Forty Years after “Heterodiene Syntheses with α,β-Unsaturated Carbonyl Compounds”: Enantioselective Syntheses of 3,4-Dihydropyran Derivatives

Abstract

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.

Recent Advances in Organocatalyzed Asymmetric Synthesis of Benzopyran and Benzodihydropyran (Chromane) Nuclei

“…Chromane [4] arenes were obtained by the Diels-Alder reaction between the o-quinone methides of resorcin [4] arene and styrenes [34]. The authors identified their compounds as chiral, but actually, they were racemic mixtures.…”

“…Great work in summarizing the asymmetric synthesis of these compounds has been carried out [3][4][5][6]. However, in the last three years, many other new synthetic methods for the preparation of benzopyran and benzodihydropyran scaffolds have appeared in the literature, and this review aims to give an overview of the new organocatalyzed syntheses.…”

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

“…The Diels–Alder (DA) reaction is a useful and easy-to-perform method for the synthesis of six-membered rings through the direct formation of C–C bonds between a diene and a dienophile (a substituted alkene); it is called a hetero-Diels–Alder (HDA) reaction when one or more heteroatoms (most often oxygen or nitrogen) are present among the reactants, such as the use of carbonyl compounds or imines as dienophiles [1–5]. An asymmetric HDA reaction is capable of introducing up to four stereogenic centers in a one-step [4 + 2] cycloaddition or cyclization reaction [6–8] and it has become hugely popular in preparing vital intermediates for the syntheses of key structural subunits of natural products with biological activities (e.g., carbohydrates, antibiotics, toxins etc.) [9–10].…”

Rhodium‐Catalysed Asymmetric Synthesis of 4‐Alkyl‐4H‐Chromenes

“…[2] Given the importance of this privileged chiral structure, considerable efforts have been devoted to developing versatile methods for their asymmetric synthesis. [3] Over the past decades, various approaches such as asymmetric nucleophilic addition to benzopyrylium ion, [4] asymmetric trapping of orthoquinone methide, [5] and intermolecular cyclization under asymmetric iminium-allenamine catalysis, [6] among others, [7] have been successfully developed to achieve a series of chiral 4H-chromenes. Despite the merits of these approaches, the existing strategies are generally not applicable to the synthesis of 4-alkyl-4Hchromenes.…”