ChemInform Abstract: General Asymmetric Synthesis of Isoquinoline Alkaloids. Enantioselective Hydrogenation of Enamides Catalyzed by BINAP- Ruthenium(II) Complexes.

Abstract

In the presence of a small amount of RuX 2 [(R)- or (S)-BINAP] (X=anionic ligand) a wide range of (Z)-2-acyl-1-benzylidene-1,2,3,4-tetrahydro- isoquinolines are hydrogenated to give the saturated products in nearly quantitative yields and in high (up to 100%) optical yields. The enamide substrates are selectively prepared by N-acylation of the corresponding 1-benzylated 3,4-dihydroisoquinolines under suitable acylation condi- tions; some crystalline materials having low solubility are obtained by a second-order Z/E stereomutation technique utilizing the double-bond photolability and lattice energy effects. This asymmetric hydrogenation sets the key stereogenic center in predictable manner, either R or S flexibly, at the C(1) position of the benzylated tetrahydroisoquinoli- nes. The chiral products are converted by standard functional group modification to tetrahydropapaverine, laudanosine, etc. This enantio- selective hydrogenation is applied to the synthesis of morphine and its artificial analogues such as morphinans and benzomorphans of either chirality. A mnemonic device is presented for predicting the reactivity and enantiofacial selection of the BINAP-Ru catalyzed hydrogenation. Reaction with BINAP-Rh catalyst proceeds with a lower enantioselectivity and an opposite sense of asymmetric induction