Desymmetrization of Cyclic Sulfonimidamides by Asymmetric Allylation.

Herein we report the first transition metal-catalyzed approach to the enantioenriched synthesis of cyclic sulfonimidamides relying on commercially available palladium catalysts and ligands. High-throughput experimentation (HTE) was employed to identify the optimal catalyst system and solvent. The method is applied to a variety of saturated and unsaturated rings and exhibits the highest selectivity for 2-substituted allyl electrophiles. The products are further elaborated to complex, tricyclic scaffolds. DFT experiments presented herein highlight the key ligand substrate interactions leading to the high levels of enantioselectivity.

1,3-Asymmetric Induction in Diastereoselective Allylations of Chiral N-Tosyl Imines.

Lewis acid mediated allylations of ß-alkoxy N-tosyl imines using allyltrimethylsilane lead to 3-alkoxy homoallylic N-tosyl amines with anti-selectivity. Two methods of Cu(OTf)2-mediated allylations are reported herein, demonstrating that diastereoselectivity can be achieved through 1,3 acyclic stereocontrol of ß-chiral aldimines. Observed selectivity trends and computational evidence suggest selectivity arises through the formation of a six-membered ring chelate. The product ratios of these allylations are dependent on conformational preferences of the chelate and steric effects in the transition-state structures.

One-Pot Assembly and Synthetic Applications of Geminal Acyl/Alkoxy Tetrasubstituted Allenes.

Polysubstituted allenes are useful synthetic intermediates in many applications, offering structural complexity, modularity, and their axial chirality in further transformations. While acyl and alkoxy-substituted allenes are known, there are currently few examples of allenes containing both functionalities and no reports of geminally substituted acyl/alkoxy allenes being isolated and characterized. Herein, we report the synthesis of tetrasubstituted allenes featuring a novel geminal acyl/alkoxy substitution. These unique "push-pull" allenes are bench-stable and exhibit interesting reactivity in several applications.