Unexpected Vulnerability of DPEphos to C−O Activation in the Presence of Nucleophilic Metal Hydrides

Abstract C−O bond activation of DPEphos occurs upon mild heating in the presence of [Ru(NHC)2(PPh3)2H2] (NHC=N‐heterocyclic carbene) to form phosphinophenolate products. When NHC=IEt2Me2, C−O activation is accompanied by C−N activation of an NHC ligand to yield a coordinated N‐phosphino‐functionalised carbene. DFT calculations define a nucleophilic mechanism in which a hydride ligand attacks the aryl carbon of the DPEphos C−O bond. This is promoted by the strongly donating NHC ligands which render a trans dihydride intermediate featuring highly nucleophilic hydride ligands accessible. C−O bond activation also occurs upon heating cis‐[Ru(DPEphos)2H2]. DFT calculations suggest this reaction is promoted by the steric encumbrance associated with two bulky DPEphos ligands. Our observations that facile degradation of the DPEphos ligand via C−O bond activation is possible under relatively mild reaction conditions has potential ramifications for the use of this ligand in high‐temperature catalysis.

Since their introductionc a. 20 years ago, [1] wide-angle phosphines such as xantphos and DPEphos (Scheme 1) have become indispensable ligands for ar ange of catalytic reactions. [2] Their usage stems from two advantageous properties; firstly,t he availability of highly flexible bite angles that allow cis-a nd trans-, as well as hemilabile P-O-P coordination modes, to be adopted [3] and, secondly,r esistancet ot he types of PÀC degradation reactions reported in tertiary phosphine metal complexes. [4] This latter property has promoted the use of xantphos andD PEphos in reactions that require high temperatures. [2c,g,l, 5] Any suggestion that such phosphines might be susceptible to degradative reactions, particularly under relativelym ildc onditions, could therefore have important ramificationsf or their applicationsi nc atalysis. While xantphos has been reported to be susceptible to PÀCb onda ctivation at room temperature, [6] cleavage of DPEphosappearstoberestricted to asingle example of high temperature CÀOb ond activation reported by Wellera nd Willis. [7] In the course of studies on [Rh(h 6 -ortho-xylene)(DPEphos)] + catalysed carbothiolation of alkynes, they reported that heating the Rh complext ogether with ortho-MeSC 6 H 4 C(O)Me at 120 8Ci nt he absence of any alkyne led to CÀOc leavage of DPEphos to afford ac atalytically inactive Rh complex with chelating phosphinea ryloxide and bidentate phosphine arylthioether ligands. Herein, we demonstrate that CÀOa ctivation of DPEphos can take place even at room temperaturei nt he presenceo fr uthenium dihydride complexes. DFT calculations reveal that such processes involve attack of highly nucleophilic hydride ligandso nt he aryl carbon on the CÀOb ond.
CÀNa ctivation of am etal-bound NHC ligand has been described previously, [15] including in studies on Ru-NHC complexesr elated to those employed here. [16] However,t his process has only rarely been observed alongside the activation of another ligand, [17] and, certainly not as aroute to the formation of ap hosphinocarbene. [18] The CÀOa ctivation of DPEphos was not restricted to NHCcontaining ruthenium hydride precursors. The reactiono f [Ru(PPh 3 ) 4 H 2 ]w ithD PEphos gave the isolable cis-dihydride complex [Ru(DPEphos) 2 H 2 ]( 5;S upporting Information), [19] which upon heating to 80 8Co vernightu nderwent CÀOa ctivation of one of the DPEphos ligandst oa fford [Ru(DPEphos)-(Ph 2 PC 6 H 4 O)H] (6,S cheme 4). [20] This was characterized by the presence of aq uartet RuÀHr esonance at d = À14 ppm with a 2 J(H,P) splitting (22 Hz) indicative of hydride cis to all three phosphorus nuclei anda 31 P{ 1 H} NMR spectrum which showed at riplet at d = 77 ppm ( 2 J(P,P) = 30 Hz), together with ab road, featureless signal at d = 50 ppm. We attribute the latter to the intact DPEphos ligand switching rapidlyb etween k 2 -P,P and k 3 -P, O,P coordination.A tÀ15 8C, this signal resolved into two doublets, the two ends of the DPEphosl igand becoming inequivalentasaresult of the oxygen now staying bound to Ru. Althougha nX -ray structure of 6 provede lusive, crystals of the chlorided erivative 7 were isolated from CH 2 Cl 2 /pentane solutions of 6,a ffording as tructure ( Figure 2) which confirmed the coordination modes at ruthenium.
DFT calculations [21] have been used to explore the mechanism of the CÀOb ond cleavage reactions in 1 and 5 and the factors promoting them. For 1,n oi ntermediates are observed experimentally and so all free energies are quotedr elative to this speciesp lus free DPEphos.P Ph 3 substitution in 1 by DPEphos gives [Ru(IMe 4 ) 2 (DPEphos)H 2 ], 8,f or which the all-cis isomer, 8 ccc (+ 3.6 kcal mol À1 ), and the cis, cis, trans-isomer, 8 cct (+ 4.2 kcal mol À1 )a re most stable. [22] The accessibility of the trans dihydride isomer 8 cct suggested ahydride nucleophilic attack mechanism may be involved, similar to that characterised for the hydrodefluorination of   [23,24] Figure 3s hows the computed reactionp rofiles for this process in 8 cct and 8 ccc .F or 8 cct the trans hydride arrangement gives a long RuÀH 1 bond (1.70 )and NBO calculations indicate significant hydridic character (À0.21). Nucleophilic attack proceeds via TS(8-2) cct at + 25.0 kcal mol À1 ,w ith as hort H 1 ···C 1 distance of 1.56 and Ru···H 1 stretching to 1.84 .T he C 1 ÀOb ond also lengthens to 1.48 and elongated C 1 ÀC 2 and C 1 ÀC 6 distances in the aryl ring suggestaMeisenheimer-type structure consistent with nucleophilic aromatic substitution. Hydride attack is also accompanied by ac onformational change in the 8-membered RuÀPÀC=CÀOÀC=CÀP ring, from ad istortedt wist-boat conformation in 8 cct to ab oat conformation in the transition state, [25] similar to the DPEphos fac-k 3 -P,O,P binding mode. [26] IRC calculations confirmt hat TS(8-2) cct links directly to 2 cct in which H 2 is trans to the phosphinophenolate oxygen. The loweste nergy conformation of 2 cct is at À31.5 kcal mol À1 . [27] The equivalent reaction of 8 ccc involves an initial conformational change of the RuÀPÀC=CÀOÀC=CÀP ring to form 8 ccc' at + 14.5 kcal mol À1 .C ÀOb ond cleavage then proceeds via TS(8-2) ccc at + 34.1 kcal mol À1 with similar geometricc hanges to those described above for TS(8-2) cct .T he shorter Ru-H 1 distances in 8 ccc and 8 ccc' (1.65 )a nd lower NBO charges (ca. À0.12) indicatet hat H 1 is now less nucleophilic than in 8 cct , and this reflects the change in the trans ligand,f rom ah ydride in 8 cct to IMe 4 in 8 ccc .T his also correlatesw ith CÀOb ond cleavage being less kinetically accessible in 8 ccc . TS(8-2) ccc leads to 2 ccc at À25.2 kcal mol À1 ,s ubstantially less stable than 2 cct as this structurel acks the favourable trans-H-Ru-O arrangement. [28] CÀOb ond cleavage was also modelled for [Ru(DPEphos) 2 H 2 ] and the most accessible pathway is showni nF igure 4. The allcis isomer, 5 ccc ,r eacts via 5 ccc' and TS (5)(6)(7)(8)(9) ccc at + 29.9 kcal mol À1 to give ap hosphinophenolatep roduct, 9 ccc ,a t À23.0 kcal mol À1 .T he short RuÀH 1 distance in 5 ccc (1.60 )a nd low NBO charge on H 1 (À0.02) indicater educed hydride nucleophilicity compared to 8 ccc ,although the barrier in the bis-DPEphos system is actually lower (see below). In stark contrast to 8 cct ,t he trans dihydride isomer of [Ru(DPEphos) 2 H 2 ] 5 cct ,h as a large barrier of + 48.5 kcal mol À1 .T his differencei sd ue in part to the highere nergy of 5 cct (+ 13.8 kcal mol À1 )a nd the reduced chargeo nH 1 (ca. À0.08 cf. À0.21 in 8 cct ). The latter result highlights how the NHC ligands also serve to enhanceh ydride nucleophilicity.D ifferential sterice ffects in the transition states may also be af actor,a sp robedb yc alculations on 5 ccc and 5 cct in which the PPh 2 groups were replaced by PH 2 .T his model system gave as imilar relative energy for 5 cct (+ 12.6 kcal mol À1 ), but ar educed barrier for the subsequent nucleophilic attack (i.e. from 5 cct to TS(5-9) cct :3 0.2 kcal mol À1 cf. 34.7 kcal mol À1 in the full system). In contrast, the computed barrierf or 5 ccc with the small model is 38.6 kcal mol À1 ,8 .7 kcal mol À1 higher than the full model. Figure 3. Computedf ree energy profiles (kcal mol À1 ,BP86(benzene, D3BJ)) for hydride attack in 8 cct and 8 ccc ,w ith selectedd istances in .E nergies are relative to 1 plus free DPEphosand NBOchargesa tR uand H 1 are indicated in italics for dihydridep recursors. For clarity,IMe 4 ligands are truncateda tthe C2 position (i.e. C 7 and C 8 in the Figure) andphenyl substituents at the ipso carbons. DPEphoshydrogens area lso omitted. 8 ccc' is aconformer of 8 ccc that lies directly on the pathway for CÀOcleavage( see text for details). Computed geometries show significant distortionsi nt he full model:i n5 ccc the trans-P-Ru-P angle is 1428 with the bulky PAr 3 moieties tilting over the hydridel igands. As this angle is only 1608 in the small model, we speculate that the greater distortion of the full model enables nucleophilic attack.
Comparing [Ru(IMe 4 ) 2 (DPEphos)H 2 ]a nd [Ru(DPEphos) 2 H 2 ] shows CÀOb ond cleavage via 8 cct (DG°= 25.0 kcal mol À1 )i s more accessible than in 5 ccc (DG°= 29.9 kcal mol À1 )a nd this is consistentw ith the lower reactivity of the bis-DPEphos system observed experimentally.L ower barriers are computed with higher trans influence ligands (H > IMe 4 ) trans to the hydride nucleophile. The mixed NHC/DPEphos systemsa ppear particularly vulnerable to CÀOb ond cleavage as the strongly donating NHC ligandsb oth enhanceh ydride nucleophilicity and render 8 cct ,t he key trans dihydride precursor,a ccessible. The hydride attack mechanism described hereh as similarities to the "asynchronous oxidative addition" pathway described by Crimmin and co-workers where aR u II metal centre acts as a nucleophile prior to CÀOb ond cleavage. [12] As imilara synchronicity is seen here, with CÀHb ond formation in the transition state being far advanced of either CÀOb ond cleavage or RuÀ Ob ond formation.
In summary,w ehave characterised the surprisingly facile CÀ Ob ond activation of DPEphos ligandsi nt he presence of nucleophilic hydrides. Ligand exchange of all-trans-[Ru-(IMe 4 ) 2 (PPh 3 ) 2 H 2 ]w ith DPEphos resultsi nt he formation of phosphinophenolate complex, 2,w hile with cis, cis, trans-[Ru(IEt 2 Me 2 ) 2 (PPh 3 ) 2 H 2 ], CÀOb ond cleavage is accompanied by CÀNa ctivation of the NHC to form the N-phosphino-functionalised carbene complex 4.D FT calculations indicatet hat CÀO activation involves an ucleophilic pathway in whichahydride ligand attacks the aryl carbon of the DPEphosC ÀOb ond. This process is promoted by the accessibility of a trans dihydride intermediate that features highly nucleophilic hydride ligands. CÀOb ond activation also occurs upon heating cis-[Ru(DPEphos) 2 H 2 ], ap rocess that DFTcalculations indicate is promoted by the steric encumbrance of the mutually cis DPEphos ligands.T his undesirable ligand degradation of DPEphos is of particularn ote given the wide use of this ligand in high temperature homogeneous catalysis. Indeed, degradation of the Rh-DPEphos system described by Weller and Willis is also thought to involven ucleophilic attack, in this case by at hiolate ligand. [7] On am ore constructive note, the hydride nucleophilic attack mechanism proposed here has already been shownt oo perate in catalytic CÀFf unctionalization, [23c,d] ands o may also be an effective means of promoting CÀOb ond activation of the type required fort he valorization of lignin and of its highly oxygenated monomers. [29] Figure 4. Computedf ree energy profile (kcal mol À1 ,BP86(benzene, D3BJ)) for hydridea ttack in 5 ccc ,w ith selected distances in and computed NBO charges at Ru and H 1 in italics for the dihydride precursors.F or clarity, phenyls ubstituents are truncated at the ipso carbons and DPEphos hydrogens are omitted. Chem. Eur.J.2020, 26,1 1141 www.chemeurj.org 2020 The Authors. Published by Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim