Absolute Asymmetric Synthesis Involving Chiral Symmetry Breaking in Diels–Alder Reaction
1
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, Yayoi-Cho, Inage-Ku, Chiba 263-8522, Japan
2
Molecular Chirality Research Center, Chiba University, Yayoi-Cho, Inage-Ku, Chiba 263-8522, Japan
*
Author to whom correspondence should be addressed.
Symmetry 2020, 12(6), 910; https://doi.org/10.3390/sym12060910
Received: 27 April 2020
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Revised: 14 May 2020
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Accepted: 18 May 2020
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Published: 1 June 2020
(This article belongs to the Special Issue Chemical Symmetry Breaking)
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.
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Keywords:
amplification of chirality; dynamic crystallization; Diels–Alder reaction; absolute asymmetric synthesis; conglomerate; racemization; attrition-enhanced deracemization; Viedma ripening; reversible reaction; enantiomorphic crystal; polymorphism
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MDPI and ACS Style
Uemura, N.; Toyoda, S.; Shimizu, W.; Yoshida, Y.; Mino, T.; Sakamoto, M. Absolute Asymmetric Synthesis Involving Chiral Symmetry Breaking in Diels–Alder Reaction. Symmetry 2020, 12, 910. https://doi.org/10.3390/sym12060910
AMA Style
Uemura N, Toyoda S, Shimizu W, Yoshida Y, Mino T, Sakamoto M. Absolute Asymmetric Synthesis Involving Chiral Symmetry Breaking in Diels–Alder Reaction. Symmetry. 2020; 12(6):910. https://doi.org/10.3390/sym12060910
Chicago/Turabian StyleUemura, Naohiro, Seiya Toyoda, Waku Shimizu, Yasushi Yoshida, Takashi Mino, and Masami Sakamoto. 2020. "Absolute Asymmetric Synthesis Involving Chiral Symmetry Breaking in Diels–Alder Reaction" Symmetry 12, no. 6: 910. https://doi.org/10.3390/sym12060910
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