- Organocatalytic Enantioselective Pictet-Spengler Approach to Biologically Relevant 1-Benzyl-1,2,3,4-Tetrahydroisoquinoline Alkaloids
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(Figure Presented) A general procedure for the synthesis of 1-benzyl-1,2,3,4-tetrahydroisoquinolines was developed, based on organocatalytic, regio- and enantioselective Pictet-Spengler reactions (86-92% ee) of N-(o-nitrophenylsulfenyl)-2-arylethylamines with arylacetaldehydes. The presence of the o-nitrophenylsulfenyl group, together with the MOM-protection in the catechol part of the tetrahydroisoquinoline ring system, appeared to be a productive combination. To demonstrate the versatility of this approach, 10 biologically and pharmaceutically relevant alkaloids were prepared using (R)-TRIP as the chiral catalyst: (R)-norcoclaurine, (R)-coclaurine, (R)-norreticuline, (R)-reticuline, (R)-trimemetoquinol, (R)-armepavine, (R)-norprotosinomenine, (R)-protosinomenine, (R)-laudanosine, and (R)-5-methoxylaudanosine.
- Ruiz-Olalla, Andrea,Würdemann, Martien A.,Wanner, Martin J.,Ingemann, Steen,Van Maarseveen, Jan H.,Hiemstra, Henk
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p. 5125 - 5132
(2015/05/27)
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- General asymmetric synthesis of isoquinoline alkaloids. Enantioselective hydrogenation of enamides catalyzed by BINAP-ruthenium(II) complexes
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In the presence of a small amount of RuX2[(R)- or (S)-BINAP] (X = anionic ligand) a wide range of (Z)-2-acyl-1-benzylidene-1,2,3,4- tetrahydroisoquinolines 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 conditions; 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 a predictable manner, either R or S flexibly, at the C(1) position of the benzylated tetrahydroisoquinolines. The chiral products are converted by standard functional group modification to tetrahydropapaverine, laudanosine, tretoquinol, norreticuline, etc. Hydrogenation of the simple 1-methylene substrate is used for synthesis of salsolidine. This enantioselective 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.
- Kitamura,Hsiao,Ohta,Tsukamoto,Ohta,Takaya,Noyori
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p. 297 - 310
(2007/10/02)
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- Asymmetric synthesis of 1-benzyltetrahydroisoquinolines using chiral oxazolo[2,3-a]tetrahydroisoquinolines
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A novel synthetic route to enantiomerically pure 1-benzyltetrahydroisoquinolines (1) was developed via the reaction of oxazolo[2,3-a]tetrahydroisoquinoline (5) with benzyltriisopropoxytitanium compounds (10). This method was applied to the synthesis of (S)-trimetoquinol (1c; a bronchodilator).
- Hashigaki,Kan,Qais,Takeuchi,Yamato
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p. 1126 - 1131
(2007/10/02)
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