Diazaphosphinanes as hydride, hydrogen atom, proton or electron donors under transition-metal-free conditions: thermodynamics, kinetics, and synthetic applications†

Exploration of new hydrogen donors is in large demand in hydrogenation chemistry. Herein, we developed a new 1,3,2-diazaphosphinane 1a, which can serve as a hydride, hydrogen atom or proton donor without transition-metal mediation. The thermodynamics and kinetics of these three pathways of 1a, together with those of its analog 1b, were investigated in acetonitrile. It is noteworthy that, the reduction potentials (Ered) of the phosphenium cations 1a-[P]+ and 1b-[P]+ are extremely low, being −1.94 and −2.39 V (vs. Fc+/0), respectively, enabling corresponding phosphinyl radicals to function as neutral super-electron-donors. Kinetic studies revealed an extraordinarily large kinetic isotope effect KIE(1a) of 31.3 for the hydrogen atom transfer from 1a to the 2,4,6-tri-(tert-butyl)-phenoxyl radical, implying a tunneling effect. Furthermore, successful applications of these diverse P–H bond energetic parameters in organic syntheses were exemplified, shedding light on more exploitations of these versatile and powerful diazaphosphinane reagents in organic chemistry.


Reactions and characterizations:
All reactions involving 1a and 1b were carried out in very dried glass wares under an argon atmosphere using Schlenk technique until the end of the reactions. 1 H and 13 C NMR spectra were recorded in acetonitrile-d 3 13,20.43) and C 6 D 6 (δ H 7.16, δc 128.06) on 400 MHz NMR instrument at Center of Basic Molecular Science (CBMS) of Tsinghua University. Data for 1 H NMR spectra are reported as follows: chemical shift (multiplicity, coupling constants, number of hydrogens). Abbreviations are as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet) and br (broad).
Electrochemical: All samples were prepared and all electrochemical experiments were performed in an inert Ar atmosphere. The supporting electrolyte was [Bu 4 N]PF 6 , which was recrystallized three times by EtOH and dried about 12 hours before use, and the concentration is about 0.1 M in acetonitrile. A standard three-electrode cell consists of a glassy carbon disk as work electrode, a platinum wire as a counter electrode, and 0.1 M AgNO 3 /Ag (in 0.1 M [Bu 4 N]PF 6 -acetonitrile) as reference electrode. Ferrocene (Fc 0/+ ) was used as an external reference and was found to be 0.04 V with respect to our reference electrode. The sample concentrations of 1a, 1b, 1a-[P] + and 1b-[P] + are about 1.0 mM. The scan rate was 100 mV/s. All potentials are reported in volts (V) vs. Fc +/0 .

Kinetics:
The rates of all reactions were determined by UV/Vis spectroscopy in CH 3 CN by using Stopped-flow apparatus. The temperature of the solutions was maintained at 20 ± 0.2 °C by using circulating bath cryostats. 1a and 1b are air-sensitive compounds, so all solutions used for measurement were prepared in glove box. Concentrations of approximate 10 -5 M were used for the acceptors A + and O • to achieve an initial absorbance A 0 of approximate 1.0. In order to satisfy pseudo first-order kinetics with k obs = k 2 [1] 0 + C, the concentrations of nucleophiles 1 were selected by the criterion [1] 0 /[A + or O • ] 0 > 10. All concentrations are specified in the Tables below. Pseudo-first order rate constants k obs (s -1 ) were obtained by fitting the monoexponential function A t = A 0 exp(-k obs t) + C to the observed time-dependent absorbance A t . To obtain the second-order rate constants k HT and k HAT (M -1 s -1 ), each acceptor-donor combination was measured in 3 to 5 different concentrations of 1a or 1b. For hydride transfers, k obs = k HT [1] and for hydrogen-atom transfers, k obs = 2k HAT [1]. As for the measurements for Arrhenius and Eyring correlations, kinetics were performed at 5 different temperatures from 292 K to 322 K. Kinetic runs were reported three times at each temperature.
Acidity estimation: N-heterocyclic phosphines with strong hydricity are generally too low to be determined or synthetically used. Although the hydricity of phosphines have been extensively exploited for synthetic applications, their acidic properties remain elusive. This stimulated us to identify the feasibility of 1a and 1b as proton donors. We first chose several strong bases, such as 1,8-diazabicyclo [5,4,0]-7-undecene (DBU, pK a = 24.34 in acetonitrile), 1,3,4,6,7,8-hexahydro-2Hpyrimido[1,2-a]pyrimidine (TBD, pK a = 26.03) and (tert-butylimino)tris(pyrrolidino)-phosphorane (BTPP, pK a = 28.42) to deprotonate 1a and 1b. 8 Disappointingly, only negative results were obtained. When stoichiometric t BuOK was added to the CD 3 CN solution of 1a, it is pleasant to find that a fast H/D exchange of P-H hydrogen was completed in about 10 minutes Such a result definitely confirmed the acidic reactivity of P-H hydrides. Reversibly, combing t BuOK with 1a-D in CH 3 CN resulted in an almost quantitative recover of 1a after 8 hours. According to the acidities of CH 3 CN (pK a = 31.3) and t BuOH (pK a = 32.3) in DMSO solution, 8 the t BuOK may be a very strong base in CH 3 CN which could react with solvent CH 3 CN or 1a. Present results indicated that a reaction between 1a and t BuOK was established in CH 3 CN (Eq. S1), and, a complete conversion of P-H into P-D demonstrates that 1a may reach the limited value of acidity in CH 3 CN.

Kinetics for the reactions of 1a and 1a-D with A1 + .
Table S1. Kinetics of the reaction of 1a with A1 + in CH 3 CN at 20 ℃ (Stopped-flow, λ = 430 nm).               A1 + (0.02 mmol) was added into the CD 3 CN (0.5 mL) solution of 1a-D (0.02 mmol), and the mixture was checked by NMR spectra after 10 minutes.

The equilibrium between 1a and A2 + in CD
Equilibrium for 1a (0.013 mmol) and A2 + (0.013 mmol) was established about 24 hours in acetonitrile-d 3 (0.5 mL) at 20 o C. All the four components in the mixture can be well monitored by 1 H NMR and 31 P NMR, albeit slight oxidative deterioration of 1a. The equilibrium constant was obtained by the concentration ratio of corresponding four components and calculated by the following equation: Referenced to the hydricity of 5-methyl-5,6-dihydrophenanthridine A2H (ΔG H -(A2H) = 61.4 kcal/mol), the hydricity ΔG H -of 1a can be obtained as 61.8 kcal/mol. Equilibrium for 1a-[P] + (0.01 mmol) and A2H (0.015 mmol) was established in about 24 hours in acetonitrile-d 3 (0.5 mL) at 20 o C. All the four components in the mixture can be well monitored by 1 H NMR and 31 P NMR, albeit slight deterioration. The equilibrium constant was obtained from the concentration ratio of the corresponding four components by using the following equation: G rxn = -RTlnK eq = -0.75 kcal/mol Referenced to the hydricity of 5-methyl-5,6-dihydrophenanthridine A2H (ΔG H -(A2H) = 61.4 kcal/mol), the hydricity ΔG H -of 1a can be obtained as 62.1 5 kcal/mol.    Excess HOTf (purity > 98%) was added into the CD 3 CN (0.5 mL) solution of 1b (0.02 mmol), and the mixture was checked by NMR spectrum immediately. Analysis: We thought the position of proton is on the nitrogen atom of 1a, because a doublet peak was detected in the 31 P NMR (a triplet peak will be detected if the position of proton is on the phosphorus atom) and the unsymmetrical peaks of naphthyl ring and isopropyl group were also shown in the 1 H NMR.   Figure S10. 1) 1 H and 2) 31 P NMR spectra comparison for the reaction between 1a and HOTf in CD 3 CN. (1) 1 HNMR in toluene-d 8

The reactions of 1a and 1b with O • in toluene-d 8 .
(2) 31 P NMR in toluene-d 8 Figure S11. 1 H and 31 P NMR spectra for the reaction between 1a and O • . The integrations of 1 H NMR spectrum are assigned to the structure shown in the spectra, and the shift of 4.76 ppm in 1 H NMR spectrum is OH of product 2,4,6-tri-tert-butylphenol, other hydrogen shifts of 2,4,6-tri-tertbutylphenol are not be marked. (1) 1 H NMR in toluene-d 8 (2) 31 P NMR in toluene-d 8 Figure S12. 1 H and 31 P NMR spectra for the reaction between 1b and O • . The integrations of 1 H NMR spectrum are assigned to the structure shown in the spectra, and the shift of 4.76 ppm in 1 H NMR spectrum is OH of product 2,4,6-tri-tert-butylphenol OH, other hydrogen shifts of 2,4,6-tritert-butylphenol are not be marked. temperature. After 10 minutes, the solvent was rotary-evaporated, and the residue was extracted with n-hexane (20 mL) and then filtered under Ar atmosphere. The filtrate was evaporated to dryness, producing 1a-D as a yellowish solid, 265 mg (97%). However, when the same reaction was performed in the more acidic MeOH solution (with other conditions identical), the P-H species didn't change at all. Similar phenomenon was also observed in the toluene solution.

The reaction of 1a and 1a-D with t BuOK.
(1) 1 H NMR in CD 3 CN (2) 31 P NMR in CD 3 CN Figure S13. 1 H and 31 P NMR spectra for the reaction mixture between 1a and t BuOK in CD 3 CN.  186 g, 40%). And the NMR spectra of mixture and product were shown as below: The NMR spectroscopic data of the product are in good agreement with those in the literature. 11 (1) 1 H NMR of the mixture in CD 3 CN H AIBN (0.03 mmol, 1.5 eq.) was added into the C 6 D 6 (0.5 mL) solution of 1a (0.02 mmol), and the mixture was heated at 80 o C for 3 hours. The reaction was monitored by NMR spectrum.
(1) 1 H NMR in C 6 D 6 (2) 31 P NMR in C 6 D 6 Figure S16. 1 H and 31 P NMR spectra comparison for the reaction between 1a and AIBN. The integrations of 1 H NMR spectrum are assigned to the structure shown in the spectra and the byproduct (CNC(CH 3 ) 2 ) 2 was not marked.
The synthesis of 1a-[P 2 ] using the reaction of 1a with AIBN.  H AIBN (0.03 mmol, 1.5 eq.) was added into the C 6 D 6 (0.5 mL) solution of 1b (0.02 mmol), and the mixture was heated at 80 o C for 3 hours. The reaction was monitored by NMR spectrum.
The NMR spectroscopic data of 1b-[P 2 ] are in good agreement with those reported in the literature. 12 (1) 1 H NMR in C 6 D 6 (2) 31 P NMR in C 6 D 6 Figure S17. 1 H and 31 P NMR spectra for the reaction between 1b and AIBN. The integrations of 1 H NMR spectrum are assigned to the structure shown in the spectrum and the byproduct (CNC(CH 3 ) 2 ) 2 was not marked. Bromobenzene (0.1 mmol), AIBN (15 mol%), 1b (0.15 mmol) and toluene-d 8 (0.5 mL) were mixed in a Schlenk tube under argon and stirred at 90 o C for 5 hours. The 1 H NMR yield was given using 1,3,5-trimethoxybenzene (0.11 mmol) as internal standard.

The hydrodehalogenation reaction of bromobenzene.
(1) 1 H NMR of the mixture in toluene-d 8 (2) 31 P NMR of the mixture in toluene-d 8 Figure S18. The NMR spectra of the mixture solution of hydrodehalogenation reaction of bromobenzene.

DFT Calculations.
Quantum calculations were conducted by using Gaussian 09 13 . Geometry optimizations and frequency computations were performed using the M06-2X 14 density functional in conjunction with the 6-31+G(d) basis set and an ultrafine integration grid. The SMD 15 model was used to account for the solvation effects of toluene, the solvent used experimentally. All of the optimized geometries were characterized as minima structures by frequency calculations. Thermal free energy corrections were obtained at 293.15 K. To obtain more accurate electronic energies, singlepoint energy calculations were performed at the (SMD)-M06-2X/6-311++G(2df,2p) level of theory with the (SMD)-M06-2X/6-31+G(d) optimized structure.
The difference of bond dissociation free energies of P-Br bonds of 1a-Br and 1b-Br was calculated on the basis of reaction Gibbs free energy changes of Eq. S1 and S2 through DFT calculations. The result showed 1a-[P] • and 1b-[P] • should have a comparable ability (with an energy difference of 1.3 kcal/mol) in abstracting bromine atom. This failed to explain the disparate yields of <10% for 1a-[P] • and 90% for 1b-[P] • . Hence, the bromine abstraction pathway seems unlikely. 20. NMR spectra.

Crystal data of 1a.
The crystal structure of 1a could be obtained by the volatilization of solution of 1a in hexane at -30 o C.