Dynamic kinetic resolution of α-chloro β-keto esters and phosphonates: hemisynthesis of Taxotere® through Ru-DIFLUORPHOS asymmetric hydrogenation
Graphical abstract
Introduction
Dynamic kinetic resolution (DKR) is an efficient method for the obtention of enantiomerically pure compounds from racemic substrates. Indeed, DKR allows the formation of a single isomer out of four stereoisomers by combining kinetic resolution with an in situ equilibration of the configurationally labile stereogenic center.1 By using this method, enantiomerically pure compounds can be synthesized in a single step with theoretical yields of 100% in a highly stereocontrolled manner. Ruthenium-mediated hydrogenation has been widely used in the DKR of β-ketoesters,2 the first examples being reported by Noyori et al.3 and Genet et al.4 We report herein the dynamic kinetic resolution of an α-chloro β-ketoester through ruthenium-mediated asymmetric hydrogenation and its application to the hemisynthesis of Taxotere®. The DKR of α-chloro β-ketophosphonates leading to the corresponding enantioenriched α-chloro β-hydroxyphosphonates is described as well.
Owing to their biological activities as enzyme inhibitors or drug candidates5, optically active hydroxy phosphonates have attracted significant attention over the years. In particular, α-halo β-hydroxyphosphonates 1 constitute an interesting class of compounds as precursors of various 1,2-epoxyalkylphosphonates,6 analogous of fosfomycin 2,7 a low molecular weight antibiotic of unusual structure, originally isolated from the fermentation broth of Streptomyces fradiae or Pseudomonas syringae (Scheme 1).
Various methods have been reported for the asymmetric synthesis of hydroxyphosphonates.8 In particular, the enantioselective hydrogenation of β-ketophosphonates into their corresponding β-hydroxyphosphonates or α-acetamido β-hydroxyphosphonates has been described.9 However, with regard to α-halo β-ketophosphonates, only one example of dynamic kinetic resolution through asymmetric hydrogenation has been previously reported in the literature by Noyori et al.10 In this study, racemic dimethyl 1-bromo-2-oxopropylphosphonate was hydrogenated in methanol at 25 °C under 4 bar of hydrogen using the [RuCl2{(S)-BINAP}(DMF)n] complex to give dimethyl (1R,2S)-1-bromo-2-hydroxypropylphosphonate in 98% ee with a 90:10 syn/anti selectivity. This most straightforward method for the preparation of enantioenriched β-hydroxy α-bromophosphonates suffers one major limitation which is the formation in a significant 15% yield of the related debrominated compound, resulting from the hydrogenolysis of the carbon–bromide bond. We postulated that the replacement of the bromide atom by a chloride atom would lower this side reaction. Moreover, since the preparation of enantioenriched α-chloro β-hydroxyphosphonates is barely reported in the literature, we were interested in investigating the dynamic kinetic resolution of α-chloro β-ketophosphonates through ruthenium-mediated asymmetric hydrogenation11 as a practical route to prepare these compounds.
Section snippets
Results and discussion
A series of α-chloro β-ketophosphonates 3a–3f was first conveniently synthesized by acylation of diethyl 1-chloromethylphosphonate 6.12 Asymmetric hydrogenation promoted by ruthenium catalysts containing the atropisomeric ligands MeO-BIPHEP or SYNPHOS13 and DIFLUORPHOS,14 developed in our group, provided the corresponding α-chloro β-hydroxyphosphonates 4a–4f (Scheme 2). As a starting point, we examined the dynamic kinetic resolution of compound 3a (Scheme 3, Table 1). The hydrogenation reaction
Conclusion
In summary, we have shown that the dynamic kinetic resolution of a series of racemic α-chloro β-keto phosphonates through ruthenium-mediated asymmetric hydrogenation allowed the formation of the corresponding syn α-chloro β-hydroxy phosphonates. Complete conversions were obtained in methanol, alongside with excellent enantioselectivities (up to >99% ee) and good diastereoselectivities were observed for substrates bearing phenyl or para-chlorophenyl substituents (up to 84% de). Moreover, under
General
All air- and/or water-sensitive reactions were carried out under an argon atmosphere. Tetrahydrofuran and diethyl ether were distilled from sodium-benzophenone. Dichloromethane was distilled from calcium hydride. Reactions were monitored by thin layer chromatography carried out on precoated silica gel plates (E. Merck Ref. 5554 60 F254) and revealed with either an ultra-violet lamp (λ = 254 nm) or a potassium permanganate solution. The nuclear magnetic resonance spectra were recorded on a Bruker
Acknowledgments
We thank Dr. D. Lavergne for preliminary experiments and Professor B. Ben Hassine for interesting discussions. We are grateful to Hoffmann La Roche for providing samples of (S)- and (R)-MeO-BIPHEP and to Dr. A. Commerçon (Sanofi-Aventis) for a gift of protected 10-DAB.
References (37)
Tetrahedron
(2008)et al.Curr. Opin. Biotechnol.
(2002)et al.Chem. Soc. Rev.
(2001)et al.Curr. Opin. Chem. Biol.
(2000)et al.Curr. Opin. Chem. Biol.
(1999)et al.Synthesis
(1997)et al.Chem. Soc. Rev.
(1996)Tetrahedron: Asymmetry
(1995)- et al.
Bull. Chem. Soc. Jpn.
(1995)et al.Can. J. Chem.
(2000) - Genet, J.-P.; Mallart, S.; Jugé, S. French Patent 8,911,159,...
- et al.
J. Med. Chem.
(1995)et al.J. Antibiot.
(1995)et al.Phosphorus, Sulfur Silicon Relat. Elem.
(1991)et al.J. Med. Chem.
(1989)et al.J. Med. Chem.
(1987)et al.J. Med. Chem.
(1986)et al.Adv. Carbohydr. Chem. Biochem.
(1984)Chem. Rev.
(1977)et al.The Chemistry of Phosphorus
(1976) Tetrahedron: Asymmetry
(2005)et al.Tetrahedron
(2009)et al.Appl. Catal., A
(2007)et al.Adv. Synth. Catal.
(2003)et al.Tetrahedron Lett.
(1999)et al.J. Org. Chem.
(1995)Tetrahedron Lett.
(1993)Acta Chem. Scand.
(1996)et al.J. Organomet. Chem.
(1998)- et al.
Org. Lett.
(2002)et al.Proc. Natl. Acad. Sci. U.S.A.
(2004)et al.J. Am. Chem. Soc.
(2006) - et al.
Tetrahedron Lett.
(1994) - et al.
Tetrahedron Lett.
(1995) - et al.
Prog. NMR Spectrosc.
(2009)
Chem. Eur. J.
J. Chem. Soc., Faraday Trans.
J. Am. Chem. Soc.
J. Am. Chem. Soc.
Synthesis
Science
J. Antibiotics
Tetrahedron Lett.
Tetrahedron Lett.
J. Am. Chem. Soc.
Cited by (40)
Multinuclear NMR in polypeptide liquid crystals: Three fertile decades of methodological developments and analytical challenges
2020, Progress in Nuclear Magnetic Resonance SpectroscopyCitation Excerpt :More recently, the synthesis of enantiopure atropisomers (ortho, ortho′-dibromobiphenyls bearing an additional substituent in the 6-position) has been experimentally examined (see Fig. 27b) [198]. Finally in 2010, in the course of a methodological study, 13C-{1H} 1D NMR in CLCs was used to address the dynamic kinetic resolution (DKR) of racemic α-chloro-β-ketoesters and α-chloro-β-keto-phosphonates through ruthenium-mediated asymmetric hydrogenation [220]. In the field of chiral analysis, the enantiodiscrimination potential of polypeptide mesophases was first explored with deuterium-labelled compounds in 1992 using 2H-{1H} 1D NMR.
Coordination determined chemo- and enantioselectivities in asymmetric hydrogenation of multi-functionalized ketones
2018, Coordination Chemistry ReviewsCitation Excerpt :In the presence of CeCl3·7H2O as the additive, the syn/anti ratio and ee's were largely increased to 99:1 and 99.8% ee, respectively (Scheme 11). Genêt and Ratovelomanana-Vidal reported the DKR of racemic α-chloro β-ketophosphonates (14b) through ruthenium-catalyzed asymmetric hydrogenation [95]. The α-chloro β-hydroxyl-phosphonates (15b) were obtained in good to high enantio- and diastereomeric excesses using DIFLUORPHOS (Scheme 10).
Lipase-mediated dynamic kinetic resolution (DKR) of secondary alcohols in the presence of zeolite using an ionic liquid solvent system
2015, Catalysis TodayCitation Excerpt :As anticipated, ionic liquid [bmim][NTf2] was proved to be the best solvent for causing rapid racemization, since it is assumed that the racemization process would proceed in a highly polar solvent system. Therefore, we next tested the racemization of (S)-1-phenylethanol (1) using six types of ionic liquids: 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide)[bdmim][NTf2]), 1-butyl-2,3-dimethylimidazolium bis(trifluoromethanesulfonyl)amide)[bmim][NTf2]), tributyl((2-methoxyethyl)phosphonium bis(trifluoromethanesulfonyl)amide ([P444ME][NTf2]) [27], tributyl((2-methoxyethoxy)methyl)phosphonium bis(trifluoromethanesulfonyl)amide ([P444MEM][NTf2])[25g], N,N-diethyl-2-methoxy-N-methylethanaminium bis(trifluoromethanesulfonyl)amide ([N221ME][NTf2]) [28], and N-ethyl-N-((2-methoxyethoxy)methyl)-N-methylethanaminium bis(trifluoromethanesulfonyl)amide ([N221MEM][NTf2])[25h], and the results are shown in Fig. 5. As shown in Fig. 5, desired racemization proceeded smoothly in imidazolium ILs, in particular in [bmim][NTf2]; (S)-1 was completely racemized after 2 h at 60 °C and racemization took place even at 35 °C, although no racemization was observed at 35 °C in other ILs tested.
Dynamic Kinetic Resolution in Asymmetric Hydrogenation and Transfer Hydrogenation
2022, Science of Synthesis