Geminal Bis Research Articles

Palladium-Catalyzed Cascade Heck Coupling and Allylboration of Iododiboron Compounds via Diboryl Radicals.

Geminal bis(boronates) are versatile synthetic building blocks in organic chemistry. The fact that they predominantly serve as nucleophiles in the previous reports, however, has restrained their synthetic potential. Herein we disclose the ambiphilic reactivity of α-halogenated geminal bis(boronates), of which the first catalytic utilization was accomplished by merging a formal Heck cross-coupling with a highly diastereoselective allylboration of aldehydes or imines, providing a new avenue for rapid assembly of polyfunctionalized boron-containing compounds. We demonstrated that this cascade reaction is highly efficient and compatible with various functional groups, and a wide range of heterocycles. In contrast to a classical Pd(0/II) scenario, mechanistic experiments and DFT calculations have provided strong evidence for a catalytic cycle involving Pd(I)/diboryl carbon radical intermediates.

Direct Synthesis of Tertiary Phosphines via Alkoxide-Mediated Deborylative Phosphination of Organoboronates.

The direct transformation of alkylboron has emerged as a versatile and powerful methodology for creating carbon-carbon and carbon-heteroatom bonds. However, its potential application in the formation of carbon and phosphorus remains unexplored. In this study, we present an alkoxide base-promoted reaction system that enables deborylative phosphination of benzylic organoboronates and geminal bis(boronates) via selective C-B bond cleavage. This approach allows for the synthesis of valuable tertiary phosphines in good yields under mild conditions. The practicality and industrial potential of this approach are underscored by the operational simplicity, broad substrate scope, and easy scalability.

Borataalkenes, boraalkenes, and the η2-B,C coordination mode in coordination chemistry and catalysis.

Borataalkenes and boraalkenes are the boron-containing isoelectronic analogues of alkenes and vinyl cations respectively. Compared with alkenes, the borataalkene and boraalkene ligand motifs in transition metal coordination chemistry are relatively underexplored. In this review, the synthesis of borataalkene and boraalkene complexes and other transition metal complexes featuring the η2-B,C coordination mode is described. The diversity of coordination modes and geometry in these complexes, and the spectroscopic and structural evidence supporting their assignments is disclosed as well as computational analysis of bonding. The applications of the borataalkene ligand motif in synthetic organic homogeneous catalysis, especially those involving geminal bis(pinacolatoboronates) and 1,4-azaborines, are discussed.

A General Method to Access Sterically Encumbered Geminal Bis(boronates) via Formal Umpolung Transformation of Terminal Diboron Compounds.

General methods for the preparation of geminal bis(boronates) are of great interest due to their widespread applications in organic synthesis. While the terminal gem-diboron compounds are readily accessible, the construction of the sterically encumbered, internal analogues has remained a prominent challenge. Herein, we report a formal umpolung strategy to access these valuable building blocks. The readily available 1,1-diborylalkanes were first converted into the corresponding α-halogenated derivatives, which then serve as electrophilic components, undergoing a formal substitution with a diverse array of nucleophiles to form a series of C-C, C-O, C-S, and C-N bonds. This protocol features good tolerance to steric hindrance and a wide variety of functional groups and heterocycles. Notably, this strategy can also be extended to the synthesis of diaryl and terminal gem-diboron compounds, therefore providing a general approach to various types of geminal bis(boronates).

A General Method to Access Sterically Encumbered Geminal Bis(boronates) via Formal Umpolung Transformation of Terminal Diboron Compounds

AbstractGeneral methods for the preparation of geminal bis(boronates) are of great interest due to their widespread applications in organic synthesis. While the terminal gem‐diboron compounds are readily accessible, the construction of the sterically encumbered, internal analogues has remained a prominent challenge. Herein, we report a formal umpolung strategy to access these valuable building blocks. The readily available 1,1‐diborylalkanes were first converted into the corresponding α‐halogenated derivatives, which then serve as electrophilic components, undergoing a formal substitution with a diverse array of nucleophiles to form a series of C−C, C−O, C−S, and C−N bonds. This protocol features good tolerance to steric hindrance and a wide variety of functional groups and heterocycles. Notably, this strategy can also be extended to the synthesis of diaryl and terminal gem‐diboron compounds, therefore providing a general approach to various types of geminal bis(boronates).

Facile Access to Cyclopropylboronates via Stereospecific Deborylative Cyclization: A Leaving Group-Assisted Activation of Geminal Diborons.

Herein we reported a transition metal-free deborylative cyclization strategy, based on which two routes have been developed, generating racemic and enantioenriched cyclopropylboronates. The cyclization of geminal-bis(boronates) bearing a leaving group was highly diastereoselective, tolerating a few functional groups and applicable to heterocycles. When optically active epoxides were used as the starting materials, enantioenriched cyclopropylboronates could be efficiently prepared with >99 % stereospecificity. Mechanistic studies showed that the leaving group at the γ-position played a crucial role and significantly promoted the activation of the gem-diboron moiety.

Facile preparation of organosilanes from benzylboronates and gem-diborylalkanes mediated by KOtBu.

Methods to efficiently synthesize organosilanes are valuable in the fields of synthetic chemistry and materials science. During the past decades, boron conversion has become a generic and powerful approach for constructing carbon-carbon and other carbon-heteroatom bonds, but its potential application in forming carbon-silicon remains unexplored. Herein, we describe an alkoxide base-promoted deborylative silylation of benzylic organoboronates, geminal bis(boronates) or alkyltriboronates, allowing for straightforward access to synthetically valuable organosilanes. This selective deborylative methodology exhibits operational simplicity, broad substrate scope, excellent functional group compatibility and convenient scalability, providing an effective and complementary platform for the generation of diversified benzyl silanes and silylboronates. Detailed experimental results and calculated studies revealed an unusual mechanistic feature of this C-Si bond formation.

Cobalt‐Catalyzed Regiodivergent Double Hydrosilylation of Arylacetylenes

AbstractDouble hydrosilylation of alkynes represents a straightforward method to synthesize bis(silane)s, yet it is challenging if α‐substituted vinylsilanes act as the intermediates. Here, a cobalt‐catalyzed regiodivergent double hydrosilylation of arylacetylenes is reported for the first time involving this challenge, accessing both vicinal and geminal bis(silane)s with exclusive regioselectivity. Various novel bis(silane)s containing Si−H bonds can be easily obtained. The gram‐scale reactions could be performed smoothly. Preliminarily mechanistic studies demonstrated that the reactions were initiated by cobalt‐catalyzed α‐hydrosilylation of alkynes, followed by cobalt‐catalyzed β‐hydrosilylation of the α‐vinylsilanes to deliver vicinal bis(silane)s, or hydride‐catalyzed α‐hydrosilylation to give geminal ones. Notably, these bis(silane)s can be used for the synthesis of high‐refractive‐index polymers (nd up to 1.83), demonstrating great potential utility in optical materials.

Cobalt-Catalyzed Regiodivergent Double Hydrosilylation of Arylacetylenes.

Double hydrosilylation of alkynes represents a straightforward method to synthesize bis(silane)s, yet it is challenging if α-substituted vinylsilanes act as the intermediates. Here, a cobalt-catalyzed regiodivergent double hydrosilylation of arylacetylenes is reported for the first time involving this challenge, accessing both vicinal and geminal bis(silane)s with exclusive regioselectivity. Various novel bis(silane)s containing Si-H bonds can be easily obtained. The gram-scale reactions could be performed smoothly. Preliminarily mechanistic studies demonstrated that the reactions were initiated by cobalt-catalyzed α-hydrosilylation of alkynes, followed by cobalt-catalyzed β-hydrosilylation of the α-vinylsilanes to deliver vicinal bis(silane)s, or hydride-catalyzed α-hydrosilylation to give geminal ones. Notably, these bis(silane)s can be used for the synthesis of high-refractive-index polymers (nd up to 1.83), demonstrating great potential utility in optical materials.

Front Cover: Synthesis of Geminal Bis‐ and Tetrakisphosphonate Ester Derivatives and Their Coordination Behavior Towards Ca(II) Ions (Eur. J. Inorg. Chem. 17/2022)

The Front Cover shows an illustration of a hip joint flanked by calcium- and phosphorus-containing capsules, representing the most essential elements of bone tissue. A geminal bisphosphonate (BP) ester-supported calcium complex forming a solvent-separated ion pair in the solid state seems to be a convenient and bio-available combination of these two components. As BPs and derived Ca(II) complexes are the leading class of therapeutics in osteoporosis treatment, the presented results contribute to the availability of differently substituted geminal BPs and Ca(II) compounds for application as potential future multi-delivery systems in osteoporosis therapy. Additionally, comprehensive X-ray- and DOSY NMR-based structure elucidation in comparison to structures and coordination motifs known in the literature offers an extended insight into their coordination behavior in the solid as well as in the liquid phase. More information can be found in the Research Article by I. Koehne and R. Pietschnig.

Synthesis of Geminal Bis‐ and Tetrakisphosphonate Ester Derivatives and Their Coordination Behavior Towards Ca(II) Ions

AbstractThe preparation and thorough characterization of a variety of (arylmethylene)phosphonate ester derivatives (S1–S7) as well as derived geminal bisphosphonate (BP) ester ligands (L1–L7) is presented. Subsequent complexation reactions of CaCl2 with selected BPs (L1–L3) and a known aliphatic tetrakisphosphonate ester (L8) yield the respective Ca(II) coordination compounds [Ca(H2O)2(L1‐‐L3)2]Cl2 (C1‐‐C3) and [Ca(L8)Cl2]n (C4) for potential future application as multi‐delivery systems in osteoporosis treatment. Obtained SCXRD and 1H DOSY‐NMR data provide a detailed insight into their solid‐ as well as solution‐state structures extending the so far scarcely found X‐ray studies on geminal BP‐supported Ca(II) complexes.

Markovnikov-selective double hydrosilylation of challenging terminal aryl alkynes under cobalt and iron catalysis.

Geminal bis(silanes) are unique compounds with interesting properties. The most straightforward way to access them is double hydrosilylation of alkynes, which was established only recently. Previous articles about transition metal-catalysed double hydrosilylation show that terminal aryl alkynes are a challenge. We report on cobalt(II) and iron(III) complexes with the easy-to-synthesise N,N,N-tridentate hydrazone ligand being active precatalysts in Markovnikov-selective double hydrosilylation of terminal aryl alkynes. The influence of the hydrazone ligand structure and the potential role of the sodium triethylborohydride activator were studied. Sets of geminal bis(silanes) with two identical or different silyl groups were synthesised, showing the applicability of the reported method.

Inherent Reactivity of Spiro-Activated Electrophilic Cyclopropanes.

The kinetics of the ring‐opening reactions of thiophenolates with geminal bis(acceptor)‐substituted cyclopropanes in DMSO at 20 °C was monitored by photometric methods. The determined second‐order rate constants of the SN2 reactions followed linear relationships with Mayr nucleophilicity parameters (N/s N) and Brønsted basicities (pK aH) of the thiophenolates as well as with Hammett substituent parameters (σ) for groups attached to the thiophenolates. Phenyl‐substituted cyclopropanes reacted by up to a factor of 15 faster than their unsubstituted analogues, in accord with the known activating effect of adjacent π‐systems in SN2 reactions. Variation of the electronic properties of substituents at the phenyl groups of the cyclopropanes gave rise to parabolic Hammett relationships. Thus, the inherent SN2 reactivity of electrophilic cyclopropanes is activated by electron‐rich π‐systems because of the more advanced C1−C2 bond polarization in the transition state. On the other hand, electron‐poor π‐systems also lower the energetic barriers for the attack of anionic nucleophiles owing to attractive electrostatic interactions.

One‐pot two‐step synthesis of fused thiazinofuranone linked geminal bis 1,2,3‐triazole hybrids and their in vitro cytotoxic screening

AbstractIn this study, a series of novel geminal bis 1,2,3‐triazoles linked to 2H‐furo[2,3‐d][1,3]thiazine‐2,4,5(1H,6H)‐trione (3a‐3m) were prepared in one pot starting from 5‐Acetyl‐4‐Hydroxy‐1,3‐thiazine‐2,6‐dione (1) to 6,6‐diazido‐2H‐furo[2,3‐d][1,3]thiazine‐2,4,5(1H,6H)‐trione (2) followed by Cu(I)‐catalyzed azide‐alkyne cycloaddition. The synthesized compounds were further explored for in vitro cytotoxic activity against PC3, A549, MCF‐7, and HeLa cell lines and results revealed that the five compounds 3c, 3d, 3g, 3l, and 3m have displayed comparable in vitro cytotoxic activity with the standard drug Etoposide.

Complexes of cyclen side-bridged with a methylene-bis(phosphinate) group

A macrobicyclic cyclen-based ligand containing a geminal bis(phosphinate) N,N′-bridge was synthesized via a Mannich-type reaction. The other two macrocycle amine groups were modified with two acetate pendants, yielding ligand H4L. The cyclen-bis(phosphinate) intermediate, the ligand salt Na0.5(H5L)(H3.5L)Cl·20H2O and CuII complex Li2[Cu(L)]·4H2O were characterized by single-crystal X-ray diffraction. The ligand protonation constants and the stability constants of H4L complexes with Cu(II) and Zn(II) and lanthanide(III) ions were determined by potentiometry. The ligand protonation constants and the stability constants of H4L complexes with Cu(II) and Zn(II) ions are similar to those of H4dota. Conversely, the stabilities of its Ln(III) complexes are ~ 7–10 orders of magnitude lower than those of H4dota complexes due to steric restrictions of the methylene-bis(phosphinate) side bridge. Therefore, these findings indicate that the ligand H4L is suitable for the complexation of transition metal ions.

Intramolecular Sakurai Allylation of Geminal Bis(silyl) Enamide with Indolenine. A Diastereoselective Cyclization To Form Functionalized Hexahydropyrido[3,4-b]Indole.

A fluoride-promoted intramolecular Sakurai allylation of geminal bis(silyl) enamide with indolenine has been developed. The reaction facilitates an efficient cyclization to give hexahydropyrido[3,4-b]indoles in good yields with high diastereoselectivity. The resulted cis, trans-stereochemistry further enables the ring-closing metathesis (RCM) reaction of two alkene moieties, giving a tetracyclic N-hetereocycle widely found as the core structure in akuammiline alkaloids.

Formation of Boron Enolates by Nucleophilic Substitution

Enolates have proven to be one of the key building blocks available to the synthetic chemist. Here we summarize a novel strategy for their preparation, involving the addition of α-borylated nucleophiles to esters to yield boron enolates. The enolates prepared by the addition of lithiated geminal bis(boron) compounds to esters can be trapped with two equivalents of halogen and alkyl electrophiles to yield α,α-difunctionalized compounds.1 Introduction2 Ketone Difunctionalization3 Boron Enolates by Coupling4 Towards Sequential Trapping5 Summary and Outlook

Catalytic Selective Dihydrosilylation of Internal Alkynes Enabled by Rare-Earth Ate Complex.

Hydrosilylation of alkynes generally yield vinylsilanes, which are inert to the further hydrosilylation because of the steric effects. Reported here is the first successful dihydrosilylation of aryl- and silyl-substituted internal alkynes enabled by a rare-earth ate complex to yield geminal bis- and tris(silanes), respectively. The lanthanum bis(amido) ate complex supported by an ene-diamido ligand proved to be the ideal catalyst for this unprecedented transformation, while the same series of yttrium and samarium alkyl and samarium bis(amido) ate complexes exhibited poor activity and selectivity, indicating significant effects of the ionic size and ate structure of the rare-earth catalysts.

Catalytic Selective Dihydrosilylation of Internal Alkynes Enabled by Rare‐Earth Ate Complex

AbstractHydrosilylation of alkynes generally yield vinylsilanes, which are inert to the further hydrosilylation because of the steric effects. Reported here is the first successful dihydrosilylation of aryl‐ and silyl‐substituted internal alkynes enabled by a rare‐earth ate complex to yield geminal bis‐ and tris(silanes), respectively. The lanthanum bis(amido) ate complex supported by an ene‐diamido ligand proved to be the ideal catalyst for this unprecedented transformation, while the same series of yttrium and samarium alkyl and samarium bis(amido) ate complexes exhibited poor activity and selectivity, indicating significant effects of the ionic size and ate structure of the rare‐earth catalysts.

Exo/endo Selectivity Control in Diels–Alder Reactions of Geminal Bis(silyl) Dienes: Theoretical and Experimental Studies

The factors controlling the reactivity and exo/ endo selectivity of Diels-Alder reactions of geminal bis(silyl) dienes catalyzed by AlEt2Cl are studied at the B3LYP-D3(BJ)(SMD,CH2Cl2)/6-31++G**//B3LYP-D3(BJ)(SMD,CH2Cl2)/6-31+G* theoretical level. The reaction proceeds via a two-stage one-step mechanism, and the AlEt2Cl as a Lewis acid catalyst enhances the electrophilicity of the carbonyl compound by coordination, consequently accelerating a cycloaddition reaction with a low energy barrier. A geminal bis(silyl) group of the diene and an α-substituent in α,β-unsaturated carbonyl compounds adjust the interaction energy (Δ Eint) as well as the deformation energy (Δ Estrain) of the diene and dienophile, affecting the barrier height and the diastereochemical outcome accordingly. The steric repulsion between the geminal bis(silyl) group and Al(III) catalyst increases the Pauli repulsion energy (Δ EPauli) and strain energy of dienophile fragment (Δ Estrain(dienophile-LA)) in the endo pathway, ensuring the exo selectivity. The introduction of a halogen atom (Cl or Br) or methyl group at the α-position of α,β-unsaturated carbonyl compounds increases the deformation energy of the diene fragment. Meanwhile, the noncovalent interactions (that is, dispersion and electrostatic interaction) stabilize the endo transition state, leading to predominant endo products. The theoretical predictions of the exo/ endo selectivity for Diels-Alder reactions of the substituted α,β-unsaturated carbonyl compound with Cl or Br atoms by the DFT method are also well confirmed by experiment.