Dehydrogenative Carbon–Carbon Bond Formation Using Alkynyloxy Moieties as Hydrogen‐Accepting Directing Groups

Abstract

In the presence of ac atalyst system consisting of Pd(OAc) 2 ,P Cy 3 ,a nd Zn(OAc) 2 ,t he reaction of alkynyl aryl ethers with bicycloalkenes, a,ß-unsaturated esters,o rh eteroarenes results in the site-selective cleavage of two CÀHb onds followed by the formation of CÀCb onds.I na ll cases,t he alkynyloxy group acts as adirecting group for the activation of an ortho C À Hbond and as ahydrogen acceptor,thus rendering the use of additives such as an oxidant or base unnecessary.Cross-dehydrogenative bond-forming reactions are highly attractive methods in the toolbox of synthetic organic chemistry,e specially considering their potential in terms of atom and step economy.R epresentative examples are the cross-dehydrogenative formation of carbon-carbon, carbonboron, and carbon-silicon bonds. [1][2][3] This concept also enables the custom-tailored construction of av ariety of highly functionalized compounds,a nd the site-selective cleavage of two CÀHbonds and the subsequent removal of the eliminated hydrogen atoms are key factors in this context. To trap the emitted hydrogen, several additives,s uch as olefins or oxidants,h ave been successfully used, as the release of dihydrogen only meets with difficulty.H owever,t he use of such additives may be problematic from ap ractical perspective,a st hey potentially interfere with the dehydrogenative reaction.Directing groups have been successfully employed for effective site-and regioselective C À Hf unctionalization.[4] In one of our previous studies,wedemonstrated that alkynyloxy groups (ÀOCCR) are able to act as directing groups for the activation of adjacent CÀHb onds,a nd subsequently engage in addition reactions.[5] Forexample,the reaction with alkynes furnishes chromene derivatives by sequential insertions into ortho C À Hbonds.[5a] On the basis of these results,weexpected that the alkynyloxy group might also be able to act as ah ydrogen acceptor and enable the cleavage of two CÀH bonds,t hus facilitating ad ehydrogenative carbon-carbon bond-forming reaction. Moreover,t his synthetic approach would avoid the use of additives,s uch as oxidants (e.g., benzoquinone) or bases,a nd the vinyloxy groups resulting from dihydrogenation of the alkynyloxy groups are highly useful functional groups.[6] Herein, we report as eries of dehydrogenative reactions between alkynyl aryl ethers and bicycloalkenes, a,ß-unsaturated esters,o rh eteroarenes.T his approach represents ac onvenient strategy for additive-free catalytic cross-dehydrogenative C À Cbond-forming reactions.Recently,w er eported that the reaction between triisopropylsilyl (TIPS)-substituted para-methoxyphenyl ether 1a and norbornene (2a)inthe presence of [Pd(PCy 3 ) 2 ](5mol %) and Zn (5 mol %) proceeds by ortho CÀHi nsertion/annulation to afford 4a.[5f] However,when the reaction between 1a and 2a was carried out in the presence of Pd(OAc) 2 (5 mol %), PCy 3 (10 mol %), and Zn(OAc) 2 (20 mol %) at 100 8 8Cf or 24 h, benzocyclobutene 3a with a Z-configured silylethenoxy moiety was obtained in 75 %y ield, most ...