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Menthyloxycarbonyl phosphonium chlorides: new derivatives for determining the enantiomeric excess of chiral tertiary phosphines
Accepted Manuscript Menthyloxycarbonyl phosphonium chlorides: new derivatives for determining the enantiomeric excess of chiral tertiary phosphines A. Christopher Garner, Roy C. Hodgkinson, John D. Wallis PII: DOI: Reference:
S0040-4039(13)01335-X http://dx.doi.org/10.1016/j.tetlet.2013.07.155 TETL 43355
To appear in:
Tetrahedron Letters
Received Date: Revised Date: Accepted Date:
13 May 2013 15 July 2013 31 July 2013
Please cite this article as: , Tetrahedron Letters (2013), doi: http://dx.doi.org/10.1016/j.tetlet.2013.07.155
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Menthyloxycarbonyl phosphonium chlorides: new derivatives for determining the enantiomeric excess of chiral tertiary phosphines A. Christopher Garner,* Roy C. Hodgkinson, John D. Wallis
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1
Tetrahedron Letters journal homepage: www.elsevier.com
Menthyloxycarbonyl phosphonium chlorides: new derivatives for determining the enantiomeric excess of chiral tertiary phosphines A. Christopher Garner,* Roy C. Hodgkinson, John D. Wallis School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, UK. E-mail: [email protected]
ARTICLE INFO
ABSTRACT
Article history: Received Received in revised form Accepted Available online
The direct alkoxycarbonylation of tertiary phosphines with alkyl chloroformates has been examined and the products characterised by NMR and X-ray crystallographic analysis. The derivatisation of representative chiral tertiary phosphines with enantiopure menthyl chloroformate allows the determination of the enantiomeric excess of scalemic mixtures by 31P NMR spectroscopic analysis.
Keywords: Oxycarbonyl phosphonium salts ee determination Menthyl chloroformate Phosphine Phosphorus NMR
Chiral phosphines continue to enjoy popularity as the ligand of choice in a wide variety of asymmetric catalytic processes and the asymmetric synthesis of these compounds is an area of significant research.1 In the absence of other functionality, methods for the determination of the enantiomeric excess of chiral synthetic phosphines are limited and they are often determined by HPLC of phosphines or protected phosphines over chiral stationary phases.2 This method offers advantages of high sensitivity and accuracy, but at the expense of time-consuming method development, and these methods may not be amenable to the rapid evaluation of enantiomeric excesses. NMR techniques, involving both chiral solvating agents and derivatisation methods, are well established for compounds containing amine and hydroxyl functional groups,3 but such methods are not applicable to the many chiral ligands utilised in asymmetric transition metal catalysis containing only phosphine functionality. Despite the ability to readily measure 31P NMR spectra, NMR based methods for assessing chiral phosphines4 are limited to utilising chiral transition metal complexes5 and some related examples using chiral liquid crystal phase experiments.6 Acyl phosphonium ions7 (A, Figure 1) are generally considered to be unstable compounds,8 implicated as important reactive intermediates in nucleophilic catalysis9 and other synthetic processes.10 The related oxycarbonyl phosphonium ions (B, Figure 1) may be expected to exhibit greater stability, however these compounds have not been well studied or characterised to date. In 1937, Jensen reported the adducts from the reaction of triethylphosphine and a number of chloroformates,11 however subsequent reports of such species have been sparse.12 The direct generation of oxycarbonyl phosphonium ions from chloroformates is a synthetically attractive process and we wished to explore this chemistry and develop a simple 31P NMR spectroscopic method to assay the enantiomeric purity of tertiary phosphines.
2009 Elsevier Ltd. All rights reserved.
Figure 1. Preliminary studies revealed that alkoxycarbonyl phosphonium chlorides could be prepared from the reaction of phosphines with moderately sterically hindered alkyl chloroformates. Hence, treatment of dimethylphenyl phosphine (1) with iso-propyl or isobutyl chloroformate in toluene gave precipitates which were collected directly via filtration to afford alkoxycarbonyl phosphonium chlorides 2 and 3 as amorphous solids in excellent yields of 80% and 97%, respectively (Scheme 1).13
Scheme 1. Reagents and conditions: (i) iso-propyl-, iso-butyl- , (S)(+)-pantolactone-, (-)-borneol- or (S)-(+)-menthyl chloroformate, toluene, room temperature.
2
Tetrahedron
13
C NMR spectroscopic data were consistent with the expected PC=O connectivity and both compounds exhibited a doublet for the carbonyl carbon peak with 1JPC couplings of 135 and 136 Hz, respectively, and proved to be bench-stable for a period of several weeks. In further support of this structural assignment, the structure of 2 was confirmed by X-ray crystallographic analysis of the corresponding PF6 salt at 120 K (Figure 2).14
Scheme 2. Reagents and conditions: (i) (-)-(1R,2S,5R)-menthyl chloroformate, toluene.
Figure 2. Ball and stick representation of the X-ray crystal structure of the PF6 salt of 2 (counter ion omitted for clarity).15 In structure 2 the P+-C(=O) bond is 1.855(2) Å long, being significantly longer than the three P+-C bonds to the phenyl and methyl groups [1.775(2) - 1.782(2) Å]. At the carbonyl carbon the widest angle is between the two O atoms [129.1(2)o] and the smallest between the alkoxy O and the P atom [111.37(16)o]. The only related structures known are those of the frustrated lone pair complexes of carbon dioxide with a phosphine and borane, which show a longer P-C(=O) bond (1.893-1.900 Å ).16 Having established the rapid and clean formation of these adducts, our investigation then turned to realising the potential of this reaction for the assay of the enantiomeric purity of tertiary phosphines utilising a chiral chloroformate as the derivatising agent. Initially, the reactivity of the achiral tertiary phosphine, phenyl dimethyl phosphine (1) towards chiral chloroformates was examined. The addition of phosphine 1 to a toluene solution of (S)-pantolactone chloroformate17 afforded the corresponding phosphonium chloride 4 as an unstable oil, while similar reactions with (-)-borneol and (S)(+)-menthol derived chloroformates17 afforded phosphonium chlorides 5 and 6 as amorphous solids in 72% and 71% isolated yields, respectively (Scheme 1).18 Given that menthyl chloroformate is cheap and commercially available in both enantiomeric forms,19 it was chosen for further investigation as a chiral derivatising agent. Initially, the preparation of a menthyl oxycarbonyl phosphonium chloride salt of a Pchirogenic tertiary phosphine was examined. Treatment of a racemic mixture of iso-propyl methyl phenylphosphine 720 (0.2 M solution in CDCl3) with a small excess of (1R,2S,5R)-menthyl chloroformate (1.1 equivalents, 0.5 M solution in CDCl3) afforded a 1:1 mixture of (RP,1R,2S,5R)- and (SP,1R,2S,5R)-menthyl oxycarbonyl-(isopropyl-methyl-phenyl)phosphonium chlorides 8 and 9 (Scheme 2). Examination of the 31P {1H} NMR spectrum showed complete conversion of the starting material into two baseline resolved singlet peaks of equal intensity (P = 30.4 and 31.4 ppm, = 1.0 ppm).
The 13C NMR spectrum of the mixture was consistent with the expected oxycarbonyl phosphonium chlorides and both compounds exhibited a carbonyl carbon peak with a 1JPC coupling of 119 Hz. The 13C and 1H NMR spectra also revealed contamination of the sample with excess of menthyl chloroformate. These data demonstrate that this reagent fulfills the requirements for a chiral derivatising agent for NMR analysis in that: (1) salt formation is rapid, (2) no kinetic resolution occurs in the formation of the diastereoisomeric salts, and (3) there is a significant, baseline resolved, difference in chemical shifts between the 31P NMR signals of the derived salts. Having demonstrated menthyl chloroformate as an effective chiral derivatising agent for a P-chirogenic tertiary phosphine containing no other functionality, the application of this method to a representative chiral tertiary mono-phosphine 10, exhibiting backbone chirality was explored. Phospholane 10 is commercially available in both enantiomeric forms, but not as a racemate, and it was convenient to determine the enantiodiscriminating capacity of the chiral derivatising agent by treating the enantiopure substrate with racemic menthyl chloroformate. Hence, in an NMR tube, a small excess of racemic menthyl chloroformate17 (1.1 equivalents, 0.5 M solution in CDCl3) was added to (S,S)-phospholane 10 in CDCl3 (0.2 M solution in CDCl3) and the 31P NMR spectrum recorded after 30 minutes. Examination of this spectrum revealed that all the starting phosphine had been consumed and showed two baseline resolved singlet peaks of near equal area (52:48, P = 57.6 and 56.4 ppm, 1.2 ppm) corresponding to (S,S)-phosphine/(R)-menthyl oxycarbonyl adduct 11 and (S,S)-phosphine/(S)-menthyl oxycarbonyl adduct 12, respectively (Scheme 3).21 Examination of the 1H and 13C NMR spectra of the mixture supported the formation of the two diastereoisomeric phosphonium salts and also revealed an excess of menthyl chloroformate.
3
Scheme 3. Reagents and conditions: CDCl3, room temperature. Having demonstrated effective enantiodiscrimination, the enantiomeric excess of scalemic mixtures of phospholanes (S,S)-10 and (R,R)-10 in ratios of 90:10 and 99:1 were determined by derivatisation with (R)-menthyl chloroformate.22 These results showed that a reliable measurement of enantiomeric excess of up to 98% could be obtained by this technique. In conclusion, the utility of menthyl chloroformate as a cheap, commercially available reagent for the determination of the enantiomeric excess of representative chiral tertiary phosphines has been demonstrated. This method is ideally suited to assessing the enantiomeric excess of nucleophilic chiral phosphines for application in organocatalysis and as ligands in transition metal catalysis, and provides a convenient and simple alternative to complementary chromatographic methods. Acknowledgements The authors would like to thank the Leverhulme Trust for funding Project Grant F/01 374/H (R.C.H.) and the EPSRC Mass Spectrometry Service at Swansea University.
References and notes 1. Phosphorus Ligands in Asymmetric Catalysis, Vol. 3 (Ed.: Borner A.), Wiley-VCH, New York, 2008, 1175. 2. (a) Colby E. A.; Jamison, T. F., J. Org. Chem. 2003, 68, 156-166; (b) Muci, A. R.;Campos, K. R.; Evans, D. A. J. Am. Chem. Soc., 1995, 117, 9075-76. 3. For a recent review, see: (a) Wenzel, T. J.; Chisholm, C. D. Prog. Nucl. Magn. Reson. Spectrosc., 2011, 59, 1-63; (b) Wenzel, T. J. Discrimination of Chiral Compounds Using NMR Spectroscopy, Wiley Interscience, Hoboken, NJ, 2007; (c) Duddeck H.; Gomez, E. D. Chirality, 2009, 21, 51-68; (d) Donnoli, M. I.; Superchi, S.; Rosini, C. Mini-Rev. Org. Chem., 2006, 3, 7792; (e) Blazewska, K. M.; Gadja, T. Tetrahedron: Asymmetry, 2009, 20, 1337-61. 4. In contrast, chiral phosphorus based reagents for derivatising amines and alcohols exploit 31P NMR spectroscopy to assess ee, see: (a) Hulst, R.; Kellogg R. M.; Feringa, B. L. Recl. Trav. Chim. Pay-B, 1995, 114, 115-138 ; For recent examples, see: (b) Reiner, T.; Naraschewski, F. N.; ; Eppinger, J. Tetrahedron: Asymmetry, 2009, 20, 362-67; (c) Gulea, M.; Kwiatkowska, M.; Lyzwa, P.; Legay, R.; Gaumont A-C.; Kielbasinski, P. Tetrahedron: Asymmetry, 2009, 20, 293-297; (d) Mastranzo, V. M.; Quintero L.; De Parrodi, C. A. Chirality, 2007, 19, 503-507. 5. (a) Wild, S. B. Coord. Chem. Rev., 1997, 166, 291-311; (b) Dunina, V. V.; Kuz'mina, L. G.; Kazakova, M. Y.; Grishin, Y. K.; Veits, Y. A.; Kazakova, E. I. Tetrahedron: Asymmetry, 1997, 8, 2537-2545. (c) For references to similar ee assays, see:, Ng, J. K. P;. Chen, S.; Tan, G. K.; Leung P-H. Tetrahedron: Asymmetry, 2007, 18, 1163-69.
6. For enantiodiscrimination of chiral phosphine oxides and boranes, see: (a) Rivard, M.; Guillen, F.; Fiaud, J-C.; Aroulanda C.; Lesot, P. Tetrahedron: Asymmetry, 2003, 14, 1141-52; For chiral phosphonium salts, see: Meddour, A.; Uziel, J.; Courtie J.; Juge, S. Tetrahedron: Asymmetry, 2006, 17, 1424-29. 7. For a review of acyl phosphonium and ammonium species, see: (a) Kolesinska, B. Cent. Eur. J. Chem., 2010, 8, 1147-71; For early reports, see: (b) Yakshin, V. V.; Sokal'skaya, L. I. Zh. Obshch. Khim., 1973, 43, 440; (c) Lukashev, N. V.; Artyushin, O. I.; Lazhko, E. I.; Tafeenko, V. A.; Kazankova M. A.; Lutsenko, I. F. Zh. Obshch. Khim., 1988, 58, 316-327. (d) Thamm R.; Fluck, E. Z. Naturforsch. Pt B, 1982, 37B, 965-74; (e) Gololobov, Y. G.; Pinchuk, V. A.; Thoennessen H.; Jones P.G.; Schmutzler, R. Phosphorus, Sulfur Silicon Relat. Elem, 1996, 115, 19-37. 8. Isolated salts are reported to be very hygroscopic but stable in the absence of moisture, see reference 7(b). 9. For reviews, on phosphine-based nucleophilic catalysis, see: (a) Zhou, Z.; Wang, Y.; Tang C. Curr. Org. Chem., 2011, 15, 4083-4107; (b) Marinetti, A.; Voituriez, A. Synlett, 2010, 174-194; (c) Cowen, B. J.; Miller, S. J. Chem. Soc. Rev., 2009, 38, 3102-3116; (d) Methot, J. L.; Roush, W. R.; Adv. Synth. Calat., 2004, 346, 1035-1050. 10. For examples of acylated phosphines as stoichiometric intermediates, see: (a) Maeda, H.; Maki T.; Ohmori, H. Tetrahedron Lett., 1995, 36, 2247-50; (b) Maeda, H.; Okamoto, J.; Ohmori, H. Tetrahedron Lett., 1996, 37, 5381-84; (c) Maeda, H.; Takahashi K.; Ohmori, H. Tetrahedron, 1998, 54, 12233-42; (d) Maeda, H.; Huang, Y.; Hino, N.; Yamauchi Y.; Hidenobu, O. Chem. Commun., 2000, 2307-8; (e) Maeda, H.; Hino, N.; Yamauchi, Y.; Ohmori, H. Chem. Pharm. Bull., 2000, 48, 1196-99. See also: (f) Weiss, R.; Bess M.; Huber S. M.; Heinemann, F. W. J. Am. Chem. Soc., 2008, 130, 4610-17. 11. Jensen, K. A. J. Prakt. Chem., 1937, 148, 101-106. 12. (a) Vedejs E.; Donde, Y. J. Am. Chem. Soc., 1997, 119, 9293-4; (b) Uncharacterised oxycarbonyl phosphonium salts have been reported as intermediates, see reference 10c. For an example of the related carbamoyl phosphine boranes, see: (c) Imamoto, T.; Tamura, K.; Ogura, T.; Ikematsu, Y.; Mayama D.; Sugiya, M. Tetrahedron: Asymmetry, 2010, 21, 1522-8. 13. General procedure for the preparation of phosphonium salts. The phosphine was added to a solution of the chloroformate in toluene. This mixture was stirred at room temperature for 30 min. The resulting precipitate was collected by filtration and washed with toluene and dried to yield the alkoxycarbonyl phosphonium salt. iso-Butoxycarbonyl dimethylphenylphosphium chloride (3) Prepared using the general procedure, using dimethylphenyl phosphine (1) (1.0 g, 1.0 mL, 7.2 mmol), iso-butyl chloroformate (1.18 g, 1.1 mL, 8.64 mmol) and toluene (2 mL), to yield phosphonium salt 3 (2.29 g, 97%) as a white solid. Decomposition point: 95-97 oC; νmax cm-1: 2963, 2875, 1727, 1440, 1211, 962, 912; H (400 MHz, CDCl3) 0.88 (3H, s, iPr(Me)), 0.90 (3H, s, iPr(Me)), 2.05 (1H, hept, J = 7 Hz, iPr(CH)), 2.95 (6H, d, J = 15 Hz, PMe2), 4.23 (2H, dd, J = 6 and 1 Hz, CH2O), 7.61-7.66 (2H, m, Ph), 7.71-7.75 (1H, m, Ph), 7.88-7.94 (2H, m, Ph); C (100 MHz, CDCl3) 8.5 (2C, 1JPC = 55 Hz), 18.8 (2C), 27.5, 75.5 (d, 3JPC = 4 Hz), 117.5 (1JPC = 117 Hz), 130.2 (2C, d, 2JPC = 14 Hz), 131.7 (2C, d, 3JPC = 10 Hz), 135.1 (d, 4JPC = 4 Hz), 163.2 (d, 1 JPC = 136, Hz); P (161 MHz, CDCl3) +20.9. LRMS(ESI+): 239.1 ([M-Cl]+, 100%), 240.1 (14); HRMS (ESI+): 239.1193 ([M-Cl]+ C13H20O2P requires 239.1195). 14. The PF6 salt of 2 was prepared by metathesis of the chloride of (isopropyl-oxycarbonyl) dimethylphenyl phosphonium chloride with sodium hexafluorophosphate in acetone. Crystal data for the PF6 salt of 2: C12H18O2P·PF6, Mr = 370.20, monoclinic, a = 8.6809(3), b = 14.0685(5), c = 14.1748(5) Å, β = 105.488(4) o, V = 1668.27(10) Å 3, Z = 4, P21/c, Dc = 1.47 g cm3, = 0.322 mm1, T = 120 K, 3875 unique reflections, 3212 with F2 > 2, R(F, F2>2) = 0.051, Rw(F2, all data) = 0.12. There are two orientations of the PF6- anion in the ratio 2:1. Crystallographic data (excluding structure factors) have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 931374. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (0) 1223 336033 or e-mail: [email protected]]. 15. Molecular illustration was prepared with Mercury (Macrae, C.F.; Edgington, P.R.; McCabe, P.; Pidcock, E.; Shields, G. P.; Taylor, R.; Towler, M.; van de Streek, J. J. Appl. Crystallogr., 2006, 39, 453-457) and POV-RAY (Persistence of Vision Pty. Ltd. 2004. Persistence of Vision™ Raytrace, Persistence of Vision Pty. Ltd., Williamstown, Victoria, Australia, http://www.povray.org). 16. (a) Sgro, M. J.; Domer, J.; Stephan, D. W. Chem. Commun., 2012, 48, 7253-55; (b) Momming, C.; Otten, E.; Kehr, G.; Frohlich, R.; Grimme, S.; Stephan, D.W.; Erker, G. Angew. Chem. Int. Ed., 2009, 48, 6643-46. 17. Prepared from the corresponding alcohol and phosgene, see reference 12(a).
4
Tetrahedron
18. {[(1S,2R,5S)-2-iso-Propyl-5-methylcyclohexyloxy]carbonyl}dimethyl(phenyl) phosphonium chloride 6 Prepared using the general procedure, using dimethylphenyl phosphine (1) (221 mg, 0.2 mL, 1.60 mmol), (1S,2R,5S)-menthyl chloroformate (350 mg, 1.60 mmol), and toluene (1 mL), to yield phosphonium salt 6 (403 mg, 71%) as a white solid. Decomposition point: 188-190 oC; νmax cm-1: 2958, 1714, 1634, 1438, 1294, 1204, 1113, 960, 939, 906; H (400 MHz, CDCl3) 0.57 (3H, d, J = 7 Hz, iPr(Me)), 0.72 (3H, d, J = 7 Hz, iPr(Me)), 0.86 (3H, d, J = 7 Hz, Me), 0.91-1.02 (1H, m, CH), 1.10 (1H, q, J = 12 Hz, CH), 1.39-1.44 (3H, m, CH), 1.61-1.65 (2H, m, CH), 2.13 (1H, app. d, J =12 Hz, CH), 2.87 (3H, d, J =15 Hz, PMe), 2.94 (3H, d, J =15 Hz, PMe), 4.98 (1H, td, J = 11 and 5 Hz, CH), 7.58-7.62 (2H, m, ArH), 7.68-7.70 (1H, m, ArH), 7.86-7.92 (2H, m, ArH); C (100 MHz, CDCl3) 8.0 (d, 1JPC = 28 Hz), 8.5 (d, 1JPC = 30 Hz), 15.9, 20.5, 21.7, 23.1, 26.2, 31.6, 33.7, 40.1, 47.0, 81.9, 117.5 (d, 1JPC = 72 Hz), 130.2 (2C, d, 2JPC = 13 Hz), 131.8 (2C, d, 3JPC = 9 Hz), 135.1 (d, 4JPC = 4 Hz), 163.5 (d, 1JPC = 142 Hz); P (161 MHz, CDCl3) +20.2. [α]20 = - 51.9 (c 0.01, CHCl3). LRMS(ESI+): 321.2 ([M-Cl]+, 100%), 322.2 (22); HRMS (ESI+): 321.1981 ([M-Cl]+ C19H30O2P requires 321.1978). 19. Both the (R)- and (S)-enantiomers are available from Sigma Aldrich for £2.50/g and £4.70/g, respectively. 20. Freshly prepared by deprotection of the borane complex of isopropylmethylphenyl phosphine with piperazinomethyl polystyrene. 21. These results reflect that no kinetic resolution has occurred in the derivatisation process and any inconsistencies in the 31P NMR response between diastereoisomeric products is negligible. 22. This experiment affords mixtures of adducts 11 and ent-12, which is spectroscopically identical to 12. The 31P NMR chemical shifts of adducts 11 and ent-12 (and hence also adduct 12) were determined by separate preparation from (R)-menthyl chloroformate and enantiopure phospholanes (S,S)-10 and (R,R)-10, respectively.
S0040-4039(13)01335-X http://dx.doi.org/10.1016/j.tetlet.2013.07.155 TETL 43355
To appear in:
Tetrahedron Letters
Received Date: Revised Date: Accepted Date:
13 May 2013 15 July 2013 31 July 2013
Please cite this article as: , Tetrahedron Letters (2013), doi: http://dx.doi.org/10.1016/j.tetlet.2013.07.155
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Graphical Abstract To create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed or altered.
Menthyloxycarbonyl phosphonium chlorides: new derivatives for determining the enantiomeric excess of chiral tertiary phosphines A. Christopher Garner,* Roy C. Hodgkinson, John D. Wallis
Leave this area blank for abstract info.
1
Tetrahedron Letters journal homepage: www.elsevier.com
Menthyloxycarbonyl phosphonium chlorides: new derivatives for determining the enantiomeric excess of chiral tertiary phosphines A. Christopher Garner,* Roy C. Hodgkinson, John D. Wallis School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, UK. E-mail: [email protected]
ARTICLE INFO
ABSTRACT
Article history: Received Received in revised form Accepted Available online
The direct alkoxycarbonylation of tertiary phosphines with alkyl chloroformates has been examined and the products characterised by NMR and X-ray crystallographic analysis. The derivatisation of representative chiral tertiary phosphines with enantiopure menthyl chloroformate allows the determination of the enantiomeric excess of scalemic mixtures by 31P NMR spectroscopic analysis.
Keywords: Oxycarbonyl phosphonium salts ee determination Menthyl chloroformate Phosphine Phosphorus NMR
Chiral phosphines continue to enjoy popularity as the ligand of choice in a wide variety of asymmetric catalytic processes and the asymmetric synthesis of these compounds is an area of significant research.1 In the absence of other functionality, methods for the determination of the enantiomeric excess of chiral synthetic phosphines are limited and they are often determined by HPLC of phosphines or protected phosphines over chiral stationary phases.2 This method offers advantages of high sensitivity and accuracy, but at the expense of time-consuming method development, and these methods may not be amenable to the rapid evaluation of enantiomeric excesses. NMR techniques, involving both chiral solvating agents and derivatisation methods, are well established for compounds containing amine and hydroxyl functional groups,3 but such methods are not applicable to the many chiral ligands utilised in asymmetric transition metal catalysis containing only phosphine functionality. Despite the ability to readily measure 31P NMR spectra, NMR based methods for assessing chiral phosphines4 are limited to utilising chiral transition metal complexes5 and some related examples using chiral liquid crystal phase experiments.6 Acyl phosphonium ions7 (A, Figure 1) are generally considered to be unstable compounds,8 implicated as important reactive intermediates in nucleophilic catalysis9 and other synthetic processes.10 The related oxycarbonyl phosphonium ions (B, Figure 1) may be expected to exhibit greater stability, however these compounds have not been well studied or characterised to date. In 1937, Jensen reported the adducts from the reaction of triethylphosphine and a number of chloroformates,11 however subsequent reports of such species have been sparse.12 The direct generation of oxycarbonyl phosphonium ions from chloroformates is a synthetically attractive process and we wished to explore this chemistry and develop a simple 31P NMR spectroscopic method to assay the enantiomeric purity of tertiary phosphines.
2009 Elsevier Ltd. All rights reserved.
Figure 1. Preliminary studies revealed that alkoxycarbonyl phosphonium chlorides could be prepared from the reaction of phosphines with moderately sterically hindered alkyl chloroformates. Hence, treatment of dimethylphenyl phosphine (1) with iso-propyl or isobutyl chloroformate in toluene gave precipitates which were collected directly via filtration to afford alkoxycarbonyl phosphonium chlorides 2 and 3 as amorphous solids in excellent yields of 80% and 97%, respectively (Scheme 1).13
Scheme 1. Reagents and conditions: (i) iso-propyl-, iso-butyl- , (S)(+)-pantolactone-, (-)-borneol- or (S)-(+)-menthyl chloroformate, toluene, room temperature.
2
Tetrahedron
13
C NMR spectroscopic data were consistent with the expected PC=O connectivity and both compounds exhibited a doublet for the carbonyl carbon peak with 1JPC couplings of 135 and 136 Hz, respectively, and proved to be bench-stable for a period of several weeks. In further support of this structural assignment, the structure of 2 was confirmed by X-ray crystallographic analysis of the corresponding PF6 salt at 120 K (Figure 2).14
Scheme 2. Reagents and conditions: (i) (-)-(1R,2S,5R)-menthyl chloroformate, toluene.
Figure 2. Ball and stick representation of the X-ray crystal structure of the PF6 salt of 2 (counter ion omitted for clarity).15 In structure 2 the P+-C(=O) bond is 1.855(2) Å long, being significantly longer than the three P+-C bonds to the phenyl and methyl groups [1.775(2) - 1.782(2) Å]. At the carbonyl carbon the widest angle is between the two O atoms [129.1(2)o] and the smallest between the alkoxy O and the P atom [111.37(16)o]. The only related structures known are those of the frustrated lone pair complexes of carbon dioxide with a phosphine and borane, which show a longer P-C(=O) bond (1.893-1.900 Å ).16 Having established the rapid and clean formation of these adducts, our investigation then turned to realising the potential of this reaction for the assay of the enantiomeric purity of tertiary phosphines utilising a chiral chloroformate as the derivatising agent. Initially, the reactivity of the achiral tertiary phosphine, phenyl dimethyl phosphine (1) towards chiral chloroformates was examined. The addition of phosphine 1 to a toluene solution of (S)-pantolactone chloroformate17 afforded the corresponding phosphonium chloride 4 as an unstable oil, while similar reactions with (-)-borneol and (S)(+)-menthol derived chloroformates17 afforded phosphonium chlorides 5 and 6 as amorphous solids in 72% and 71% isolated yields, respectively (Scheme 1).18 Given that menthyl chloroformate is cheap and commercially available in both enantiomeric forms,19 it was chosen for further investigation as a chiral derivatising agent. Initially, the preparation of a menthyl oxycarbonyl phosphonium chloride salt of a Pchirogenic tertiary phosphine was examined. Treatment of a racemic mixture of iso-propyl methyl phenylphosphine 720 (0.2 M solution in CDCl3) with a small excess of (1R,2S,5R)-menthyl chloroformate (1.1 equivalents, 0.5 M solution in CDCl3) afforded a 1:1 mixture of (RP,1R,2S,5R)- and (SP,1R,2S,5R)-menthyl oxycarbonyl-(isopropyl-methyl-phenyl)phosphonium chlorides 8 and 9 (Scheme 2). Examination of the 31P {1H} NMR spectrum showed complete conversion of the starting material into two baseline resolved singlet peaks of equal intensity (P = 30.4 and 31.4 ppm, = 1.0 ppm).
The 13C NMR spectrum of the mixture was consistent with the expected oxycarbonyl phosphonium chlorides and both compounds exhibited a carbonyl carbon peak with a 1JPC coupling of 119 Hz. The 13C and 1H NMR spectra also revealed contamination of the sample with excess of menthyl chloroformate. These data demonstrate that this reagent fulfills the requirements for a chiral derivatising agent for NMR analysis in that: (1) salt formation is rapid, (2) no kinetic resolution occurs in the formation of the diastereoisomeric salts, and (3) there is a significant, baseline resolved, difference in chemical shifts between the 31P NMR signals of the derived salts. Having demonstrated menthyl chloroformate as an effective chiral derivatising agent for a P-chirogenic tertiary phosphine containing no other functionality, the application of this method to a representative chiral tertiary mono-phosphine 10, exhibiting backbone chirality was explored. Phospholane 10 is commercially available in both enantiomeric forms, but not as a racemate, and it was convenient to determine the enantiodiscriminating capacity of the chiral derivatising agent by treating the enantiopure substrate with racemic menthyl chloroformate. Hence, in an NMR tube, a small excess of racemic menthyl chloroformate17 (1.1 equivalents, 0.5 M solution in CDCl3) was added to (S,S)-phospholane 10 in CDCl3 (0.2 M solution in CDCl3) and the 31P NMR spectrum recorded after 30 minutes. Examination of this spectrum revealed that all the starting phosphine had been consumed and showed two baseline resolved singlet peaks of near equal area (52:48, P = 57.6 and 56.4 ppm, 1.2 ppm) corresponding to (S,S)-phosphine/(R)-menthyl oxycarbonyl adduct 11 and (S,S)-phosphine/(S)-menthyl oxycarbonyl adduct 12, respectively (Scheme 3).21 Examination of the 1H and 13C NMR spectra of the mixture supported the formation of the two diastereoisomeric phosphonium salts and also revealed an excess of menthyl chloroformate.
3
Scheme 3. Reagents and conditions: CDCl3, room temperature. Having demonstrated effective enantiodiscrimination, the enantiomeric excess of scalemic mixtures of phospholanes (S,S)-10 and (R,R)-10 in ratios of 90:10 and 99:1 were determined by derivatisation with (R)-menthyl chloroformate.22 These results showed that a reliable measurement of enantiomeric excess of up to 98% could be obtained by this technique. In conclusion, the utility of menthyl chloroformate as a cheap, commercially available reagent for the determination of the enantiomeric excess of representative chiral tertiary phosphines has been demonstrated. This method is ideally suited to assessing the enantiomeric excess of nucleophilic chiral phosphines for application in organocatalysis and as ligands in transition metal catalysis, and provides a convenient and simple alternative to complementary chromatographic methods. Acknowledgements The authors would like to thank the Leverhulme Trust for funding Project Grant F/01 374/H (R.C.H.) and the EPSRC Mass Spectrometry Service at Swansea University.
References and notes 1. Phosphorus Ligands in Asymmetric Catalysis, Vol. 3 (Ed.: Borner A.), Wiley-VCH, New York, 2008, 1175. 2. (a) Colby E. A.; Jamison, T. F., J. Org. Chem. 2003, 68, 156-166; (b) Muci, A. R.;Campos, K. R.; Evans, D. A. J. Am. Chem. Soc., 1995, 117, 9075-76. 3. For a recent review, see: (a) Wenzel, T. J.; Chisholm, C. D. Prog. Nucl. Magn. Reson. Spectrosc., 2011, 59, 1-63; (b) Wenzel, T. J. Discrimination of Chiral Compounds Using NMR Spectroscopy, Wiley Interscience, Hoboken, NJ, 2007; (c) Duddeck H.; Gomez, E. D. Chirality, 2009, 21, 51-68; (d) Donnoli, M. I.; Superchi, S.; Rosini, C. Mini-Rev. Org. Chem., 2006, 3, 7792; (e) Blazewska, K. M.; Gadja, T. Tetrahedron: Asymmetry, 2009, 20, 1337-61. 4. In contrast, chiral phosphorus based reagents for derivatising amines and alcohols exploit 31P NMR spectroscopy to assess ee, see: (a) Hulst, R.; Kellogg R. M.; Feringa, B. L. Recl. Trav. Chim. Pay-B, 1995, 114, 115-138 ; For recent examples, see: (b) Reiner, T.; Naraschewski, F. N.; ; Eppinger, J. Tetrahedron: Asymmetry, 2009, 20, 362-67; (c) Gulea, M.; Kwiatkowska, M.; Lyzwa, P.; Legay, R.; Gaumont A-C.; Kielbasinski, P. Tetrahedron: Asymmetry, 2009, 20, 293-297; (d) Mastranzo, V. M.; Quintero L.; De Parrodi, C. A. Chirality, 2007, 19, 503-507. 5. (a) Wild, S. B. Coord. Chem. Rev., 1997, 166, 291-311; (b) Dunina, V. V.; Kuz'mina, L. G.; Kazakova, M. Y.; Grishin, Y. K.; Veits, Y. A.; Kazakova, E. I. Tetrahedron: Asymmetry, 1997, 8, 2537-2545. (c) For references to similar ee assays, see:, Ng, J. K. P;. Chen, S.; Tan, G. K.; Leung P-H. Tetrahedron: Asymmetry, 2007, 18, 1163-69.
6. For enantiodiscrimination of chiral phosphine oxides and boranes, see: (a) Rivard, M.; Guillen, F.; Fiaud, J-C.; Aroulanda C.; Lesot, P. Tetrahedron: Asymmetry, 2003, 14, 1141-52; For chiral phosphonium salts, see: Meddour, A.; Uziel, J.; Courtie J.; Juge, S. Tetrahedron: Asymmetry, 2006, 17, 1424-29. 7. For a review of acyl phosphonium and ammonium species, see: (a) Kolesinska, B. Cent. Eur. J. Chem., 2010, 8, 1147-71; For early reports, see: (b) Yakshin, V. V.; Sokal'skaya, L. I. Zh. Obshch. Khim., 1973, 43, 440; (c) Lukashev, N. V.; Artyushin, O. I.; Lazhko, E. I.; Tafeenko, V. A.; Kazankova M. A.; Lutsenko, I. F. Zh. Obshch. Khim., 1988, 58, 316-327. (d) Thamm R.; Fluck, E. Z. Naturforsch. Pt B, 1982, 37B, 965-74; (e) Gololobov, Y. G.; Pinchuk, V. A.; Thoennessen H.; Jones P.G.; Schmutzler, R. Phosphorus, Sulfur Silicon Relat. Elem, 1996, 115, 19-37. 8. Isolated salts are reported to be very hygroscopic but stable in the absence of moisture, see reference 7(b). 9. For reviews, on phosphine-based nucleophilic catalysis, see: (a) Zhou, Z.; Wang, Y.; Tang C. Curr. Org. Chem., 2011, 15, 4083-4107; (b) Marinetti, A.; Voituriez, A. Synlett, 2010, 174-194; (c) Cowen, B. J.; Miller, S. J. Chem. Soc. Rev., 2009, 38, 3102-3116; (d) Methot, J. L.; Roush, W. R.; Adv. Synth. Calat., 2004, 346, 1035-1050. 10. For examples of acylated phosphines as stoichiometric intermediates, see: (a) Maeda, H.; Maki T.; Ohmori, H. Tetrahedron Lett., 1995, 36, 2247-50; (b) Maeda, H.; Okamoto, J.; Ohmori, H. Tetrahedron Lett., 1996, 37, 5381-84; (c) Maeda, H.; Takahashi K.; Ohmori, H. Tetrahedron, 1998, 54, 12233-42; (d) Maeda, H.; Huang, Y.; Hino, N.; Yamauchi Y.; Hidenobu, O. Chem. Commun., 2000, 2307-8; (e) Maeda, H.; Hino, N.; Yamauchi, Y.; Ohmori, H. Chem. Pharm. Bull., 2000, 48, 1196-99. See also: (f) Weiss, R.; Bess M.; Huber S. M.; Heinemann, F. W. J. Am. Chem. Soc., 2008, 130, 4610-17. 11. Jensen, K. A. J. Prakt. Chem., 1937, 148, 101-106. 12. (a) Vedejs E.; Donde, Y. J. Am. Chem. Soc., 1997, 119, 9293-4; (b) Uncharacterised oxycarbonyl phosphonium salts have been reported as intermediates, see reference 10c. For an example of the related carbamoyl phosphine boranes, see: (c) Imamoto, T.; Tamura, K.; Ogura, T.; Ikematsu, Y.; Mayama D.; Sugiya, M. Tetrahedron: Asymmetry, 2010, 21, 1522-8. 13. General procedure for the preparation of phosphonium salts. The phosphine was added to a solution of the chloroformate in toluene. This mixture was stirred at room temperature for 30 min. The resulting precipitate was collected by filtration and washed with toluene and dried to yield the alkoxycarbonyl phosphonium salt. iso-Butoxycarbonyl dimethylphenylphosphium chloride (3) Prepared using the general procedure, using dimethylphenyl phosphine (1) (1.0 g, 1.0 mL, 7.2 mmol), iso-butyl chloroformate (1.18 g, 1.1 mL, 8.64 mmol) and toluene (2 mL), to yield phosphonium salt 3 (2.29 g, 97%) as a white solid. Decomposition point: 95-97 oC; νmax cm-1: 2963, 2875, 1727, 1440, 1211, 962, 912; H (400 MHz, CDCl3) 0.88 (3H, s, iPr(Me)), 0.90 (3H, s, iPr(Me)), 2.05 (1H, hept, J = 7 Hz, iPr(CH)), 2.95 (6H, d, J = 15 Hz, PMe2), 4.23 (2H, dd, J = 6 and 1 Hz, CH2O), 7.61-7.66 (2H, m, Ph), 7.71-7.75 (1H, m, Ph), 7.88-7.94 (2H, m, Ph); C (100 MHz, CDCl3) 8.5 (2C, 1JPC = 55 Hz), 18.8 (2C), 27.5, 75.5 (d, 3JPC = 4 Hz), 117.5 (1JPC = 117 Hz), 130.2 (2C, d, 2JPC = 14 Hz), 131.7 (2C, d, 3JPC = 10 Hz), 135.1 (d, 4JPC = 4 Hz), 163.2 (d, 1 JPC = 136, Hz); P (161 MHz, CDCl3) +20.9. LRMS(ESI+): 239.1 ([M-Cl]+, 100%), 240.1 (14); HRMS (ESI+): 239.1193 ([M-Cl]+ C13H20O2P requires 239.1195). 14. The PF6 salt of 2 was prepared by metathesis of the chloride of (isopropyl-oxycarbonyl) dimethylphenyl phosphonium chloride with sodium hexafluorophosphate in acetone. Crystal data for the PF6 salt of 2: C12H18O2P·PF6, Mr = 370.20, monoclinic, a = 8.6809(3), b = 14.0685(5), c = 14.1748(5) Å, β = 105.488(4) o, V = 1668.27(10) Å 3, Z = 4, P21/c, Dc = 1.47 g cm3, = 0.322 mm1, T = 120 K, 3875 unique reflections, 3212 with F2 > 2, R(F, F2>2) = 0.051, Rw(F2, all data) = 0.12. There are two orientations of the PF6- anion in the ratio 2:1. Crystallographic data (excluding structure factors) have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 931374. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (0) 1223 336033 or e-mail: [email protected]]. 15. Molecular illustration was prepared with Mercury (Macrae, C.F.; Edgington, P.R.; McCabe, P.; Pidcock, E.; Shields, G. P.; Taylor, R.; Towler, M.; van de Streek, J. J. Appl. Crystallogr., 2006, 39, 453-457) and POV-RAY (Persistence of Vision Pty. Ltd. 2004. Persistence of Vision™ Raytrace, Persistence of Vision Pty. Ltd., Williamstown, Victoria, Australia, http://www.povray.org). 16. (a) Sgro, M. J.; Domer, J.; Stephan, D. W. Chem. Commun., 2012, 48, 7253-55; (b) Momming, C.; Otten, E.; Kehr, G.; Frohlich, R.; Grimme, S.; Stephan, D.W.; Erker, G. Angew. Chem. Int. Ed., 2009, 48, 6643-46. 17. Prepared from the corresponding alcohol and phosgene, see reference 12(a).
4
Tetrahedron
18. {[(1S,2R,5S)-2-iso-Propyl-5-methylcyclohexyloxy]carbonyl}dimethyl(phenyl) phosphonium chloride 6 Prepared using the general procedure, using dimethylphenyl phosphine (1) (221 mg, 0.2 mL, 1.60 mmol), (1S,2R,5S)-menthyl chloroformate (350 mg, 1.60 mmol), and toluene (1 mL), to yield phosphonium salt 6 (403 mg, 71%) as a white solid. Decomposition point: 188-190 oC; νmax cm-1: 2958, 1714, 1634, 1438, 1294, 1204, 1113, 960, 939, 906; H (400 MHz, CDCl3) 0.57 (3H, d, J = 7 Hz, iPr(Me)), 0.72 (3H, d, J = 7 Hz, iPr(Me)), 0.86 (3H, d, J = 7 Hz, Me), 0.91-1.02 (1H, m, CH), 1.10 (1H, q, J = 12 Hz, CH), 1.39-1.44 (3H, m, CH), 1.61-1.65 (2H, m, CH), 2.13 (1H, app. d, J =12 Hz, CH), 2.87 (3H, d, J =15 Hz, PMe), 2.94 (3H, d, J =15 Hz, PMe), 4.98 (1H, td, J = 11 and 5 Hz, CH), 7.58-7.62 (2H, m, ArH), 7.68-7.70 (1H, m, ArH), 7.86-7.92 (2H, m, ArH); C (100 MHz, CDCl3) 8.0 (d, 1JPC = 28 Hz), 8.5 (d, 1JPC = 30 Hz), 15.9, 20.5, 21.7, 23.1, 26.2, 31.6, 33.7, 40.1, 47.0, 81.9, 117.5 (d, 1JPC = 72 Hz), 130.2 (2C, d, 2JPC = 13 Hz), 131.8 (2C, d, 3JPC = 9 Hz), 135.1 (d, 4JPC = 4 Hz), 163.5 (d, 1JPC = 142 Hz); P (161 MHz, CDCl3) +20.2. [α]20 = - 51.9 (c 0.01, CHCl3). LRMS(ESI+): 321.2 ([M-Cl]+, 100%), 322.2 (22); HRMS (ESI+): 321.1981 ([M-Cl]+ C19H30O2P requires 321.1978). 19. Both the (R)- and (S)-enantiomers are available from Sigma Aldrich for £2.50/g and £4.70/g, respectively. 20. Freshly prepared by deprotection of the borane complex of isopropylmethylphenyl phosphine with piperazinomethyl polystyrene. 21. These results reflect that no kinetic resolution has occurred in the derivatisation process and any inconsistencies in the 31P NMR response between diastereoisomeric products is negligible. 22. This experiment affords mixtures of adducts 11 and ent-12, which is spectroscopically identical to 12. The 31P NMR chemical shifts of adducts 11 and ent-12 (and hence also adduct 12) were determined by separate preparation from (R)-menthyl chloroformate and enantiopure phospholanes (S,S)-10 and (R,R)-10, respectively.