Synthesis of non-racemic dihydrofurans via Ni(II)-catalyzed asymmetric Michael addition

First synthesis of acylated nitrocyclopropanes

“…The reaction of chlorinated nitrostyrene 2b with acetylacetone ( 3b ) was in the same way, and the obtained product 9 was converted to the 2,4-dinitrophenylhydrazone 10 to facilitate the crystallization for X-ray crystallography, which showed that a 2,3-dihydrofuran framework had formed ( Scheme 4 , bottom). Hence, we clarified that product 8b was not the desired cyclopropane, but a dihydrofuran, so the cyclopropane 1b’ reported in the literature [ 12 – 13 19 ] is presumably incorrect [ 22 ]. In the cases of donor–acceptor cyclopropanes possessing an electron-donating group such as an alkoxy or amino group, ring expansion caused by an intramolecular attack of nitro oxygen occurs, leading to five-membered cyclic nitronates [ 23 ].…”

“…Furthermore, the latter cyclization predominantly proceeded as the acyl group became bulkier. The polyfunctionality of products 1 and 8 facilitate further chemical conversion [ 22 ]. Nitrocyclopropane 1e was converted into furan 13 by treatment with tin(II) chloride.…”

Recent developments in enantioselective nickel(ii)-catalyzed conjugate additions

“…With the aim of developing a simple methodology for the synthesis of chiral trans -4,5-dihydrofurans that constitute the key skeletons of numerous bioactive and natural products, Nikerov et al applied in 2021 2 mol% of chiral nickel catalyst 1 to promote the asymmetric Michael addition of 1,3-diketones to α-bromonitroolefins. 23 As shown in Scheme 5, the process performed at 20 °C in toluene as solvent afforded the corresponding chiral nitroketones as mixture of diastereomers in moderate to high yields (40–95%) and low to moderate diastereoselectivities (6–66% de). This mixture was subsequently submitted to cyclization by treatment with DMAP in acetonitrile as solvent, resulting in the formation of desired chiral tetrasubstituted 4,5-dihydrofurans obtained with good yields (50–85%), combined with both high trans -diastereo- (80–>99% de) and enantioselectivities (84–99% ee).…”

Microwave Assisted Synthesis of 2,3‐Dihydro‐4H‐ furo[2,3‐d]pyrido[1,2‐a]pyrimidin‐4‐ones and furo[2,3‐d]pyrido[1,2‐a]pyrimidin‐4‐one

“…Dihydrofurans are important pharmacophores exist in many natural compounds such as jiadifenlactone A, [5] inoscavin A, [6] clerodin [7] and austocystin [8] (Figure 2).…”