Diarylprolinol Derivatives in Organocatalysis From Another Point of View: Structural Aspects

Abstract

The synthesis of complex active molecules has afforded the search for new methods and new processes in organic synthesis. In this context, organic metal free catalysis has appeared as a powerful tool being complementary to metal catalysis in the field of asymmetric synthesis. The success of this methodology has been increasing in the last decade and the research for new organocatalytic systems as well as new applications has attracted the interest of many research groups. Among all organocatalysts, diarylprolinol derivatives have emerged as powerful scaffolds for asymmetric catalysis, proof of that is the huge number of publications reported using this kind of structure as catalysts. However, only in a few cases, different aspects of the catalysts structures and additional additives have been largely studied and a plausible explanation has been given. In this sense, this review treats to illustrate these important and scarce examples and to give a very general vision relating to the application of diarylprolinol derivatives in organocatalytic transformations from another point of view: structural aspects. The influence of catalyst structure, electronic effects, and the use of additives will be the aim of discussion and comment in this work.

Proline bulky substituents consecutively act as steric hindrances and directing groups in a Michael/Conia-ene cascade reaction under synergistic catalysis

“…Most importantly, the most stable TS-I steps lead to Michael reactions that occur on the opposite side of the proline substituent (–CPh 2 OTMS), as previously proposed by other authors (Fig. 5A, Type II attack) 48. Furthermore, no significant noncovalent interactions occur between this group of the catalyst and the attacking pyrazolone group ( 5a ).…”

Enhanced Efficiency of Thiourea Catalysts by External Brønsted Acids in the Friedel–Crafts Alkylation of Indoles

“…The use of a carefully chosen acidic or basic additive has been extensively studied in aminocatalysis; [14] however, it has been less considered in the field of (thio)urea catalysis; in these few cases the thiourea was the additive in the catalytic system, and it was used to enhance the activity of the corresponding acid catalyst. [15] To evaluate the potential of this idea, we started our investigation by exploring the reactivity of thiourea 1a with l-mandelic acid in a comparative study in the Friedel-Crafts alkylation reaction described in Scheme 1.…”

(S)-Proline-catalyzed nitro-Michael reactions: towards a better understanding of the catalytic mechanism and enantioselectivity

“…In our ongoing effort towards understanding the mechanism and origin of stereoselectivities of organocatalyzed Michael reactions, 18 we find that it is necessary to go beyond the simple hydrogen bond catalysis to offer a satisfactory explanation to observed enantioselectivity. In particular, we note that Michael reactions can be catalyzed by amine catalysts that lack a hydrogen bond donor, such as diarylprolinol ethers 19 and the above mentioned diamine catalysts, [15][16][17] without significant lost of catalytic efficiency or enantioselectivity compared to proline. This prompts us to carefully investigate the non-hydrogen bonded type of transition state.…”