Computational insight into the mechanism and origin of high regioselectivity in the ring-opening cyclization of spirocyc
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ORIGINAL PAPER
Computational insight into the mechanism and origin of high regioselectivity in the ring-opening cyclization of spirocyclopropanes with stabilized sulfonium ylides by the DFT Ruyu Zhu 1 & Yan Zhang 1 & Junxia Yang 1 & Yongsheng Yang 1 & Ying Xue 1 Received: 22 May 2020 / Accepted: 26 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Chromanes with high bioactivity play an important role in nature, and cyclization reactions of cyclopropanes with sulfonium ylides to form chromane skeletons have attracted great attention of scientists. The mechanism as well as origins of regioselectivity and stereoselectivity for the ring-opening/cyclization reactions between cyclohexane-1,3-dione-2-spirocyclopropanes and stabilized sulfonium ylides in CH2Cl2 were investigated by using the density functional theory (DFT) M06-2X/6–311+G(d,p)//M062X/6-31G(d,p) method combined with the SMD model. The calculated results revealed that the reaction process involved two key steps: the ring-opening step and the cyclization step, with the former being the rate-determining and stereoselectivitydetermining step. The regioselectivity of the ring-opening step of spirocyclopropane indicated that the tertiary carbon was more preferential than the secondary one when sulfonium ylide attacked spirocyclopropane. The theoretical results confirmed that the stereoselectivity of the reaction to form the trans-isomer product is more favorable than the cis-isomer, and the calculated trans/ cis ratio is in accordance with the experiment. Moreover, the conceptual density functional theory reactivity indices suggest that the electronic effect controls the regioselectivity. What is more, the stereoselectivity analyzed by weak non-covalent interaction also shows the importance of electronic effect. Keywords Sulfonium ylides . Spirocyclopropane . Cyclization reaction . Selectivity . CDFT calculation
Introduction It is well known that chromanes and their derivatives are important structural units of numerous natural products and bioactive molecules, and widely used in the field of medicine [1–4], as shown in Figure 1. Their structural diversity arises from the different substituents on the benzene moiety and the hydropyran ring, as well as further structural modifications [5, 6]. Their application as pharmacophore has been testified by a range of biological activities, such as anticancer, anti-HIV, antiparasitic, antibacterial, anti-inflammatory, antidiabetic, Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00894-020-04522-1) contains supplementary material, which is available to authorized users. * Ying Xue [email protected] 1
Key Lab of Green Chemistry and Technology in Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, People’s Republic of China
and antihypertensive activities [7–15]. Owing to their outstanding performance in biology and medicine, the simple and high efficient synthesis methods to obtain chromane and its derivatives have
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