The enantioselective reduction of prochiral ketones is a most productiveway towards enantio enriched secondary alcohols used in the preparation of biologically active compounds. There are numerous transition metal catalyzed methods for this transformation, particularly based on Ru(II)-and Rh(I)-complexes, but there is a demand for a larger substrate scope. Heteroaromatic ketones are traditionally more challenging substrates. Normally a catalyst is developed for one benchmark substrate, and asubstrate screen is made with the best performing catalyst. Using this methodology, there is a high probability that for different substrates, another catalyst could outperform the one used. We have executed a multiple screen, containing a variety of different ligands together with both Ru and Rh, and heteroaromatic ketones to fine-tune, and find the optimum catalyst depending on the substrate. The acquired information was used to synthesize known, biologically active compounds, where the key reduction steps were performed with high enantioselectivities and yields.
The development, scope and application of the highly enantioselective organocatalytic aziridination of a, b- unsaturated aldehydes is presented. The aminocatalytic aziridination of a, b- unsaturated aldehydes enables the asymmetric formation of b-formylaziridines with up to >19:1 dr and 99% ee. The aminocatalytic aziridination of a-monosobstituted enals gives access to terminal a-substituted-a-formyl aziridines in high yields and up to 99% ee. In the case of the organocatalytic aziridination of disubstituted a, b-unsaturated aldehydes, the transformations gives nearly enantiomeric pure b-formyl-functionalized aziridine products. A higly enantioselective one-pot cascade sequence based on combination of asymmetric amine and N-heterocyclic carbene catalysis is also disclosed. This transformation gives the corresponding N-Boc and N-Cbz protected b-amino acid esters with ee´s ranging from 92-99%.
Diaryl ethers are common structural features in numerous natural products and biol. active compds. Despite more than a century of immense focus on finding efficient synthetic routes to this compd. class, diaryl ethers remain difficult to obtain. Routes that are catalytic in copper have been developed, but high catalyst loadings, excess reagents, elevated temps. and long reaction times are still needed. Pd-catalyzed cross-couplings of phenols and aryl halides at temps. up to 100 °C have recently been reported to give high yields of diaryl ethers. Diaryliodonium salts are non-toxic alternatives to transition metals in the synthesis of diaryl ethers and we have recently developed effective synthetic routes to these salts. Herein we report a fast, high-yielding synthesis of diaryl ethers. The reaction conditions are mild, metal-free, and avoid the use of halogenated solvents, additives, or excess reagents. Precautions to avoid air or moisture are not needed. The scope includes ortho- and halo-substituted diaryl ethers, which are difficult to obtain by metal-catalyzed protocols .
CarbBuilder is a software tool for building 3D structures of carbohydrates, which are the most structurally varied of all molecular classes. CarbBuilder was designed with the dual aims of portability and adaptability, using an iterative software development approach. CarbBuilder employs a simple algorithm, using heuristics based upon experimental data to convert a primary structure description of a carbohydrate molecule into a three-dimensional structure file. This straightforward approach means that CarbBuilder can be easily adapted: users can add additional monosaccharide building blocks or alter the conformational defaults to suit specific requirements. The output carbohydrate structure can be used for subsequent molecular simulation investigations. CarbBuilder is freely available and portable: it is a text-based stand-alone program that can run on Windows, Linux and MacOS X systems without installation.
Separate diastereomers of protected dithymidine (3'-5')-phenylphosphonates and dithymidine (3'-5')phenylphosphonothioate were obtained via a palladium(0) catalysed stereo-specific cross-coupling reaction of separate diastereomers of corresponding dinucleoside H-phosphonate and dinucleoside H-phosphonothioate with halobenzenes.
A ruthenium catalyst formed in situ by combining [Ru(p-cymene)Cl2]2 and an amino acid hydroxy-amide was found to catalyze efficiently the asymmetric reduction of aryl alkyl ketones under transfer hydrogenation conditions using ethanol as the hydrogen donor. The secondary alcohol products were obtained in moderate to good yields and with good to excellent enantioselectivity (up to 97% ee).
We have developed a direct arylation reaction of cyclohexanones employing diaryl iodonium(Ill) salts as electrophiles. The
reaction was made enantiosilective by the use of a chiral base, resultinginZ,4-disubstituted cyclohexanones in high yields and with high enantiomeric excesses and diastereoselectivities. Novel heteroaryl iodonium salts were subsequently synthesized and employed in the coupling to variously substituted cyclohexanones.
A Europium-based turn-on bioconjugatable luminescent probe for detecting hydrogen peroxide in live cells is presented. The probe relies on a chemoselective boronate-to-phenol switch in response to hydrogen peroxide, resulting in an enhanced lanthanide sensitization. Excitation can be performed by visible light. Bioconjugation is achived by Cu(I) catalyzed azide-alkyne cycloaddn.