Intramolecular Aryne-Ene Reaction: Synthetic and Mechanistic Studies
ABSTRACT Although the chemistry of arynes is well developed, some challenges still remain. The ene reaction of arynes has not gained widespread use in synthesis as a result of poor yields and selectivity. A general, high yielding and selective intramolecular aryne-ene reaction is described providing various benzofused carbo- and heterocycles. Mechanistic data is presented, and a rationale for the resulting stereochemistry is discussed.
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ABSTRACT: We have studied reactions of secondary and primary alcohols with benzynes generated by the hexadehydro-Diels-Alder (HDDA) reaction. These alcohols undergo competitive addition vs dihydrogen transfer to produce aryl ethers vs reduced benzenoid products, respectively. During the latter process, an equivalent amount of oxidized ketone (or aldehyde) is formed. Using deuterium labeling studies, we determined that (i) it is the carbinol C-H and adjacent O-H hydrogen atoms that are transferred during this process and (ii) the mechanism is consistent with a hydride-like transfer of the C-H. Substrates bearing an internal trap attached to the reactive, HDDA-derived benzyne intermediate were used to probe the kinetic order of the alcohol trapping agent in the H2-transfer as well as in the alcohol addition process. The H2-transfer reaction is first order in alcohol. Our results are suggestive of a concerted H2-transfer process, which is further supported by density functional theory (DFT) computational studies and results of a kinetic isotope effect experiment. In contrast, alcohol addition to the benzyne is second order in alcohol, a previously unrecognized phenomenon. Additional DFT studies were used to further probe the mechanistic aspects of the alcohol addition process.Journal of the American Chemical Society 09/2014; 136(39). DOI:10.1021/ja502595m · 11.44 Impact Factor
Article: Reaction of Arynes with Sulfoxides[Show abstract] [Hide abstract]
ABSTRACT: A S-O bond insertion reaction of sulfoxides with arynes is reported. This reaction represents a rare instance of semipolar single bond insertion in aryne chemistry. The study of mechanism indicates that a sulfur ylide triggered by aryne is the key intermediate, which further transfers its methylene group to carbonyl compounds to give epoxides and thioethers through a sequential process.Organic Letters 02/2015; DOI:10.1021/ol5036326 · 6.32 Impact Factor
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ABSTRACT: Under basic conditions in alcoholic solvents, bromoenynamides undergo palladium‐catalyzed cyclization to cyclic 2‐amidodienes in good to excellent yields. This process represents the first use of an alcohol as a hydride source in an alkyne carbopalladation/termination sequence, with the site selectivity of the reduction showing a strong dependence on the tethering ring size (5–8), and the nature of the alcohol and base. Reaction of the dienes with a range of dienophiles (including alkenes, alkynes and arynes) under various conditions gives bi‐ and tricyclic azacycles, which can be further oxidized to the aromatic azacycles.Advanced Synthesis & Catalysis 11/2012; 354(17). DOI:10.1002/adsc.201200703 · 5.54 Impact Factor