 7.26 Higher substituted a,a-diarylprolinol catalysts employed in epoxidation reactions...

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