Novel, Tunable, and Efficient Chiral Bisdihydrobenzooxaphosphole Ligands for Asymmetric Hydrogenation

Tang, Wenjun; Qu, Bo; Capacci, Andrew G.; Rodrı́guez, Sonia; Wei, Xudong; Haddad, Nizar; Narayanan, Bikashandarkoil; Ma, Shengli; Grinberg, Nelu; Yee, Nathan K.; Krishnamurthy, Dhileepkumar; Senanayake, Chris H.

doi:10.1021/ol9025815

Cited by 147 publications

(84 citation statements)

References 28 publications

(5 reference statements)

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“…Fully aware of the challenges associated with the asymmetric hydrogenation of tetrasubstituted olefins, 9 we aspired to engineer a new catalytic system for this important transformation by leveraging our recently developed dihydrobenzooxaphosphole (BOP)-based ligand series ( vide infra ). 10,11 To access requisite hydrogenation precursor A , a conceptually concise sequence was devised involving an S N Ar coupling of fragments 4 and 5 followed by an intramolecular C–H arylation. At the outset, the proposed cyclization to the C-3 position of pyridine was expected to be challenging, with few related examples found in the literature.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, our group has reported a highly modular dihydrobenzooxaphosphole (BOP) core for ligand design. 10 Many effective ligands have been derived from this motif and have been found to mediate a variety of different catalytic transformations. 11 In particular, the rigid bidentate BoQPhos P,N-ligands, which were constructed from the BOP core by anchoring a less basic nitrogen-containing pyridine fragment onto the carbon atom of the O,P ring system (see Figure 4), have been successfully demonstrated for asymmetric hydrogenation of nonfunctionalized tri- and tetrasubstituted olefins.…”

Section: Resultsmentioning

confidence: 99%

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Sequential C–H Arylation and Enantioselective Hydrogenation Enables Ideal Asymmetric Entry to the Indenopiperidine Core of an 11β-HSD-1 Inhibitor

Wei

Zeng

et al. 2016

J. Am. Chem. Soc.

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A concise asymmetric synthesis of an 11β-HSD-1 inhibitor has been achieved using inexpensive starting materials with excellent step-economy at low catalyst loadings. The catalytic enantioselective total synthesis of 1 was accomplished in 7 steps and 38% overall yield aided by the development of an innovative, sequential strategy involving Pd-catalyzed pyridinium C–H arylation and Ir-catalyzed asymmetric hydrogenation of the resulting fused tricyclic indenopyridinium salt highlighted by the use of a unique P,N-ligand (MeO-BoQPhos) with 1000 ppm of [Ir(COD)Cl]2.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Sequential C–H Arylation and Enantioselective Hydrogenation Enables Ideal Asymmetric Entry to the Indenopiperidine Core of an 11β-HSD-1 Inhibitor

Wei

Zeng

et al. 2016

J. Am. Chem. Soc.

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“…Many examples can be found in the literature for the resolution of 3 cyclic P-chiral phosphines, phosphine oxides and phosphonium salts via the formation of covalent diasteromers [11][12][13], diastereomeric coordination [14][15][16][17][18][19], molecular complexes [10,20,21] or diastereomeric salts [22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

“…In the literature, the synthesis of a few optically active P-chiral heterocyclic ligands was described and the transition metal complexes of these P(III)-compounds were used as catalysts mainly in enantioselective hydrogenation reactions [11,13,16,18,21,[28][29][30][31][32]. There are only a few examples for P-heterocyclic ligands that were used in hydroformylation [5].…”

Section: Introductionmentioning

confidence: 99%

A study on the optical resolution of 1-isopropyl-3-methyl-3-phospholene 1-oxide and its use in the synthesis of borane and platinum complexes

Bagi

Juhász

Timári

et al. 2015

Journal of Organometallic Chemistry

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A 1-isopropyl-3-phospholene 1-oxide was prepared and the two enantiomers were isolated from the racemate by resolution using optically active TADDOL derivatives or the acidic Ca 2+ salts of (-)-O,O-diaroyl-(2R,3R)-tartaric acids. The single crystal X-ray structure of the 2 1-isopropyl-3-phospholene oxide -spiro-TADDOL 1:2 associate revealed the mode of binding between the host and guest molecules. The role of the interactions between the three molecules was supported not only by the contact data, but also force field and semiempirical calculations. Beside X-ray analysis, the absolute configuration of the P-stereogenic center was also determined on the basis of CD spectroscopy and high level quantum chemical calculations. The racemic and optically active 1-isopropyl-3-phospholenes obtained after deoxygenation were converted to the corresponding borane complexes and Pt(II) complexes.Stereostructure of the latter species was evaluated by high level quantum chemical calculations and the Pt complexes were tested as catalysts in the hydroformylation of styrene.

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“…The hydrogenations were conducted at room temperature at a hydrogen pressure of 300 psi for 12 h. It was found that well-known chiral ligands such as BINAP, Josiphos, and Tangphos [8] did not provide superb enantioselectivities (Table 1, entries 1-2). Ligand BIBOP (L1), which was highly effective for hydrogenation of a-aryl-N-acetyl enamides in our previous study, [14] proved to be inefficient (Table 1, entry 3). A low ee was also observed when MeO-BIBOP (L2) was applied ( Table 1, entry 4).…”

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confidence: 96%

Design of Phosphorus Ligands with Deep Chiral Pockets: Practical Synthesis of Chiral β‐Arylamines by Asymmetric Hydrogenation

Liu

Cai

et al. 2013

Angewandte Chemie

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Despite the signficant advances in asymmetric hydrogenation, the development of novel and efficient chiral phosphorus ligands to solve new synthetic challenges continues to an important goal. [1] C 2 -Symmetric chiral bisphosphorus ligands such BINAP, [2] DuPhos, [3] and TangPhos [4] are among the most versatile and important ligands for asymmetric hydrogenation, yet they are not universal. To expand their synthetic utilities, one common strategy is to develop structurally similar ligands, such as Tol-BINAP, Xyl-BINAP, Et-DuPhos, or iPr-DuPhos by increasing the size of the substituents on the phosphorus centers (Figure 1 a). Such modifications lead to the design of ligands with deeper chiral pockets mainly owing to the increased bulk of the R groups, which protrude slightly forward to the substrate coordination. In this study we adopt a new strategy to design a ligand with a deep chiral pocket by installing R groups that protrude directly forward to the substrate coordination site. There are two advantages of this strategy: 1) The R groups that protrude directly forward to the substrate coordination site can lead to a dramatic conformational variation of the chiral pocket; 2) the R groups are in close proximity to the metal center and the substrate, thereby providing a well-defined and deep chiral pocket. We herein report the development of WingPhos (L5) by using this strategy.Chiral b-arylamines exist in numerous biologically interesting natural products and therapeutic agents. For examples, such moieties commonly exist in a series of naphthylisoquinoline alkaloids such as michellamine B and korupensamine A (Scheme 1). [5] They also serve as pivotal structural units for many active pharmaceutical ingredients such as 3,4-methylenedioxyamphetamine (MDA), [6a] tamsulosin, [6b] selegiline, [6c] arformoterol, [6d] rotigotine, [6e] and silodosin. [6f] Development of efficient asymmetric synthetic methods of chiral b-arylamines has thus become a subject of significant interest. [7] However, the asymmetric hydrogenation of b-aryl enamides to prepare chiral b-arylamines remains underdeveloped. Zhang, Lei, and co-workers reported high enantioselectivities on the asymmetric hydrogenation of (Z)-b-aryl enamides by using a Rh-TangPhos catalyst. [8] Nevertheless, low ee values were observed with thermodynamically more stable sub-Figure 1. Design of novel chiral bisphosphorus ligand L5 (WingPhos) with a deep chiral pocket (9-An = 9-anthracenyl). Scheme 1. Selected natural products and therapeutic agents containing chiral b-arylamines.

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Novel, Tunable, and Efficient Chiral Bisdihydrobenzooxaphosphole Ligands for Asymmetric Hydrogenation

Cited by 147 publications

References 28 publications

Sequential C–H Arylation and Enantioselective Hydrogenation Enables Ideal Asymmetric Entry to the Indenopiperidine Core of an 11β-HSD-1 Inhibitor

Sequential C–H Arylation and Enantioselective Hydrogenation Enables Ideal Asymmetric Entry to the Indenopiperidine Core of an 11β-HSD-1 Inhibitor

A study on the optical resolution of 1-isopropyl-3-methyl-3-phospholene 1-oxide and its use in the synthesis of borane and platinum complexes

Design of Phosphorus Ligands with Deep Chiral Pockets: Practical Synthesis of Chiral β‐Arylamines by Asymmetric Hydrogenation

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