A convenient route from simple sugars to new chiral bis(phosphinoesters) for asymmetric catalysis

Inorganic Chemistry Communications 10 (2007) 618–622 www.elsevier.com/locate/inoche

A convenient route from simple sugars to new chiral bis(phosphinoesters) for asymmetric catalysis Raffaella Del Litto, Antonella De Roma, Francesco Ruffo

*

Dipartimento di Chimica, Universita` di Napoli ‘‘Federico II’’, Complesso Universitario di Monte S. Angelo, via Cintia, I-80126 Napoli, Italy Received 29 November 2006; accepted 12 February 2007 Available online 20 February 2007

Abstract Readily available chiral bis(phosphinoesters) based on D-glucose, D-mannose and D-galactose have been prepared in only two steps and in large scale starting from inexpensive commercial precursors. Their Pd complexes catalyze the asymmetric desymmetrization of meso-cyclopent-4-ene-1,3-diol biscarbamate in ee’s up to 82%. Ó 2007 Elsevier B.V. All rights reserved. Keywords: Asymmetric catalysis; Sugars; Palladium; Allylic substitution

Metal-promoted asymmetric catalysis is one of the core technologies for fine chemical production [1]. Its valuable application guarantees high reactions selectivity, energy saving, low environmental impact, and, in general, highly performing processes [2]. Within this frame, ligand design has great importance, as reflected by the incessant proposal of new chiral structures. Remarkably, a selected few ligands are acknowledged as ‘‘privileged’’ [3], given their extraordinary adaptability and skill to promote asymmetry under several catalytic conditions. Recently [4], we have proposed a strategy for improving the performance of ‘‘privileged ligands’’, by incorporating their ligand functions into a sugar backbone [5]. Carbohydrates were selected because they are naturally chiral and often easily available. Furthermore, an appropriate derivatisation of the hydroxyls present in their skeleton is suited for tailoring the physical properties of the ligands. This may allow their use in innovative bi-phasic conditions [6], because an efficient immobilisation of the catalyst in a second phase is possible by properly functionalising the sugar sites not involved in coordination. *

Corresponding author. Tel.: +39081674460; fax: +39081674090. E-mail address: ruff[email protected] (F. Ruffo).

1387-7003/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.inoche.2007.02.009

On these grounds, we were able to prepare [4] sugar versions of ‘‘privileged ligands’’ based on trans-1,2-cyclohexanediamine, such as ‘‘salens’’ [7] or Trost ligands [8], successfully used in several fine chemical manufactures (Fig. 1). Their use in asymmetric catalysis was promising, e.g. bis(phosphinoamides) [4c] derived from D-glucose (1G) and from D-mannose (1M) promoted the asymmetric desymmetrization of meso-cyclopent-4-ene-1,3-diol biscarbamate (4) with ee’s up to 97% (Scheme 1). A limit of this strategy is that the synthesis of 0G, 1G, 0M and 1M requires 2,3-D-gluco- and 2,3-D-manno-diamines as key precursors. Though simple, their synthesis is quite tiresome and is accomplished through several steps [9]. For this reason, we were interested in designing new ligands with similar structure and hopefully analogous performance, by reducing the experimental effort. This target has been pursued by preparing 2G, 2M, and 2Gt (i.e. the ester version of 1G and 1M, Fig. 2) through a straightforward procedure, which can be easily carried out in large scale directly starting, respectively, from commercial methyl-a-D-glucoside, methyl-a-D-mannoside and methyla-D-galactoside. Notably, the corresponding ligands based on chiral trans-1,2-cyclohexanediol are not as easily affordable, because this is a very expensive compound.

R. Del Litto et al. / Inorganic Chemistry Communications 10 (2007) 618–622

O

O

Ph

O

Ph

O

OR

O

O

6 4

N

OH HO t-Bu

t-Bu

N

N

OH

HO

Ph

O 1

O

t-Bu t-Bu 0G (from D-glucose) 0M (from D-mannose)

salen

5

OMe O

3 2

O N

P Ph Ph

O O

OR O NH

O

O HN

NH

HN

P Ph Ph

P Ph Ph

P Ph Ph

P Ph Ph

1G (from D-glucose) 1M (from D-mannose)

Trost ligand

Fig. 1. Structures of ‘‘privileged ligands’’ and corresponding sugar versions.

Ts TsNCO HO

O

OH

-CO2 -TsNH2

HN

O

3 Pd(dba)2 ligand

Ts

NH

O

O 4

O

Ts H N

O

Ts H N

O

O

H 5 +(S,R)

H 5 -(R,S)

Scheme 1. The asymmetric desymmetrization of meso-cyclopent-4-ene1,3-diol biscarbamate.

In this communication, we describe the synthesis and characterisation of the new ligands, accompanied by an examination of their catalytic ability in comparison with 1G and 1M. The synthesis of 2G, 2M, and 2Gt is summarised in Scheme 2 [10]. Commercial precursors are inexpensive glycosides, i.e. methyl-a-D-glucoside (6G), methyl-a-D-mannoside (6M) and methyl-a-D-galactoside (6Gt). The monosaccharides are initially protected [11] in positions C4 and C6 with a benzylidene function (path i) affording intermediate products 7. These are converted into the target ligands of type 2 by reaction with 2-diphenylphosphinobenzoic acid in dichloromethane in the presence of DCC and DMAP (ii). In these conditions the hydroxyl functions at C2 and C3 are readily esterified, and the products can be isolated in high yield as white powders by crystallisation in ethanol. The molecules have been characterised through monoand two-dimensional proton and carbon NMR spectros-

4

5

O 1

3 2

O

P Ph Ph

2G

OMe O

O

P Ph Ph

P Ph Ph

2M

O

O

6

O

O Ph

O

O

Ph

O

619

6 5

O 1

4 3 2

O O

OMe O

O

P Ph Ph

P Ph Ph

2Gt Fig. 2. Structures of ligands 2G, 2M and 2Gt.

copy [12]. The formation of the ester groups is clearly demonstrated by the high-frequency shift of H2 and H3, which resonate in the range 4.5–6 ppm. D-Glucose and D-galactose are epimers at C4 and, therefore, 2G and 2Gt differ for the relative orientation of the sugar and benzylidene chairs. Both display the ester functions in the equatorial positions (Fig. 2). Instead, D-glucose and D-mannose are epimers at C2, and this is reflected in the diverse arrangement of the coordinating ester functions of 2G and 2M (respectively, equatorial–equatorial and axial-equatorial, Fig. 2). Of course, 2M and 2Gt differ for both geometrical motifs. This assortment has been used for an evaluation of the geometrical influence of the sugar coordination environment in the asymmetric desymmetrization of meso-cyclopent-4-ene-1,3-diol biscarbamate according to Scheme 1. This intramolecular allylic substitution affords the key precursors of mannostatines [13], and is also a standard test for the assessment of the stereo-orienting properties of new ligands [14]. The reactions [15] were performed at 273 K in dry THF by using 5% Pd(dba)2 as pre-catalyst. In the case of the Dglucose derivative 2G the action of the temperature has been considered, and two different values (273 and 258 K) have been examined. Previous findings on ligands of type 1 disclosed a significant influence of triethylamine on the enantioselectivity of the reaction. Therefore, the effect of an added base has also been investigated. The results are reported in Table 1, along with the outcomes obtained by using the corresponding diamides 1G and 1M in the same conditions. It is worth noting that – D-glucose ligand 2G largely favours formation of the – (R,S) enantiomer, in analogy with the corresponding diamide 1G (entries 1–4). This is reasonable because

620

R. Del Litto et al. / Inorganic Chemistry Communications 10 (2007) 618–622

O Ph HO O HO HO

CHO

OH

O HO

6G (from D-glucose) 6M (from D-mannose) 6Gt (from D-galactose)

HO

O

(i) Ph OMe +

O O

O

O

(ii) DCC, DMAP

O

OMe + 2 CH2Cl2

P Ph Ph

OH

OMe O

O O

P Ph Ph

7G (from D-glucose) 7M (from D-mannose) 7Gt (from D-galactose)

P Ph Ph

2G (from D-glucose) 2M (from D-mannose) 2Gt (from D-galactose)

Scheme 2. Synthesis of 2G, 2M and 2Gt. Step (i) has been performed according to known procedures [11].

changing the organic linker is expected to affect the sole flexibility of the ligand, with a minor influence on its stereochemistry of coordination. Of course this latter feature plays also a role, identifiable in the fact that 1G and 2G display different enantioselectivities in the same conditions (see below). – D-mannose derivative 2M affords product 5 as a racemic mixture (entries 6 and 7). This result is not completely unexpected, because previous work [4a] demonstrated that ligands based on 2,3-disubstitued D-mannose are generally poorly effective, due to the relative arrangement of the coordinating functions (axial–equatorial). Nevertheless, this unsatisfactory result is in great contrast with the high ee’s (up to 97% of +(S,R)-5) obtained by using the corresponding diamide 1M. A combination of factors may determine this finding, i.e. steric hindrance afforded by the D-mannose chair (schematised in Fig. 3) may force the flexible ester linkers in a conformation unfavourable to enantiodiscrimination.

Table 1 Catalytic reactions according to Scheme 1a Entry

Ligand T (K)

1

2G 273

2

2G 258

Time

Conversionb (%)

ee(%) of 4c,d

0

30 0

99

0

30 0

99

80 (80d) (R,S) 82 (68d) (R,S) 74 (93d) (R,S) 75 (97d) (R,S) 70 (R,S) 0 (91d) +(S,R) 0 (95d) +(S,R) 70 (R,S) 48 (R,S)

NEt3 (eqvs)

3

2G 273

1

30 0

99

4

2G 258

1

30 0

99

5 6

2G 273 2M 273

10 0

30 0 30 0

99 99

7

2M 273

1

30 0

99

8 9

2Gt 273 2Gt 273

0 1

30 0 30 0

99 99

– galactose ligand 2Gt has the ester groups in the equatorial positions at C2 and C3 of the sugar chair, similarly to 2G. Accordingly, 2Gt significantly promotes formation of (R,S)-5, though less effectively than 2G (entries 8–9). The decrease of values switching from D-glucose to D-galactose (e.g., from 80% to 70% ee, entries 2 and 8) reveals that even the stereochemistry of substituents quite distant from the metal coordination sphere is decisive for the selectivity. – the influence of triethylamine has revealed to be small for 2G and 2M, if compared to that observed with 1G and 1M. Instead, the performance of 2Gt is more affected by the presence of a base. In all cases, a negative variation of ee’s has been observed by adding one equivalent of triethylamine to the reaction mixture (entries 1 vs 3, 2 vs 4, 8 vs 9). Accordingly, a large excess of triethylamine reduces even more considerably the selectivity, which decreases for 2G at 70% when 10 equivalents of base is present (entry 5). – the temperature plays an even minor effect, and no significant variation of ee’s has been recorded by performing the reactions at 273 or 258 K (entries 1 vs 2, or 3 vs 4).

Ph

Ph O

O O

O

PPh2 2G

O O O

O OMe

O PPh2

O OMe

Ph2P

Ph2P

2M

O

O

Ph O

O

O O

O

a

In dry THF, catalyst:substrate 1:20. b Determined by NMR spectra of the crude reaction mixtures. c Determined by HPLC on Chiracel OD-H, using 2-propanol/hexane 1:10, 1.0 mL/min, UV. d The ee obtained by using the corresponding diamide of type 1 (see Ref. [4c]) is reported in parentheses.

O

PPh2 2Gt

Ph2P

O

O OMe

Fig. 3. Schematic views of the geometry of 2G, 2M and 2Gt.

R. Del Litto et al. / Inorganic Chemistry Communications 10 (2007) 618–622

Thus, the most convenient conditions have been found by using 2G at 258 or 273 K in absence of an added base, which affords (R,S)-5 in quantitative yield and 80–82% ee within 30 min. It should be noted that diester 2G does not reach the high performance of the corresponding diamide 1G, according to a general trend previously described by Trost et al. [14b], and ascribed to the higher conformational rigidity of the amido function. Notably, 2G is more effective than Trost’s bis(phosphinoesters), which promoted ee’s up to 75.1% in the same conditions [14b]. This favourable comparison gives more emphasis to the quality of the new sugar-based ligands, and further stimulates investigation on their use in asymmetric catalysis. The current work involves a tailored functionalisation of the available C4 and C6 positions of the D-glucose ring, for extending the use of 2G in innovative bi-phasic systems based on fluorous solvents [6] or homogeneously supported catalysts.

[11]

[12]

Acknowledgements The authors thank the MIUR for financial support. Thanks are also given to the Centro Interdipartimentale di Metodologie Chimico-Fisiche, Universita` di Napoli ‘‘Federico II’’ for NMR facilities. The authors also thank Mr. Nicola Fedele (Mpacolı`) for technical assistance. References [1] H.U. Blaser, E. Schmidt (Eds.), Asymmetric Catalysis on Industrial Scale, first ed., Wiley-VCH, Weinheim, Germany, 2004. [2] P.T. Anastas, J.C. Warner, Green Chemistry: Theory and Practice, first ed., Oxford University Press Inc., New York, USA, 1998. [3] T.P. Yoon, E.N. Jacobsen, Science 299 (2003) 1691. [4] (a) C. Borriello, R. Del Litto, A. Panunzi, F. Ruffo, Tetrahedron: Asymm. 15 (2004) 681; (b) C. Borriello, R. Del Litto, A. Panunzi, F. Ruffo, Inorg. Chem. Commun. 8 (2005) 717; (c) R. Del Litto, A. De Roma, A. D’Errico, S. Magnolia, F. Ruffo, Tetrahedron: Asymm. 17 (2006) 2265. [5] (a) Other categories of ligands based on sugars are known: D. Steinborn, H. Junicke, Chem. Rev. 100 (2000) 4283; (b) M. Die´guez, O. Pa`mies, A. Ruiz, Y. Diaz, S. Castillo´n, C. Claver, Coord. Chem. Rev. 248 (2004) 2165; (c) M. Die´guez, O. Pa`mies, C. Claver, Chem. Rev. 104 (2004) 3189; (d) Y. Diaz, S. Castillo´n, C. Claver, Chem. Soc. Rev. 34 (2005) 702. [6] B. Cornils, W.A. Herrmann, I.T. Horvath, W. Leitner, S. Mecking, H. Olivier-Borbigou, D. Vogt (Eds.), Multiphase Homogeneous Catalysis, first ed., Wiley-VCH, Weinheim, Germany, 2005. [7] E.N. Jacobsen, A. Pfaltz, H. Yamamoto (Eds.), Comprehensive Asymmetric Catalysis, Springer, Berlin, Germany, 1999. [8] (a) B.M. Trost, M.L. Crawley, Chem. Rev. 103 (2003) 2921; (b) B.M. Trost, M. Machacek, A. Aponick, Acc. Chem. Res. 39 (2006) 747. [9] (a) W. Meyer zu Reckendorf, R. Weber, H. Hehenberger, Chem. Ber. 14 (1981) 1306; (b) R.D. Guthriue, D. Murphy, J. Chem. Soc. (1965) 6956. [10] Synthesis of 2G, 2M and 2Gt. A solution of 2-(diphenylphosphino)benzoic acid (1.29 g, 4.2 mmol), 4-dimethylaminopyridine (0.048 g, 0.43 mmol) and 1,3-dicyclohexylcarbodiimide (0.89 g, 4.3 mmol) in dry dichloromethane (7 mL) was added to a solution of the appropriate precursor of type 7 (2.0 mmol) in the same solvent

[13] [14]

[15]

621

(7 mL). The resulting mixture was stirred overnight at room temperature under inert atmosphere affording a suspension. After filtration, the solvent was removed under vacuum, and the residue was crystallised in hot ethanol affording the product as a white solid (yields: 2G, 85%; 2M, 85%; 2Gt, 80%). (a) K. Freudenberg, H. Toepffer, C.C. Andersen, Berichte der Deutschen Chemischen Gesellschaft B: Abhandlungen 61B (1928) 1750; (b) J.G. Buchanan, J.C.P. Schwarz, J. Chem. Soc. (1962) 4770; (c) E. Sorkin, T. Reichstein, Helv. Chim. Acta 28 (1945) 1. Compound 2G: Anal. Calcd for C52H44O8P2: C, 72.72; H, 5.16. Found: C, 72.78; H, 5.09. Selected 1H NMR data (200 MHz, CDCl3): d 5.92 (t, 1H, H3, 3JH3–H2 = 3JH3–H4 = 9.9 Hz), 5.30 (s, 1H, PhCHO2), 4.89 (d, 1H, H1, 3JH1–H2 = 3.6 Hz), 4.83 (dd, 1H, H2), 4.25 (dd, 1H, H6eq, 3JH6eq–H5 = 4.8, 3JH6eqH6ax = 10.5 Hz), 3.86 (dt, 1H, H5, 3JH5–H6ax = 3JH5–H4 = 9.9 Hz), 3.62 (t, 1H, H6ax), 3.26 (s, 3H, OMe), 3.23 (t, 1H, H4). Selected 13C NMR data (50.2 MHz, CDCl3): d 166.1, 165.5, 101.2, 97.5, 79.0, 72.6, 69.7, 68.8, 62.3, 55.3. [a](298 K, in dichloromethane, 589 nm): 41.5°. Compound 2M: Anal. Calcd for C52H44O8P2: C, 72.72; H, 5.16. Found: C, 72.55; H, 5.24. Selected 1H NMR data (200 MHz, CDCl3): d 5.70 (dd, 1H, H3, 3 JH3–H2 = 3.4, 3JH3–H4 = 10.0 Hz), 5.49 (s, 1H, PhCHO2), 5.43 (dd, 1H, H2, 3JH2–H1 = 1.6 Hz), 4.58 (d, 1H, H1), 4.25 (dd, 1H, H6eq, 3 JH6eq–H5 = 4.2, 3JH6eq–H6ax = 9.8 Hz), 4.09 (t, 1H, H4, 3JH4– 3 H5 = 10.0 Hz), 3.92 (dt, 1H, H5, JH5–H6ax = 10.0 Hz), 3.77 (t, 1H, H6ax), 3.22 (s, 3H, OMe). Selected 13C NMR data (50.2 MHz, CDCl3): d 162.4, 162.3, 100.8, 98.6, 76.8, 70.7, 68.2, 68.0, 63.0, 54.4. [a] (298 K, in dichloromethane, 589 nm): 26.9°. Compound 2Gt: Anal. Calcd for C52H44O8P2: C, 72.72; H, 5.16. Found: C, 72.68; H, 5.30. Selected 1H NMR data (200 MHz, CDCl3): d5.61 (m, 2H, H2 and H3, 3JH2–H1 = 3.0 Hz, 3JH3–H4 = 2.4 Hz,), 5.43 (s, 1H, PhCHO2), 4.93 (d, 1H, H1), 4.39 (s, 1H, H4), 4.11 (ABq, 2H, H6ax and H6eq, 2 Jgem = 14 Hz), 3.69 (s, 1H, H5), 3.26 (s, 3H, OMe); Selected 13C NMR data (50.2 MHz, CDCl3): d165.9 (2C), 100.6, 97.8, 74.0, 69.3, 69.0, 68.8, 62.0, 55.4. [a] (298 K, in dichloromethane, 589 nm): +27.7°. B.M. Trost, D.L. Van Vranken, J. Am. Chem. Soc. 113 (1991) 6317. (a) B.M. Trost, D.L. Van Vranken, Angew. Chem. Int. Ed. Engl. 31 (1992) 228; (b) B.M. Trost, D.L. Van Vranken, C.J. Bingel, J. Am. Chem. Soc. 114 (1992) 9327; (c) B.M. Trost, D.L. Van Vranken, J. Am. Chem. Soc. 115 (1993) 444; (d) B.M. Trost, B. Breit, Tetrahedron Lett. 35 (1994) 5817; (e) B.M. Trost, B. Breit, S. Peukert, J. Zambrano, W. Ziller, Angew. Chem. Int. Ed. Engl. 34 (1995) 2386; (f) B.M. Trost, D.E. Patterson, J. Org. Chem. 63 (1998) 1339; (g) S. Lee, C.W. Lim, C.E. Song, K.M. Kim, C.H. Jun, J. Org. Chem. 64 (1999) 4445; (h) C.W. Lim, S. Lee, Tetrahedron 56 (2000) 5131; (i) B.M. Trost, J.L. Zambrano, W. Richter, Synlett (2001) 907; (j) N. Buschmann, A. Rueckert, S.J. Blechert, J. Org. Chem. 67 (2002) 4325; (k) C.E. Song, J.W. Yang, E.J. Roh, S.-G. Lee, J.H. Ahn, H. Han, Angew. Chem. Int. Ed. Engl. 41 (2002) 3852; (l) B.M. Trost, Z. Pan, J. Zambrano, C. Kujat, Angew. Chem. Int. Ed. Engl. 41 (2002) 4691; (m) A. Agarkov, E.W. Uffman, S.R. Gilbertson, Org. Lett. 5 (2003) 2091; (n) D. Zhao, Z. Wang, K. Ding, Synlett (2005) 2067. General procedures for catalytic reactions. Without NEt3: to a solution of cis-2,4-cyclopentenediol (0.100 g, 1.00 mmol) in 1.75 mL of dry THF was added tosyl isocyanate (0.463 g, 2.35 mmol). The colourless solution was stirred at room temperature for 15 min and at 333 K for 30 min. The reaction mixture was cooled at 273 K (or 258 K), and then dropwise added to an orange solution of [Pd(dba)2] (0.050 mmol) and 2G (or 2M or 2Gt) (0.085 mmol) in 1.75 mL of dry THF. The orange reaction mixture was stirred at 273 K (or 258 K) for 30 min. The solvent was removed under vacuum and column

622

R. Del Litto et al. / Inorganic Chemistry Communications 10 (2007) 618–622 chromatography on silica gel (1:10 ethyl acetate:hexane) gave the desired product as a white solid. The enantiomeric excesses were determined by chiral HPLC, Chiracel OD-H, 1:10 isopropanol:hexane, UV 254 nm, retention times: 5 [()R,S], 22–24 min; 5 [(+)S,R], 30–32 min. The absolute configuration was obtained by comparison with a sample of known chirality. With NEt3: to a solution of cis-2,4cyclopentenediol (0.112 g, 1.00 mmol) in 1.75 mL of dry THF was added tosyl isocyanate (0.463 g, 2.35 mmol). The colourless solution was stirred at room temperature for 15 min and at 333 K for 30 min. The reaction mixture was allowed to cool to room temperature, and triethylamine (0.101 g, 1.00 mmol) was added. The resulting white

slurry was cooled at 273 K (or 258 K), and an orange solution of [Pd(dba)2] (0.028 g, 0.050 mmol) and 2G (or 2M or 2Gt) (0.085 mmol) in 1.75 mL of THF was added. The orange reaction mixture was stirred at 273 K (or 258 K) for 30 min. The solvent was removed under vacuum and column chromatography on silica gel (1:10 ethyl acetate:hexane) gave the desired product as a white solid. The enantiomeric excesses were determined by chiral HPLC, Chiracel OD-H, 1:10 isopropanol:hexane, UV 254 nm, retention times: 5 [()R,S], 22–24 min; 5 [(+)S,R], 30–32 min. The absolute configuration was obtained by comparison with a sample of known chirality.