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The development of protocols for the construction of congested quaternary centers is highly sought-after. Herein, we report a method for the cross-coupling of C(sp 3 ) tertiary Grignard reagents with C(sp 2 ) styrenyl bromides using readily available nickel precatalysts. We identified conditions that afford the products in practical yield for several combinations of electrophiles and nucleophiles, including sensitive α-magnesiated Grignard reagents. Dependent upon the nature of their substituents, regiodivergency was observed when α-vinyl bromides were employed.

In recent years, progress has been made in the development of catalytic methods that allow remote functionalizations based on alkene isomerization. In contrast, protocols based on alkyne isomerization are comparatively rare. Herein, we report a general Pd-catalyzed long-range isomerization of alkynyl alcohols. Starting from aryl-, heteroaryl-, or alkyl-substituted precursors, the optimized system provides access preferentially to the thermodynamically more stable α,β-unsaturated aldehydes and is compatible with potentially sensitive functional groups. We showed that the migration of both π-components of the carbon-carbon triple bond can be sustained over several methylene units. Computational investigations served to shed light on the key elementary steps responsible for the reactivity and selectivity. These include an unorthodox phosphine-assisted deprotonation rather than a more conventional β-hydride elimination in the final tautomerization event.

We report the copper-catalyzed borylation of unactivated vinylcyclopropanes to form six-membered cyclic borate salts. A copper complex bearing an N-heterocyclic ligand in combination with bis(pinacolato)diboron and LiO t Bu catalyzes the ring-opening of the substrate under mild reaction conditions. The protocol can be applied to aryl- and heteroaryl-substituted vinylcyclopropanes and can be conducted on a gram scale. The synthetic utility of the lithium salts of the cyclic borate has been demonstrated through regioselective ring-opening functionalizations.

A Cu-catalyzed regio- and enantioselective protoboration of 2,3-disubstituted 1,3-dienes is described. The protocol operates under mild conditions and is applicable to symmetrically and unsymmetrically substituted dienes, providing access to homoallylic boronates in consistently high yield, regioselectivity, and enantiomeric ratio. Preliminary investigations point to a complex mechanism.

A Pd-catalyzed 3,4-regioselective cyclopropanation of 2-substituted 1,3-dienes by decomposition of diazo esters is reported. The vinylcyclopropanes generated are isolated in practical chemical yields with high levels of regioselectivity but low diastereoselectivity. The system operates under mild reaction conditions, is scalable, and tolerates various sensitive functional groups. A series of original postcatalytic derivatizations is presented to highlight the synthetic potential of the catalytic method., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Two complementary regiodivergent Pd-catalyzed assisted tandem [isomerization/Heck arylation] reactions are reported. They provide access to a broad array of acyclic trisubstituted vinyl ethers starting from readily available alkenyl ethers. In both cases, the isomerization is conducted with a [Pd-H] precatalyst supported by tris- tert -butyl phosphine ligands. When the catalyst is modified by the addition of a chelating bisphosphine ligand (dppp), an organic base (Cy 2 NMe), sodium acetate, and aryl triflates are used as electrophiles, the α-arylation pathway is promoted preferentially. The β-arylation pathway is favored for electron-deficient and electron-neutral aryl halides when the catalyst is simply modified by the addition of an excess of an organic base (Et 3 N) after completion of the isomerization reaction. Electron-rich aryl halides lead to reduced levels of regiocontrol. The moderate stereoselectivity obtained are proposed to reflect the absence of stereocontrol in the isomerization step. Computational analyses suggest that migratory insertion is selectivity-determining for both the arylations. For the β-selective arylation, an energy decomposition analysis underscored that electronic factors favor α-regioselectivity and steric effects favor β-regioselectivity. Preliminary investigations show that high levels of stereoselectivity can be achieved for the α-selective arylation by ligand control. Complementarily, reaction conditions for postcatalytic stereo-correction have also been identified for each catalytic system., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Ni-catalyzed enantioselective hydrofunctionalizations of conjugated dienes are particularly demanding reactions to devise because they require not only addressing the inherent challenges associated with the development of an enantioselective transformation but also overcoming all other aspects of selective catalysis (chemoselectivity, regioselectivity, diastereoselectivity, etc.). However, the value-added nature of the chiral allylic and homoallylic derivatives obtained by these methods, the lack of efficient alternatives, and the use of an earth-abundant first-row transition metal have led to renewed interest over the past decade. In this Perspective, we give an overview of the developments in this field, from the original findings (often dating back to the last century) to the most recent contributions. Emphasis is placed on the nature of the hydrofunctionalization agent (C(sp), C(sp 2 ), C(sp 3 ), N, P, or O)., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Two complementary catalytic protocols for the isomerization of stereoisomeric mixtures of vinylcyclopropanes are described. A commercially available cationic rhodium complex provides access to conjugated dienoates in high yield with excellent stereocontrol. The combination of a bisphosphine ligand and a ruthenium precatalyst affords cross-conjugated dienoates via a formal 1,3-ring opening. The products are obtained with moderate to high stereoselectivity. The ability of each type of dienoate to engage in [4 + 2] cycloaddition reactions has been demonstrated.

A [Ni/Mg]-catalyzed orthogonal tandem polymerization has been developed starting from enol phosphates. Initial investigations conducted on branched 1,3-dienes as monomers enabled identification of a Mg-initiated polymerization process leading to 1,4- cis -polydienes. When aryl enol phosphates are used as monomers, the [Ni/Mg]-catalyzed tandem polymerization affords 1,4- cis -polydienes with selectivities up to 99%. Elastomeric or crystalline materials were obtained by simple structural modifications of the monomeric unit. This tandem approach appears as a straightforward and efficient way to enforce diversity and selectivity in diene polymerization while retaining a fair degree of control, just as observed for stepwise systems that are accessible through established time- and manpower-consuming synthetic procedures.

While the integration of supramolecular principles in catalysis attracts increasing attention, a direct comparative assessment of the resulting systems catalysts to work out distinct characteristics is often difficult. Herein is reported how the broad responsiveness of ether cyclizations to diverse inputs promises to fill this gap. Cyclizations in the confined, π-basic and Brønsted acidic interior of supramolecular capsules, for instance, are found to excel with speed (exceeding general Brønsted acid and hydrogen-bonding catalysts by far) and selective violations of the Baldwin rules (as extreme as the so far unique pnictogen-bonding catalysts). The complementary cyclization on π-acidic aromatic surfaces remains unique with regard to autocatalysis, which is shown to be chemo- and diastereoselective with regard to product-like co-catalysts but, so far, not enantioselective., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

One-pot reactions elaborated around transition metal-catalyzed isomerization of alkenes not only offer the inherent advantages of atom-, step- and redox-economy but also enable the preparation of value-added products that would be difficult to access by conventional methods. In this Review, we cover seminal and recent examples of tandem, sequential and domino processes, which incorporate the most attractive features of olefin isomerization.

We report the development of two complementary methods for the Cu-catalyzed anti -Markovnikov borylation of one specific olefin in 2-substituted [ n ]dendralenes ( n = 3-6). The first protocol operates with a bisphosphine ligand and occurs with high regio- and chemoselectivity for the terminal double bond, independently of the number of cross-conjugated alkenes. We show that the use of a chiral phosphanamine ligand enables the highly chemo-, regio-, and enantioselective borylation of the alkene cross-conjugated with the terminal olefin in [ n ]dendralenes.

Two complementary regiodivergent [(P,N)Ni]-catalyzed hydroalkylations of branched dienes are reported. When amides are employed as unstabilized C(sp 3 ) nucleophiles, a highly regioselective 1,4-addition process is favored. The addition products are obtained in high yield and with excellent stereocontrol of the internal olefin. With use of a chiral ligand and imides as carbon nucleophiles, a 3,4-addition protocol was developed, enabling construction of two contiguous tertiary stereocenters in a single step with moderate to high levels of diastereocontrol and excellent enantiocontrol. Both methods operate under mild reaction conditions, display a broad scope, and show excellent functional group tolerance. The synthetic potential of the 3,4-hydroalkylation reaction was established via a series of postcatalytic modifications.

A catalytic sequence for the diastereo- and enantioselective preparation of homoallylic alcohols with an adjacent quaternary (stereo)center is reported. The one-pot process relies on the use of a single (achiral or chiral) iridium complex to catalyze the concomitant isomerization of primary allylic alcohols and homoallylboronates into (chiral) aldehydes and allylboronates, respectively. In the same flask, a chiral Brønsted acid is added next to engage the isomerization products into a stereocontrolled allylboration reaction. Structural variations have been performed on both the allylic alcohols and the homoallylboronates. This mild process affords an array of stereochemically congested and complex chiral secondary homoallylic alcohols in high yield, excellent diastereoselectivity, and usually high enantioselectivity.

A Cu-catalyzed borylative carboxamidation reaction has been developed using vinylarenes and isocyanates. Alkynes, branched 1,3-dienes, and bicyclic alkenes were also found to be competent coupling partners. Using a chiral phosphanamine ligand, an enantioselective variant of this transformation was developed, affording a set of α-chiral amides with unprecedented levels of enantioselectivity. The synthetic utility of the method was demonstrated through a series of representative stereoretentive postcatalytic derivatizations.

A highly regioselective Ni-catalyzed hydroalkoxylation of 1,3-dienes is reported. The use of a (P,N) ligand is essential in achieving high levels of selectivity. The optimized protocol operates under particularly mild conditions, it provides access to a broad range of structurally diverse allylic ethers, and tolerates a number of sensitive functional groups.

The remote functionalization of α,β-unsaturated carbonyls by an array of multimetallic sequential catalytic systems is described. The reactions are triggered by hydrometalation using [Pd-H] or [Ru-H] isomerization catalysts and driven by the formation of thermodynamically more stable 1,2-vinyl arenes. The Pd-catalyzed deconjugative isomerization was combined with a Cu-catalyzed β-borylation of the transiently generated styrenyl derivatives to deliver a range of products that would not be accessible with the use of a single catalyst. [Pd/Cu] catalytic systems were also identified for the highly enantioselective α-hydroboration and α-hydroamination of the styrenyl intermediates. Difunctionalization simultaneously at the benzylic and homobenzylic positions was achieved by combining the isomerization process with Sharpless asymmetric dihydroxylation (SAD) using [Pd/Os] or [Ru/Os] couples. Starting from a simple α,β-unsaturated ester, an isomerization/dihydroxylation/lactonization sequence gave access to a naturally occurring γ-butyrolactone in good yield, with excellent diastereo- and enantioselectivity.

A Ni-catalyzed intermolecular enantioselective hydroamination of branched 1,3-dienes is reported. The method is broadly applicable, highly regio-, chemo-, and enantioselective, and provides direct access to valuable chiral allylic amines starting from linear or α-branched aliphatic primary amines or secondary amines. Mechanistic studies have been conducted using 31 P NMR spectroscopy for reaction progress monitoring, isotopic labeling experiments ( 2 H), and kinetic analysis. The resting state of the catalyst is a Ni-π-allyl complex, and the outer-sphere nucleophilic attack of H-bonded amine aggregates is proposed to be the rate-determining step. This hypothesis guided the identification of an improved set of reaction conditions for the enantioselective hydroamination of branched 1,3-dienes.

A highly enantioselective Cu-catalyzed borylation of 2-substituted 1,3-dienes is reported. The use of a chiral phosphanamine ligand is essential in achieving high chemo-, regio-, diastereo- and enantioselectivity. It provides access to a variety of homoallylic boronates in consistently high yield and enantiomeric excess with 2-aryl and 2-heteroaryl 1,3-dienes as well as sterically demanding 2-alkyl 1,3-dienes. Preliminary investigations based on a non-linear effect study point to a mechanism involving more than one metal center.

Starting from readily available alkenyl methyl ethers, the stereoselective preparation of highly substituted alkenes by two complementary multicatalytic sequential isomerization/cross-coupling sequences is described. Both elementary steps of these sequences are challenging processes when considered independently. A cationic iridium catalyst was identified for the stereoselective isomerization of allyl methyl ethers and was found to be compatible with a nickel catalyst for the subsequent cross-coupling of the in situ generated methyl vinyl ethers with various Grignard reagents. The method is compatible with sensitive functional groups and a multitude of olefinic substitution patterns to deliver products with high control of the newly generated C═C bond. A highly enantioselective variant of this [Ir/Ni] sequence has been established using a chiral iridium precatalyst. A complementary [Pd/Ni] catalytic sequence has been optimized for alkenyl methyl ethers with a remote C═C bond. The final alkenes were isolated with a lower level of stereocontrol. Upon proper choice of the Grignard reagent, we demonstrated that C( sp 2 )-C( sp 2 ) and C( sp 2 )-C( sp 3 ) bonds can be constructed with both systems delivering products that would be difficult to access by conventional methods.

We report herein the highly diastereoselective synthesis of octahedral cationic Ir(iii) hydride complexes with a stereogenic metal centre following various strategies. The configurational stability of these compounds has also been investigated.

The long-range deconjugative isomerization of a broad range of α,β-unsaturated amides, esters, and ketones by an in situ generated palladium hydride catalyst is described. This redox-economical process is triggered by a hydrometalation event and is thermodynamically driven by the refunctionalization of a primary or a secondary alcohol into an aldehyde or a ketone. Di-, tri-, and tetrasubstituted carbon-carbon double bonds react with similar efficiency; the system is tolerant toward a variety of functional groups, and olefin migration can be sustained over 30 carbon atoms. The refunctionalized products are usually isolated in good to excellent yield. Mechanistic investigations are in support of a chain-walking process consisting of repeated migratory insertions and β-H eliminations. The bidirectionality of the isomerization reaction was established by isotopic labeling experiments using a substrate with a double bond isolated from both terminal functions. The palladium hydride was also found to be directly involved in the product-forming tautomerization step. The ambiphilic character of the in situ generated [Pd-H] was demonstrated using isomeric trisubstituted α,β-unsaturated esters. Finally, the high levels of enantioselectivity obtained in the isomerization of a small set of α-substituted α,β-unsaturated ketones augur well for the successful development of an enantioselective version of this unconventional isomerization.

This Account presents the development of the iridium-catalyzed isomerization of primary allylic alcohols in our laboratory over the past 8 years. Our initial interest was driven by the long-standing challenge associated with the development of a general catalyst even for the nonasymmetric version of this seemingly simple chemical transformation. The added value of the aldehyde products and the possibility to rapidly generate molecular complexity from readily accessible allylic alcohols upon a redox-economical isomerization reaction were additional sources of motivation. Certainly influenced by the success story of the related isomerization of allylic amines, most catalysts developed for the selective isomerization of allylic alcohols were focused on rhodium as a transition metal of choice. Our approach has been based on the commonly accepted precept that hydrogenation and isomerization are often competing processes, with the latter being usually suppressed in favor of the former. The cationic iridium complexes [(Cy3P)(pyridine)Ir(cod)]X developed by Crabtree (X = PF6) and Pfaltz (X = BArF) are usually considered as the most versatile catalysts for the hydrogenation of allylic alcohols. Using molecular hydrogen to generate controlled amounts of the active form of these complexes but performing the reaction in the absence of molecular hydrogen enabled deviation from the typical hydrogenation manifold and favored exclusively the isomerization of allylic alcohols into aldehydes. Isotopic labeling and crossover experiments revealed the intermolecular nature of the process. Systematic variation of the ligand on the iridium center allowed us to identify the structural features beneficial for catalytic activity. Subsequently, three generations of chiral catalysts have been investigated and enabled us to reach excellent levels of enantioselectivity for a wide range of 3,3-disubstituted aryl/alkyl and alkyl/alkyl primary allylic alcohols leading to β-chiral aldehydes. The combination of the isomerization reaction with enamine catalysis in a sequential process gave access to α,β-chiral aldehydes in high diastereomeric ratio and excellent enantioselectivity. Catalyst-controlled diastereoselective isomerization of stereochemically complex steroid scaffolds has been achieved, giving access indifferently to derivatives with the natural and unnatural C20 configuration, a long-standing challenge in the field. Structural diversification at close proximity of the reactive site and within the polycyclic domain served to further demonstrate the generality and the potential of the method. Models based on quadrant diagrams enabled rationalization of the high levels of enantio- and diastereocontrol obtained in the isomerization of allylic alcohols.

[Purpose] Poor posture in children and adolescents is a well-known problem. Therefore, early detection of incorrect posture is important. Photometric posture analysis is a cost-efficient and easy method, but needs reliable reference values. As children's posture changes as they grow, the assessment needs to be age-specific. This study aimed to investigate the development of both one-dimensional posture parameter (body inclination angle) and complex parameter (posture index) in different age groups (childhood to adolescence). [Subjects and Methods] The participants were 372 symptom-free children and adolescents (140 girls and 232 boys aged 6-17). Images of their habitual posture were obtained in the sagittal plane. High-contrast marker points and marker spheres were placed on anatomical landmarks. Based on the marker points, the body inclination angle (INC) and posture index (PI) were calculated using the Corpus concepts software. [Results] The INC angle significantly increased with age. The PI did not change significantly among the age groups. No significant differences between the corresponding age groups were found for PI and INC for both sexes. [Conclusion] When evaluating posture using the body inclination angle, the age of the subject needs to be considered. Posture assessment with an age-independent parameter may be more suitable.

A novel enantioselective Pd-catalyzed intermolecular carboetherification of dihydrofurans is reported. The in situ generation of chiral bis-phosphine mono-oxide ligands is crucial, and a general catalytic system has been identified based on this approach. It provides access to a variety of fused tetrahydrofurobenzofurans in consistently high yield and enantiomeric excess.

Introduction: Poor posture in children and adolescents has a prevalence of 22-65% and is suggested to be responsible for back pain. To assess posture, photometric imaging of sagittal posture is widely used, but usually only habitual posture positions (resting position with minimal muscle activity) are analysed., Aim: The objective of this study was 1) to investigate possible changes in posture-describing parameters in the sagittal plane, when the subjects changed from a habitual passive posture to an actively corrected posture, and 2) to investigate the changes in posture parameters when an actively corrected posture was to be maintained with closed eyes., Materials and Methods: In a group of 216 male children and adolescents (average 12.4 ± 2.5 years, range 7.0 - 17.6 years), six sagittal posture parameters (body tilt BT, trunk incline TI, posture index PI, horizontal distances between ear, shoulder and hip and the perpendicular to the ankle joint) were determined by means of photometric imaging in an habitual passive posture position, in an actively erect posture with eyes open, and in active stance with eyes closed. The change in these parameters during the transition between the posture positions was analysed statistically (dependent t-Test or Wilcoxon-Test) after Bonferroni correction (p<0.004)., Results: When moving from a habitual passive to an active posture BT, TI, PI, dEar, dShoulder, and dHip decreased significantly(p< 0.004). When the eyes were closed, only the perpendicular distances (dEar, dShoulder, and dHip) increased significantly. The parameters that describe the alignment of the trunk sections in relation to each other (BT, TI, PI), remained unchanged in both actively regulated posture positions., Conclusion: Changes in sagittal posture parameters that occur when a habitual passive posture switches into an active posture or when an active posture is to be maintained while the eyes are closed can be used for diagnostic purposes regarding poor posture and posture regulation.

The location of the Pd atoms in Pd2Au36(SC2H4Ph)24, is studied both experimentally and theoretically. X-ray photoelectron spectroscopy (XPS) indicates oxidized Pd atoms. Palladium K-edge extended X-ray absorption fine-structure (EXAFS) data clearly show Pd-S bonds, which is supported by far infrared spectroscopy and by comparing theoretical EXAFS spectra in R space and circular dichroism spectra of the staple, surface and core doped structures with experimental spectra.

The stereoselective construction of C20 in steroidal derivatives by a highly diastereoselective Ir-catalyzed isomerization of primary allylic alcohols is reported. A key aspect of this strategy is a straightforward access to geometrically pure steroidal enol tosylate and enol triflate intermediates for subsequent high yielding stereoretentive Negishi cross-coupling reactions to allow structural diversity to be introduced. A range of allylic alcohols participates in the diastereoselective isomerization under the optimized reaction conditions. Electron-rich and electron-poor aryl or heteroaryl substituents are particularly well-tolerated, and the stereospecific nature of the reaction provides indifferently access to the natural C20-(R) and unnatural C20-(S) configurations. Alkyl containing substrates are more challenging as they affect regioselectivity of iridium-hydride insertion. A rationale for the high diastereoselectivities observed is proposed for aryl containing precursors. The scope of our method is further highlighted through topological diversification in the side chain and within the polycyclic domain of advanced and complex steroidal architectures. These findings have the potential to greatly simplify access to epimeric structural analogues of important steroid scaffolds for applications in biological, pharmaceutical, and medical sciences.

A palladium-catalyzed intermolecular asymmetric Heck reaction with dihydrofurans with a trisubstituted double bond is reported. The use of two different chiral ligands provides access to valuable 2,3- and 2,5-dihydrofurans with a fully substituted C2 stereocenter with high levels of regio- and enantiocontrol.

A palladium-catalyzed benzylation of α-branched aldehydes has been developed using benzyl methyl carbonates. The method gives access to congested quaternary centers in the vicinity of one of the most sensitive carbonyl functionalities and displays unprecedented generality with respect to both coupling partners. Evidence for the direct involvement of a Pd-η(3)-benzyl intermediate is provided. Extension of this strategy to the γ-benzylation of α,β-unsaturated aldehydes is further demonstrated.

Herein we report the palladium-catalyzed isomerization of highly substituted allylic alcohols and alkenyl alcohols by means of a single catalytic system. The operationally simple reaction protocol is applicable to a broad range of substrates and displays a wide functional group tolerance, and the products are usually isolated in high chemical yield. Experimental and computational mechanistic investigations provide complementary and converging evidence for a chain-walking process consisting of repeated migratory insertion/β-H elimination sequences. Interestingly, the catalyst does not dissociate from the substrate in the isomerization of allylic alcohols, whereas it disengages during the isomerization of alkenyl alcohols when additional substituents are present on the alkyl chain.

We describe the use of an air-stable iridium hydride catalyst for the isomerization of terminal epoxides into aldehydes with perfect regioselectivity. The system operates at low loadings of catalyst (0.5 mol%), is highly practical, scalable, and tolerates functional groups that would not be compatible with Lewis acids typically used in stoichiometric amounts. Evidence for a rare hydride mechanism are provided.

This Feature Article intends to provide an overview of a variety of catalytic isomerization reactions that have been performed using well-defined transition metal hydride precatalysts. A particular emphasis is placed on the underlying mechanistic features of the transformations discussed. These have been categorized depending upon the nature of the substrate and in most cases discussed following a chronological order.

Recent advances in the palladium-catalyzed remote functionalization of carbonyl derivatives are highlighted in this review. The structure of the article is based on the three strategies that have emerged in recent years as the most viable tactics to construct C(sp(3))-C, C(sp(3))-N or C(sp(3))-O bonds at a distance of at least three carbon atoms from the carbonyl functionality. The specific aspects of each of these approaches are discussed in detail (reaction conditions, substrate scope and limitations). As the reading progresses, their complementarity should also appear clearly.

An improved synthesis of a novel class of bidentate (P,N) ligands is presented, the structures of which are characterized by three distinct elements of chirality. The stereoselective installation of the elements of central chirality (at the benzylic carbon and the phosphorus atom) depends on the size of the phosphorus substituent. Thermal inversion of the phosphorus center has been studied experimentally and further correlated by DFT calculations. The potential of these ligands and the role of the phosphorus atom in the asymmetric α-arylation of aldehydes (Pd) and hydrogenation of allylic alcohols (Ir) have also been investigated., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)