The direct, catalytic, asymmetric α-functionalization of acyclic esters constitutes a significant challenge in the area of asymmetric catalysis, particularly where the configurational integrity of the products is problematic. Through the unprecedented merger of two independent, yet complementary, catalysis events it has been possible to facilitate the direct asymmetric α-allylation of readily available aryl acetic acid esters. Since enantioselection is determined by the nucleophile, this conceptual approach to cooperative catalysis constitutes a potentially general solution to the direct catalytic asymmetric α-functionalization of acyclic esters.

Introducing ThX, a next-generation ThT derivative that allows for the early detection of amyloid aggregates at the bulk and single-aggregate levels.

A productive total synthesis of both enantiomers of berkelic acid (1) is outlined that takes the structure revision of this bioactive fungal metabolite previously proposed by our group into account. The successful route relies on a fully optimized triple-deprotection/1,4-addition/spiroacetalization cascade reaction sequence, which delivers the tetracyclic core 32 of the target as a single isomer in excellent yield. The required cyclization precursor 31 is assembled from the polysubstituted benzaldehyde derivative 20 and methyl ketone 25 by an aldol condensation, in which the acetyl residue in 20 transforms from a passive protecting group into an active participant. Access to fragment 25 takes advantage of the Collum-Godenschwager variant of the ester enolate Claisen rearrangement, which clearly surpasses the classical Ireland-Claisen procedure in terms of diastereoselectivity. Although it is possible to elaborate 32 into the target without any additional manipulations of protecting groups, a short detour consisting in the conversion of the phenolic -OH into the corresponding TBS-ether is beneficial. It tempers the sensitivity of the compound toward oxidation and hence improves the efficiency and reliability of the final stages. Orthogonal ester groups for the benzoate and the aliphatic carboxylate terminus of the side chain secure an efficient liberation of free berkelic acid in the final step of the route.

A subtle difference: A single step suffices to transform a linear precursor into the chromane spiroketal core of the metalloproteinase-3 inhibitor berkelic acid by an acid-catalyzed deprotection/Michael addition/acetalization cascade. This efficient route resulted from the realization that the originally proposed structure is neither thermodynamically nor kinetically favored and has led to revision of the structure

Herein, we report a modular synthetic route to linear and branched homoallylic amines that operates through a sequential one‐pot Lewis base/transition‐metal catalyzed allylic alkylation/Hofmann rearrangement strategy. This protocol is operationally trivial, proceeds from simple and easily prepared substrates and catalysts, and enables all aspects of regio‐ and stereoselectivity to be controlled through a conserved experimental protocol. Overall, the high levels of enantio‐, regio‐, and diastereoselectivity obtained, in concert with the ability to access orthogonally protected or free amines, render this a straightforward and effective approach for the preparation of useful enantioenriched homoallylic amines. We have also demonstrated the utility of the products in the context of pharmaceutical synthesis.

Caught in the middle: The ionomycin calcium complex (see structure; O red, Ca green) was the target of an approach featuring the efficient asymmetric synthesis of an allene by a copper(I)-mediated anti-selective S(N)2' reaction, a highly stereoselective gold(III)-catalyzed cycloisomerization of an alpha-hydroxyallene, and a Rh-catalyzed rearrangement of an alpha-diazo-beta-hydroxyketone.

The benzothiazolium salt, Thioflavin T (ThT), has been widely adopted as the 'gold-standard' fluorescent reporter of amyloid in vitro. Its properties as a molecular rotor result in a largescale (~1000-fold) fluorescence turn-on upon binding to β-sheets in amyloidogenic proteins.However, the complex photophysics of ThT combined with the intricate and varied nature of the amyloid binding motif means these interactions are poorly understood. To study this important class of fluorophore, we present a detailed photophysical characterisation and comparison of a novel library of twelve ThT-inspired fluorescent probes for amyloid protein (PAPs), where both the charge and donor capacity of the heterocyclic and aminobenzene components have been interrogated, respectively. This enables direct photophysical juxtaposition of two structural groups; Class 1 the neutral 'PAP' and Class 2 the charged 'mPAP' fluorophores. We quantify binding and optical properties at both the bulk and singleaggregate levels with some derivatives showing higher aggregate affinity and brightness than ThT. Finally, we demonstrate their abilities to perform super-resolution imaging of αsynuclein fibrils with localisation precisions of ~16 nm. The properties of the derivatives provide new insights into the relationship between chemical structure and function of benzothiazole probes.

The first asymmetric cooperative Lewis base/palladium catalyzed benzylic alkylation of acyclic esters is reported. This reaction proceeds via stereodefined C1-ammonium enolate nucleophiles. Critical to its success was the identification of benzylic phosphate electrophiles, which were uniquely reactive. Alkylated products were obtained with very high levels of enantioselectivity, and this method has been applied toward the synthesis of the thrombin inhibitor DX-9065a.