CO2 Valorization toward Selective N-Formylation of Nitroarenes and Aminoarenes under Homogeneous Titanium Catalysis

Key words tantalum catalysis - titanium catalysis - substrate-directed reaction

Key words aldehydes - aldol reaction - malonic acid half thioesters - titanium catalysis

Key words carbonyl coupling - indole synthesis - reductive cyclization - titanium catalysis

Amination of allylic alcohols is facilitated via cooperative catalysis. Catalytic Ti(O- i-Pr)4 is shown to dramatically increase the rate of nickel-catalyzed allylic amination, and mechanistic experiments confirm activation of the allylic alcohol by titanium. Aminations of primary and secondary allylic alcohols are demonstrated with a variety of amine nucleophiles. Diene-containing substrates also cyclize onto the nickel allyl intermediate prior to amination, generating carbocyclic amine products. This tandem process is only achieved under our cooperative catalytic system.

[reaction: see text] Ugi reaction between an (S)-alpha-amino acid, an aromatic aldehyde, and an isonitrile proceeds best under catalysis by TiCl(4) in MeOH. The sense of diastereoinduction is (S,S).

Transition-metal-catalyzed reductive coupling of electrophiles has emerged as a powerful tool for the construction of molecules. While major achievements have been made in the field of cross-couplings between organic halides and pseudohalides, an increasing number of reports demonstrates reactions involving more readily available, low-cost, and stable, but unreactive electrophiles. This account summarizes the recent results in our laboratory focusing on this topic. These findings typically include deoxygenative C-C coupling of alcohols, reductive alkylation of alkenyl acetates, reductive C-Si coupling of chlorosilanes, and reductive C-Ge coupling of chlorogermanes.The reductive deoxygenative coupling of alcohols with electrophiles is synthetically appealing, but the potential of this chemistry remains to be disclosed. Our initial study focused on the reaction of allylic alcohols and aryl bromides by the combination of nickel and Lewis acid catalysis. This method offers a selectivity that is opposite to that of the classic Tsuji-Trost reactions. Further investigation on the reaction of benzylic alcohols led to the foundation of a dynamic kinetic cross-coupling strategy with applications in the nickel-catalyzed reductive arylation of benzylic alcohols and cobalt-catalyzed enantiospecific reductive alkenylation of allylic alcohols. The titanium catalysis was later established to produce carbon radicals directly from unactivated tertiary alcohols via C-OH cleavage. The development of their coupling reactions with carbon fragments delivers new methods for the construction of all-carbon quaternary centers. These reactions have shown high selectivity for the functionalization of tertiary alcohols, leaving primary and secondary alcohols intact. Alkenyl acetates are inexpensive, stable, and environmentally friendly and are considered the most attractive alkenyl reagents. The development of reductive alkylation of alkenyl acetates with benzyl ammoniums and alkyl bromides offers mild approaches for the conversion of ketones into aliphatic alkenes.Extensive studies in this field have enabled us to extend the cross-electrophile coupling from carbon to silicon and germanium chemistry. These reactions harness the ready availability of chlorosilanes and chlorogermanes but suffer from the challenge of their low reactivity toward transition metals. Under reductive nickel catalysis, a broad range of alkenyl and aryl electrophiles couple well with vinyl- and hydrochlorosilanes. The use of alkyl halides as coupling partners led to the formation of functionalized alkylsilanes. The C-Ge coupling seems less substrate-dependent, and various common chlorogermanes couple well with aryl, alkenyl, and alkyl electrophiles. In general, functionalities such as Grignard-sensitive groups (e.g., acid, amide, alcohol, ketone, and ester), acid-sensitive groups (e.g., ketal and THP protection), alkyl fluoride and chloride, aryl bromide, alkyl tosylate and mesylate, silyl ether, and amine are tolerated. These methods provide new access to organosilicon and organogermanium compounds, some of which are challenging to obtain otherwise.

Nitrogen-based heterocycles are important frameworks for pharmaceuticals, natural products, organic dyes for solar cells, and many other applications. Catalysis for the formation of heterocyclic scaffolds, like many C-C and C-N bond-forming reactions, has focused on the use of rare, late transition metals like palladium and gold. Our group is interested in the use of Earth-abundant catalysts based on titanium to generate heterocycles using multicomponent coupling strategies, often in one-pot reactions. To be of maximal utility, the catalysts need to be easily prepared from inexpensive reagents, and that has been one guiding principle in the research. For this purpose, a series of easily prepared pyrrole-based ligands has been developed. Titanium imido complexes are known to catalyze the hydroamination of alkynes, and this reaction has been used to advantage in the production of α,β-unsaturated imines from 1,3-enynes and pyrroles from 1,4-diynes. Likewise, catalyst design can be used to find complexes applicable to hydrohydrazination, coupling of a hydrazine and alkyne, which is a method for the production of hydrazones. Many of the hydrazones synthesized are converted to indoles through Fischer cyclization by addition of a Lewis acid. However, more complex products are available in a single catalytic cycle through coupling of isonitriles, primary amines, and alkynes to give tautomers of 1,3-diimines, iminoamination (IA). The products of IA are useful intermediates for the one-pot synthesis of pyrazoles, pyrimidines, isoxazoles, quinolines, and 2-amino-3-cyanopyridines. The regioselectivity of the reactions is elucidated in some detail for some of these heterocycles. The 2-amino-3-cyanopyridines are synthesized through isolable intermediates, 1,2-dihydro-2-iminopyridines, which undergo Dimroth rearrangement driven by aromatization of the pyridine ring; the proposed mechanism of the reaction is discussed. The IA-based heterocyclic syntheses can be accomplished start to finish (catalyst generation to heterocyclic synthesis) in a single vessel. The catalyst can be formed in situ from commercially available Ti(NMe2)4 and the protonated form of the ligand. Then, the primary amine, alkyne, and isonitrile are added to the flask, and the IA product is synthesized. The volatiles are removed (if necessary), and the next reagent is added. A brief video showing the process for the simple heterocycle 4-phenylpyrazole from phenylacetylene, cyclohexylamine, tert-butylisonitrile, and hydrazine hydrate is included. Further development in this field will unlock new, efficient reactions for the production of carbon-carbon and carbon-nitrogen bonds. As an example of such a process recently discovered, a catalyst for the regioselective production of pyrazoles in a single step from terminal alkynes, hydrazines, and cyclohexylisonitrile is discussed. Using titanium catalysis, many heterocyclic cores can be accessed easily and efficiently. Further, the early metal chemistry described is often orthogonal to late metal-based reactions, which use substrates like aryl halides, silyl groups, boryl groups, and so forth. As a result, earth-abundant and nontoxic titanium can fulfill important roles in the synthesis of useful classes of compounds like heterocycles.

Herein, a straightforward and practical strategy involving radicals for the three-component carbonyl propargylation via dual photoredox and titanium catalysis is presented. This strategy delivers homopropargyl alcohols and includes readily available starting materials, a broad substrate scope, high functional group tolerance, and mild reaction conditions. Catalytic Cp2TiCl2, recognized as an inexpensive, nontoxic, and bench-stable titanium source, is employed.

Three-Component Synthesis of Pyrazoles Using Titanium Catalysis

Recently, radical difunctionalization of the feedstock 1,3-butadiene has become an attractive strategy for increasing molecular complexity. Herein, we present a novel approach that effectively combines radical thiol-ene chemistry with TiIII catalysis to enable a three-component aldehyde allylation using 1,3-butadiene as an allyl group source under visible light conditions. This sustainable and straightforward method has facilitated the rapid production of diverse allylic 1,3-thioalcohols with exceptional regio- and diastereoselectivity.

Dienes have a wide importance throughout synthetic chemistry. While there are many methods for their preparation, this paper provides an excellent protocol for the stereoselective synthesis of Si/Sn 2,3-bis-metallo-dienes. The first step involves hydromagnesiation of alkynyl silanes via titanium catalysis. This vinyl magnesium bromide is then coupled with a vinyl iodide under palladium catalysis.

Ammonia-borane, shown previously to react with carboxylic acids under reflux to form primary amides, reduces acids to alcohols at room temperature in the presence of catalytic TiCl4. The process, which is tolerant of a variety of potentially reactive functional groups, including N-protected amino acids, can be employed for the selective reduction of acids in the presence of amides, nitriles and, to some extent, esters. Aliphatic acids can be selectively reduced in the presence of aromatic acids.

The integrity and thermal decomposition of calcium apatite are influenced by the underlying titanium during plasma-spraying deposition, especially at the apatite/titanium interface. The destruction of apatite at the interface is governed by substrate temperature, titanium catalysis, and its reaction with titanium dioxide produced from oxidation of titanium in the plasma gas. The apatite in the outer layer of coatings is affected mainly by the substrate temperature and can keep its integrity with a suitable plasma-spraying procedure to minimize the increase of substrate temperature. The heat treatment of the coatings in vacuum results in the decomposition of apatite to α-tricalcium phosphate (α-TCP) and tetracalcium phosphate monoxide (TCPM) with the increase of intensity approaching the interface, which roughens the surface of the coatings. In the air-heat treatment, oxidation of titanium produces a thickened, dense rutile layer at the interface which prevents titanium atoms from diffusing into the coatings and inhibits the titanium-catalyzed decomposition of apatite. The apatite adjacent to the rutile layer reacts moderately with rutile to produce calcium titanate (CaTiO3), α- and β-TCP, while the apatite in the outer layer, separated from the rutile layer, maintains its integrity without decomposition even in a prolonged air-heat treatment. The retention of apatite integrity leads to a decreased surface roughness of the coating. © 1996 John Wiley & Sons, Inc.

For Abstract see ChemInform Abstract in Full Text.

This work demonstrates the synthesis of functionalized polyolefins via titanium catalysis and post-polymerization modification. The key to success is the lack of coordination of the cyclopropane moiety to the propagating titanium species.