Contra-thermodynamic Hydrogen Atom Abstraction in the Selective C–H Functionalization of Trialkylamine <i>N</i>‑CH₃ Groups

We report a simple one-pot protocol that affords functionalization of <i>N</i>-C<b>H</b>₃ groups in <i>N</i>-methyl-<i>N</i>,<i>N</i>-dialkylamines with high selectivity over <i>N</i>-C<b>H</b>₂R or <i>N</i>-C<b>H</b>R₂ groups. The radical cation DABCO^+•, prepared in situ by oxidation of DABCO with a triarylaminium salt, effects highly selective and contra-thermodynamic C–H abstraction from <i>N</i>-C<b>H</b>₃ groups. The intermediates that result react in situ with organometallic nucleophiles in a single pot, affording novel and highly selective homologation of <i>N</i>-C<b>H</b>₃ groups. Chemoselectivity, scalability, and recyclability of reagents are demonstrated, and a mechanistic proposal is corroborated by computational and experimental results. The utility of the transformation is demonstrated in the late-stage site-selective functionalization of natural products and pharmaceuticals, allowing rapid derivatization for investigation of structure–activity relationships

Overturning Established Chemoselectivities: Selective Reduction of Arenes over Malonates and Cyanoacetates by Photoactivated Organic Electron Donors

The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate–metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor <b>5</b> selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates

Amidine Dications: Isolation and [Fe]-Hydrogenase-Related Hydrogenation

Amidine Dications: Isolation and [Fe]-Hydrogenase-Related Hydrogenatio

Amidine Dications: Isolation and [Fe]-Hydrogenase-Related Hydrogenation

Amidine Dications: Isolation and [Fe]-Hydrogenase-Related Hydrogenatio

Mechanistic Exploration of the Palladium-catalyzed Process for the Synthesis of Benzoxazoles and Benzothiazoles

A convenient one-pot palladium-catalyzed cascade process for the preparation of both benzoxazoles and benzothiazoles has been developed. While these reactions proceed to give similar compounds the mechanisms governing the processes are different as are the experimental conditions employed

One-Carbon Extrusion from a Tetraazafulvalene. Isolation of Aldehydes and a Study of Their Origin

Reaction of imidazolylidene-derived enetetramine <b>2</b> with aliphatic iodides and bromides (and with aryl iodides bearing alkene-containing side-chains in the ortho-position) leads to formation of aliphatic aldehydes through an unprecedented extrusion of a one-carbon unit from the enetetramine. An intermediate 2-alkylimidazoline <b>24</b> is proposed, where the alkyl group derives from the substrate; this imidazoline undergoes further reaction in situ to afford the observed aldehydes on acidic workup. Modified substrates were designed and prepared to probe the chemistry of the alkylimidazoline adducts and provided extensive information on the chemistry of the adducts

Amidine Dications as Superelectrophiles

2-Dimethylalkylammonium pyridinium and 2-dimethylalkylammonium pyrimidinium ditriflate salts are very powerful methylating agents toward phosphorus (triphenylphosphine) and nitrogen (triethylamine) nucleophiles. In competition experiments with triethylamine as nucleophile, these <i>N</i>-methyl disalts are more reactive methylating agents than dimethyl sulfate. Reaction of the pyridinium dications with water as an oxygen nucleophile leads to attack at the 2-position of the heteroaromatic ring and displacement of an ammonium group; 2-hydroxypyridinium compounds are formed in the first instance, which are easily converted to 2-pyridones. Extending the scope of the reactions, a tricationic 2,6-bis(dimethylalkylammonium)pyridinium salt has also been prepared and characterized and its reactivity as a methylating agent assessed in comparison with that of the dications

A Hierarchy of Ligands Controls Formation and Reaction of Aryl Radicals in Pd-Catalyzed Ground-State Base-Promoted Coupling Reactions

Palladium salts and complexes were tested separately and in the presence of added ligands as potential sources of aryl radicals in ground-state coupling reactions of aryl halide with arenes under basic conditions (KOtBu). Our recently developed assay for aryl radicals was employed to test for aryl radicals. In this assay, aryl radicals derived from the test substrate, 1-iodo-2,6-dimethylbenzene 7, undergo base-promoted homolytic aromatic substitution (BHAS) with benzene to produce 2,6-dimethylbiphenyl 8 and biphenyl 9 in an approximately 1:4 ratio as well as m-xylene 10. The biphenyl arises from a diagnostic radical transfer reaction with the solvent benzene. Using substrate 7 with a range of Pd sources as potential initiators led to formation of 8, 9, and 10 in varying amounts. However, when any one of a range of diphosphinoferrocenes (e.g., dppf or dippf) or BINAP or the monophosphine, diphenylphosphinoferrocene, was added as a ligand to Pd(OAc)2, the ratio of [2,6-dimethylbiphenyl 8: biphenyl 9] moved decisively to that expected from the BHAS (radical) pathway. Further studies were conducted with dppf. When dppf was added to each of the other Pd sources, the ratio of coupled products was also diverted to that expected for radical BHAS chemistry. Deuterium isotope studies and radical trap experiments provide strong additional support for the involvement of aryl radicals. Accordingly, under these ground-state conditions, palladium sources, in the presence of defined ligands, convert aryl iodides to aryl radicals. A rationale is proposed for these observations

Electron Transfer Reactions: KO<i>t</i>Bu (but not NaO<i>t</i>Bu) Photoreduces Benzophenone under Activation by Visible Light

Long-standing controversial reports of electron transfer from KO<i>t</i>Bu to benzophenone have been investigated and resolved. The mismatch in the oxidation potential of KO<i>t</i>Bu (+0.10 V vs SCE in DMF) and the first reduction potential of benzophenone (of many values cited in the literature, the least negative value is −1.31 V vs SCE in DMF), preclude direct electron transfer. Experimental and computational results now establish that a complex is formed between the two reagents, with the potassium ion providing the linkage, which markedly shifts the absorption spectrum to provide a tail in the visible light region. Photoactivation at room temperature by irradiation at defined wavelength (365 or 400 nm), or even by winter daylight, leads to the development of the blue color of the potassium salt of benzophenone ketyl, whereas no reaction is observed when the reaction mixture is maintained in darkness. So, <i>no</i> electron transfer occurs in the ground state. However, when photoexcited, electron transfer occurs within a complex formed from benzophenone and KO<i>t</i>Bu. TDDFT studies match experimental findings and also define the electronic transition within the complex as n → π*, originating on the butoxide oxygen. Computation and experiment also align in showing that this reaction is selective for KO<i>t</i>Bu; no such effect occurs with NaO<i>t</i>Bu, providing the first case where such alkali metal ion selectivity is rationalized in detail. Chemical evidence is provided for the photoactivated electron transfer from KO<i>t</i>Bu to benzophenone: <i>tert</i>-butoxyl radicals are formed and undergo fragmentation to form (acetone and) methyl radicals, some of which are trapped by benzophenone. Likewise, when KOC­(Et)₃ is used in place of KO<i>t</i>Bu, then ethylation of benzophenone is seen. Further evidence of electron transfer was seen when the reaction was conducted in benzene, in the presence of <i>p-</i>iodotoluene; this triggered BHAS coupling to form 4-methylbiphenyl in 74% yield

Reductions of Challenging Organic Substrates by a Nickel Complex of a Noninnocent Crown Carbene Ligand

The first crown-tetracarbene complex of Ni(II) has been prepared, and its crystal structure determined. The complex can be reduced by Na/Hg, with an uptake of two electrons. The reduced complex reductively cleaves arenesulfonamides, including those derived from secondary aliphatic amines, and effects Birch reduction of anthracenes as well as reductive cleavage of stilbene oxides. Computational studies show that the orbital that receives electrons upon reduction of the complex <b>2</b> is predominantly based on the crown carbene ligand and also that the HOMO of the parent complex <b>2</b> is based on the ligand