Synthesis, crystal structure and hydrolysis of novel isomeric cage (P–C/P–O)-phosphoranes on the basis of 4,4,5,5-tetramethyl-2-(2-oxo-1,2-diphenylethoxy)-1,3,2-dioxaphospholane and hexafluoroacetone

The reaction of 4,4,5,5-tetramethyl-2-(2-oxo-1,2-diphenylethoxy)-1,3,2-dioxaphospholane with hexafluoroacetone leads to the simultaneous formation of regioisomeric cage (P–C/P–O)-phosphoranes, the structures of which are unequivocally confirmed by XRD. The rearrangement of the P–C-isomer to P–O-isomer with high stereoselectivity (>96%) takes place in methylene chloride solution with the retention of the phosphorus coordination. It was found that the stepwise hydrolysis of the P–O-isomer initially gives 2-(2,3-dihydroxy-1,2-diphenyl-3-trifluoromethyl-4,4,4-trifluorobutyloxy)-4,4,5,5-tetramethyl-2-oxo-1,3,2-dioxaphospholane as the only stereoisomer whose structure is also confirmed by XRD. Further hydrolysis of this compound leads to the formation of 2,3-dihydroxy-3-trifluoromethyl-4,4,4-trifluoro-1,2-diphenylbutylphosphate and pinacol, which forms the solvate in the crystal. Hydrolysis of the P–C-isomer yields 2-hydroxy-4,4,5,5-tetramethyl-2-oxo-1,3,2-dioxaphospholane, benzoin and hexafluoroisopropanol.

Recently, we developed a new approach for the preparation of phosphoranes based on the cascade reactions of P(III)-derivatives, containing an unsaturated moiety with carbonyl compounds, which leads to P(V)-C cage heterocycles. [30][31][32][33][34] Scheme 1, which shows the synthetic possibilities of this approach, is an example of the reactions of benzodioxaphosphole derivatives 1 with hex-auoroacetone. It is assumed that the reactions proceed through intermediate P + -C-O À bipolar ions followed by the transfer of the reactive center on the exocyclic unsaturated substituent, which lead to the formation of the corresponding cage phosphoranes 2-4 bearing the P-C-bond. [30][31][32] Scheme 2 demonstrates the synthetic potential of the intramolecular cascade cyclization of P(III)-derivatives 1 under the Scheme 1 Use of P(III)-derivatives bearing an exocyclic C]O or C]N bond in the synthesis of cage phosphoranes. action of prochiral triuoropyruvic acid ethyl ester and chloral, which allows the P-C-cage phosphoranes 5-8 to be obtained with high stereoselectivity. 33,34 None of these reactions afford pentaalkoxyphosphoranes, the products of intramolecular PCO/POC-rearrangement, which is characteristic to the reaction of ordinary trialkylphosphites with the carbonyl compounds mentioned above. 35,36 Recently, we have shown 37 that the inclusion of a phosphorus(III) atom in the dioxaphospholane cycle results in the simultaneous formation of PCO-and POC-isomers (1 : 1) of cage phosphoranes 10,11 in the reaction of 4,5-dimethyl-2-(2-oxo-1,2-diphenylethoxy)-1,3,2-dioxaphospholane 9 with hexauoro acetone (Scheme 3). PCO-phosphorane 10 is subjected to intramolecular PCO/POC-rearrangement during storage (CH 2 Cl 2 , 20 C, 30 days) and yields the POC-species 11.

Results and discussion
Considering that the related PCO/POC-rearrangement in a series of 1-hydroxyalkylphosphonates (-phosphinates) is facilitated not only by electron-withdrawing substituents at the carbon atom bonded with OH-group, but also electron-donor substituents at the phosphorus atom, 38 we introduced 4,4,5,5-tetramethyl-2-(2oxo-1,2-diphenylethoxy)-1,3,2-dioxaphospholane 12 in the reaction with hexauoroacetone. Tetramethyl-substituted dioxaphospholane 12 has essentially more electron donor cyclic moieties as compared with the dimethyl-substituted phospholane 9, which, however, also effectively stabilizes the phosphorus pentacoordinated state. Compound 12 was obtained by the phosphorylation of benzoin with 2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxaphospholane in the presence of triethylamine according to the data. 39 The reaction of phosphite 12 with hexauoroacetone proceeds in mild conditions (CCl 4 , À40 C) with the simultaneous formation of two isomeric pentacoordinated phosphorus species 13 and 14 (Scheme 4), which have two high-eld signals at d P À24.5 and d P À26.5 ppm in a ratio of 10 : 1 in their 31 P-{ 1 H} NMR spectra (a day aer the reaction). The molecular ion peaks for compounds 13 and 14 are identical (ESI, m/z 523.9) and correspond to the reaction products with a composition of 1 : 1, and their fragmentation is not signicantly different. Aer the removal of the solvent, the oily residue crystallizes with the formation of compound 13 during storage. It manifests itself as a doublet in the high-eld region (CCl 4 , d P À25.1 ppm, 3 J PCCH ¼ 15.6 Hz) of the 31 P-{ 1 H} NMR spectrum. Taking into account the spectral data (see ESI †), we determined the structure of compound 13 to be 1-(2,3-butylenedioxy)-6,6-bis (triuoromethyl)-3,4-diphenyl-1,2,5,7-phosphatrioxabicyclo [2.  Hz) with an equal integral intensity, which correspond to the non-equivalent uorine atoms of CF 3 -groups. In contrast to the abovementioned phosphite 9, which is a hexauoroacetone system, the formation of PC-phosphorane 13 is a kinetically preferred process.
The structure of phosphorane 13 was conrmed by single crystal XRD. The geometry of molecule 13 in the crystal (conglomerate) is shown in Fig. 1, and the main geometrical parameters (bond lengths and bond and torsion angles) are listed in the gure caption. The conguration of the chiral atoms is P R  (7)Å] can be considered as evidence of the regular trigonal bipyramidal phosphorus conguration. The P 1 -C 6 bond length is equal to 1.930(7)Å. A ve-membered dioxaphospholane cycle occupies the axial-equatorial position in the trigonal bipyramid (O 1 is axial and O 3 is equatorial), its conformation is envelope, where four atoms, O 1 , P 1 , O 3 and C 8 , lie in one plane [planar within 0.004(5)Å], and the C 7 atom deviates from this plane by 0.518 (9) A. The C 9 and C 12 atoms deviate from this plane by 2.05(1) and À1.43(1)Å, respectively, and they occupy axial positions in the cycle. The C 10 and C 11 atoms also deviate from the O 1 P 1 O 3 C 8 plane by À0.05(1) and 0.91(1)Å, respectively, and are located in equatorial positions. The O 2 and C 6 atoms deviate in opposite sides from the O 1 P 1 O 3 C 7 plane [their deviations are 1.377(5) and À1.297(8)Å, respectively] and occupy equatorial and axial positions in the ve-membered cycle. The C 10 and O 7 deviations are minimal [they deviate by À0.05(1) and À0.213(5)Å, respectively] and we can assume that they lie in the O 1 P 1 O 3 C 8 plane.
During storage in very polar dichloromethane at 20 C for about ve days, compound 13 underwent a gradual conversion to compound 14 (aer four days, the ratio of compounds 13/14 was 1 to 20). Fig. 2 shows the spectral image of this process according to 31 P-{ 1 H} NMR. The gure shows that phosphorane 13 (CH 2 Cl 2 , d P À25.0 ppm) was completely converted to pentaoxyphosphorane 14 (CH 2 Cl 2 , d P À26.7 ppm), which is a minor compound in the reaction in tetrachloromethane. This compound was isolated in the individual state by crystallization under a layer of pentane and characterized by spectral methods, which allowed the assignment of the structure of 1-(2,3-butylenedioxy)-5,5-bis(triuoromethyl)-3,4-diphenyl-1,2,6,7-phosphatrioxabicyclo[2.2.1 1,4 ]heptane 14, the product of PCO/POCrearrangement. In the 13 C-{ 1 H} NMR spectrum of compound 14, the carbon atom bonded to CF 3 -groups resonates at 83.41 ppm as a septet with coupling through two bonds from uorine ( 2 J CCF ¼ 29.3 Hz), unlike the spectrum of compound 13 in which the oxygenated carbon in the OC(CF 3 ) 2 fragment manifests itself as a doublet of septets at 77.78 ppm with direct spin-spin coupling from phosphorus ( 1 J PC ¼ 154. 8 Hz,2 The signals of the CF 3 -groups in the 19 F NMR spectrum of compound 14 appear as two quartets at d F À68.22 ppm and À72.35 ppm ( 4 J FCCCF ¼ 9.5 Hz).
Its structure was also conrmed by single crystal XRD. Fig. 3 presents the geometry of the molecule in a crystal (the main geometrical parameters, including bond length, valence and torsion angles of the molecule above, are presented in the ESI le †). The conguration of the chiral atoms is P R   (5), P 1 -C 6 1.930 (7), Hereinafter, non-hydrogen atoms are shown in view of thermal ellipsoids with a probability of 30%, and the trigonal pyramid base is outlined with thin lines.
the above plane by the values of À1.625(2) and 1.700 (2) Considering that compounds 13 and 14 are formed simultaneously under very mild conditions (À40 C) and the rearrangement of P-C-isomer 13 into P-O-isomer 14 is slow, it can  be assumed that they are formed from the common unstable phosphorane intermediate A, which contains an oxaphosphirane cycle (Scheme 4). This intermediate is a product of the symmetry allowed [1 + 2]-cycloaddition reaction of phosphorus to the double bond of hexauoroacetone. At low temperature, the cleavage of the three-membered ring occurs readily in two directions, I and II, which nally results in the formation of compounds 13 and 14. The direction I, which includes P-O bond cleavage and the formation of intermediate bipolar ions B and C, is a kinetically controlled and reversible process. Direction II, which includes P-C bond cleavage and the formation of intermediate bipolar ions D and E, irreversibly results in a thermodynamically controlled reaction product, the P-Oisomer 14. Thus, the driving force of the PCO/POCrearrangements seems to be the greater thermodynamic stability of the resulting pentaalkoxyphosphorane 14 in comparison with its P-C-analogue 13. Furthermore, oxygen is more electronegative than carbon, and it is important for the stabilization of the phosphorus trigonal bipyramid, which increases its stability when acceptors are introduced to the phosphorus atom.
Due to the fact that racemic benzoin was used in the synthesis of phospholane 12 and in the reaction with hexa-uoroacetone another chiral carbon (C 4 ) formation occurred, two P-C diastereoisomers of isomer 13 should be formed. The formation of only one diastereoisomer indicates the high stereoselectivity of the second chiral center (C 4 ) formed, which is probably due to the rigid spatial requirements for the attack of the alkoxide-anion to the carbonyl group of the bipolar ion B. The very important fact that the relative conguration of the chiral C 3 and C 4 atoms in the P-C-and P-O-isomers 13 and 14, according to XRD data, is the same indicates the highly stereoselective nature of the intramolecular PCO/POCrearrangement.
Hydrolysis of P-C-isomer 13 leads to the formation of dioxaphospholane 15, benzoin, and hexauoroisopropanol. Benzoin and compound 15 were isolated by crystallization of the reaction mixture from diethyl ester. The structures of benzoin and hexauoroisopropanol were proven by comparison of their spectral characteristics ( 1 H, 13 C and 19 F NMR) with the literature. [40][41][42][43] The structure of dioxaphospholane 15 was established based on the comparison of its spectral parameters with that described in the literature 44,45 and XRD.
The geometry of the molecule in a crystal (solvate with one water molecule) is presented in Fig. 4. The ve-membered cycle of molecule 15 has an envelope conformation, accordingly with a planar O 1 P 1 O 3 C 8 fragment within 0.115(4)Å, and the C 7 atom deviates from the abovementioned plane by À0.492(8)Å. The O 2 , C 9 and C 12 atoms are located in axial positions (they deviate from the O 1 P 1 O 3 C 8 plane by 1.574(5), À1.990 (8) (9) , and symmetry operation 1 + x, y, z]. Using the classical hydrogen interactions, the molecules in the crystal 15 form ribbons along the 0a crystallographic axis (see Fig. 5).
Mild stepwise hydrolysis of P-O-isomer 14 leads to the initial formation of dioxaphospholane 16. The 31 P NMR spectrum of this compound contains a doublet (d P 11.0 ppm, 3 J PCCH 5.9 Hz) with a coupling constant from the proton at C 3 , which indicates the retention of the P-O-C 3 fragment. Its 13 C NMR spectrum shows spin-spin coupling of all the methyl carbons with the phosphorus atom, which clearly points to the retention of the 4,4,5,5-tetramethyl-1,3,2-dioxaphospholane cycle. This data are in accordance with the breaking of the P 1 -O 2 and P 1 -O 7 bonds in phosphorane 14 during hydrolysis. The result of the hydrolysis of phosphorane 14 differs by one for compound 11, which  contains a 4,5-dimethyl-1,3,2-dioxaphospholane moiety. In the last case, the 2,3-butanediol elimination proceeds. 37 The structure of phospholane 16 was conrmed using single crystal XRD. In Fig. 6, the geometry of the molecule in a crystal is presented (the main geometrical parameters, including bond length and valence and torsion angles of molecule 16 are presented in the ESI †). The phosphorus atom has a distorted tetrahedral conguration. The dioxaphospholane cycle has an envelope conformation with a planar four-membered O 1 P 1 O 3 C 7 fragment within 0.080(6)Å, and the C 8 atom deviates from this plane by 0.510(9)Å (see Fig. 7). The O 2 , C 10 and C 12 atoms are in axial positions (they deviate from the O 1 P 1 O 3 C 8 plane by the values of 1.260(5), À1.52(1) and 2.05(1)Å, respectively). The O 4 , C 9 and C 11 atoms are in equatorial positions (they deviate from the O 1 P 1 O 3 C 8 plane by the values of À1.265(6), 0.74(1) and À0.05(1)Å, respectively). The presence of four methyl groups leads to a noticeable deviation of conformation along the C 7 -C 8 bond from the regular staggered gauche conformation due to steric repulsion (the torsion angles C 9 C 7 C 8 C 12 and C 10 C 7 C 8 C 11 are equal to À39(1) and À36(1) , respectively). The envelope conformation is probably realized in a solution for the investigated compound also, which is conrmed by the nonequivalence of these four methyl groups in NMR 1 H and 13 C spectra, and also by the different spin-spin coupling constants 3 J PCCC , which depend on the P-C-C-C torsion angle values. The same situation is realized for the conformation along the C 3 -C 4 bond (the torsion angles of O 2 C 3 C 4 O 7 and C 13 C 3 C 4 C 16 are 46.2(9) and À45.2(9) , respectively). The repulsion between the two phenyl groups probably has less meaning in comparison with the phenyl and hexauoroisopropylhydroxy substituent repulsion, which leads to the same conformation along the C 3 -C 4 bond (the torsion angle of C 5 C 4 C 3 C 13 is À166.7 (7) ). Prolonged hydrolysis of phosphorane 14 leads to the cleavage of not only the exocyclic P 1 -O 6 and P 1 -O 7 bonds but also the 1,3,2-dioxaphospholane P-O bonds. This process is accompanied by the formation of 2,3-dihydroxy-3-triuoromethyl-4,4,4-triuoro-1,2-diphenylbutylphosphate 17 and pinacol. It should be noted that phosphate 17 (d P À1.4 ppm, d F À67.05 and À67.82 ppm (CDCl 3 /DMSO-d 6 , 3 : 1)) exists in equilibrium with the cyclic form 19 (d P 14.7 ppm (CD 3 CN), d F À68.42 and À69.98 ppm (CDCl 3 /DMSO-d 6 , 3 : 1)) (Scheme 5) in a solution. 37 The ratio of cyclic and acyclic phosphates in the reaction medium is close to 1 : 10; however, this equilibrium shis to the formation of the cyclic derivative 19 upon heating (40 C) and the ratio becomes 2 : 1. Long crystallization of the hydrolysis products from CH 2 Cl 2 allowed the isolation of the crystalline complex 18 of the acyclic monophosphate 17 with pinacol in a 2 : 1 ratio. The structure of complex 18 was   conrmed by XRD. The geometry of the complex in a crystal and atom numbering are shown in Fig. 9, and the main geometrical parameters (bond lengths and bond and torsion angles) are listed in the gure caption. The phosphorus atom has a distorted tetrahedral conguration, and the conguration of the chiral atoms is C S 3 C R 4 /C R 3 C S 4 . The conformations of the monophosphate 17 and pinacol molecules along the C 4 -C 3 , C 5 -C 4 and C 6 -C 6a bonds are shown in Fig. 10. All of them are closely related to the almost regular staggered species. The phenyl substituents are located in the gauche-conformation along the C 4 -C 3 bond [the torsion angle of C 13 -C 3 -C 4 -C 19 is À50.1 (6) ].
The triuoromethyl groups have different orientations relative to the phenyl ring at the C 4 atom (see Fig. 10) and therefore uorine atoms exhibit non-equivalence in the 19   Hexauoroacetone (4.81 g, 30 mmol) was condensed into a CCl 4 /CH 2 Cl 2 (1 : 1) solution (40 mL) of dioxaphosphole 12 (10.4 g, 30 mmol) at À40 C. The reaction mixture was warmed up to 20 C (10 h) and then evaporated under reduced pressure (14 Torr) to give a white precipitate of 13, which was ltered off and dried in vacuo (14 Torr). Yield 7.12 g (47%), mp 122-125 C. The ltrate was evaporated in vacuo (14 Torr) under an argon atmosphere to give a pale yellow oil, which gradually crystallized under a pentane layer (À18 C). Clear white crystals of compound 13 were ltered off. Yield 3.62 g (24%), mp 123-125 C. Anal. calcd for C 23

Hydrolysis of compound 13
To a suspension of compound 13 (1 g, 1.91 mmol) in diethyl ester (5 mL , d P : 10.6 ppm (s). The 1 H NMR spectral data of an aliquot of the ltrate contain the benzoin and hexauoroisopropanol signals. The structure of hexa-uoroisopropanol was proven by a comparison of its spectral characteristics ( 1 H, 13 C, 19 F NMR) with previously published data. 43 The ltrate was evaporated in vacuo (14 Torr) to give a white precipitate of benzoin, mp 132-134 C. 1