Efficient Capture and Release of the Rare-Earth Element Neodymium in Aqueous Solution by Recyclable Covalent Organic Frameworks.

Rare-earth elements (REEs) are present in a broad range of critical materials. The development of solid adsorbents for REE capture could enable the cost-effective recycling of REE-containing magnets and electronics. In this context, covalent organic frameworks (COFs) are promising candidates for REE adsorption due to their exceptionally high surface area. Despite having attractive physical properties, COFs are heavily underutilized for REE capture applications due to their limited lifecycle in aqueous acidic environments, as well as synthetic challenges associated with the incorporation of ligands suitable for REE capture. Here, we show how the Ugi multicomponent reaction can be leveraged to postsynthetically modify imine-based COFs for the introduction of a diglycolic acid (DGA) moiety, an efficient scaffold for REE capture. The adsorption capacity of the DGA-functionalized COF was found to be more than 40 times higher than that of the pristine imine COF precursor and more than four times higher than that of the next-best reported DGA-functionalized solid support. This rationally designed COF has appealing characteristics of high adsorption capacity, fast and efficient capture and release of the REE ions, and reliable recyclability, making it one of the most promising adsorbents for solid-liquid REE ion extractions reported to date.

Nickel-Catalyzed Isomerization of Homoallylic Alcohols.

Nickel-catalyzed isomerizations of homoallylic alcohols and a bishomoallylic alcohol are presented. These isomerization reactions occur in the presence of a simple nickel catalyst that does not require addition of an exogenous ligand. The corresponding ketone products are generated in ≤98% yield.

General Strategy for Incorporation of Functional Group Handles into Covalent Organic Frameworks via the Ugi Reaction.

The library of imine-linked covalent organic frameworks (COFs) has grown significantly over the last two decades, featuring a variety of morphologies, pore sizes, and applications. An array of synthetic methods has been developed to expand the scope of the COF functionalities; however, most of these methods were designed to introduce functional scaffolds tailored to a specific application. Having a general approach to diversify COFs via late-stage incorporation of functional group handles would greatly facilitate the transformation of these materials into platforms for a variety of useful applications. Herein, we report a general strategy to introduce functional group handles in COFs via the Ugi multicomponent reaction. To demonstrate the versatility of this approach, we have synthesized two COFs with hexagonal and kagome morphologies. We then introduced azide, alkyne, and vinyl functional groups, which could be readily utilized for a variety of post-synthetic modifications. This facile approach enables the functionalization of any COFs containing imine linkages.

Nickel-Catalyzed Formation of α-Substituted γ-Amino Ketones via Alkene Carboacylation.

Herein, we report Ni-catalyzed intramolecular carboacylation of imides containing a tethered alkene and tetraarylborate nucleophiles. Using a nickel-phosphine catalyst system, α-substituted, γ-amino ketones are generated in up to 92% yield with site selectivity. Deprotection and cyclization of the γ-amino ketone product afforded a cyclic imine in 71% yield, and a stereoselective reduction formed the ß-substituted, δ-amino alcohol in 66% yield with 2.3:1 d.r. and 94% ee (major diastereomer).

Nickel-catalyzed arylative substitution of homoallylic alcohols.

Direct coupling of unactivated alcohols remains a challenge in synthetic chemistry. Current approaches to cross-coupling of alcohol-derived electrophiles often involve activated alcohols such as tosylates or carbonates. We report the direct arylative substitution of homoallylic alcohols catalyzed by a nickel-bisphosphine complex as a facile method to generate allylic arenes. These reactions proceed via formation of an allylic alcohol intermediate. Subsequent allylic substitution with arylboroxine nucleophiles enables the formation of a variety of allylic arenes. The presence of p-methoxyphenylboronic acid is crucial to activate the allylic alcohol to achieve high product yields.

Synthesis of oxaboranes via nickel-catalyzed dearylative cyclocondensation.

We report Ni-catalyzed dearylative cyclocondensation of aldehydes, alkynes, and triphenylborane. The reaction is initiated by oxidative cyclization of the aldehyde and alkyne coupling partners to generate an oxanickelacyclopentene which reacts with triphenylborane to form oxaboranes. This formal dearylative cyclocondensation reaction generates oxaboranes in moderate-to-high yields (47-99%) with high regioselectivities under mild reaction conditions. This approach represents a direct and modular synthesis of oxaboranes which are difficult to access using current methods. These oxaboranes are readily transformed into valuable building blocks for organic synthesis and an additional class of boron heterocycles. Selective homocoupling forms oxaboroles, oxidation generates aldol products, and reduction and arylation form substituted allylic alcohols.

Nickel-Catalyzed Enantioselective Hydroboration of Vinylarenes.

The enantioselective hydroboration of vinylarenes catalyzed by a chiral, nonracemic nickel catalyst is presented as a facile method for generating chiral benzylic boronate esters. Various vinylarenes react with bis(pinacolato)diboron (B2pin2) in the presence of MeOH as a hydride source to form chiral boronate esters in up to 92% yield with up to 94% ee. The use of anhydrous Me4NF to activate B2pin2 is crucial for ensuring fast transmetalation to achieve high enantioselectivities.

Palladium-Catalyzed Intermolecular Alkene Carboacylation via Ester C-O Bond Activation.

We report palladium-catalyzed intermolecular carboacylation of alkenes with ester electrophiles and tetraarylborate nucleophiles. Bicyclic alkenes react with a variety of pentafluorophenyl benzoate and alkanoate esters and sodium tetraarylborates to form ketone products in ≤99% yields. These reactions occur in the absence of a directing group and demonstrate esters are competent acyl electrophiles for intermolecular alkene carboacylation reactions.

Palladium-Catalyzed Intermolecular Acylative Heck Reactions with Imides as Acyl Electrophiles.

We disclose palladium-catalyzed, intermolecular, acylative Heck reactions that use imides as acyl electrophiles. The catalyst generated from [Pd(allyl)Cl]2 and DPEphos promotes the reaction between N-benzoylglutarimides and norbornene in the presence of silver phosphate. The acylative Heck reaction encompasses an array of N-benzoylglutarimide electrophiles that contain electron-donating, halogenated, and electron-withdrawing substituents to generate α,ß-unsaturated ketones in moderate to high yields (25-82%). The bicylic α,ß-unsaturated ketones are readily transformed into polycyclic architectures via thermal hetero-Diels-Alder reactions that occur by the dimerization of the α,ß-unsaturated ketones.

Nickel-Catalyzed Asymmetric Hydroarylation of Vinylarenes: Direct Enantioselective Synthesis of Chiral 1,1-Diarylethanes.

The enantioselective hydroarylation of vinylarenes catalyzed by a chiral, non-racemic nickel catalyst is presented as a facile method to generate chiral 1,1-diarylethanes. These reactions proceed via formation of a chiral, non-racemic nickel benzyl intermediate. Transmetalation with arylboron nucleophiles and subsequent reductive elimination enable the formation of a variety of chiral 1,1-diarylethanes. The 1,1-diarylethane products from reactions of arylboronic acids containing electron-donating substituents are formed with typically greater than 90% ee, while the 1,1-diarylethanes generated from reactions of arylboronic acids containing electron-withdrawing groups are generated with typically less than 80% ee. These results are consistent with the rate of transmetalation with an arylboron nucleophile playing a key role in the enantioselectivity of these hydroarylation reactions. This mechanistic insight has led to the development of reactions of neo-pentylglycolate esters of arylboronic acids with vinylarenes that occur with higher enantioselectivities based on increased rates of transmetalation.

Ni-Catalyzed Intermolecular Carboacylation of Internal Alkynes via Amide C-N Bond Activation.

The Ni-catalyzed carboacylation of alkynes with amide electrophiles and triarylboroxines is presented. The reaction generates all-carbon tetrasubstituted alkene products in up to 62% yield. NiCl2·glyme is used as an inexpensive precatalyst in the absence of any external reductant or exogenous ligand. Design of Experiment (DoE) was used to achieve the best combination of yield and stereoselectivity in this acylative carbodifunctionalization of alkynes to generate highly substituted enones.

An Acid-Catalyzed Addition and Dehydration Sequence for the Synthesis of Heteroarylated Steroidal Dienes.

Additions of heteroarenes to hormone steroids containing an α,ß-unsaturated ketone are reported. Additions of a range of electron-rich heteroarene nucleophiles, including indoles, a pyrrole, and a thiophene, to a variety of commercially available steroids and subsequent dehydration formed 3-heteroarylated steroidal dienes in up to 93% yield. This atom-economical reaction sequence occurs under mild reaction conditions in the presence of catalytic bismuth triflate.

Catalytic, Enantioselective Synthesis of Polycyclic Nitrogen, Oxygen, and Sulfur Heterocycles via Rh-Catalyzed Alkene Hydroacylation.

Enantioselective synthesis of polycyclic nitrogen, oxygen, and sulfur heterocycles by rhodium-catalyzed intramolecular alkene hydroacylation is reported. The intramolecular hydroacylation reactions generate 1,4-dihydrocyclopenta[b]indol-3(2H)-ones and 3,4-dihydrocyclopenta[b]indol-1(2H)-one in moderate-to-high yields (65-99%) with good-to-excellent enantioselectivities (84-99% ee). The catalyst system also promotes alkene hydroacylation of 3-vinylfuran-, 3-vinylbenzothiophene-, and 3-vinylthiophene-2-carboxaldehydes to generate the corresponding ketone products in moderate-to-high yields (71-91% yield) with excellent enantioselectivities (97-99% ee).

Enantioselective, Palladium-Catalyzed Conjugate Additions of Arylboronic Acids to Form Bis-benzylic Quaternary Stereocenters.

We report enantioselective, palladium-catalyzed conjugate additions of arylboronic acids to ß-aryl, ß,ß-disubstituted enones to generate ketones containing bis-benzylic quaternary stereocenters. A catalyst generated from palladium trifluoroacetate and (S)-4-tert-butyl-2-(2-pyridyl)oxazoline ligand ((S)-t-BuPyOx) promotes conjugate additions of a wide range of arylboronic acids to a variety of ß-aryl, ß,ß-disubstituted enones. Iterative addition of the arylboronic acid to minimize undesired protodeboronation pathways leads to efficient formation of the corresponding ketones containing bis-benzylic quaternary stereocenters in up to 92% yield and up to 93% enantioselectivity.

Ni-Catalyzed Alkene Carboacylation via Amide C-N Bond Activation.

We report Ni-catalyzed formal carboacylation of o-allylbenzamides with arylboronic acid pinacol esters. The reaction is triggered by oxidative addition of an activated amide C-N bond to a Ni(0) catalyst and proceeds via alkene insertion into a Ni(II)-acyl bond. The exo-selective carboacylation reaction generates 2-benzyl-2,3-dihydro-1H-inden-1-ones in moderate to high yields (46-99%) from a variety of arylboronic acid pinacol esters and substituted o-allylbenzamides. These results show that amides are practical substrates for alkene carboacylation via amide C-N bond activation, and this approach bypasses challenges associated with alkene carboacylation triggered by C-C bond activation.

Catalytic Conjugate Addition of Electron-Rich Heteroarenes to ß,ß-Disubstituted Enones.

Catalytic conjugate additions of heteroarenes to ß,ß-disubstituted enones are reported. Additions of a range of heteroarene nucleophiles, including furans, indoles, a pyrrole, and a thiophene, to a variety of ß,ß-disubstituted enones occur to form the corresponding ketone products containing heteroarylated, all-carbon quaternary centers in up to 90% yield. These reactions occur under mild reaction conditions in the presence of low loadings of bismuth triflate.

N-Heterocyclic carbene-catalysed intramolecular hydroacylation to form basic nitrogen-containing heterocycles.

We report catalytic, intramolecular hydroacylations of N-allylimidazole-2-carboxaldehydes and N-allylbenzimidazole-2-carboxaldehydes. These exo-selective hydroacylations occur in the presence of a N-heterocyclic carbene catalyst to generate 5,6-dihydro-7H-pyrrolo[1,2-α]imidazol-7-ones and 1,2-dihydro-3H-benzo[d]pyrrolo[1,2-α]imidazol-2-ones in high yields (66-99%). In addition, hydroacylations of N-allylimidazole-2-carboxaldehydes in the presence of a chiral, non-racemic NHC catalyst occur, forming 5,6-dihydro-7H-pyrrolo[1,2-α]imidazol-7-ones in moderate-to-high yields (39-98%) with modest enantioselectivities (56-79% ee).

Enantioselective Model Synthesis and Progress toward the Putative Structure of Yuremamine.

An enantioselective model synthesis of the 2,3-dihydro-1H-pyrrolo[1,2-a]indole core of the putative structure of yuremamine is reported in 39% overall yield and 96% ee over five steps. The model synthesis leverages enantioselective, rhodium-catalyzed hydroacylation of an N-vinylindole-2-carboxaldehyde as the key step in the installation of the stereochemical triad. An enantioselective synthesis of a densely functionalized dihydropyrroloindolone that maps onto the putative structure of yuremamine is demonstrated in 26% yield and 97% ee over eight steps.

Rhodium-Catalyzed Enantioselective Intramolecular Hydroacylation of Trisubstituted Alkenes.

We report the first examples of transition metal-catalyzed enantioselective alkene hydroacylations with 1,1,2-trisubstituted alkenes. DFT and mechanistic studies are consistent with a reaction pathway for these rhodium-catalyzed processes including intramolecular alkene hydroacylation and α-epimerization to generate highly enantioenriched, polycyclic architectures. This reaction sequence enables the hydroacylation of 2-(cyclohex-1-en-1-yl)benzaldehydes to form hexahydro-9H-fluoren-9-ones in moderate to high yields (68-91 %) with high enantioselectivities (up to 99 % ee) and diastereoselectivities (typically >20:1).

Rhodium-Catalyzed, Enantioselective Hydroacylation of ortho-Allylbenzaldehydes.

The development of a rhodium catalyst for endo- and enantioselective hydroacylation of ortho-allylbenzaldehydes is reported. A catalyst generated in situ from [Rh(COD)Cl]2, (R)-DTBM-SEGPHOS, and NaBARF promotes the desired hydroacylation reactions and minimizes the formation of byproducts from competitive alkene isomerization and ene/dehydration pathways. These rhodium-catalyzed processes generate the 3,4-dihydronaphthalen-1(2H)-one products in moderate-to-high yields (49-91%) with excellent enantioselectivities (96-99% ee).