SPINOL-Derived Phosphoric Acids: Synthesis and Application in Enantioselective Friedel−Crafts Reaction of Indoles with Imines

Abstract

A new class of chiral phosphoric acids with spirobiindane as scaffold were conveniently synthesized from (S)-1,1'-spirobiindane-7,7'-diol ((S)-SPINOL) and employed to catalyze the asymmetric Friedel-Crafts reaction of indoles with imines to afford 3-indolyl methanamines. High yields (68-97%) and excellent enantioselectivities (up to 99% ee) were obtained.

Highly Enantioselective Pictet–Spengler Reaction Catalyzed by SPINOL‐Phosphoric Acids

“…As shown in Table 1, the sterically congested SPINOL-phosphoric acids were found to be crucial for a high activity and enantioselectivity. Interestingly, catalyst 1 f, which gave excellent enantioselectivities in our previous report, [5] also was the best catalyst for the present reaction, affording tetrahydro-b-carboline 5 a in 96 % yield with 98 % ee (Table 1, entry 6). However, BINOL-phosphoric acids 2 a and b gave low yields with poor enantioselectivities in this model reaction (Table 1, entries 7 and 8).…”

“…[5] In our initial experiments, we found that these chiral SPINOLphosphoric acids nicely promote the asymmetric FriedelCrafts reaction of various indoles with a range of imines, giving comparable results to BINOL-phosphoric acids. List et al independently reported a highly enantioselective kinetic resolution of homoaldols through a transacetalization reaction by using this novel class of chiral phosphoric acids.…”

Selecting Chiral BINOL‐Derived Phosphoric Acid Catalysts: General Model To Identify Steric Features Essential for Enantioselectivity

“…If the Z configuration is energetically inaccessible the reaction proceeds via a Type I  E pathway, the correct catalyst has large proximal and medium AREA(θ) 10, 11, 12, 13c, 14b, 19, 20, 21, 22, 40, 41, 42, 43, 44, 45, 46, 47. However, reactions involving displaced nucleophiles the best choice of catalyst has large proximal and small AREA(θ) 5, 8, 9, 30, 31, 48, 49, 50, 51, 52, 53. Higher enantioselectivities with small proximal bulk catalysts are not uncommon with displaced nucleophiles.…”

A New Methodology for Functionalization at the 3-Position of Indoles by a Combination of Boron Lewis Acid with Nitriles

“…[28][29][30] Moreover, Friedel-Crafts alkylation of indole with N-tosylaldimine to form a compound similar to 4 in the presence of a Brønsted acid has been reported. [31][32][33][34][35] However, these synthetic methods are limited, we are convinced that our reaction using a nitrile is worth studying. This work, as well as the acylation described in Tables 2-4, began synthesizing an electrophilic substitution reaction by a combination of a variety of indoles and various nitriles to result in the iminium intermediate (2).…”