Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs.

Juanjuan Feng,Jiaxin Zhang,Peng Jiao,Tianyu Li

doi:10.3762/bjoc.15.179

Abstract

The asymmetric cycloaddition of TIPS nitronate catalyzed by “Cu(II)-bisoxazoline” gave the 2-isoxazoline product in 95% yield, which was converted into tert-butyl (3S,5R)-6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate in 14 steps through a β-hydroxy ketone.

Highlights

The chiral 1,3-diol structure is widespread in a broad spectrum of natural products [1,2]. (3R)-β-Hydroxy-δ-lactone or its openring equivalent (3R)-syn-3,5-dihydroxypentanoic acid, is a common structure in naturally occurring mevastatin, lovastatin or closely related statins, and synthetic statins
We report the preparations of tert-butyl (3S,5R)-6-hydroxy-3,5-Oisopropylidene-3,5-dihydroxyhexanoate and related syn-1,3-diol analogs from a chiral 2-isoxazoline (Scheme 1b)
Our synthesis commenced with a chiral 3,5-disubstituted-2isoxazoline 3 or 4, which were prepared from silyl nitronate through an asymmetric 1,3-dipolar cycloaddition developed in our lab (Table 1) [49]

Summary

Introduction

The chiral 1,3-diol structure is widespread in a broad spectrum of natural products [1,2]. (3R)-β-Hydroxy-δ-lactone or its openring equivalent (3R)-syn-3,5-dihydroxypentanoic acid, is a common structure in naturally occurring mevastatin (or compactin), lovastatin or closely related statins, and synthetic statins. The chiral 1,3-diol structure is widespread in a broad spectrum of natural products [1,2]. (3R)-β-Hydroxy-δ-lactone or its openring equivalent (3R)-syn-3,5-dihydroxypentanoic acid, is a common structure in naturally occurring mevastatin (or compactin), lovastatin or closely related statins, and synthetic statins. The Narasaka–Prasad reduction of a δ-hydroxyβ-keto esters derived from β-hydroxy esters [12-23] is widely used to prepare tert-butyl (3R)-3,5-O-isopropylidene-3,5-dihydroxyhexanoate (Scheme 1a) [24-37], which is a building block for synthetic statins [38-41], though enzymatic syntheses [4248] of the chiral β-hydroxy-δ-lactone moiety or its equivalents, pioneered by Wong [42], is competitive. We report the preparations of tert-butyl (3S,5R)-6-hydroxy-3,5-Oisopropylidene-3,5-dihydroxyhexanoate and related syn-1,3-diol analogs from a chiral 2-isoxazoline (Scheme 1b). This work is part of our continuous efforts in asymmetric syntheses and applications of chiral 2-isoxazolines [49-51]

Results and Discussion

Conclusion

72. Crystallographic data of 17