An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

Two chlorophosphites, the biphenyl-based BIFOP–Cl and the diphenyl ether-based O–BIFOP–Cl, exhibit striking differences regarding their reaction with water. While BIFOP–Cl is nearly completely unreactive, its oxo-derivative O–BIFOP–Cl reacts instantly with water, yielding a tricyclic hydrocarbon unit after rearrangement. The analysis of the crystal structure of O–BIFOP–Cl and BIFOP–Cl revealed that the large steric demand of encapsulating fenchane units renders the phosphorus atom nearly inaccessible by nucleophilic reagents, but only for BIFOP–Cl. In addition to the steric effect, a hypervalent P(III)–O interaction as well as an electronic conjugation effect causes the high reactivity of O–BIFOP–Cl. A DFT study of the hydrolysis in BIFOP–Cl verifies a higher repulsive interaction to water and a decreased leaving tendency of the chloride nucleofuge, which is caused by the fenchane units. This high stability of BIFOP–Cl against nucleophiles supports its application as a chiral ligand, for example, in Pd catalysts.

The chlorophosphite BIFOP-Cl (1) is air-stable and very resistant to hydrolysis (Scheme 2) [13,15]. The low reactivity of 1 to O-and C-nucleophiles is explained by the tight encapsulation of the P-Cl unit of the endo-fenchane moieties [15]. This unusual stability of the BIFOP-halides prompted the comparison of BIFOP-Cl (1) with its diphenyl ether derivative O-BIFOP-Cl (3). Despite similar encapsulation by two fencholate moieties, O-BIFOP-Cl 3 exhibits a significantly higher reactivity with nucleophiles (e.g., with water). Here we rationalize the different reactivities of 1 and 3.
The analysis of the crystal structure of BIFOP-Cl (1) reveals the large steric demand of the fenchane units, which embed the phosphorus atom, thus making it inaccessible to nucleophilic     [14]. b Angle sum at phosphorous atom (pyramidality). c Fenchyl-aryl dihedral angles (FAA, C1-C2-C3-O1) on the lone-pair side of phosphorus (FAA-lp) and at the substituent side (FAA) biaryl axis.
The computational analysis of the hydrolysis of the chlorophosphites BIFOP-Cl (1) and O-BIFOP-Cl (3, as well as the  smaller model system 2-chloro-1,3,2-dioxaphospholane 8) provides further comparison of the >P-Cl reactivity. The nucleophilic substitution reaction takes place at a triple-coordinated chlorophosphite (in R 2 PCl) due to a single-well potential energy surface [50,51]. The initial step of the water addition proceeds through the formation of the transition state (TS1) in which the oxygen atom of the water molecule binds to the phosphorous atom (Scheme 3, Table 2) and chloride substitution forms the product (G2). Here, chloride is replaced at the phosphorus center with the hydroxide nucleophile (  (1) is unusually robust against hydrolysis (Figure 1 and Figure 3). The lower hydrolysis barriers of 3 and 8 agree with the expected high reactivity of the >P-Cl in water [52][53][54][55][56][57].  tures in reactions with water explains the surprisingly low reactivity of BIFOP-Cl (1, Figure 6) relative to the much more reactive O-BIFOP-Cl (3, Figure 7).

Conclusion
Two fenchole-based chlorophosphites, BIFOP-Cl (1) and O-BIFOP-Cl (3), were studied with respect to their striking differences in regards to their reaction with water. While BIFOP-Cl (1) exhibits a surprisingly high stability against  Figure 6 and Figure 7.
hydrolysis, O-BIFOP-Cl (3) reacts instantly with water, leading to cyclofenchene 6. X-ray studies revealed that the increased reactivity of the intermediate carbenium ion and cyclopropane formation is due to a steric effect caused by the shielding of the fenchane groups and a hypervalent P(III)-O interaction. Formation of the cyclofenchene derivative 7 is explained by rearrangement via a 2-fenchyl carbocation. The DFT computations of the hydrolysis revealed a higher degree of steric congestion in BIFOP-Cl (1) caused by the fenchane units, relative to the less-shielded and hence much more reactive O-BIFOP-Cl (3). This result demonstrates that steric and electronic effects can be used to render the inherently highly reactive and electrophilic phosphorus-halogen units essentially inert against nucleophilic reagents. The stability of BIFOP-Cl (and other phosphorus-halogen systems) against nucleophiles promotes its application as a chiral ligand to be used in, for example, Pd catalysis [13][14][15].

Experimental
All reactions were carried out under an inert argon atmosphere and in heated glassware using standard Schlenk techniques. Anhydrous solvents were obtained by distillation from sodium benzophenone ketyl. The NMR spectra were measured with Bruker instruments (Avance II 600, Avance II 300 and DPX Acance 300). Deuterated chloroform was used as solvent. The proton shifts are reported in ppm (δ) downfield from TMS and are referenced to residual signals of the solvent (CHCl 3 7.24 ppm for hydrogen, 77.0 ppm for carbon atoms). The coupling constants (J) are given in Hz. As an external standard, 85% phosphoric acid was used for the 31 P NMR spectra. The infrared spectra were recorded on a Shimadzu, IRAffinity-1 instrument. The wavenumbers (ν) of the recorded IR signals are given in cm −1 . The GC-MS spectra were recorded using an Agilent Technologies, Model GC 6890N gas chromatograph coupled with an HP 5973N series mass selective detector and an HP 7683 GC autosampler. Optical rotation was measured with an IBZ, Messtechnik POLAR LµP-WR polarimeter, using a 1 dm path length cell. The reactions were carried out under dry argon. X-ray analysis was performed with a Nonius, Kappa CCD diffractometer (Mo Kα, λ = 0.71073). The starting material, O-BIFOL, was obtained in an analogous manner to a procedure previously described [15].
Diphenyl ether-2,2'-bisfencholphosphane chloride (O-BIFOP-Cl, 3) The O-BIFOP-Cl compound was prepared in a manner analogous to the procedure described in [15]. The O-BIFOP-H compound was prepared in a manner analogous to the procedure as described in [15]

Computational details
The computations were performed with the program package TURBOMOLE-5.10 [58][59][60]. The employed functional was BP86 with an m3 grid size combined with the contracted, SVP basis set from Ahlrichs et al. The resolution-of-identity approximation for a two-electron integral evaluation was used. All stationary points were fully optimized and confirmed by separate analytical frequency calculations. The transition state structures were optimized with quasi-Newton-Raphson methods by using the Powell update algorithm for Hessian matrix approximation (analytical frequency calculation subsequent). The absolute energies were zero-point-corrected with the vibrational information resulting from the harmonic analytical frequency calculations.