Burns DH, Chan HK, Miller JD, Jayne CL, Eichhorn DM
Department of Chemistry, Wichita State University, Kansas 67260, USA.
J Org Chem. 2000 Aug 25;65(17):5185-96. doi: 10.1021/jo0003044.
A general strategy for the preparation of the family of exo-[n.m.n.m]metacyclophanes (n,m > or = 3) in 6-steps (starting from 2-bromoanisole) that utilizes a [2 + 2] approach to furnish the exo-metacyclophane ring in good to moderate yield is described. The soluble copper catalyst [CuBr-LiSPh-LiBr-THF] is used to efficiently couple Grignard and alkyl or ether tosylate reagents in several of the synthetic steps, including the ring construction in the final step. The exo-[n.m.n.m]metacyclophane ring is conformationally mobile on the NMR time scale, and X-ray crystallography reveals that exo-[3.3.3.3]metacyclophane 2a assumes a cone conformation, and that exo-[6.6.6.6]metacyclophane 6a assumes a chair conformation. Molecular mechanics calculations show that both conformations for each exo-metacyclophane are very similar in energy. Regiocontrol over the alkylation and acylation of the phenolic oxygens of 2b is problematic, although the preparation of the tetraacetylated 18 and alkylation of 2b with CH2BrCl to furnish the methylene-linked mono- and bis-adducts 19 and 20 are straightforward.
描述了一种以2-溴苯甲醚为起始原料，通过6步反应制备外消旋-[n.m.n.m]间环环烷烃（n,m≥3）家族的通用策略，该策略采用[2 + 2]方法以良好至中等产率提供外消旋间环环烷烃环。可溶性铜催化剂[CuBr-LiSPh-LiBr-THF]用于在几个合成步骤中有效地偶联格氏试剂与烷基或醚对甲苯磺酸盐试剂，包括最后一步的环构建。外消旋-[n.m.n.m]间环环烷烃环在NMR时间尺度上构象可变，X射线晶体学表明外消旋-[3.3.3.3]间环环烷烃2a呈锥形构象，外消旋-[6.6.6.6]间环环烷烃6a呈椅式构象。分子力学计算表明，每个外消旋间环环烷烃的两种构象在能量上非常相似。尽管制备四乙酰化产物18以及用CH2BrCl对2b进行烷基化以提供亚甲基连接的单加合物和双加合物19和20很简单，但对2b的酚氧基进行烷基化和酰化的区域控制存在问题。
