title: Scope and limitation of organocuprates, and copper or nickel catalyst-modified Grignard reagents for installation of an alkyl group onto cis-4-cyclopentene-1,3-diol monoacetate.
abstract: Alkylation of the title compound 1 was investigated with two types of reagents. One is a copper reagent derived from R(T)MgX (X = Cl, Br) and CuX (X = CN, I) and the other is R(T)MgX in the presence of a copper or a nickel catalyst. First, butylation was studied with BuCu(CN)(MgX), Bu(2)Cu(CN)(MgX)(2), BuMgX/CuCN (10 mol %), BuCu (derived from BuMgCl and CuI), and BuMgCl/CuI (10 mol %) in THF or Et(2)O. We found that trans 1,4-isomer 2a and/or trans 1,2-isomer 3a were produced exclusively with these reagents and that the stoichiometry of BuMgX/CuX and the choice of solvent were critical to attain high regioselectivity and efficient yield. Reaction with Bu(2)Cu(CN)(MgCl)(2) and BuMgCl/CuX (X = CN, I; 10 mol %) both in THF produced 2a with 93-94% regioselectivity in 87-92% yields. On the other hand, BuCu(CN)(MgX) in THF, Bu(2)Cu(CN)(MgX)(2) in Et(2)O, and BuMgX/CuCN (10 mol %) in Et(2)O furnished 3a in good yields with >90% selectively, irrespective of X of BuMgX. In the nickel-catalyzed butylation of 1 with BuMgCl, NiCl(2)(dppp) among NiCl(2)(tpp)(2), NiCl(2)(dppf), and NiCl(2)(dppp) furnished the best result to produce 2a. The CuCN-based protocol was then applied to other alkyl Grignard reagents, which include Me, Et, (CH(2))(3)Ph, c-C(6)H(11), (CH(2))(6)OMOM, (CH(2))(9)CH=CH(2), and CH(2)Ph as the alkyl group (R(T)). In addition, the Mitsunobu inversion of 2a and 3a afforded the corresponding cis isomers stereoselectively with AcOH as an acid at -78 degrees C in toluene for 2a and with 4-(NO(2))C(6)H(4)COOH in THF at r.t. for 3a. No racemization during the alkylation was confirmed by the reaction using (1R,3S)-1 (>99% ee) to produce (1S,4S)-2a and (1S,2S)-3a, respectively.
authors.affiliation: Department of Biomolecular Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: M
authors.initials: M
authors.lastname: Matsuumi
authors.forename: M G
authors.initials: MG
authors.lastname: Murugesh
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi