Regioselectivity of Pictet–Spengler cyclization: synthesis of halotetrahydroisoquinolines

The intermolecular Pictet-Spengler condensation with chiral carbonyl derivatives in the stereoselective syntheses of optically-active isoquinoline and indole alkaloids

“…A Korean team disclosed the synthesis of 1-substituted THIQ carboxylates by the activated Pictet-Spengler protocol. 62 In their approach, methanesulfonyl derivatives of homoveratrylamine 48a-d were condensed with L-menthyl glyoxylate 49, furnishing 6,7-dimethoxy tetrahydroisoquinolines 50 and/or their 7,8-dimethoxy-substituted congeners 51, as shown in Table 2. Diastereomeric excesses of the soproduced THIQ were not informed.…”

Heterogeneous Catalysts in Pictet‐Spengler‐Type Reactions

“…Regioselectivity depends on activating the phenylethylamine aromatic ring and the less hindered ortho position usually predominates for cyclisation. Such pattern improves when the reaction is carried out in protic solvents [9,10].…”

Chemistry of α-Oxoesters: A Powerful Tool for the Synthesis of Heterocycles

“…Moreover, menthyloxy carbonyl-substituted tetrahydroisoquinolines were prepared via Pictet−Spengler cyclization reaction of dopamine derivatives with menthyl pyruvate 246 and menthyl glyoxalate. 247 Hammad and Smith 248 He et al 250 described the synthesis of β-carbolines via Pictet−Spengler reaction of α-siloxy α,β-unsaturated esters, silyl enol ethers of α-oxoesters, with tryptamine hydrochloride. Reactions were performed either by heating a mixture of tryptamine hydrochloride, α-siloxy α,β-unsaturated esters (1 equiv), and p-TsOH·H 2 O (1 equiv) in EtOH at 80°C under an atmosphere of N 2 overnight or by reaction of α-siloxy α,β-unsaturated esters with p-TsOH·H 2 O (2 equiv) in EtOH at 80°C under N 2 atmosphere for 6 h, followed by addition of tryptamine hydrochloride (1 equiv) and heating at the same temperature overnight, to afford the corresponding β-carbolines 533 in 67−88% yields.…”

“…Moreover, menthyloxy carbonyl-substituted tetrahydroisoqui-nolines were prepared via Pictet−Spengler cyclization reaction of dopamine derivatives with menthyl pyruvate 246 and menthyl glyoxalate. 247 Hammad and Smith 248 °C under N 2 atmosphere for 6 h, followed by addition of tryptamine hydrochloride (1 equiv) and heating at the same temperature overnight, to afford the corresponding β-carbolines 533 in 67−88% yields. Starting silyl enol ethers of α-oxoesters were prepared from reaction of phosphonate 532 with carbonyl compounds in the presence of LiHMDS in THF at room temperature overnight (Scheme 158).…”

“…A similar structural scaffold was prepared by two-step reaction of ( S )-4-(4-methoxybenzyl)­oxazolidin-2-one 526 with ethyl glyoxalate (1.1 equiv) in the presence of 1 H -benzotriazole (1.1 equiv) and p -TsOH (10 mol %) in toluene under reflux condition with azeotropic removal of water using Dean–Stark apparatus for overnight, followed by treatment of the obtained product with TiCl 4 in CH 3 CN at 60 °C for 2 days to give the corresponding tetrahydroisoquinoline 527 in 76% yield (Scheme ). Moreover, menthyloxy carbonyl-substituted tetrahydroisoquinolines were prepared via Pictet–Spengler cyclization reaction of dopamine derivatives with menthyl pyruvate and menthyl glyoxalate …”