Bifunctional Ion Pair Catalysts from Chiral α‐Amino Acids

Abstract

Asymmetric ion pair catalysis presents a powerful strategy for the construction of chiral molecules. However, the ion‐pair interactions are weakly directional and result in difficultly controlling the conformational constraint for high stereo‐ inductions. Based on the hydrogen bonding interactions, we have successfully designed and synthesized a new family of bifunctional ion pair catalysts derived from chiral amino acids via simple operations. With these chiral ammonium salts and phosphonium salts in hand, the enantioselective construction of C—C and C—X bonds was realized in our lab.

Study of Ground State Interactions of Enantiopure Chiral Quaternary Ammonium Salts and Amides, Nitroalkanes, Nitroalkenes, Esters, Heterocycles, Ketones and Fluoroamides

“…an hydroxyl, had a dichotomic effect on the mechanism of catalysis, [10,11,47] independently of the ammonium being either inherently chiral with one of the tetrahedral faces open for ion pairing [48–50] or being achiral but residing in a chiral environment [51–54] . Hence, chiral bifunctional ammonium salts have emerged as a powerful strategy to control the enantioselectivity in those cases where classical “monofunctional” ammoniums failed [55–57] . Noteworthy, the majority of such bifunctional ammonium salts contain a free OH‐group as the second coordination site [58–65] .…”

“…[ 51 , 52 , 53 , 54 ] Hence, chiral bifunctional ammonium salts have emerged as a powerful strategy to control the enantioselectivity in those cases where classical “monofunctional” ammoniums failed. [ 55 , 56 , 57 ] Noteworthy, the majority of such bifunctional ammonium salts contain a free OH‐group as the second coordination site. [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ] However, over the last five years, several groups have started to systematically investigate the introduction of alternative H‐bonding donors, i.e.…”

Enantiodivergent Kinetic Resolution of 1,1′‐Biaryl‐2,2′‐Diols and Amino Alcohols by Dipeptide‐Phosphonium Salt Catalysis Inspired by the Atherton–Todd Reaction

“…[13,14] Particularly,t he classical Atherton-Todd-type reaction, involving in situ halogenation of P(O)-H substrates with tetrachloromethane/chloroform (CCl 4 /CHCl 3 )t og enerate the key intermediates of phosphoryl chlorides (A), has been well studied in the past years (Figure 1b,t he former). [13] However,s urprisingly,t he catalytic asymmetric variant of the A-T reaction has never been developed so far;a nd thus, ahighly efficient and generally practical catalytic system that can solve the principal stereoinduction issue of the A-T reaction remains elusive.I nc onnection to our disclosure of dipeptide-based phosphonium salts and their applications in asymmetric synthesis, [15,16] we envisioned that such bifunctional phosphonium halides may differentiate between the insitu-generated P-species having either phosphoryl chlorides (A)o rp hosphoric anhydrides (B)a sm ajor intermediates which can be further precisely identified by the matched chiral phosphonium catalysts,t hus leading to the enantiodivergent phosphorylation reaction (Figure 1b,t he latter). Whereas the idea of obtaining both axially chiral biaryl enantioisomers by chiral phosphonium salt catalysts with single configuration was very appealing to us,w ew ere mindful that the catalytic enantioselective cross-coupling between 1,1'-biaryl diols or amino alcohols and P(O)-H compounds is extremely challenging and has never been utilized in asymmetric resolution processes.…”

Asymmetric Synthesis of 3-Phenyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-3-carbonitriles Catalyzed by Phase-Transfer Catalyst Derived from tert-Leucine

“…In a large number of literature reports, many phase-transfer catalysts derived from chiral natural products have good universality. 1 Organic chemists hope to develop a series of chiral phase-transfer catalysts based on green and inexpensive chiral frameworks to investigate a wide range of asymmetric reactions. 2 In recent years, amino acid derived phasetransfer catalysts have shown better activity and better enantioselectivity in Strecker reaction, 3 Rauhut-Currier reaction, 4 Mannich reaction, 5 and addition reaction.…”