Pseudo‐Stereodivergent Synthesis of Enantioenriched Tetrasubstituted Alkenes by Cascade 1,3‐Oxo‐Allylation/Cope Rearrangement

Abstract

The catalytic diastereodivergent construction of stereoisomers having two or more stereogenic centers has been extensively studied. In contrast, the switchablei ntroduction of another stereogenic element, that is,Z/E configuration involving ap olysubstituted alkene group,i nto the optically active stereoisomers,h as not been recognized yet. Disclosed here is the pseudo-stereodivergent synthesis of highly enantioenriched tetrasubstituted alkene architectures from isatin-based Morita-Baylis-Hillman carbonates and allylic derivatives,u nder the cooperative catalysis of at ertiary amine and ac hiral iridium complex. The success of the switchable construction of the tetrasubstituted alkene motif relies on the diastereodivergent 1,3-oxo-allylation reaction between N-allylic ylides and chiral p-allyliridium complex intermediates by ligand and substrate control, followed by the stereoselective concerted 3,3-Cope rearrangement process.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.Scheme 5. Mechanism study for the cascade 1,3-oxo-allylation and Cope rearrangement process. Angewandte ChemieForschungsartikel 7153

Solvent‐Regulated Diastereodivergent [3 + 2] Annulations of CF3‐Containing Morita−Baylis−Hillman Carbonates with Cyclic Sulfonimines

“…donating or an electron-withdrawing substituent on the aryl ring were applied to the asymmetric [3+2] annulations with MBH adduct 1a under the standard conditions, and the corresponding products 3f-3k were produced in moderate yields with excellent enantioselectivity (entries [7][8][9][10][11][12]. Besides, cyclic sulfonimine 2 bearing a methyl ester group was well tolerated, giving comparable results (entry 13), whereas the one with a benzyl group afforded product 3m and its diastereomer 4m as an inseparable mixture in a good yield with excellent enantioselectivity (entry 14).…”

“…[2] Most of the reported strategies relied on the employment of distinct catalysts (or different assemblies of cooperative catalytic systems) [3] or different additives [4] to accomplish diastereodivergence (Figure 1), while a more convenient protocol, by simply tuning the reaction conditions, such as solvents [5] or temperature, [6] without changing any reactants, reagents and catalysts, has been less disclosed. [7] Actually, chemists have recognized that different solvents would impose effects on enthalpy and entropy for the stereodetermining step, [8] but the solventcontrolled diastereodivergent synthesis in a catalytic asymmetric manner is still rather limited. On the other hand, the fluoro-containing groups, especially trifluoromethyl (CF 3 ) one, are ubiquitous in numerous biologically active molecules, as they can improve bioavailability, lipophilicity, metabolic stability, etc.…”