Article Cite This: J. Org. Chem. 2019, 84, 579−588
pubs.acs.org/joc
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*,†
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†
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 UrbanaChampaign, Urbana, Illinois 61801, United States § Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, United States S Supporting Information *
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 (R1′), formation of the C-2-arylalkynyl cyclic ether (P1) via hydroalkynylation of R1′ with phenylacetylene (R2), and conversion from P1 to 2,3-dihydro-oxepine (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 ratiocontrolled divergent reactivity is attributed to different catalytic activities of the gold catalyst toward different reaction stages. In the 1:3 situation, the excess 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 R2, the Au catalysis follows a general cascade reaction, leading to product P2. Theoretical results described a general strategy controlling the reaction divergence by a different reactant stoichiometric ratio. This strategy may be enlightening for chemists who are exploring various synthesis methods with high chemo-, regio-, and enantioselectivities.
1. INTRODUCTION Homogeneous Au-catalyzed reactions in the area of organic synthesis have received considerable attention 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 heterocycles, 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 heterocycles 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 been devoted to revealing how these parameters control chemo-, regio-, and stereoselectivities of transition-metal-catalyzed reactions and have made enormous progress and achievements.18−23 Recently, Shi and co-workers24−26 reported a series of interesting Au-catalyzed chemodivergent intermolecular condensations between homopropargyl alcohols and terminal © 2018 American Chemical Society
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 out by Shi et al.26 With a 1:3 stoichiometric ratio of homopropargyl alcohol (R1) to terminal alkynes (R2), arylalkynyl-substituted cyclic ether (P1) was detected in excellent yield (91%) in 4 h, and even in 48 h, the yield of the corresponding ring expansion product, diphenylsubstituted 2,3-dihydro-oxepine (P2), was still low (
