DOI: 10.15125/bath-01255
title: Dataset for the Synthesis of N-alkoxycarbonyl pyrroles from O-substituted carbamates – A synthetically enabling pyrrole protection strategy

description: This dataset contains nuclear magnetic resonance (NMR) raw data for all novel compounds reported in the associated publication, "Synthesis of N-alkoxycarbonyl pyrroles from O-substituted carbamates – A synthetically enabling pyrrole protection strategy".

The NMR files are provided as FID (Free Induction Decay) files, the standard format for NMR raw data. There are multiple software packages that can read this data, including but not limited to MestreNova, TopSpinACD/Labs NMR Workbook suite, ACD/Labs Spectrus JS.
description: NMR Spectroscopy: 1H and 13C NMR spectra were obtained using a 500 MHz Agilent ProPulse 500 or a 400 MHz Bruker NMR spectrometer, for which proton decoupling was active for 13C NMR. Spectra were acquired at 298 K and were referenced to residual solvent peaks. Chemical shifts are reported in parts per million (ppm) relative to residual chloroform (δ = 7.26 ppm, 1H; 77.16 ppm, 13C), acetone (δ = 2.05 ppm, 1H; 29.84, 206.26 ppm, 13C) or dimethyl sulfoxide (δ = 2.50 ppm, 1H; 39.52 ppm, 13C). Coupling constants, J, reported in Hz, were calculated using MestreNova x64 to the nearest 0.1 Hz. 1H and 13C{1H} assignments for novel compounds are corroborated though 2D NMR experiments (COSY, NOESY, HSQC, HMBC).

Further details of the methodology may be found in the associated paper.
description: MestreNova - NMR analysis
description: General procedure for N-Carboxy pyrrole synthesis: Carbamate (4 mmol, 1.0 equiv) and 1,4-dimethoxytetrahydrofuran (0.63 mL, 4.4 mmol, 1.1 equiv, mixture of cis and trans) were added to a flask and purged with nitrogen. AcOH (2.2 mL) was added, and the reaction was heated to reflux (110 °C) using a heating mantle. The reaction was monitored by TLC, and upon completion was cooled to ambient temperature. (Vanillin TLC stain used for non-UV active substrates). CH2Cl2 (50 mL) was added, then washed with saturated Na2CO3(aq) (50 mL × 2), then brine (50 mL). The organic layer was dried over MgSO4 and filtered, then the filtrate was concentrated in vacuo. The crude product was purified by passage through a silica plug (elution with CH2Cl2) and any residual 1,4-dimethoxytetrahydrofuran starting material was removed under vacuum.

General Procedure for Acylation reactions using TFAA: To a nitrogen-purged flask of N-carboxy pyrrole (1.0 equiv), and carboxylic acid (3.0 equiv) in dry dichloromethane (c = 0.44 M), trifluoroacetic anhydride (10 equiv.) was added dropwise at ambient temperature. The reaction was monitored by TLC, and upon completion the reaction was diluted with CH2Cl2 and washed with 1 M Na2CO3(aq). The organic layer was separated, and the aqueous layer extracted with CH2Cl2 (×2). The combined organic solutions were then washed with brine, dried over MgSO4, and filtered, then the filtrate was concentrated in vacuo.  The crude product was purified by column chromatography (SiO2, EtOAc–Pet Ether).

General Procedure for Acylation reactions using Tf2O: To a nitrogen-purged flask of N-carboxy pyrrole (1 equiv.), and carboxylic acid (1 equiv.) in dry dichloromethane (c = 0.44 M), trifluoromethanesulfonic anhydride (10 equiv.) was added dropwise at 0 oC. The reaction was stirred without further cooling and monitored by TLC, and upon completion the reaction was diluted with CH2Cl2 and washed with 1 M Na2CO3 (aq).  The organic layer was separated, and the aqueous layer extracted with CH2Cl2 (×2). The combined organic solutions were then washed with brine, dried over MgSO4, and filtered, then the filtrate was concentrated in vacuo.  The crude product was purified by column chromatography (SiO2, EtOAc–Pet Ether).

General Procedure for N-Troc deprotection: To zinc dust (1.72 mmol) and the N-Troc protected product (0.44 mmol), CH2Cl2 (3.2 mL) and AcOH (0.66 mL) were added. The reaction was stirred at ambient temperature and monitored by TLC until consumption of starting material. The reaction mixture was diluted with acetone (30 mL) and filtered through celite, then concentrated under vacuum to obtain analytically pure product.

General Procedure for N-Tosyl deprotection: NaOH pellets (3 equiv.) were crushed and added to a solution of N-Tosyl pyrrole product in (9:1) MeOH/H2O (0.81 M) and stirred overnight at ambient temperature. EtOAc was added, the phases were separated, and the aqueous phase was extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4 and filtered. The filtrate was evaporated to dryness to obtain analytically pure product.
description: The data are labelled with compound name and number according to paper.