Ghosh, Subrata Kumar (2017-12). The Development of New Classes of Enantioselective Hydrogen Bond Donor Catalysts for Organic Synthesis Based upon Werner Complexes. Doctoral Dissertation. Thesis uri icon

abstract

  • In this dissertation, the development of highly effective, chiral monofunctional and bifunctional hydrogen bond donor catalysts based on cobalt(III) Werner complexes and their applications in enantioselective catalysis have been described. Furthermore, a protocol was developed to extend this chemistry into the fluorous media. Section 1 provides an overview of the hydrogen bond mediated organocatalysis and the scope of Werner complexes as hydrogen bond donors. Section 2 describes the fundamental stereochemical features of the trication [Co(en)3]3+ (en = ethylenediamine). Interactions between the trication, counter anions, and solvates are analyzed and a systematic nomenclature is developed. Section 3 provides highly diastereoselective syntheses of variety of diastereopure salts ?- and ?-[Co((S,S)-NHv2CHArCHArNHv2)v3]^3+ 2X-X'- (Ar = Cv6Hv5, vCv6Hv4n-Bu, 4- Cv6Hv4Cl, 4-Cv6Hv4CFv3, 4-Cv6Hv4OCHv3, ?-naphthyl, ss-naphthyl, 2-Cv6Hv4OBn; X/X' = Cl/BArvf (BArvf = B(3,5-Cv6Hv3(CFv3)v2)v4), PFv6/BArf, BF4/BArf, PhBF3/BArf, Cl/BArf20 (BArvf20 = B(Cv6F5)4), BArf/BArf, BArf20/BArvf20, BFv4/BFv4, PFv6/PFv6) and probes their properties. Sections 4 and 5 provide detail applications of the lipophilic salts of ?- or ?- [Co((S,S)-dpen)v3]^3+ ((S,S)-dpen = (S,S)-1,2-diphenylethylenediamine) in enantioselective addition reactions. Under optimized conditions, ?-[Co((S,S)-dpen)v3]^3+ 3BFv4- catalyzes the Michael addition of dialkyl malonate to nitroalkenes in the presence of Et3N, affording adducts in up to 98% yields and 96% ee. Interestingly, ?-[Co((S,S)- dpen)v3]^3+ 2Cl-BArvf20- is superior for the additions of cyclic ss-ketoesters to azodicarboylate diesters (up to 99% yields and >99% ee). Section 6 describes efficient syntheses of tris(hydrochloric acid) salts of chiral triamines Hv2NCH((CHv2)nNMe2)CHv2NHv2 (n = 1-4) from commercial starting materials in overall yields of 38-18%. Section 7 highlights syntheses of bifunctional catalysts and their applications in additions of dialkyl malonates to nitroalkenes. Racemic [Co(en)v2Ov2CO]^+ Cl^- and enantiopure (S)-[Hv3NCH((CH2)nNHMe2)CHv2NHv3]^3+ 3Cl^- (n = 1-4) are combined (water/ charcoal/100 ?C) to give [Co(en)v2((S)-Hv2NCH((CHv2)vnNMev2H)CHv2NHv2)]4^+ 4Cl^-. The cobalt diastereomers (?/?)are separated via chiral Sephadex columns. Reactions with NaOH and Na^+ BArvf^- give the catalysts ?- or ?-[Co(en)v2((S)-Hv2NCH- ((CHv2)nNMev2)CHv2NHv2)]^3+ 3BArvf^-. Under optimized condition, ?-[Co(en)v2((S)- Hv2NCH((CHv2)v3NMev2)CHv2NHv2)]^3+ 3BArvf^- gives addition products up to 98% yield and 99% ee. Section 8 describes an optimized procedure for the synthesis of highly fluorous Na^+ B(3,5-Cv6Hv3((CFv2)5CFv3)v2)v4- and its application in transporting polycations into fluorous media.
  • In this dissertation, the development of highly effective, chiral monofunctional and
    bifunctional hydrogen bond donor catalysts based on cobalt(III) Werner complexes and
    their applications in enantioselective catalysis have been described. Furthermore, a
    protocol was developed to extend this chemistry into the fluorous media.

    Section 1 provides an overview of the hydrogen bond mediated organocatalysis
    and the scope of Werner complexes as hydrogen bond donors.

    Section 2 describes the fundamental stereochemical features of the trication
    [Co(en)3]3+ (en = ethylenediamine). Interactions between the trication, counter anions,
    and solvates are analyzed and a systematic nomenclature is developed.

    Section 3 provides highly diastereoselective syntheses of variety of diastereopure
    salts ?- and ?-[Co((S,S)-NHv2CHArCHArNHv2)v3]^3+ 2X-X'- (Ar = Cv6Hv5, vCv6Hv4n-Bu, 4-
    Cv6Hv4Cl, 4-Cv6Hv4CFv3, 4-Cv6Hv4OCHv3, ?-naphthyl, ss-naphthyl, 2-Cv6Hv4OBn; X/X' =
    Cl/BArvf (BArvf = B(3,5-Cv6Hv3(CFv3)v2)v4), PFv6/BArf, BF4/BArf, PhBF3/BArf, Cl/BArf20
    (BArvf20 = B(Cv6F5)4), BArf/BArf, BArf20/BArvf20, BFv4/BFv4, PFv6/PFv6) and probes their
    properties.

    Sections 4 and 5 provide detail applications of the lipophilic salts of ?- or ?-
    [Co((S,S)-dpen)v3]^3+ ((S,S)-dpen = (S,S)-1,2-diphenylethylenediamine) in enantioselective
    addition reactions. Under optimized conditions, ?-[Co((S,S)-dpen)v3]^3+ 3BFv4-
    catalyzes the Michael addition of dialkyl malonate to nitroalkenes in the presence of
    Et3N, affording adducts in up to 98% yields and 96% ee. Interestingly, ?-[Co((S,S)-
    dpen)v3]^3+ 2Cl-BArvf20- is superior for the additions of cyclic ss-ketoesters to
    azodicarboylate diesters (up to 99% yields and >99% ee).

    Section 6 describes efficient syntheses of tris(hydrochloric acid) salts of chiral
    triamines Hv2NCH((CHv2)nNMe2)CHv2NHv2 (n = 1-4) from commercial starting materials
    in overall yields of 38-18%.

    Section 7 highlights syntheses of bifunctional catalysts and their applications in
    additions of dialkyl malonates to nitroalkenes. Racemic [Co(en)v2Ov2CO]^+ Cl^- and
    enantiopure (S)-[Hv3NCH((CH2)nNHMe2)CHv2NHv3]^3+ 3Cl^- (n = 1-4) are combined (water/
    charcoal/100 ?C) to give [Co(en)v2((S)-Hv2NCH((CHv2)vnNMev2H)CHv2NHv2)]4^+ 4Cl^-.
    The cobalt diastereomers (?/?)are separated via chiral Sephadex columns. Reactions
    with NaOH and Na^+ BArvf^- give the catalysts ?- or ?-[Co(en)v2((S)-Hv2NCH-
    ((CHv2)nNMev2)CHv2NHv2)]^3+ 3BArvf^-. Under optimized condition, ?-[Co(en)v2((S)-
    Hv2NCH((CHv2)v3NMev2)CHv2NHv2)]^3+ 3BArvf^- gives addition products up to 98% yield and
    99% ee.

    Section 8 describes an optimized procedure for the synthesis of highly fluorous
    Na^+ B(3,5-Cv6Hv3((CFv2)5CFv3)v2)v4- and its application in transporting polycations into
    fluorous media.

publication date

  • December 2017