Alkyl Boron Research Articles

Programmable Amine Synthesis via Iterative Boron Homologation.

The value of Matteson-type reactions has been increasingly recognized for developing automated organic synthesis. However, the typical Matteson reactions almost exclusively focus on homologation of carbon units. Here, we report the detailed development of sequential insertion of nitrogen and carbon atoms into boronate C-B bonds, which provides a modular and iterative approach to access functionalized tertiary amines. A new class of nitrenoid reagents is uncovered to allow direct formation of aminoboranes from aryl or alkyl boronates via N-insertion. The one-pot N-insertion followed by controlled mono- or double-carbenoid insertion has been realized with widely available aryl boronates. The resulting aminoalkyl boronate products can undergo further homologation and various other transformations. Preliminary success on homologation of N,N-dialkylaminoboranes and sequential N- and C-insertions with alkyl boronates have also been achieved. To broaden the synthetic utility, selective removal of a benzyl or aryl substituent permits access to secondary or primary amine products. The application of this method has been demonstrated in the modular synthesis of bioactive compoundsand the programmable construction of diamines and aminoethers. A plausible reaction mechanism, supported by preliminary NMR (nuclear magnetic resonance) and computational studies, is also proposed.

Programmable Amine Synthesis via Iterative Boron Homologation

AbstractThe value of Matteson‐type reactions has been increasingly recognized for developing automated organic synthesis. However, the typical Matteson reactions almost exclusively focus on homologation of carbon units. Here, we report the detailed development of sequential insertion of nitrogen and carbon atoms into boronate C−B bonds, which provides a modular and iterative approach to access functionalized tertiary amines. A new class of nitrenoid reagents is uncovered to allow direct formation of aminoboranes from aryl or alkyl boronates viaN‐insertion. The one‐potN‐insertion followed by controlled mono‐ or double‐carbenoid insertion has been realized with widely available aryl boronates. The resulting aminoalkyl boronate products can undergo further homologation and various other transformations. Preliminary success on homologation ofN,N‐dialkylaminoboranes and sequentialN‐and C‐insertions with alkyl boronates have also been achieved. To broaden the synthetic utility, selective removal of a benzyl or aryl substituent permits access to secondary or primary amine products. The application of this method has been demonstrated in the modular synthesis of bioactive compounds and the programmable construction of diamines and aminoethers. A plausible reaction mechanism, supported by preliminary NMR (nuclear magnetic resonance) and computational studies, is also proposed.

Divergent Synthesis of 1,1-Carbonyl Amino Alkyl Borons from Indoles.

α-Boryl carbonyl species and α-boryl amino compounds are valuable and important frameworks in organic synthesis. However, the strategies that could merge the two scaffolds into one compound, named 1,1-carbonyl amino alkyl boron, are elusive and underdeveloped. Herein, we present an efficient method that could address this gap and produce 1,1-carbonyl amino alkyl borons from readily accessible indoles via oxidation by m-CPBA or oxone. This reaction features operational simplicity, divergent synthesis, broad substrate scope, and valuable products.

CeO2‐Nanorods‐Catalyzed Protoboration of Alkenes and Alkynes with Bis(pinacolato)diboron

AbstractThe protoboration of alkenes and alkynes with B2pin2 (pin=OCMe2CMe2O) using a heterogeneous CeO2 nanorods catalyst has been developed to afford the corresponding alkyl and vinyl boronate esters in 41–99% yield under mild reaction conditions. A series of aromatic and aliphatic alkenes and alkynes with synthetically important functional groups were well tolerated. In both the systems, the catalyst could be reused for up to six runs without significant loss in activity. Stoichiometric reactions revealed that the protoboration may proceed through the in situ formed catalytically active boryl species.magnified image

Cross-coupling of Cinnamyl Bromides and Alkyl Boronates Catalyzed by a Pd-Fe MOF

Cross-coupling of Cinnamyl Bromides and Alkyl Boronates Catalyzed by a Pd-Fe MOF

Facile synthesis of alkyl- and arylboronate esters enabled by a carbon nanotube supported copper catalyst

An efficient and reusable copper nanoparticle stabilised on carbon nanotubes system has been developed for the synthesis of alkyl and aryl boronate esters via C–X borylation of alkyl and aryl halides and hydroboration of vinylarenes with B2pin2.

Transition metal-catalyzed reactivity of carbenes with boronic acid derivatives for arylation (alkylation) and beyond.

This comprehensive review article discussed the reactivity of carbenes with boronic acid derivatives for the one-pot synthesis of diarylmethanes, difluoromethylated arenes, aryl and alkyl boron compounds, arylacetic acid derivatives, furan derivatives, and many other compounds. We have summarized the arylation, vinylation, and alkylation of carbenes utilizing various transition metals, viz. palladium, rhodium, copper, and platinum, for the construction of carbon-carbon bonds, carbon-boron bonds, and beyond through the cross-coupling strategy. The reason for the increasing popularity of these novel methodologies is their application in the synthesis and late-stage functionalization of biologically active compounds and natural products. Notably, organoboron compounds are exemplified as versatile synthetic intermediates for constructing various bonds.

Transition metal- and solvent-free anti-Markovnikov selective protoboration of alkenes with bis(pinacolato)diboron.

An efficient anti-Markovnikov selective transition metal- and solvent-free Lewis base-mediated protoboration of aromatic and aliphatic alkenes with bis(pinacolato)diboron (B2pin2) as the boron reagent is reported. This protocol is practical and demonstrates broad substrate scope and good functional-group tolerance on alkenes to give synthetically useful alkyl boronate esters in excellent yields under mild reaction conditions. The gram-scale reaction further highlighted the usefulness of this method.

Blue Light-Emitting Diode-Induced Direct C-H Functionalization of 1,4-Quinones with Aryl and Alkyl Boronic Acids.

A direct functionalization of numerous 1,4-quinones with various aryl boronic acids is reported under blue light-emitting diodes (LEDs). This reaction occurs at room temperature in an open flask without any catalysts, base, and oxidants in acetonitrile (ACN) and is scalable in grams. With diverse 1,4-quinones like 1,4-benzo-, naphtho-, anthra-, and 4-bromonaphthoquinones as substrates, facile cross coupling reactions occur with aryl and alkyl boronic acids without assistance from any photocatalysts. 2-Alkylated cyclohexene-1,4-diones were obtained when the 1,4-quinones were reacted with alkyl boronic acids under standard reaction conditions. However, slight warming of the reaction mixture afforded the desired alkylated 1,4-quinones. The reaction is believed to proceed through the blue LED-induced radical formation of the aryl rings assisted by the 1,4-quinones.

Ligand cooperativity enables highly enantioselective C–C σ-bond hydroboration of cyclopropanes

<h2>Summary</h2> Given the utility of enantioenriched alkylboronates, asymmetric borylation has attracted substantial research interest in recent decades. Herein, a catalytic enantioselective hydroboration through desymmetrization of enantiotopic carbons in cyclopropanes involving C–C bond activation is reported. Treatment of cyclopropanes bearing an amide directing group in the presence of rhodium catalysis using HBpin as a boron source allows the construction of a series of alkyl boronates containing γ-stereogenic amines. The key to high enantioselectivity relies on two distinct ligands that act cooperatively: an exogenous monodentate chiral phosphite that induces enantioselectivity and an endogenous acetylacetonate that exerts a remarkably positive influence on the enhancement of enantioselectivity. Detailed experimental and computational studies elucidate the effect of ligand cooperativity and the key steps involving σ-bond activation process, C–B bond formation, and the absolute configuration of products.

Cross-Coupling of Aryl Halides and Alkyl Boronic Esters under Dual Photoredox/Nickel Catalysis

Cross-Coupling of Aryl Halides and Alkyl Boronic Esters under Dual Photoredox/Nickel Catalysis

Markovnikov‐Selective Hydroboration of Aryl Alkenes Enabled by a Simple Nickel Salt

Comprehensive SummaryThe sustainable development of synthetic reactions catalyzed by earth‐abundant metals is one of the principal goals in homogeneous catalysis. However, so far most of the protocols are still plagued by sophisticated ligands, hazardous activators, high catalyst loading (1—10 mol%) and/or multistep synthesis of the metal complexes in the process development. Consequently, the development of earth‐abundant metal catalysts with high activity from commercially available metal salts is highly desirable for practical utilization of base metal catalyzed synthetic methodology. Herein, we report the catalyst generated in situ from a mixture of catalytic amounts of Ni(acac)2 (as low as 0.005 mol%) and CsF, which is found highly active for Markovnikov‐selective hydroboration of vinylarenes, including 1,1‐disubstituted vinylarenes and internal olefins, affording a wide range of secondary and tertiary alkyl boronates in excellent yields. Mechanistic experiments indicate that the key to the success of this catalysis is the use of CsF, which in combination with pinacolborane acts as an effective activator for Ni(acac)2, probably generating metastable Ni nanoparticles in situ that demonstrate high activity in the catalytic hydroboration (TON up to 18800).

Sustainable Synthesis of Noroxymorphone via a Key Electrochemical N-Demethylation Step

Noroxymorphone is a pivotal intermediate in the synthesis of important opioid antagonists such as naloxone and naltrexone. The preparation of noroxymorphone from thebaine, a naturally occurring opioate isolated from poppy extract, is a multistep sequence in which oxycodone is first generated and then N- and O-demethylated. Both demethylations are problematic from the safety and sustainability viewpoint, as they involve harmful reagents such as alkyl chloroformates or boron tribromide. Herein, we present a green, safe, and efficient process for the N- and O-demethylation of oxycodone. The method is based on the anodic oxidative intramolecular cyclization of the N-methyl tertiary amine with the 14-hydroxyl group of the morphinan, followed by hydrolysis with hydrobromic acid, which releases the carbon from both heteroatoms. The electrolysis process has been transferred to a scalable flow electrolysis cell, significantly improving the reaction throughput and increasing the space-time yield over 300-fold with respect to batch. The sustainability of the new methodology has been assessed by means of green metrics and qualitative indicators. The sustainability assessment has demonstrated that the new methodology is far superior to the conventional chloroformate process.

Group 4 Metallocene Complexes Supported by a Redox-Active O,C-Chelating Ligand

Group 4 metallocene complexes Cp2M[OC] (Cp = η5-C5H5; M = Ti (1) or Zr (2); [OC] = κ2-O,C-OC6H2-2-CPh2-4,6-tBu2) supported with a redox-active bidentate O,C-ligand were successfully synthesized through salt metathesis. X-ray crystallographic results showed that both complexes maintained similar bent metallocene coordination geometry. A close inspection of the structural parameters revealed a remarkably long Ti–C bond in 1, indicating concomitant intramolecular charge transfer upon metathesis and coordination. The electronic structure of 1 was investigated by electron paramagnetic resonance (EPR) measurements, revealing the presence of a Ti(III) center and one [OC]•– radical anion. In contrast, the diamagnetic complex 2 was found to comprise a Zr(IV) center and an alkyl/aryloxo dianion. Divergent catalytic reactivity was observed for the two group 4 derivatives in the reaction between alkenes and HBpin. Specifically, dehydrogenative boration products (i.e., vinyl boronate esters) were obtained exclusively in the presence of the Zr complex (18 examples, up to 90% yield), while the Ti compound selectively promoted the formation of alkyl boronate esters via hydroboration (19 examples, up to 99% yield).

A Fruitful Decade of Organofluorine Chemistry: New Reagents and Reactions

A Fruitful Decade of Organofluorine Chemistry: New Reagents and Reactions

Nickel-Catalyzed Migratory Benzylboration of Allylbenzenes

While 1,2-regioselective difunctionalizations of alkenes are well developed, their migratory difunctionalization of alkenes remains comparatively under-researched. Herein, we report a nickel-catalyzed, divergent, solvent-controlled 1,1- or 1,3-regioselective benzylboration of allylbenzenes, that provides efficient access to primary and secondary alkyl boronates. The mild reaction conditions of these transformations allow good regioselectivity and wide functional group tolerance.

Photo-induced trifunctionalization of bromostyrenes via remote radical migration reactions of tetracoordinate boron species

Tetracoordinate boron species have emerged as radical precursors via deboronation by photo-induced single electron transfer (SET) pathway. These reactions usually produce an alkyl radical and boron-bound species, and the valuable boron species are always discarded as a by-product. Given the importance of boron species, it will be very attractive if the two parts could be incorporated into the eventual products. Herein we report a photo-catalyzed strategy in which in situ generated tetracoordinated boron species decomposed into both alkyl radicals and boron species under visible light irradiation, due to the pre-installation of a vinyl group on the aromatic ring, the newly generated alkyl radical attacks the vinyl group while leaving the boron species on ipso-position, then both radical part and boron moiety are safely incorporated into the final product. Tertiary borons, secondary borons, gem-diborons as well as 1,2-diborons, and versatile electrophiles are all well tolerated under this transformation, of note, ortho-, meta- and para-bromostyrenes all demonstrated good capabilities. The reaction portraits high atom economy, broad substrate scope, and diversified valuable products with tertiary or quaternary carbon center generated, with diborons as substrates, Csp2-B and Csp3-B are established simultaneously, which are precious synthetic building blocks in chemical synthesis.

Improvement of catalytic activity for α‐diimine nickel complex with active sites stabilized by bulky boron counterions at elevated temperature

Three α‐diimine Ni (II) catalysts (Cat.1, Cat.2 and Cat.3) were synthesized and investigated for ethylene polymerization using alkyl aluminum and organoboron compounds as binary cocatalyst. The effects of different alkyl aluminum and boron complexes on ethylene polymerization catalyzed by Cat.1, Cat.2, and Cat.3 were studied. The sodium tetrakis[3,5‐bis (trifluoromethyl)phenyl]borate (NaBArF) was found to have best promotion for the catalytic activity of Cat.1, compared to negative effect of dimethylanilinium tetrakis (pentafluorophenyl)borate (TTB) and trityl tetrakis (pentafluorophenyl)borate (AB). All the three catalysts showed higher catalytic activity when NaBArF was introduced into the catalytic system, especially for Cat.3 (increased by 41.3% at 70°C). There was still minor increase of the catalytic activity for Cat.2 which have much better thermostability than Cat.3. The charging sequence of NaBArF and the [B]/[Ni] ratio have significant effects on the catalytic activity. The better catalytic performance of Cat.1/AlEt2Cl/NaBArF could be explained by its ability to raise the number of active centers. Namely, the molar percentage of active centers of Cat.1/AlEt2Cl/NaBArF was still above 30%, which was 1.7 times that of Cat.1/AlEt2Cl even if polymerization ran up to 30 min based on 2‐thiophenecarbonyl chloride (TPCC) quench‐labeling method. Lower [Al]/[Ni] ratio but more active centers and longer active centers lifetime of this binary cocatalyst is promising for improving the activity of ethylene polymerization industrially at elevated temperature.

Radical boron migration of allylboronic esters.

A photocatalyzed 1,3-boron shift of allylboronic esters is reported. The boron atom migration through the allylic carbon skeleton proceeds via consecutive 1,2-boron migrations and Smiles-type rearrangement to furnish a variety of terminally functionalized alkyl boronates. Several types of migrating variations of heteronuclei radicals and dearomatization processes are also tolerated, allowing for further elaboration of highly functionalized boron-containing frameworks.

A Lewis Base Nucleofugality Parameter, NFB, and Its Application in an Analysis of MIDA-Boronate Hydrolysis Kinetics.

The kinetics of quinuclidine displacement of BH3 from a wide range of Lewis base borane adducts have been measured. Parameterization of these rates has enabled the development of a nucleofugality scale (NFB), shown to quantify and predict the leaving group ability of a range of other Lewis bases. Additivity observed across a number of series R'3-nRnX (X = P, N; R' = aryl, alkyl) has allowed the formulation of related substituent parameters (nfPB, nfAB), providing a means of calculating NFB values for a range of Lewis bases that extends far beyond those experimentally derived. The utility of the nucleofugality parameter is explored by the correlation of the substituent parameter nfPB with the hydrolyses rates of a series of alkyl and aryl MIDA boronates under neutral conditions. This has allowed the identification of MIDA boronates with heteroatoms proximal to the reacting center, showing unusual kinetic lability or stability to hydrolysis.