Enantioselective protonations deracemization

When the reaction sequence starts from racemic 1, it is known as deracemization 146, l47. Highly enantioselective protonations of this type constitute an important new methodology in enantioselective synthesis. However, the results obtained with one class of anions cannot be transferred to another, for reasons similar to those previously discussed (Section 2.1.2.). The protonations described below must be performed under strictly kinetic control and any racemization must be excluded during isolation of the product. 

Enantioselective Protonation of Enamines (Deracemization of Carbonyl Compounds)... 

Use of a chiral proton source, a chiral base or base/chiral ligand complex circumvents the problem of incorporation and removal of a chiral auxiliary. Simpkins and coworkers opened the possibility of enantioselective protonation as a method for the asymmetric syntheses of 1-substituted tetrahydroisoquinolines [77]. Using the chiral amine 98 as a proton source, deracemization of 97 proceeded in up to 93 7 er, alleviating the requirement for a chiral auxiliary (Scheme 28). 

Duhamel L, Plaquevent JC. Deracemization by enantioselective protonation. A new method for the enantiomeric enrichment of a-amino acids. J. Am. Ghent. Soc. 1978 100 7415-7416. 

Claraz A, Oudeyer S, Levacher V Deracemization of a-Substituted Carbonyl Compounds via Catal3ftic Enantioselective Protonation of their Corresponding Enolates Current Organic Chemistry, 2012 16 2192-2205. 

Martin J, Plaquevent JC, Maddaluno J, Rouden J, Lasne MC. Efficient deracemization of pipecoUc acid amides through enantioselective protonation of their lithium enolates insights into the origin of the transferred proton. Eur. J. Org. Chem. 2009 5414-5422. 

The thiolester group was used for deracemization of terpenic esters [254]. Racemic 5-phenyl thiocyclogeranate was deprotonated by n-BuLi, and the resulting enolate was protonated by a chiral aminoalcohol, ( )-N-isopropylephedrine. The thiolester was obtained with the highest enantioselectivity (99% e.e.) reported for such a process (carried out on a 40 g scale). With a sulfur group a selective (Z)-enolate was formed and protonation was slower than for esters. 

Vedejs E, Lee N, Sakata ST. Deracemization via highly enantioselective enolate protonation using a chiral aniline as the acid. J. Am. Chem. Soc. 1994 16 2175 2176. 

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