Protocol for the preparation of primary amine-containing catalysts on the resin.

In light of escalating sustainability concerns, addressing catalyst usage and waste production challenges becomes crucial. Here, we introduce a robust protocol for crafting recyclable polystyrene-supported primary amines, providing a promising solution via heterogeneous catalysis. The protocol details immobilization onto insoluble resins through ester, ether, or amide bonds, facilitating the synthesis of heterogeneous catalysts with diverse organic components. For complete details on the use and execution of this protocol, please refer to Kanger et al.1.

Primary amines as heterogeneous catalysts in an enantioselective [2,3]-Wittig rearrangement reaction.

A series of heterogeneous catalysts anchored to different polystyrene-based supports has been prepared and applied in an asymmetric [2,3]-Wittig rearrangement reaction of cyclohexanone derivatives. Among them, primary amino acid-derived (aminomethylated)polystyrene-supported catalysts showed excellent reactivity leading to the formation of rearranged products in good enantioselectivities of both diastereomers. Reusability issues connected to the deactivation of the catalyst were proved to be dependent on the end-capping strategy chosen for the blocking of the unreacted active sites of the resin. This issue of end-capping has not previously been in focus. Using bulkier pivaloyl end-capping moiety, we were able to recycle the catalyst in six consecutive cycles with only marginal deceleration of the reaction. Moreover, the epimerization of the product that occurred while conducting a rearrangement reaction in the presence of a homogeneous catalyst was almost fully eliminated by switching the catalytic system to heterogeneous.

Multifunctional Catalysts in the Asymmetric Mannich Reaction of Malononitrile with N-Phosphinoylimines: Coactivation by Halogen Bonding versus Hydrogen Bonding.

A multifunctional (noncovalent) catalyst containing halogen-bond donor, hydrogen-bond donor, and Lewis basic sites was developed and applied in an enantioselective Mannich reaction between malononitrile and diphenylphosphinoyl-protected aldimine affording products in high yields (up to 98%) and moderate to high enantiomeric purities (ee up to 89%). Typically, noncovalent catalysts rely on several weak interactions to activate the substrate, with one or two of these giving the most notable contribution to activation. In this instance, instead of the initially proposed coactivation by halogen bonding, it was revealed that hydrogen bonding plays a key role in determining the enantioselectivity.

Asymmetric Chemoenzymatic One-Pot Synthesis of α-Hydroxy Half-Esters.

A new chemoenzymatic one-pot strategy has been developed for the synthesis of α-hydroxy half-esters containing consecutive quaternary and tertiary stereocenters using asymmetric cascade catalysis. In this study, an asymmetric Ca2+-catalyzed [2,3]-Wittig rearrangement reaction was proven to be suitable for a combination with porcine liver esterase-mediated hydrolysis resulting in the enhanced enantiomeric purity of the obtained products in a one-pot synthesis compared to the stepwise method.

Enantioselective Michael addition to vinyl phosphonates via hydrogen bond-enhanced halogen bond catalysis.

An asymmetric Michael addition of malononitrile to vinyl phosphonates was accomplished by hydrogen bond-enhanced bifunctional halogen bond (XB) catalysis. NMR titration experiments were used to demonstrate that halogen bonding, with the support of hydrogen-bonding, played a key role in the activation of the Michael acceptors through the phosphonate group. This is the first example of the use of XBs for the activation of organophosphorus compounds in synthesis. In addition, the iodo-perfluorophenyl group proved to be a better directing unit than different iodo- and nitro-substituted phenyl groups. The developed approach afforded products with up to excellent yields and diastereoselectivities and up to good enantioselectivities.

Enantioselective Organocatalytic Michael Addition to Unsaturated Indolyl Ketones.

An efficient enantioselective organocatalytic method for the synthesis of N-alkylated indoles with α-branched alkyl substituents from the corresponding unsaturated indolyl ketones via a Michael addition has been developed. The resulting products were obtained in high enantioselectivities and in good yields. Various nucleophiles (nitroalkanes, malononitrile, malonic esters) can be used. The substitution pattern of the indole ring had no significant impact on the reaction outcome. Both electron-withdrawing and electron-donating substituents in any position of the heteroaromatic ring were well-tolerated.