In pursuit of β-amino α-nitro β-trifluoromethyl ketones: nitro-Mannich vs Mannich-type reactions

The reactivity of alfa-nitro ketones with trifluoromethyl aldimines is studied for the first time. While under nitro-Mannich conditions only the facial stereoselectivity can be controlled, organocatalysed Mannich-type reactions allowed a complete control of absolute and relative stereoselectivity, leading to highly functionalised β-amino alfa-nitro β-trifluoromethyl compounds as diastereomerically pure compounds. A key role on the geometrical and/or facial stereoselectivity is played by the structure of reactants

A Simple Nickel Catalyst Enabling an E‐Selective Alkyne Semihydrogenation

Stereoselective alkyne semihydrogenations are attractive approaches to alkenes, which are key building blocks for synthesis. With regards to the most atom economic reducing agent dihydrogen (H 2 ), only few catalysts for the challenging E ‐selective alkyne semihydrogenation have been disclosed, each with a unique substrate scope profile. Here, we show that a commercially available nickel catalyst facilitates the E ‐selective alkyne semihydrogenation of a wide variety of substituted internal alkynes. This results in a simple and broadly applicable overall protocol to stereoselectively access E ‐alkenes employing H 2 which could serve as a general method for synthesis.DFG, 352364740, Diwasserstoff-vermittelte nachhaltige BindungsknüpfungsreaktionenTU Berlin, Open-Access-Mittel - 201

Organocatalytic stereodivergent synthesis of β,β-disubstituted-α-aminoacids

In this work, we present an organocatalytic stereodivergent synthesis of β,β-disubstituted-α-aminoacids using arylidene azlactones as starting materials. The developed two step synthesis involves a sequential catalysis approach, in which two different catalysts act sequentially to control the absolute configuration of two different stereocenters. With an accurate selection of the catalysts absolute configuration it is possible to obtain all the stereoisomers of the product. The first synthetic step is a catalytic asymmetric transfer hydrogenation of the azlactone C=C double bond. A Jacobsen type thiourea and a Hantzsch ester were chosen as chiral catalyst and hydride donor, respectively. Different azlactones, Hantzsch esters and thioureas were synthetized and tested in the asymmetric transfer hydrogenation to achieve the best stereoselectivity. The second step involves a dynamic kinetic resolution on the reduced azlactone, through a nucleophilic addition to the carbonyl moiety promoted by a bifunctional chiral catalyst. A wide range of nucleophiles and organocatalysts were tested; the best results were reached with alcohols as nucleophiles and squaramide-based cinchona alkaloids as a chiral catalysts. With the optimized conditions two stereodivergent syntheses were then performed, enabling the selective obtainment of both diastereoisomeric product with high enantioselectivities

Enantioselective Organocatalytic Diels-Alder Trapping of Photochemically Generated Hydroxy-o-Quinodimethanes

The photoenolization/Diels-Alder strategy offers straightforward access to synthetically valuable benzannulated carbocyclic products. This historical light-triggered process has never before succumbed to efforts to develop an enantioselective catalytic approach. Herein, we demonstrate how asymmetric organocatalysis provides simple yet effective catalytic tools to intercept photochemically generated hydroxy-o-quinodimethanes with high stereoselectivity. We used a chiral organic catalyst, derived from natural cinchona alkaloids, to activate maleimides toward highly stereoselective Diels-Alder reactions. An unconventional mechanism of stereocontrol is operative, wherein the organocatalyst is actively involved in both the photochemical pathway, by leveraging the formation of the reactive photoenol, and the stereoselectivity-defining event

Combined experimental and computational investigations of rhodium-catalysed C-H functionalisation of pyrazoles with alkenes

Detailed experimental and computational studies have been carried out on the oxidative coupling of the alkenes C(2)H(3)Y (Y=CO(2)Me (a), Ph (b), C(O)Me (c)) with 3-aryl-5-R-pyrazoles (R=Me (1 a), Ph (1 b), CF(3) (1 c)) using a [Rh(MeCN)(3)Cp*][PF(6)](2)/Cu(OAc)(2)⋅H(2)O catalyst system. In the reaction of methyl acrylate with 1 a, up to five products (2 aa–6 aa) were formed, including the trans monovinyl product, either complexed within a novel Cu(I) dimer (2 aa) or as the free species (3 aa), and a divinyl species (6 aa); both 3 aa and 6 aa underwent cyclisation by an aza-Michael reaction to give fused heterocycles 4 aa and 5 aa, respectively. With styrene, only trans mono- and divinylation products were observed, whereas with methyl vinyl ketone, a stronger Michael acceptor, only cyclised oxidative coupling products were formed. Density functional theory calculations were performed to characterise the different migratory insertion and β-H transfer steps implicated in the reactions of 1 a with methyl acrylate and styrene. The calculations showed a clear kinetic preference for 2,1-insertion and the formation of trans vinyl products, consistent with the experimental results

Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

The asymmetric synthesis of new chiral gamma-chloro-alpha,beta-diaminocarboxylamide derivatives by highly diastereoselective Mannich-type reactions of N-(diphenylmethylene) glycinamides across chiral alpha-chloro-N-p-toluenesulfinylaldimines was developed. The resulting (S-S,2S,3S)-gamma-chloro-alpha,beta-diaminocarboxylamides were formed with the opposite enantiotopic face selectivity as compared to the (S-S,2R,3R)-gamma-chloro-alpha,beta-diaminocarboxyl esters obtained via Mannich-type addition of analogous N-(diphenylmethylene) glycine esters across a chiral alpha-chloro-N-p-toluenesulfinylaldimine. Selective deprotection under different acidic reaction conditions and ring closure of the gamma-chloro-alpha,beta-diaminocarboxylamides was optimized, which resulted in N-alpha-deprotected syn-gamma-chloro-alpha,beta-diaminocarboxylamides, N-sulfinyl-beta,gamma-aziridino-alpha-aminocarboxylamide derivatives, a trans-imidazolidine, and an N-alpha,N-beta-deprotected syn-gamma-chloro-alpha,beta-diaminocarboxylamide

Structural basis of the chiral selectivity of Pseudomonas cepacia lipase

To investigate the enantioselectivity of Pseudomonas cepacia lipase, inhibition studies were performed with SC- and RC-(RP,SP)-1,2-dialkylcarbamoylglycero-3-O-p-nitrophenyl alkylphosphonates of different alkyl chain lengths. P. cepacia lipase was most rapidly inactivated by RC-(RP,SP)-1,2-dioctylcarbamoylglycero-3-O-p-nitrophenyl octylphosphonate (RC-trioctyl) with an inactivation half-time of 75 min, while that for the SC-(RP,SP)-1,2-dioctylcarbamoylglycero-3-O-p-nitrophenyl octyl-phosphonate (SC-trioctyl) compound was 530 min. X-ray structures were obtained of P. cepacia lipase after reaction with RC-trioctyl to 0.29-nm resolution at pH 4 and covalently modified with RC-(RP,SP)-1,2-dibutylcarbamoylglycero-3-O-p-nitrophenyl butyl-phosphonate (RC-tributyl) to 0.175-nm resolution at pH 8.5. The three-dimensional structures reveal that both triacylglycerol analogues had reacted with the active-site Ser87, forming a covalent complex. The bound phosphorus atom shows the same chirality (SP) in both complexes despite the use of a racemic (RP,SP) mixture at the phosphorus atom of the triacylglycerol analogues. In the structure of RC-tributyl-complexed P. cepacia lipase, the diacylglycerol moiety has been lost due to an aging reaction, and only the butyl phosphonate remains visible in the electron density. In the RC-trioctyl complex the complete inhibitor is clearly defined; it adopts a bent tuning fork conformation. Unambiguously, four binding pockets for the triacylglycerol could be detected: an oxyanion hole and three pockets which accommodate the sn-1, sn-2, and sn-3 fatty acid chains. Van der Waals’ interactions are the main forces that keep the radyl groups of the triacylglycerol analogue in position and, in addition, a hydrogen bond to the carbonyl oxygen of the sn-2 chain contributes to fixing the position of the inhibitor.