Direct C?C Cross‐Coupling of Secondary and Primary Alcohols Catalyzed by a γ‐Alumina‐Supported Silver Subnanocluster

Let's drink to that! Two alcohols (one primary and one secondary) can be coupled in an atom‐efficient process by a hydrogen‐autotransfer catalytic system in the form of silver subnanoclusters supported on γ‐Al₂O₃. The recyclable heterogeneous catalyst promoted the one‐pot C? C cross‐coupling in the presence of a catalytic amount of the weak base Cs₂CO₃ (see reaction mechanism).

     

Enantioselective ortho‐C?H Cross‐Coupling of Diarylmethylamines with Organoborons

The commonly used para‐nitrobenzenesulfonyl (nosyl) protecting group is employed to direct the C H activation of amines for the first time. An enantioselective ortho‐C H cross‐coupling between nosyl‐protected diarylmethylamines and arylboronic acid pinacol esters has been achieved utilizing chiral mono‐N‐protected amino acid (MPAA) ligands as a promoter.     

Copper‐Catalyzed Radical/Radical C?H/P?H Cross‐Coupling: α‐Phosphorylation of Aryl Ketone O‐Acetyloximes

The selective radical/radical cross‐coupling of two different organic radicals is a great challenge due to the inherent activity of radicals. In this paper, a copper‐catalyzed radical/radical C H/P H cross‐coupling has been developed. It provides a radical/radical cross‐coupling in a selective manner. This work offers a simple way toward β‐ketophosphonates by oxidative coupling of aryl ketone o‐acetyloximes with phosphine oxides using CuCl as catalyst and PCy₃ as ligand in dioxane under N₂ atmosphere at 130 °C for 5 h, and yields ranging from 47 % to 86 %. The preliminary mechanistic studies by electron paramagnetic resonance (EPR) showed that, 1) the reduction of ketone o‐acetyloximes generates iminium radicals, which could isomerize to α‐sp³‐carbon radical species; 2) phosphorus radicals were generated from the oxidation of phosphine oxides. Various aryl ketone o‐acetyloximes and phosphine oxides were suitable for this transformation.     

The Liebeskind–Srogl C?C Cross‐Coupling Reaction

New kid on the block : The cross‐coupling of thioorganic compounds with boronic acids under neutral conditions in the presence of catalytic palladium(0) and a stoichiometric amount of a copper(I) oxygenate has emerged as a very useful method for the construction of C C bonds (see scheme). This intriguing and mechanistically unprecedented base‐free coupling has distinct advantages, in particular when traditional Pd⁰‐catalyzed cross‐coupling is not possible.

     

How Can Theory Predict the Selectivity of Palladium‐Catalyzed Cross‐Coupling of Pristine Aromatic Molecules?

The new approach for palladium‐catalyzed cross‐coupling of two non‐activated aromatic compounds (D. R. Stuart, K. Fagnou, Science 2007 , 316, 1172) was studied theoretically. The energetic span model (S. Kozuch, S. Shaik, Acc. Chem. Res. 2011 , 44, 101, and references therein) was employed to analyze the kinetic behavior of the catalytic cycle. The computed energy profile, combined with the energetic span model, accounts for the experimental selectivity, which favors the hetero‐coupling of benzene with indole. This selectivity is driven by a fine balance of the entropic contributions and the high ratio of concentrations used for benzene over indole. This analysis may allow future theoretical predictions of how different aromatic compounds can be effectively coupled.     

6‐Chloroisocytosine and 5‐bromo‐6‐methylisocytosine: again,one or two tautomers present in the same crystal?

It is well known that pyrimidin‐4‐one derivatives are able to adopt either the 1H‐ or the 3H‐tautomeric form in (co)crystals, depending on the coformer. As part of ongoing research to investigate the preferred hydrogen‐bonding patterns of active pharmaceutical ingredients and their model systems, 2‐amino‐6‐chloropyrimidin‐4‐one and 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4‐one have been cocrystallized with several coformers and with each other. Since Cl and Br atoms both have versatile possibilities to interact with the coformers, such as via hydrogen or halogen bonds, their behaviour within the crystal packing was also of interest. The experiments yielded five crystal structures, namely 2‐aminopyridin‐1‐ium 2‐amino‐6‐chloro‐4‐oxo‐4H‐pyrimidin‐3‐ide–2‐amino‐6‐chloropyrimidin‐4(3H)‐one (1/3), C₅H₇N₂⁺·C₄H₃ClN₃O⁻·3C₄H₄ClN₃O, (Ia), 2‐aminopyridin‐1‐ium 2‐amino‐6‐chloro‐4‐oxo‐4H‐pyrimidin‐3‐ide–2‐amino‐6‐chloropyrimidin‐4(3H)‐one–2‐aminopyridine (2/10/1), 2C₅H₇N₂⁺·2C₄H₃ClN₃O⁻·10C₄H₄ClN₃O·C₅H₆N₂, (Ib), the solvent‐free cocrystal 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(1H)‐one (1/1), C₅H₆BrN₃O·C₅H₆BrN₃O, (II), the solvate 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(1H)‐one–N‐methylpyrrolidin‐2‐one (1/1/1), C₅H₆BrN₃O·C₅H₆BrN₃O·C₅H₉NO, (III), and the partial cocrystal 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(1H)‐one–2‐amino‐6‐chloropyrimidin‐4(3H)‐one (0.635/1/0.365), C₅H₆BrN₃O·C₅H₆BrN₃O·C₄H₄ClN₃O, (IV). All five structures show R₂²(8) hydrogen‐bond‐based patterns, either by synthon 2 or by synthon 3, which are related to the Watson–Crick base pairs.     

A Straightforward Synthesis of 2‐[1‐Alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic Acid Derivatives via Domino Michael Addition?Cyclization Reaction

A new and efficient synthesis of 2‐[1‐alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic acid derivatives by a one‐pot three‐component reaction between primary amine, dialkyl acetylenedicarboxylate, and itaconic anhydride (=3,4‐dihydro‐3‐methylidenefuran‐2,5‐dione) is reported. The reaction was performed without catalyst and under solvent‐free conditions with excellent yields. Notably, the ready availability of the starting materials, and the high level of practicability of the reaction and workup make this approach an attractive complementary method to access to unknown 2‐[1‐alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic acid derivatives. The structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of domino Michael addition? cyclization reaction is proposed (Scheme 2).     

Redox‐Triggered C?C Coupling of Diols and Alkynes: Synthesis of β,γ‐Unsaturated α‐Hydroxyketones and Furans by Ruthenium‐Catalyzed Hydrohydroxyalkylation

Direct ruthenium‐catalyzed C C coupling of alkynes and vicinal diols to form β,γ‐unsaturated ketones occurs with complete levels of regioselectivity and good to complete control over the alkene geometry. Exposure of the reaction products to substoichiometric quantities of p‐toluenesulfonic acid induces cyclodehydration to form tetrasubstituted furans. These alkyne‐diol hydrohydroxyalkylations contribute to a growing body of merged redox‐construction events that bypass the use of premetalated reagents and, hence, stoichiometric quantities of metallic by‐products.     

Palladium(II)‐Catalyzed C?H Activation/C?C Cross‐Coupling Reactions: Versatility and Practicality

Pick your Pd partners : A number of catalytic systems have been developed for palladium‐catalyzed C? H activation/C? C bond formation. Recent studies concerning the palladium(II)‐catalyzed coupling of C? H bonds with organometallic reagents through a Pd^II/Pd⁰ catalytic cycle are discussed (see scheme), and the versatility and practicality of this new mode of catalysis are presented. Unaddressed questions and the potential for development in the field are also addressed.

     

Aerobic Asymmetric Dehydrogenative Cross‐Coupling between Two C?H Groups Catalyzed by a Chiral‐at‐Metal Rhodium Complex

A sustainable C C bond formation is merged with the catalytic asymmetric generation of one or two stereocenters. The introduced catalytic asymmetric cross‐coupling of two C H groups with molecular oxygen as the oxidant profits from the oxidative robustness of a chiral‐at‐metal rhodium(III) catalyst and exploits an autoxidation mechanism or visible‐light photosensitized oxidation. In the latter case, the catalyst serves a dual function, namely as a chiral Lewis acid for catalyzing enantioselective enolate chemistry and at the same time as a visible‐light‐driven photoredox catalyst.