Jessica M. Hoover

Highly Practical Copper(I)/TEMPO Catalyst System for Chemoselective Aerobic Oxidation of Primary Alcohols

Aerobic oxidation reactions have been the focus of considerable attention, but their use in mainstream organic chemistry has been constrained by limitations in their synthetic scope and by practical factors, such as the use of pure O(2) as the oxidant or complex catalyst synthesis. Here, we report a new (bpy)Cu(I)/TEMPO catalyst system that enables efficient and selective aerobic oxidation of a broad range of primary alcohols, including allylic, benzylic, and aliphatic derivatives, to the corresponding aldehydes using readily available reagents, at room temperature with ambient air as the oxidant. The catalyst system is compatible with a wide range of functional groups and the high selectivity for 1° alcohols enables selective oxidation of diols that lack protecting groups.

Copper(I)/TEMPO-catalyzed aerobic oxidation of primary alcohols to aldehydes with ambient air

This protocol describes a practical laboratory-scale method for aerobic oxidation of primary alcohols to aldehydes, using a chemoselective CuI/TEMPO (TEMPO = 2,2,6,6-tetramethyl-1-piperidinyloxyl) catalyst system. The catalyst is prepared in situ from commercially available reagents, and the reactions are performed in a common organic solvent (acetonitrile) with ambient air as the oxidant. Three different reaction conditions and three procedures for the isolation and purification of the aldehyde product are presented. The oxidations of eight different alcohols, described here, include representative examples of each reaction condition and purification method. Reaction times vary from 20 min to 24 h, depending on the alcohol, whereas the purification methods each take about 2 h. The total time necessary for the complete protocol ranges from 3 to 26 h.

Platinum-Catalyzed Intramolecular Hydrohydrazination: Evidence for Alkene Insertion into a Pt−N Bond

Dicationic (bpy)Pt(II) complexes were found to catalyze the intramolecular hydrohydrazination of alkenes. Reaction optimization revealed Pt(bpy)Cl(2) (10 mol %) and AgOTf (20 mol %) in DMF-d(7) to be an effective catalyst system for the conversion of substituted hydrazides to five- and six-membered N-amino lactams (N-amino = N-acetamido at 120 degrees C, N-phthalimido at 80 degrees C, (-)OTf = trifluoromethanesulfonate). Of the four possible regioisomeric products, only the product of 5-exo cyclization at the proximal nitrogen is formed, without reaction at the distal nitrogen or 6-endo cyclization. The resting states were found to be a 2:1 Pt-amidate complex (25, for N-acetamido) of the deprotonated hydrazide and a Pt-alkyl complex of the cyclized pyrrolidinone (20 for N-phthalimido). Both complexes are catalytically competent. Catalysis using 25 as the precatalyst shows no rate dependence on added acid (HOTf) or base (2,6-lutidine). The available mechanistic data are all consistent with a mechanism involving N-H activation of the hydrazide, followed by insertion of the alkene into the Pt-N bond, and finally protonation of the resulting cyclized alkyl complex by hydrazide to release the hydrohydrazination product and regenerate the active Pt-amidate catalyst.

Silver-Mediated Oxidative Decarboxylative Trifluoromethylthiolation of Coumarin-3-carboxylic Acids

The introduction of trifluoromethylthio groups into organic compounds, in particular heterocycles, is important because of the prevalence of these structures in medicinally and agriculturally relevant molecules. Herein, the silver-mediated oxidative decarboxylative trifluoromethylthiolation of coumarin-3-carboxylic acids is reported. This methodology utilizes existing carboxylic acid functionalities for the direct conversion to CF3S groups and results in a broad scope of 3-trifluoromethylthiolated coumarins, including analogues of natural products, in moderate to excellent yields.

Copper and silver benzoate and aryl complexes and their implications for oxidative decarboxylative coupling reactions

The synthesis and reactivity of phenanthroline-ligated copper and silver benzoate and aryl complexes are reported. The commonly proposed copper(I) and silver(I) aryl species are shown to be unlikely intermediates in the oxidative decarboxylative coupling reaction. Instead, the copper(II) benzoate undergoes decarboxylative coupling suggesting an unexpected copper(II) based pathway.

Ammonia activation at a metal

A cationic molybdenum complex weakens the N–H bond of ammonia and generates H2 Although ammonia (NH3) is made on a vast scale for use in fertilizers, its use as a chemical feedstock or as an energy carrier is much more limited. Many reactions that occur easily with its substitution products (amines) are sluggish for NH3, in part because of the difficulty of activating the N-H bond. For fuel cells, NH3 is attractive because it does not generate greenhouse gases, as do methanol and methane (1), and is more easily stored than hydrogen (H2). Amine-containing organic molecules are used in pharmaceutical and materials applications, and accessing these structures directly from ammonia could limit the generation of by-products during their synthesis (2). Bringing NH3 up to speed for these applications will require both the development of catalysts that can activate the strong N–H bond of ammonia and a fundamental understanding of the N–H bond cleavage step. On page 730 of this issue, Bezdek et al. (3) report a molybdenum complex capable of weakening the N–H bond of NH3 and releasing a H atom to generate H2 under mild conditions.

A Predictive Model for the Decarboxylation of Silver Benzoate Complexes Relevant to Decarboxylative Coupling Reactions

Decarboxylative coupling reactions offer an attractive route to generate functionalized arenes from simple and readily available carboxylic acid coupling partners, yet they are underutilized due to limitations in the scope of carboxylic acid coupling partner. Here we report that the field effect parameter (F) has a substantial influence on the rate of decarboxylation of well-defined silver benzoate complexes. This finding provides the opportunity to surpass current substrate limitations associated with decarboxylation and to enable widespread utilization of decarboxylative coupling reactions.

Mechanistic Aspects of Copper-Catalyzed Decarboxylative Coupling Reactions of (Hetero)Aryl Carboxylic Acids

Copper-catalyzed oxidative decarboxylative coupling reactions of benzoic acids have emerged as attractive routes to access functionalized arenes. Unfortunately, substrate scope limitations and forcing reaction conditions have prevented the widespread implementation of these methodologies. A mechanistic understanding of these systems could enable the development of more robust reactions, yet few studies have targeted the mechanistic elucidation of these complex systems. This article reviews the copper-catalyzed decarboxylation reactions of hetero(aromatic) acids, including protodecarboxylations, redox-neutral decarboxylative couplings, and oxidative decarboxylative coupling reactions. We emphasize the mechanistic insights learned from each system to build a framework for understanding copper-catalyzed decarboxylative coupling reactions.