885696-47-9

Upstream product

• 155396-71-7 tert-butyl N-(phenyl(phenylsulfonyl)methyl)carbamate 
• 67-56-1 methanol 
• 150884-50-7 benzaldehyde N-boc imine 
• 108-59-8 malonic acid dimethyl ester 
• 926913-48-6 malonic acid bis(4-methoxyphenyl) ester 
• 271600-36-3 N-[phenyl(toluene-4-sulfonyl)methyl]tert-butoxycarboxyamide 
• 177896-09-2 tert-butyl benzylidenecarbamate 

Downstream Products

• 83649-47-2 (S)-(-)-β-Phenyl-β-alanine hydrochloride 
• 103365-47-5 (S)-3-(tert-butoxycarbonylamino)-3-phenylpropanoic acid 

Relevant academic research and scientific papers

Organocatalysts Fold to Generate an Active Site Pocket for the Mannich Reaction

Catalysts containing urea, thiourea, and tertiary amine groups fold into a three-dimensional organized structure in solution both in the absence as well as in the presence of substrates or substrate analogues, as indicated by solution NMR and computational studies. These foldamer catalysts promote Mannich reactions with both aliphatic and aromatic imines and malonate esters. Hammett plot and secondary kinetic isotope effects provide evidence for the C-C bond forming event as the turnover-limiting step of the Mannich reaction. Computational studies suggest two viable pathways for the C-C bond formation step, differing in the activation modes of the malonate and imine substrates. The results show that the foldamer catalysts may promote C-C bond formation with an aliphatic substrate bearing a cyclohexyl group by enhanced binding of the substrates by dispersion interactions, but these interactions are largely absent with a simpler catalyst. Additional control experiments demonstrate the ability of simple thiourea catalysts to promote competing side reactions with aliphatic substrates, such as reversible covalent binding of the thiourea sulfur to the imine which deactivates the catalyst, and imine to enamine isomerization reactions. In foldamer catalysts, the nucleophilicity of sulfur is reduced, which prevents catalyst deactivation. The results indicate that the improved catalytic performance of foldamer catalysts in Mannich reactions may not be due to cooperative effects of intramolecular hydrogen bonds but simply due to the presence of the folded structure that provides an active site pocket, accommodating the substrate and at the same time impeding undesirable side reactions.

Direct Catalytic Asymmetric Mannich Reaction with Dithiomalonates as Excellent Mannich Donors: Organocatalytic Synthesis of (R)-Sitagliptin

In this study, dithiomalonates (DTMs) were demonstrated to be exceptionally efficient Mannich donors in terms of reactivity and stereoselectivity in cinchona-based-squaramide-catalyzed enantioselective Mannich reactions of diverse imines or α-amidosulfones as imine surrogates. Owing to the superior reactivity of DTMs as compared to conventional malonates, the catalyst loading could be reduced to 0.1 mol % without the erosion of enantioselectivity (up to 99 % ee). Furthermore, by the use of a DTM, even some highly challenging primary alkyl α-amidosulfones were smoothly converted into the desired adducts with excellent enantioselectivity (up to 97 % ee), whereas the use of a malonate or monothiomalonate resulted in no reaction under identical conditions. The synthetic utility of the chiral Mannich adducts obtained from primary alkyl substrates was highlighted by the organocatalytic, coupling-reagent-free synthesis of the antidiabetic drug (?)-(R)-sitagliptin.

Sequential enantiodivergent organocatalysis: Reversibility in enantioswitching controlled by a conformationally flexible guanidine/bisthiourea organocatalyst

Here we describe our studies on solvent-dependent enantiodivergent Mannich-type reactions utilizing conformationally flexible guanidine/bisthiourea organocatalyst (S,S)-1. Our mechanistic investigations revealed that the stereo-determining steps in both t

Highly efficient catalytic enantioselective mannich reaction of malonates with N-tert-butoxycarbonyl imines by using Yb(OTf)3/pybox catalysts at room temperature

Go Mannich! A highly efficient and enantioselective method for the direct asymmetric reaction of dibenzyl malonate with N-tert-butoxycarbonyl aldimines in the presence of Yb(OTf)3 and iPr-pybox complexes is described (see scheme; pybox=pyridine

Cooperative assistance in bifunctional organocatalysis: Enantioselective mannich reactions with aliphatic and aromatic imines

Hold them tight: Guided by X-ray structures, bifunctional thiourea catalysts containing an activating intramolecular hydrogen bond were redesigned. The new catalysts were used to effect a highly enantioselective Mannich reaction between malonates and both aliphatic and aromatic imines (see scheme; Boc=tert-butoxycarbonyl).

OPTICALLY ACTIVE DINICKEL COMPLEX AND METHOD FOR PRODUCING OPTICALLY ACTIVE AMINE USING THE OPTICALLY ACTIVE DINICKEL COMPLEX AS CATALYST

There is provided a novel optically active dinickel complex and/or a production method of an optically active amine by an asymmetric Mannich reaction using the dinickel complex as a catalyst. An optically active dinickel complex of Formula (I) or Formula

Asymmetric Mannich reaction of malonates with imines catalyzed by a chiral calcium complex

(Chemical Equation Presented) Achiral calcium complex was found to be effective for the Mannich reactions of malonates with N-Boc imines. The desired adducts were obtained in excellent yields (up to 95%) with moderate to good enantioselectivities (up to 77% ee).

Magnesium(II)-binaphtholate as a practical chiral catalyst for the enantioselective direct mannich-type reaction with malonates

(Equation Presented). A highly enantioselective direct Mannich-type reaction of aldimines with dialkyl malonates was developed with the use of a Mg(II)-BINOLate salt, which was designed as a cooperative acid-base catalyst that can activate both aldimines and malonates. Optically active β-aminoesters and α-halo-β-aminoesters could be synthesized in high yields and with high enantioselectivities. This inexpensive and practical Mg(II)-BINOLate salt could be used in gram-scale catalysis.

Solvent-dependent enantiodivergent mannich-type reaction: Utilizing a conformationally flexible guanidine/bisthiourea organocatalyst

Flex control: Malonate and tert-butoxycarbonyl (Boc)-protected imines react in the presence of the flexible catalyst 1 to furnish the S or the R adduct depending upon the solvent used. Kinetic analyses in this enantiodivergent organocatalysis show that en

Asymmetric Mannich-type reaction of aromatic α-amido sulfone with malonate using guanidine-thiourea bifunctional organocatalyst

Asymmetric Mannich-type reaction of aromatic α-amido sulfone with malonate, catalyzed by a guanidine-thiourea bifunctional organocatalyst, affords β-amino acid derivatives in high yield with good to excellent enantioselectivity. Georg Thieme Verlag Stuttg