Chiral Cp‐Rhodium(III)‐Catalyzed Asymmetric Hydroarylations of 1,1‐Disubstituted Alkenes

Abstract

Metal‐catalyzed functionalizations at the ortho position of a directing group have become an efficient bond‐forming strategy. A wide range of transformations that employ Cp*RhIII catalysts have been described, but despite their synthetic potential, enantioselective variants that use chiral versions of the Cp* ligand remain scarce (Cp*=pentamethyl cyclopentadienyl). Cyclopentadienyl compounds with an atropchiral biaryl backbone are shown to be suitable ligands for the efficient intramolecular enantioselective hydroarylation of aryl hydroxamates. Dihydrofurans that bear methyl‐substituted quaternary stereocenters are thus obtained by CH functionalization under mild conditions.

Construction of Quaternary Stereogenic Carbon Centers through Copper‐Catalyzed Enantioselective Allylic Alkylation of Azoles

“…[12] Based on this,t he NHC ligand L1, which exhibited high performance in the our previous study of copper catalysis,w as initially used in the reaction between benzothiazole (1a;1 .5 equiv) and the E-allylic phosphate (E)-2a in the presence of CuCl (10 mol %) and LiOtBu (2.2 equiv) in 1,4-dioxane at 25 8 8C ( Table 1, entry 1). In contrast to the results obtained using oxygen-functionalized NHC ligands,n or eaction occurred with either NHC ligands lacking an oxygen functional group, such as L5,I Mes,a nd SIMes,o rw ithout exogenous ligand (entries [6][7][8][9]. [13] To our delight, however, changing the phenol group of L1 to an aphthol group,togive the new ligand L2,caused marked increases in product yield (77 %) and enantioselectivity (68 %), with the exclusive regioselectivity unchanged (entry 2).…”

“…Changing the hydroxy group of L3 to am ethoxy group was unfavorable for both product yield and branch regioselectivity,a lthough the reduction in enantioselectivity was not significant (entry 5). In contrast to the results obtained using oxygen-functionalized NHC ligands,n or eaction occurred with either NHC ligands lacking an oxygen functional group, such as L5,I Mes,a nd SIMes,o rw ithout exogenous ligand (entries [6][7][8][9]. Thus,f unctional roles were suggested for the OH and OMe groups in L3 and L4,respectively,asinthe case of copper-catalyzed enantioselective allylic alkylation of terminal alkynes.…”

“…[3,4] More recently,S igman and coworkers reported tertiary alkylation of indoles through ap alladium-catalyzed enantioselective dehydrogenative Heck reaction with trisubstituted alkenes. [6][7][8] We previously reported that copper-catalyzed allylic alkylation of electron-deficient heteroarenes (oxazoles,o xadiazoles,t hiazoles,a nd pyridine N-oxide) and fluoroarenes with enantioenriched chiral secondary Z-allylic phosphates occurred in the presence of as toichiometric amount of LiOtBu as abase with excellent S N 2'-type regioselectivity and 1,3-anti stereospecificity.T he reaction afforded chiral secondary alkylated (hetero)arenes. [6][7][8] We previously reported that copper-catalyzed allylic alkylation of electron-deficient heteroarenes (oxazoles,o xadiazoles,t hiazoles,a nd pyridine N-oxide) and fluoroarenes with enantioenriched chiral secondary Z-allylic phosphates occurred in the presence of as toichiometric amount of LiOtBu as abase with excellent S N 2'-type regioselectivity and 1,3-anti stereospecificity.T he reaction afforded chiral secondary alkylated (hetero)arenes.…”

“…[5] In contrast, enantioselective introduction of tertiary alkyl groups through C(sp 2 ) À Ha lkylation of electron-deficient heteroarenes, ar eaction which should be mechanistically different from that of electron-rich heteroarenes,remains achallenge. [6][7][8] We previously reported that copper-catalyzed allylic alkylation of electron-deficient heteroarenes (oxazoles,o xadiazoles,t hiazoles,a nd pyridine N-oxide) and fluoroarenes with enantioenriched chiral secondary Z-allylic phosphates occurred in the presence of as toichiometric amount of LiOtBu as abase with excellent S N 2'-type regioselectivity and 1,3-anti stereospecificity.T he reaction afforded chiral secondary alkylated (hetero)arenes. [9] Herein we report coppercatalyzed enantioselective allylic alkylation of azoles,w hich are electron-deficient heteroarenes,w ith g,g-disubstituted primary allylic phosphates to form ac ontrolled all-carbon quaternary stereogenic center at the position a to the heteroaromatic ring.…”

A Simple and Versatile Amide Directing Group for C−H Functionalizations

“…[48] Tuning the size of the R group on the biaryl backbone enabled an enantioselective hydroarylation of tethered alkenes, providing enantioenriched dihydrobenzofurans derivatives. For the hydroarylation reaction, it was revealed that the meta -alkoxy group was serving as a secondary directing group, thereby allowing activation of the more hindered ortho -C(sp 2 )–H bond.…”