Exploiting C3-symmetry in the dynamic coordination of a chiral trisoxazoline to copper(ii): improved enantioselectivity, and catalyst stability in asymmetric lewis acid catalysis

Self Cite

Threefold symmetrical chiral podands may simplify the stereochemistry of key catalytic intermediates for cases in which they only act as bidentate ligands. This applies to systems in which chemical exchange between the different kappa2-coordinated forms takes place and in which the non-coordinated sidearm may play a direct or indirect role at some earlier or later stage in the catalytic cycle. Palladium(II)-catalysed allylic substitutions provide appropriate test reactions along these lines. A series of neutral dichloropalladium(II) complexes, [PdCl2(iPr-trisox)] (1a), [PdCl2(Ph-trisox)] (1b), [PdCl2(Bn-trisox)] (1c) and [PdCl2(Ind-trisox)] (1d) (trisox=1,1,1-tris(oxazolinyl)ethane) were synthesised by reaction of the respective trisox derivative with [PdCl2(PhCN)2] and characterised inter alia by 15N NMR spectroscopy. Direct detection of the heteronuclei without isotope enrichment and with "normal" sample concentrations was achieved with the aid of a cryogenically cooled NMR probe on a 600 MHz NMR spectrometer. Whereas the 15N nuclei of the coordinated oxazoline rings resonate at delta=160-167 ppm and appear as two singlets due to their diastereotopicity, the signal assigned to the dangling oxazoline "arm" is observed at delta=238-240 ppm. Variable-temperature NMR studies along with a systematic series of magnetisation transfer experiments established exchange between ligating and non-ligating oxazoline rings. Reaction of [Pd(allyl)(cod)]BF4 (cod=cyclooctadiene) with Ph-trisox in CH(2)Cl(2) gave the corresponding allyl complex 2, for which fast exchange between the three oxazoline heterocycles as well as between the exo and endo diastereomers was observed along with a very slow eta3-eta1-eta3 process of the allyl fragment (magnetisation transfer). Palladium(0) complexes were prepared by reaction of trisox derivatives or sidearm-functionalised BOX (BOX=bis(oxazolinyl)dimethylmethane) ligands with [Pd(nbd)(alkene)] (nbd=norbornadiene, alkene=maleic anhydride or tetracyanoethylene). X-ray diffraction studies of the iPr-trisox and Ph-trisox complexes (3a and 3b) established Y-shaped trigonal planar coordination geometries with the trisox ligand coordinated in a bidentate fashion, whilst the pi-coordinated maleic anhydride ligand adopts one of the two possible diastereotopic orientations. As the catalytic test reaction, the allylic alkylation of 1,3-diphenylprop-2-enyl acetate substrate with dimethyl malonate as nucleophile (in the presence of N,O-bis(trimethylsilyl)acetamide) was investigated for the trisox derivatives, their BOX analogues, and a series of less symmetric "sidearm" functionalised bisoxazolines. The trisoxazoline-based catalysts generally induce a better enantioselectivity compared to their bisoxazoline analogues and display significant reduction of the induction period as well as rate enhancement.

Section: Introductionmentioning

confidence: 99%

Using a Tripod as a Chiral Chelating Ligand: Chemical Exchange Between Equivalent Molecular Structures in Palladium Catalysis with 1,1,1‐Tris(oxazolinyl)ethane (“Trisox”)

Foltz

Enders

Bellemin‐Laponnaz

et al. 2007

Self Cite

“…The highest enantioselectivities were observed for the BOX(Ph) derivatives-a trend which had already been noted earlier. [24] Enantiomeric excesses of between 97 and 99 % were obtained with these catalysts, whereas BOXA C H T U N G T R E N N U N G (iPr) and trisoxA C H T U N G T R E N N U N G (iPr) ranged between 90 and 97 % ee. There are some notable aspects concerning the results obtained with BOXA C H T U N G T R E N N U N G (iPr) and trisoxA C H T U N G T R E N N U N G (iPr) derivatives, namely an increase of ee values from 94 % ee for the catalysts with the parent ligand systems A and C to 97 and 96 % with propargyl-substituted ligands 3 a and 2 a, respectively.…”

Section: Preparation Of the Oxazoline-functionalised Dendrimersmentioning

confidence: 98%

“…a-Hydrazination of ethyl 2-methylacetoacetate: This reaction has been studied extensively [24] and therefore lent itself to assess the influence of the dendritic support (and subsequently the recycling in a membrane bag, vide infra) on the catalytic system. The results obtained for the catalytic a-hydrazination of ethyl 2-methylacetoacetate are displayed in Table 1.…”

Section: Preparation Of the Oxazoline-functionalised Dendrimersmentioning

confidence: 99%

See 1 more Smart Citation

“Catalysis in a Tea Bag”: Synthesis, Catalytic Performance and Recycling of Dendrimer‐Immobilised Bis‐ and Trisoxazoline Copper Catalysts

Gaab

Bellemin‐Laponnaz

Gade

2009

Self Cite

Bis- and trisoxazolines (BOX and trisox), containing a linker unit in the ligand backbone that allows their covalent attachment to carbosilane dendrimers, have been employed as polyfunctional ligands for recyclable Cu(II) Lewis acid catalysts that were immobilised in a membrane bag. The oxazolines contained an alkynyl unit attached to their backbone that was deprotonated with LDA or BuLi and then reacted with the chlorosilyl termini of zeroth-, first- and second-generation carbosilane dendrimers in the presence of TlPF(6). The functionalised dendritic systems were subsequently separated from excess ligand by way of dialysis. The general catalytic potential of these systems was assessed by studying two benchmark reactions, the alpha-hydrazination of a beta-keto ester as well as the Henry reaction of 2-nitrobenzaldehyde with nitromethane. For both reactions the bisoxazoline-based catalysts displayed superior selectivity and, in particular, catalyst activity. The latter was interpreted as being due to the hindered decoordination of the third oxazoline unit, the key step in the generation of the active catalyst, in the immobilised trisox-copper complexes. Solutions of the second-generation dendrimer catalysts were placed in membrane bags, fabricated from commercially available dialysis membranes, with the purpose of catalyst recycling based on dialysis. Overall, the supported BOX catalyst gave good and highly reproducible results throughout the study, whereas the performance of the trisox dendrimer system decreased monotonically. The reason for the different behaviour is the markedly lower activity of trisox-based catalysts relative to those based on the BOX ligand. This necessitated an increased reaction time for each cycle of the trisox derivatives, resulting in higher levels of catalyst leaching, which was attributed to a modification of the structure of the membrane by its exposure to the solvent trifluoroethanol at 40 degrees C.

“…[1] Since the catalytic enantioselective electrophilic a-amination of carbonyl compounds with azodicarboxylates pioneered by Evans and Nelson, [2] a great effort has been devoted to the development of more selective and efficient catalytic systems for this kind of synthetically useful transformation, [3] such as chiral metal complexes, [4] chiral phase-transfer catalysts, [5] cinchona alkaloid derivatives, [6] chiral amine catalysts, [7] chiral thiourea catalysts, [8] and chiral guanidine catalysts. [9] Furthermore, the application of prochiral 3-substituted oxindoles as nucleophiles provides a very simple and straightforward approach for the synthesis of optically active 3-amino-2-oxindole derivatives with a chiral quaternary center, and studies in this field have received special attention because oxindoles bearing C3-quaternary structures are widely distributed in a number of natural products and pharmaceutical molecules.…”

Section: Introductionmentioning

confidence: 99%

Highly Enantioselective Synthesis of 3‐Amino‐2‐oxindole Derivatives: Catalytic Asymmetric α‐Amination of 3‐Substituted 2‐Oxindoles with a Chiral Scandium Complex

Yang

Wang

Bai

et al. 2010

103

A highly enantioselective alpha-amination of 3-substituted oxindoles with azodicarboxylates catalyzed by a chiral Sc(OTf)(3)/N,N'-dioxide complex (Tf: triflate) has been developed and affords the corresponding 3-amino-2-oxindole derivatives in high yields (up to 98%) with excellent enantioselectivities (up to 99% ee). The procedure is capable of tolerating a relatively wide range of substrates, and excellent results (92-96% ee) can also be obtained, even in the presence of 0.5 mol % of catalyst loading under mild conditions. These results showed the potential value of the catalytic approach. Moreover, with high synthetic versatility, the product could be easily transformed into optically active 3-amino-3-methyloxindole bearing a chiral quaternary stereogenic center.