Construction of Pyrrolidinyl Spirooxindoles via a 1,3-Dipolar Cycloaddition Reaction of (E)-N-Boc-3-Alkylidene-Indolin-2(3H)ones with Azomethine Ylides

Abstract

A mild and efficient method for the construction of pyrrolidinyl spirooxindoles via a 1,3-dipolar cycloaddition reaction of (E)-N-Boc-3-alkylidene-indolin-2(3H)ones with azomethine ylides has been established. The presence of an N-Boc group in the indolin-2(3H)ones obviously increased the activity and stereoselectivity of the reaction, affording the desired pyrrolidinyl spirooxindoles 4 with up to 85% yield and up to >99/1 dr value. Furthermore, the antibacterial activity of these compounds against Staphylococcus aureus (ATCC-25825) has been tested at minimum concentration, and some of them exhibit moderate antibacterial activity.

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GRAPHICAL ABSTRACT

Keywords:

• Azomethine ylides
• cycloaddition reaction
• spirooxindoles

ACKNOWLEDGMENTS

We are grateful for financial support from the National Natural Science Foundation of China (No. 21062003); Modernization of Traditional Chinese Medicine special of Guiyang ([2010] Zhu Ke Hetongzi 1-Zhong-18); and Excellent Young Scientific Talents Foundation of Guizhou ([2011(34)] Qian Ke Herenzi).

Notes

^a Unless noted, reactions were carried out with 0.5 mmol of 2b, 2.5 mmol of sarcosine, and 5.0 mmol of paraformaldehyde.

^b Isolated yield after flash chromatography.

^c Determined by ¹H NMR analysis of the crude products.

^d The reaction was carried out with 0.5 mmol of 2b, 2.0 mmol of sarcosine, and 4.0 mmol of paraformaldehyde.

^e Only 1.0 mmol of sarcosine was used under otherwise identical conditions.

^a Unless noted, reactions were carried out with 0.5 mmol of 2, 2.0 mmol of sarcosine, and 4.0 mmol of paraformaldehyde in 8 mL CHCl₃CH₃ at 75 °C for 8 h.

^b Isolated yield after flash chromatography.

^c Determined by ¹H NMR analysis of the crude products.

^d —, no inhibition against Staphylococcus aureus even at maximum concentration.