Domino Michael/Michael reaction catalyzed by switchable modularly designed organocatalysts

Both the enamine and iminium catalysis of the MDOs are switchable. Upon switching on both catalytic modes, the MDOs were used for catalyzing the domino Michael/Michael reaction between (E)-7-aryl-7-oxohept-5-enals and trans-cinnamaldehydes.

Highly diastereoselective cascade [5 + 1] double Michael reaction, a route for the synthesis of spiro(thio)oxindoles

The first diastereoselective synthesis of spirothiooxindoles is reported via the Michael reaction between thiooxindoles and dibenzalacetones. The reaction was conducted without any catalyst or additive under green conditions, i.e., ethanol as the solvent and at room temperature. In addition, the described robust method benefits from scalability, simple work-up, and column chromatography-free purification. This work demonstrates the art of governing regio- and stereoselectivity, which has been discussed in the light of Density Functional Theory calculations. Our method represents the first synthesis of spiro[cyclohexanone-thiooxindoles] with the relative configuration of the aryl moieties at the cyclohexanone ring as cis. The obtained cis-spirothiooxindoles, can be used to afford cis-spirooxindoles, which their synthesis had not been explored before. According to our molecular docking studies, cis-spirooxindoles demonstrate higher binding affinities than corresponding trans-spirooxindoles for the OPRT domain of the Leishmania donovani uridine 5′-monophosphate synthase (LdUMPS). Thus, the reported method may eventually be utilized to develop new hit compounds for leishmaniasis treatment.

The Use of Chiro-Inositols in Asymmetric Synthesis

<p>D- and L- chiro-inositols are readily and inexpensively available as their O-methyl ethers pinitol and quebrachitol. To date the use of the choro-inositols in synthesis has not been exploited as fully as that of the more common isomer myo-inositol. The chiro-inositols were protected as either the di-isopropylidene or the di-cyclohexylidene systems to give them more steric bulk and were subsequently evaluated in the three areas of asymmetric synthesis: as chiral reagents, as chiral auxiliaries, as chiral ligands. Outside of these areas was the successful application of methodology for the mono esterification of C-2 symmetric diols to these inositol systems. This allowed a series of molecules to be generated that proved useful in the areas outlined above. For the use of chiro-inositols as chiral reagents, two reagents were investigated. The first was a hydroboration reagent similar to pinenyl borane. The second was the generation of a strained silacycle for use as a reagent in the enantioselective allylation of aldehydes. In the area of chiral auxiliaries, these inositols were successfully used to give selectivity in the Michael reaction. Unfortunately this success was not repeatable in the aldol reaction. Investigations into the development of chiral ligands were unsuccessful in that we were unable to synthesize either a diamine or an amino alcohol from this system. A diol and an amino ether were trialed in asymmetric reactions but failed to provide any catalytic effect. This section of the project did lead to some interesting chemistry and a better understanding of this system that can be applied to future work.</p>

The Use of Chiro-Inositols in Asymmetric Synthesis

<p>D- and L- chiro-inositols are readily and inexpensively available as their O-methyl ethers pinitol and quebrachitol. To date the use of the choro-inositols in synthesis has not been exploited as fully as that of the more common isomer myo-inositol. The chiro-inositols were protected as either the di-isopropylidene or the di-cyclohexylidene systems to give them more steric bulk and were subsequently evaluated in the three areas of asymmetric synthesis: as chiral reagents, as chiral auxiliaries, as chiral ligands. Outside of these areas was the successful application of methodology for the mono esterification of C-2 symmetric diols to these inositol systems. This allowed a series of molecules to be generated that proved useful in the areas outlined above. For the use of chiro-inositols as chiral reagents, two reagents were investigated. The first was a hydroboration reagent similar to pinenyl borane. The second was the generation of a strained silacycle for use as a reagent in the enantioselective allylation of aldehydes. In the area of chiral auxiliaries, these inositols were successfully used to give selectivity in the Michael reaction. Unfortunately this success was not repeatable in the aldol reaction. Investigations into the development of chiral ligands were unsuccessful in that we were unable to synthesize either a diamine or an amino alcohol from this system. A diol and an amino ether were trialed in asymmetric reactions but failed to provide any catalytic effect. This section of the project did lead to some interesting chemistry and a better understanding of this system that can be applied to future work.</p>

Reactions of 1-trifluoromethyl-propyne 1-iminium salts with nitroanilines: synthesis of 4-CF3-nitroquinolines and 1,2,3-trisubstituted-5-CF3-pyrroles

A variety of 4-CF3-quinolines bearing an aryl (or cyclopropyl, tert-butyl, trimethylsilyl) group at C-2 and a nitro group at ring position 6, 7 or 8 have been prepared in good to high yields from 3-substituted 1-CF3-prop-2-yne 1-iminium triflate salts and o-, m- or p-nitroaniline. These reactions include an aza-Michael reaction at room temperature followed by an intramolecular electrophilic aromatic substitution step, which requires additional thermal activation in most cases. In contrast, the conjugate addition of 2,4-dinitroanilines at the acetylenic iminium ions proceeds much more slowly and some of the adducts can be converted thermally into 2-(2,4-dinitrophenyl)-5-CF3-pyrroles. Analogously, 2-(4-pyridyl)-5-CF3-pyrroles were obtained from 3-aryl-1-CF3-propyne iminium salts and 4-aminopyridinium triflate. A novel variation of the Truce-Smiles rearrangement is probably involved in the formation of these pyrroles.

Progress in the Synthesis of Heterocyclic Compounds Catalyzed by Lipases

Heterocyclic compounds are representative of a larger class of organic compounds, and worthy of attention for many reasons, chief of which is the participation of heterocyclic scaffolds in the skeleton structure of many drugs. Lipases are enzymes with catalytic versatility, and play a key role in catalyzing the reaction of carbon–carbon bond formation, allowing the production of different compounds. This article reviewed the lipase-catalyzed aldol reaction, Knoevenagel reaction, Michael reaction, Mannich reaction, etc., in the synthesis of several classes of heterocyclic compounds with important physiological and pharmacological activities, and also prospected the research focus in lipase-catalyzed chemistry transformations in the future.

Recent Advance of Domino Michael Reaction in Natural Product Synthesis

Recent advances in the total syntheses of cyclic natural products and related compounds from 2005 to 2021, which employ domino Michael reactions as key steps, have been reviewed, focusing mainly on the domino Michael reactions catalyzed by organocatalysts.