Diverse Reactivity of Amidinate-Supported Boron Centers with the Hypersilyl Anion and Access to a Monomeric Secondary Boron Hydride.

Diverse reactivity of the bulky tris(trimethylsilyl)silyl substituent [Si(SiMe3)3], also known as the hypersilyl group, was observed for amidinate-supported dichloro- and phenylchloroborane complexes. Treatment of the dichloroborane with potassium tris(trimethylsilyl)silyl led to the activation of the backbone ß-carbon center and formation of saturated four-membered heterocyclic chloroboranes R'{Si(SiMe3)3}C(NR)2BCl [R' = Ph, R = Cy (3); R' = Ph, R = iPr (6); R' = tBu, R = Cy (8)], whereas the four-membered amidinate hypersilyl-substituted phenyl borane 4 {PhC(NCy)2B(Ph)[Si(SiMe3)3]} was observed for the case of an amidinate-supported phenylchloroborane. The highly deshielded 11B NMR spectroscopic resonance and the distinct difference in the 29Si NMR spectrum confirmed the presence of a σ-donating hypersilyl effect on compounds 3, 6, and 8. Reaction of 3 with the Lewis acid AlCl3 led to the formation of complex 11 in which an unusual cleavage of one of the C-N bonds of the amidinate backbone is observed. Nucleophilic substitution at the boron center of saturated chloroborane 3 with phenyllithium generated the phenylborane derivative 12, whereas the secondary monomeric boron hydride 13 was observed after treatment with alane (AlH3). All compounds (2-13) have been fully characterized by NMR spectroscopy and single-crystal X-ray structure determination studies.

An un-forgotten classic: the nitro-Mannich reaction between nitrones and silyl nitronates catalysed by B(C6F5)3.

Herein we report the B(C6F5)3-catalysed nitro-Mannich reaction between nitrones and silyl nitronates, affording silyl-protected α-nitro hydroxylamines with yields up to 99% and diastereoselectivities up to 99 : 1. Crucially, the obtained products can be converted into 1,2-diamines under simple reductive conditions. This work provides a new orthogonal method to the existing routes for the instalment of a nitro moiety under Lewis acid catalysed conditions, and expands the state-of-the-art substrate scope with respect to the silyl nitronates.

B(3,4,5-F3H2C6)3 Lewis acid-catalysed C3-allylation of indoles.

Herein we report the B(3,4,5-F3H2C6)3-catalysed C3-allylation of indoles using allylic esters. 25 examples of C3-allylated products are presented in up to 97% yield. The mechanism for the reaction was explored using detailed Density Functional Theory (DFT) studies.

Flow Electrochemistry for the N-Nitrosation of Secondary Amines.

A flow electrochemical method towards the synthesis of N-nitroso compounds from secondary amines using cheap and readily available sodium nitrite has been developed. Sodium nitrite dissolved in aqueous acetonitrile made additional electrolytes unnecessary. This mild and straightforward approach made the use of acids or other harsh and toxic chemicals redundant. This procedure was applied to an assortment of cyclic and acyclic secondary amines (27 examples) resulting in yields of N-nitrosamines as high as 99 %. To demonstrate the practicality of the process, scaled-up reactions were performed. Finally, selected products could be purified by using an in-line acidic extraction.

Understanding the Influence of Donor-Acceptor Diazo Compounds on the Catalyst Efficiency of B(C6 F5 )3 Towards Carbene Formation.

Diazo compounds have been largely used as carbene precursors for carbene transfer reactions in a variety of functionalization reactions. However, the ease of carbene generation from the corresponding diazo compounds depends upon the electron donating/withdrawing substituents either side of the diazo functionality. These groups strongly impact the ease of N2 release. Recently, tris(pentafluorophenyl)borane [B(C6 F5 )3 ] has been shown to be an alternative transition metal-free catalyst for carbene transfer reactions. Herein, a density functional theory (DFT) study on the generation of carbene species from α-aryl α-diazocarbonyl compounds using catalytic amounts of B(C6 F5 )3 is reported. The significant finding is that the efficiency of the catalyst depends directly on the nature of the substituents on both the aryl ring and the carbonyl group of the substrate. In some cases, the boron catalyst has negligible effect on the ease of the carbene formation, while in other cases there is a dramatic reduction in the activation energy of the reaction. This direct dependence is not commonly observed in catalysis and this finding opens the way for intelligent design of this and other similar catalytic reactions.

Exploring Cyclization Strategies to Access Stemona Alkaloids: Subtle Effects Influencing Reactivity in Intramolecular Michael Additions.

This report investigates the fundamental basis for rather surprising patterns of reactivity in Brønsted acid-mediated cyclizations of pyrrole substrates bearing pendant Michael acceptors that were identified during syntheses of Stemona alkaloids. Integrated experimental and theoretical studies reveal the profound influence that substituent effects have on the viability of these transformations. Additionally, we identify that electronic effects, in addition to barrier-lowering secondary orbital interactions within transition states, account for the exclusive preference for 7-endo-trig cyclizations over 6-exo-trig cyclizations.

Tris(pentafluorophenyl)borane-Catalyzed Carbenium Ion Generation and Autocatalytic Pyrazole Synthesis-A Computational and Experimental Study.

In recent years, metal-free organic synthesis using triarylboranes as catalysts has become a prevalent research area. Herein we report a comprehensive computational and experimental study for the highly selective synthesis of N-substituted pyrazoles through the generation of carbenium species from the reaction between aryl esters and vinyl diazoacetates in the presence of catalytic tris(pentafluorophenyl)borane [B(C6 F5 )3 ]. DFT studies were undertaken to illuminate the reaction mechanism revealing that the in situ generation of a carbenium species acts as an autocatalyst to prompt the regiospecific formation of N-substituted pyrazoles in good to excellent yields (up to 81 %).

Site-Selective Csp3-Csp/Csp3-Csp2 Cross-Coupling Reactions Using Frustrated Lewis Pairs.

The donor-acceptor ability of frustrated Lewis pairs (FLPs) has led to widespread applications in organic synthesis. Single electron transfer from a donor Lewis base to an acceptor Lewis acid can generate a frustrated radical pair (FRP) depending on the substrate and energy required (thermal or photochemical) to promote an FLP into an FRP system. Herein, we report the Csp3-Csp cross-coupling reaction of aryl esters with terminal alkynes using the B(C6F5)3/Mes3P FLP. Significantly, when the 1-ethynyl-4-vinylbenzene substrate was employed, the exclusive formation of Csp3-Csp cross-coupled products was observed. However, when 1-ethynyl-2-vinylbenzene was employed, solvent-dependent site-selective Csp3-Csp or Csp3-Csp2 cross-coupling resulted. The nature of these reaction pathways and their selectivity has been investigated by extensive electron paramagnetic resonance (EPR) studies, kinetic studies, and density functional theory (DFT) calculations both to elucidate the mechanism of these coupling reactions and to explain the solvent-dependent site selectivity.

Triarylborane-Catalyzed Alkenylation Reactions of Aryl Esters with Diazo Compounds.

Herein we report a facile, mild reaction protocol to form carbon-carbon bonds in the absence of transition metal catalysts. We demonstrate the metal-free alkenylation reactions of aryl esters with α-diazoesters to give highly functionalized enyne products. Catalytic amounts of tris(pentafluorophenyl)borane (10-20 mol %) are employed to afford the C=C coupled products (31 examples) in good to excellent yields (36-87 %). DFT studies were used to elucidate the mechanism for this alkenylation reaction.

Gold-Catalyzed Regiospecific Annulation of Unsymmetrically Substituted 1,5-Diynes for the Precise Synthesis of Bispentalenes.

Precise control of the selectivity in organic synthesis is important to access the desired molecules. We demonstrate a regiospecific annulation of unsymmetrically substituted 1,2-di(arylethynyl)benzene derivatives for a geometry-controlled synthesis of linear bispentalenes, which is one of the promising structures for material science. A gold-catalyzed annulation of unsymmetrically substituted 1,2-di(arylethynyl)benzene could produce two isomeric pentalenes, but both electronic and steric effects on the aromatics at the terminal position of the alkyne prove to be crucial for the selectivity; especially a regiospecific annulation was achieved with sterically blocked substituents; namely, 2,4,6-trimetyl benzene or 2,4-dimethyl benzene. This approach enables the geometrically controlled synthesis of linear bispentalenes from 1,2,4,5-tetraethynylbenzene or 2,3,6,7-tetraethynylnaphthalene. Moreover, the annulation of a series of tetraynes with a different substitution pattern regioselectively provided the bispentalene scaffolds. A computational study revealed that this is the result of a kinetic control induced by the bulky NHC ligands.

Rationale for the reactivity differences between main group and d0 transition metal complexes toward olefin polymerisation.

In contrast to early transition metal complexes of d0 electron configuration, their main group metal analogues are usually poor catalysts for ethylene polymerisation due to their diminished tendency to insert ethylene into an M-R bond. Interestingly, we found that ring strain in the transition structure of the insertion reaction is most likely responsible to set the ease of the process. Ethylene insertion into an M-R bond requires a four-membered ring transition structure. Strain in a four-membered ring was shown to be dependent on the metal identity (transition or main group/d or p block). For early transition metals, due to the presence of empty valence d orbitals, the strain is negligible but, for main group metals, the strain is significant and so destabilizes the corresponding transition structure. Our claim gains support from investigation of ethylene insertion into an M-allyl bond. In this case, the relevant insertion preferentially passes through a six-membered ring transition structure with an accessibly low activation barrier. In contrast to four-membered ring transition structures, six-membered ones do not suffer significantly from ring strain, causing the insertion activation barrier to become independent of the metal identity. It becomes obvious from our study that this previously undisclosed factor should play the pivotal role in determining the reactivity of many catalysts.

Dual Gold-Catalyzed Cycloaromatization of Unconjugated (E)-Enediynes.

A synthesis of unconjugated (E)-enediynes from allenyl amino alcohols is reported and their gold-catalyzed cascade cycloaromatization to a broad range of enantioenriched substituted isoindolinones has been developed. Experimental and computational studies support the reaction proceeding via a dual-gold σ,π-activation mode, involving a key gold-vinylidene- and allenyl-gold-containing intermediate.

Nazarov cyclisations initiated by DDQ-oxidised pentadienyl ether: a mechanistic investigation from the DFT perspective.

The Nazarov cyclisation is an important and reliable reaction for the synthesis of cyclopentenones. Density functional theory (DFT) has been utilised to study the mechanism of Nazarov cyclisations initiated by oxidation of pentadienyl ethers by a benzoquinone derivative (DDQ), as recently reported by West et al. (Angew. Chem., Int. Ed., 2017, 56, 6335). We determined that the reaction is most likely initiated by a hydride transfer from the pentadienyl ether to an oxygen of DDQ through a concerted pathway and not a single electron transfer mechanism. This oxidation by hydride abstraction leads to the formation of a pentadienyl cation from which the 4π electrocyclisation occurs, giving an alkoxycyclopentenyl cation. The ensuing cation is subsequently deprotonated by the reduced DDQ to afford an enol ether product. Consistent with experimental results, the hydride transfer is calculated to be the rate determining step and it can be accelerated by using electron donating substituents on the pentadienyl ether substrate. Indeed, the electron donating substituents increase the HOMO energy of the ether, making it more reactive toward oxidation. It is predicted that an unsubstituted benzoquinone, due to having a higher lying LUMO, shows much less reactivity than DDQ. Interestingly, we found an excellent correlation between the hydride transfer activation energy and the gap between the ether HOMO and the benzoquinone LUMO. From this correlation, we propose a predictive formula for reactivity of different types of substrates in the corresponding reaction.

Different Selectivities in the Insertions into C(sp2 )-H Bonds: Benzofulvenes by Dual Gold Catalysis Competition Experiments.

An unprecedented, often almost quantitative access to tricyclic aromatic compounds by dual gold catalysis was developed. This synthetic route expands the scope of benzofulvene derivatives through a C(sp2 )-H bond insertion in easily available starting materials. The insertion takes place with an exclusive chemoselectivity with respect to the competing aromatic C-H positions. A bidirectional synthesis with two competing ortho-aryl C-H bonds in the selectivity-determining step also shows perfect selectivity; this result is explained by a computational investigation of the two conceivable intermediates. The intramolecular competition of two non-equivalent aryl C-H bonds with a benzylic methyl group also showed perfect selectivity.

Theoretical rationalisation for the mechanism of N-heterocyclic carbene-halide reductive elimination at Cu(III), Ag(III) and Au(III).

Reductive elimination of imidazolium salts from Cu(III) is extremely sensitive to the anionic ligand (X or Y) type on Cu (e.g.ΔG(‡) ranges from 4.7 kcal mol(-1) to 31.8 kcal mol(-1), from chloride to benzyl). Weakly σ-donating ligands dramatically accelerate reductive elimination. Comparison with Ag/Au shows that the HOMO energy, strength of M-NHC and M-Y bonds and inherent stability of M(III) with respect to M(I) are critical to governing reaction feasibility.

Theoretical study on the ring-opening reactions of cyclopropenes mediated by a AuI complex.

DFT calculations have been carried out in order to rationalize and predict the ring-opening regioselectivity of substituted cyclopropenes in the presence of gold(I) catalysts. It has been shown that the regioselectivity of these ring-opening processes is driven by the relative π-donor ability of the substituents on the cyclopropene double bond (C1 and C2). A stronger π-donor substituent at C2 favors Au(I)-induced polarization of the double bond toward C1, resulting in preferential breaking of the C1-C3 bond. An excellent correlation between ΔE(++) and the difference in the C1-C2 p(π) orbital population was observed for a broad range of substituents, providing a useful predictive model for gold-induced cyclopropene ring-opening. Furthermore, it was found that the stability of the resulting gold-stabilized allyl-cation intermediates do not follow the same trend as the ring-opening reaction energies. Generally, the more facile ring-opening process led to the less thermodynamically stable intermediate, which lacked stabilization of the carbocation by a π-donor in the α-position.