Synthesis of Modified Methyl Furanosides by Intramolecular Oxa-Michael Reaction followed by Pummerer Rearrangement

Abstract

A new method is described for the synthesis of ribofuranoses modified at the C3 and C5 positions. The key step is an intramolecular oxa-Michael reaction on a vinyl sulfoxide to install the C2 hydroxy group. The methyl furanosides are obtained by Pummerer rearrangement of the sulfoxide into the corresponding aldehyde, acidic deprotection of the benzylidene acetal, and cyclization.

Diastereoselective synthesis of trifluoromethylated 1,3-dioxanes by intramolecular oxa-Michael reaction

“…The most usual reagent is benzaldehyde but there are several examples in the literature where p-methoxy benzaldehyde has been used successfully. 5 Concerning the Michael acceptor and the substitution pattern the reaction has been explored with esters and amides, 3 sulfones 6 and sulfoxides, 7 and in very few cases with substituents α to the Michael acceptor. 8 Inspired by those previous results and by the need for a simple method to synthesise CF 3 -containing dioxanes, we decided to explore the intramolecular oxa-Michael reaction using trifluoroacetophenone and a homoallylic alcohol functionalised with an ester as substrates (Scheme 1).…”

“…acceptors such as Weinreb amides or sulfones were explored. The cited literature [3][4][5][6][7][8] shows that the reactivity of the Michael acceptors does not have a great influence on the yield of the oxa-Michael reaction. The main difference is the diastereoselectivity.…”

High Regio- and Diastereo-Selective Synthesis of 1,5-Dicarbonyls by Michael Addition

“…Column chromatography was carried out on silica gel. 1 H and 13 C NMR spectra were recorded at 300, 75 and 125 MHz, respectively. All reagents were used directly as obtained commercially unless otherwise noted.…”

“…Aromatic substrates with an electron-withdrawing group as well as electron-donating group all work well to give the desired products in good yields with good diastereoselectivities ( Table 2, entries [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. A 60% yield with good diastereoselectivity was obtained when (E)-3-(furan-2-yl)-1-phenylprop-2-en-1-one was employed as Michael acceptor ( Table 2, entry 15).…”

Water‐Compatible Synthesis of 2‐Trifluoromethyl‐1,3‐Dioxanes

“…The method is based on the in situ generation of a hemiacetal anion that reacts in a Michael addition. This reaction, known since 1993, has been applied to the synthesis of many natural products – as a method to obtain protected syn 1,3‐diols –, used with different Michael acceptors and reviewed very recently in the literature . Unfortunately, this reaction uses strong bases and requires anhydrous conditions.…”