Highly Regioselective 3-Hydroxyalkylations of Boron 4-Methoxy-2-furanolates: A New Entry to 5-Unsubstituted and 5-Monosubstituted 3-Acyl-4-O-Methyl Tetronates

Abstract

Boron 4-methoxy-2-furanolates generated in situ from 5-unsubstituted and 5-monosubstituted 4-O-methyl tetronates undergo highly regioselective 3-hydroxyalkylations with aldehydes to give 5-unsubstituted and 5-monosubstituted 3-acyl-4-O-methyl tetronates, respectively, in good overall yields after oxidation of the intermediate alcohols with 2-iodoxybenzoic acid.

Key words

antibiotics - furanones - boron furanolates - hydroxyalkylation - regioselectivity

References

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4

4-Methoxyfuran-2(5H)-one (5) is commercially available e.g. from Acros Organics BVBA, Janssen Pharmaceutica-laan 3a, B-2440 Geel, Belgium.

12

Comparable yields were obtained running the reactions at
-78 °C for 18 h.

13

A major advantage of the commercially available PhBCl₂ is that it can be stored at r.t. under N₂ for several months without deterioration (determined by ¹¹B NMR spectroscopy) in contrast to the more common dialkylboron triflates, which are relatively unstable and may have to be freshly prepared. [10]

14

The formation of complex 9 was indicated by the appearance of a voluminous precipitate, which dissolves gradually on addition of base.

16

Since yields of 7a based on both recovered starting materials 5 and pivalaldehyde are excellent (>90%) using 1.05 equiv PhBCl₂, a twofold excess of the relative expensive boron reagent was avoided in the following reactions for reasons of efficiency.