Bicyclic cycloadduct fragmentations as a means of stereocontrol

Diversity in the Synthesis of Functionalized Cyclohexene Oxide Derivatives by a Cycloaddition–Fragmentation Sequence from Benzene Oxide

“…This compound is a byproduct in the synthesis of 1 that could be observed in cycloaddition crude products. Brown oil; 1 2,4 ]non-8en-7-yl)phosphine Oxide (3). A solution of N-hydroxy-P,Pdiphenylphosphinic amide SI-7 (150 mg, 0.64 mmol, 1.0 equiv) in methanol (12 mL) was added dropwise to a stirred mixture of tetrabutylammonium periodate (303 mg, 0.70 mmol, 1.1 equiv) and crude benzene oxide 1 (3.20 mmol, 5.0 equiv) in DCM (6 mL) at 0 °C under argon.…”

“…Di-tert-butyl (1R,2S,4R,5S)-3-Oxa-6,7-diazatricyclo[3.2.2.0 2,4 ]non-8-ene-6,7-dicarboxylate (5a). The reaction of di-tert-butyl azodicarboxylate (1.0 g, 4.34 mmol, 1.0 equiv) with crude benzene oxide 1 (21.7 mmol, 5.0 equiv) according to the general procedure afforded the corresponding cycloadduct 5a (1.4 g, 99% yield over two steps) as a white powder.…”

“…The reaction of di-tert-butyl azodicarboxylate (1.0 g, 4.34 mmol, 1.0 equiv) with crude benzene oxide 1 (21.7 mmol, 5.0 equiv) according to the general procedure afforded the corresponding cycloadduct 5a (1.4 g, 99% yield over two steps) as a white powder. 1 H NMR (360 MHz, CDCl 3 ) δ 6.24 (t, J = 6.8 Hz, 1H), 6.01 (t, J = 7.3 Hz, 1H), 5.16−5.23 (m, 2H), 3.61 (brs, 1H), 3.46 (brs, 1H), 1.47 (s, 9H), 1.41 (s, 9H); 13 Diisopropyl (1R,2S,4R,5S)-3-Oxa-6,7-diazatricyclo[3.2.2.0 2,4 ]non-8-ene-6,7-dicarboxylate (5b). The reaction of diisopropyl azodicarboxylate (0.48 mL, 2.47 mmol, 1.0 equiv) with crude benzene oxide 1 (12.4 mmol, 5.0 equiv) according to the general procedure afforded the corresponding cycloadduct 5b (648 mg, 89% yield over two steps) as a white powder.…”

“…as a white powder. 1 2,4 ]nonane-7-carboxylate (15). The reaction of cycloadduct 6 (200 mg, 0.62 mmol, 1.0 equiv) with palladium on carbon (53 mg, 0.050 mmol, 0.08 equiv) according to the general procedure afforded the corresponding reduced cycloadduct 15 (202 mg, quant.)…”

“…Synthetic sequences including cycloaddition and fragmentation reactions have been widely used in the synthesis of natural products, as they benefit from the high level of stereocontrol in the cycloaddition step. − Diels–Alder/fragmentation sequences often use cyclic dienes as starting materials, with fragmentation reactions involving retro-Diels–Alder reactions, reductive cleavage of a heteroatom–heteroatom bond, or anionic elimination (Figure ).…”