Decarboxylative, Diastereoselective and exo-Selective 1,3-Dipolar Cycloaddition for Diversity-Oriented Construction of Structural Spiro[Butyrolactone–Pyrrolidine–Chromanone] Hybrids
Dong-Gui Guo
a
College of Food and Pharmaceutical Engineering, Guizhou Institute of Technology, Guiyang, 550025, P. R. of China
,
Zheng Li
b
National & Local Joint Engineering Research Center for the Exploitation of Homology Resources of Medicine and Food, Guizhou University, Guiyang, Guizhou 550025, P. R. of China
,
Xiao-Xue Han
b
National & Local Joint Engineering Research Center for the Exploitation of Homology Resources of Medicine and Food, Guizhou University, Guiyang, Guizhou 550025, P. R. of China
,
Lei Zhang
b
National & Local Joint Engineering Research Center for the Exploitation of Homology Resources of Medicine and Food, Guizhou University, Guiyang, Guizhou 550025, P. R. of China
,
Min Zhang
b
National & Local Joint Engineering Research Center for the Exploitation of Homology Resources of Medicine and Food, Guizhou University, Guiyang, Guizhou 550025, P. R. of China
b
National & Local Joint Engineering Research Center for the Exploitation of Homology Resources of Medicine and Food, Guizhou University, Guiyang, Guizhou 550025, P. R. of China
› InstitutsangabenWe are grateful for the financial support from the NSFC (81760625 and 22061006) and Science and Technology Program of Guizhou Province ([2020]4Y205, [2020]1Z074, [2018]5781, and [2017]7295).
Inspired by the chemistry and biology of butyrolactones, pyrrolidines, and chromanones, we successfully developed a simple domino 1,3-dipolar cycloaddition of homoserine-lactone-derived azomethine ylides for the construction of biologically important spiro[butyrolactone–pyrrolidine–chromanone] hybrids in the presence of Et3N as a catalyst under mild conditions. The reaction is based on the application of carboxylic-acid-activated chromones as dienophiles, followed by a decarboxylation process. This reaction displayed good substrate tolerance and gave the desired products in moderate to good yields with high diastereoselectivities (up to 85% yield and >20:1 diastereomeric ratio) via an exo-transition state. This is the first example of an introduction of a chromanone moiety into a spiro[butyrolactone-pyrrolidine] framework, which might be valuable in medicinal chemistry.
127-Methyl-1-phenyl-1,4′,5′,9a-tetrahydro-3aH-spiro[chromeno[2,3-c]pyrrole-3,3′-furan]-2′,9(2H)-dione (3b); Typical Procedure
Compound 1a (0.30 mmol) and compound 2b (0.20 mmol) were dissolved in CH2Cl2 (1.5 mL). Et3N (1.3 equiv, 0.26 mmol) was added to this solution at rt, and the mixture was stirred for 48 h. After the removal of the solvent, purification by flash column chromatography [silica gel, hexane–EtOAc (5:1)] gave a light-yellow solid; yield: 49.6 mg (71%; 16:1 dr); mp 216.3–216.9 °C.
1H NMR (400 MHz, CDCl3): δ = 2.23 (s, 3 H), 2.29–2.34 (m, 1 H), 2.44–2.52 (m, 1 H), 2.99–3.02 (m, 1 H), 4.26–4.33 (m, 1 H), 4.36–4.41 (m, 1 H), 4.91–4.96 (m, 2 H), 6.82 (d, J = 8.8 Hz, 1 H), 7.19–7.32 (m, 6 H), 7.57 (s, 1 H). 13C NMR (100 MHz, CDCl3): δ = 19.4, 36.0, 55.0, 62.5, 63.9, 68.7, 83.5, 116.9, 117.8, 125.4, 125.8, 126.9, 127.5, 130.8, 136.7, 140.1, 155.9, 174.5, 188.3. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C21H19NNaO4: 372.1206; found: 372.1207.
13 CCDC 2074189 and 2074188 contain the supplementary crystallographic data for compounds 3b and 3t, respectively. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.
