Absolute Asymmetric Synthesis Involving Chiral Symmetry Breaking in Diels–Alder Reaction

Abstract

Efficient generation and amplification of chirality from prochiral substrates in the Diels–Alder reaction (DA reaction) followed by dynamic crystallization were achieved without using an external chiral source. Since the DA reaction of 2-methylfuran and various maleimides proceeds reversibly, an exo-adduct was obtained as the main product as the reaction proceeded. From single crystal X-ray structure analysis, it was found that five of ten exo-adducts gave conglomerates. When 2-methylfuran and various maleimides with a catalytic amount of TFA were reacted in a sealed tube, the exo-DA adducts were precipitated from the solution, while the reaction mixtures were continuously ground and stirred using glass beads. Deracemization occurred and chiral amplification was observed for four of the substrates. Each final enantiomeric purity was influenced by the crystal structure, and when enantiomers were included in the disorder, they reached an enantiomeric purity reflecting the ratio of the disorder. The final ee value of the 3,5-dimethylphenyl derivative after chiral amplification was 98% ee.

Resonance in Chirogenesis and Photochirogenesis: Colloidal Polymers Meet Chiral Optofluidics

“…Previously, Ghosh and Fischer [193] and Silverman et al [194] simulated that the optical rotation from chiral liquids is boosted by several orders of magnitude when a coupled geometry of multiple prisms is filled with optically active biomolecular liquids, such as limonene, carvone, and a mixture of camphorquinone and methanol. The concept of AAS with light, one of the curious topics in the present special issue of Symmetry [197], is classified to: (i) absolute asymmetric photosynthesis; (ii) photodestruction; and (iii) photoresolution [47][48][49].…”

Supramolecular Diversity of Oxabicyclo[2.2.2]octenes Formed between Substituted 2H-Pyran-2-ones and Vinyl-Moiety-Containing Dienophiles

“…All hydrogen atoms were readily located in difference Fourier maps and were subsequently treated as riding atoms in geometrically idealized positions with U iso (H) = kUeq(C,N), where k = 1.5 for NH and methyl groups, which were permitted to rotate but not to tilt, and 1.2 for all the other H atoms. In endo-3b atoms C9-C10 and C24 in each ethoxy group were disordered over two positions with the refined ratios 0.805 (19):0.195 (19) and 0.444(11):0.556 (11), respectively. Atoms C9A, C9B, C10A and C10B were refined with restrained U ij components.…”

“…Generally accepted Alder endo rule predicts the formation of the endo product as the predominant one. As a consequence of all this, the Diels-Alder reaction is currently in the spotlight of various investigations where amplification of chirality is achieved by dynamic crystallization, an example demonstrated with maleimides and 2-methylfuran (Scheme 1) [11]. Another recent application of cycloaddition reactions, albeit under photochemical conditions, is for the preparation of photochromic organic crystals [12], offering promising properties.…”

“…On the other hand, aromatization of the cyclohexadiene systems can Scheme 1. Highly enantioselective Diels-Alder reactions with 2-methylfuran as diene and N-substituted maleimides [11].…”

Attrition-Enhanced Deracemization and Absolute Asymmetric Synthesis of Flavanones from Prochiral Precursors

“…In recent years, asymmetric transformations using naturally generated crystal chirality have provided chiral symmetry breaking of racemic mixtures by dynamic crystallization, − and absolute asymmetric synthesis from a prochiral substrate to form an asymmetric center that racemizes into a product with high enantiomeric purity. − Some novel examples have been demonstrated, such as an asymmetric aza-Michael addition involving the racemization of the products leading to enantiomorphic crystals. − Products with very high enantiomeric purity were successfully obtained from prochiral materials. Here, we designed a new reaction protocol for the absolute asymmetric synthesis of flavanones, as shown in Figure , in which flavanone 4 can be obtained by aldol condensation of an achiral 2-hydroxyacetophenone 1 and an aromatic aldehyde 2 , followed by intramolecular oxa-Michael addition.…”