Selective dehydrogenation of small and large molecules by a chloroiridium catalyst

Abstract

The dehydrogenation of abundant alkane feedstocks to olefins is one of the mostly intensively investigated reactions in organic catalysis. A long-standing, pervasive challenge in this transformation is the direct dehydrogenation of unactivated 1,1-disubstituted ethane, an aliphatic motif commonly found in organic molecules. Here, we report the design of a diphosphine chloroiridium catalyst for undirected dehydrogenation of this aliphatic class to form valuable 1,1-disubstituted ethylene. Featuring high site selectivity and excellent functional group compatibility, this catalytic system is applicable to late-stage dehydrogenation of complex bioactive molecules. Moreover, the system enables unprecedented dehydrogenation of polypropene with controllable degree of desaturation, dehydrogenating more than 10 in 100 propene units. Further derivatizations of the resulting double bonds afford functionalized polypropenes.

A molecular complex catalyzes undirected site-selective desaturation of a broad range of unactivated aliphatics to olefins.

INTRODUCTION

Olefins are ubiquitous as intermediates and reagents for the synthesis of commodity and fine chemicals (1). As a result, the dehydrogenation of vast alkane feedstocks and, more widely, alkyl groups directly to give olefins is a reaction with enormous potential applicability (Eq. 1) (2, 3)

The yields and selectivity afforded by heterogeneous catalysts are generally very low, and the substrate scopes are limited to simple alkanes (e.g., ethane and propane), mainly due to harsh reaction conditions that the heterogeneous system requires (4). For this reason, the dehydrogenation using mild, reactive homogeneous organometallic systems is an area where the development of efficient and broadly applicable catalysts is highly desirable. One potential advantage that the milder organometallic system may have is the control of site selectivity. Because there are five classes of aliphatic substructures (beyond ethane) that can, in principle, be desaturated (Fig. 1A), the site selectivity is important but could be extremely difficult to achieve in complex or large molecules containing multiple desaturatable sites (see examples in Fig. 1B).

Fig. 1. Undirected catalytic dehydrogenation of various unactivated aliphatics.

(A) Five classes of aliphatic substructures that are subject to desaturation to form olefins. (B) Representative examples contain multiple desaturatable aliphatic substructures. (C) Proposed tricoordinate 14-electron iridium species that are catalytically active for thermal alkane dehydrogenation.

Pioneering works by Crabtree and co-workers (5, 6) and Felkin and co-workers (7) have showed that monophosphine-ligated 14-electron Ir(I) fragments of the form of trans-L₂XM (1; L is a phosphine, and X is an anionic ligand; see Fig. 1C) are catalytically active for thermal transfer dehydrogenation (TD) of alkanes (i.e., using a hydrogen acceptor). Although groundbreaking, this system suffers from facile ligand degradation, thus severely limiting catalytic turnover (TO) numbers. Since then, many soluble transition metal catalysts have been developed for undirected alkane dehydrogenation (8–17). Among them, the most effective thermocatalytic system is that containing 14-electron (^RPCP)Ir fragments [2; ^RPCP is a bis(phosphino) aryl pincer ligand; R is substituents on the P atoms; see Fig. 1C] (8). For example, Goldman and co-workers (10) and this group (14) have showed that the iPr-substituted pincer complexes with (^iPrPCP)Ir (2c) and (^iPrP^SC^OP)Ir (2d) fragments (see Table 1 for structures) could afford thousands of TOs in the TD of simple small alkanes. The (^RPCP)Ir system with a mer-type configuration shares the same symmetrical trans-L₂XM coordination geometry with Crabtree’s monophosphine system: The anionic X ligand (which is an aryl group in the pincer) is trans to a vacant coordination site that is subject to substrate binding (Fig. 1C). The outperformance of the pincer complexes is in large part attributed to their high thermal stability (8). Nevertheless, the undirected dehydrogenation has been barely applied to organic synthesis because of low functional group tolerance and poor substrate scope (18). A key challenge limiting the scope and diversity is that the known reaction occurs effectively only with monosubstituted ethane (MSE) and 1,2-disubstituted ethane (1,2-DSE) (8). In contrast, the dehydrogenation of congested, unactivated 1,1-disubstituted ethane (1,1-DSE) has been exhibited with very scarce examples (19), and no examples of unactivated 1,1,2-trisubstituted ethane (1,1,2-TriSE) and 1,1,2,2-tetrasubstituted ethane (1,1,2,2-TetraSE) have been reported (Fig. 1A).

Table 1. Catalyst development for dehydrogenation of 1,1-DSE.

Reaction conditions: catalyst (2 mol %), 4a (0.2 mmol), TBE (0.2 mmol) in toluene-d8 (0.5 ml), 150°C, 1 hour. Yields were determined by ¹H NMR spectroscopy with CH₃NO₂ as the internal standard.

*For entries 5 to 13 using the Ir dimer as the Ir source, x mol % Ir refers to the use of x/2 mol % Ir dimer and x mol % bidentate ligand or 2x mol % monodentate ligand.

To broaden the applicability of the dehydrogenation chemistry, it is imperative to invent a broadly applicable catalyst for the desaturation of different aliphatic classes. The structural motif of 1,1-DSE is prevalent in natural and synthetic products [e.g., terpenoids and polypropene (PP); see Fig. 1B]. While directed dehydrogenation of 1,1-DSE using existing directing groups or pendant radical precursors (20–23) and dehydrogenation of activated 1,1-DSE (24–26) have been reported, methods of undirected dehydrogenation of unactivated 1,1-DSE have remained underexplored. In this work, we present the first examples of site-selective catalytic desaturation of unactivated 1,1-DSE to form 1,1-disubstituted ethylene without the need for a directing group. A diphosphine chloroiridium complex of the form of cis-L₂XM [which, contrasting with the classic trans-L₂XM type catalysts (27, 28), has the anionic X ligand cis to the vacant coordination site; see 3 in Fig. 1C] was found to catalyze the TD of unactivated alkanes and aliphatics, including 1,1-DSE, with high selectivity and excellent functional group compatibility; the synthetic application has been demonstrated by late-stage dehydrogenation of complex molecules and postfunctionalization of PP.

RESULTS

We embarked on our study with the identification of a catalyst for the TD of 1,1-DSE. An arene (4a) containing an isopropyl (1,1-DSE) and ethyl (MSE) groups para to each other was chosen as the model substrate for the purpose of assessing the site selectivity (Table 1). On the basis of the previous (^RPCP)Ir-catalyzed TD with tert-butylethylene (TBE) as the hydrogen acceptor, we initially examined the known pincer catalysts for the TD of 4a with TBE (1 equiv.). With the tBu-substituted complexes (^tBuPCP)IrHCl (2a) (9) and (^tBuP^OC^OP)IrHCl (2b) (12) as the precatalysts [2 mole percent (mol %)] and NaOtBu as the catalyst activator, the reaction at 150°C gave low conversion after 1 hour, and the dehydrogenation occurred at the Et group (to form 5a′) but not the iPr group (entries 1 and 2). Under the same conditions, the runs using the less hindered, iPr-substituted complexes 2c and 2d gave enhanced conversion (10 to 19%; entries 3 and 4). With 2d, two products corresponding to the dehydrogenation of the iPr (5a) and Et (5a′) groups, respectively, were observed (5a:5a′ = 5:95). The reaction with 2c afforded an additional product resulting from the double dehydrogenation of both the iPr and Et groups (5a″). Although 5a′ was still the major product, the selectivity for 5a was improved (5a:5a′:5a″ = 28:69:3). These data suggest that the use of a less hindered pincer ligand favors the desaturation of the congested aliphatics.

However, earlier studies have shown that (^RPCP)Ir complexes with R smaller than iPr tend to form catalytically inactive di- or multinuclear clusters (29). Considering this, we turned to bidentate diphosphine (P₂) ligands. The combination of such a ligand with an appropriate bite angle (~60° to 90°) and an X-type anionic ligand would generate a cis-P₂XIr fragment (30). The scaffold of cis-P₂XIr is expected to be more flexible than that of the isoelectronic (^RPCP)Ir ligated by rigid tridentate pincers. We envisioned that the employment of a sterically hindered bidentate ligand in cis-P₂XIr might be sufficient to offer protection against bimolecular catalyst deactivation or cluster formation, while the replacement of one bulky phosphine in trans-P₂XIr [or (^RPCP)Ir] at the position cis to the vacant coordination site with a sterically less demanding X ligand might favor the dehydrogenation of congested aliphatics (29).

With this in mind, a series of P₂ ligands were explored with [Ir(COD)Cl]₂ as the Ir source (using 2 equiv. of P₂ relative to [Ir(COD)Cl]₂; COD, cyclooctadiene). While the reaction with bis(diphenylphosphino)butane (DPPB) (L1) (entry 5), bis(diphenylphosphino)methane (DPPM) (L2), and bis(diphenylphosphino)ethane (DPPE) (L3) showed no activity (fig. S1), the run with 2,2′-bis (diphenylphosphino)-1,1′-binaphthyl (BINAP) (L4) gave 8% conversion. Despite the low activity, the site selectivity was promising, furnishing 5a as the major product (5a:5a′:5a″ = 59:35:6; entry 6). SEGPHOS (L5) afforded higher conversion (19%) and selectivity (5a:5a′:5a″ = 65:30:5; entry 7). DTBM-SEGPHOS (L6) was found to be the most effective among the ligands investigated, giving 5a with 83% selectivity at 40% conversion (entry 8). Increasing the loadings of the catalyst (10 mol % Ir) furnished 65% conversion, and the fraction of the double-dehydrogenation product 5a″ increased as expected (5a:5a′:5a″ = 75:10:15; entry 9). The combination using a monophosphine ligand (4 equiv. PCy₃ or PPh₃ relative to [Ir(COD)Cl]₂) showed no activity (entries 10 and 11), presumably because of low thermal stability (5–7). The replacement of [Ir(COD)Cl]₂ with [Ir(COE)₂Cl]₂ [cyclooctene (COE)] had negligible impact on the reaction outcome (entry 12 versus 8), but the use of [Ir(COD)OMe]₂ was completely inactive for the dehydrogenation (entry 13).

The substrate scope of the TD reaction with an emphasis on illustrating the reactivity, compatibility, and site selectivity was then explored (Fig. 2). We first studied the catalytic activity of the L6/[Ir(COD)Cl]₂ combination (1 L6 + 0.5 [Ir(COD)Cl]₂) in the benchmark reactions, the TD of n-octane, and cyclooctane with TBE (Fig. 2A). Heating the solution containing 20,000 n-octane:2000 TBE:1 Ir at 150°C gave octenes (5b) with 1020 TOs after 18 hours (see table S1 for product distribution). The catalytic efficiency and product selectivity are comparable to those obtained by the most effective pincer iridium catalysts (10, 14). This catalyst also showed good activity for the conversion of cyclooctane to COE (5c), giving 357 TOs under the conditions used for n-octane.

Fig. 2. Scope.

(A) Reactivity of L6/[Ir(COD)Cl]₂ toward various aliphatic substructures. (B) Compatibility of L6/[Ir(COD)Cl]₂ toward various organic functional groups. (C) Site selectivity of L6/[Ir(COD)Cl]₂. Yields and TOs were determined by GC with internal standard unless otherwise noted. *L6/[Ir(COD)Cl]₂ = 1 L6 + 0.5 [Ir(COD)Cl]₂. †The mole ratios refer to moles of Ir atom, not moles of the dimer [Ir(COD)Cl]₂. ‡The dehydrogenation of 4f was conducted in toluene-d₈, and yields were determined by ¹H NMR with internal standard. §Using 1.5 equiv. of TBE relative to 4f (0.4 M 4f in toluene-d₈), 4f:TBE:Ir = 50:75:1, 150°C, 4 hours. ¶Isolated yield. #Yield was determined by ¹H NMR with internal standard.

With a focus of this study on the dehydrogenation of 1,1-DSE, we next investigated the reactivity of several small molecules of this class (Fig. 2A). For comparison, the reactions were conducted by using L6/[Ir(COD)Cl]₂, 2c/NaOtBu, and 2d/NaOtBu, respectively. Heating the solution containing 10,000 cumene (4d):1000 TBE:1 Ir at 150°C gave 980 TOs with L6/[Ir(COD)Cl]₂, 276 TOs with 2c/NaOtBu, and 68 TOs with 2d/NaOtBu after 18 hours. The dehydrogenation of a bulkier substrate, 1,1-diphenyl substituted ethane (4e), occurred at 150°C with L6/[Ir(COD)Cl]₂ using 2 mol % Ir and 1 equiv. TBE (relative to 4e) in mesitylene and furnished the desaturated product 5e in 51% yield after 4 hours. In contrast, the runs with 2c/NaOtBu or 2d/NaOtBu gave minimal conversion. L6/[Ir(COD)Cl]₂ is even effective for the desaturation of a highly congested, adamantyl-substituted 1,1-DSE (4f), whereas 2c/NaOtBu and 2d/NaOtBu are completely inactive in this case. The dehydrogenation of 2,4-dimethyl-pentane (4g) with L6/[Ir(COD)Cl]₂ afforded two products, 1,1-disubstituted olefin 5g and trisubstituted olefin 5g′, in 43% combined yield after 4 hours with the former as the major product (5g:5 g′ = 5.3:1). As a comparison, the pincer catalysts are hardly active toward 4g. Since 4g can be viewed as a model substrate of PP, these results suggest that the L6/[Ir(COD)Cl]₂ combination may hold promise for the dehydrogenation of this polymer class (vide infra). The superior performance of L6/[Ir(COD)Cl]₂ in the desaturation of 1,1-DSE was further demonstrated by the example of 2,4-diphenyl-pentane (4h). The reaction produced three products in 32% total yields: one 1,1-disubstituted olefin (5h) and two dienes (5h′ and 5h″) [5h:(5h + 5h′) = 90:10], while only trace amounts of the dehydrogenation products were observed when 2c/NaOtBu or 2d/NaOtBu was used. Note that L6/[Ir(COD)Cl]₂ is inactive toward the more congested 1,1,2-triphenyl and 1,1,2,2-tetraphenyl substituted ethanes (4i and 4j).

As aforementioned, one key issue of the undirected dehydrogenation reactions limiting their applications is the low functional group compatibility. In this context, we explored the dehydrogenation of 1-aryl, 1-methyl disubstituted ethanes bearing various functionalities on the aryl rings (Fig. 2B). To enhance the yields of desaturated products, the reactions were performed with 10 mol % catalyst (i.e., 10 mol % L6 + 5 mol % [Ir(COD)Cl]₂) and 1.5 equiv. TBE (relative to the substrate) in mesitylene. Under these conditions, the dehydrogenation of 4d gave 81% yield after 4 hours (5d), and the substrates with Me groups in the ortho, meta, and para positions of the aryl groups afforded similar yields (5k to 5m). Various functional groups are well tolerated. The ether (5n), ester (5o and 5p), and acetyl (5q) groups are compatible with the catalyst. The cyanide (5r) and thioether (5s) groups with fair coordination ability exert a notable impact on the dehydrogenation, but reasonable yields were still achieved. The catalyst tolerates an unprotected hydroxyl group in the ortho or para position of the aryl ring (5t and 5u), although a carboxylic acid causes the catalyst poisoning (5v). The dehydrogenation of substrates bearing primary and secondary amines proceeded effectively (5w and 5x). The F and Cl groups could be tolerated (5y and 5z), but the reaction with Br- or I-containing substrate gave low or no conversion (5aa and 5ab). 2-Benzylthiophene and 2-indole substituted aliphatics were dehydrogenated smoothly, showing the compatibility of this catalyst with heteroarenes (5ac and 5ad). Moreover, the boron-substituted 1,1-DSE was desaturated to vinyl boronate ester (5ae) in high yield.

The site selectivity is critical in dehydrogenating molecules containing two or multiple inequivalent desaturatable aliphatics (Fig. 2C). This selective desaturation of the 1,1-DSE over the MSE moiety was observed for the pilot substrate 4a using L6/[Ir(COD)Cl]₂ (vide supra). Monitoring the TD process revealed that the ratio of 5a:5a′ was 3.6:1 at the earliest time (3 min), and the ratios increased over time (e.g., 9.7:1 at 4 hours; see fig. S26 for more data). These results suggest a kinetic preference for the dehydrogenation of 1,1-DSE versus MSE, although the site selectivity for the disubstituted olefin could be enhanced by the thermodynamics of reversible hydrogenation (in accord with this hypothesis, submission of 5a′ to the catalytic conditions, but without TBE, resulted in the formation of 4a, 5a, and 5a″; fig. S27).

To eliminate the potential effect of conjugation with the aryl ring on the site selectivity, we conducted the TD using 2-methyltridecane (4af) as the substrate. With a specific purpose to elucidate the selectivity between 1,1-DSE and MSE, the reaction was conducted at a relatively low temperature (at 110°C) to minimize the isomerization of the olefin products. The reactions with L6/[Ir(COD)Cl]₂ yielded 1,1-disubstituted olefin 5af as the dominant product, along with multiple minor products including monosubstituted (5af′) and trisubstituted (5af″) olefins (Fig. 2C; see fig. S28 for more data), whereas the run with the pincer system 2d/NaOtBu under the otherwise identical conditions gave the monosubstituted olefin 5af′ as the major product at the early stages of the reaction (fig. S28) (10, 14).

The selectivity for 1,1-DSE over MSE was further demonstrated by the reactions of diarylamines (4ag and 4ah) and diarylethers (4ai and 4aj) bearing iPr and Et groups on two different aryl rings. All these reactions with L6/[Ir(COD)Cl]₂ afforded three products, two mono-dehydrogenation and one double-dehydrogenation products, among which the 1,1-DSE desaturation species (5ag to 5aj) constituted the major products (76 to 90% selectivity).

In addition, the system L6/[Ir(COD)Cl]₂ exhibits excellent site selectivity for 1,1-DSE over 1,2-DSE. For example, the reaction of 4ak produced 1,1-disubstituted ethylene exclusively (5ak, 52%), leaving the aryl-substituted 1,2-DSE untouched. The reaction of 1,2-diphenyl substituted propane (4al) furnished 53% 1,1-disubstituted (5al) and 6% trisubstituted olefin (5al′) after 2 hours. Monitoring the reaction for a longer period of time unveiled a 5al-to-5al′ conversion, albeit slowly (see table S2), indicating that the trisubstituted olefin was derived from the 1,1-disubstituted olefin via isomerization. The example of 1-Ph,3-Me butane (4am) is also illustrative as it contains a 1,2-DSE moiety between a 1,1-DSE and an aryl ring. 1,1-Disubstituted olefin was formed as the dominant product (5am) in the beginning (10 min), together with a small amount of trisubstituted olefin (5am″) stemming from the isomerization of 5am; no product of direct dehydrogenation of the 1,2-DSE moiety (5am′) was observed. As the reaction proceeded, we observed the accumulation of a conjugated diene (5am*), which was presumably produced via further dehydrogenation of the 1,2-DSE moiety in 5am (in support of this hypothesis, submission of 5am to the catalytic conditions formed 5am* readily; see fig. S29). At the late stage of the reaction, we did observe a minimal amount of 5am′, which was likely formed via hydrogenation of the 1,1-disubstituted olefin in 5am*, rather than direct dehydrogenation of 4am (31).

With an understanding of the compatibility and site selectivity of this catalytic system, we evaluated the applicability of the TD reaction in more complex settings (Fig. 3A). Submission of guaiazulene, a natural product for anti-inflammation, to the catalytic conditions gave the desaturated product 5an in high yield. The dehydrogenation of tubulin polymerization inhibitor produced 1,1-diarylethylene 5ao in useful yield. The selective desaturation of the 1,1-DSE moiety in totarol proceeded effectively (5ap) despite the presence of multiple 1,2-DSE moieties and an ortho-OH group. The reaction of cedrol derivative is another example showing the exquisite site selectivity in complex settings: The 1,1-DSE moiety was desaturated preferentially over two 1,2-DSE and two 1,1,2-TriSE moieties, furnishing 1,1-dialkylethylene (5aq) in useful yield. 5-HT7 receptor inhibitor (4ar) contains two different desaturatable aliphatics, one 1,2-DSE between two N atoms and one 1,1-DSE. With L6/[Ir(COD)Cl]₂, the dehydrogenation occurred exclusively at the latter to form 5ar. Such a site selectivity is complementary to that obtained by the photochemical dehydrogenation involving a hydrogen atom transfer mechanism (26), wherein the dehydrogenation occurred preferentially at the 1,2-DSE bearing the electron-rich C─H bonds adjacent to the N atoms (see fig. S30 for the comparative experiment).

Fig. 3. Dehydrogenation in complex settings and derivatization of desaturated product.

(A) Late-stage dehydrogenation of bioactive molecules. (B) Synthesis of fine chemicals and pharmaceutical ingredients via dehydrogenation. *“x mol % Ir” refers to the use of x/2 mol % [Ir(COD)Cl]₂ and x mol % DTBM-SEGPHOS (L6). cata., catalyst; Bpin, pinacolate boryl.

The dehydrogenation of dehydroabietic acid derivatives has been investigated by Voica and co-workers (20) and Parasram and co-workers (21) independently: Using a guided desaturase, the reaction of dehydroabietyl amine derivative led to desaturation of the decalin system at the C2 and C3 positions (20), whereas the Pd-catalyzed visible light–induced dehydrogenation of dehydroabietol derivative occurred at the C6 and C7 positions (21). In contrast, treatment of dehydroabietic ester (4as) with this Ir catalyst resulted in selective formation of the 1,1-disubstituted olefin 5as (Fig. 3A). These results highlight the potential applicability of the dehydrogenation chemistry for late-stage modification of complex molecules in a controlled and complementary fashion, editing structures with tailored C─C double-bond allocations.

In addition, the dehydrogenation-functionalization sequence with no need for purification of the olefin intermediates allowed for selective incorporation of the desired functionalities. For example, the bromomethoxylation of 5at generated in situ from the TD of 2-iPr–substituted naphthalene gave 6 in 81% isolated yield, and catalytic asymmetric hydroboration (32) and hydrosilylation (33) afforded the formal borylation (7) and silylation (8) products with high isolated yields and enantioselectivity. The dehydrogenation-hydroboration starting from 4au furnished chiral alkyl boronate ester (9), which was oxidized to fenoprofen 10 with 97% enantiomeric excess (ee) and 54% total yield. Moreover, the dehydrogenation, coupled with isomerization, provides a previously unknown approach to stereodefined trisubstituted olefins (Fig. 3B). For example, the site-selective dehydrogenation of 4av bearing a benzyl substituent yielded 1,1-disubstituted olefin 5av as the dominate product, along with a trace amount of the trisubstituted olefin 11 (5av:11 = 96:4; 56% combined yield). Using the Fe-catalyzed di-to-trisubstituted olefin isomerization (34), 5av was converted to 11, temarotene, with excellent stereoselectivity. (The trans configuration of the trisubstituted olefin was confirmed by x-ray diffraction.)

The chemoselective incorporation of functionalities into polyolefins can, to a great extent, improve their physical properties (35–38). Given the ability of L6/[Ir(COD)Cl]₂ to dehydrogenate the small-molecule 4g (vide supra), we envisioned that this catalyst might catalyze the dehydrogenation of PP (Fig. 4A). Treatment of a PP [12, M_w = 28,400, PDI (polymer dispersity index) = 2.8] with L6/[Ir(COD)Cl]₂ (0.8 mol % Ir relative to the total amount of propene units) and TBE (0.10 M; propene unit:TBE = 8:1) in mesitylene at 150°C for 5 hours generated seven double bonds per 100 propene units (i.e., the level of desaturation was 7%), including 6 1,1-disubstituted olefins and 1 trisubstituted olefin (13). Under similar conditions, prolonging the reaction to 18 hours furnished 11 double bonds per 100 propene units with the di:trisubstituted olefin ratio being 3.5:1 (14). Using a higher–molecular weight (MW) PP (15; M_w = 362,400, PDI = 4.0), the reaction with TBE (0.10 M) after 1.5 hours formed two double bonds per 100 propene units with high selectivity for the disubstituted olefin (di:tri = 9:1; 16). Doubling the loading of TBE (0.2 M) and prolonging the time (18 hours) produced the desaturated PP containing 12 double bonds per 100 propene units (di:tri = 4:1; 17). These results indicate that the desaturation level can be controlled by the reaction time and the stoichiometry, and extending the time results in a higher fraction of trisubstituted olefins located in the polymer chain due to olefin isomerization.

Fig. 4. Dehydrogenation of PP.

(A) Dehydrogenation of two types of PPs with different MW. (B) Hydroxylation and epoxidation of the desaturated PP. (C) Polymeric materials of 15, 16, 17, and 19. T_m, melting temperature; T_g, glass transition temperature.

GPC (gel permeation chromatography) analysis of the desaturated PPs (with the exception of 17) showed no substantial changes in the MWs compared with the parent PPs, implying no chain cleavage or cross-linking. We hypothesized that the high olefin incorporation rate in the polymer chain of 17 might alter its conformation, thus affecting the GPC MW measurement. The hydrogenation of 17 yielded a PP 18 with MW comparable to the parent PP 15 (fig. S32). While the desaturated PPs 13 and 16 are white, the polymers 14 and 17 are light yellow, likely a result of the high-degree olefin incorporation. Note that the desaturation of PPs led to lower melting temperatures (if available) and improved solubility compared to parent PPs [e.g., 14 and 17 are even soluble in toluene at room temperature (RT)]. No melting transition was observed for 17, and the high-degree incorporation of the double bonds into this high-MW PP yielded a polymer with elastic property (Fig. 4C; see movie S1 for the elastic behavior), which was neither observed for the lower–olefin incorporation variant 16 nor for the lower-MW variant 14 with similar olefin content.

The desaturated PPs can potentially undergo various functionalizations via derivatization of the resulting C─C double bonds (Fig. 4B). For example, the hydroxylation of 13 through a hydroboration-oxidation sequence resulted in the disappearance of all double bonds and the incorporation of 7 hydroxyls per 100 propene units, furnishing white, plate-shaped materials (19; Fig. 4C). The epoxidation of 13 occurred selectively at the less hindered 1,1-disubstituted olefins over the trisubstituted one, generating ca. five epoxides per 100 propene units (20). The characteristic signals for these functionalities were identified spectroscopically (see the Supplementary Materials). Again, GPC analysis of the functionalized PPs showed no substantial changes in the MWs. The introduction of functionalities at a controllable level into the commodity PPs may create new approaches to preparing polymeric materials unattainable by conventional means (39, 40).

Stoichiometric experiments were conducted to determine the potential catalytic intermediates (Fig. 5A). Reaction of [Ir(COD)Cl]₂ with DTBM-SEGPHOS (L6) in mesitylene at RT for 15 min formed a monomeric pentacoordinate complex (κ²-P₂)IrCl(COD) (21) as the dominant species [90% nuclear magnetic resonance (NMR) yield; structure corroborated by NMR data]. Along with 21, another species (22) was observed as well, albeit in very low yield (2%; see Fig. 5B for ³¹P{¹H} NMR data). Heating the solution at 60°C for 9 hours resulted in the conversion of 21 to 22 as the major product (56%), and changing the reaction solvent to pentane allowed for the isolation of 22 in 70% yield. Although attempts to obtain x-ray quality crystals failed, the observation of a single ³¹P NMR signal (Fig. 5B), together with mass and elemental analysis, establishes that 22 is a Cl-bridged dimeric complex [(κ²-P₂)IrCl]₂ with a centrosymmetric structure (41).

Fig. 5. Studies of the competent catalytic intermediates.

(A) Synthesis of cis-P₂ClIr complexes. H atoms in the crystal structure of 24 were omitted for clarity. The inset only shows the Ir and the atoms bound to it. (B) ³¹P{¹H} NMR stack plots. (C) Schematic illustration of the favorable steric effect of cis-P₂ClIr versus trans-P₂XIr on the C─H bond addition and BHE steps in the reaction with 1,1-DSE. R, large substituent; R′, small substituent.

Treatment of the isolated complex 22 with 1-octene formed an Ir(I) 1-octene adduct (23) (Fig. 5B), which has been previously crystallographically characterized, showing a square-planar geometry with the Cl ligand cis to the bound olefin (42). Moreover, 22 reacted with PhI to give a pentacoordinate Ir(III) phenyl iodo chloro complex 24; x-ray diffraction analysis of 24 revealed a distorted trigonal bipyramid geometry, with Cl and one P atom at the axial positions (Fig. 5A). In contrast, the analogous Ir dimer [(BINAP)IrCl]₂ with the less hindered BINAP ligand (L4) is unreactive to 1-octene (see the Supplementary Materials for details), which appears to be inconsistent with a route that olefin addition precedes dimer cleavage. These observations imply that the dimeric complex 22 may break into a monomeric, tricoordinate Ir(I) species, cis-P₂ClIr (3) (Fig. 5A), which then undergoes the addition with olefin or PhI; apparently, the Cl group remains bound to the Ir, and the mer-type coordination geometry of the fragment cis-P₂ClIr is retained over the course of these addition reactions. Using 22 for the dehydrogenation of cumene (4d) afforded catalytic efficiency similar to that obtained by L6/[Ir(COD)Cl]₂ (see the Supplementary Materials). Collectively, these results suggest that the cis-P₂ClIr fragment 3 is the catalytically active species, which mediates alkane C─H bond addition to initiate the Ir(I)/Ir(III) dehydrogenation cycle (see fig. S34 for the proposed catalytic cycle) (43, 44). Attempted synthesis of the hydride species by treatment of L6/[Ir(COD)Cl]₂ with NaBEt₃H led to a product tentatively assigned as (L6)IrH(L′)_n (L′ is a neutral ligand) based on in situ NMR analysis, although further characterization was precluded because of low stability. The in situ formed species exhibited poor catalytic performance, suggesting that the hydride species is not likely a relevant on-cycle catalytic species (see the Supplementary Materials for details).

DISSCUSSION

The key difference between this cis-L₂XM and the traditional trans-L₂XM systems lies in the ligand arrangement: The vacant coordination site available for alkane C─H bond activation is cis to the X ligand in the former whereas trans in the latter. Seminal works by Krogh-Jespersen and co-workers (45) and Riehl and co-workers (46) have elucidated that the π-donation from the trans-X into the d orbital orthogonal to the P─Ir─P linkage has a favorable effect on the thermodynamics of alkane C─H addition (47). Thus, it is notable to note that the present cis-P₂ClIr system without the trans-X → Ir π-donation is effective for alkane dehydrogenation. With the trans-P₂ClIr systems, the alkane C─H addition (29, 43, 44) and the β-H elimination (BHE) step (6, 29, 48) both were found to be rate-determining of alkane dehydrogenation. It is our belief that the potentially unfavorable electronic effect in cis-P₂ClIr as a result of the lack of the trans-X → Ir π-donation could be outweighed by favorable steric effect. The substitution of one of the bulky phosphine groups in trans-P₂XIr with the small Cl group in cis-P₂ClIr, to a great extent, reduces the steric hindrance around the Ir center and would consequently lower the activation barrier for both the C─H addition and BHE steps (Fig. 5C). The steric contribution is expected to be particularly significant in the dehydrogenation of the relatively crowded 1,1-DSE. One possible explanation for the success of cis-P₂ClIr is that its ligand arrangement would allow for the formation of a favorable BHE transition state, in which the bulker substituent of 1,1-DSE is oriented toward the unbulky Cl group (Fig. 5C), although further computational and experimental studies are needed to provide insights into the origin of the reactivity. The design of organometallic catalysts of the form of cis-L₂XM for which the dehydrogenation could be applicable to more congested trisubstituted (1,1,2-TriSE) or tetrasubstituted ethane (1,1,2,2-TetraSE) is under way.

MATERIALS AND METHODS

Materials

Toluene and tetrahydrofuran were freshly distilled from sodium benzophenone ketyl before use. Mesitylene was distilled from LiAlH₄ and stored under argon. C₆D₆ and toluene-d₈ were dried under Na/K alloy and stored under argon. All other reagents and solvents used in this study were purchased from commercial sources and used as received unless otherwise stated.

Typical procedure for TD of small molecules

In an Ar-filled glove box, an oven-dried 10-ml thick-wall glass tube was charged with [Ir(COD)Cl]₂ (6.7 mg, 10 μmol, 5.0 mol %), DTBM-SEGPHOS (L6, 23.6 mg, 20 μmol, 10 mol %), cumene (4d, 24.0 mg, 0.2 mmol, 1.0 equiv.), TBE (39 μl, 0.3 mmol, 1.5 equiv.), and mesitylene (1.0 ml). The tube was sealed with a Teflon plug, and the reaction mixture was stirred at 150°C in a preheated oil bath for 4 hours. After that, the reaction was cooled to RT, and the resulting mixture was analyzed by gas chromatography (GC) with toluene as the internal standard (82% yield).

Typical procedure for dehydrogenation reaction of PP

In an Ar-filled glove box, an oven-dried 100-ml thick-wall glass tube was charged with [Ir(COD)Cl]₂ (67.2 mg, 0.1 mmol), DTBM-SEGPHOS (L6, 235.9 mg, 0.2 mmol), PP 12 (1.0 g), TBE (390 μl, 3 mmol, 0.1 M), and mesitylene (30.0 ml). The tube was sealed with a Teflon plug, and the reaction mixture was stirred at 150°C in a preheated oil bath for 5 hours. After that, the reaction mixture was poured into a flask containing cold methanol (−20°C). The precipitate was collected and then dried under reduced pressure to a constant weight to afford polymer PP 13 (980.0 mg).

Supplementary Materials

This PDF file includes:

Materials and Methods

Supplementary Text

Figs. S1 to S146

Tables S1 to S11

X-ray Data

Spectra

References

Other Supplementary Material for this manuscript includes the following:

Movies S1 to S4