Enantioselective Construction of Functionalized Thiochromans via Squaramide‐Catalyzed Asymmetric Cascade Sulfa‐Michael/Michael Addition

An efficient enantioselective cascade sulfa‐Michael/Michael addition reaction of trans‐3‐(2‐mercaptophenyl)‐2‐propenoic acid ethyl ester with nitroalkenes catalyzed by a chiral squaramide catalyst was disclosed. This cascade reaction afforded thiochroman derivatives with three contiguous stereocenters in high yields (up to 94%), excellent diastereoselectivities (up to >25:1 dr) and enantioselectivities (up to 99% ee).     

Enantioselective Synthesis of N‐Phenyl‐dihydropyrano[2,3‐c]pyrazoles via Cascade Michael Addition/Thorpe‐Ziegler Type Cyclization Catalyzed by a Chiral Squaramide

Enantioselective synthesis of biologically active dihydropyrano[2,3‐c]pyrazoles has been achieved through a squaramide‐catalysed Michael addition/Thorpe‐Ziegler type cyclization cascade reaction between arylidenepyrazolones and malononitrile. A series of optically active dihydropyano[2,3‐c]pyrazoles were obtained in excellent yields (up to 99%) and moderate to good enantioselectivities (up to 79% ee) under mild reaction conditions.     

Asymmetric Organocatalytic Domino Michael/Aldol Reactions: Enantioselective Synthesis of Chiral Cycloheptanones,Tetrahydrochromenones, and Polyfunctionalized Bicyclo[3.2.1]octanes

C′mon 1,2‐dione : A new diastereo‐ and enantioselective Lewis base catalyzed domino Michael/aldol reaction converts α,β‐unsaturated aldehydes and 1,2‐diones into chiral bicyclo[3.2.1]octane‐6‐carbaldehydes. The products are produced in good to excellent enantioselectivities (90–98 % ee) and can be transformed into bicyclic diols and triols. Additionally, a retro‐aldol cyclization provides access to valuable tetrahydrochromenones (see scheme).

     

Highly E‐Selective and Enantioselective Michael Addition to Electron‐Deficient Internal Alkynes Under Chiral Iminophosphorane Catalysis

A highly E‐selective and enantioselective conjugate addition of 2‐benzyloxythiazol‐5(4H)‐ones to β‐substituted alkynyl N‐acyl pyrazoles is achieved under the catalysis of a P‐spiro chiral iminophosphorane. Simultaneous control of the newly generated central chirality and olefin geometry is possible with a wide array of the alkynyl Michael acceptors possessing different aromatic and aliphatic β‐substituents, as well as the various α‐amino acid‐derived thiazolone nucleophiles. This protocol provides access to structurally diverse, optically active α‐amino acids bearing a geometrically defined trisubstituted olefinic component at the α‐position.     

Polymer‐Supported Enantioselective Bifunctional Catalysts for Nitro‐Michael Addition of Ketones and Aldehydes

Introduction of an L ‐amino acid as a spacer and a urea‐forming moiety in a polymer‐supported bifunctional urea–primary amine catalyst, based on (1R, 2R)‐(+)‐1,2‐diphenylethylenediamine, significantly improves the catalyst’s activity and stereoselectivity in the asymmetric addition of ketones and aldehydes to nitroolefins. Yields and enantioselectivities, unprecedented for immobilized catalysts, were obtained with such challenging donors as acetone, cyclopentanone, and α,α‐disubstituted aldehydes, which usually perform inadequately in this reaction (particularly when a secondary‐amine‐based catalyst is used). Remarkably, though in the examined catalysts the D ‐amino acids as spacers were significantly inferior to the L isomers, for the chosen configuration of the diamine (match–mismatch pairs) the size of the side chain of the amino acid hardly influenced the enantioselectivity of the catalyst. These results, combined with the reactivity profile of the catalysts with substrates bearing two electron‐withdrawing groups and the behavior of the catalysts’ analogues based on tertiary (rather than primary) amine, suggest an enamine‐involving addition mechanism and a particular ordered C? C bond‐forming transition state as being responsible for the catalytic reactions with high enantioselectivity.     

Nitrile Containing Bisphosphonates: Easy Synthesis through Metal Catalyzed Michael Addition

New nitrile‐containing gem‐bisphosphonates as drug candidates for the contrast of osteoporosis are presented, their synthesis being based on the metal catalyzed Michael conjugate addition of trimethylsilyl cyanide to unsaturated bisphosphonate precursors. Zn(OT f)₂ turned out to be the most efficient metal catalyst for the reaction enabling the formation of β‐nitrile substituted bisphosphonates in good yields. The corresponding final bisphosphonic acids bearing the nitrile moiety were obtained by deprotection of the ethyl ester moiety. They showed aggregation properties in water due to their amphiphilic nature and will be evaluated in order to assess their biological anti‐osteoclast activity.     

Organocatalyzed Cascade Aza‐Michael/Michael Addition for the Asymmetric Construction of Highly Functionalized Spiropyrazolone Tetrahydroquinolines

An organocatalyzed diastereo‐ and enantioselective cascade aza‐Michael/Michael addition of 2‐tosylaminoenones to unsaturated pyrazolones has been developed to afford novel chiral spiropyrazolone tetrahydroquinolines containing three contiguous stereocenters. This cascade reaction proceeded well with 2 mol % chiral bifunctional tertiary amine squaramide catalyst to give the desired products in excellent yields (up to 99 %) with excellent diastereoselectivity (up to >25:1 diastereomeric ratio) and high enantioselectivity (up to 91 % enantiomeric excess).     

Novel Polycarbonate Copolymer as Organocatalyst for Aldol and Michael Reaction

A new polymeric organocatalyst is prepared by free radical copolymerization of allyl diglycol carbonate (ADC) and Boc-protected allyl prolinate and evaluated as a chiral catalyst for aldol and Michael reaction.     

Asymmetric Organocatalytic Addition Reactions of Maleimides: A Promising Approach Towards the Synthesis of Chiral Succinimide Derivatives

Recent progress in asymmetric organocatalysis has led to the development of several asymmetric transformations that employ various substrates. Among these substrates, maleimides have emerged as excellent Michael acceptors, dienophiles, and dipolarophiles. In this Focus Review we highlight the advances in the asymmetric synthesis of succinimide derivatives through asymmetric organocatalytic addition reactions of maleimides.     

One-Pot Tandem Michael Addition/Enantioselective Conia-Ene Cyclization Mediated by Chiral Iron(III)/Silver(I) Cooperative Catalysis

The first one-pot tandem Michael addition/enantioselective Conia-ene cyclization of N-protected prop-2-yn-1-amines with 2-methylene-3-oxoalkanoates promoted by chiral iron(III)/silver(I) cooperative catalysts has been developed. Alkyl 4-methylenepyrrolidine-3-acyl-3-carboxylates, which can be transformed into β-proline derivatives, are obtained in high yield with high enantioselectivity.