Towards the rational design of ylide-substituted phosphines for gold(<scp>i</scp>)-catalysis: from inactive to ppm-level catalysis

Handelmann, Jens; Babu, Chatla Naga; Steinert, Henning; Schwarz, Christopher; Scherpf, Thorsten; Kroll, Alexander; Gessner, Viktoria H.

doi:10.1039/d1sc00105a

“…Recently, we reported on transition metal catalysts based on ylide‐functionalized phosphines (YPhos) [8] . In gold(I)‐catalyzed transformations with moderately ( A ) [8a] as well as highly electron‐rich ( B and C ) [9] YPhos systems exceptionally high turnover numbers were observed. All of these YPhos catalysts so far have relied on triphenyl phosphonium groups which likewise foster arene–gold interactions, thus contributing to the stability and high catalytic performance of the corresponding LAu(I) + species.…”

Section: Introductionmentioning

confidence: 99%

Au⋅⋅⋅H−C Hydrogen Bonds as Design Principle in Gold(I) Catalysis

Darmandeh

¹

,

Löffler

²

,

Tzouras

³

et al. 2021

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Secondary ligand–metal interactions are decisive in many catalytic transformations. While arene–gold interactions have repeatedly been reported as critical structural feature in many high‐performance gold catalysts, we herein report that these interactions can also be replaced by Au⋅⋅⋅H−C hydrogen bonds without suffering any reduction in catalytic performance. Systematic experimental and computational studies on a series of ylide‐substituted phosphines featuring either a PPh3 (PhYPhos) or PCy3 (CyYPhos) moiety showed that the arene‐gold interaction in the aryl‐substituted compounds is efficiently compensated by the formation of Au⋅⋅⋅H−C hydrogen bonds. The strongest interaction is found with the C−H moiety next to the onium center, which due to the polarization results in remarkably strong interactions with the shortest Au⋅⋅⋅H−C hydrogen bonds reported to date. Calorimetric studies on the formation of the gold complexes further confirmed that the PhYPhos and CyYPhos ligands form similarly stable complexes. Consequently, both ligands showed the same catalytic performance in the hydroamination, hydrophenoxylation and hydrocarboxylation of alkynes, thus demonstrating that Au⋅⋅⋅H−C hydrogen bonds are equally suited for the generation of highly effective gold catalysts than gold‐arene interactions. The generality of this observation was confirmed by a comparative study between a biaryl phosphine ligand and its cyclohexyl‐substituted derivative, which again showed identical catalytic performance. These observations clearly support Au⋅⋅⋅H−C hydrogen bonds as fundamental secondary interactions in gold catalysts, thus further increasing the number of design elements that can be used for future catalyst construction.

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“…From this structure, the buried volume was calculated using SambVca . The obtained buried volume of 42.5% is lower than that of other acyclic YPhos ligands with PCy 3 or PPh 3 moieties, which usually showed volumes of approximately 50%. − Furthermore, the steric map of L1 shows areas of steric bulk only on one side of the of the ligand, namely, the phosphonium moiety. The cyclohexyl groups are unable to reach toward the metal center.…”

Section: Resultsmentioning

confidence: 99%

“…As a result of this ylide group and its strong electron-donating abilities, these phosphines exhibited strong electron-donating capabilities, with donor capacities surpassing those of simple phosphines and NHCs. These ligands were shown to be ideal scaffolds for catalytic applications, ranging from gold-catalyzed hydroamination and cyclization reactions to palladium catalysis, such as Buchwald–Hartwig aminations as well as Negishi couplings and α-arylation reactions under mild conditions . Recently, it has been shown that YPhos palladium catalysts are even capable of directly coupling aryl chlorides and alkyl lithium reagents, giving very high selectivities while supplementing the need for any additional transmetalation reagents …”

Section: Introductionmentioning

confidence: 99%

Ylide-Substituted Phosphines with a Cyclic Ylide-Backbone: Angle Dependence of the Donor Strength

Löffler

¹

,

Gauld

²

,

Feichtner

³

et al. 2021

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Ylide-substituted phosphines (YPhos) have been shown to be highly electron-rich and efficient ligands in a variety of palladium catalyzed transformations. Here, the synthesis and characterization of novel YPhos ligands containing a cyclic backbone architecture are reported. The ligands are easily synthesized from a cyclic phosphonium salt and the chlorophosphines Cy 2 PCl ( L1 ) and Cy(Flu Me )PCl ( L2 , with Flu Me = 9-methylfluorenyl) and were characterized in both solution and solid states. The smaller PCy 2 -substituted ligand, L1 , readily formed the biscoordinate L1 2 Pd species when treated with Pd 2 (dba) 3 and showed no activity in palladium-catalyzed amination reactions even when applied as defined palladium(II) η 3 -allyl, t -Bu-indenyl, or cinnamyl precursors. Bulkier fluorenyl-substituted ligand L2 similarly was inactive, despite its ability to form the stable monophosphine complex L2 ·Pd(dba). Assessment of the electronic properties by experimental and computational methods revealed that L1 and L2 are considerably less electron-rich than previously synthesized YPhos ligands. This was shown to be the result of the small P–C–S bond angle, which is sterically enforced due to the cyclic nature of the backbone. Density functional theory calculations revealed that the small angle results in an increased s-character of the lone pair at the ylidic carbon atom and leads to a polarization of the C–P bond toward the carbon atom, thus decreasing the electron density at the phosphorus atom. The results demonstrate the tunability of the donor strength of YPhos ligands by modification of the ligand backbone beyond simple changes of the substitution pattern and are thus important for future ligand design, with a careful balance of many factors to be considered to achieve catalytic activity.

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“…[b] Values taken from reference [8a]. [c] Values taken from reference [9a]. [d] Values taken form reference [10].…”

Section: Resultsmentioning

confidence: 99%

“…[7] Recently,wereported on transition metal catalysts based on ylide-functionalized phosphines (YPhos). [8] In gold(I)catalyzed transformations with moderately (A) [8a] as well as highly electron-rich (B and C) [9] YPhos systems exceptionally high turnover numbers were observed. All of these YPhos catalysts so far have relied on triphenyl phosphonium groups which likewise foster arene-gold interactions,t hus contributing to the stability and high catalytic performance of the corresponding LAu(I) + species.…”

Section: Introductionmentioning

confidence: 99%

Au⋅⋅⋅H−C Hydrogen Bonds as Design Principle in Gold(I) Catalysis

Darmandeh

¹

,

Löffler

²

,

Tzouras

³

et al. 2021

Self Cite

View full text Add to dashboard Cite

Secondary ligand–metal interactions are decisive in many catalytic transformations. While arene–gold interactions have repeatedly been reported as critical structural feature in many high‐performance gold catalysts, we herein report that these interactions can also be replaced by Au⋅⋅⋅H−C hydrogen bonds without suffering any reduction in catalytic performance. Systematic experimental and computational studies on a series of ylide‐substituted phosphines featuring either a PPh3 (PhYPhos) or PCy3 (CyYPhos) moiety showed that the arene‐gold interaction in the aryl‐substituted compounds is efficiently compensated by the formation of Au⋅⋅⋅H−C hydrogen bonds. The strongest interaction is found with the C−H moiety next to the onium center, which due to the polarization results in remarkably strong interactions with the shortest Au⋅⋅⋅H−C hydrogen bonds reported to date. Calorimetric studies on the formation of the gold complexes further confirmed that the PhYPhos and CyYPhos ligands form similarly stable complexes. Consequently, both ligands showed the same catalytic performance in the hydroamination, hydrophenoxylation and hydrocarboxylation of alkynes, thus demonstrating that Au⋅⋅⋅H−C hydrogen bonds are equally suited for the generation of highly effective gold catalysts than gold‐arene interactions. The generality of this observation was confirmed by a comparative study between a biaryl phosphine ligand and its cyclohexyl‐substituted derivative, which again showed identical catalytic performance. These observations clearly support Au⋅⋅⋅H−C hydrogen bonds as fundamental secondary interactions in gold catalysts, thus further increasing the number of design elements that can be used for future catalyst construction.

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Towards the rational design of ylide-substituted phosphines for gold(i)-catalysis: from inactive to ppm-level catalysis

Abstract: The implementation of gold catalysis into large-scale processes suffers from the fact that most reactions still require high catalyst loadings to achieve efficient catalysis thus making upscaling impractial. Here, we...

Cited by 37 publications

References 61 publications

Au⋅⋅⋅H−C Hydrogen Bonds as Design Principle in Gold(I) Catalysis

Au⋅⋅⋅H−C Hydrogen Bonds as Design Principle in Gold(I) Catalysis

Ylide-Substituted Phosphines with a Cyclic Ylide-Backbone: Angle Dependence of the Donor Strength

Au⋅⋅⋅H−C Hydrogen Bonds as Design Principle in Gold(I) Catalysis

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