GENERAL ASYMMETRIC-SYNTHESIS OF ISOQUINOLINE ALKALOIDS - ENANTIOSELECTIVE HYDROGENATION OF ENAMIDES CATALYZED BY BINAP-RUTHENIUM(II) COMPLEXES

In the presence of a small amount of RuX(2)[(R)- or (S)-BINAP] (X = an ionic ligand) a wide range of acyl-1-benzylidene-1,2,3,4-tetrahydroiso quinolines are hydrogenated to give the saturated products in nearly q uantitative yields and in high (up to 100 %) optical yields. The enami de substrates are selectively prepared by N-acylation of the correspon ding 1-benzylated 3,4-dihydroisoquinolines under suitable acylation co nditions; some crystalline materials having low solubility are obtaine d by a second-order Z/E stereomutation technique utilizing the double- bond photolability and lattice energy effects. This asymmetric hydroge nation sets the key stereogenic center in a predictable manner, either R or S flexibly, at the C(1) position of the benzylated tetrahydroiso quinolines. The chiral products are converted by standard functional g roup modification to tetrahydropapaverine, laudanosine, tretoquinol, n orreticuline, etc. Hydrogenation of the simple 1-methylene substrate i s used fbr synthesis of salsolidine. This enantioselective hydrogenati on is applied to the synthesis of morphine and its artificial analogue s such as morphinans and benzomorphans of either chirality. A mnemonic device is presented for predicting the reactivity and enantiofacial s election of the BINAP-Ru catalyzed hydrogenation. Reaction with BINAP- Rh catalyst proceeds with a lower enantioselectivity and an opposite s ense of asymmetric induction.