Role of Configuration at C6 in Catalytic Activity of l-Proline-Derived Bifunctional Organocatalysts

Abstract

l-Proline-derived chiral bifunctional (thio)urea organocatalysts epi-PTU and epi-PU were newly synthesized, and their catalytic performances were compared with their C6 epimeric catalysts PTU and PU in various Michael reactions of nitrostyrene in terms of reactivities and stereoselectivities. The experimental results indicate that a proper relative stereochemistry at C2 and C6 in l-proline-derived bifunctional organocatalysts is important for successful catalysis and that catalysts (PTU and PU) with the 2S,6R configuration are much more efficient.

Catalytically Active Imine-based Covalent Organic Frameworks for Detoxification of Nerve Agent Simulants in Aqueous Media

“…In order to address this decrease of pore accessibility in the COF after the methylation reaction, we have carried out an alternative synthesis of [( S )-PyMe] 0.5 -TPB-DMTP-COF by using a one-step room-temperature post-synthetic functionalization of [HC≡C] 0.5 -TPB-DMTP-COF . With this aim, we have synthesized ( S )-2-(azidomethyl)-1-methylpyrrolidine ( 2 , Scheme 1) [39], in which the pyrrolidine moiety was already methylated. Subsequent copper-catalyzed Huisgen’s 1,3-dipolar cycloaddition reaction of 2 with [HC≡C] 0.5 -TPB-DMTP-COF afforded [( S )-PyMe] 0.5 -TPB-DMTP-COF .…”

“…The following reagents were commercially available and were used as received: 2,5-dimethoxyterephthaldehyde ( DMTA ), CuI, o -DCB, n -butanol, NaN 3 and N , N -diisopropylethylamine (DIPEA). 2,5-dihydroxyterephthaldehyde ( DHTA ) [25], 2,5-bis(prop-2-in-1-yloxy)terephthaldehyde ( BPTA ) [25], 1,3,5-tris-(4-aminophenyl)benzene ( TAPB ) [37], [HC≡C] 0.5 -TPB-DMTP-COF (TPB, triphenylbenzene; DMTP, dimethoxyterephthaldehyde) [25], [( S )-Py] 0.5 -TPB-DMTP-COF [25], ( S )-2-(azidomethyl)pyrrolidine ( 1 ) [38], and ( S )-2-(azidomethyl)-1-methylpyrrolidine ( 2 ) [39] were prepared according to reported procedures.…”

Stereoselective Aldol and Conjugate Addition Reactions Mediated by Proline‐Based Catalysts and Its Analogues: A Concise Review

“…Subsequently, Ryu et al ., [66] compared the proline‐derived bifunctional (thio)urea catalysts 81 a , 81 b , epi ‐ 81 a , epi ‐ 81 b , H ‐ 81 a (C6‐unsubstituted), and Ph‐ 81 a (C6‐disubstituted with phenyl groups) in conjugate addition reaction of nitrostyrenes 79 to diketones 83 and noted the crucial change in stereoselectivity by changing the configuration at C6 was altered relative to C2 stereochemistry. ( 2S , 6R )‐Type catalysts 81 a and 81 b worked much better than their epi‐ form ( 2S , 6S ).…”

Bioinspired Synthesis of Chiral 3,4-Dihydropyranones via S-to-O Acyl-Transfer Reactions

“…Recently, our group has developed highly efficient asymmetric Michael addition reactions of nitroolefins with dithiomalonates catalyzed by proline-derived urea catalyst PU . Enlightened by these findings, we became interested in whether dithiomalonates (DTMs) 1 can be interconnected with β,γ-unsaturated α-keto esters 2 through asymmetric Michael addition to form δ-ketothioester intermediates 3 that then undergo biomimetic lactonization to afford chiral 3,4-dihydropyranones (Scheme , eq 2).…”

“…The developed one-pot reaction was further optimized. At first, bifunctional organocatalysts PTU , PU , epi - PU , and PSQA were screened (Table , entries 1–4); among these, PU provided the best result, affording product 5a in 89% yield with 89% ee (Table , entry 2). Among the solvents tested (MTBE, CH 2 Cl 2 , toluene, and PhCl), toluene was the most suitable (Table , entries 5–7).…”