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Synlett 2020; 31(12): 1197-1200
DOI: 10.1055/s-0040-1707522
DOI: 10.1055/s-0040-1707522
letter
Dual In Situ Generation of Aliphatic Vinyl Ethers and Electron-Deficient ortho-Quinone Methides for Inverse-Electron-Demand [4+2] Cycloaddition: A Selective One-Pot Synthesis of 3-Alkylchromanes
Further Information
Publication History
Received: 05 March 2020
Accepted after revision: 02 April 2020
Publication Date:
06 May 2020 (online)
![](https://www.thieme-connect.de/media/synlett/202012/lookinside/thumbnails/st-2020-u0130-l_10-1055_s-0040-1707522-1.jpg)
Abstract
An inverse-electron-demand [4+2] cycloaddition of in situ generated aliphatic vinyl ethers and electron-deficient ortho-quinone methides (o-QMs) has been developed. The reaction of in situ generated aliphatic vinyl ethers with o-QMs afforded the corresponding 3-alkylchromanes with high stereo- and regioselectivities. The method provides a versatile access to functionalized 3-alkylchromanes and it constitutes a useful tool for the synthesis of biologically active chromanes.
Key words
catalysis - [4+2] cycloaddition - vinyl ethers - ortho-quinone methides - salicylaldehydes - chromanesSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707522.
- Supporting Information
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References and Notes
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- 11 3-Substituted Chromanes 3a–m and 4a–c; General Procedure The appropriate salicylaldehyde 1 (0.50 mmol), aliphatic or aryl aldehyde 2 (1.50 mmol), and CH(OMe)3 (2.00 mmol) were dissolved in dry toluene (5.0 mL) under N2. TfOH (20 mol%) was added, and the mixture was stirred at 60 °C for 24 h. The reaction was then quenched with 5% aq NaHCO3, and the organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography [silica gel, hexane–EtOAc (30:1)] to afford 3-substituted chromane 3 or 4. 2,4-Dimethoxy-3,3-dimethyl-6-nitrochromane (3a) Prepared by using 5-nitrosalicylaldehyde (83.7 mg, 0.50 mmol), isobutyraldehyde (135 μL, 1.50 mmol), CH(OMe)3 (219 μL, 2.00 mmol), and anhyd toluene (5.0 mL) to give a yellow solid; yield: 135 mg (quant); mp 97.8–98.2 °C. IR (ATR): 2928, 1588, 1520, 1481, 1253, 1091, 977, 833, 751 cm–1. 1H NMR (500 MHz, CDCl3): δ = 8.20 (d, J = 2.8 Hz, 1 H), 8.11 (dd, J = 9.1, 2.8 Hz, 1 H), 6.92 (d, J = 8.8 Hz, 1 H), 4.83 (s, 1 H), 4.04 (s, 1 H), 3.62 (s, 3 H), 3.56 (s, 3 H), 1.04 (s, 3 H), 1.00 (s, 3 H). 13C{1H} NMR (126 MHz, CDCl3): δ = 157.3, 141.4, 125.1, 124.6, 123.9, 117.0, 106.6, 80.6, 60.4, 57.2, 37.0, 20.3, 18.9. HRMS (ESI+): m/z [M + H]+ calcd for C13H18NO5: 268.1180; found: 268.1190.
For a representative in situ generation of an o-QM from 2-[hydroxy(phenyl)methyl]phenol, see:
For representative syntheses of 3-alkylchromanes, see: