Correction to "Iterative Dual-Metal and Energy Transfer Catalysis Enables Stereodivergence in Alkyne Difunctionalization: Carboboration as Case Study".

[This corrects the article DOI: 10.1021/acscatal.3c03570.].

Atroposelective Synthesis of Axially Chiral Naphthylpyrroles by a Catalytic Asymmetric 1,3-Dipolar Cycloaddition/Aromatization Sequence.

A straightforward methodology for the enantioselective preparation of axially chiral 2-naphthylpyrroles has been developed. This protocol is based on a CuI/Fesulphos-catalyzed highly enantioselective 1,3-dipolar cycloaddition of an azomethine ylide followed by pyrrolidine alkylation and pyrrolidine to pyrrole oxidation. The mild conditions employed in the DDQ/blue light-mediated aromatization process facilitate an effective central-to-axial chirality transfer affording the corresponding pyrroles with high atroposelectivity.

Iterative Dual-Metal and Energy Transfer Catalysis Enables Stereodivergence in Alkyne Difunctionalization: Carboboration as Case Study.

Stereochemically defined tetrasubstituted olefins are widespread structural elements of organic molecules and key intermediates in organic synthesis. However, flexible methods enabling stereodivergent access to E and Z isomers of fully substituted alkenes from a common precursor represent a significant challenge and are actively sought after in catalysis, especially those amenable to complex multifunctional molecules. Herein, we demonstrate that iterative dual-metal and energy transfer catalysis constitutes a unique platform for achieving stereodivergence in the difunctionalization of internal alkynes. The utility of this approach is showcased by the stereodivergent synthesis of both stereoisomers of tetrasubstituted ß-boryl acrylates from internal alkynoates with excellent stereocontrol via sequential carboboration and photoisomerization. The reluctance of electron-deficient internal alkynes to undergo catalytic carboboration has been overcome through cooperative Cu/Pd-catalysis, whereas an Ir complex was identified as a versatile sensitizer that is able to photoisomerize the resulting sterically crowded alkenes. Mechanistic studies by means of quantum-chemical calculations, quenching experiments, and transient absorption spectroscopy have been applied to unveil the mechanism of both steps.

Enantioselective transformations of 5-hydroxymethylfurfural via catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides.

A catalytic asymmetric 1,3-dipolar cycloaddition between iminoesters derived from 5-hydroxymethylfurfural (HMF) and different activated alkenes is reported. Excellent levels of diastereo and enantioselectivity were obtained when Fesulphos/CuI complex was used as catalyst. This metodology provides an effective and sustainable access to challenging enantioenriched heterocyclic scaffolds and represents one of the rare examples of catalytic asymmetric transformations using HMF as a starting material.

Palladium-Catalyzed PIDA-Mediated δ-C(sp3 )-H Acetoxylation of Amino Acid Derivatives: Overriding Competitive Intramolecular Amination.

The selective δ-C(sp3 )-H acetoxylation of N-(SO2 Py)-protected amino acid derivatives has been accomplished by using palladium-catalysis and PhI(OAc)2 (PIDA) as both terminal oxidant and acetoxy source. The distinct structural and electronic features of the SO2 Py compared to more traditional carbonyl-based directing groups is essential to override the otherwise more favourable competitive intramolecular C-H amination. The δ-site selectivity predominates over traditionally more favorable 5-membered cyclopalladation at competitive γ-CH2 . Experimental and DFT mechanistic studies provide important insights about the mechanism and the underlying factors controlling the chemo- and regioselectivity.

One-Metal/Two-Ligand for Dual Activation Tandem Catalysis: Photoinduced Cu-Catalyzed Anti-hydroboration of Alkynes.

A dual catalyst system based on ligand exchange of two diphosphine ligands possessing different properties in a copper complex has been devised to merge metal- and photocatalytic activation modes. This strategy has been applied to the formal anti-hydroboration of activated internal alkynes via a tandem sequence in which Cu/Xantphos catalyzes the B2pin2-syn-hydroboration of the alkyne whereas Cu/BINAP serves as a photocatalyst for visible light-mediated isomerization of the resulting alkenyl boronic ester. Photochemical studies by means of UV-vis absorption, steady-state and time-resolved fluorescence, and transient absorption spectroscopy have allowed characterizing the photoactive Cu/BINAP species in the isomerization reaction and its interaction with the intermediate syn-alkenyl boronic ester through energy transfer from the triplet excited state of the copper catalyst. In addition, mechanistic studies shed light into catalyst speciation and the interplay between the two catalytic cycles as critical success factors.

Beyond classical sulfone chemistry: metal- and photocatalytic approaches for C-S bond functionalization of sulfones.

The exceptional versatility of sulfones has been extensively exploited in organic synthesis across several decades. Since the first demonstration in 2005 that sulfones can participate in Pd-catalysed Suzuki-Miyaura type reactions, tremendous advances in catalytic desulfitative functionalizations have opened a new area of research with burgeoning activity in recent years. This emerging field is displaying sulfone derivatives as a new class of substrates enabling catalytic C-C and C-X bond construction. In this review, we will discuss new facets of sulfone reactivity toward further expanding the flexibility of C-S bonds, with an emphasis on key mechanistic features. The inherent challenges confronting the development of these strategies will be presented, along with the potential application of this chemistry for the synthesis of natural products. Taken together, this knowledge should stimulate impactful improvements on the use of sulfones in catalytic desulfitative C-C and C-X bond formation. A main goal of this article is to bring this technology to the mainstream catalysis practice and to serve as inspiration for new perspectives in catalytic transformations.

Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed anti-Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes.

The cooperative action of the acetate ligand, the 2-pyridyl sulfonyl (SO2Py) directing group on the alkyne substrate, and the palladium catalyst has been shown to be crucial for controlling reactivity, regioselectivity, and stereoselectivity in the acetoxylation of unsymmetrical internal alkynes under mild reaction conditions. The corresponding alkenyl acetates were obtained in good yields with complete levels of ß-regioselectivity and anti-acetoxypalladation stereocontrol. Experimental and computational analyses provide insight into the reasons behind this delicate interplay between the ligand, directing group, and the metal in the reaction mechanism. In fact, these studies unveil the multiple important roles of the acetate ligand in the coordination sphere at the Pd center: (i) it brings the acetic acid reagent into close proximity to the metal to allow the simultaneous activation of the alkyne and the acetic acid, (ii) it serves as an inner-sphere base while enhancing the nucleophilicity of the acid, and (iii) it acts as an intramolecular acid to facilitate protodemetalation and regeneration of the catalyst. Further insight into the origin of the observed regiocontrol is provided by the mapping of potential energy profiles and distortion-interaction analysis.

Catalytic enantioselective intramolecular 1,3-dipolar cycloaddition of azomethine ylides with fluorinated dipolarophiles.

An enantioselective synthesis of polycyclic fluorinated pyrrolidines has been achieved by Cu-catalyzed intramolecular 1,3-dipolar cycloaddition of azomethine ylides with fluorinated dipolarophiles. The method displays a wide scope and afforded the desired cycloadducts in high yields with up to 99% ee. These results demonstrate that fluoroalkyl substituents are excellent activating groups in this transformation.

Remote ortho-C-H functionalization via medium-sized cyclopalladation.

Compared to the tremendous progress made in directed ortho-C-H functionalization via five- or six-membered cyclopalladation, protocols with the ability to selectively activate more remote C-H bonds through the intermediacy of larger, less favorable, seven- or eight-membered metalacycles are particularly challenging and remain rare. However, such a strategy would provide new retrosynthetic opportunities for generating structural diversity and complexity. Intense recent research based on the use of either mono-anionic bidentate or monodentate directing groups is characterizing this approach as an increasingly viable tool for selective C-C and C-X bond-forming reactions. This short review provides an overview of these strategies with an emphasis on mechanistic details, synthetic applicability, limitations, and key challenges.

anti-Hydroarylation of Activated Internal Alkynes: Merging Pd and Energy Transfer Catalysis.

A general catalytic anti-hydroarylation of electron-deficient internal alkynes compatible with both electron-poor and electron-rich aryl reagents is reported. This selectivity is achieved through a sequential syn-carbopalladation of the alkyne by an Ar-Pd species, followed by a tandem, Ir-photocatalyzed, counter-thermodynamic E → Z isomerization. The use of ortho-substituted boronic acids enables direct access to pharmaceutically relevant heterocyclic cores via a cascade process. Mechanistic insight into the involvement of Ar-Pd versus Pd-H as an active species is provided.

Idiopathic dilatation of the right atrium: a not so benign entity.

Idiopathic dilatation of the right atrium is an isolated enlargement of the right atrium in the absence of other cardiac lesions. This rare anomaly has a clinical spectrum ranging from asymptomatic to heart failure or even sudden death. It can be associated with atrial arrhythmias and thrombus formation. Antiplatelet therapy is prescribed in most cases reported in the literature, and reduction plasty is indicated when there is rapid growth of the right atrium, compression of adjacent structures, or refractory arrhythmias. We report four cases of idiopathic dilatation of the right atrium diagnosed during prenatal screening. We describe the intrauterine course and management in postnatal life until early childhood.

Catalytic asymmetric synthesis of diazabicyclo[3.1.0]hexanes by 1,3-dipolar cycloaddition of azomethine ylides with azirines.

Substituted 1,3-diazabicyclo[3.1.0]hexanes with two contiguous quaternary stereocentres are readily prepared by catalytic asymmetric [3+2] cycloaddition of α-substituted iminoesters with azirines. High diastereoselectivities and enantioselectivities (up to 98% ee) are achieved using CuI/(R)-Fesulphos as the catalytic system.

Comprehensive Functional Echocardiographic Assessment of Transposition of the Great Arteries: From Fetus to Newborn.

To improve the understanding of the pathophysiology of transposition of the great arteries with intact ventricular septum (TGA/IVS) and the cardiac remodeling occurring from fetal to neonatal life, we performed a morphometric and functional echocardiographic assessment in fetuses and newborns. This was a prospective case-control study performed in a tertiary referral center, which included fetuses and newborns with a diagnosis of TGA/IVS between 2011 and 2018. Morphometry and systolic and diastolic function parameters were compared with age and body surface-matched healthy controls. Twenty-one TGA/IVS patients were included during the study period and morphometric and functional echocardiographic data were recorded. TGA/IVS patients showed morphometric and functional changes of increased overall volume and output, predominantly in the aortic component from fetus to newborn, probably due to compensatory mechanisms secondary to brain hypoxia.

Stereochemical diversity in pyrrolidine synthesis by catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides.

The pyrrolidine ring is a privileged structural motif in synthetic and medicinal chemisty. This review aims to highlight the high versatility of the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides for access to different types of stereochemical patterns in enantioselective pyrrolidine synthesis. Special attention will be paid to stereodivergent procedures giving rise to different stereoisomers from the same starting materials.

Access to Benzazepinones by Pd-Catalyzed Remote C-H Carbonylation of γ-Arylpropylamine Derivatives.

A general method for the construction of seven-membered rings through Pd-catalyzed C(sp2)-H carbonylation at the remote ε-position of γ-arylpropylamine derivatives, including chiral α-amino acids, has been developed using Mo(CO)6 as the CO source, furnishing richly functionalized benzo[ c]azepin-1-one derivatives. The readily removable N-SO2Py protecting/directing group provides high levels of chemo-, regio- and diastereoselectivity. Furthermore, this method is amenable to the postsynthetic modification of complex molecules such as small peptides.

Rhodium-Catalyzed Copper-Assisted Intermolecular Domino C-H Annulation of 1,3-Diynes with Picolinamides: Access to Pentacyclic π-Extended Systems.

A new mode of reactivity of 1,3-diynes in rhodium-catalyzed oxidative annulation reactions has enabled the rapid assembly of extended π systems from readily available picolinamide derivatives. The process involves a double C-H bond activation and the iterative annulation of two 1,3-diyne units, with each alkyne moiety engaged in an orchestrated insertion sequence with high regiocontrol, leading to the formation of five new C-C bonds and the construction of four fused rings in a single operation. Either isoquinoline-1-carboxamides or fused polycyclic systems can be accessed by a switch in the regioselectivity of the second diyne insertion depending on the reaction conditions. DFT theoretical calculations have elucidated that the cooperative participation of both rhodium and copper in substrate activation, favored in the presence of excess of the copper(II) salt, is key to such a reversal of regioselectivity and subsequent multiple cyclization leading to fused polycyclic products. The role of copper was found to be essential in assisting both multiple insertion and rhodium-walking sequences, with the implication of intermediates with a Rh-Cu bond (2.60 Å).

CuI-Catalyzed Asymmetric [3 + 2] Cycloaddition of Azomethine Ylides with Cyclobutenones.

The catalytic asymmetric 1,3-dipolar cycloaddition of cyclobutenones with azomethine ylides provides straightforward access to densely substituted 3-azabicyclo[3.2.0]heptanes. In the presence of CuI/(R)-Fesulphos as the catalytic system, high levels of diastereoselectivity and enantioselectivity were achieved (up to 98% enantiomeric excess (ee)).

Isolated aortic dilation without osteoarthritis: a case of SMAD3 mutation.

Aneurysm-osteoarthritis syndrome is a recently discovered inherited autosomal dominant connective tissue disease caused by SMAD3 mutations. Aneurysm-osteoarthritis syndrome is responsible for 2% of familial thoracic aortic aneurysms and dissections and is characterised by aneurysms, dissections, and tortuosity throughout the arterial tree in combination with osteoarthritis. Early-onset osteoarthritis is present in almost all patients. We present the case of a non-syndromic young boy with SMAD3 mutation isolated from the dilated aortic root and ascending aorta without osteoarthritis.

Cardiovascular adaptation to extrauterine life after intrauterine growth restriction.

Introduction The adaptive changes of the foetal heart in intrauterine growth restriction can persist postnatally. Data regarding its consequences for early circulatory adaptation to extrauterine life are scarce. The aim of this study was to assess cardiac morphometry and function in newborns with late-onset intrauterine growth restriction to test the hypothesis that intrauterine growth restriction causes cardiac shape and functional changes at birth. METHODS: A comprehensive echocardiographic study was performed in 25 neonates with intrauterine growth restriction and 25 adequate-for-gestational-age neonates. RESULTS: Compared with controls, neonates with intrauterine growth restriction had more globular ventricles, lower longitudinal tricuspid annular motion, and higher left stroke volume without differences in the heart rate. Neonates with intrauterine growth restriction also showed subclinical signs of diastolic dysfunction in the tissue Doppler imaging with lower values of early (e') diastolic annular peak velocities in the septal annulus. Finally, the Tei index in the tricuspid annulus was higher in the intrauterine growth restriction group. CONCLUSION: Neonates with history of intrauterine growth restriction showed cardiac remodelling and signs of systolic and diastolic dysfunction. Overall, there was a significant tendency to worse cardiac function results in the right heart. The adaptation to extrauterine life occurred with more globular hearts, higher stroke volumes but a similar heart rate compared to adequate-for-gestational-age neonates.