A General Strategy for the Asymmetric Preparation of α‐Stereogenic Allyl Silanes, Germanes, and Boronate Esters via Dual Copper Hydride‐ and Palladium‐Catalysis

Abstract

α‐Stereogenic allyl metalloids are versatile synthetic intermediates which can undergo various stereocontrolled transformations. Most existing methods to prepare α‐stereogenic allyl metalloids involve multi‐step sequences that curtail the number of compatible substrates and are limited to the synthesis of boronates. Here, we report a general method for the enantioselective preparation of α‐stereogenic allyl metalloids utilizing dual CuH‐ and Pd‐catalysis. This approach leverages a stereoretentive Cu‐to‐Pd transmetalation of an in situ generated alkyl copper species to allow access to enantioenriched allyl silanes, germanes, and boronate esters with broad functional group compatibility.

Ligand-Controlled On–Off Switch of a Silicon-Tethered Directing Group Enabling the Regiodivergent Hydroalkylation of Vinylsilanes under Ni–H Catalysis

“…Vinylsilanes and -germanes are synthetically valuable building blocks that have already found application as pronucleophiles in hydrocarbonation reactions . In line with our interest in silicon and germanium chemistry, we recently reported a linear-selective hydroalkylation of these vinyl metalloids .…”

Enantio- and Regioconvergent Synthesis of γ-Stereogenic Vinyl Germanes and Their Use as Masked Vinyl Halides

“…Key contributions include a procedure by Buchwald and co-workers from last year (Scheme 1, top). 8 An enantioselective hydrocupration of vinyl germanes followed by a palladium-catalyzed crosscoupling with vinyl triflates enabled the synthesis of α-chiral allyl germanes. At the same time, He and co-workers disclosed an enantioselective hydrogermylation under copper catalysis to access β-chiral alkyl germanes, i.e., β-germylated α-amino acids (Scheme 1, middle).…”

“…To the best of our knowledge, there has been little progress regarding the formation of chiral germanium-substituted building blocks. Key contributions include a procedure by Buchwald and co-workers from last year (Scheme , top) . An enantioselective hydrocupration of vinyl germanes followed by a palladium-catalyzed cross-coupling with vinyl triflates enabled the synthesis of α-chiral allyl germanes.…”

Regioselective Hydroalkylation of Vinyl- and Allylsilanes as Well as Vinylgermanes under Ni–H Catalysis

“…Key contributions using these synthetically useful building blocks in transition-metal-catalyzed hydrocarbonation include an asymmetric hydroallylation of vinylsilanes under Cu–H catalysis by Xiong and co-workers (Scheme , eq 1) . Furthermore, Buchwald and co-workers reported a formal enantioselective hydroalkenylation of alkenyl metalloids (with [M] = −BR 2 , −SiR 3 , and −GeR 3 ) under dual Cu–H and palladium catalysis (Scheme , eq 2) . Parallel to these advances, Hu and co-workers disclosed a Ni–H-catalyzed enantioselective hydroalkylation of alkenyl boronates, followed by an enantioconvergent and diastereoselective hydroalkylation using racemic alkyl bromides (Scheme , eq 3). , …”

“…7 Furthermore, Buchwald and coworkers reported a formal enantioselective hydroalkenylation of alkenyl metalloids (with [M] = −BR 2 , −SiR 3 , and −GeR 3 ) under dual Cu−H and palladium catalysis (Scheme 1, eq 2). 8 Parallel to these advances, Hu and co-workers disclosed a Ni− H-catalyzed enantioselective hydroalkylation of alkenyl boronates, followed by an enantioconvergent and diastereoselective hydroalkylation using racemic alkyl bromides (Scheme 1, eq 3). 5j,n In light of Hu's findings, we anticipated that vinylsilanes or -germanes would also favor the formation of the α-stereogenic metalloids and as such the branched product.…”