Hydrogen-bonding activation nucleophiles

Redistribution of electron density in CT complexes results in a modification of the chemical properties of coordinated arenes, and this effect is widely used in organometallic catalysis [2]. To demonstrate the relationship between charge transfer in arene complexes and their reactivity, we focus our attention on carbon-hydrogen bond activation, nucleophilic/ electrophilic umpolung, and the donor/acceptor properties of arenes in a wide variety of organometallic reactions. 

Scheme 6.104 Key intermediates of the proposed catalytic cycle for the 100-catalyzed Michael addition of a,a-disubstituted aldehydes to aliphatic and aromatic nitroalkenes Formation of imine (A) and F-enamine (B), double hydrogen-bonding activation of the nitroalkene and nucleophilic enamine attack (C), zwitterionic structure (D), product-forming proton transfer, and hydrolysis.

Charge-Transfer Activation of Coordinated Arenes 452 Carbon-Hydrogen Bond Activation 453 Nucleophilic/ Electrophilic Umpolung 455... 

Looking at the mode of activation, one should consider two commonly accepted mechanisms (a) specific acid catalysis and (b) general acid catalysis. While specific acid catalysis refers to the reversible protonation of the electrophile with a strong acid in a pre-equilibrium step prior to nucleophilic attack, general acid catalysis involves the proton transfer or hydrogen bonding activation to the transition state in the rate-determining step e.g. nucleophilic attack), usually under weakly acidic or neutral conditions (Scheme 95) 366). 

The mechanism and stereochemistry of hydrophosphonylation of a-ketoesters by dimethylphosphonate [H-P(=0)(0Me)2l has been studied theoretically by the ONIOM method, for catalysis by cinchona-thioureas. Deprotonation of the phosphonate 0 is rate determining. It is followed by C-P bond formation (the stereo-controlhng step) via nucleophilic addition, and then reprotonation (regenerating the catalyst). Multiple hydrogen bonds activate the substrates, facilitate charge transfer and stabihze transition states. 

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