Enantioselective organocatalytic transfer hydrogenation

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... 

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%. 

The organocatalytic transfer hydrogenation of cyclic enones has been also successfully achieved employing the imidazolidinone 12 [24], catalyst that also promotes enantioselective Diels-Alder reactions with cyclic enones [25]. The structure of the dihydropyridine reagent seems to have an important effect on the selectivity of the process since better enantioselectivities are observed when increasing the steric hindrance of the ester moiety 13 (Scheme 2.6). The reduction, which is performed with substoichiometric amounts of imidazolidinone 12 in ether at 0°C,... 

Rueping M, Antonchick AR, Theissmann T (2006) A Highly Enantioselective Br0nsted Acid Catalyzed Cascade Reaction Organocatalytic Transfer Hydrogenation of Quinolines and Their Application in the Synthesis of Alkaloids. Angew Chem Int Ed 45 3683... 

Rueping M, Antonchick AP, Theissmann T. A highly enantioselective Brpnsted acid catalyzed cascade reaction organocatalytic transfer hydrogenation of quinolines and their application in the synthesis of alkaloids. Angew. Chem. Int. Ed. 2006 45 3683-3686. 

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). 

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... 

Kumaraswamy G, Padmaja M (2008) Enantioselective Total Synthesis of Eicosanoid and its Congener, Using Organocatalytic Cyclopropanation, and Catalytic Asymmetric Transfer Hydrogenation Reactions as Key Steps. J Org Chem 73 5198... 

Since the first catalyst (7) used in the organocatalytic Diels-Alder reaction, several modificahons have been made to improve its catalytic properties. In 2002 the commonly called MacMillan second-generation catalyst (25) was used in the addihon of indoles to enals [10]. A few years later, MacMillan s third-generation catalyst (26) was used for the enantioselective transfer hydrogenation of enals (Figure 33.3) [11]. 

Kumaraswamy G, Padmaja M. Enantioselective total synthesis of eicosanoid and its congener, using organocatalytic cyclopropanation, and catalytic asymmetric transfer hydrogenation reactions as key steps. J. Org. Chem. 2008 73 (13) 5198-5201. 

Rueping M, Sugiono E, Azap C, Theissmann T, Bolte M. Enantioselective Brpnsted acid catalyzed transfer hydrogenation organocatalytic reduction of imines. Org. Lett. 2005 7 3781-3783. 

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