Towards a Paradigm Shift in Polar Organometallic Chemistry

Core tools of synthetic chemistry, polar organometallic reagents (typified by organolithium and Grignard reagents) are used worldwide for constructing compounds, especially aromatic compounds, which are ubiquitous in organic chemistry and thus in numerous commodities essential to everyday life. By isolation and characterisation of key organometallic intermediates, research in our group has led to the design of polar mixed-metal reagents imbued with synergistic effects that display chemical properties and reactivity profiles far exceeding the limits of traditional single-metal reagents. These studies have improved existing, or established new fundamentally important, synthetic methodologies based on either stoichiometric or catalytic reactions. Bimetallic cooperative effects have been demonstrated in an impressive array of important bond forming reactions including deprotonative metallation, transition metal-free C–C bond formation and metal–halogen exchange to name just a few. Towards greener, more sustainable, safer chemical transformations, our group has also pioneered the use of polar organometallic reagents under air and/or with water present using biorenewable solvents such as Deep Eutectic Solvents (DES) and 2-methyl THF. Herein we summarize some of our recent efforts in this intriguing area, which we believe can make inroads towards a step change in the practice and future scope of polar organometallic chemistry.

N-Heterocyclic Carbene-Supported Aryl- and Alk- oxides of Beryllium and Magnesium

Recently, we have witnessed significant progress with regard to the synthesis of molecular alkaline earth metal reagents and catalysts. To provide new precursors for light alkaline earth metal chemistry, molecular aryloxide and alkoxide complexes of beryllium and magnesium are reported. The reaction of beryllium chloride dietherate with two equivalents of 1,3-diisopropyl-4,5-dimethylimidizol-2-ylidine (sIPr) results in the formation of a bis(N-heterocyclic carbene) (NHC) beryllium dichloride complex, (sIPr)2BeCl2 (1). Compound 1 reacts with lithium diisopropylphenoxide (LiODipp) or sodium ethoxide (NaOEt) to form the terminal aryloxide (sIPr)Be(ODipp)2 (2) and alkoxide dimer [(sIPr)Be(OEt)Cl]2 (3), respectively. Compounds 2 and 3 represent the first beryllium alkoxide and aryloxide species supported by NHCs. Structurally related dimers of magnesium, [(sIPr)Mg(OEt)Brl]2 (4) and [(sIPr)Mg(OEt)Me]2 (5), were also prepared. Compounds 1-5 were characterized by single crystal X-ray diffraction studies, 1H, 13C, and 9Be NMR spectroscopy where applicable.

Oligothiophene Synthesis by a Distinct, General C−H Activation Mechanism: Electrophilic Concerted Metalation-Deprotonation (eCMD)

Oxidative C–H/C–H coupling is a promising synthetic route for the streamlined construction of conjugated organic materials for optoelectronic applications. Broader adoption of these methods is nevertheless hindered by the need for catalysts that excel in forging core semiconductor motifs, such as ubiquitous oligothiophenes, with high efficiency in the absence of metal reagents. We report a (thioether)Pd-catalyzed oxidative coupling method for the rapid assembly of both privileged oligothiophenes and challenging hindered cases, even at low catalyst loading under Ag- and Cu-free conditions. A combined experimental and computational mechanistic study was undertaken to understand how a simple thioether ligand, MeS(CH₂)₃SO₃Na, leads to such potent reactivity toward electron-rich substrates. The consensus from these data is that a concerted, base-assisted C–H cleavage transition state is operative, but thioether coordination to Pd is associated with decreased synchronicity (bond formation exceeding bond breaking) versus the classic concerted metalation-deprotonation (CMD) model. Enhanced positive charge build-up on the substrate results from this perturbation, which rationalizes experimental trends strongly favoring π-basic sites. The term <i>electrophilic</i> CMD (<i>e</i>CMD) is introduced to distinguish this mechanism. More O'Ferrall-Jencks analysis further suggests <i>e</i>CMD should be a general mechanism manifested by many metal complexes. A preliminary classification of complexes into those favoring <i>e</i>CMD or standard CMD is proposed, which should be informative for studies toward tunable catalyst-controlled reactivity.

Oligothiophene Synthesis by a Distinct, General C−H Activation Mechanism: Electrophilic Concerted Metalation-Deprotonation (eCMD)

Oxidative C–H/C–H coupling is a promising synthetic route for the streamlined construction of conjugated organic materials for optoelectronic applications. Broader adoption of these methods is nevertheless hindered by the need for catalysts that excel in forging core semiconductor motifs, such as ubiquitous oligothiophenes, with high efficiency in the absence of metal reagents. We report a (thioether)Pd-catalyzed oxidative coupling method for the rapid assembly of both privileged oligothiophenes and challenging hindered cases, even at low catalyst loading under Ag- and Cu-free conditions. A combined experimental and computational mechanistic study was undertaken to understand how a simple thioether ligand, MeS(CH₂)₃SO₃Na, leads to such potent reactivity toward electron-rich substrates. The consensus from these data is that a concerted, base-assisted C–H cleavage transition state is operative, but thioether coordination to Pd is associated with decreased synchronicity (bond formation exceeding bond breaking) versus the classic concerted metalation-deprotonation (CMD) model. Enhanced positive charge build-up on the substrate results from this perturbation, which rationalizes experimental trends strongly favoring π-basic sites. The term <i>electrophilic</i> CMD (<i>e</i>CMD) is introduced to distinguish this mechanism. More O'Ferrall-Jencks analysis further suggests <i>e</i>CMD should be a general mechanism manifested by many metal complexes. A preliminary classification of complexes into those favoring <i>e</i>CMD or standard CMD is proposed, which should be informative for studies toward tunable catalyst-controlled reactivity.

Oligothiophene Synthesis by a Distinct, General C−H Activation Mechanism: Electrophilic Concerted Metalation-Deprotonation (eCMD)

Oxidative C–H/C–H coupling is a promising synthetic route for the streamlined construction of conjugated organic materials for optoelectronic applications. Broader adoption of these methods is nevertheless hindered by the need for catalysts that excel in forging core semiconductor motifs, such as ubiquitous oligothiophenes, with high efficiency in the absence of metal reagents. We report a (thioether)Pd-catalyzed oxidative coupling method for the rapid assembly of both privileged oligothiophenes and challenging hindered cases, even at low catalyst loading under Ag- and Cu-free conditions. A combined experimental and computational mechanistic study was undertaken to understand how a simple thioether ligand, MeS(CH₂)₃SO₃Na, leads to such potent reactivity toward electron-rich substrates. The consensus from these data is that a concerted, base-assisted C–H cleavage transition state is operative, but thioether coordination to Pd is associated with decreased synchronicity (bond formation exceeding bond breaking) versus the classic concerted metalation-deprotonation (CMD) model. Enhanced positive charge build-up on the substrate results from this perturbation, which rationalizes experimental trends strongly favoring π-basic sites. The term <i>electrophilic</i> CMD (<i>e</i>CMD) is introduced to distinguish this mechanism. More O'Ferrall-Jencks analysis further suggests <i>e</i>CMD should be a general mechanism manifested by many metal complexes. A preliminary classification of complexes into those favoring <i>e</i>CMD or standard CMD is proposed, which should be informative for studies toward tunable catalyst-controlled reactivity.