Advances in the stereoselective synthesis of antifungal agents and ...

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Chapter 2 69Yamanaka and coworkers have studied 65a-c an approach to thesynthesis of 2-substituted indoles in presence of a Copper-Palladiumcatalyst. Essentially, this procedure allowed the use of copper (I) incatalytic amounts and did not require prior preparation and isolation ofcopper(I) acetylide. Palladium then catalyzed the coupling between the aryliodide and the copper (I) acetylide. Conditions to achieve only the couplingreaction or both coupling and cyclization have been studied in depthshowing the important role of the R group on the aniline (scheme 2.22).HINHRR= Ms, CO 2 EtR= Alkyl, Aryl.+HR'PdCl 2 (PPh 3 ) 2CuI, TEA, 120°sealed tubeR'NRR=MsR'NHR EtO - Na +R=CO 2 EtHNHR'Scheme 2.22.: Influence of activating groups in the Yamanaka cyclization.In particular, when R is a mesyl group, 2-substituted indoles can bedirectly obtained, while with less electron withdrawing R groups, such asCO 2 Et the reaction affords the intermediate, uncyclized coupling product.This, in turn, can be transformed into the heteroannulated compound by theaction of a base.2.4.2.2. Cacchi's procedure for the synthesis of 2-substitutedbenzo[b]furanes using Palladium catalyst.Cacchi and coworkers 66 reported a procedure for the synthesis of 2-substituted benzo[b]furanes from 1-alkynes using a Copper-Palladiumcatalyst. The reaction of 2-hydroxyaryl or 2-hydroxyheteroaryl halides withseveral 1-alkynes in the presence of a base, bistriphenylphosphine Pd (II)diacetate and Copper (I) iodide in DMF at RT or 60° C leads to 2-substituted benzo[b]furanes in usually good yields (scheme 2.23).
Chapter 2 70R 1AXR 2 H R 3OH+A = N, CH.X =I,Br.R1 =H, CH3,CHO.R2 =H, OCH3.R3 =Alkyl,CH(OH)Akyl or Aryl,EstersPd(OAc) 2 /CuIPiperidine/RT or 60°CR 2R 1AOR 3Scheme 2.23: Synthesis of benzofuranes according to Cacchi's procedure.A short communication published in 1992 from Kundu N.G. 67a,brepresented our most important reference. This paper described thesynthesis of 2-benzo[b]furanyl carbinol by coupling and cyclization of 1-phenyl 2-propyn-1-ol with o-iodophenol(scheme 2.24).The molar ratio between propargylic alcohol and 2-iodophenol was 2:1and the yield was calculated on the basis of the conversion of o-iodophenolas 66%. It is important to emphasize that all of the above describedprocedures were reported with achiral or racemic acetylenic compoundswhile our investigation is related to the possibility of applying thesemethodologies to chiral alkynes.IOH+HPhOHPdCl 2 (PPh 3 ) 2TEA , CuI 80°COOHPhScheme 2.24: Kundu's procedure for the synthesis of arylbenzofuranylmethanols.To our knowledge, these are the best conditions reported to date forthe synthesis of 2-substituted benzo[b]furanes.2.4.2.3 Larock's procedure for the annulation of internalalkynes to various heterocycles.Larock R.C. 68 and coworkers in 1995 reported a very goodprocedure to synthesize aromatic heterocycles via Palladium catalyzedannulation of internal alkynes. Syntheses of various heterocycles,including 1,2-dihydroquinolines, benzofuranes, benzopyranes andisocumarines are reported in this article. Generally, 5% molar Pd(OAc)2,
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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
Page 34 and 35: Chapter 1 19HOHODesmolaseHOCholeste
Page 36 and 37: Chapter 1 21formic acid results in
Page 38 and 39: Chapter 1 23inactivation. 113 . Bec
Page 40 and 41: Chapter 1 25Two newer compounds whi
Page 42 and 43: Chapter 1 2715 is an advanced repre
Page 44 and 45: Chapter 1 29transformation of the a
Page 46 and 47: Chapter 1 31Enantioselective synthe
Page 48 and 49: Chapter 1 33+R,S DRUG ANCHOR R MOLE
Page 50 and 51: Chapter 1 35solubilized in hot etha
Page 52 and 53: Chapter 2 37RsORmRmRsRLRL RRRLH - A
Page 54 and 55: Chapter 2 39The stereochemistry and
Page 56 and 57: Chapter 2 41An asymmetric reducing
Page 58 and 59: Chapter 2 43This approach clearly e
Page 60 and 61: Chapter 2 45PhaxeqP 1MP 2axeqPhP 2M
Page 62 and 63: Chapter 2 47pyrrolidine ] 20 , LAH-
Page 64 and 65: Chapter 2 49Enzymatic reactions are
Page 66 and 67: Chapter 2 51As [ES] in equation 4 c
Page 68 and 69: Chapter 2 53E+AK 1AK -1AEAK 2AE+PE+
Page 70 and 71: Chapter 2 552.2.4 Lipases.Most lipa
Page 72 and 73: Chapter 2 57enzyme intermediate can
Page 74 and 75: Chapter 2 59projecting above the pl
Page 76 and 77: Chapter 2 612.3.1.1. Step 1: Adduct
Page 78 and 79: Chapter 2 63A -+ ROHRO - + AH'RO 2
Page 80 and 81: Chapter 2 65There are various effec
Page 82 and 83: Chapter 2 67The reactions were foun
Page 86 and 87: Chapter 2 71sodium or potassium car
Page 88 and 89: Chapter 3 73The reaction is quite s
Page 90 and 91: Chapter 3 75literature as the best
Page 92 and 93: Chapter 3 77dry solvents and, is ch
Page 94 and 95: Chapter 3 79XXOH+ H 2 NDry K 2 CO 3
Page 96 and 97: Chapter 3 81substituents are the mo
Page 98 and 99: Chapter 3 83induces a rotation of t
Page 100 and 101: Chapter 3 85very sharp and it was p
Page 102 and 103: Chapter 3 87Raney NickelOH Br MeOH;
Page 104 and 105: Chapter 4 8933a-m were hydrolysed t
Page 106 and 107: Chapter 4 91benzo[b]furane (entries
Page 108 and 109: Chapter 4 93hydroxy or amine groups
Page 110 and 111: Chapter 4 95the products with ethyl
Page 112 and 113: Chapter 4 97NCO 2 HNCO 2 H(±)34c(-
Page 114 and 115: Chapter 4 99NNH37CO2EtOH(±)-27a(+)
Page 116 and 117: Chapter 4 101As already outlined ab
Page 118 and 119: Chapter 4 103(+)-(S)-2-octylimidazo
Page 120 and 121: Chapter 4 105CNNH N2 NCN nC 6 H 13N
Page 122 and 123: Chapter 4 107key step is the conver
Page 124 and 125: Chapter 4 109reverse addition in th
Page 126 and 127: Chapter 4 111which was eliminated e
Page 128 and 129: Chapter 4 113separate (±)-57a and
Page 130 and 131: Chapter 5 115to avoid this side rea
Page 132 and 133: 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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Chapter 7 155derivatives were tried
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Chapter 7 157Finally an hypothesis
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Chapter 8 159were washed with a sat
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Chapter 8 16145 min, the mixture wa
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Chapter 8 1638.9 Decarboxylation of
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Chapter 8 165Alcohol 27a (0.2 mmol)
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Chapter 8 167for 48 h. After coolin
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Chapter 8 169room temperature for t
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Chapter 8 171in CH 2 Cl 2 and washe
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Chapter 8 1738.26 Screening of lipa
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Chapter 8 175Na 2 SO 4 . After remo
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Chapter 8 177NMR and MS analysis we
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Chapter 8 179Argon was bubbled thru
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Chapter 8 181IR (CHCl 3 ): ν cm-1=
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Chapter 8 183GC-MS: 305 M + (68%),
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Chapter 8 185[α] 20 D -5.7 (c 1.75
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Chapter 8 187Synthetic method 7.7.1
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Chapter 8 189(R,S)-(±)-1-(2-Octyl)
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Chapter 8 191M.P. = oil.Elementary
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Chapter 8 193Synthetic method 7.11.
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Chapter 8 195(±)-N-1-(2-Octyl)-2-t
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Chapter 8 197IR (CHCl 3 ) ν cm-1 =
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Chapter 8 199(±)-1-(4-Fluorophenyl
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Chapter 8 201Physical and spectral
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Chapter 8 203(±)-1-(Phenyl)-2-prop
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Chapter 8 205128.61, 128.87, 130.39
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Chapter 8 207min.Physical and spect
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Chapter 8 20913C J MOD NMR (CDCl 3
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Chapter 8 211(±)-2'-Methylphenyl-2
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Chapter 9 213References chapter 1:1
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Chapter 9 21531) De Felice, R.; Joh
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Chapter 9 21768) Brodie, A.M.H. in
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Chapter 9 219112) Brodie, A. M. H.;
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Chapter 9 2214) Karabatsos, M.C. J.
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Chapter 9 22334c) Blow D. Nature 19
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Chapter 9 22567a) Kundu, N.G.; Pal,
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Chapter 9 22712) Thompson,A.S.; Hum
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