Bu₂BOTf: A Powerful Tool in Stereoselective Synthesis

Introduction

In 1980 Mukaiyama et al. published the first synthesis of di-n-butylboryl trifluoromethanesulfonate (Bu₂BOTf) and demonstrated that this Lewis acid is particularly suitable for the generation of vinyloxyboranes (boron enolates). [1] In the presence of a sterically hindered amine base (typically i-Pr₂EtN, Et₃N or 2,6-lutidine) and Bu₂BOTf vinyloxyboranes are conveniently prepared from active methylene-carbonyl containing compounds. The boron enolates turned out to be efficient intermediates for addition to carbonyls in cross-aldol reactions. With unsymmetrical ketones, use of Bu₂BOTf and i-PrEt₂N results in the regioselective formation of the vinyloxyborane at the least hindered carbon. The relative stereochemistry of the new chiral centers formed in the aldol product is a direct consequence of vinyloxyborane enolate geometry with Z-enolates affording the 2,3-syn aldol products and the E-vinyloxyboranes leading to the 2,3-trans isomers. With Bu₂BOTf a remarkably high stereoselectivity towards the Z-enolate is observed which results in highly syn-selective aldol reactions. Probably the greatest utility of this reagent has been in the stereoselective formation of vinyloxyboranes attached to a chiral auxilary. [2] These are typified by the chiral oxazolidinones derived from α-amino alcohols initially developed by Evans. This modern methodology is a powerful tool for the highly enantioselective construction of two new chiral centers in an aldol addition under recycling of the auxilary. Vinyloxyboranes also react with electrophiles other than aldehydes, furthermore it is possible to generate boryl azaenolates with Bu₂BOTf. In the area of macrolactonization Bu₂BOTf has also been used.

References

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