Analysis Of Indole 3a

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Our initial investigation of the asymmetric Mannich reaction of indole 2a with phenyl α-amidosulfone 3a is summarized in Table 1. The effect of catalyst structure on the reaction outcome was first investigated at 10 mol% catalyst loading in toluene (Table 1, Entries 1–5). As we expected, based on our knowledge of the catalytic performance of chiral oligoEG 1,[7] the ether chain length (Entries 1–3) as well as suitable acidity of the phenolic protons (Entry 2 vs. Entries 4 and 5) are critical for the catalytic performance in this reaction. Consistently, catalyst 1b bearing iodine atom at the 3 and 3′ positions of the binaphthyl scaffold showed the best results in terms of catalytic activity (70% yield) and enantioselectivity (98% ee) (Entry …show more content…
Optimization of the BINOL-based polyether catalyzed asymmetric Friedel-Crafts (FC) reactions of indole [a]

Entry Catalyst Indole 2a (equiv.) Solvent Yield (%)[b] ee (%)[c]
1 (R)-1a 1.0 Toluene 68 61
2 (R)-1b 1.0 Toluene 70 98
3 (R)-1c 1.0 Toluene 59
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This catalytic condition was found to be general with α-amido sulfones 3 bearing different substituents (Scheme 2). Regardless of the electronic and steric nature of the substituents on the aromatic ring, all α-amido sulfones 3 as the imine precursors tested in this study smoothly converted to the corresponding Friedel-Crafts products 4a–4p with high yields and excellent ees after 12 h. Notably, the sterically demanding 1-naphthyl substituted amido sulfone 3b also smoothly converted to the corresponding Friedel-Crafts product 3b in 98% yield with 99% ee. Heteroaromatic substrates such as 2-furanyl (3l) and 3-thienyl (3m) also afforded almost quantitative yields and excellent ees. In addition, various aliphatic substrates 3n–3p were also explored for this reaction. To our delight, the reaction turned out to be highly tolerant to the ene-carbamate[10] formation, and essentially all the investigated alkyl chain substituted substrates including highly challenging primary alkyl substituted substrates afforded good to excellent chemical yields and enantioselectivities (see 4n–4p in Scheme 2). Furthermore, as shown in Scheme 3, this reaction was also found to be very general with respect to

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