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Synlett 2019; 30(11): 1329-1333
DOI: 10.1055/s-0037-1611825
DOI: 10.1055/s-0037-1611825
letter
Synthesis of 2,3-Dihydrotryptamines from Amide Solvents and Acyclic Materials through Metal-Free Amidoalkylarylation of Unactivated Alkenes
We gratefully acknowledge the financial support from the National Natural Science Foundation of China (21702083), the Program for Innovative Research Team (in Science and Technology) in Universities of Yunnan Province, the Yunnan Ten Thousand Talent Program for Young Top-Notch Talents, and the Science Foundation Project of Harbin University of Commerce (18XN067).Further Information
Publication History
Received: 12 March 2019
Accepted after revision: 24 April 2019
Publication Date:
03 May 2019 (online)
![](https://www.thieme-connect.de/media/synlett/201911/lookinside/thumbnails/st-2019-l0145-l_10-1055_s-0037-1611825-1.jpg)
Abstract
The first synthesis of 2,3-dihydrotryptamines from acyclic materials and an exo-selective amidoalkylation/cyclization cascade of N-allyl anilines through α-C(sp3)–H functionalization of simple amides across unactivated alkenes are presented. This reaction proceeds in mixed aqueous media and under metal-free conditions and features a broad substrate scope and a simple operation.
Key words
amides - cross-coupling - cyclization - green chemistry - radical reaction - tandem reactionSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1611825.
- Supporting Information
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- 21 General Procedure for the Synthesis of 2,3-Dihydrotryptamines (2a1 as an Example) A 10 mL Schlenk tube, equipped with a magnetic stirring bar, was charged under argon with N-(2-methylallyl)-N-phenylacetamide (1a1, 38 mg, 0.2 mmol), DCP (162 mg, 0.6 mmol), DMA (1.0 mL), and H2O (0.2 mL). The mixture was stirred at 120 °C for 6 h, then it was quenched with saturated aqueous Na2S2O3 (0.5 mL) and water (5.0 mL) and extracted with CH2Cl2 (10.0 mL) three times. The residue obtained after evaporation of the solvent was purified by flash column chromatography on silica gel (petroleum ether/acetone = 6:1, v/v) to afford N-[2-(1-acetyl-3-methylindolin-3-yl)ethyl]-N-methylacetamide (2a1) as a pale-yellow oil (39 mg, 71% yield) as a 20:10:3:2 inseparable mixture of 4 rotamers (major, minor, and two more isomers appearing in minute quantities, and only the major and the minor are characterized) due to the restricted rotation of the N–(CO) bonds. 1H NMR (400 MHz, CDCl3): δ = 1.38 (s, 3 H major), 1.43 (s, 3 H minor), 1.79–1.98 (stack, 2 H major and 5 H minor), 2.02 (s, 3 H major), 2.24 (s, 3 H minor), 2.25 (s, 3 H major), 2.84 (s, 3 H minor), 2.87 (s, 3 H major), 2.95–3.04 (stack, 1 H major and 1 H minor), 3.16–3.24 (m, 1 H minor), 3.42–3.49 (m, 1 H major), 3.72 (d, J = 10.4 Hz, 1 H major), 3.78 (d, J = 10.3 Hz, 1 H minor), 3.87 (d, J = 10.4 Hz, 1 H minor), 4.11 (d, J = 10.4 Hz, 1 H major), 7.03–7.13 (stack, 2 H major and 2 H minor), 7.19–7.27 (stack, 1 H major and 1 H minor), 8.19 (d, J = 8.1 Hz, 1 H major), 8.22 (d, J = 8.1 Hz, 1 H minor). 13C{1H} NMR (100 MHz, CDCl3): δ = 170.3 (major), 170.0 (minor), 168.8 (major), 168.5 (minor), 142.12 (minor), 142.08 (major), 138.2 (major), 137.0 (minor), 128.5 (minor), 128.0 (major), 124.1 (minor), 123.8 (major), 122.1 (major), 122.0 (minor), 117.2 (minor), 117.0 (major), 61.1 (minor), 60.8 (major), 46.8 (minor), 44.1 (major), 42.5 (major), 42.3 (minor), 39.8 (minor), 38.3 (major), 36.2 (major), 33.3 (minor), 27.2 (major and minor), 24.32 (major), 24.29 (minor), 21.8 (major), 20.9 (minor). HRMS (ESI-TOF): m/z calcd for C16H23N2O2 + [M + H]+: 275.1754; found: 275.1762.
For recent reviews, see:
1-Methylpiperidine was also reported to react with N-arylacrylamides to afford 2,3-dihydrotryptamine-2-ones:
For selected examples, see:
For some examples:
For recent examples, see:
For some examples:
For recent examples: