Chelating a,p-Unsaturated Compounds

Specifically, with 10 mol% of AgAsFg and lb in THF at -20 °C, the reaction of indoles with p,y-unsaturated a-keto esters 67 proceeded smoothly to give 

While in the presence of 0.5 mol% Sm(OTf)3-lc complex in CH2CI2, the absolute configuration of products 68 was reversed from (5) to (7 ) (Table 6.8). This highly efficient system also showed broad substrate scope and insensitivity to the electronic properties of the substituents. It should be noted that this catalytic protocol allowed the catalyst loading to be as low as 0.01 mol% without considerable loss in both reactivity and enantioselectivity. 

Chiral polycyclic indoles are ubiquitous and important ring systems found in many bioactive alkaloids and pharmaceuticals. Various methods have been developed for the efficient construction of the polycyclic indole derivatives. Recently, an unprecedented approach to a wide range of diverse, enantioenriched 2,3-dihydro-lH-pyrrolo[l,2-a]indoles 75 was demonstrated by Chen, Xiao, and co-workers. In the presence of 5 mol% Cu(OTf)2 and 5 mol% commercially available bisoxazoline 76 in toluene at 0 °C, the AFC alkylation/N-hemiacetalization cascade reaction of substituted indoles with P,y-unsaturated a-keto esters 74 occurred smoothly to afford products 75 in high yields with excellent diastereo- and enantioselectivity (Table 6.9). 

4-CNPh, 4-N02Ph, 4-Cp3Ph 2-CIPh, 3-BrPh, 3-CNPh, etc. 

Notably, a gram scale reaction of 3-methylindole (0.83 g, 6.3 mmol) with P,y-unsaturated a-keto ester (1.14 g, 6.0 mmol) was performed, affording the desired product in 92% yield with 91 9 dr and 99% ee. Moreover, this approach was further applied in the formal total synthesis of natural products, such as Flinderoles B and C. 

---