Highly Enantioselective Pictet–Spengler Reaction Catalyzed by SPINOL‐Phosphoric Acids

Stereoselective Synthesis of Chiral Polycyclic Indolic Architectures through Pd0‐Catalyzed Tandem Deprotection/Cyclization of Tetrahydro‐β‐carbolines on Allenes

“…In our initial studies,18 we demonstrated the ability of the allyl group to act as a protecting group for tryptamine in Pictet–Spengler reactions and the compatibility of the allene function with the reaction conditions. In particular, we found that the spinol‐derived14d chiral phosphoric acid 15 was the best catalyst for the asymmetric Pictet–Spengler reaction of N ‐allyl tryptamines 3 with allenals 4 . Asymmetric catalytic Pictet–Spengler reactions were accordingly performed by reaction of N ‐allyl tryptamines 3 a – c with the extended set of aldehydes 4 (3 equiv)29 in the presence of the Spinol‐derived catalyst 10 (2 mol %; Scheme ).…”

“…The asymmetric Pictet–Spengler reaction was used as the key step for the asymmetric construction of 1 . Tryptamines previously reported in such process were protected either by sulfenyl,14b benzyl,14c or 2‐naphthylmethyl (NAP)14d groups. The key point for our strategy was accordingly the compatibility of the N ‐allyl protecting group28 and the 1, n ‐allenals 4 with phosphoric acid‐catalyzed asymmetric Pictet–Spengler reactions.…”

“…This method is mostly limited to aromatic aldehydes 15. On the other hand, chiral phosphoric acids, when applied to gem ‐diester tryptamines14a or N ‐protected tryptamines14b–d afford good conversion and ee values. In most cases, the tryptamine protecting group must be removed prior to further functionalization, unless it has been conveniently designed to be involved in further steps 2.…”

Synthesis of Heterocycles through Transition‐Metal‐Catalyzed Isomerization Reactions

“…An enantioselective version of the tandem isomerization/iminium cyclization for the synthesis of tetrahydro-b-carbolines was later reported by Cai et al [27] Here, the combination of Hoveyda-Grubbs II (5 mol %) with SPINOL-phosphoric acid (R)-51 (5 mol %), previously reported to induce high levels of enantioselectivity in Pictet-Spengler cyclizations, [28] was used to promote isomerization and stereoselective iminium cyclization of N-allyltryptamines 49 to afford 50 in good to excellent Scheme 3. Dual mode of reactivity of unsaturated lactams generated via tandem RCM/tautomerization.…”

Harmicine, a Tetracyclic Tetrahydro-β-Carboline: From the First Synthetic Precedent to Isolation from Natural Sources to Target-Oriented Synthesis (Review)*

“…List employed BINOL-derived phosphoric acids, such as TRIP (62), and geminally disubstituted tryptamines together with aromatic and aliphatic aldehydes, obtaining THβC in good yields and good enantioselectivities [83]. In 2012, the concept was further developed by Wang [84]. Wang showed that SPINOL-derived chiral phosphoric acids of type 63 could in some cases show enhanced catalytic activity as well as enhanced enantioselectivity.…”