NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

Padevet, Jaroslav; Schrems, Marcus G.; Scheil, Robin; Pfaltz, Andreas

doi:10.3762/bjoc.12.114

Cited by 12 publications

(6 citation statements)

References 32 publications

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“…[6] As the substrate scope of Ir (PHOX) catalysts was limited, we subsequently explored many other oxazoline-based P,N ligands (Figure 1). Among them, NeoPHOX [7,8] and ThrePHOX [9] emerged as particularly effective ligands for several substrate classes. Meanwhile, two ThrePHOX com-plexes have also become commercially available.…”

Section: Introductionmentioning

confidence: 99%

Optimized Scalable Synthesis of Chiral Iridium Pyridyl‐Phosphinite (Pyridophos) Catalysts

Müller

Ganić

Hörmann

et al. 2020

Helvetica Chimica Acta

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Dedicated to Prof. Antonio Togni on the occasion of his 65th birthday Iridium catalysts with chiral P,N ligands have greatly enhanced the scope of asymmetric olefin hydrogenation because they do not require a coordinating group near the C=C bond like Rh and Ru catalysts. Pyridophos ligands, possessing a conformationally restricted annulated pyridine framework linked to a phosphinite group, proved to be particularly effective, inducing high enantioselectivities in the hydrogenation of a remarkably broad range of substrates. Here we report the development of an efficient scalable synthesis for the two most versatile Ir-pyridophos catalysts, derived from 2-phenyl-8-hydroxy-5,6,7,8-tetrahydroquinoline or the analogue with a fivemembered carbocyclic ring, respectively, by modification and optimization of the original synthetic route. The optimized route renders both catalysts readily accessible in multi-gram quantities in analytically pure form in overall yields of 26-37 %, starting from acetophenone and cyclopentanone or cyclohexanone, respectively. A major advantage of the new synthesis is the efficient and practical kinetic resolution of the late-stage pyridyl alcohol intermediates with commercial immobilized Candida antarctica lipase B, giving access to both enantiomers of these catalysts as essentially enantiopure compounds. The catalysts are obtained as crystalline solids, which are air-stable and can be stored for years at À 20°C without notable decomposition.

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Section: Introductionmentioning

confidence: 99%

Optimized Scalable Synthesis of Chiral Iridium Pyridyl‐Phosphinite (Pyridophos) Catalysts

Müller

Ganić

Hörmann

et al. 2020

Helvetica Chimica Acta

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“…Compounds with a phosphorus atom attached to a stereogenic carbon center in acyclic and cyclic structures play an important role as chiral ligands in transition metal complexes [2]. They were applied to various catalytic asymmetric reactions [3–4], such as hydrogenations [3–6], conjugated additions to enones [7], and allylic alkylations [8–9]. Another direction of research is the use of phosphines in organocatalysis [10–11] and bifunctional catalysis [12].…”

Section: Introductionmentioning

confidence: 99%

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

Kmieciak¹,

Krzemiński²

2019

Beilstein J. Org. Chem.

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New chiral regioisomeric γ-hydroxyphosphine ligands were synthesized from α-pinene. The key transformation was the thermal [2,3]-sigmatropic rearrangement of allyldiphenylphosphinites, obtained from (1R,2R,4S,5R)-3-methyleneneoisoverbanol and (1R,2R,3R,5R)-4-methyleneneoisopinocampheol, to allylphosphine oxides. Hydroxy groups were introduced stereoselectively through a hydroboration–oxidation reaction proceeding from the less hindered site providing a trans relationship between the hydroxy and the phosphine substituents.

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“…Although related phosphine‐oxazoline ligands have been developed to solve these limitations (such as SimplePHOX, ThrePHOX, NeoPHOX, etc. ) they are limited in substrate and reaction scope and/or require more reaction steps . The discovery of efficient ligands prepared in only a few steps from inexpensive raw materials, easy to handle (i.e., solid, robust and air stable) and that tolerate a broad range of substrates has therefore attracted the attention of many researchers.…”

Section: Introductionmentioning

confidence: 99%

Alternatives to Phosphinooxazoline (t‐BuPHOX) Ligands in the Metal‐Catalyzed Hydrogenation of Minimally Functionalized Olefins and Cyclic β‐Enamides

et al. 2017

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This studyp resents an ew serieso fr eadily accessible iridium-and rhodium-phosphite/oxazoline catalytic systems that can efficiently hydrogenate,f or the first time,b othm inimally functionalized olefins and functionalized olefins (62 examples in total) in high enantioselectivities( eesu pt o> 99%) and conversions. Thep hosphite-oxazoline ligands,w hich are readily available in only two synthetic steps,a re derived from previous privileged 4-alkyl-2-[2-(diphenylphosphino)phenyl]-2-oxazoline (PHOX) ligands by replacing the phosphinemoiety by ab iaryl phosphite group and/or the introductiono famethylene spacer between the oxazoline and the phenylr ing. The modular design of the ligands hasgiven us the opportunity not only to overcome the limitations of the iridium-PHOX catalytic systems in the hydrogenation of minimally functionalized Z-olefins and 1,1-disubstitutedo lefins, but also to expand theiru se to unfunctionalized olefins containing other challenging scaffolds (e.g.,e xocyclic benzofused andt riaryl-substitutedo lefins) anda lso to olefinsw ith poorly coor-dinativeg roups (e.g., a,b-unsaturated lactams,l actones,a lkenylboronic esters, etc.) with enantioselectivities typically > 95% ee. Moreover, both enantiomers of the hydrogenation product could be obtained by simply changing the configuration of the biaryl phosphite moiety.R emarkably, the new catalytic systems also provided excellent enantioselectivities (up to 99% ee)i nt he asymmetric hydrogenation of another challengingc lass of olefins -t he functionalized cyclic b-enamides.A gain, both enantiomers of the reduceda midesc ould be obtained by changing the metal from Ir to Rh. We also demonstrated that environmentally friendly propylene carbonate can be used with no loss of enantioselectivity.A nothera dvantage of the new ligands over the PHOX ligands is that the best ligands are derived from the affordable (S)-phenylglycinolr ather than from the expensive (S)-tert-leucinol.

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NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

Cited by 12 publications

References 32 publications

Optimized Scalable Synthesis of Chiral Iridium Pyridyl‐Phosphinite (Pyridophos) Catalysts

Optimized Scalable Synthesis of Chiral Iridium Pyridyl‐Phosphinite (Pyridophos) Catalysts

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

Alternatives to Phosphinooxazoline (t‐BuPHOX) Ligands in the Metal‐Catalyzed Hydrogenation of Minimally Functionalized Olefins and Cyclic β‐Enamides

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