Abstract
Catalytic asymmetric [2 + 4] cycloadditions of 3-vinylindoles with ortho-quinone methides and their precursors were carried out in the presence of chiral phosphoric acid to afford a series of indole-containing chroman derivatives with structural diversity in overall high yields (up to 98%), good diastereoselectivities (up to 93:7 dr) and moderate to excellent enantioselectivities (up to 98% ee). This approach not only enriches the chemistry of catalytic asymmetric cycloadditions involving 3-vinylindoles but is also useful for synthesizing chiral chroman derivatives.
Highlights
Chiral indole derivatives are ubiquitous in biologically important natural products, 1
3-vinylindole 1a was reacted with sesamol-derived ortho-quinone methides (o-QMs) 2a in the presence of chiral phosphoric acid [36–44] (CPA) (R)4a at 25 ◦ C in toluene (Table 1, entry 1)
The CPA (R)-4c bearing two bulky 3,30 -(1-naphthyl) groups facilitated the [2 + 4] cycloaddition with the highest enantioselectivity of 66% ee among the investigated catalysts, which could be ascribed to the steric hindrance effect of the 3,30 -disubstituents of CPA in creating a chiral environment for controlling the enantioselectivity [64,65]
Summary
Chiral indole derivatives are ubiquitous in biologically important natural products, 1. To fulfill this task and in continuation of our ongoing efforts in the enantioselective synthesis of indole-based chiral heterocycles [32,33,34,35], we designed a chiral phosphoric acid [36,37,38,39,40,41,42,43,44] (CPA)-catalyzed asymmetric [2 + 4] cycloaddition of 3-vinylindoles with ortho-quinone methides (o-QMs) and their precursors (Figure 4).
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