P-Chirogenic silylphosphine-boranes: synthesis and phospha-Michael reactions

Chiral and achiral silylphosphine-boranes were prepared in high yields by reaction of phosphide boranes with halogenosilanes. Their reaction at room temperature with Michael acceptors afforded 1,4-addition products as silylenol ether or ketone derivatives in good to excellent yields. In the case of the 2,3-dihalogeno-maleimides, the double addition of silylphosphine-borane led to the corresponding trans-diphosphine-boranes in 86% yield. Noteworthy, the reaction of P-chirogenic silylphosphine-boranes with enones afforded the phospha-Michael adducts without racemization at the P-center. While the silylphosphine-boranes have been scarcely described so far, these compounds demonstrate their great interest for the synthesis of chiral and achiral functionalized organophosphorus compounds.


Introduction
3][4][5] Indeed, they played a significant role as ligands in metal based asymmetric catalysis 9 as well as Brönsted acid or Lewis bases in organocatalysis. 10Usually, the stereoselective synthesis of chiral organophosphorus compounds with P-C bond formation was performed using chlorophosphines or phosphides as electrophilic or nucleophilic reagents, respectively. 9,11In the last decade, the asymmetric hydrophosphination 12,13 and phospha-Michael addition 14 have also emerged as powerful methodologies for the synthesis of functional derivatives such as chiral organophosphorus compounds, that hold promise for applications in asymmetric catalysis.In this last case, typical reactions of Michael acceptor with free secondary phosphines or their oxide, sulfur or other borane derivatives, were achieved either in basic conditions or by heating. 14,150][21] Among the nucleophilic phosphorus reagents, the silylphosphines have recently retained the attention because these compounds are considered more electron-rich than the parent secondary phosphines due to the electrodonating effect of the silicon moiety. 22,231][32][33] Thus, the silylphosphines 1 and 2 have been used for the stereoselective synthesis of MalPHOS 5 and Pchirogenic phosphines 6, by double phospha-Michael addition with the 2,3-dichloromaleic anhydride 3, 34 or Pd-catalyzed enantioselective arylation of the iodo compound 4, 35 respectively (Scheme 1a,b).

Scheme 1
While in the last decades the use of borane as P(III)-protecting group has resulted in significant breakthroughs for the stereoselective synthesis of tricoordinated organophosphorus compounds, surprisingly the silylphosphine-borane complexes have been scarcely studied. 36s part of our on-going program on the stereoselective synthesis of P-chirogenic organophosphorus compounds, we recently reported a new method for the preparation of Pchirogenic phosphide-boranes that involves metal-halide exchange of the corresponding chlorophosphines. 37,38This method, which proceeds with retention of configuration at the Pcenter, was used for the synthesis of P-chirogenic phosphines by reaction with alkyl halide or aryne reagents. 37,38These results led us to envisage the synthesis and study of silylphosphineboranes.Herein we report the first examples of P-chirogenic silylphosphane-boranes and their application to the stereoselective synthesis of functionalized phosphine-boranes by phospha-Michael addition under mild uncatalyzed conditions.

Results and Discussion
The silylphosphine-boranes 11a,b were prepared in 80-93% yields by reaction of phosphideboranes 9, previously obtained by deprotonation of the secondary diphenylphosphine-borane 7a, with the corresponding halogenosilane 10a or 10b (Scheme 2).After removal of the solvent, the residue was dissolved in toluene, then filtered to afford the silylphosphine-boranes 11a,b which were used without further purification.In these conditions, when the P-chirogenic (S)-o-anisylor (R)-ferrocenylphosphine-boranes 7c,d, previously prepared from the chlorophosphine-boranes 8c,d, 37,38 were used, the corresponding silylphosphine-boranes 11c,d were obtained with ee up to 87%, by reaction with TMSBr 10c (Scheme 2).As the deprotonation of secondary P-chirogenic phosphine-boranes 7c,d and their reactions proceed with retention of configuration at the phosphorus center, 37,38 it is reasonable to think that silylation with TMSBr 10c follows the same stereochemistry.All silylphosphine-boranes 11 could be purified by chromatography, but in low isolated yields.Therefore, they were better used immediately after preparation without further purification.

Scheme 2
Firstly, the reactivity of the silylphosphine-borane 11a was investigated in the Michael addition to enones 13 by comparison with the free trimethylsilylphosphine 12 (Scheme 3).When the trimethylsilylphosphine 12 was stirred with the enone 13a (or 13b) in THF during 16 hours at room temperature, the β-phosphinoketone 14a (or 14b) was obtained after purification by chromatography on silica gel in 51% (or 58%) yield (Scheme 3). 39

Scheme 3
Surprisingly, when the silylphosphine-borane 11a was used in the same conditions the reaction with enones 13a,b led to the corresponding trimethylsilylenol ethers 15a (or 15b) as an isomeric mixture in 2:1 ratio and with yields up to 48% (Table 1, entries 1,2).In the case where the silylphosphine-borane 11a was reacted with cyclohexenone 13c in THF or toluene, the silylenol ether 15c was successfully isolated in 84 or 63% yields (entries 3,4).Similarly, the reaction of the t-butyldimethylsilyl phosphine-borane 11b with the cyclohexenone 13c led to the corresponding silylenol ether 15d in 77 % yield (entry 5).Interestingly, treatment of phosphine-borane 15c with DABCO led quantitatively to the corresponding free phosphine silylenol ether 16 by decomplexation of the borane moiety (Scheme 4).
Interestingly, the phospha-Michael additions of Table 2 proceeded without racemization as the enantiomeric excesses of 15e, 14c, and 14d, were close to those of the corresponding secondary phosphines 7c and 7d used for the preparation of the intermediate silyl phosphines 11c and 11d, respectively (entry 1).While the absolute configuration of the products 14c,d or 15e was not established, we believe that the reaction proceeds with a concerted mechanism involving retention of configuration at the P-center as showed in Scheme 5b.

Scheme 5
Indeed, in the case where the mechanism would lead to the formation of P-chirogenic phosphide-borane 9 by nucleophilic attack of the enone 13 first on the silyl group, a racemized product 15 would be obtained due to the poor configurational stability of 9 at room temperature (Scheme 5a). 37,38On the contrary, when a concerted transition state 17 is formed by interaction of the enone 13 with the silyphosphine-borane 11 both on the Si-and P-atoms, precisely in anti position of the P-B bond, the product 15 is obtained with retention of configuration at the phosphorus center (Scheme 5b).
The formation of the succinimide or maleimide derivatives 19 (or 20) could be explained by two possible pathways via the intermediate 23 depending on the substrate 13, the solvent and the halide.The compound 23 was formed by addition of two equivalents of silylphosphine-borane 11a to the dihalogenomaleimide 13e (or 13f), via the diphenylphosphine-borane 22 (Scheme 6).The intermediate 23 can evolve either towards the formation of the bis-silylether derivative 24 by reaction with a trimethylsilyl reagent (e.g.TMSX), or the conventional double Michael-addition product 25 (Scheme 6).Finally, the hydrolysis of 24 and the loss of a borane moiety due to steric congestion in compound 25 led to the succinimide and maleimide products 19 and 20, respectively (Scheme 6).

Scheme 6
On the other hand, when the dichloroquinoxaline 13g was used as electrophilic acceptor, the reaction with the silylphosphine-borane 11a in THF (or toluene) led to the monophosphine product 21 in 41 or 46% yield, respectively (entries 8,9).The formation of compound 21 was explained by only one addition of silylphosphine-borane 11a to the 2,3-dichloroquinoxaline substrate 18 and the decomplexation of borane due to steric hindrance of the 2-chloroquinoxaline substituent.The structure of compound 21 was established by X-ray analysis (Figure 2).This structure shows the chloroquinoxaline substituent in staggered conformation with respect to both phenyl groups borne by the phosphorus atom, the chlorine atom facing the lone pair of the phosphorus atom (Figure 2)

Conclusions
The silylphosphine-boranes were prepared in high yields by reaction of phosphide boranes, previously obtained either by deprotonation of the secondary phosphine-boranes or by metal halide exchange of the chlorophosphine-boranes with halogenosilanes.The reaction of silylphosphine-boranes with various Michael-acceptors led to the addition products in yields up to 96% under uncatalyzed mild conditions.In the case of the reaction with enones the product are mainly isolated as silylenol ether derivatives.Moreover, the silylphosphine-boranes also react with 2,3-dihalogenomaleimides to afford the corresponding trans diphosphine-diborane complexes in yields up to 86%.The trans configuration of both phosphine-borane moieties has been established by X-ray crystal structure analysis.Interestingly, when P-chirogenic silylphosphine-borane were used, the reaction with enones led to the phospha-Michael products without racemization at the P-center.While the silylphosphine-boranes have been scarcely described so far, these compounds reveal a great potential for the synthesis of chiral and achiral functionalized organophosphorus compounds.

Supporting information available
NMR spectra and crystallographic data in CIF format for compounds 19a and 21.This material is available free of charge via the internet at http://www.arkat-usa.org.

Experimental Section
All reactions were carried out under inert atmosphere.Solvents were dried and purified by conventional methods prior to use.Tetrahydrofuran (THF) and toluene were distilled from sodium/benzophenone and stored under argon.Diphenyl(trimethylsilyl)phosphine 12 was purchased from commercial sources and used without purification.The P-chirogenic secondary phosphine-boranes (S)-7c and (R)-7d were prepared using the (-)-and (+)-ephedrine methodology, respectively. 37,38Reactions were monitored by thin-layer chromatography (TLC) using 0.25 mm E. Merck precoated silica gel plates.Flash chromatography was performed with the indicated solvents using silica gel 60 (60AAC, 35-70 µm).NMR spectra ( 1 H, 13 C, 31 P, 29 Si) were recorded on Bruker Avance 600, 500 or 300 MHz spectrometers at ambient temperature and chemical shifts are reported in ppm using TMS as internal reference for 1 H, 13 C and 29 Si NMR or 85% phosphoric acid as external reference for 31 P NMR.The signals are reported as s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br.s = broad signal, coupling constant(s) in Hertz and with their integration.The infrared spectra were recorded on a FT-IR Bruker Vector 22 and the bands are reported in cm -1 .Melting points were mesured on a Kofler melting points apparatus and are uncorrected.Optical rotation values were determined at 20°C on polarimeter Perkin Elmer 341 at 589 nm (sodium lamp).HPLC analyses were performed on a chromatograph equipped with a UV detector at λ = 210 nm and λ = 254 nm.High Resolution Mass Spectra (HRMS) were performed on Thermo Orbitrap XL under ESI conditions with a micro Q-TOF detector.Elemental analyses were measured on Thermo EA 1112 with a precision superior to 0.3% on a CHNS-O instrument apparatus.

Crystal Structure Determination
Diffraction data were collected on a Nonius Kappa CCD diffractometer equipped with an Oxford Cryosystems low-temperature apparatus operating at T = 115 K. Data were measured using ϕ and ω scans using MoK α radiation (λ = 0.71073 Å, X-ray tube, 50 kV, 32 mA).The total number of runs and images was based on the strategy calculation the program Collect. 41Cell parameters were retrieved using the SCALEPACK software and refined using DENZO. 42Data reduction was performed using the DENZO 42 software which corrects for Lorentz polarisation.The structure was solved by Direct Methods using the SIR92 43 program structure solution program and refined by Least Squares using version of the ShelXL 44,45  (Sheldrick, 2008).All nonhydrogen atoms were refined anisotropically.Hydrogen atom positions were calculated geometrically and refined using the riding model.CCDC Deposition Number: Compound 19a (CCDC 1048105); Compound 21 (CCDC 1048106).

Table 1 (continued)
a Reaction at rt for 16 hours.b Isolated yield.c Obtained as an isomeric mixture in 2:1 ratio.