NHC-Promoted Asymmetric β-Lactone Formation from Arylalkylketenes and Electron-Deficient Benzaldehydes or Pyridinecarboxaldehydes
NHC-Promoted Asymmetric β-Lactone Formation from Arylalkylketenes and Electron-Deficient Benzaldehydes or Pyridinecarboxaldehydes
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DOI：
10.1021/jo4003079
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发表时间：
2013-04-19
影响因子：
3.6
通讯作者：
Smith, Andrew D.
中科院分区：
文献类型：
--
作者：
Douglas, James;Taylor, James E.;Smith, Andrew D.
手性NHC催化烷基芳基烯酮与缺电子苯甲醛和2-和4-吡啶甲醛的不对称缩甲醛[2 + 2]环加成反应，生成立体定向的β-内酯。在苯甲醛系列中，使用2-硝基苯甲醛观察到最佳产物非对映体和对映体控制（高达93：7 dr（顺式：反式）和93%ee）。取代的2-和4-吡啶甲醛在该过程中也可以耐受，以良好的产率和对映体选择性生成相应的β-内酯，尽管这些过程中的非对映体控制高度依赖于醛取代。这些方法易于规模化，允许制备多克量的β-内酯产物。这些产物的衍生化，通过开环成相应的立体定向的β-羟基和β-氨基酸衍生物而不损失立体化学完整性或通过交叉偶联，得到证明。
A chiral NHC catalyzes the asymmetric formal [2 + 2] cycloaddition of alkylarylketenes with both electrondeficient benzaldehydes and 2- and 4-pyridinecarboxaldehydes to generate stereodefined beta-lactones. In the benzaldehyde series, optimal product diastereo- and enantiocontrol is observed using 2-nitrobenzaldehyde (up to 93:7 dr (syn:anti) and 93% ee). Substituted 2- and 4-pyridinecarboxaldehydes are also tolerated in this process, generating the corresponding beta-lactones in good yield and enantioselectivity, although the diastereocontrol in these processes is highly dependent upon the aldehyde substitution. These processes are readily scalable, allowing multigram quantities of the beta-lactone products to be prepared Derivatization of these products, either through ring opening into the corresponding stereodefined beta-hydroxy and beta-amino acid derivatives without loss of stereochemical integrity or via cross coupling, is demonstrated.