C4 Pictet–Spengler Reactions for the Synthesis of Core Structures in Hyrtiazepine Alkaloids

Abe, Takumi; Haruyama, Tomohiro; Yamada, Koji

doi:10.1055/s-0036-1588438

Cited by 35 publications

(3 citation statements)

References 16 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, because of the nucleophilicity of indole at C2 and C3, numerous variants of the Pictet–Spengler reaction lead to structurally related compounds, such as 1,2,3,4-tetrahydropyrazino[1,2- a ]indoles 2 , tetrahydro-γ-carbolines 3 , and 1,3,4,5-tetrahydropyrrolo[4,3,2- de ]isoquinolines 4 , (Figure ). These so-called iso-Pictet–Spengler reactions are far less studied than the venerable historical reaction, despite allowing access to interesting heterocycles …”

Section: Introductionmentioning

confidence: 99%

Au(I)-Catalyzed Pictet–Spengler Reactions All around the Indole Ring

et al. 2021

View full text Add to dashboard Cite

Au(I) complexes catalyze iso-Pictet-Spengler reactions. Ethylamine or methylamine chains were introduced at C2, C4 or at the nitrogen atom of the indole ring, and the corresponding substrates were reacted in the presence of aldehydes and catalytic amounts of Au(I) complexes, leading to a variety of polycyclic scaffolds. Selectivity could be achieved in the course of a double iso-Pictet-Spengler reaction involving two successive aldehydes, leading to highly complex molecules.iso Pictet-Spengler reaction, operating with lower catalyst loading and temperature, should occur faster than the N-iso reaction, requiring higher catalyst loading and temperature. Indeed, when 5d was engaged in the reaction with 1 equivalent of p-bromobenzaldehyde, the C4-iso Pictet-Spengler product 10a was selectively obtained at room temperature in 71% yield with 10 mol% cat b (Scheme 3b, eq. 1).Control experiments revealed that: 1) no background reaction occurs in the absence of Au(I) catalyst on substrate 5d and 2) it is necessary to increase the catalyst loading to ensure a good conversion in this step. Compound 10a was then engaged in the N-iso Pictet-Spengler reaction with benzaldehyde that led to 11a in 70% yield as a mixture of diastereomers (Scheme 3b, eq. 2, dr 25/75). We then developed the one-pot formation of compounds 11 by sequential addition of two different aldehydes from 5d in the presence of 10 mol% of the gold complex b as catalyst (Scheme 3c). After 15 h of reaction in the presence of p-bromobenzaldehyde (1 equiv) at room temperature, benzaldehyde was added to the reaction mixture and further 24 h reaction led to compound 11a in 72% yield (dr 35/65) in favor of the syn isomer.

show abstract

Section: Introductionmentioning

confidence: 99%

Au(I)-Catalyzed Pictet–Spengler Reactions All around the Indole Ring

et al. 2021

View full text Add to dashboard Cite

show abstract

“…They can be roughly classified into two categories. One focuses on the functional group manipulations of 3,4-disubstituted indoles as the key strategy to form the tricyclic azepino[5,4,3- cd ]indole skeleton . The other generally involves the construction of this core structure starting from the indole ring formation .…”

Section: Introductionmentioning

confidence: 99%

Access to Polycyclic Azepino[5,4,3-cd]indoles via a Gold-Catalyzed Post-Ugi Dearomatization Cascade

Song

Liu

et al. 2020

J. Org. Chem.

View full text Add to dashboard Cite

The development of a rapid and diverse access to complex natural product-like 3,4-fused indole scaffolds has always attracted considerable attention from synthetic and medicinal communities. We herein disclose a modular and straightforward protocol to prepare the densely substituted polycyclic azepino[5,4,3-cd]indole scaffolds. This synthetic process involves an Ugi four-component reaction from easily available starting materials and a gold-catalyzed post-Ugi domino dearomatization/Michael addition sequence, enabling facile access to the highly functionalized azepino[5,4,3-cd]indole core with excellent chemo-, regio-, and diastereoselectivity.

show abstract

“…In our continuing efforts in the indole chemistry, [31][32][33][34][35][36][37][38][39][40][41][42][43] we recently reported a concise formation of isochromeno [3,4-b]indolines from 2-benzyloxy-3-bromoindolines were achieved using a silver salt. 44) While extending the utility of the silver-mediated functionalization, we preliminary found that the protocol is also applicable for the synthesis of 2,3-dialkoxyinolines by using alcohol as a nucleophile, which could be converting to 3-alkoxyindoles through a selective elimination of the alkoxide at the C-2 position (Chart 2b).…”

mentioning

confidence: 99%

Revisiting 2-Alkoxy-3-bromoindolines: Control C-2 <i>vs</i>. C-3 Elimination for Regioselective Synthesis of Alkoxyindoles

Abe

Kosaka

Kawasaki

et al. 2020

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

The regioselective synthesis of both 2-and 3-alkoxyindoles from a common intermediate, 2-alkoxy-3-bromoindolines (ROBIN), is described. The 2-alkoxyindoles are obtained by a base-promoted regioselective elimination of HBr from ROBIN, whereas the synthesis of 3-alkoxyindoles is achieved by a silvermediated alkoxylation followed by an acid-promoted elimination of alkoxide. This key elimination features the complete regioselectivity and no need for catalysts, that makes it have potential synthetic applications. Furthermore, this protocol is user friendly because ROBIN is able to be prepared from commercially available indoles and is a bench-stable easy-to-handle crystalline substrate, thus allowing the concise synthesis of a variety of both 2-and 3-alkoxyindoles.

show abstract

C4 Pictet–Spengler Reactions for the Synthesis of Core Structures in Hyrtiazepine Alkaloids

Cited by 35 publications

References 16 publications

Au(I)-Catalyzed Pictet–Spengler Reactions All around the Indole Ring

Au(I)-Catalyzed Pictet–Spengler Reactions All around the Indole Ring

Access to Polycyclic Azepino[5,4,3-cd]indoles via a Gold-Catalyzed Post-Ugi Dearomatization Cascade

Revisiting 2-Alkoxy-3-bromoindolines: Control C-2 <i>vs</i>. C-3 Elimination for Regioselective Synthesis of Alkoxyindoles

Contact Info

Product

Resources

About