Catalytic Asymmetric Induction with Chiral Thiols

3 Catalytic Asymmetric Induction with Chiral Thiols 

Comprehensive Enantioselective OrganocatalYsis Catalysts, Reactions, and Applications, First Edition. 

R =Aryl, and aliphatic group r2 = Aryl and heteroaromatic group  

2 Hantzsch Ester as the Hydride Source 945 B NHR2 NHR2 

In addition to quinolines, pyridines were also found to be suitable substrates for this cascade reduction. Chiral tetrahydropyridines 36 and 37 were synthesized with up to 92% ee by employing (R)-7 as the catalyst [25]. Phenanthroline, which has the same functional group as quinoline and pyridine, was reported by Metallinos et al. to undergo transfer hydrogenation to the corresponding octahy-drophenanthroline 38 with up to 99% ee, whereas most other substrates provided moderate ee [26]. 

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More recently. Miller and coworkers reported that ortho-mercaptobenzoic acid and ortho-mercaptophenols 159 could be used as efficient thiol catalysts in both the intramolecular MBH and Rauhut-Currier reaction and they also demonstrated that chiral mercaptophenol afforded the reaction with low to moderate enantiose-lectivities (Scheme 31.53) [64]. Under estabhshed conditions, chiral catalysts (S)-and (R)-160 afforded high yields and moderate asymmetric inductions in the MBH reactions. The obtained enantioselectivities remained largely unaffected by the amount of water and base added, catalyst loading, and substrate concentration but were markedly influenced by the reaction temperature. Interestingly, both increasing and decreasing the temperature from the established value of 70 °C resulted in lower ee values. The complete absence of catalytic activity of (R)-161 further emphasizes the crucial importance of a protic substituent at the ortho-position to the nucleophilic thiol. 

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