2,5-Disubstituted Pyrrolidines as Chiral Auxiliaries in Radical Reactions: A Theoretical Approach

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The radical addition to amides derived from chiral 2,5-disubstituted pyrrolidines has been theoretically studied by the use of density functional methods and the results compared with known experimental data. The results agree quite well with those obtained experimentally and allow the full rationalization of the factors influencing the diastereoselectivity. Steric effects are the main factors determining the selectivity, but electronic interactions can also be very important when the attacking alkene is alpha,beta-conjugated, as in acrylic esters or acrylamides. Additions at the alpha- and beta-positions of the amide chain in the auxiliary are subject to different rules, with the former usually yielding high diastereoselectivities both experimentally and theoretically, whereas the latter is theoretically predicted to occur with low selectivity. We fully rationalize these two opposite behaviours and suggest several ways to circumvent this limitation, thus strongly increasing the interest of this type of structure as chiral auxiliaries in radical reactions.
Original languageUnknown
Pages (from-to)4841-4850
JournalEuropean Journal of Organic Chemistry
Volumen/d
Issue number25
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

    Cite this

    @article{5bfbaede65a64b4e9d488bc24c7e02f1,
    title = "2,5-Disubstituted Pyrrolidines as Chiral Auxiliaries in Radical Reactions: A Theoretical Approach",
    abstract = "The radical addition to amides derived from chiral 2,5-disubstituted pyrrolidines has been theoretically studied by the use of density functional methods and the results compared with known experimental data. The results agree quite well with those obtained experimentally and allow the full rationalization of the factors influencing the diastereoselectivity. Steric effects are the main factors determining the selectivity, but electronic interactions can also be very important when the attacking alkene is alpha,beta-conjugated, as in acrylic esters or acrylamides. Additions at the alpha- and beta-positions of the amide chain in the auxiliary are subject to different rules, with the former usually yielding high diastereoselectivities both experimentally and theoretically, whereas the latter is theoretically predicted to occur with low selectivity. We fully rationalize these two opposite behaviours and suggest several ways to circumvent this limitation, thus strongly increasing the interest of this type of structure as chiral auxiliaries in radical reactions.",
    keywords = "Ab, imidazolidinones, catalysis, Radical, resolution, states, acid, conjugate, atom-transfer, alpha-haloacyl, lewis-acid, initio, dynamic, carbon-carbon, reaction, additions, Chiral, auxiliaries, thermal-reactions, alkenes, bond, cyclization, transfer, diels-alder, Lewis, Transition, reactions, calculations, asymmetric, kinetic, amide-substituted",
    author = "Santos, {Ant{\'o}nio Gil de Oliveira}",
    year = "2010",
    month = "1",
    day = "1",
    doi = "10.1002/ejoc.201000479",
    language = "Unknown",
    volume = "n/d",
    pages = "4841--4850",
    journal = "European Journal of Organic Chemistry",
    issn = "1434-193X",
    publisher = "WILEY-V C H VERLAG GMBH",
    number = "25",

    }

    TY - JOUR

    T1 - 2,5-Disubstituted Pyrrolidines as Chiral Auxiliaries in Radical Reactions: A Theoretical Approach

    AU - Santos, António Gil de Oliveira

    PY - 2010/1/1

    Y1 - 2010/1/1

    N2 - The radical addition to amides derived from chiral 2,5-disubstituted pyrrolidines has been theoretically studied by the use of density functional methods and the results compared with known experimental data. The results agree quite well with those obtained experimentally and allow the full rationalization of the factors influencing the diastereoselectivity. Steric effects are the main factors determining the selectivity, but electronic interactions can also be very important when the attacking alkene is alpha,beta-conjugated, as in acrylic esters or acrylamides. Additions at the alpha- and beta-positions of the amide chain in the auxiliary are subject to different rules, with the former usually yielding high diastereoselectivities both experimentally and theoretically, whereas the latter is theoretically predicted to occur with low selectivity. We fully rationalize these two opposite behaviours and suggest several ways to circumvent this limitation, thus strongly increasing the interest of this type of structure as chiral auxiliaries in radical reactions.

    AB - The radical addition to amides derived from chiral 2,5-disubstituted pyrrolidines has been theoretically studied by the use of density functional methods and the results compared with known experimental data. The results agree quite well with those obtained experimentally and allow the full rationalization of the factors influencing the diastereoselectivity. Steric effects are the main factors determining the selectivity, but electronic interactions can also be very important when the attacking alkene is alpha,beta-conjugated, as in acrylic esters or acrylamides. Additions at the alpha- and beta-positions of the amide chain in the auxiliary are subject to different rules, with the former usually yielding high diastereoselectivities both experimentally and theoretically, whereas the latter is theoretically predicted to occur with low selectivity. We fully rationalize these two opposite behaviours and suggest several ways to circumvent this limitation, thus strongly increasing the interest of this type of structure as chiral auxiliaries in radical reactions.

    KW - Ab

    KW - imidazolidinones

    KW - catalysis

    KW - Radical

    KW - resolution

    KW - states

    KW - acid

    KW - conjugate

    KW - atom-transfer

    KW - alpha-haloacyl

    KW - lewis-acid

    KW - initio

    KW - dynamic

    KW - carbon-carbon

    KW - reaction

    KW - additions

    KW - Chiral

    KW - auxiliaries

    KW - thermal-reactions

    KW - alkenes

    KW - bond

    KW - cyclization

    KW - transfer

    KW - diels-alder

    KW - Lewis

    KW - Transition

    KW - reactions

    KW - calculations

    KW - asymmetric

    KW - kinetic

    KW - amide-substituted

    U2 - 10.1002/ejoc.201000479

    DO - 10.1002/ejoc.201000479

    M3 - Article

    VL - n/d

    SP - 4841

    EP - 4850

    JO - European Journal of Organic Chemistry

    JF - European Journal of Organic Chemistry

    SN - 1434-193X

    IS - 25

    ER -