Since their discovery in 1997, iridium-catalysed asymmetric allylic substitutions have been developed into a broadly applicable tool for the synthesis of chiral building blocks
via
CC and Cheteroatom ...bond formation. The remarkable generality of these reactions and the high levels of regio- and enantioselectivity that are usually obtained in favour of the branched products have been made possible by a thorough investigation of the catalyst system and its mode of action. Therefore, today the Ir-catalysed asymmetric allylic substitution is a powerful reaction in the organic chemist's repertoire and has been used extensively for several applications. This article aims to provide an overview of the development of iridium catalysts derived from an Ir salt and a chiral phosphoramidite and their application to the enantioselective synthesis of natural products and biologically relevant compounds.
The development of chiral iridium catalysts for asymmetric allylic substitution reactions and their application to the synthesis of natural products and other biologically relevant compounds is reviewed.
Cu-catalysed arylation reactions devoted to the formation of C-C and C-heteroatom bonds (Ullmann-type couplings) have acquired great importance in the last decade. This review discusses the history ...and development of coupling reactions between aryl halides and various classes of nucleophiles, focusing mostly on the different mechanisms proposed through the years. Selected mechanistic investigations are treated more in depth than others. For example, evidence in favour or against radical mechanisms is discussed. Cu(
i
) and Cu(
iii
) complexes involved in the Ullmann reaction and N/O selectivity in aminoalcohol arylation are discussed. A separate section has been dedicated to the synthesis of heterocyclic rings through intramolecular couplings. Finally, recent developments in green chemistry for these reactions, such as reactions in aqueous media and heterogeneous catalysis, have also been reviewed.
Copper-catalysed arylations represent valid and complementary alternatives to Pd catalysis. This review discusses the different mechanisms suggested for these reactions, and summarises some of their latest applications in synthesis.
Main-sequence low-mass stars are known to spin down as a consequence of their magnetized stellar winds. However, estimating the precise rate of this spin-down is an open problem. The mass-loss rate, ...angular momentum loss rate, and magnetic field properties of low-mass stars are fundamentally linked, making this a challenging task. Of particular interest is the stellar magnetic field geometry. In this work, we consider whether non-dipolar field modes contribute significantly to the spin-down of low-mass stars. We do this using a sample of stars that have all been previously mapped with Zeeman-Doppler imaging. For a given star, as long as its mass-loss rate is below some critical mass-loss rate, only the dipolar fields contribute to its spin-down torque. However, if it has a larger mass-loss rate, higher-order modes need to be considered. For each star, we calculate this critical mass-loss rate, which is a simple function of the field geometry. Additionally, we use two methods of estimating mass-loss rates for our sample of stars. In the majority of cases, we find that the estimated mass-loss rates do not exceed the critical mass-loss rate; hence, the dipolar magnetic field alone is sufficient to determine the spin-down torque. However, we find some evidence that, at large Rossby numbers, non-dipolar modes may start to contribute.
3‐Amino‐substituted saturated nitrogen heterocycles are an important subclass of β‐diamines, appearing in a number of clinical agents. Herein, we report a unified approach to these products based ...upon the regioselective photoredox‐mediated hydroamination of enecarbamates. The amine coupling partner can encompass diverse amine types under a single set of reaction conditions, including primary alkyl amines, ammonia, aryl and heteroaryl amines, and N−H heterocycles. The method enables the synthesis of a wide range of pharmaceutically relevant building blocks.
Medicinally important 3‐amino‐substituted cyclic amines can be accessed in a single step by photoredox‐catalysed hydroamination of cyclic enecarbamates. A diverse range of drug‐relevant amine substituents can be introduced under unified reaction conditions, including primary alkyl amines, ammonia, (hetero)aromatic amines, and N‐heterocycles (see scheme).
The behavior of electron-rich alkenes in rhodium-catalyzed C–H activation/annulation reactions is investigated. Vinyl acetate emerges as a convenient acetylene equivalent, facilitating the synthesis ...of sixteen 3,4-unsubstituted isoquinolones, as well as select heteroaryl-fused pyridones. The complementary regiochemical preferences of enol ethers versus enol esters/enamides is discussed.
As our understanding of the impact of specific molecular properties on applications in discovery‐based disciplines improves, the extent to which published synthetic methods meet (or do not meet) ...desirable criteria is ever clearer. Herein, we show how the application of simple (and in many cases freely available) computational tools can be used to develop a semiquantitative understanding of the potential of new methods to support molecular discovery. This analysis can, among other things, inform the design of improved substrate scoping studies; direct the prioritization of specific exemplar structures for synthesis; and substantiate claims of potential future applications for new methods.
The property ladder: Careful control of molecular properties is closely linked to success in small‐molecule‐led discovery ventures. Computational tools to calculate molecular properties are now widely available, many of them as freeware. These tools can be used to help guide the application of new synthetic methods and to evaluate alignment with future discovery needs.
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Current fragment sets tend to be dominated by flatter molecules, and their shape diversity does not reflect that of the fragments that are theoretically possible. The design and ...synthesis of a set of bridged fragments containing a bridgehead nitrogen is described. Many of these fragments contain twisted lactams whose modulated electronic properties may present unusual opportunities for interaction with target proteins. The demonstrated novelty, three-dimensionality and molecular properties of the set of 22 fragments may provide valuable, and highly distinctive, starting points for fragment-based drug discovery.
A convenient and simple three-component synthesis of substituted pyridylacetic acid derivatives is reported. The approach centers on the dual reactivity of Meldrum’s acid derivatives, initially as ...nucleophiles to perform substitution on activated pyridine-N-oxides, then as electrophiles with a range of nucleophiles to trigger ring-opening and decarboxylation.
Low-mass stars are known to have magnetic fields that are believed to be of dynamo origin. Two complementary techniques are principally used to characterize them. Zeeman-Doppler imaging (ZDI) can ...determine the geometry of the large-scale magnetic field while Zeeman broadening can assess the total unsigned flux including that associated with small-scale structures such as spots. In this work, we study a sample of stars that have been previously mapped with ZDI. We show that the average unsigned magnetic flux follows an activity-rotation relation separating into saturated and unsaturated regimes. We also compare the average photospheric magnetic flux recovered by ZDI, , with that recovered by Zeeman broadening studies, . In line with previous studies, ranges from a few % to ∼20% of . We show that a power-law relationship between and exists and that ZDI recovers a larger fraction of the magnetic flux in more active stars. Using this relation, we improve on previous attempts to estimate filling factors, i.e., the fraction of the stellar surface covered with magnetic field, for stars mapped only with ZDI. Our estimated filling factors follow the well-known activity-rotation relation, which is in agreement with filling factors obtained directly from Zeeman broadening studies. We discuss the possible implications of these results for flux tube expansion above the stellar surface and stellar wind models.
The regioselective γ-C-H amination of the side-chain of saturated 2-alkyl nitrogen heterocycles is reported, proceeding through a sulfamide-directed 1,6-radical translocation. The practicality of ...this rapid access to 1,3-diamines is highlighted in a short synthesis of the alkaloid tetraponerine T8 and non-natural analogues.
Radical translocation facilitates the regioselective γ-amination of 2-alkyl-substituted azacycles, leading to 1,3-diamines including the alkaloidal natural product tetraponerine T8.
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