Ring opening of pymisyl-protected aziridines with organocuprates

TY - JOUR

T1 - Ring opening of pymisyl-protected aziridines with organocuprates

AU - Bornholdt, Jan

AU - Felding, Jakob

AU - Clausen, Rasmus Prætorius

AU - Kristensen, Jesper Langgaard

N1 - Keywords: nitrogen heterocycles; protecting groups; ring opening; small ring systems; synthetic methods

PY - 2010/11/2

Y1 - 2010/11/2

N2 - The pyrimidine-2-sulfonyl (pymisyl) group is introduced as a new protecting group that can be used to activate aziridines towards ring opening. It is readily introduced and removed under mild conditions. Regioselective ring opening of pymisyl-protected 2-methyl-aziridine with organocuprates gives the corresponding sulfonamides in high yields, and the pymisyl group can subsequently be removed upon treatment with a thiolate. The versatility of this new nitrogen protecting group is illustrated with a new synthesis of Selegiline, a monoamine oxidase-B inhibitor marketed for the treatment of Parkinson's disease. Easy on'easy off: The pymisyl group is introduced as a new protecting group for the activation of aziridines towards ring opening with organocuprates (see scheme). It is readily removed under very mild conditions with thiolates. The versatility of the approach is illustrated in a new synthesis of Selegiline, a drug marketed for the treatment of Parkinson's disease.

AB - The pyrimidine-2-sulfonyl (pymisyl) group is introduced as a new protecting group that can be used to activate aziridines towards ring opening. It is readily introduced and removed under mild conditions. Regioselective ring opening of pymisyl-protected 2-methyl-aziridine with organocuprates gives the corresponding sulfonamides in high yields, and the pymisyl group can subsequently be removed upon treatment with a thiolate. The versatility of this new nitrogen protecting group is illustrated with a new synthesis of Selegiline, a monoamine oxidase-B inhibitor marketed for the treatment of Parkinson's disease. Easy on'easy off: The pymisyl group is introduced as a new protecting group for the activation of aziridines towards ring opening with organocuprates (see scheme). It is readily removed under very mild conditions with thiolates. The versatility of the approach is illustrated in a new synthesis of Selegiline, a drug marketed for the treatment of Parkinson's disease.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1002/chem.201001026

DO - 10.1002/chem.201001026

M3 - Journal article

C2 - 20839183

SN - 0947-6539

VL - 16

SP - 12474

EP - 12480

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

IS - 41

ER -