Hydrogen bonds organocatalytic transition states

Consequently, the processes most relevant to the topic of this chapter, that is, hydrogen bonds in organocatalytic transition states, are (i) transition state stabilization by pure hydrogen bonding (without full proton transfer), and (ii) general Bronsted-acid/Bronsted-based catalyzed reactions which are initiated by hydrogen bonding but move further to distinct proton transfer. 

The different solvents, additives, and cosolvents present in the reaction media can assist in the stabilization of the transition state and favor one facial preference for the approaching of the substrates as depicted in proposed transition state D [52b] (Fig. 2.10) for the 32-catalyzed Michael addition of ketones to nitrostyrene. In this case, a cooperative hydrogen-bond solvent participation (represented by H O) takes place resembling the oxyanion hole commonly found in enzymes for stabilizing transition states. It seems then very clear that intra- and intermolecular hydrogenbonding interactions play a key role in the organocatalytic cycle. 

A similar scenario has been demonstrated by Najera et al. to support the bifunc-tional Br0nsted acid-base organocatalytic character and the origin of the observed enantioselectivity achieved by protonated 2-aminobenzimidazol-derived catalyst 163 in the conjugate addition of malonates and 1,3-diketones to nitroolefins [251]. DFT calculations have shown that the lowest energy transition state corresponds to the addition of the malonate or diketone to the electrophile with activation of the nucleophile by formation of two hydrogen bonds with the amino-benzimidazole moiety and activation of the nitroolefin better achieved by the protonated tertiary amine (C, Fig. 2.19). 

Xu, et al. developed an asymmetric organocatalytic Diels-Alder reaction of cyclohexenones (e.g., 38) with aromatic nitroolefins 60 in seawater and brine with excellent chemo-, regio- and stereoselectivities, Scheme 3.24 [38]. The study suggested that seawater or brine play a role in stabilizing the transition state through a hydrogen-bonding interaction and the cycUzation is involved in the one-step concerted addition pathway rather than a sequence of the Michael-Michael mechanism. 

A review has illustrated the importance of atomic-level DFT studies in elucidation of the function of hydrogen bonds in organocatalytic reactions through influence on the mechanism of substrate activation and orientation, and the stabilization of transition states and intermediates. Examples discussed include stereoselective catalysis by bifunctional thioureas, solvent catalysis by fluorinated alcohols in epoxidation by hydrogen peroxide, and intra-molecular cooperative hydrogen bonding in trans-a,a -(dimethyl-l,3-dioxolane-4,5-diyl)bis(diphenyl methanol) (TADDOL) (7)-type catalysts. ... 

---