Solid-Phase Synthesis of Piperidines by N-Acyliminium Ion Chemistry

Abstract

An efficient solid-phase procedure for the synthesis of a number of 2-substituted piperidines is reported. Starting from solid-supported carbamate-tethered δ-amino acetals, 2-benzotriazolyl-substituted (Bt-substituted) piperidines were obtained by acid-induced ring-closure followed by trapping of the transient N-acyliminium ions with benzotriazole.

Preparation of Enantiopure Substituted Piperidines Containing 2-Alkene or 2-Alkyne Chains: Application to Total Syntheses of Natural Quinolizidine-Alkaloids

“…Many attempts proved that H 2 CCHCH 2 MgBr was not a suitable reagent for this alkylation. But, this problem was easily resolved by using H 2 CCHCH 2 TMS as an alternative in the presence of BF 3 ·Et 2 O and the diastereoselectivity was controlled by temperature. At room temperature, a mixture with 11 R -isomer as the major product (11 R :11 S = 9:1) was obtained.…”

Preparation of Enantiopure Substituted Piperidines Containing 2-Alkene or 2-Alkyne Chains: Application to Total Syntheses of Natural Quinolizidine-Alkaloids

“…Many attempts proved that H 2 CCHCH 2 MgBr was not a suitable reagent for this alkylation. But, this problem was easily resolved by using H 2 CCHCH 2 TMS as an alternative in the presence of BF 3 ·Et 2 O and the diastereoselectivity was controlled by temperature. At room temperature, a mixture with 11 R -isomer as the major product (11 R :11 S = 9:1) was obtained.…”

High-Pressure Promoted Cycloadditions of Enol Ethers and 3-Aryl-2-cyano-2-propenoates

“…Other applications of 3 in the generation and use of N-acyliminium ions will be given in the following paper. [8] Compounds 3 have a high potential to be used as scaffolds in combinatorial synthesis as they contain three different functionalities, which can be selectively modified, and because they can be transformed into a large variety of cyclic and noncyclic compounds having an aryl propylamine moiety. This moiety is an important motif in several compounds acting on the central nervous system.…”

Synthesis of Substituted Cyclic Amines From Protected Amino Acids Using Oxidative Decarboxylation and Alkylation

“…Additional supporting information can be found online in the Supporting Information section. The authors have cited additional references within the Supporting Information [63][64][65][66][67][68][69][70][71][72][73][74][75]. Supporting File 1: ajoc70319-sup-0001-SuppMat.pdf.…”

“… The authors have cited additional references within the Supporting Information [63–75]. Supporting File 1 : ajoc70319‐sup‐0001‐SuppMat.pdf.…”

Preparation of Enantiopure Substituted Piperidines Containing 2-Alkene or 2-Alkyne Chains: Application to Total Syntheses of Natural Quinolizidine-Alkaloids

“…Many attempts proved that H 2 CCHCH 2 MgBr was not a suitable reagent for this alkylation. But, this problem was easily resolved by using H 2 CCHCH 2 TMS as an alternative in the presence of BF 3 ·Et 2 O and the diastereoselectivity was controlled by temperature. At room temperature, a mixture with 11 R -isomer as the major product (11 R :11 S = 9:1) was obtained.…”

High-Pressure Promoted Cycloadditions of Enol Ethers and 3-Aryl-2-cyano-2-propenoates

“…Other applications of 3 in the generation and use of N-acyliminium ions will be given in the following paper. [8] Compounds 3 have a high potential to be used as scaffolds in combinatorial synthesis as they contain three different functionalities, which can be selectively modified, and because they can be transformed into a large variety of cyclic and noncyclic compounds having an aryl propylamine moiety. This moiety is an important motif in several compounds acting on the central nervous system.…”

Synthesis of Substituted Cyclic Amines From Protected Amino Acids Using Oxidative Decarboxylation and Alkylation

“…Additional supporting information can be found online in the Supporting Information section. The authors have cited additional references within the Supporting Information [63][64][65][66][67][68][69][70][71][72][73][74][75]. Supporting File 1: ajoc70319-sup-0001-SuppMat.pdf.…”

“… The authors have cited additional references within the Supporting Information [63–75]. Supporting File 1 : ajoc70319‐sup‐0001‐SuppMat.pdf.…”

Preparation of Enantiopure Substituted Piperidines Containing 2-Alkene or 2-Alkyne Chains: Application to Total Syntheses of Natural Quinolizidine-Alkaloids

“…Many attempts proved that H 2 CCHCH 2 MgBr was not a suitable reagent for this alkylation. But, this problem was easily resolved by using H 2 CCHCH 2 TMS as an alternative in the presence of BF 3 ·Et 2 O and the diastereoselectivity was controlled by temperature. At room temperature, a mixture with 11 R -isomer as the major product (11 R :11 S = 9:1) was obtained.…”

High-Pressure Promoted Cycloadditions of Enol Ethers and 3-Aryl-2-cyano-2-propenoates

“…Other applications of 3 in the generation and use of N-acyliminium ions will be given in the following paper. [8] Compounds 3 have a high potential to be used as scaffolds in combinatorial synthesis as they contain three different functionalities, which can be selectively modified, and because they can be transformed into a large variety of cyclic and noncyclic compounds having an aryl propylamine moiety. This moiety is an important motif in several compounds acting on the central nervous system.…”

Synthesis of Substituted Cyclic Amines From Protected Amino Acids Using Oxidative Decarboxylation and Alkylation

“…Additional supporting information can be found online in the Supporting Information section. The authors have cited additional references within the Supporting Information [63][64][65][66][67][68][69][70][71][72][73][74][75]. Supporting File 1: ajoc70319-sup-0001-SuppMat.pdf.…”

“… The authors have cited additional references within the Supporting Information [63–75]. Supporting File 1 : ajoc70319‐sup‐0001‐SuppMat.pdf.…”