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Theoretical Insight into the Au(I)-Catalyzed Intermolecular Condensation of Homopropargyl Alcohols with Terminal Alkynes: Reactant Stoichiometric Ratio-Controlled Chemodivergence Yiying Yang, Jinghua Li, Rongxiu Zhu, Chengbu Liu, and Dongju Zhang J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02411 • Publication Date (Web): 05 Nov 2018 Downloaded from http://pubs.acs.org on November 8, 2018
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The Journal of Organic Chemistry
Theoretical Insight into the Au(I)-Catalyzed Intermolecular Condensation of Homopropargyl Alcohols with Terminal Alkynes: Reactant Stoichiometric Ratio-Controlled Chemodivergence
Yiying Yang,† Jinghua Li,‡, § Rongxiu Zhu,*,† Chengbu Liu,† and Dongju Zhang*,†
†Key
Lab of Colloid and Interface Chemistry, Ministry of Education, Institute of Theoretical
Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. China
‡Department
of Materials Science and Engineering, Frederick Seitz Materials Research
Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States
§Department
of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, United States
Author E-mail Addresses:
[email protected];
[email protected] 1
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ABSTRACT The mechanisms and chemoselectivities on the Au(I)-catalyzed intermolecular condensation between homopropargyl alcohols and terminal alkynes were investigated by performing DFT calculations. The reaction was indicated to involve three stages: transformation of the homopropargyl alcohol (R1) via intramolecular cyclization to the cyclic vinyl ether (R1ʹ), formation of the C-2-arylalkynyl cyclic ether (P1) via hydroalkynylation of R1ʹ with phenylacetylene (R2), and conversion from P1 to 2,3-dihydrooxepine (P2). The results revealed the origin of the reaction divergence and rationalized the experimental observations that a 1:3 reactant stoichiometric ratio affords P1 as the major product, whereas the 1:1.1 ratio results in P2 in high yield. The reactant stoichiometric ratio-controlled divergent reactivity is attributed to different catalytic activities of the gold catalyst toward different reaction stages. In the 1:3 situation, the excessive R2 induces the Au catalyst toward its dimerization and/or hydration, inhibiting the conversion of P1 to P2 and resulting in product P1. Without excess of R2, the Au catalysis follows a general cascade reaction, leading to product P2. Theoretical results described a general strategy controlling the reaction divergence by different reactant stoichiometric ratio. This strategy may be enlightening for chemists who are exploring various synthesis methods with high chemo-, regio-, and enantio-selectivities.
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The Journal of Organic Chemistry
1. INTRODUCTION Homogeneous Au-catalyzed reactions in the area of organic synthesis have received considerable attentions over the past decade, which provided an effective strategy for constructing a diverse range of useful complex molecules.1‒5 In particular, Au(I) catalyzed cycloisomerization reactions of alkenes or alkynes have developed into a powerful approach for producing carbo- and hetero-cycles, which are widely applied to the synthesis of complex molecules and natural products.6‒8 However, controlling the selectivity to enable the selective formation of diverse carbo- and hetero-cycles is a considerable challenge, because the reactions are sensitive to even slight variations in reaction parameters, such as ligand,9‒11 counterion,12,13 substrate,14,15 solvent,16 and additives.17 Until now, researchers have devoted to revealing how these parameters control chemo-, regio-, and stereo-selectivities of transition metal-catalyzed reactions and made enormous progresses and achievements.18‒23 Scheme 1. Au(I)-Catalyzed Intermolecular Condensation between Homopropargyl Alcohols and Terminal Alkynes with Different Reactant Stoichiometric Ratios26
Recently, Shi and his coworkers24‒26 reported a series of interesting Au-catalyzed chemodivergent intermolecular condensations between homopropargyl alcohols and terminal alkynes to synthesize different cyclic ether skeletons. Based on their experimental observations, we note an impressive fact that the reactant stoichiometric ratio can control the chemoselectivity of the reaction. Scheme 1 shows a typical example of the reactions carried 3
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out by Shi et al..26 With a 1:3 stoichiometric ratio of homopropargyl alcohol (R1) to terminal alkynes (R2), arylalkynyl-subtituted cyclic ether (P1) was detected in excellent yield (91%) in 4 hours, and even in 48 hours, the yield of the corresponding ring expansion product, dipheny-subtituted 2,3-dihydrooxepine (P2), was still low (
