Hydrogenation enantioselective organocatalytic

An enantioselective organocatalytic reductive amination has been achieved using Hantzsch ester for hydrogen transfer and compound (21) as catalyst. This mild and operationally simple fragment coupling has been accomplished with a wide range of ketones in combination with aryl and heterocyclic amines.359... 

Kunz RK, MacMillan DWC (2005) Enantioselective organocatalytic cyclopro-panations. The identification of a new class of iminium catalyst based upon directed electrostatic activation. J Am Chem Soc 127 3240-3241 Lacour J, Hebbe-Viton V (2003) Recent developments in chiral anion mediated asymmetric chemistry. Chem Soc Rev 32 373-382 Li X, List B (2007) Catalytic asymmetric hydrogenation of aldehydes. Chem Commun 17 1739-1741... 

Wilson RM, Jen WS, MacMillan DWC (2005) Enantioselective organocatalytic intramolecular Diels-Alder reactions. The asymmetric synthesis of solana-pyrone D. J Am Chem Soc 127 11616-11617 Xie JH, Zhou ZT, Kong WL, Zhou QL (2007) Ru-catalyzed asymmetric hydrogenation of racemic aldehydes via dynamic kinetic resolution efficient synthesis of optically active primary alcohols. J Am Chem Soc 129 1868-1869... 

One of the most interesting developments in recent years is the non-enzy-matic, enantioselective, organocatalytic addition of hydrogen cyanide to aldehydes. This reaction is, for example, very efficiently catalysed by optically pure diketopiperazines, such as cydo-(f )-Phe-(i )-His), which are readily accessible from the corresponding amino acids. [114-116]... 

Later, the first enantioselective organocatalytic transfer hydrogenation involving cyclic enones was reported by MacMillan and co-workers following an operationally simple and rapid protocol that allowed access to chiral / -substituted... 

S. Saha, J.N. Moorthy, Enantioselective organocatalytic Biginelli reaction, dependence of the catalyst on sterics, hydrogen bonding, and reinforced chirality, J. Org. Chem. 72 (2011) 396-402. 

Ouellet, S.G., Walji, A.M., and MacMillan, D.W.C. (2007) Enantioselective organocatalytic transfer hydrogenation reactions using Hantzsch esters. Acc. Chem. Res., 40, 1327-1339. 

BOTH (Enantioselective Organocatalytic Transfer Hydrogenation) The group led by MacMillan showed that the combination of an imidazolidine catalyst 3 and a Hantzsch ester 4a is a powerful and versatile reducing agent (Scheme 32.2). They were able to selectively reduce 1,4-unsaturated enals and enones with yields up to 95% and ees up to 97%. 

In 2007, AntiUa and coworkers disclosed the first asymmetric organocatalytic reduction of acyclic a-imino esters (Scheme 23) [39], Chiral VAPOL phosphate (5)-16 (5 mol%) served as a catalyst for the transfer hydrogenation of the latter (62) employing commercially available dihydropyridine 44a to give both aromatic and aliphatic a-amino esters 63 in very high yields (85-98%) and enantioselectivities (94-99% ee). 

It should be noted that not only the Lewis base but also typical Lewis acid roles can be emulated by organocatalytic systems. The proton is arguably the most common Lewis acid found in Nature, and these exist in two forms classified by the nature of the hydrogen bond polar covalent (RX-H) and polar ionic (RX+H-Y ). In the former case, in asymmetric transformations the chiral information is dictated by the chiral anion, whilst in the latter case the anion is non-chiral and the enantioselectivity is introduced by a chiral ligand (usually an amine base), which complexates the proton. This activation is discussed more extensively in Chapter 7. 

---