Synthesis of C2-symmetric P-chiral bis(phosphine borane)s and their application in rhodium(I) catalyzed asymmetric transformation by Holly Ann Heath A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry Montana State University © Copyright by Holly Ann Heath (2001) Abstract: A new development for the synthesis C2-Synnnetric P-Chiral Bis(phosphine borane) ligands is reported, These ligands are based on the asymmetric induction of prochiral phosphine ligands with organolithium/chiral diamine complexes. These ligands have been evaluated in asymmetric rhodium(I) catalyzed hydrogenation and [4 + 2] cycloisomerization reactions. Enantiomeric excesses as high as 99% were obtained for ene-diene cycloadditions. Synthesis of C2-Symmetric P-Chiral Bis(phosphine borane)s and Their Application in Rhodium(I) Catalyzed Asymmetric Transformation by Holly Ann Heath A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry Montana State University Bozeman, Montana March 2001 ii APPROVAL of a dissertation submitted by Holly Ann Heath This dissertation has been read by each member of the dissertation committee and has been found to be satisfactory regarding content, English usage, format, citations, bibliographic style, and consistency, and is ready for submission to the College of Graduate Studies. Dr. Thomas Livinghouse < Chairperson, Graduate Committee Date Approved for the Department of Chemistry Dr. Paul A. Grieco Department Head Approved for the College of Graduate Studies Dr. Bruce R. McLeod Graduate Dean Date iii STATEMENT OF PERMISSION TO USE In presenting this dissertation .in partial fulfillment of the requirements for a doctoral degree at Montana State University-Bozeman, I agree that the Library shall make it available to borrowers under rules of the Library. I further agree that copying of the dissertation is allowable only for scholarly purposes, consistent with “fair use” as prescribed in the U. S. Copyright Law. Requests for extensive copying or reproduction of this dissertation should be referred to University Microfilms International, 300 North Zeeb Road, Ann Arbor, Michigan 48106, to whom I have granted “the exclusive right to reproduce and distribute my dissertation in and from microform along with the non-exclusive right to reproduce and distribute my abstract in any format in whole or in part.” iv TABLE OF CONTENTS 1. INTRODUCTION............................................................................................ I 2. BACKGROUND................................................................................................3 OrganolithiunVChiral Diamine Complexes........................................................3 Chiral Phosphine Ligands...................................................................................8 Catalytic Asymmetric Hydrogenation..............................................................16 Transition Metal-Catalyzed [4 + 2] Cycloadditions........................................ 22 3. RESULTS AND DISCUSSION............................................... '......................33 Organolithium/Chiral Diamine Complexes......................................................33 Chiral Bisphosphine Ligands............................................................................39 Asymmetric Rhodium(I) Catalyzed Hydrogenation., .................................... 50 Asymmetric Rhodium(I) Catalyzed [4 + 2] Cycloaddition..............................54 4. CONCLUSION.............................................................................. 69 5. EXPERIMENTAL................................................................ 70 PHOSPHINE LIGAND SYNTHESIS.............................................................72 Chloro-P,P-dimethylphosphinoborane (100)............................................72 P,P-Dimethyl(bisethylammino)phosphinoborane (101)................... 73 P,P-Dimethylphenylphosphine borane (57)...............................................74 P,P-Dihalide-2-(trifluoromethyl)phenylphosphine borane (halide = Br or Cl) (102)............................. 76 P,P-Dimethyl-2-(trifluoromethyl)phenylphosphine borane (59).............. 77 P,P-Dimethylferrocenylphosphine borane (62)........................................ 79 ‘ P,P-Dimethyl-2,6-(dimethoxyphenyl)phosphine borane (60).................. 80 (Rp,Rp)-Bis[(ferrocenylmethylphosphineborane)r methyl] dimethylsilane (83)........................................................................ 82 (Rp,Rp)-Bis[methyl-2-(trifluoromethyl)phenyl- phosphine borane]ethane (80).................................................... 83 (Rp5Rp)-Bis {[methyl-2-(trifluoromethyl)phenyl- phosphine borane]methyl} dimethylsilane (85).........................................85 (Rp,Rp)-Bis{[methyl-2-(trifluoromethyl)phenyl- phosphine borane]methyl}diisopropylsilane (87).....................................87 (i?P,i?p)-Bis{[methyl-2-(trifluoromethyl)phenyl- phosphine borane]methyl} dicyclohexylsilane (88)............................... 89 (i?P,i?p)-Bis {[methyl-2-(txifluoromethyl)phenyl- phosphine borane]methyl}diphenylsilane (89)..........................................90 (i?P,i?p)-2,6-Bis{[methyl-2-(trifluoromethyl)phenyl- phosphine borane]ethyljpyridine (76).......................................................93 (i?P,^p)-Bis{[methyl-2,6-(dimethoxy)phenyl- phosphine borane]methyl}bis(dimethylsilane) (103)............ 95 Deprotection of Phosphine Boranes.................................................... ............97 P,P-Dimethyl-2-(trifluoromethyl)phenylphosphine (104)..................... 98 (R P,R p)-Bis [methyl-2-(trifluoromethyl)phenyl- phosphine] ethane (105)..............................................................................98 (R P,R p)-Bis {[methyl-2-(trifluoromethyl)phenyl- phosphine]methyl} dimethylsilane (106)............................. 99 (f?P,i?p)-Bis{[methyl-2-(trifluoromethyl)phenyl- phosphinejmethyl} diisopropylsilane (107).............................................100 (RpfR p)-Bis {[methyl-2-(trifluoromethyl)phenyl- phosphine]methyl} dicyclohexylsilane (108)...........................................101 (RpfRp)-Bis {l[methyl-2-(trifluoromethyl)phenyl- phosphinejmethyl} diphenylsilane (109)..................................................102 (i?P,i?p)-2)6-Bis{[methyl-2-(trifluoromethyl)phenyl- phosphine]ethyl}pyridine (HO)...............................................................103 Substrate Synthesis; Ene-dienes and Dien-ynes..... ............... 104 2-Methyh(E)-2,4-pentadien-1 -ethyl ester (111).............. .'.....................104 N-(E,E)-2,4-hexadienyl-N-[(E)-but-2-enyl]- 4-methylbenzenesulfonamide (92)..........................................................105 N- [2-methyl-(£)-2,4-pentadienyl] -N-(prop-2-enyl)-4- methylbenzenesulfonamide (96)..............................................................106 N-(£,£)-2,4-hexadienyl-N-(prop-2-ynyl-3-trimethylsilyl)-4- methylbenzenesulfonamide (98).'............................................................ 108 4-Oxo-(E,E)-6,8-decadien-l-yne (52).....................................................109 4-Oxo-l,6(E),8(E)-decatriene (49)..........................................................110 Rhodium(I) Catalyzed [4 + 2] Cycloadditions..............................................112 Catalyst Synthesis....................................................................................112 Cycloaddition............................................'..............................................112 Cis-2f3f3a.-(RfS)-6f7fla.-hQxahydvo-6-trans-meth.yl-2- (4-methylb enzenesulfonamido) -1 H-isoindole (47).................................113 Gb-2,3,3a-(f?,6)-6,7,7a-hexahydro-6-tra^-7-czb-dimethyl- 2-(4-methylbenzenesulfonamido)-lH-isoindole (93)..............................114 REFERENCES CITED.................................................. ................................... 116 vi LIST OF TABLES Table Page 1. Enantioselective Ortho Lithiation of Phenylcarbamate Chromium Complexes.............................................................................6 2. Asymmetric Hydrogenation of Dehydro-a-Acylamino Acids.................. 21 3. Enantioselective Rh(I) Catalyzed [4 + 2] Cycloisomerization Using (+)-DIOP Related Ligands..........................................................26 4. Counterion Effect of Enantioselective Cyclization.................................... 28 5. Asymmetric Induction of Triene 49........................................................... 30 6. Asymmetric Induction of Dienyne 52.........................................................32 7. Benzophenone Trapped Asymmetric Lithiation using Chiral Diamines 54 - 56 of Dimethylphenylphosphine borane.................36 8. Benzophenone Trapped Lithiation Using of Phosphine boranes 59 - 62 Using (-)-Sparteine........................................................................ 42 9. Asymmetric Hydrogenation of Z-a-Acylaminoacrylic Acid Derivative 77 with Catalyst Complex 79...................................................52 10. Asymmetric Rhodium(I) Catalyzed Cycloaddition of Ene-diene 46 with Cf" as the Counterion...................................................57 11. Asymmetric Rhodium(I) Catalyzed Cycloaddition of Ene-diene 46 with SbF6- as the Counterion............................................. 58 12. Asymmetric Rhodium(I) Catalyzed Cycloaddition of Ene-diene 92 with SbFe- as the Counterion............................................