Chapter 8 205128.61, 128.87, 130.39, 135.66, 138.81, 166.28.IR (film): __cm-1= 3290, 2135, 1785,1740,1610.GC-MS = 222 M+ (18%), 128 (100%).MP= oil(S)-(-)1-(3-Methylphenyl)-2-propyn-1-chloroacetate (S)-(-)-61h:Syn<strong>the</strong>tic method 7.28.2[α] 20 D - 13.9 (c 0.84, CHCl 3 ). 99.2% ee .Physical <strong>and</strong> spectral data were identical to those described below for<strong>the</strong> racemate (±)-61 h.(±)-1-(3-Fluorophenyl)-2-propyn-1-chloroacetate (±)-61i:Syn<strong>the</strong>tic method 7.27.1H-NMR (200 MHz, CDCl 3 ) δ = 2.77 (d 1H, J=2.22 Hz), 4.15 (m2H), 6.53 (d 1H; 2.22 Hz), 7.13 (m 1H), 7.36 (m 3H).13C NMR (CDCl 3 ) = 40.79, 66.48, 78.89, 115.11, 116.72, 123.56,130.61, 161.73, 164.19, 166.19.IR (film): ν cm-1= 2980, 2135, 1745,1590.MP= oil.(S)-(-)1-(3-Fluorophenyl)-2-propyn-1-chloroacetate (S)-(-)-61 i:Syn<strong>the</strong>tic method 7.28.2[α] 20 D - 5.3 (c 1.33, CHCl 3 ). 99.4% ee .Physical <strong>and</strong> spectral data were identical to those described below for<strong>the</strong> racemate (±)-61 i.1-(2-Methylphenyl)-2-propyn-1-chloroacetate (±)-61 l:Syn<strong>the</strong>tic method 7.27.1H-NMR (200 MHz, CDCl 3 ) δ = 2.48 (s 3H), 2.73 (d 1H, J=2.2Hz),4.15 (m2H), 6.67 (d 1H, J=2.2Hz), 7.36-7.24 (m 3H), 7.66 (d 1H,J=7.82).13C NMR (CDCl 3 ) δ = 19.85, 40.84, 65.44, 76.44, 79.37, 126.57,128.25, 129.61, 131.11, 133.87, 166.21.IR (film): ν cm-1= 3290, 2120, 1770,1730.MP= oil.(S)-(+)1-(2-Methylphenyl)-2-propyn-1-chloroacetate (S)-(+)-61 l:Syn<strong>the</strong>tic method 7.28.2[α] 20 D + 16.2 (c 1.25, CHCl 3 ). 94.0% ee .
Chapter 8 206Physical <strong>and</strong> spectral data were identical to those described below for<strong>the</strong> racemate (±)-61 b.1-(2,4-Dichlorophenyl)-2-propyn-1-chloroacetate (±)-61m:Syn<strong>the</strong>tic method 7.27.1H-NMR (200 MHz, CDCl 3 ) δ = 2.77 (d 1H, J=2.21 Hz), 4.14 (m2H), 6.78 (d 1H, J=2.21 Hz), 7.36 (d 2H, J=8.51 Hz), 7.46 (s 1H),7.77 (d 1H, J=8.51 Hz).MP= oil.(2'-HydroxyPhenyl)-2-propyn-1-phenyl-1-ol (±)-62.Syn<strong>the</strong>tic method 7.351H NMR (CDCl 3 ) δ =2.90 (s, 1H), 5.65 (s, 1H), 6.85 (m,3H), 7.32(m,4H), 7.68 (m, 2H).13C NMR (CDCl 3 ) δ= 65.165, 81.590, 98.845, 108.809, 115.346,120.174, 126.708, 128.568, 128.722, 130.589, 131.951, 140.068,157.028.13C J MOD NMR (CDCl 3 ) δ= (+)65.165, (-)81.590, (-)98.845, (-)108.809, (+)115.346, (+)120.174, (+)126.708, (+)128.568,(+)128.722, (+)130.589, 131.951, (-) 140.068, (-)157.028.GC-MS M + 224(100%), M + -OH 207 (80%).M.P.: oil.(±)-(4'-Methylphenyl)-2-benzo[b]furanyl carb<strong>in</strong>ol (±)-63a:Syn<strong>the</strong>tic method 7.301H NMR (CDCl 3 ) δ= 2.35 (s,3H), 2.44 (d, 2H, 4.5Hz), 5.90 (d, 2H,4.5Hz), 6.52 (s,1H), 7.27-7.14 (m 5H), 7.51-7.34 (m 3H);13C NMR (CDCl 3 ) δ= 21.076, 70.388, 103.729, 111.224, 121.002,122.673, 124.078, 126.706, 128.032, 129.150, 137.392, 137.957,155.003, 158.743;13C J MOD NMR (CDCl 3 ) δ= (+)21.076, (+)70.388, (+)103.729,(+)111.224, (+)121.002, (+)122.673, (+)124.078, (+)126.706, (-)128.032, (+)129.150, (-)137.392, (-)137.957, (-)155.003, 1(-)58.743;GC-MS M + 238 (100%); M + -OH 221.(R)-(-)-4'-Methylphenyl- 2 benzo[b]furanyl carb<strong>in</strong>ol (R)-(-)-63a:Syn<strong>the</strong>tic method 7.30[α] 20 D -8.05, (c 1.6 CHCl 3) ; 99.0% ee (Chiracel OD n-hexane/isopropanole), rt (S)-(+)-2b 55.28 m<strong>in</strong>., (R)-(-)-2b 59.44
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Advances in the stereoselectivesynt
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ACKNOWLEDGMENT:I would like to than
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Summary:Numerous drugs are chiral,
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IndexII2.2 Synthesis of enantiopure
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IndexIV4.4. Stereochemical Assignme
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IndexVImethyl amine 69 1446.6. Stud
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IndexVIII8.23.3.1 Desilylation usin
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Chapter 1 11.Introduction1.1. Chira
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Chapter 1 3The concept of stereoche
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Chapter 1 5switches is in the area
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Chapter 1 7-bonds 9 . It is now wid
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Chapter 1 914CH 3Cyt P-450 DMOH3O 2
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Chapter 1 11piperazine) is also the
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Chapter 1 13The four stereoisomers
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Chapter 1 15single enantiomers and
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Chapter 1 17was synthesized by the
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Chapter 1 19HOHODesmolaseHOCholeste
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Chapter 1 21formic acid results in
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Chapter 1 23inactivation. 113 . Bec
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Chapter 1 25Two newer compounds whi
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Chapter 1 2715 is an advanced repre
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Chapter 1 29transformation of the a
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Chapter 1 31Enantioselective synthe
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Chapter 1 33+R,S DRUG ANCHOR R MOLE
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Chapter 1 35solubilized in hot etha
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Chapter 2 37RsORmRmRsRLRL RRRLH - A
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Chapter 2 39The stereochemistry and
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Chapter 2 41An asymmetric reducing
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Chapter 2 43This approach clearly e
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Chapter 2 45PhaxeqP 1MP 2axeqPhP 2M
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Chapter 2 47pyrrolidine ] 20 , LAH-
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Chapter 2 49Enzymatic reactions are
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Chapter 2 51As [ES] in equation 4 c
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Chapter 2 53E+AK 1AK -1AEAK 2AE+PE+
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Chapter 2 552.2.4 Lipases.Most lipa
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Chapter 2 57enzyme intermediate can
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Chapter 2 59projecting above the pl
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Chapter 2 612.3.1.1. Step 1: Adduct
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Chapter 2 63A -+ ROHRO - + AH'RO 2
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Chapter 2 65There are various effec
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Chapter 2 67The reactions were foun
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Chapter 2 69Yamanaka and coworkers
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Chapter 2 71sodium or potassium car
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Chapter 3 73The reaction is quite s
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Chapter 3 75literature as the best
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Chapter 3 77dry solvents and, is ch
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Chapter 3 79XXOH+ H 2 NDry K 2 CO 3
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Chapter 3 81substituents are the mo
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Chapter 3 83induces a rotation of t
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Chapter 3 85very sharp and it was p
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Chapter 3 87Raney NickelOH Br MeOH;
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Chapter 4 8933a-m were hydrolysed t
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Chapter 4 91benzo[b]furane (entries
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Chapter 4 93hydroxy or amine groups
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Chapter 4 95the products with ethyl
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Chapter 4 97NCO 2 HNCO 2 H(±)34c(-
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Chapter 4 99NNH37CO2EtOH(±)-27a(+)
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Chapter 4 101As already outlined ab
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Chapter 4 103(+)-(S)-2-octylimidazo
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Chapter 4 105CNNH N2 NCN nC 6 H 13N
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Chapter 4 107key step is the conver
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Chapter 4 109reverse addition in th
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Chapter 4 111which was eliminated e
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Chapter 4 113separate (±)-57a and
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Chapter 5 115to avoid this side rea
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Chapter 5 117Complete degradation o
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Chapter 5 119Entry R T °C Product
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Chapter 5 1212:1:3 in weight. All t
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Chapter 5 123reaction conditions we
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Chapter 5 125Entry Substrate R Time
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Chapter 5 127experiments. But it wa
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Chapter 5 129OClOSAM IIPH=7; R.T.OH
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Chapter 5 131OHOXHOHRHK 2 CO 3 ; Me
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Chapter 6 133HCuSO 4 .5H 2 O,NH 4 O
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Chapter 6 1356.2.1 Heteroannullatio
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Chapter 6 137This discovery allowed
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Chapter 6 139OH(±)-62OHFigure 6.1
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Chapter 6 141Entry Substrate R Time
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Chapter 6 143HOH58-a-c,e,h-lRPdCl 2
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Chapter 6 145afforded the benzo[b]f
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Chapter 6 147RR[P(Ph) 3 ]Pd°OHOPh
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Chapter 6 149H2-IodophenolOHOH(±)-
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Chapter 6 151presence of base as de
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Chapter 7 153A chiral lithium alumi
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- Page 228 and 229: Chapter 9 213References chapter 1:1
- Page 230 and 231: Chapter 9 21531) De Felice, R.; Joh
- Page 232 and 233: Chapter 9 21768) Brodie, A.M.H. in
- Page 234 and 235: Chapter 9 219112) Brodie, A. M. H.;
- Page 236 and 237: Chapter 9 2214) Karabatsos, M.C. J.
- Page 238 and 239: Chapter 9 22334c) Blow D. Nature 19
- Page 240 and 241: Chapter 9 22567a) Kundu, N.G.; Pal,
- Page 242: Chapter 9 22712) Thompson,A.S.; Hum