Exploring endoperoxides as a new entry for the synthesis of branched azasugars

A new class of nitrogen-containing endoperoxides were synthesised by a photochemical [4 + 2]-cycloaddition between a diene and singlet oxygen. The endoperoxides were dihydroxylated and protected to provide a series of endoperoxide building blocks for organic synthesis, with potential use as precursors for the synthesis of branched azasugars. Preliminary exploration of the chemistry of these building blocks provided access to a variety of derivatives including tetrahydrofurans, epoxides and protected amino-tetraols.


S3
connected to an Agilent 1200 HPLC system using an electrospray ionization (ESI) mass detector. Bruker Daltonics DataAnalysis Version 3.3 was used for data analysis. High resolution mass spectrometry (HRMS) was performed in positive ion mode with MALDI ionisation on a Thermo QExactive Orbitrap mass spectrometer equipped with an APSMALDI 10 ion source and operated at mass resolving power 140,000@m/z200. DHB was used as matrix and lock-mass for internal mass calibration.
The photochemical reactor used herein was made by modification of a standard photochemical reactor with a mercury lamp. A glassblower attached a gas inlet tube with a sintered glass filter to the bottom of the reactor to allow bubbling oxygen gas through the solution. Finally, the mercury lamp from the original system was replaced by three 100 W halogen bulbs from Philips (Capsuleline 100W GY6.35 12V CL 4000H 1CT/10X10F Single-ended low-voltage halogen capsule giving crisp white halogen light).
The analytical data is in agreement with that reported previously [2].
S6 TLC R f = 0.45 (60% EtOAc in n-heptane, v/v). The analytical data is in agreement with that previously reported [3].

2-(4-Hydroxybutyl)isoindoline-1,3-dione (6)
4-Aminobutan-1-ol (1.78 g, 20 mmol) was added to a 100 ml round bottom flask fitted with a Dean-Stark receiver and suspended in dry toluene (60 ml). Phthalic anhydride (2.96 g, 20 mmol) was added and the mixture was heated to reflux with stirring for 3.5 h. The solvent was evaporated in vacuo and the residue purified by flash column chromatography (60% EtOAc in n-heptane, v/v) to give phthalimide 6 (3.32 g, 76%) as a white amorphous solid. The analytical data is in agreement with that previously reported [4].
Triethylamine (12 ml, 85.7 mmol) and sulfur trioxide pyridine complex (2.7 g, 17.1 mmol) were added and the mixture was stirred at rt for 4.5 h. The mixture was transferred to a separatory funnel with sulfate buffer (40 ml) and extracted with EtOAc (3 × 30 ml). The combined organic phases were washed with saturated aq.
HPLC t R = 7.32 min. The analytical data is in agreement with that previously reported [7]. S10
The reaction mixture was transferred to a separating funnel with sulfate buffer (40 ml) and extracted with EtOAc (3 × 40 ml). The combined organic phases were washed with NaHCO 3 (90 ml), and brine (90 ml), dried (Na 2 SO 4 ), filtered and concentrated in vacuo to give alkene 11 (0.37 g, 82%) as a white amorphous solid that required no further purification. Compound 11 has been reported previously with no characterisation [8].