Applications of Mn(III) in Organic Chemistry Florina Voica

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Transcript of Applications of Mn(III) in Organic Chemistry Florina Voica

  • Applications of Mn(III) in Organic Chemistry Florina VoicaBaran lab GM 2/6/2010Contents: Oxidative radical cyclization of -keto acids Discussion of the reaction mechanism Oxidative radical cyclization of -keto esters Oxidative radical cyclization of 1,3-diketones Oxidative cyclization of ketones Oxidative fragmentation-cyclization Asymmetric radical cyclization Miscellaneous applications of Mn(III) salts

    Some common commercially available Mn(III) species:Mn(OAc)32H2O (Aldrich, $6/g)Mn(acac)3 (Aldrich, $3.1/g)MnF3 (Aldrich, $3.2/g)Mn2O3 (Aldrich, $10/g)

    Excluding the applications in olefin epoxidation (or alkane oxidation), Mn(III) is most commonly used for oxidative radical cyclizations. This chemistry, largely developed by Barry Snider (Chem. Rev. 1996, 96, 339) has found broad applications in the total synthesis of natural products.

    Mn(OAc)3

    Thornton, J. Chem. Soc. Chem. Comm., 1978, 62.

    - crystallizes as Mn3O(OAc)7- anhydrous form does not exist- sold as Mn(OAc)2 2H2O- insoluble in most organic solvents; soluble in hot AcOH- can be prepared in situ from Mn(OAc)2 and KMnO4 in AcOH

    First reports...

    Bush J. Am. Chem. Soc. 1968, 90, 5903Heiba J. Am. Chem. Soc. 1968, 90, 5905

    Ph + 2 MnIII AcOH

    refluxxsOPh

    O

    60%

    a)

    b) O

    OR

    OPh

    Mn(OAc)32H2O AcOH, 45 C

    Ph

    O O

    OR

    Heiba J. Org. Chem. 1974, 39, 3456

    This summary will not address the chemistry of Mn(III)salen complexesand Mn(III)porphyrins.For a review on the Jacobsen-Katsuki epoxidation see:Jacobsen, Catal. Asymmetric Synth. (ed. Ojima, I.), 159-202,(VCH, New York, 1993) and ref thereinFor a representative example in the field of Mn(III) porphyrins seeGroves, J. Am. Chem. Soc., 1988, 110, 8628.

    Br

    R3Sn R 3

    SnH

    H

    Reductive processes

    Oxidative processes

    cyclization

    O

    MnIII

    MnIII MnIII

    O

    AcO-

    slowO

    MnIIIMnIII

    MnIII

    O

    O

    fastO

    MnIIIMnIII

    MnII

    O

    O

    Ph

    OMnIII

    MnIIIMnII

    O

    O

    PhO

    OMnIII

    Ph

    O

    O

    Ph

    -MnII

  • Applications of Mn(III) in Organic Chemistry Florina VoicaBaran lab GM 2/6/2010The experts: Barry Snider E. J. Corey M. P. Bertrand Janine Cossy Phillip Zoretic and others

    O

    OH

    O

    1.3 eq Mn3O(OAc)7 AcOH, 20 min, rt

    O

    O

    H

    H

    HH

    63%

    OO

    O

    H

    H

    HO

    H

    O

    Corey, J. Am. Chem. Soc. 1984, 106, 5384

    Early paper by Corey hinted at the potential of this new methodology to efficiently assemble complex polycyclic structures.

    OH

    OX

    O

    X OMn(OAc)3AcOH, 70 C

    H

    X = CN (50%), only cisX = CO2Me (64%) cis:trans 4:1

    Fristad, Tetrahedron Lett. 1985, 26, 3761

    CHO

    OMOM

    CO2MeMeO2C

    the major isomerafter a Luche reduction

    1. KOH, MeOH2. Mn3O(OAc)7 (2 eq) AcOH, 70 C

    (one pot) OO

    H OMOM

    OMe

    O

    68% yield

    OO

    CHO

    () - 14-epiupial

    Upial could not be obtainedby the same strategy sincethe other isomer did notreact in the radical cyclization!

    Paquette, Tetrahedron Lett. 1987, 43, 5567For syntheses of upial see:Taschner, J. Am. Chem. Soc. 1985, 107, 5570 (key step: intramolecular aldol); Honda, Angew. Chem. Int. Ed. 2008, 47, 131 (key step: carbonyl ene reaction)

    O

    OCO2Me

    O

    OO

    O Mn(OAc)3AcOH, 80 C

    58%

    O

    OCO2Me

    H

    HOMeO2C O

    H

    Mn(OAc)3AcOH, 65 C

    31%

    Mechanism?Wallace, J. Chem. Soc. Perkin Trans. 1, 2001, 206.

    Oxidative cyclization of -keto acids

    Reaction mechanism

    O

    CO2Me

    Et

    R

    R = HR = Me

    Mn(OAc)3 AcOH

    Mn(OAc)3Cu(OAc)2 AcOH

    OR

    CO2Me

    HO

    RCO2Me R = H 71%

    R = Me 56%

    Key concepts: - single electron oxidant - oxidative radical cyclization - radical oxidation - tandem radical cyclization - hydrogen abstraction

  • Applications of Mn(III) in Organic Chemistry Florina VoicaBaran lab GM 2/6/2010Factors that determine the reaction mechanism/product distribution:

    The oxidant

    Mn(OAc)3 - most common oxidant/initiator for these reactions. Other oxidants/initiators used: Fe(ClO4)3; CAN; Co(OAc)2 - in the termination step, its oxidative ability is limited: -carboxy radicals (2 and 3) will be oxidized to carbocations tertiary radicals will be oxidized to carbocations to give alkene or to form a tertiary acetate allylic radicals will be oxidized to allylic acetates isolated 1 and 2 radicals wont be oxidized. If no oxidant is present they will be quenched by H-abstraction from the solvent or

    Cu(OAc)2 - oxidizes 2 radicals 350X faster than Mn(OAc)3 - reacts rapidly with radicals ( 106 M/sec) to form alkyl-CuIII species - 1 and 2 radicals are taken to alkenes via direct oxidative elimination from the alkyl-Cu intermediate (E-olefins and the less substituted alkene) - allylic, 3 radicals are oxidized to carbocations

    Kochi, Acc. Chem. Res. 1974, 7, 351

    The solvent

    AcOH is the most common solvent with Mn(OAc)3.

    DMSO, MeOH, dioxane, CH3CN can also be used but they requirehigher temp and the yields are sometimes lower.

    EtOH is a better H-donor than AcOH so it is preferred when vinyl radicalsare involved in the termination step (vinyl radicals cannot be oxidized sothey need to be quenched).

    CuX2 (X = Cl, Br, I, SCN) - oxidize radicals to carbocations or they undergo ligand transfer

    O

    Et

    OMe

    O O

    fast

    O O

    OMe

    Et

    slow

    Cu(O

    Ac) 2

    O O

    OMe

    solventO O

    OMe

    O

    Et

    OMe

    O

    Me

    Mn(OAc)3

    - MnII

    Mn(OAc)3slow

    MnIIIO

    Et

    CO2Me fast

    - MnII

    O

    Et

    CO2Me

    Et

    OMe

    CO2Me

    O

    Me

    CO2Me

    Cu(OAc)2

    O

    OMe

    OMe

    H

    OMe

    OMnIII

    Et

    56%

    or

    OMe

    CO2Me

    HEtO

    Me

    CO2Me

    Et

    O

    OMe

    OMe

    14%O

    OMe

    OMe

    H3%

    CuII

    Et

    Snider, J. Org. Chem. 1988, 53, 2137

    boat TS

    OH O

    OMe

    no discrete keto-ester radical detected!

    cis

    trans

  • Applications of Mn(III) in Organic Chemistry Florina VoicaBaran lab GM 2/6/2010Radical cyclizations of -keto esters

    OMe

    OMe CO2Me

    Mn(OAc)3 AcOH

    50%O

    MeO2C Me

    Me

    OMe

    H MeO2C Me

    Me

    OMe

    H

    Zn, HCl

    60%

    O-methylpodocarpateSnider, J. Org. Chem. 1985, 50, 3659

    OMe CO2Me

    MeO

    OMeMn(OAc)3 AcOH

    70%O

    MeO2C Me

    Me

    H

    MeO

    OMe

    ()-Triptoquinone B and C

    Takaishi, J. Chem. Soc., Chem. Commun. 1993, 793

    Proposed reaction mechanism:

    OMe CO2Me

    R'Mn(OAc)3

    O

    CO2Me

    Me

    Me

    RO

    MeO2C

    Me

    Me

    R

    Mn(OAc)3

    O

    MeO2C

    Me

    Me

    R

    O

    OMe

    MeOR'

    Me

    H

    HH

    MeMeO2C

    MeHO

    R'

    OCO2Me

    O

    O

    Mn(OAc)22H2O AcOH

    O

    O

    OMeO2C

    Me

    H 40%

    O

    O

    HOMeO2C

    Me

    H 7%+O

    OHO

    OMe

    HO

    O

    triptolide

    Yang, J. Org. Chem. 1998, 63, 6446

    Trick to improve selectivity... (we shall see more of this later)

    OCO2Et

    OMe

    Cl

    Mn(OAc)22H2O AcOH OMe

    OEtO2C

    Me

    HCl

    90%

    triptolide

    OO

    MeOOMe

    Mn(OAc)3 (3 eq)Cu(OAc)2 (2 eq) AcOH, 80 C

    O

    MeOO

    OMe

    76% vannusal A

    Nicolaou, Chem Commun. 2002, 2480

    O Mn(OAc)3 (1eq)Cu(OAc)2 (1 eq) AcOH, rt

    61%

    O

    CO2Me

    H

    HMeO2C

    H

    HO

    dehydropallescensin DWhite, Tetrahedron Lett. 1990, 31, 59

    a. Monocylization

    b. Bicycle formation with termination onto an arene

  • Applications of Mn(III) in Organic Chemistry Florina VoicaBaran lab GM 2/6/2010

    Oxidative cyclization of ketones

    Me

    Me

    Me

    TMS

    O

    Mn(OAc)3 (15eq)9:1 EtOH/AcOH 90 C, 22h

    TMS

    Me

    Me

    O

    Me

    25%

    Me

    Me

    O

    Me

    TMS37%

    +

    Me

    Me

    O

    MeNaBH4, MeOH88%

    Me

    Me

    HO

    Me

    H

    gymnomitrol

    AcOH100 C

    80%

    Snider, J. Org. Chem. 1997, 62, 1970

    O

    Cl

    +

    OMe

    Mn(OAc)3 (4eq)benzene, 100 C

    25%

    O

    Me

    OMe

    Cl

    1. KOtBu (92%)2. LiPPh2 (84%)O

    Me

    OH

    conocarpan

    Mechanism?

    Snider, J. Org. Chem. 1997, 6978

    Oxidative fragmentation-cyclization

    H

    Me

    Me

    HO

    Mn(pic)3 DMF

    58%

    Me

    H

    MeO

    Me

    H

    Mesilphiperfol-6-ene

    Snider, J. Org. Chem. 1994, 59, 5419

    O

    OO

    Ph2t-BuOO

    OO

    O

    H

    OO

    O

    H

    tricycloillicinone

    Mn(OAc)3Cu(OAc)2

    AcOH, 50 C75%

    Danishefsky, J. Am. Chem. Soc. 1998, 120, 12684

    N

    O

    Mn(OAc)3AcOH, reflux

    60%

    OO

    N

    O

    O

    O

    N

    N

    Omersicarpine Kerr, Org. Lett. 2008, 10, 1437

    HO

    OTHP

    Mn(pic)3Bu3SnH

    DMF, 0 C

    H Me

    HTHPO

    O

    H Me

    HSCN Me10-isothiocyanatoguaia-6-ene

    Narasaka, Chem. Lett. 1994, 1697