Giuseppe Faita

This review is focused on the enantioselective synthesis of 3,4-dihydropyran derivatives, whose importance as chiral building blocks in the synthesis of bioactive molecules and natural products is well established. The review analyzes the different synthetic strategies by grouping them as a function of the atom numbers of the reagents involved. Starting from the classical [4 + 2] and [2 + 4] approaches, the [3 + 3], [5 + 1], and [6] strategies have been sequentially analyzed, and for each of them, the asymmetry induced by both chiral metal complexes and different kinds of organocatalysts has been examined. More than 400 papers have been reviewed, whose results have been described in the highest synthetic manner, in the attempt to emphasize the mechanism of the chirality transfer from the chiral messengers to the reaction products. This analysis allows the great flexibility of the diverse catalytic systems, the complementary of the results obtained from the different reaction pathways, and the very high level of control of the achievable molecular complexity to be evidenced.

Asymmetric reactions involving (E)‐3‐aryl‐1‐(pyridin‐2‐yl‐N‐oxide)prop‐2‐en‐1‐ones and cyclic enol silyl ethers show good yields and excellent enantioselectivities (up to 99.9 % ee) when catalysed by bis(oxazoline)–Cu^II complexes. Different reaction pathways can be followed by different enol silyl ethers: with 2‐(trimethylsilyloxy)furan, a Mukaiyama–Michael adduct is obtained, whereas a hetero Diels–Alder cycloadduct was formed by using (1,2‐dihydronaphthalen‐4‐yloxy)trimethylsilane. In the latter reaction, the absolute configuration of the product is consistent with a reagent approach to the less hindered Re face of the coordinated substrate in the reactive complex.

Diels–Alder and 1,3‐dipolar cycloadditions involving (E)‐3‐aryl‐1‐(pyridin‐2‐yl‐N‐oxide)prop‐2‐en‐1‐ones as the 2π components are efficiently catalysed by bis(oxazoline)–Cu^II complexes. The cycloadducts are obtained in quantitative yields with up to 98 % ee; absolute configurations were determined by X‐ray analysis. The structure of the reactive complex, determined by X‐ray analysis, is fully consistent with the stereochemical outcome of the catalysed process (approach of the diene or nitrone to the less hindered face of the coordinated pyridine‐N‐oxide derivative).