Crystal structure of the RuPhos ligand

The solid-state structure of RuPhos (2-dicyclohexylphosphanyl-2′,6′-diisopropoxybiphenyl) is presented for the first time and discussed in detail. The phosphine cone angle is computed and compared to the cone angles of other phosphine ligands.

The steric and electronic properties of the ancillary phosphine ligand can have a profound impact on the outcome of the cross-coupling reaction. For example, in the Buchwald-Hartwig amination, Pd-RuPhos displays high catalytic activity for cross-coupling reactions with sterically hindered substrates such as cyclic secondary amines, whereas the related congener, Pd-BrettPhos, demonstrates high catalytic activity with primary amines (Tian et al., 2020;Charles et al., 2005). The electronic properties and steric profile of the ligand scaffold impact the elementary steps and catalytic performance of the resulting metal complex (van Leeuwen et al., 2000). Recent density functional calculations corroborate the importance of ligand properties on the kinetics of cross-coupling chemistry: the rate-limiting step for Pd-RuPhos is predicted to be reductive elimination, while that of the congener Pd-Brett-Phos is predicted to be oxidative addition (Tian et al., 2020). Curiously, the solid-state structure of RuPhos remains absent from the literature. Knowledge of the structural metrics of RuPhos will benefit mechanistic and computational studies of this important ligand and will aid in the rational design of new RuPhos-derivative catalysts.

Structural commentary
The free RuPhos ligand ( Fig. 1) was characterized by singlecrystal X-ray diffraction, with pertinent bond metrics listed in Table 1 and experimental structural details delineated in Table 2. The asymmetric unit contains two independent molecules, RuPhos A and RuPhos B, which differ modestly in conformation. For conciseness, only the structural metrics of RuPhos B are described hereafter, and RuPhos B is simply referred to as RuPhos. Details of the structural metrics of both molecules in the asymmetric unit can be found in the supporting information.
The C-C bond lengths (Table S3) in the arene rings differ minimally, ranging from 1.385 (2) to 1.402 (2) Å . The P-Csp 2 and P-Csp 3 bond lengths (Table 1) were observed to vary minimally between RuPhos A and RuPhos B. The P-C Ar bond length (P1B-C18B) is 1.848 (2) Å and it is comparable to the previously reported P--C Ar bond lengths in PPh 3 (Samouei et al., 2014). As expected, the P-C Cy bond lengths are somewhat longer [P1B-C19B: 1.877 (2) Å ; P1B-C25B: 1.862 (2) Å ] and comparable to those observed in PCy 3 (Davies et al., 1991). The Cy(C25B)-P1B-Cy(19B) angle is 105.46 (8) . The two C Ar -P-C Cy angles are 97.03 (8) (C18B-P1B-C19B) and 101.86 (8) (C18B-P1B-C25B). The cyclohexyl rings each adopt a chair conformation relative to P1B and are in an asymmetric orientation relative to the biaryl substituent. No notable interactions between the cyclohexyl rings and other atoms within RuPhos are observed. Additional electron density close to the phosphorus is resolved and assigned to a lone pair rather than a light atom based on its proximity to the phosphorous atom.
The Tolman cone angle quantifies steric and electronic effects of phosphine ligands (Tolman, 1977) and is defined as the angle from a hypothetical metal M located 2.28 Å from the phosphorus atom to the van der Waals radii of the outermost atoms of the phosphine ligand. Half angles are defined by the angle between the M-P bond and the line between M-H i , where H i is the outermost atom on the substituent, calculated as: i = a i + sin À1 (r H /d i ) where i is the angle defined between M-H i and M-P and d i is the distance between M and H i (Mü ller & Mingos, 1995). For unligated RuPhos, the computed Tolman cone angle is 201.53 (Table S5). For comparison, the cone angle for Pd-RuPhos is 198.06 (Arrechea & Buchwald, 2016). The RuPhos cone angle is larger than those found in PCy 3 (170 ) and PPh 3 (145 ) (Jover & Cirera, 2019) and is attributed to the steric profile of the biaryl substituent. The cone angle of free RuPhos is larger than the cone angle of Pd-RuPhos, consistent  Ellipsoid plot (50% probability ellipsoids) of RuPhos. Hydrogen atoms are omitted for clarity.
with slight modification of the P hybridization accompanying complexation to the Pd center.

Supramolecular features
The crystal packing of RuPhos follows a parallelepiped geometry (Fig. 2), showing two types of intermolecular channel-like interfaces, which alternate in parallel planes. In the first type of interface channel, cyclohexyl substituents from different RuPhos molecules face towards each other. The distance between cyclohexyl rings (Table S6)  In the second type of channel, biaryl substituents from different RuPhos molecules arrange themselves in a zigzag offset chain pattern (Fig. S2).
Within the asymmetric unit, RuPhos A and RuPhos B are spaced apart by ca 3 Å , as defined by the distance between the isopropyl units [H9BAÁ Á ÁH9AC: 2.91839 (9) Å ]. No void space is observed in the asymmetric unit as evident by a spacefilling model (Fig. S3).
The crystal structure of RuPhos shows consistency in atomic composition and connectivity with the reported structure. Coordination by the phosphine to a metal should occlude equatorial ligands on one side of the metal, though less so than its BrettPhos congener would. The small hindrance of Pd-RuPhos is thought to contribute to its high catalytic activity for hindered secondary amines while the larger hindrance of BrettPhos contributes to its high catalytic activity for primary amines (Arrechea & Buchwald, 2016;Tian et al., 2020).
The cone angles of free RuPhos and Pd-RuPhos (Arrechea & Buchwald, 2016) measure 201.54 and 198.07 , respectively. They are smaller than that of free BrettPhos and Pd-Brett-Phos (Dikundwar et al., 2017;DeAngelis et al., 2015), which are 220.29 and 204.22 , respectively. Because the proportion of s character in the lone pair of a phosphine ligand is inversely proportional to the cone angle of the ligand (Tolman, 1977), the smaller Tolman cone angle of RuPhos implies that RuPhos donates less electron density to its coordinated metal than BrettPhos does. This electronic implication of the RuPhos cone angle corroborates calculations that reductive elimination is the rate-limiting step for Pd-RuPhos-catalyzed couplings (Tian et al., 2020).

Database survey
The structure of the unligated RuPhos ligand has not been previously published according to a search of the Cambridge Structural Database using ConQuest 2020.3.0 (CSD, version 5.42, November 2020; Groom et al., 2016). The structure of metallated Pd II RuPhos has been reported (Arrechea & Buchwald, 2016).

Synthesis and crystallization
RuPhos was purchased from Oakwood Chemical and purified by column chromatography (silica, ethyl acetate). Fractions containing RuPhos were concentrated in vacuo and allowed to stand at room temperature under air with slow evaporation for two weeks in a hexanes/ethyl acetate (10:1) mixture. Colorless plates were observed (Fig. S1) and employed for data collection.   No evidence for phosphine oxidation was observed in the final refinement. This is attributed to hindered phosphine rotation and the steric profile of the biaryl substituent (Barder et al., 2007).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms were placed in calculated positions (C-H = 0.95-1.00 Å ) and refined as riding with U iso (H) = 1.2U eq (C) or 1.5U eq (C-methyl).

Computing details
Data collection: APEX3 (Bruker, 2015); cell refinement: SAINT (Bruker, 2015); data reduction: SAINT (Bruker, 2015); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: SHELXTL (Sheldrick, 2008); Mercury (Macrae et al., 2020); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).  Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. No significant disordering was present.