Magnesium‐Catalyzed Hydroboration of Terminal and Internal Alkynes

A magnesium‐catalyzed hydroboration of alkynes providing good yields and selectivities for a wide range of terminal and symmetrical and unsymmetrical internal alkynes has been developed. The compatibility with many functional groups makes this magnesium catalyzed procedure attractive for late stage functionalization. Experimental mechanistic investigations and DFT calculations reveal insights into the reaction mechanism of the magnesium catalyzed protocol.     

Asymmetric Imine Hydroboration Catalyzed by Chiral Diazaphospholenes

The first use of diazaphospholenes as chiral catalysts has been demonstrated with enantioselective imine hydroboration. A chiral diazaphospholene prepared in a simple three‐step synthesis from commercial materials has been shown to achieve the highest enantioselectivity for the hydroboration of alkyl imines with pinacolborane reported to date. Enantiomer ratios of up to 88:12 were obtained with low (2 mol %) catalyst loadings. Twenty examples of asymmetric reduction employing this main‐group catalysis protocol, including the synthesis of the pharmaceuticals ent‐rasagiline and fendiline, are shown.     

Cobalt‐Catalyzed Enantioselective Hydroboration/Cyclization of 1,7‐Enynes: Asymmetric Synthesis of Chiral Quinolinones Containing Quaternary Stereogenic Centers

An asymmetric cobalt‐catalyzed hydroboration/cyclization of 1,7‐enynes to synthesize chiral six‐membered N‐heterocyclic compounds was developed. A variety of aniline‐tethered 1,7‐enynes react with pinacolborane to afford the corresponding chiral boryl‐functionalized quinoline derivatives in high yields with high enantioselectivity. This cobalt‐catalyzed asymmetric cyclization of 1,7‐enyens provides a general approach to access a series of chiral quinoline derivatives containing quaternary stereocenters.     

Asymmetric Iron‐Catalyzed C−H Alkylation Enabled by Remote Ligand meta‐Substitution

Highly enantioselective iron‐catalyzed C−H alkylations by inner‐sphere C−H activation were accomplished with ample scope. High levels of enantiocontrol proved viable through a novel ligand design that exploits a remote meta‐substitution on N‐heterocyclic carbenes within a facile ligand‐to‐ligand H‐transfer C−H cleavage.     

Enantioselective Tandem Cyclization of Alkyne‐Tethered Indoles Using Cooperative Silver(I)/Chiral Phosphoric Acid Catalysis

Reported is the enantioselective synthesis of tetracyclic indolines using silver(I)/chiral phosphoric acid catalysis. A variety of alkyne‐tethered indoles are suitable for this process. Mechanistic studies suggest that the in situ generated silver(I) chiral phosphate activates both the alkyne and the indole nucleophile in the initial cyclization step through an intermolecular hydrogen bond and the phosphate anion promotes proton transfer. In addition, further modifications of the cyclization products enabled stereochemistry–function studies of a series of bioactive indolines.     

Automated Quantum Mechanical Predictions of Enantioselectivity in a Rhodium‐Catalyzed Asymmetric Hydrogenation

A computational toolkit (AARON: An automated reaction optimizer for new catalysts) is described that automates the density functional theory (DFT) based screening of chiral ligands for transition‐metal‐catalyzed reactions with well‐defined reaction mechanisms but multiple stereocontrolling transition states. This is demonstrated for the Rh‐catalyzed asymmetric hydrogenation of (E )‐β‐aryl‐N ‐acetyl enamides, for which a new C ₂‐symmetric phosphorus ligand is designed.     

Ligand‐Controlled Regiodivergent Enantioselective Rhodium‐Catalyzed Alkene Hydroboration

Regiocontrol in the rhodium‐catalyzed boration of vinyl arenes is typically dominated by the presence of the conjugated aryl substituent. However, small differences in TADDOL‐derived chiral monophosphite ligands can override this effect and direct rhodium‐catalyzed hydroboration of β‐aryl and β‐heteroaryl methylidenes by pinacolborane to selectively produce either chiral primary or tertiary borated products. The regiodivergent behavior is coupled with enantiodivergent addition of the borane. The nature of the TADDOL backbone substituents and that of the phosphite moiety function synergistically to direct the sense and extent of regioselectivity and enantioinduction. Twenty substrates are shown to undergo each reaction mode with regioselectivity values reaching greater than 20:1 and enantiomer ratios reaching up to 98:2. A variety of subsequent transformations illustrate the potential utility of each product.