Homogenous asymmetric hydrogenation: Recent trends and industrial applications

Current Opinion in Drug Discovery and Development

Volumn 13, Issue 6, 2010, Pages 698-716

  Palmer, Andreas M ^a   Zanotti Gerosa, Antonio ^b  

^a Nycomed GmbH   (Germany)

^b JOHNSON MATTHEY TECHNOLOGY CENTRE   (United Kingdom)

Author keywords

Asymmetric hydrogenation; chiral active pharmaceutical ingredient; diamine ligand; diphosphine ligand; enamide; enamine; imine; iridium catalyst; ketone; rhodium catalyst; ruthenium catalyst; stereoselective synthesis; unsaturated acid

Indexed keywords

3 QUINUCLIDINOL; ACTELION; ALMOREXANT; CARBENE; CARBONYL DERIVATIVE; CATHEPSIN S INHIBITOR; CENTRAL NERVOUS SYSTEM AGENTS; IMINE; INTEGRASE INHIBITOR; IRIDIUM; PHOSPHINE; PROPANOL; RENIN INHIBITOR; SIBUTRAMINE; TARANABANT; TRIFLUOROPROPANOL; UNCLASSIFIED DRUG;

CATALYSIS; DRUG SYNTHESIS; HYDROGENATION; REVIEW;

BIPHENYL COMPOUNDS; CATALYSIS; CHEMISTRY, PHARMACEUTICAL; HYDROGENATION; IMIDAZOLES; IMINES; MOLECULAR STRUCTURE; STEREOISOMERISM;

EID: 78650098688     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (99)

1. Farina V, Reeves JT, Senanayake CH, Song JJ: Asymmetric synthesis of active pharmaceutical ingredients. Chem Rev (2006) 106(7):2734-2793.
2. Jäkel C, Paciello R: High-throughput and parallel screening methods in asymmetric hydrogenation. Chem Rev (2006) 106(7):2912-2942.
3. Church TL, Andersson PG: Iridium catalysts for the asymmetric hydrogenation of olefns with nontraditional functional groups. Coord Chem Rev (2008) 252(5-7):513-531.
4. Roseblade SJ, Pfaltz A: Iridium-catalyzed asymmetric hydrogenation of olefns. Acc Chem Res (2007) 40(12):1402-1411.
5. Roseblade SJ, Pfaltz A: Recent advances in iridium-catalysed asymmetric hydrogenation of unfunctionalised olefns. C R Chimie (2007) 10(3):178-187.
6. Cui X, Burgess K: Catalytic homogeneous asymmetric hydrogenations of largely unfunctionalized alkenes. Chem Rev (2005) 105(9):3272-3296.
7. Schrems M, Pfaltz A: NeoPHOX - An easily accessible P,N-ligand for iridium-catalyzed asymmetric hydrogenation: Preparation, scope and application in the synthesis of demethyl methoxycalamenene. Chem Commun (Camb) (2009) (41):6210-6212.
8. Bianco GG, Ferraz HM, Costa AM, Costa-Lotufo LV, Pessoa C, de Moraes MO, Schrems MG, Pfaltz A, Silva LF Jr: (+)- and (-)-mutisianthol: First total synthesis, absolute confguration, and antitumor activity. J Org Chem (2009) 74(6):2561-2566.
9. Tolstoy P, Engman M, Paptchikhine A, Bergquist J, Church TL, Leung AW, Andersson PG: Iridium-catalyzed asymmetric hydrogenation yielding chiral diarylmethines with weakly coordinating or noncoordinating substituents. J Am Chem Soc (2009) 131(25):8855-8860.
10. Mazuela J, Verendel JJ, Coll M, Schäffner B, Börner A, Andersson PG, Pàmies O, Diéguez M: Iridium-oxazoline catalysts for the highly enantioselective hydrogenation of terminal alkenes. J Am Chem Soc (2009) 131(34):12344-12345.
11. Woodmansee DH, Mueller M-A, Neuburger M, Pfaltz A: Chiral pyridyl phosphinites with large aryl substituents as effcient ligands for the asymmetric iridium-catalyzed hydrogenation of diffcult substrates. Chem Sci (2010) 1(1):72-77.
12. Kaukoranta P, Engman M, Hedberg C, Bergquist J, Andersson PG: Iridium catalysts with chiral imidazole-phosphine ligands for asymmetric hydrogenation of vinyl fuorides and other olefns. Adv Synth Catal (2008) 350(7-8):1168-1176.
13. Engman M, Cheruku P, Tolstoy P, Bergquist J, Voelker SF, Andersson PG: Highly selective iridium-catalyzed asymmetric hydrogenation of trifuoromethyl olefns: A new route to trifuoromethyl-bearing stereocentres. Adv Synth Catal (2009) 351(3):375-378.
14. Baeza A, Pfaltz A: Iridium-catalyzed asymmetric hydrogenation of unfunctionalized enamines. Chemistry (2009) 15(10): 2266-2269.
15. Paptchikhine A, Cheruku P, Engman M, Andersson PG: Iridium-catalyzed enantioselective hydrogenation of vinyl boronates. Chem Commun (Camb) (2009) (40):5996-5998.
16. Baeza A, Pfaltz A: Iridium-catalyzed asymmetric hydrogenation of N-protected indoles. Chem Eur J (2010) 16(7):2036-2039.
17. Lu W-J, Chen Y-W, Hou X-L: Highly enantioselective iridium-catalyzed hydrogenation of trisubstituted olefns, α,β-unsaturated ketones and imines with chiral benzylic substituted P,N ligands. Adv Synth Catal (2010) 352(1):103-107.
18. Lu WJ, Chen YW, Hou XL: Iridium-catalyzed highly enanatio-selective hydrogenation of the C=C bond of α,β-unsaturated ketones. Angew Chem Int Ed Engl (2008) 47(52):10133-10136.
19. Lu SM, Bolm C: Highly enantioselective synthesis of optically active ketones by iridium-catalyzed asymmetric hydrogenation. Angew Chem Int Ed Engl (2008) 47(46):8920-8923.
20. Lu S-M, Bolm K: Highly chemo- and enantioselective hydrogenation of linear α,β-unsaturated ketones. Chem Eur J (2008) 14(25):7513-7516.
21. Cheruku P, Paptchikhine A, Church TL, Andersson PG: Iridium N,P-ligand-catalyzed enantioselective hydrogenation of diphenylvinylphosphine oxides and vinylphosphonates. J Am Chem Soc (2009) 131(23):8285-8289.
22. Wang D-S, Zhou J, Wang D-W, Guo Y-L, Zhou Y-G: Inhibiting deactivation of iridium catalysts with bulky substituents on coordination atoms. Tetrahedron Lett (2010) 51(3):525-528.
23. Zhao J, Burgess K: Aldol-type chirons from asymmetric hydrogenations of trisubstituted alkenes. Org Lett (2009) 11(10):2053-2056.
24. Zhao J, Burgess K: Synthesis of vicinal dimethyl chirons by asymmetric hydrogenation of trisubstituted alkenes. J Am Chem Soc (2009) 131(37):13236-13237.
25. 3 integrin antagonist intermediate via asymmetric hydrogenation of an α,β-unsaturated ester with BoPhoz-iridium and BoPhoz-rhodium catalysts. Tetrahedron Asymmetry (2008) 19(8):938-944.
26. Wang X-B, Wang D-W, Lu S-M, Yu C-B, Zhou Y-G: Highly enantioselective Ir-catalyzed hydrogenation of exocyclic enamines. Tetrahedron Asymmetry (2009) 20(9):1040-1045.
27. Yan P-C, Xie J-H, Hou G-H, Wang L-X, Zhou Q-L: Enantioselective synthesis of chiral tetrahydroisoquinolines by iridium-catalyzed asymmetric hydrogenation of enamines. Adv Synth Catal (2009) 351(18):3243-3250.
28. Hou G, Gosselin F, Li W, McWilliams JC, Sun Y, Weisel M, O'Shea PD, Chen CY, Davies IW, Zhang X: Enantioselective hydrogenation of N-H imines. J Am Chem Soc (2009) 131(29): 9882-9883.
29. Hou G, Tao R, Sun Y, Zhang X, Gosselin F: Iridium-monodentate phosphoroamidite-catalyzed asymmetric hydrogenation of substituted benzophenone N-H imines. J Am Chem Soc (2010) 132(7):2124-2125.
30. Zhou YG: Asymmetric hydrogenation of heteroaromatic compounds. Acc Chem Res (2007) 40(12):1357-1366.
31. Wang DW, Wang XB, Wang DS, Lu SM, Zhou YG, Li YX: Highly enantioselective iridium-catalyzed hydrogenation of 2-benzylquinolines and 2-functionalized and 2,3-disubstituted quinolines. J Org Chem (2009) 74(7):2780-2787.
32. Wang X-B, Zeng W, Zhou Y-G: Iridium-catalyzed hydrogenation of pyridine derivatives, 7,8-dihydro-quinolin-5(6H)-ones. Tetrahedron Lett (2008) 49(33):4922-4924.
33. Wang D-S, Zhou Y-G: Asymmetric hydrogenation of quinolines activated by Brønsted acids. Tetrahedron Lett (2010) 51(22):3014-3017.
34. Tadaoka H, Cartigny D, Nagano T, Gosavi T, Ayad T, Genêt JP, Ohshima T, Ratovelomanana-Vidal V, Mashima K: Unprecedented halide dependence on catalytic asymmetric hydrogenation of 2-aryl and 2-alkyl-substituted quinolinium salts by using Ir complexes with Difuorphos and halide ligands. Chem Eur J (2009) 15(39):9990-9994.
35. Mrsic N, Jerphagnon T, Minnaard AJ, Feringa BL, de Vries JG: Asymmetric hydrogenation of quinoxalines catalyzed by iridium/PipPhos. Adv Synth Catal (2009) 351(6):2549-2552.
36. Li ZW, Wang TL, He YM, Wang ZJ, Fan QH, Pan J, Xu LJ: Air-stable and phosphine-free iridium catalysts for highly enantio-selective hydrogenation of quinoline derivatives. Org Lett (2008) 10(22):5265-5268.
37. Mrii N, Jerphagnon T, Minnaard AJ, Feringa BL, de Vries JG: Asymmetric hydrogenation of 2-substituted N-protected-indoles catalyzed by rhodium complexes of BINOL-derived phosphoroamidites. Tetrahedron Asymmetry (2010) 21(1):7-10.
38. Kuwano R, Kashiwabara M, Ohsumi M, Kusano H: Catalytic asymmetric hydrogenation of 2,3,5-trisubstituted pyrroles. J Am Chem Soc (2008) 130(3):808-809.
39. Noyori R, Ohkuma T: Asymmetric catalysis by architectural and functional molecular engineering: Practical chemo- and stereoselective hydrogenation of ketones. Angew Chem Int Ed Engl (2001) 40(1):40-73.
40. Noyori R: Asymmetric catalysis: Science and opportunities (Nobel lecture). Angew Chem Int Ed Engl (2002) 41(12):2008-2022.
41. Li W, Sun X, Zhou L, Hou G, Yu S, Zhang Z: Highly effcient and highly enantioselective asymmetric hydrogenation of ketones with TunePhos/1,2-diamine- ruthenium(II) complexes. J Org Chem (2009) 74(3):1397-1399.
42. F Hoffmann-La Roche AG (Püntener K, Waldmeier P): Catalysts for asymmetric hydrogenation of 1,1,1-trifuoroacetone. WO-2008012240 (2008).
43. Palmer AM, Webel M, Scheufer C, Haag D, Mueller B: Large-scale asymmetric synthesis of the 3,6,7,8-tetra-hydrochromeno[7,8-d]imidazole BYK 405879: A promising candidate for treatment of acid-related diseases. Org Process Res Dev (2008) 12(6):1170-1182.
44. Xie JH, Liu S, Kong WL, Bai WJ, Wang XC, Wang LX, Zhou QL: Highly enantioselective and diastereoselective synthesis of chiral amino alcohols by ruthenium-catalyzed asymmetric hydrogenation of α-amino aliphatic ketones. J Am Chem Soc (2009) 131(12):4222-4223.
45. Liu S, Xie JH, Li W, Kong WL, Wang LX, Zhou QL: Highly enantioselective synthesis of chiral cyclic amino alcohols and conhydrine by ruthenium-catalyzed asymmetric hydrogenation. Org Lett (2009) 11(21):4994-4997.
46. Arai N, Azuma K, Nii N, Ohkuma T: Highly enantioselective hydrogenation of aryl vinyl ketones to allylic alcohols catalyzed by the Tol-Binap/DMAPEN ruthenium(II) complex. Angew Chem Int Ed Engl (2008) 47(39):7567-7570.
47. Arai N, Suzuki K, Sugizaki S, Sorimachi H, Ohkuma T: Asymmetric hydrogenation of aromatic, aliphatic, and α,β-unsaturated acyl silanes catalyzed by Tol-Binap/PICA ruthenium(II) complexes: Practical synthesis of optically active α-hydroxysilanes. Angew Chem Int Ed Engl (2008) 47(9):1770-1773.
48. 2(Binap)(PICA)] complexes. Chem Asian J (2008) 3(10):1801-1810.
49. Naud F, Malan C, Spindler F, Rüggerberg C, Schmidt AT, Blaser H-U: Ru-(phosphine-oxazoline) complexes as effective, industrially viable catalysts for the enantioselective hydrogenation of aryl ketones. Adv Synth Catal (2006) 348 (1-2):47-50.
50. Wang Y, Liu D, Meng Q, Zhang W: Asymmetric hydrogenation of simple ketones with planar ruthenocenyl phosphino-oxazoline ligands. Tetrahedron Asymmetry (2009) 20(21):2510-2512.
51. Baratta W, Ballico M, Baldino S, Chelucci G, Herdtweck E, Siega K, Magnolia S, Rigo P: New benzo[h]quinoline-based ligands and their pincer Ru and Os complexes for effcient catalytic transfer hydrogenation of carbonyl compounds. Chemistry (2008) 14(30):9148-9160.
52. Baratta W, Fanfoni L, Magnolia S, Siega K, Rigo P: Benzo[/i] quinoline pincer ruthenium and osmium catalysts for hydrogenation of ketones. Eur J Inorg Chem (2010) (9): 1419-1423.
53. Baratta W, Chelucci G, Magnolia S, Siega K, Rigo P: Highly productive CNN pincer ruthenium catalysts for the asymmetric reduction of alkyl aryl ketones. Chemistry (2009) 15(3):726-732.
54. Xie JB, Xie JH, Liu XY, Kong WL, Li S, Zhou QL: Highly enantio-selective hydrogenation of -arylmethylene cycloalkanones catalyzed by iridium complexes of chiral spiroaminophosphine ligands. J Am Chem Soc (2010) 132(13):4538-4539.
55. Sandoval CA, Ohkuma T, Utsumi N, Tsutsumi K, Murata K, Noyori R: Mechanism of asymmetric hydrogenation of acetophenone catalyzed by chiral i -arene-/V-tosylethylenediamine-ruthenium(II) complexes. Chem Asian J (2006) 1(1-2):102-110.
56. Li C, Xiao J: Asymmetric hydrogenation of cyclic imines with ionic Cp*Rh(III) catalysts. J Am Chem Soc (2008) 130(40):13208-13209.
57. Martins JED, Morris DJ, Wills M: Asymmetric hydrogenation of ketones using Ir(III) complexes of /V-alkyl-/V'-tosyl-1,2-ethanediamine ligands. Tetrahedron Lett (2009) 50(6):688-692.
58. Yu CB, Wang DW, Zhou YG: Highly enantioselective synthesis of sultams via Pd-catalyzed hydrogenation. J Org Chem (2009) 74(15):5633-5635.
59. Yang Q, Shang G, Gao W, Deng J, Zhang X: A highly enantioselective, Pd-TangPhos-catalyzed hydrogenation of /V-tosylimines. Angew Chem Int Ed Engl (2006) 45(23):3832-3835. (Pubitemid 44098935)
60. Hibino T, Makino K, Sugiyama T, Hamada Y: Homogeneous chiral nickel-catalyzed asymmetric hydrogenation of substituted aromatic -aminoketone hydrochlorides through dynamic kinetic resolution. ChemCatChem (2009) 1(2):237-240.
61. Hamada Y, Koseki Y, Fujii T, Maeda T, Hibino T, Makino K: Catalytic asymmetric hydrogenation of a-amino-p-keto ester hydrochlorides using homogeneous chiral nickel-bisphosphine complexes through DKR. Chem Commun (2008) (46):6206-6208.
62. Shimizu H, Nagano T, Sayo N, Saito T, Ohshima T, Mashima K: Asymmetric hydrogenation of heteroaromatic ketones and cyclic and acyclic enones mediated by Cu(I)-chiral diphosphine catalysts. Synlett (2009) (19):3143-3146.
63. Baratta W, Ballico M, Del Zotto A, Siega K, Magnolia S, Rigo P: Osmium Pyme complexes for fast hydrogenation and asymmetric transfer hydrogenation of ketones. Chem Eur J (2008) 14(8):2557-2563.
64. Baratta W, Ballico M, Chelucci G, Siega K, Magnolia S, Rigo P: Osmium(II) CNN pincer complexes as effcient catalysts for both asymmetric transfer and H hydrogenation of ketones. Angew Chem Int Ed Engl (2008) 47(23):1-5.
65. Baratta W, Barbato C, Magnolia S, Siega K, Rigo P: Chiral and nonchiral [OsX (diphosphane)(diamine)] (X: Cl, OCH CF ) complexes for fast hydrogenation of carbonyl compounds. Chemistry (2010) 16(10):3201-3206.
66. Morris RH: Asymmetric hydrogenation, transfer hydrogenation and hydrosilylation of ketones catalyzed by iron complexes. Chem Soc Rev (2009) 38(8):2282-2291.
67. Sui-Seng C, Haque FN, Hadzovic A, Pütz AM, Reuss V, Meyer N, Lough AJ, Zimmer-De Iuliis M, Morris RH: Synthesis and characterization of iron(II) complexes with tetradentate diiminodiphosphine or diaminodiphosphine ligands as precatalysts for the hydrogenation of acetophenone. Inorg Chem (2009) 48(2):735-743.
68. Li C, Wang C, Villa-Marcos B, Xiao J: Chiral counterion-aided asymmetric hydrogenation of acyclic imines. J Am Chem Soc (2008) 130(44):14450-14451.
69. Li C, Villa-Marcos B, Xiao J: Metal-Brønsted acid cooperative catalysis for asymmetric reductive amination. J Am Chem Soc (2009) 131(20):6967-6969.
70. Villa-Marcos B, Li C, Mulholland KR, Hogan PJ, Xiao J: Bifunctional catalysis: Direct reductive amination of aliphatic ketones with an iridium-phosphate catalyst. Molecules (2010) 15(4): 2453-2472.
71. Chen D, Sundararaju B, Krause R, Klankermayer J, Dixneuf PH, Leitner W: Asymmetric induction by chiral borate anions in enantioselective hydrogenation using a racemic Rh-Binap catalyst. ChemCatChem (2010) 2(1):55-57.
72. Doherty S, Smyth CH, Harriman A, Harrington RW, Clegg W: Can a butadiene-based architecture compete with its biaryl counterpart in asymmetric catalysis Enantiopure Me-CATPHOS a remarkably effcient ligand for asymmetric hydrogenation. Organometallics (2009) 28(3):888-895.
73. Doherty S, Knoght J, Bell AL, El-Menabawey S, Vogels CM, Decken A, Westcott SA: Rodium complexes of (R)-Me-CATPHOS and (R)-(S)-Josiphos: Highly enantioselective catalysts for the asymmetric hydrogenation of (E)-and (Z)-p-aryl- -(enamido)phosphonates. Tetrahedron Asymmetry (2009) 20(12):1437-1444.
74. Duan ZC, Hu XP, Zhang C, Wang DY, Yu SB, Zheng Z: Highly enantioselective Rh-catalyzed hydrogenation of p,y-unsaturated phosphonates with chiral ferrocene-based monophosphoroamidite ligands. J Org Chem (2009) 74(23): 9191-9194.
75. Pulmann T, Engedahl B, Zhang Z, Hölsher M, Zanotti-Gerosa A, Dyke A, Francio G, Leitner W: Quinaphos and Dihydro-Quinaphos phosphine- phosphoroamidite ligands for asymmetric hydrogenation. Chemistry (2010) 16(25):7517-7526.
76. Lorenz JC, Busacca CA, Feng X, Grinberg N, Haddad N, Johnson J, Kapadia S, Lee H, Saha A, Sarvestani M, Spinelli EM et al : Large-scale asymmetric synthesis of a cathepsin S inhibitor. J Org Chem (2010) 75(4):1155-1161.
77. Magano J, Conway B, Bowles D, Nelson J, Nanninga TN, Winkle DD, Wu H, Chen MH: Diastereoselective, large scale synthesis of p-amino acids via asymmetric enamide hydrogenation as a28 ligands for the treatment of generalized anxiety disorder and insomnia. Tetrahedron Lett (2009) 50(46):6329-6331.
78. Wallace DJ, Campos KR, Shultz CS, Klapars A, Zwege D, Crump BR, Phenix BD, McWilliams JC, Krska S, Sun Y, Chen C et al: New effcient asymmetric synthesis of taranabant, a CBR inverse agonist for the treatment of obesity. Org Process Res Dev (2009) 13(1):84-90.
79. Chen C, Frey LF, Shultz S, Wallace DJ, Marcantonio K, Payack JF, Vazquez E, Springfeld SA, Zhou G, Liu P, Kieczykowski GR et al: Catalytic, enantioselective synthesis of taranabant, a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity. Org Process Res Dev (2007) 11(3): 616-623.
80. Berens U, Hafner A, Dosenbach O, Tritschler T, Schwarzenbach F, Kirner HJ, Malan C, Mai-Huynh O: Highly enantioselective catalytic asymmetric synthesis of a (R)-sibutramine precursor. Chimia (2010) 64(1):59-64.
81. Hsieh DS, Lin D, Wang SSY, Cann RO, Sausker JB, Kiang S: Asymmetric hydrogenation of an amino acid intermediate in the synthesis of complex drug targets: From kinetic modeling to process development. In: Catalysis of Organic Reactions - Twenty-second Conference. Prunier ML (Ed) CRC Press, Boca Raton, FL, USA (2009):23-37.
82. Merck & Co Inc/Merck Frosst Canada Ltd (Angelaud R, Davies I, Maguire C, Lau S, O'Shea P, Shultz S): Process for making a renin inhibitor. WO-2010011584 (2010).
83. Maligres PE, Humphrey GR, Marcoux JF, Hillier MC, Zhao D, Krska S, Grabowski EJJ: Practical, highly convergent, asymmetric synthesis of a selective PPARγ modulator. Org Process Res Dev (2009) 13(3):525-534.
84. Qiu M, Wang DY, Hu XP, Huang JD, Yu SB, Deng J, Duan, ZC, Zheng Z: Asymmetric synthesis of chiral Roche ester and its derivatives via Rh-catalyzed enantioselective hydrogenation with chiral phosphine-phosphoramidite ligands. Tetrahedron Asymmetry (2009) 20(2):210-213.
85. Boehringer Ingelheim International Gmbh (Haddad N, Krishnamurthy D, Reeves DC, Senanayake CH, Tang W, Yee NK): Synthesis of intermediates useful for the production of certain CGRP inhibitors and intermediates used in such synthesis. WO-2010048138 (2010).
86. Janssen Pharmaceutica NV (Kinney WA, Teleha CA, Ghosh S, Maryanoff BE): Enantioselective process for preparing a substituted alkanoic acid. WO-2009058314 (2009).
87. De Vries MAH, Domin D, Helms M, Imboden C, Koberstein R, Nazir Z, Skranc W, Stanek M, Tschebull W, Verzijl MGK, Stichler J: Trisubstituted 3,4-dihydro-1H-isoquinolin compound, process for its preparation, and its use. US-20100010226 (2010).
88. Actelion Pharmaceuticals Ltd (Bappert E, De Vries AHM, Domin D, Helms M, Imboden C, Nazir Z, Skranc W, Spindler F, Stanek M, Tschebull W, Verzijl GKM): Process for the preparation of an enantiomeric trisubstituted 3,4-dihydro-1H-isoquinoline derivative. WO-2009083899 (2009).
89. Actelion Pharmaceuticals Ltd (De Vries AHM, Domin D, Helms M, Imboden C, Koberstein R, Nazir Z, Skranc W, Stanek M, T schebull W, Verzijl GKM): Trisubstituted 3,4-dihydro-1H-isoquinolin compound, process for its preparation, and its use. WO-2009083903 (2009).
90. Zhong YL, Krska SW, Zhou H, Reamer RA, Lee J, Sun Y, Askin D: Catalytic asymmetric synthesis of an HIV integrase inhibitor. Org Lett (2009) 11(2):369-372.
91. Hansen KB, Hsiao Y, Xu F, Rivera N, Clausen A, Kubryk M, Krska S, Rosner T, Simmons B, Balsells J, Ikemoto N et al: Highly effcient asymmetric synthesis of sitagliptin. J Am Chem Soc (2009) 131(25):8798-8804.
92. Shibasaki M, Kumagai N, Mashiko T: Inventing and understanding catalytic, enantioselective reactions. Curr Opin Drug Discov Devel (2009) 12(6):862-875.
93. Steinhuebel D, Sun Y, Matsumura K, Sayo N, Saito T: Direct asymmetric reductive amination. J Am Chem Soc (2009) 131(32):11316-11317.
94. Tsutsumi K, Katayama T, Utsumi N, Murata K, Arai N, Kurono N, Ohkuma T: Practical asymmetric hydrogenation of 3-quinuclidinone catalyzed by the XylSkewphos/PICA-ruthenium(II) complex. Org Process Res Dev (2009) 13(3): 625-628.
95. Püntener K, Scalone M: Enantioselective hydrogenation: Applications in process R&D of pharmaceuticals. In: Asymmetric catalysis on industrial scale. Blaser HU, Federsel HJ (Eds), Wiley VCH, Weinheim, Germany (2010):13-25.
96. Generics (UK) Ltd/Mylan Development Centre Private Ltd (Gaitonde A, Datta D, Manojkumar B, Phadtare S): Processes to pregabalin. WO-2009081208 (2009).
97. Ratiopharm Gmbh (Boerner A, Koenig G, Andrushko N, Andrushko V): Process for preparing pentanoic diacid derivatives. WO-2009027081 (2009).
98. Krska SW, Mitten JV, Dormer PG, Mowrey D, Machrouhi F, Sun Y, Nelson TD: Enantioselective synthesis of chiral fuoropiperidine via asymmetric hydrogenation of a vinyl fuoride. Tetrahedron (2009) 65(44):8987-8994.
99. Teva Pharmaceutical Industries Ltd/Teva Pharmaceuticals USA Inc (Kansal VK, Mistry DN, Vasoya SL, Jadav, AM, Dadhaniya P, Nalawade J): Process for the synthesis of ramelteon and its intermediates. WO-2010045565 (2010).