ABSTRACT
Unprotected alicyclic amines undergo α-C-H bond phosphonylation via a two-stage one-pot process involving the oxidation of amine-derived lithium amides with simple ketone oxidants, generating transient imines which are then captured with phosphites or phosphine oxides. Amines with an existing α-substituent undergo regioselective α'-phosphonylation. Amine α-arylation and α'-phosphonylation can be combined, generating a difunctionalized product in a single operation.
ABSTRACT
A readily accessible conjugate-base-stabilized carboxylic acid (CBSCA) catalyst facilitates highly enantioselective [4+2] cycloaddition reactions of salicylaldehyde-derived acetals and cyclic enol ethers, resulting in the formation of polycyclic chromanes with oxygenation in the 2- and 4-positions. Stereochemically more complex products can be obtained from racemic enol ethers. Spirocyclic products are also accessible.
ABSTRACT
A new strategy to access α-functionalized alicyclic amines via their corresponding imine-BF3 complexes is reported. Isolable imine-BF3 complexes, readily prepared via dehydrohalogenation of N-bromoamines in a base-promoted/18-crown-6 catalyzed process followed by addition of boron trifluoride etherate, undergo reactions with a wide range of organometallic nucleophiles to afford α-functionalized azacycles. Organozinc and organomagnesium nucleophiles add at ambient temperatures, obviating the need for cryogenic conditions. In situ preparation of imine-BF3 complexes provides access to α-functionalized morpholines and piperazines directly from their parent amines in a single operation. α-Functionalized morpholines can be elaborated further, for instance by installing a second substituent in the α'-position.
ABSTRACT
Synthesis of olefin-styrene copolymers with defined architecture is challenging due to the limitations associated with the inherent reactivity ratios for these monomers in radical or metal-catalyzed polymerizations. Herein, we developed a straightforward approach to alternating styrene-propylene and styrene-ethylene copolymers by combining radical polymerizations and powerful post-polymerization modification reactions. We employed reversible addition-fragmentation chain transfer (RAFT) copolymerization between styrene derivatives and saccharin (meth)acrylamide to generate alternating copolymers. Once polymerized, the amide bond of the saccharin monomers was highly reactive toward hydrolysis, an observation exploited to obtain alternating styrene-acrylic acid/methacrylic acid copolymers. Subsequent mild decarboxylation of the (meth)acrylic acid groups in the presence of a photocatalyst and a hydrogen source under visible light resulted in the styrene-alt-ethylene/propylene copolymers. Alternating copolymers comprised of either propylene or ethylene units alternating with functional styrene derivatives were also prepared, illustrating the compatibility of this approach for functional polymer synthesis. Finally, the thermal properties of the alternating copolymers were compared to those from statistical copolymer analogs to elucidate the effect of microarchitecture and styrene substituents on the glass transition temperature.
ABSTRACT
Enantioselective oxa-Pictet-Spengler reactions of tryptophol with aldehydes proceed under weakly acidic conditions utilizing a combination of two catalysts, an indoline HCl salt and a bisthiourea compound. Mechanistic investigations revealed the roles of both catalysts and confirmed the involvement of oxocarbenium ion intermediates, ruling out alternative scenarios. A stereochemical model was derived from density functional theory calculations, which provided the basis for the development of a highly enantioselective stereodivergent variant with racemic tryptophol derivatives.
ABSTRACT
Unprotected cis-2,3-diarylpiperidines are synthesized through an unprecedented palladium-catalyzed cross-coupling reaction between aryl halides and elusive endocyclic 1-azaallyl anions. These intermediates are generated in situ by the deprotonation of 2-aryl-1-piperideines, precursors that are readily prepared in two operations from simple piperidines. An asymmetric version of this reaction with (2R, 3R)-iPr-BI-DIME as the ligand provides products in moderate to good yields and enantioselectivities. This study significantly expands the synthetic utility of endocyclic 1-azaallyl anions.
ABSTRACT
We establish a synthetically convenient method to degrade polyacrylate homopolymers. Carboxylic acids are installed along the polymer backbone by partial hydrolysis of the ester side chains, and then, in a one-pot sequential procedure, the carboxylic acids are converted into alkenes and oxidatively cleaved. This process enables the robustness and properties of polyacrylates to be maintained during their usable lifetime. The ability to tune the degree of degradation was demonstrated by varying the carboxylic acid content of the polymers. This method is compatible with a wide range of polymers prepared from vinyl monomers through copolymerization of acrylic acid with different monomers including acrylates, acrylamides, and styrenics.
ABSTRACT
Secondary alicyclic amines are converted to their corresponding ring-fused imidazoles in a simple procedure consisting of oxidative imine formation followed by a van Leusen reaction. Amines with an existing α-substituent undergo regioselective ring-fusion at the α'-position. This method was utilized in a synthesis of fadrozole.
ABSTRACT
Experimental 13C kinetic isotope effects (KIEs) provide unprecedented mechanistic insight into three intermolecular anti-Markovnikov alkene hydrofunctionalization reactionsâhydroesterification, hydroamination, and hydroetherificationâenabled by organophotoredox catalysis. All three reactions are found to proceed via initial oxidation of the model alkenes to form a radical cation intermediate, followed by sequential nucleophilic attack and hydrogen-atom transfer to deliver the hydrofunctionalized product. A normal 13C KIE on the olefinic carbon that undergoes nucleophilic attack provides qualitative evidence for rate-limiting nucleophilic attack in all three reactions. Comparison to predicted 13C KIE values obtained from density functional theory (DFT) calculations for this step reveals that alkene oxidation has partial rate-limiting influence in hydroesterification and hydroamination, while the nucleophilic attack is solely rate-limiting in the hydroetherification reaction. The basic additive (2,6-lutidine) activates the nucleophile via deprotonation and is an integral part of the transition state for nucleophilic attack on the radical cation, providing an important design principle for the development of asymmetric versions of these reactions. A more electron-rich pyridine base (2,6-dimethoxypyridine) exhibits considerable rate enhancements in both inter- and intramolecular hydrofunctionalization reactions.
Subject(s)
Alkenes , Hydrogen , Carbon , Catalysis , Cations , PyridinesABSTRACT
Visible light-mediated direct decarboxylation of carboxylic acids with an acridine photocatalyst is a convenient and powerful method to generate carbon-centered radicals in polymer chains. Advantageously, this process proceeds under mild conditions, without preactivation of the acid groups. We utilize decarboxylation in the presence of a hydrogen atom donor to form statistical acrylate-ethylene and acrylate-propylene copolymers, which are challenging to obtain by direct polymerization. We additionally show that decarboxylation of methacrylic acid units within polymethacrylates can trigger degradation of the polymer backbones. Moreover, a dual catalytic approach, which combines the function of an acridine photocatalyst with that of a cobaloxime catalyst, is leveraged to furnish unique copolymers with pendent alkenes. Our work indicates that direct decarboxylation is a versatile technique for the synthesis of functional materials with tailored compositions and properties.
ABSTRACT
Secondary alicyclic amines are converted to α-aminonitriles via addition of TMSCN to their corresponding imines, intermediates that are produced in situ via the oxidation of amine-derived lithium amides with simple ketone oxidants. Amines with an existing α-substituent undergo regioselective α'-cyanation even if the C-H bonds at that site are less activated. Amine α-arylation can be combined with α'-cyanation to generate difunctionalized products in a single operation.
ABSTRACT
Relatively unstable cyclic imines, generated in situ from their corresponding alicyclic amines via oxidation of their lithium amides with simple ketone oxidants, engage aryllithium compounds containing a leaving group on an ortho-methylene functionality to provide polycyclic isoindolines in a single operation. The scope of this transformation includes pyrrolidine, piperidine, azepane, azocane, and piperazines.
ABSTRACT
To control highly-dynamic compliant motions such as running or hopping, vertebrates rely on reflexes and Central Pattern Generators (CPGs) as core strategies. However, decoding how much each strategy contributes to the control and how they are adjusted under different conditions is still a major challenge. To help solve this question, the present paper provides a comprehensive comparison of reflexes, CPGs and a commonly used combination of the two applied to a biomimetic robot. It leverages recent findings indicating that in mammals both control principles act within a low-dimensional control submanifold. This substantially reduces the search space of parameters and enables the quantifiable comparison of the different control strategies. The chosen metrics are motion stability and energy efficiency, both key aspects for the evolution of the central nervous system. We find that neither for stability nor energy efficiency it is favorable to apply the state-of-the-art approach of a continuously feedback-adapted CPG. In both aspects, a pure reflex is more effective, but the pure CPG allows easy signal alteration when needed. Additionally, the hardware experiments clearly show that the shape of a control signal has a strong influence on energy efficiency, while previous research usually only focused on frequency alignment. Both findings suggest that currently used methods to combine the advantages of reflexes and CPGs can be improved. In future research, possible combinations of the control strategies should be reconsidered, specifically including the modulation of the control signal's shape. For this endeavor, the presented setup provides a valuable benchmark framework to enable the quantitative comparison of different bioinspired control principles.
ABSTRACT
This Graphical Review provides a concise overview of the manifold and mechanistically diverse methods that enable the functionalization of sp3 C-H bonds in amines and their derivatives.
ABSTRACT
A simple one-pot procedure enables the sequential, regioselective, and diastereoselective introduction of the same or two different substituents to the α- and α'-positions of unprotected azacycles. Aryl, alkyl, and alkenyl substituents are introduced via their corresponding organolithium compounds. The scope of this transformation includes pyrrolidines, piperidines, azepanes, and piperazines.
ABSTRACT
Polycyclic lactams are prepared in a single operation from o-toluamides and cyclic amines in a process that involves transient cyclic imines, species that are conveniently obtained in situ from the corresponding lithium amides and simple ketone oxidants. Imines thus generated, such as 1-pyrroline and 1-piperideine, engage lithiated o-toluamides in a facile annulation process. Undesired side reactions such as imine deprotonation and o-toluamide dimerization are suppressed through the judicious choice of reaction conditions.
Subject(s)
Amines/chemistry , Imines/chemistry , Lactams/chemistry , Dimerization , Molecular Structure , StereoisomerismABSTRACT
Enolizable cyclic imines, obtained in situ from their corresponding lithium amides by oxidation with simple ketone oxidants, are readily alkylated with a range of enolates to provide mono- and polycyclic ß-aminoketones in a single operation, including the natural product (±)-myrtine. Nitrile anions also serve as competent nucleophiles in these transformations, which are promoted by BF3 etherate. ß-Aminoesters derived from ester enolates can be converted to the corresponding ß-lactams.
ABSTRACT
This review aims to provide a comprehensive overview of condensation-based methods for the C-H bond functionalization of amines that feature azomethine ylides as key intermediates. These transformations are typically redox-neutral and share common attributes with classic name reactions such as the Strecker, Mannich, Friedel-Crafts, Pictet-Spengler, and Kabachnik-Fields reaction, while incorporating a redox-isomerization step. This approach provides an ideal platform to rapidly transform simple starting materials into complex amines.
ABSTRACT
Despite extensive efforts by many practitioners in the field, methods for the direct α-C-H bond functionalization of unprotected alicyclic amines remain rare. A new advance in this area utilizes N-lithiated alicyclic amines. These readily accessible intermediates are converted to transient imines through the action of a simple ketone oxidant, followed by alkylation with a ß-ketoacid under mild conditions to provide valuable ß-amino ketones with unprecedented ease. Regioselective α'-alkylation is achieved for substrates with existing α-substituents. The method is further applicable to the convenient one-pot synthesis of polycyclic dihydroquinolones through the incorporation of a SN Ar step.
Subject(s)
Amines/chemistry , Carbon/chemistry , Hydrogen/chemistry , Imines/chemistry , Alkylation , Molecular StructureABSTRACT
Readily available 1,2-amino alcohols provide the framework for a new generation of chiral carboxylic acid catalysts that rival the acidity of the widely used chiral phosphoric acid catalyst (S)-TRIP. Covalently linked thiourea sites stabilize the carboxylate conjugate bases of these catalysts via anion-binding, an interaction that is largely responsible for the low pKa values. The utility of the new catalysts is illustrated in the context of challenging [4 + 2] cycloadditions of salicylaldehyde-derived acetals with homoallylic and bishomoallylic alcohols, providing polycyclic chromanes in a highly enantioselective fashion.