Direct Synthesis of anti-1,3-Diols through Nonclassical Reaction of Aryl Grignard Reagents with Isopropenyl Acetate

Abstract

A series of symmetrical aromatic 1,3-diols were efficiently synthesized from substituted aryl Grignard reagents and isopropenyl acetate in a one-step reaction that formed anti products as the major species. Both experimental and theoretical studies suggested that the reaction involves the formation of a relatively stable intermediate E containing a six-membered ring from intermediate A. The stereoselectivity of the reactions and the molecular structure of the products were confirmed by NMR spectroscopy, X-ray diffraction, and gas chromatography.

A one-pot diastereoselective synthesis of 1,3-diols and 1,3,5-triols via cascade reactions of arylalkynyl Grignard reagents with enol esters

“…The preferred formation of the 1,3-anti-diols 4 may involve chelation control. 30 1,3,5-Triols 5 are expected via similar mechanisms.…”

“…The reaction between PhC≡CMgBr and 1a was first carried out under the same conditions as those used in the reaction of PhMgBr with 1a. 30 At 0 °C to room temperature (rt), the expected products 4aa and unexpected byproduct 5aa were obtained in 65% yield under N 2 overnight ( Table 1, entry 1). Further measurements revealed that the ratio of anti/syn-1,3-diols 4aa is 2.2:1 and that of anti,syn/anti,anti-1,3,5-triols 5aa is 7.7:1.…”

“…28,29 We have previously reported on the reactions of substituted aryl Grignard reagents with isopropenyl acetate in one step to form a series of symmetrical aromatic anti/syn-1,3-diols with the antiproducts as the major species. [30][31][32] The stereoselectivity of the reaction was confirmed, and the reaction mechanism of the reaction was speculated upon. In subsequent studies, we found that a 1,3,5-triol was the trace by-product of the reaction and this aroused our interest in further research on this process.…”

Crystal structure of syn-2,4-di-o-tolylpentane-2,4-diol, C19H24O2

“…After the mixture was stirred for 5 h, the reaction was terminated by a saturated NH4Cl solution. The organic product was extracted with ethyl acetate [3][4][5]. The combined organic layer was washed with brine, dried over Na 2 SO4 and concentrated in vacuo to give a crude oil.…”

Enol Acetates

“…18 The 1,3-diol moiety is present in a number of natural products, including polyene macrolide antibiotics.…”