Recent advances in earth-abundant transition metal-catalyzed dihydrosilylation of terminal alkynes

Over the past few years, earth-abundant transition metal-catalyzed hydrosilylation has emerged as an ideal strategy for the synthesis of organosilanes. The success in this area of research has expanded to the advancements of alkyne dihydrosilylation reactions, offering broadened synthetic applications through the selective installation of two silyl groups. In particular, catalysts based on Fe, Co, and Ni have engendered enabling platforms for mild transformations with a range of distinct regioselectivity. This mini-review summarizes recent advances in this research field, highlighting the unique features of each system from both synthetic and mechanistic perspectives

Laboratory experiment: Synthesis and characterization of 4-methyl-N-(phenylacetyl)benzenesulfonamide through Cu(I)-catalysis

A three-component coupling reaction of phenylacetylene, p-toluenesulfonyl azide, and water through copper catalysis is described to provide knowledge of spectroscopy and catalytic reactions and to introduce current research topics in organic chemistry for second-year undergraduate students. In the presence of stoichiometric amounts of phenylacetylene, p-toluenesulfonyl azide, and triethylamine, the reaction was performed with 4 mol% CuCl in water as the sole solvent and was completed in 1.5 h. A practical purification method and recrystallization of the crude reaction mixture resulted in the rapid isolation of the desired product with yields of 42~65%. Students characterized 4-methyl-N-(phenylacetyl)benzenesulfonamide by using melting-point determination, infrared spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. This experimental procedure and spectroscopic data analysis will serve as a platform for students to apply classroom knowledge in practical state-of-the-art research. © Korean Chemical Society. All Rights Reserved.1

Stereoselective Formal Hydroamidation of Si-Substituted Arylacetylenes with DIBAL-H and Isocyanates: Synthesis of (E)- and (Z)-alpha-Silyl-alpha,beta-unsaturated Amides

An efficient and stereoselective method for the synthesis of (E)- and (Z)-alpha-silyl-alpha,beta-unsaturated amides and its synthetic applications are presented herein. The solvent-controlled hydroaluminations of Si-substituted alkynes with DIBAL-H generate diastereomerically enriched alkenylaluminum reagents that are directly reacted with isocyanates at ambient temperature to afford alpha-silyl-alpha,beta-unsaturated amides in high yields with retained stereoselectivity. In particular, this process enables the synthesis of a broad range of (E)-alpha-silyl-alpha,beta-unsaturated amides, which are the less studied isomers. The synthetic utility of this method is highlighted by its short reaction time, ease of purification, easily accessible substrates and reagents, gram-scale synthesis, and the further transformations of C-Si bonds into C-H, C-X, and C-C bonds. © 2020 American Chemical Society.1

Site- and Enantioselective Formation of Allene-Bearing Tertiary or Quaternary Carbon Stereogenic Centers through NHC–Cu-Catalyzed Allylic Substitution

Catalytic enantioselective allylic substitutions that result in addition of an allenyl group (<2% propargyl addition) and formation of tertiary or quaternary C–C bonds are described. Commercially available allenylboronic acid pinacol ester is used. Reactions are promoted by a 5.0–10 mol % loading of sulfonate-bearing chiral bidentate N-heterocyclic carbene (NHC) complexes of copper, which exhibit the unique ability to furnish chiral products arising from the S_N2′ mode of addition. Allenyl-containing products are generated in up to 95% yield, >98% S_N2′ selectivity, and 99:1 enantiomeric ratio (er). Site-selective NHC–Cu-catalyzed hydroboration of enantiomerically enriched allenes and conversion to the corresponding β-vinyl ketones demonstrates the method's utility

Catalytic Enantioselective Protoboration of Disubstituted Allenes. Access to Alkenylboron Compounds in High Enantiomeric Purity

Proto-boryl additions to 1,1-disubstituted allenes in the presence of 1.0–5.0 mol % of chiral NHC–Cu complexes, B₂(pin)₂, and <i>t</i>-BuOH proceed to afford alkenyl–B­(pin) products in up to 98% yield, >98:2 site selectivity, and 98:2 er. The enantiomerically enriched alkenylboron products can be converted to otherwise difficult-to-access alkenyl bromides, methyl ketones or carboxylic acids. What’s more, the corresponding boronic acids may be used in highly stereoselective NHC−Cu-catalyzed allylic substitution reactions

Transient Directing Group-Assisted C-H Bond Functionalization of Aliphatic Amines: Strategies for Efficiency and Site-Selectivity

The synthesis of amine skeletons and catalytic bond formation in aliphatic amines are important synthetic methodologies. Although various metal-catalyzed organic transformations have been successfully used to functionalize and construct amine molecules, there are still many hurdles toward practical application. Moreover, site-selectivity is generally achieved using a traditional directing group (DG) strategy, which requires at least two additional steps for the installation and removal of the DGs. Recently, a transient directing group (TDG) strategy, also known as traceless DG and temporary DG, has been widely studied for a range of selective transition metal-catalyzed C─H bond functionalization. In this account, we have focused on the recent developments of the TDG strategy toward the site-selective C─H bond functionalization of aliphatic amines. The design of the TDGs used for the target reaction and their critical roles in the reaction mechanism will be covered along with their selectivity and synthetic utility. © 2020 Korean Chemical Society, Seoul &amp; Wiley-VCH Verlag GmbH &amp; Co. KGaA, WeinheimFALS

Synthesis of alkynamides through reaction of alkyl- or aryl-substituted alkynylaluminums with isocyanates

An efficient and facile method for the preparation of alkynamides through Et3N-catalyzed alumination of alkyl- or aryl-substituted terminal alkynes with AlMe3and sequential nucleophilic addition ofin situgenerated alkynylaluminums to isocyanates is described. This method has the merits of using readily available isocyanates and monosubstituted alkynes, easy access to organoaluminums, short reaction times, and high efficiency. A gram-scale synthesis of the desired alkynamide and its application to the formation of α-methylene-β-lactams demonstrates the synthetic utility of this method. © The Royal Society of Chemistry 2021.FALS

Total synthesis of laidlomycin

The synthesis of laidlomycin is described. With an established stereocontrolled synthetic route to the aldehyde 5, the known β-keto phosphonate 4 was coupled with 5 and the resulting enone was subjected to a sequential hydrogenolysis/hydrogenation and equilibration process to effect the correct spiroketalization for the natural product. The stereogenic carbons were elaborated by desymmetrization for C12, allylation for C13, vanadyl-induced epoxidation for C16, Zn(BH4)2 reduction for C17, a chiral building block for C18 and C24, Shi epoxidation for C20 and C21, Myers&apos; alkylation for C22, and thermodynamic control for C25. © The Royal Society of Chemistry 2016.

Stereocontrolled Synthesis of the C1-C10 Fragments of Monensin B and Laidlomycin

An efficient synthetic route to the C1-C10 fragments of laidlomycin and monensin B has been developed toward their total synthesis. The asymmetric carbons have been elaborated by a syn-aldol reaction using the oxazolidinone chiral auxiliary for C6 and C7, an anti-aldol reaction for C3 and C4, the Tishchenko-Evans reaction for C5, and a chiral building block for C2. © 2015 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.

N‑Heterocyclic Carbene–Copper-Catalyzed Group‑, Site‑, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes

The first instances of catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multigram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75–90% yield, 87:13 to >98:2 S_N2′/S_N2 (branched/linear) selectivity and 83:17–99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units (e.g., homoallenyl and <i>Z</i>-homoalkenyl iodide), direct access to which by other enantioselective protocols would otherwise entail longer routes. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC–Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate’s phosphate group to form the branched propargyl addition products as the dominant isomers via Cu­(III) π-allyl intermediate complexes