Protic chiral ligands

One of the most intensively studied protic chiral ligands, which moreover allows enantioselectivities of up to 95% ee, is the proline-derived (25 )-l- [(25,)-l-methyl-2-pyrrolidinyl]methyl -2-pyrrolidine methanol (6)19-21. 

Principles. How shall we proceed toward catalytic asymmetric induction Scheme 5 illustrates a possible way to achieve enantioselective alkylation by using a small amount of chiral source. Under certain conditions, the presence of a protic chiral auxiliary HX can catalyze the addition of organometallic reagent, R2M, to a prochiral carbonyl substrate by way of RMX. To obtain sufficient chiral efficiency, the anionic ligand X must have a three-dimensional structure that allows differentiation between the diastereomeric transition states of the alkyl transfer step. In addition, unlike in stoichiometric reactions, the rate of... 

Organometallic reagents can be rendered chiral by coordination of a chiral ligand on the metal, or by covalent linkage of a protic chiral auxiliary (amine or alcohol) to the metal. In the second case, the auxiliary usually bears other base sites that can also coordinate to the metal. In this chapter, nonfimctionalized... 

It is interesting that the condensation between electron-rich phenol, amine, and a chiral a -A, A -dibenzylamino aldehyde has been reported to be temperature sensitive, with high syn selectivity at high reaction temperatures while high anti selectivity is observed at low reaction temperatures. Similar to the Aldol Condensation, the Mannich reaction can be promoted or catalyzed by either acid or base. Furthermore, different protic acids or Lewis acid alone or in combination with a different chiral ligand or auxiliary group is used to enhance the stereoselectivity of the Mannich reaction, such as proline, (,S )-amino sulfonamide, BINOL phosphate," At-spiro chiral quaternary ammonium bromide, and dodecylbenzenesulfonic acid" as well as Lewis acids, such as Cu(OAc)2, CuC104, " Cu(OTf)2-chiral diamine complexes,... 

Addition of Na2S to the methylidene complex 307 gives rise to a trinu-clear sulfonium salt (308) (108). The action of a protic nucleophile, like H2S, on the prochiral phosphinoketene ligand in 309 (R = Me, Ph) leads to five-membered chiral metallaheterocycles (310), which are organometallic derivates of y-thiolactones (197). 

Chiral ruthenium catalysts bearing BINAP-type ligands were effectively dissolved in ILs and used for enantioselective hydrogenation of prochiral a,/i-unsaturated acids, followed by subsequent C02 extraction [40]. A pronounced effect of protic co-solvents such as water or PrOH was noted for the reaction stage with certain substrates. The catalyst solution could be recycled four times without any noticeable decrease in conversion or enantioselectivity. 

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