Development of the BIPI ligands for asymmetric hydrogenation

Busacca, Carl A.; Lorenz, Jon C.; Saha, Anjan K.; Cheekoori, Sreedhar; Haddad, Nizar; Reeves, Diana C.; Lee, Heewon; Li, Zhibin; Rodrı́guez, Sonia; Senanayake, Chris H.

doi:10.1039/c2cy20337e

Cited by 13 publications

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“…The BIPI ligands are a modular and electronically tunable ligand platform invented in the late 1990s4 and designed for ready optimization to enable asymmetric transformations with differing electronic and steric requirements. Highly selective asymmetric hydrogenations of ene‐ureas,5 ene‐carbamates, and enamides6 with the rhodium complexes of a variety of these engineered ligands (Figure 1) have been achieved. The first applications of these systems to unfunctionalized olefins are described below.…”

Section: Methodsmentioning

confidence: 99%

“…[6] This may involve conformational restriction of the phosphine substituents leading to increased selectivity. For the former substrate class, strong evidence for the importance of the naphthyl peri proton (H-8) was gathered.…”

Section: Communicationsmentioning

confidence: 99%

“…

The modular nature of the BIPI ligands allows for systematic optimization of each ligand region. [5,6,9] There are four subclasses of possible substitution patterns when either aryl or alkyl groups are chosen for the phosphorus and imidazoline substituents of the ligand. The naphthyl peri position, C-8, has been identified as a critical stereocontrol element in the design of these ligands.

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confidence: 99%

“…The naphthyl peri position, C-8, has been identified as a critical stereocontrol element in the design of these ligands. [6] This may involve conformational restriction of the phosphine substituents leading to increased selectivity.Efforts to incorporate a larger peri substituent on the naphthalene core were then undertaken. Only N-acyl-containing ligands were chosen, as we have previously shown that all successful AH ligands require this functionality.…”

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confidence: 99%

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Tuning the Peri Effect for Enantioselectivity: Asymmetric Hydrogenation of Unfunctionalized Olefins with the BIPI Ligands

Busacca

Grět

et al. 2013

Adv Synth Catal

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The modular nature of the BIPI ligands allows for systematic optimization of each ligand region. The development of ligands optimized for asymmetric hydrogenation of the challenging unfunctionalized olefin substrate class is described. The naphthyl peri position, C-8, has been identified as a critical stereocontrol element in the design of these ligands. Highly enantioselective ligands suitable for hydrogenation of tri-and tetrasubstituted olefins are detailed. COMMUNICATIONSA variety of structurally diverse BIPI ligands ( Figure 2) were converted to their cationic iridium-A C H T U N G T R E N N U N G (COD)BAr F complexes, and all were purified by silica gel chromatography. Only N-acyl-containing ligands were chosen, as we have previously shown that all successful AH ligands require this functionality. [5,6,9] There are four subclasses of possible substitution patterns when either aryl or alkyl groups are chosen for the phosphorus and imidazoline substituents of the ligand. Examples of all four types were thus selected so that the different systems could be compared. Methanol, CH 2 Cl 2 and toluene were examined as hydrogenation solvents for several of these complexes, and the highest conversions were consistently observed in CH 2 Cl 2 . Examination of these ligands in the asymmetric hydrogenation of dimethylindene 1 was then carried out under 1 bar of H 2 in CH 2 Cl 2 . The results for this screening set are shown in Table 1.The complexes derived from ligands with dialkylphosphines and diarylimidazolines (BIPI 81, 83, and 84) showed low conversion, low selectivity, or both. Ligands with aryl groups on phosphorus and carbon (BIPI 93,(201)(202)(203) 205) all gave full conversion, yet the highest selectivity observed was 89:11 er (BIPI 93). Aryl P-substitution paired with C-alkyl groups (BIPI 206) gave full conversion yet a diminished er of 84:16. The fourth subclass, with alkyl substitution for both elements, proved to be optimum as long as small alkyl groups (Et, i-Pr) were avoided. BIPI 207, with a phenyl ligand core and cyclohexyl on phosphorus, provided product 2 with full conversion and 94:6 er. When the analogous naphthyl core ligand to BIPI 207, (BIPI 210), was examined, quantitative conversion with a slightly higher selectivity (95:5 er) was observed.Thus, the advantage of the naphthyl core ligands over the phenyl core, first observed in functionalized olefin hydrogenations, may also be in effect for the unfunctionalized substrates. For the former substrate class, strong evidence for the importance of the naphthyl peri proton (H-8) was gathered. [6] This may involve conformational restriction of the phosphine substituents leading to increased selectivity.Efforts to incorporate a larger peri substituent on the naphthalene core were then undertaken. Fluoro-A C H T U N G T R E N N U N G imidazoline 3 with a methyl group at the peri position was prepared, yet the subsequent S N Ar reaction with the anion of dicyclohexylphosphine·borane failed (Scheme 1). The most likely explanation for this is the severe ste...

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Section: Methodsmentioning

confidence: 99%

Section: Communicationsmentioning

confidence: 99%

“…

…”

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confidence: 99%

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confidence: 99%

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Tuning the Peri Effect for Enantioselectivity: Asymmetric Hydrogenation of Unfunctionalized Olefins with the BIPI Ligands

Busacca

Grět

et al. 2013

Adv Synth Catal

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“…After examining L2-L4, we found that a bulky and rigid N-coordination arm is beneficial for favoring the syn product by suppressing secondary isomerization. In particular, the phosphinoimidazoline ligand L1, which is derived from diphenylethlenediamine and was previously developed at Boehringer-Ingelheim, [33][34][35][36][37] was identified as the best ligand in terms of regio-and stereoselectivity. Further screening showed that the palladium source and the additive are important for reactivity (Entry 6-12).…”

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Atom-Economical Cross-Coupling of Internal and Terminal Alkynes to Access 1,3-Enynes

Li¹,

Tang²,

Apolinar³

et al. 2020

Preprint

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Selective carbon–carbon (C–C) bond formation in chemical synthesis generally requires pre-functionalized building blocks. However, the requisite pre-functionalization steps undermine the efficiency of multi-step synthetic sequences, which is particularly problematic in large-scale applications, such as in the commercial production of pharmaceuticals. Herein, we describe a selective and catalytic method for synthesizing 1,3-enynes without pre-functionalized building blocks. This method is facilitated by a tailored P,N-ligand that enables regioselective coupling and suppresses secondary <i>E</i>/<i>Z</i>-isomerization of the product. The transformation enables several classes of unactivated internal acceptor alkynes to be coupled with terminal donor alkynes to deliver 1,3-enynes in a highly regio- and stereoselective manner. The scope of compatible acceptor alkynes includes propargyl alcohols, (homo)propargyl amine derivatives, and (homo)propargyl carboxamides. The reaction is scalable and can operate effectively with 0.5 mol% catalyst loading. The products are versatile intermediates that can participate in various downstream transformations. We also present preliminary mechanistic experiments that are consistent with a redox-neutral Pd(II) catalytic cycle.

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Synthesis and Applications of Cyclohexenyl Halides Obtained by a Cationic Carbocyclisation Reaction

Alonso

Pardo

Fontaneda

et al. 2017

Chemistry A European J

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The synthesis of cyclic alkenyl halides (mainly fluorides, chlorides and bromides) from alkynol or enyne derivatives by an acid-mediated cationic cyclisation reaction is disclosed. This high-yielding, scalable and technically simple method complements and challenges conventional methodologies. This study includes the development of biomimetic cationic cyclisation reactions of polyenyne derivatives to give interesting halogen-containing polycyclic compounds. The application of this reaction in the key step of the synthesis of two terpenes, namely austrodoral and pallescensin A, and the potent odorant 9-epi-Ambrox demonstrates the potential of the reaction for natural product synthesis.

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Development of the BIPI ligands for asymmetric hydrogenation

Cited by 13 publications

References 21 publications

Tuning the Peri Effect for Enantioselectivity: Asymmetric Hydrogenation of Unfunctionalized Olefins with the BIPI Ligands

Tuning the Peri Effect for Enantioselectivity: Asymmetric Hydrogenation of Unfunctionalized Olefins with the BIPI Ligands

Atom-Economical Cross-Coupling of Internal and Terminal Alkynes to Access 1,3-Enynes

Synthesis and Applications of Cyclohexenyl Halides Obtained by a Cationic Carbocyclisation Reaction

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