Asymmetric Synthesis of Spirocyclopentane Oxindoles Containing Four Consecutive Stereocenters and Quaternary ?-Nitro Esters via Organocatalytic Enantioselective Michael-Michael Cascade Reactions.
ABSTRACT: An enantioselective domino Michael-Michael reaction of nitroolefins and 2-nitro-3-arylacrylates has been established, which provided a series of spirocyclopentane oxindoles with four consecutive stereocenters including quaternary ?-nitro esters with good yields (up to 73%) and excellent enantioselectivities (up to 97% ee). The reaction was realized and optimized with the aid of a chiral squaramide-amine catalyst. The structures of 11 products were confirmed by single-crystal X-ray diffraction analysis.
Project description:A low loading of a quinine-derived squaramide efficiently catalyzes the triple-domino Michael/aza-Henry/cyclization reaction between 1,3-dicarbonyl compounds, ?-nitroolefins, and aldimines to provide tetrahydropyridines bearing three contiguous stereogenic centers in good yields, excellent enantiomeric excesses, and up to high diastereomeric ratios.
Project description:A highly stereoselective one-pot procedure involving an enantioselective Michael addition promoted by low loading of an amino-squaramide catalyst followed by an achiral base catalyzed domino Michael-Knoevenagel-type 1,2-addition sequence provides efficient access to fully substituted cyclohexanes bearing five contiguous stereogenic centers in good yields (68-86%) and excellent stereoselectivities (>30?:?1 dr and 96-99% ee).
Project description:A highly diastereo- and enantioselective domino Michael/Henry reaction of 1-acetylindolin-3-ones with o-formyl-(E)-?-nitrostyrenes catalyzed by low loading of a quinine-derived amine-squaramide provides the corresponding indolin-3-one derivatives bearing four adjacent stereogenic centers in good to high yields and with excellent stereoselectivities.
Project description:We reported the first example of organocatalytic Michael addition of unprotected 3-prochiral oxindoles 1 to 1,4-naphthoquinone. Quinidine derivative (DHQD)(2)PYR was found to be able to catalyze this reaction in up to 83% ee, with moderate to excellent yields. This method could be used for the synthesis of enantioenriched 3,3-diaryloxindoles, and the catalytic synthesis of which was unprecedented.
Project description:The new hybrid-type squaramide-fused amino alcohol containing both a Brønsted basic site and hydrogen-bonding sites in the molecule showed a high catalytic activity as an organocatalyst in the enantioselective domino Michael addition/cyclization reaction of oxoindolines with cyclic 1,3-diketones to afford the chiral spiro-conjugated oxindoles featuring 2-aminopyrans fusing with carbo-heterocyclic ring systems with excellent chemical yields (up to 98%) and enantioselectivities (up to 95% ee). The obtained chiral spiro-conjugated 2-aminopyrans bearing quaternary stereogenic carbon center could be used as synthetic precursors for several natural products that have a broad spectrum of fascinating biological activities.
Project description:We have synthesized novel chiral polymers containing a cinchona-based squaramide in the main chain. We designed a novel cinchona squaramide dimer that contains two cinchona squaramide units connected by diamines. The olefinic double bonds in the cinchona squaramide dimer were used for Mizoroki-Heck (MH) polymerization with aromatic diiodides. The MH polymerization of the cinchona squaramide dimer and aromatic diiodide proceeded well to give the corresponding chiral polymers in good yields. The catalytic activity of the chiral polymers was investigated for asymmetric Michael addition reactions. The effect of the squaramide structure of the polymeric catalyst on the catalytic performance is discussed in detail. We have surveyed the influence of the chiral polymer structure on the catalytic activity and enantioselectivity of the asymmetric reaction. The asymmetric Michael addition of ?-ketoesters to nitroolefins was successfully catalyzed by polymeric cinchona squaramide organocatalysts to obtain the corresponding Michael adducts in good yields with excellent enantio- and diastereoselectivities. The polymeric catalysts were insoluble in commonly used organic solvents and easily recovered from the reaction mixture and reused several times without the loss of catalytic activity.
Project description:Organocatalytic reactions of 3-olefinic oxindoles and pentane-1,5-dial were investigated to provide access to substituted spirocyclohexane oxindoles via Michael/Aldol cascade reactions. Of particular interest, we have examined the stereochemical outcome of electron withdrawing and electron-donating groups on the oxindole ring nitrogen. Interestingly, we have observed that the N-protecting group on the oxindole has critical effect on aldol ring closure leading to ultimate stereochemical outcome of the hydroxyl center. The overall process is quite efficient and afforded products with multiple stereocenters in high yields and excellent enantioselectivities (>99% ee).
Project description:An efficient, highly stereoselective asymmetric synthesis of fully functionalized cyclopentanes bearing an oxindole moiety and several other functional groups in one pot has been developed. Key step is an organocatalytic triple Michael domino reaction forming three C-C bonds and six stereocenters, including a quaternary one. Starting from equimolar amounts of simple substrates, a high molecular complexity can be reached after a Wittig olefination in one pot. The new protocol can easily be scaled up to gram amounts.
Project description:An NHC-catalyzed Michael/Michael/esterification domino reaction via homoenolate/enolate intermediates for the asymmetric synthesis of tetrasubstituted cyclopentanes bearing four contiguous stereocenters is described. A variety of ?,?-unsaturated aldehydes and 2-nitroallylic acetates react well with good domino yields and high stereoselectivities.
Project description:We disclose a novel high yielding and highly enantioselective chiral calcium VAPOL phosphate-catalyzed chlorination of 3-substituted oxindoles with N-chlorosuccinimide (NCS). The reaction conditions are also shown to be effective for the catalytic enantioselective Michael addition of 3-aryloxindoles to methyl vinyl ketone.