Title Slide 2 Title Slide Ar Ar CH3 B(OR)2 Ar CH3 CO2R Ar CH3 CH2OH Ar CH3 OH Ar CH3 NH2 Ar CH3 NHR

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Text of Title Slide 2 Title Slide Ar Ar CH3 B(OR)2 Ar CH3 CO2R Ar CH3 CH2OH Ar CH3 OH Ar CH3 NH2 Ar CH3 NHR

  • Title Slide

    Ar Ar CH3

    B(OR)2

    Ar CH3

    CO2R

    Ar CH3

    CH2OH

    Ar CH3

    OH

    Ar CH3

    NH2

    Ar CH3

    NHR

    Catalytic Olefin Hydroboration Mechanistic Features, Practical Considerations and Synthetic Applications

    Alexander Goldberg Stoltz Group Literature Presentation

    March 1, 2010 8 PM, 147 Noyes

    Ar CH3

    Ar'

  • Introduction to Hydroboration

    H H

    HR

    BH3 H H

    HR H BH2 B

    R

    R

    R

    H

    H

    H

    First Publication: Brown, H. C. J. Am. Chem. Soc. 1956, 78, 5694–5695. Review: Brown, H. C. Org. React. 1963, 13, 1–54.

    R

    OH[O]

    • Convenient method for anti-Markovnikoff hydration of olefins

    H H R H

    H BR2

    H H R H

    H BR2 δ-

    δ+

    H BR2 H R H

    H

    • Asynchronous transition state: partial charge buildup

    • Substituent most capable of stabilizing partial positive charge receives proton

    Mechanism:

    Intro to Hydroboration

  • Stoichiometric Enantioselective

    Stoichiometric Enantioselective Hydroboration

    First Publication: Brown, H. C. J. Am. Chem. Soc. 1961, 83, 486–487. Review: Brown, H. C. Acc. Chem. Res. 1988, 21, 287–293.

    Diisopinocampheylborane (Ipc2BH)

    • Allowing Ipc2BH to stand @ 0 °C • in presence of slight excess of • α-pinene gives enantiopure • reagent

    • "The first truly successful, • nonenzymatic, asymmetric • synthesis"

    α-pinene ( + or – ) 92% ee

    BH3•THF

    0 °C

    BH 2

    Ipc2BH > 99% ee

    HO

    HO

    HO

    HO

    98% ee

    92% ee

    93% ee

    83% ee

  • Männig and Nöth

    Late Transition Metal Catalysis

    Catecholborane: Brown, H. C. J. Am. Chem. Soc. 1971, 93, 1816–1818 Catalyzed: Nöth, H. Angew. Chem. Int. Ed. Engl. 1985, 24, 878–879.

    • ~4:1 selectivity for olefin in presence of ketone with Wilkinson's catalyst

    • Temperature & Reaction time greatly reduced for catalyzed variant

    • No noticeable rate difference for BH3

    • Catecholborane is much less lewis acidic than borane: • slower uncatalyzed hydroboration

    OHBCatO

    H

    BCat O

    CatB H

    HBCat

    RhCl(PPh3)3

    HBCat = O

    BH O

    catecholborane

    HBCat

    BCat

    No catalyst: 100 °C, 2 h, 90% yield

    0.05 mol% RhCl(PPh3)3 20 °C, 20 min, 83% yield

    H

  • Initial Mechanism

    Initial Proposed Mechanism

    Nöth, H. Angew. Chem. Int. Ed. Engl. 1985, 24, 878–879.

    • Supported by catalytic viability of catecholborane adduct • Loose ends: reversibility of each step? • Boryl v. Hydride insertion?

    RhL3Cl

    RhL2Cl

    -L HBCat

    Rh H

    Cl CatB

    L L

    Rh H

    Cl CatB

    L

    Rh Cl

    CatB L L

    H

    CatB H

    CH2 CH2

    -L+L

  • Evans Alkyl

    Deuterium Labelling Studies

    Evans, D. A. J. Am. Chem. Soc. 1992, 114, 6679–6685.

    n-Oct n-Oct HO

    5%

    DBCat (0.1 equiv)

    RhCl(PPh3)3 (0.2 mol%)

    28% + n-Oct

    33%

    33% Deuterium distribution

  • RhB D

    RhB H

    RhB H

    Deuterium Labelling Studies

    Evans, D. A. J. Am. Chem. Soc. 1992, 114, 6679–6685.

    n-Oct n-Oct HO

    5%

    DBCat (0.1 equiv)

    RhCl(PPh3)3 (0.2 mol%)

    28% + n-Oct

    33%

    33% Deuterium distribution

    n-Oct

    D

    n-Oct n-Oct

    n-Oct

    D

    n-Oct n-Oct

    D

    D

    n-Oct H

    D

    RhB

    n-Oct D

    RhB

    n-Oct Rh

    D

    B n-Oct

    RhB

    D

    n-Oct H

    D

    B

    n-Oct D

    B n-Oct

    B

    D

    n-Oct B

    D

    X X

    hydride migration

    β-H elim.

    β-H elim.

    reductive elimination

  • RhB D

    RhB H

    RhB H

    Deuterium Labelling Studies

    Evans, D. A. J. Am. Chem. Soc. 1992, 114, 6679–6685.

    n-Oct n-Oct HO

    5%

    DBCat (0.1 equiv)

    RhCl(PPh3)3 (0.2 mol%)

    28% + n-Oct

    33%

    33%

    n-Oct

    D

    n-Oct n-Oct

    n-Oct

    D

    n-Oct n-Oct

    D

    D

    n-Oct H

    D

    RhB

    n-Oct D

    RhB

    n-Oct Rh

    D

    B n-Oct

    RhB

    D

    n-Oct H

    D

    B

    n-Oct D

    B n-Oct

    B

    D

    n-Oct B

    D

    X X

    hydride migration

    β-H elim.

    β-H elim.

    reductive elimination

    D

  • RhB D

    RhB H

    RhB H

    Deuterium Labelling Studies

    Evans, D. A. J. Am. Chem. Soc. 1992, 114, 6679–6685.

    n-Oct n-Oct HO

    5%

    DBCat (0.1 equiv)

    RhCl(PPh3)3 (0.2 mol%)

    28% + n-Oct

    33%

    33%

    n-Oct

    D

    n-Oct n-Oct

    n-Oct

    D

    n-Oct n-Oct

    D

    D

    n-Oct H

    D

    RhB

    n-Oct D

    RhB

    n-Oct Rh

    D

    B n-Oct

    RhB

    D

    n-Oct H

    D

    B

    n-Oct D

    B n-Oct

    B

    D

    n-Oct B

    D

    X X

    hydride migration

    β-H elim.

    β-H elim.

    reductive elimination

    D

  • RhB D

    RhB H

    RhB H

    Deuterium Labelling Studies

    Evans, D. A. J. Am. Chem. Soc. 1992, 114, 6679–6685.

    n-Oct n-Oct HO

    5%

    DBCat (0.1 equiv)

    RhCl(PPh3)3 (0.2 mol%)

    28% + n-Oct

    33%

    33%

    n-Oct

    D

    n-Oct n-Oct

    n-Oct

    D

    n-Oct n-Oct

    D

    D

    n-Oct H

    D

    RhB

    n-Oct D

    RhB

    n-Oct Rh

    D

    B n-Oct

    RhB

    D

    n-Oct H

    D

    B

    n-Oct D

    B n-Oct

    B

    D

    n-Oct B

    D

    X X

    hydride migration

    β-H elim.

    β-H elim.

    reductive elimination

    D

  • RhB D

    RhB H

    RhB H

    Deuterium Labelling Studies

    Evans, D. A. J. Am. Chem. Soc. 1992, 114, 6679–6685.

    n-Oct n-Oct HO

    5%

    DBCat (0.1 equiv)

    RhCl(PPh3)3 (0.2 mol%)

    28% + n-Oct

    33%

    33%

    n-Oct

    D

    n-Oct n-Oct

    n-Oct

    D

    n-Oct n-Oct

    D

    D

    n-Oct H

    D

    RhB

    n-Oct D

    RhB

    n-Oct Rh

    D

    B n-Oct

    RhB

    D

    n-Oct H

    D

    B

    n-Oct D

    B n-Oct

    B

    D

    n-Oct B

    D

    X X

    hydride migration

    β-H elim.

    β-H elim.

    reductive elimination

    D

  • Alkyl - not observed

    RhB D

    RhB H

    RhB H

    Deuterium Labelling Studies

    Evans, D. A. J. Am. Chem. Soc. 1992, 114, 6679–6685.

    n-Oct n-Oct HO

    5%

    DBCat (0.1 equiv)

    RhCl(PPh3)3 (0.2 mol%)

    28% + n-Oct

    33%

    33% Deuterium distribution

    n-Oct

    D

    n-Oct n-Oct

    n-Oct

    D

    n-Oct n-Oct

    D

    D

    n-Oct H

    D

    RhB

    n-Oct D

    RhB

    n-Oct Rh

    D

    B n-Oct

    RhB

    D

    n-Oct H

    D

    B

    n-Oct D

    B n-Oct

    B

    D

    X X

    hydride migration

    β-H elim.

    β-H elim.

    reductive elimination

    β-Hydride elimination to form olefins is faster than reductive elimination at a secondary carbon

    not observed

  • Internal v Terminal

    Rh CatB H

    Internal v. Terminal Olefin Isomers

    Evans, D. A. J. Am. Chem. Soc. 1992, 114, 6679–6685.

    HBCat

    Catalyst (2.5 mol%)

    β-Hydride elimination to form olefins is faster than reductive elimination at a secondary carbon

    OH 3-ol + 2-ol 1-ol++

    RhCl(PPh3)3 – – –100

    product ratios

    Rh

    R R'

    CatB BCat

    R R'

    R H

    [Rh(nbd)(dppb)]BF4 87 7 2 4

    nbd = dppb = PPh2 Ph2P

    H

    Rh

    R H

    CatB

    H H H H H H

    β-hydride elimination

    reductive elimination

    vs.

    • Generation of an internal olefin complex: less facile than reductive elimination?

  • Internal v. Terminal Olefin Isomers

    Evans, D. A. J. Am. Chem. Soc. 1992, 114, 6679–6685.

    HBCat

    Catalyst (2.5 mol%)

    β-Hydride elimination to form terminal olefins is faster than reductive elimination at a secondary carbon

    OH 3-ol + 2-ol 1-ol++

    RhCl(PPh3)3 [Rh(nbd)(dppb)]BF4

    – – –100

    87 7 2 4

    product ratios

    n-pent HBCat

    [Rh(nbd)(dppb)]BF4 (2.5 mol%) n-pent n-pent n-pent+ +

    B B B 12% 20% 68%

    • Generation of an internal olefin complex: less facile than reductive elimination?

    • Examine a system which has access to both internal and terminal olefin complexes

    product ratios

    nbd = dppb = PPh2 Ph2P

  • Rh B H

    Rh B H

    Rh B H

    Internal v. Terminal Olefin Isomers

    Evans, D. A. J. Am. Chem. Soc. 1992, 114, 6679–6685. β-Hydride elimination to form terminal olefins is f