Enantioselective organocatalytic hydride reduction

5 Michael-type Alltylations with Trifluorohorate Salts 

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Ouellet SG, Tuttle JB, MacMillan DWC (2005) Enantioselective organocatalytic hydride reduction. J Am Chem Soc 127 32-33 Paras NA, MacMillan DWC (2001) New strategies in organic catalysis the first enantioselective organocatalytic Friedel-Crafts alkylation. J Am Chem Soc... 

Ouellet SG, Tuttle JB, MacMillan DWC (2005) Enantioselective Organocatalytic Hydride Reduction. J Am Chem Soc 127 32... 

Scheme 2.2 Proposed mechanism for the enantioselective organocatalytic hydride conjugate reduction of entds...

The asymmetric organocatalytic enantioselective conjugate hydrogen transfer reaction is clearly inspired by the mode of action in biological processes, in which reductions are accomplished by enzymes using hydride reduction cofactors like NADH. 

The organocatalytic enantioselective reduction of C=C, C=0, and C=N double bonds is a relatively young area for which many new and exciting developments can be expected in the near future. Hantzsch esters are useful organic hydrides, and a recent review has summarized the results obtained to date in organocataly-sis [27]. The case of silicon hydrides is convenient for imine or ketone reductions, as a chiral base can act as an organic catalyst. The asymmetric reductions of ketones catalyzed by oxazaborolidines and pioneered by Itsuno [28] and Corey [29] could not be included in this chapter. 

Nature makes use of NADH (reduced nicotinamide adenine dinucleotide) as a cofactor for enantioselective biochemical hydrogenations, which are typical hydride-transfer reactions. Dihydropyridines and benzimidazolines derivatives are active hydride donors due to the presence of the nitrogen atom and the ability of the molecule to undergo aromatisation. Organocatalytic enantioselective reductions carried out using hydride donors has been studied, and effective reductions have been achieved with imidazoli-dinone organocatalysts, both with a,p unsaturated aldehydes and ketones. Generally, a stoichiometric quantity of reductant (Hantzsch ester 4) is required for these transformations (Scheme 18.5). 

Later on, the Rueping group reported an organocatalytic enantioselective reduction of pyridine 180 (Scheme 17.30) [74], according to the procedure described by Bohlmann and Rahtz [75]. The key step in the synthesis of decahydroquinolines from the pumiliotoxin family involved Hantzsch dUiydropyridine 172 as the hydride source and involved BINOL-phosphoric acid 181 as a chiral Br0nsted acid catalyst... 

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