An in silico study examined the stabilities of hydrogen-bonded complexes between simple thiourea catalysts and three different electrophiles and identified a novel, highly active N-tosyl urea catalyst for the promotion of addition reactions to epoxide electrophiles. Synthesis and evaluation of 6 revealed it to be a powerful catalyst for the addition of 1,2-dimethylindole to styrene oxide under conditions in which simple N,N-bis-aryl ureas and thioureas (including 1) are inactive. Subsequent studies determined 6 to be compatible with a range of indole and epoxide substrates (including (E)-stilbene oxide) and found that relatively poor nucleophiles such as sterically and electronically deactivated anilines, thiophenol, and benzyl alcohol could be efficiently and regioselectively added to oxiranes under mild conditions.

Bifunctional urea-based cinchona alkaloid derivatives have been shown to promote highly efficient DKR reactions of azalactones using an alcohol nucleophile. The optimum catalyst is remarkably insensitive to the steric bulk of the amino acid residue, allowing alanine-, methionine-, and phenylalanine-derived azalactones to undergo DKR with unprecedented levels of enantioselectivity using a synthetic catalyst. The first DKR of these substrates by thiols and the highly enantioselective desymmetrization of a meso-glutaric anhydride by thiolysis are also reported.

We report the design and evaluation of a library of chiral bifunctional organocatalysts in which the distance between the catalytically active units can be systematically varied.The inexpensive cinchona alkaloids quinine (1) and quinidine (2) have been intensely studied as structural templates upon which bifunctional hydrogen-bond donating organocatalysts can be constructed.1 For instance, C-9 substituted (thio)urea-, sulfonamide-, and more recently squaramide derivatives (e.g. 3,2,3 4 4 and 5 5 respectively) together with C-6 0 demethylated cupreine-derived materials (e.g. 6-8 1,6 ) have been developed (inter alia) with the goal of controlling the encounter of two reacting components in a chiral environment via interaction between the substrates and the hydrogen bond donating (blue)/Brønsted basic (red) catalyst functionality. 1While undoubtedly broad in scope, there is an inherent inflexibility associated with these materials which frustrates the ambition of designing catalysts genuinely tuned to meet the demands of any given process. For example, the relative positioning of the nucleophile-and electrophile-activating components is key to successful bifunctional catalyst design ( Fig. 1). An examination of 3-8 reveals that the practitioner is offered two options: hydrogen bond donating functionality at either C-9 or C-6 0 . 7 Therefore if the stereoelectronic demands of a particular general acid/base catalysed process do not correlate well with the spatial relationship between the catalyst's C-9/C-6 0 substituted bifunctional components, it is unlikely that any modification of the catalytically relevant functionality will improve efficacy.More desirable and potentially useful would be the identification of a stable structural template, the chemical space around which could be easily modified in such a way that the relative positioning (and relative orientation) of the catalytically critical groups could be systematically modified.With this in mind, we noted a recent report from Skarżewski et al. detailing the synthesis of 9-phenyl-9-deoxyquinine (9, Fig. 2) and its quinidine counterpart, 8 together with a number of derivatives. We were intrigued as to the catalytic potential of such templates, as they seem to represent a potential (partial) solution to the questions posed above: they are stable, easily synthesised 8 materials, the conformation of 9 (i.e. 9a, Fig. 2) in both the solid state and solution is known 8 and would seem to be conducive to bifunctional catalysis if a phenolic hydrogen bond donor were installed (due to its relative proximity to the quinuclidine base). However, no catalytic applications of this class of materials have been reported thus far. We reasoned that we would be able to design a small library of catalysts based on this motif (i.e. 10, Fig. 2) which would be tunable to an unprecedented extent: for example: (a) the C-9 position would be devoid of a heteroatom, thus one would expect the basicity of the quinuclidine nitrogen atom to be augmented relative to traditional catalyst struc...

A significant improvement of the available organocatalytic methods (in terms of product substrate scope and product enantiomeric excess) for the generation of enantioenriched α-amino acid thioesters via the dynamic kinetic resolution of azlactones is reported. C-9 arylated cinchona alkaloid catalysts have been found to be considerably superior to other bifunctional alkaloid catalysts as the promoters of this asymmetric process.

Chitin, the second most abundant biopolymer on earth, is utilised in a wide range of applications including wastewater treatment, drug delivery, wound healing, tissue engineering, and stem cell technology among others. This review compares the most prevalent strategies for the extraction of chitin from crustacean sources including chemical methods that involve the use of harsh solvents and emerging methods using deep eutectic solvents (DES). In recent years, a significant amount of research has been carried out to identify and develop environmentally friendly processes which might facilitate the replacement of problematic chemicals utilised in conventional chemical extraction strategies with DES. This article provides an overview of different experimental parameters used in the DES-mediated extraction of chitin while also comparing the purity and yields of associated extracts with conventional methods. As part of this review, we compare the relative proportions of chitin and extraneous materials in different marine crustaceans. We show the importance of the species of crustacean shell in relation to chitin purity and discuss the significance of varying process parameters associated with different extraction strategies. The review also describes some recent applications associated with chitin. Following on from this review, we suggest recommendations for further investigation into chitin extraction, especially for experimental research pertaining to the enhancement of the “environmentally friendly” nature of the process. It is hoped that this article will provide researchers with a platform to better understand the benefits and limitations of DES-mediated extractions thereby further promoting knowledge in this area.