EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, U.K.
J Org Chem. 2023 Jun 16;88(12):7784-7799. doi: 10.1021/acs.joc.2c02688. Epub 2023 May 15.
The isothiourea-catalyzed regio- and enantioselective formal [2 + 2] cycloaddition of C(1)-alkyl and C(1)-unsubstituted ammonium enolates with β- and α,β-substituted trifluoromethylenones has been developed. In all cases, preferential [2 + 2]-cycloaddition over the alternative [4 + 2]-cycloaddition is observed, giving β-lactones with excellent diastereo- and enantioselectivity (34 examples, up to >95:5 dr, >99:1 er). The regioselectivity of the process was dictated by the nature of the substituents on both reaction components. Solely [2 + 2] cycloaddition products are observed when using α,β-substituted trifluoromethylenones or α-trialkylsilyl acetic acid derivatives; both [2 + 2] and [4 + 2] cycloaddition products are observed when using β-substituted trifluoromethylenones and α-alkyl-α-trialkylsilyl acetic acids as reactants, with the [2 + 2] cycloaddition as the major reaction product. The beneficial role of the α-silyl substituent within the acid component in this protocol has been demonstrated by control experiments.
异硫脲催化 C(1)-烷基和 C(1)-未取代的铵烯醇化物与 β-和 α,β-取代的三氟甲基烯酮的区域和对映选择性的形式 [2 + 2]环加成已经被开发出来。在所有情况下，都观察到优先发生 [2 + 2]-环加成而不是替代的 [4 + 2]-环加成，从而得到具有极好的非对映选择性和对映选择性的 β-内酰胺（34 个例子，高达 >95:5 dr，>99:1 er）。该过程的区域选择性由两个反应组分上取代基的性质决定。当使用 α,β-取代的三氟甲基烯酮或 α-三烷基甲硅烷基乙酸衍生物时，仅观察到 [2 + 2]环加成产物；当使用 β-取代的三氟甲基烯酮和 α-烷基-α-三烷基甲硅烷基乙酸作为反应物时，同时观察到 [2 + 2]和 [4 + 2]环加成产物，其中 [2 + 2]环加成是主要的反应产物。通过控制实验证明了酸组分中 α-硅烷基取代基在该方案中的有益作用。
