Enantioselective Pictet–Spengler Condensation to Access the Total Synthesis of (+)‐Tabertinggine

Abstract

A chiral phosphoric acid (CPA)‐catalyzed enantioselective Pictet–Spengler condensation/lactamization cascade reaction was established, which paved the way of the collective synthesis of iboga‐type indole alkaloids. Herein, we presented the asymmetric total synthesis of iboga‐type indole alkaloid (+)‐tabertinggine.

Polymer‐Supported Phosphoric‐Acid Catalysed Enantioselective Pictet‐Spengler Cyclisation for the Synthesis of Quaternary Tryptolines in Batch/Continuous Flow

“…This intermediate has been previously converted into the iboga-type indole alkaloid (+)-tabertinggine. [12] On the other hand, the reaction of 1 a with ethyl 2-oxohexanoate (7) also worked smoothly to afford 8 in 80% yield and 64% ee (Scheme 4a, left). Later, we investigated the effect of an α-substituent on the tryptamine unit on yield and enantioselectivity (Scheme 4b).…”

“…[9] An elegant enantioselective protocol for the synthesis of spiroindolinones has been previously achieved in batch by using chiral phosphoric acids (CPAs) as catalysts to promote asymmetric Pictet-Spengler cyclizations. [10][11][12] Recently, the use of αketoester, and α-ketoamides as electrophilic partners along with tryptamines in the presence of organocatalysts has been shown to afford substituted tryptolines via PSR. [13] As a significant drawback, all these protocols involve non-recyclable homogeneous catalysts with poor atom efficiency and cost effectiveness.…”

Accessing unnatural α-amino acids with tetrasubstituted stereogenic centersviacatalytic enantioselective reactions of ketimine-type α-iminoesters/α-iminoamides

“…An enantioselective cascade involving the Pictet–Spengler reaction of di(iso-propyl) 2-oxopentanedioate ( 196d ) with tryptamine and subsequent lactamization was reported by She and co-workers (Scheme 85). 138 This method was used in the key step in the total synthesis of tetracyclic (+)-tabertinggine.…”

Organocatalytic Enantioselective Pictet–Spengler Reaction of α‐Ketoesters: Development and Application to the Total Synthesis of (+)‐Alstratine A

“…In 2022, Nakamura reported a chiral phosphoric acid (CPA)-catalyzed enantioselective PSR of tryptamine 3 with acyclic α-ketoester 4 (Scheme 1b). [12] She and co-workers described a CPA catalyzed PSR of 3 with diisopropyl-2oxopentanedioate (one single example) [13] aimed at developing a concise total synthesis of tabertinggine. [14,15] In a more general context, catalytic enantioselective PSR of ketones [16][17][18][19][20][21][22] is known to be highly challenging and is unfortunately poorly developed in sharp contrast to that of aldehydes.…”