Application of chlorotrimethylsilane in Pictet–Spengler reaction

Abstract

Chlorotrimethylsilane has been found to be an efficient condensing agent in the Pictet-Spengler reaction, affording an extremely straightforward synthetic route to tetrahydro-b-carboline derivatives and their analogs. The applicability of the method has been studied, and a representative library of structurally diverse products has been created.

Identification of 5-HT2 Serotonin Receptor Modulators through the Synthesis of a Diverse, Tropane- and Quinuclidine-alkaloid-Inspired Compound Library

“…Employing the Kabbe reaction, 27 spirocyclic chromanones (16a−16d) were also obtained in good to excellent yields, while a spirocyclic βcarboline (17) was obtained in one step from 5-methoxytriptamine employing the Pictet−Spengler reaction. 28 Finally, spirocyclic γ-lactones (18a−18b) were synthesized using 2bromobenzoic acids following a lithium-halogen exchange, nucleophilic attack and cyclization sequence. 29 In total, the final library consisted of 58 compounds from 12 diverse pseudo-NP scaffolds, of which 8 contained spirocyclic fragment fusions (Supporting Information Figure S2).…”

“…Starting from the free base of commercially available quinuclidin-3-one hydrochloric acid salt ( 14 ), under analogous conditions to tropinone, spirocyclic dihydroquinazolinones ( 15a–15d ) were prepared in good yields. Employing the Kabbe reaction, spirocyclic chromanones ( 16a–16d ) were also obtained in good to excellent yields, while a spirocyclic β-carboline ( 17 ) was obtained in one step from 5-methoxytriptamine employing the Pictet–Spengler reaction . Finally, spirocyclic γ-lactones ( 18a–18b ) were synthesized using 2-bromobenzoic acids following a lithium-halogen exchange, nucleophilic attack and cyclization sequence …”

Synthesis of rigid tryptophan mimetics by the diastereoselective Pictet-Spengler reaction ofβ3-homo-tryptophan derivatives with chiralα-amino aldehydes

“…The heterocyclic skeleton of 1,2,3,4‐tetrahydro‐ β ‐carbolines possess multiple sites for functionalization. Therefore, they are an ideal choice for the design of pharmacophore‐based libraries in drug discovery, through the generation of a large number of structurally diverse compounds . There is also a possibility to incorporate such 1,2,3,4‐tetrahydro‐ β ‐carbolines into a peptide chain to obtain peptidomimetics with rigid analogues of tryptophan.…”

Metal‐Templated Asymmetric Catalysis: (Z)‐1‐Bromo‐1‐Nitrostyrenes as Versatile Substrates for Friedel–Crafts Alkylation of Indoles

“…Using as imilarr eactions equence, compound 7i was obtained with al ow d.r.b ut retained enantioselectivity. [14] In summary,w er eported an enantioselective Friedel-Crafts alkylation of indoles with a-bromo nitrostyrenes catalyzed by am etal-templated hydrogenbond-mediated catalyst. The proposed transition state exploits an etwork of hydrogen bonds, which is well illustratedb yt he co-crystal structure of as implified iridium catalyst with (Z)-2-bromo-3-phenylacrylate as as tructural analog of the nitro substrate.…”