Regioselectivity in the 1,3-dipolar cycloaddition of adamantylidenefulvene and its modification by inclusion in cyclodextrins' solutions

Jean Ho Chu, Wan Sheung Li, Ito Chao*, Gene Hsiang Lee, Wen-Sheng Chung

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The 1,3-dipolar cycloaddition of adamantylidenefulvene (1) with 2 equiv of nitrile oxides 2a-d gave 1/1 cycloadducts, 3a-d and 4a-d, as the major products, and four other 1/2 minor cycloadducts 5-8a,b. The ratios of 1/1 cycloadducts 3a-d to 4a-d in THF solution were about 1/1 in the four different nitrile oxides 2a-d studied and microwave was found to accelerate the reactions and enhance their yields. It is noteworthy that the regioselectivity of 3a/4a was enhanced to 71/29 in β-cyclodextrin (β-CD) aqueous solution compared to that of 40/60 in the absence of β-CD. The regioselectivity of 3b/4b was further enhanced to 99/1 when 4-tert-butylphenyl hydroximinoyl chloride (9b) was complexed with β-CD and then proceeded to react with 1; this is in sharp contrast with that of 33/67 in the absence of β-CD. The binding constant of 1·β-CD in acetone-d6/D2O (1/1) was determined to be 188±9 M-1 by 1H NMR titration experiments. The binding mode of 1·β-CD was further determined by ROESY experiment. Furthermore, molecular dynamic simulations were carried out to provide information of the complexation modes of 1·β-CD, 3a·β-CD, 4a·β-CD, 9a·β-CD, and 9b·β-CD. It was found that both steric and electrostatic effects play important roles in determining the regio- and stereochemistry of 1,3-dipolar cycloaddition of 1. Finally, β-CD is shown to serve as a chiral shift reagent to differentiate the enantiomers of 4a in 1H NMR.

Original languageEnglish
Pages (from-to)7380-7389
Number of pages10
JournalTetrahedron
Volume62
Issue number31
DOIs
StatePublished - 31 Jul 2006

Keywords

  • 1,3-Dipolar cycloaddition
  • Chiral shift reagent
  • Fulvene
  • Inclusion complex
  • Molecular reactor
  • Regioselectivity
  • Steric effect

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