A boron-transfer mechanism mediating the thermally induced revival of frustrated carbene–borane pairs from their shelf-stable adducts

Chemists have designed strategies that trigger the conformational isomerization of molecules in response to external stimuli, which can be further applied to regulate the complexation between Lewis acids and bases. We have recently developed a system in which frustrated carbene–borane pairs are revived from shelf-stable but external-stimuli-responsive carbene–borane adducts comprised of N-phosphine-oxide-substituted imidazolylidenes (PoxIms) and triarylboranes. Herein, we report the detailed mechanism on this revival process. A thermally induced borane-transfer process from the carbene carbon atom to the N-phosphinoyl oxygen atom initiates the transformation of the carbene–borane adduct. Subsequent conformational isomerization via the rotation of the N-phosphinoyl group in PoxIm moieties eventually leads to the revival of frustrated carbene–borane pairs that can cleave H2. We believe that this work illustrates an essential role of dynamic conformational isomerization in the regulation of the reactivity of external-stimuli-responsive Lewis acid-base adducts that contain multifunctional substituents.

In our system that uses PoxIms, the revival mechanism has not been fully explained. A tentative mechanism in which a B(C 6 F 5 ) 3 moiety is repelled by the N-phosphinoyl group via a thermally induced isomerization from the syn to anti conformation had been proposed. In this case, the syn/anti conformation refers to the relative orientation of the carbene carbon atom and the N-phosphinoyl oxygen atom with respect to the N-P bond (Fig. 1a) 17 . Herein, we report the results of a combined experimental and theoretical mechanistic study that demonstrates the key role of a transfer step where the triarylborane (BAr 3 ) unit on the carbene carbon atom moves to the N-phosphinoyl oxygen atom (Fig. 1b). In this study, PoxIms with 2,6-i Pr 2 -C 6 H 3 , 2,4,6-Me 3 -C 6 H 2 , and 3,5-t Bu 2 -C 6 H 3 groups were studied and are herein referred to as 1a, 1b, and 1c, respectively.

Results and discussion
Effects of Lewis acidity. To explore the impact of the Lewis acidity of BAr 3 on the formation and reactivity of the carbene-borane adducts, the reaction between 1a and B(p-HC 6 F 4 ) 3 (B 2 ) was undertaken (Fig. 2a). Full consumption of 1a was confirmed after 20 min, resulting in the formation of two CLAs, i.e., 2aB 2 , which contains a N-phosphinoyl oxygen-boron bond, and 3aB 2 , which contains a carbene-boron bond, in 61% and 29% yield, respectively. Previously, we have reported that, even at -30°C, 2aB 1 could be converted to 3aB 1 and that full identification of 2aB 1 could therefore be achieved using NMR analysis conducted at -90°C 17 . In the present case, 2aB 2 exhibited a longer life-time at room temperature than 2aB 1 , which enabled us to prepare single crystals of 2aB 2 by recrystallization from the reaction mixture at -30°C. The molecular structure of 2aB 2 was unambiguously confirmed using single-crystal X-ray diffraction (SC-XRD) analysis. A set of (R a ) and (S a ) atropisomers of 2aB 2 was identified in the asymmetric unit of the single crystal. The molecular structure of (R a )-2aB 2 is shown in Fig. 2b and demonstrates a rare example of complexation-induced N-P axial chirality 29 . As the reaction progressed, 2aB 2 was converted to 3aB 2 and 4a; 2aB 2 was fully consumed within 6 h to afford these compounds in 75% and 25% yield, respectively. It should be noted that 4a is likely furnished via the migration of the Nphosphinoyl group from the nitrogen atom to the carbene carbon atom. However, in the absence of B 2 , this migration only proceeded to 9% at 100°C, even after 25 h 30 . The formation of 4a was therefore promoted by the enhancement of the electrophilicity of the P center via the coordination of the N-phosphinoyl moiety to B 2 . Regeneration of B 2 was observed along with the production of 4a. The molecular structure of 3aB 2 was also confirmed by SC-XRD analysis (Fig. 2c). Comparison of the structural parameters between the solid-state structures of 3aB 2 and 3aB 1 shows their similarity. For example, the C1-B distances in 3aB 2 and in 3aB 1 are 1.710(3) Å and 1.696(3) Å, respectively. The interatomic distance of 3.257(3) Å between the O and B atoms in 3aB 2 suggests the absence of a specific interaction between these atoms, similar to that in 3aB 1 (3.234(3) Å).
Thermolysis of 3aB 2 at 60°C for 3 h resulted in the generation of 4a and B 2 in 77% and 73% yield, respectively, with concomitant formation of [1a-H][HO(B 2 ) 2 ] in 4% yield (conversion of 3aB 2 = 81%; Fig. 3a). Although 2aB 2 was not observed via NMR analysis of this reaction at 60°C, the formation of 4a and B 2 indicates the in situ regeneration of 2aB 2 (vide supra). The formation of [1a-H][HO(B 2 ) 2 ] can be rationalized in terms of a reaction between contaminated H 2 O and the FLP species regenerated from 3aB 2 via 2aB 2 . The regeneration of the FLP species from 3aB 2 was then clearly confirmed by treating 3aB 2 with H 2 (5 atm) at 22°C, resulting in the formation of [1a-H][H- (Fig. 3b). Under identical conditions, no reaction occurred when 3aB 1 was used 17 . At 60°C, 5aB 2 was generated in 90% yield after 3 h, which is almost comparable with the production of 5aB 1 (89%) from 3aB 1 . Thus, the lower Lewis acidity of B 2 relative to B 1 allowed a more facile revival of the FLP species from 3aB 2 than from 3aB 1 . However, the lower Lewis acidity did not affect the progress of the heterolytic cleavage of H 2 by FLPs at 60°C.
Kinetic studies. To gain further insight into the reaction mechanism, the initial rate constants for the generation of 5aB 1 , k int [10 -5 s -1 ], from the reaction between 3aB 1 and H 2 in 1,2dichloroethane-d 4 (DCE-d 4 ) at 60°C were estimated by varying the H 2 pressure from 0.5 to 5.0 atm (Fig. 4a). It should be noted here that when H 2 was pressurized at 5.0 atm, an excess of H 2 (ca. 0.3 mmol) with respect to 3aB 1 (0.010 mmol) was added to the pressure-tight NMR tube. The concentration of H 2 clearly influenced the progress of the reaction, suggesting that the heterolytic cleavage of H 2 by the FLP species is involved in the ratedetermining events. Next, the reaction between 3aB 1 and H 2 at 5.0 atm of pressure was monitored in DCE-d 4 whilst the temperature was varied from 50 to 80°C (Supplementary Figure 27). Pseudo-first order rate constants, k obs [10 -5 s -1 ], of 2.95(2), 11.2(8), 46.4(4) and 183(2) were estimated for the reactions at 50, 60, 70, and 80°C, respectively. Thus, the activation energy and pre-exponential factor obtained from the plot based on the Arrhenius equation, lnk obs = -(E a /R)(1/T) + lnA, are E a = 31.2 [kcal mol -1 ] and A = 3.3(36) × 10 16 [s -1 ] (Fig. 4b). Given the close relation between E a and ΔH ‡ , the values obtained for E a suggest that the formation of 5aB 1 via the reaction between 3aB 1 and H 2 only occurs at temperatures higher than 25°C 32 .
Based on the results presented here and those previously reported 17 , the reaction between the carbene-borane adducts and H 2 to give [PoxIm-H][H-BAr 3 ] likely proceeds via the heterolytic cleavage of H 2 by the FLP species that are formed following the regeneration of the N-phosphinoyl oxygen-borane adducts. These steps are expected to be the rate-determining events because the concentration of H 2 (Fig. 4a), the steric bulk of the N-aryl group 17 and the Lewis acidity of the BAr 3 moiety (Fig. 3b) influence the reaction rates and/or the temperature required to initiate the reaction between the carbene-borane adducts and H 2 .
Two plausible mechanisms were evaluated for the FLPmediated cleavage of H 2 on the basis that the Lewis-basic center reacts with H 2 via cooperation with B 1 (Fig. 5b). One possibility is that the carbene carbon atom works as a Lewis base (path I; the right path in Fig. 5b) [1][2][3][4][5][6][7][8][9]35,36 , while the other is that the Nphosphinoyl oxygen functions as a Lewis base (path II; the left path in Fig. 5b) 37 . In path I, the heterolytic cleavage of H 2 takes places via TS4a (+11.4 kcal·mol -1 ), which arises from the insertion of H 2 into the reaction field around the carbene carbon and boron atoms in FLP-1aB 1 , affording 5aB 1 (-34.8 kcal·mol -1 ), a species more thermodynamically stable than 3aB 1 . In the optimized structure of TS4a (Fig. 5d), the dissociation of the H1-H2 bond (H1···H2 = 0.84 Å) occurs with the partial formation of the H2-C1/H1-B bonds (H2···C1 = 1.83 Å/H1···B = 1.49 Å). Based on these results, the overall path from 3aB 1 to 5aB 1 via FLP-1aB 1 is substantially exothermic (ΔG°=-17.6 kcal·mol -1 ) and includes an overall activation energy barrier of +28.6 kcal·mol -1 required to overcome TS4a. In path II, which takes place via TS5a (a transition state for the insertion of H 2 into the O-P bond) and TS6a (a transition state for the cleavage of H 2 between the O and P atoms), a higher activation energy barrier of +32.7 kcal·mol -1 is predicted to yield intermediate 8aB 1 , which contains a P=O-H + and B-H − species. It should be noted that the potential energy of the optimized TS6a (-3633.288355 hartree) is almost identical to that of the optimized 7aB 1 (-3633.288363 hartree), which causes the reversed Gibbs energy levels as shown in Fig. 5b after the Gibbs energy correction and implementation of solvent effect. Therefore, the discussion on the activation energy barrier to overcome TS6a from 7aB 1 should be not essential. The subsequent transfer of H + from the Nphosphinoyl oxygen atom to the carbene carbon atom furnishes 5aB 1 , although the details of this process remain unclear at this point. The molecular structure of TS6a shows that the cleavage of the H1-H2 bond (H1···H2 = 0.85 Å) by the N-phosphinoyl oxygen and boron atoms occurs in a cooperative fashion (Fig. 5d). Given the experimental and theoretical results reported here, we conclude that path I is the more likely one.
The impact of the N-aryl substituents on the activation energy barriers for the regeneration of [1 + B 1 ] was evaluated using calculations on 3bB 1 , which contains an N-2,4,6-Me 3 -C 6 H 2 group, as well as 3cB 1 , which contains an N-3,5-t Bu 2 -C 6 H 3 group. This afforded ΔG ‡ values of +28.3 and +32.8 kcal·mol -1 for 3bB 1 and 3cB 1 , respectively (Fig. 5a). These results are consistent with the experimental observations, i.e., that 3aB 1 −3cB 1 did not react in the presence or absence of H 2 under ambient conditions under the applied conditions. Furthermore, these results might rationalize the fact that temperature to induce the reaction between these CLAs and H 2 increases in the order 3aB 1 (60°C) < 3bB 1 (80°C) < 3cB 1 (120°C) 17 .
Conclusion. In summary, the reaction mechanism for the revival of frustrated carbene-borane pairs from external-stimuliresponsive classical Lewis adducts (CLAs), comprised of N-phosphine-oxide-substituted imidazolylidene (PoxIm) and triarylboranes (BAr 3 ), is reported based on a combination of experimental and theoretical studies. Remarkably, a transfer of the borane moiety from the carbene carbon atom to the Nphosphinoyl oxygen atom was identified as a key step in the heterolytic cleavage of H 2 by the regenerated FLP species. The optimized transition-state structure for this borane-transfer process was confirmed to include no bonding interactions between the carbene carbon/phosphinoyl oxygen and boron atoms, albeit that it is stabilized by intermolecular non-covalent interactions between the PoxIm and BAr 3 moieties. The heterolytic cleavage of H 2 takes place via the cooperation of the carbene carbon and the boron atoms, and exhibits a lower overall activation energy barrier than that of the path in which a combination of the Nphosphinoyl oxygen and boron atom mediates the H 2 cleavage. These results demonstrate the essential role of dynamic conformational isomerization in the regulation of the reactivity of shelf-stable but external-stimuli-responsive Lewis acid-base adducts by multifunctional Lewis bases.

Methods
Synthesis of 3aB 2 . PoxIm 1a (154.8 mg, 0.40 mmol) and B(p-HC 6 F 4 ) 3 (B 2 ) (183.4 mg, 0.40 mmol) were mixed in toluene (10 mL) at room temperature to furnish the yellow solution. Stirring this mixture for 4 h resulted into the precipitation of a white solid that was collected via removal of the supernatant solution. The obtained solid was washed with hexane (5 mL) and dried in vacuo to afford 3aB 2 as a white solid (230.2 mg, 0.27 mmol, 68%). A single crystal suitable for X-ray diffraction analysis was prepared by recrystallization from CH 2 Cl 2 /hexane at -30°C.
Synthesis of 5aB 2 . A solution of 3aB 2 (51.6 mg, 0.06 mmol) in CH 2 Cl 2 (3 mL) was transferred into an autoclave reactor, which was then pressurized with H 2 (5 atm). Subsequently, the reaction mixture was stirred at 60°C for 4 h, before the solvent was removed in vacuo to give 5aB 2 as a white solid (51.8 mg, 0.06 mmol, >99%). A single crystal suitable for X-ray diffraction analysis was prepared by recrystallization from THF/hexane at -30°C.
Reaction between 1a and B 2 giving 2aB 2 . A solution of 1a (7.4 mg, 0.02 mmol) and B 2 (9.3 mg, 0.02 mmol) in CD 2 Cl 2 (0.5 mL) was prepared at -30°C and then transferred into a J. Young NMR tube. The quantitative formation of 2aB 2 was confirmed at -90°C by 1 H, 13 C, 19 F, and 31 P NMR analysis . A single crystal suitable for X-ray diffraction analysis was prepared by recrystallization from toluene/hexane at -30°C.

Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Details for the preparation of   , 1 atm). a Proposed mechanism for the regeneration of [1 + B 1 ] from the carbene-borane complexes 3aB 1 -3cB 1 . b Proposed mechanism for the heterolytic cleavage of H 2 , enabled by the phosphinoyl oxygen and B(C 6 F 5 ) 3 moieties (left) or by the carbene and B(C 6 F 5 ) 3 moieties (right). c DFT-optimized molecular structures for TS1a and 2a′B 1 . d DFT-optimized molecular structures for TS4a and TS6a.