Diastereoselective Friedel−Crafts Alkylation of Indoles with Chiral α-Phenyl Benzylic Cations. Asymmetric Synthesis of Anti-1,1,2-Triarylalkanes

Abstract

The reactions of chiral benzyl carbocations bearing alpha-phenyl substituents with N-sulfonylated indoles afford 1,1,2-triarylalkanes with anti-selectivities. This outcome is a reversal of facial diastereoselectivity relative to Bach's alpha-alkyl-bearing benzyl cations. The reactions are promoted by either a Brønsted acid (TFA) or Lewis acid (BF3.OEt2), offering differential diastereoselectivities and reactivities. The electronic properties of both reacting partners strongly influence the reaction rates and the product diastereoselectivities and appear to operate under kinetic control. This chemistry provides an efficient access to sterically congested tetrasubstituted ethanes.

Role of Free Space and Conformational Control on Photoproduct Selectivity of Optically Pure α-Alkyldeoxybenzoins within a Water-Soluble Organic Capsule

“…25 As expected, the synthesized ADBs ((R)-1) gave a single peak upon analysis by HPLC (Chiralpak ADH, hexane/2-propanol 98:2, 0.35 mL/min, T = 25°C, λ = 254 nm) as opposed to the racemic ADBs (1) with two peaks ( Figure S1, Supporting Information). As shown in Scheme 4, optically pure (R,R)-diastereomer (8) was prepared by asymmetric hydrogenation reaction via dynamic kinetic resolution with excellent enantio-and diastereoselectivities by using the chiral catalyst (RuCl 2 [(S)-(DM-SEGPHOS)][(S)-DAIPEN]).…”

“…16 Racemic as well as chiral guest molecules (1a−d) were prepared by adopting the procedure detailed below. 25 General Synthetic Protocol for Chiral α-Alkyl Deoxybenzoin. Synthesis of 1.…”

“…24,25 Similar to α-alkyl dibenzyl ketones, these deoxybenzoins are established to undergo both Type I and Type II reactions (Scheme 3) from excited triplet state. 26,27 By HPLC monitoring of the racemization of photoexcited optically pure 1a−d we have established the cage recombination of the primary radical pair to yield the starting ketone within the OA capsule regardless of the alkyl chain.…”

Stereoselective Reactions with Stabilized Carbocations

“…al have developed a highly diastereoselective reaction to solve a synthetic problem connected to the development of a drug containing a 1,1,2-triarylalkane fragment, which was achieved by the addition of indole to a benzylic carbocation (Scheme 3). [14] The reaction was carried out on optically active chiral benzylic alcohol 3 obtained by asymmetric hydrogenation through a dynamic kinetic resolution. The alcohols were subjected to an intermolecular Friedel-Crafts reaction with tosyl-protected indole.…”

Chemoselective S-benzylation of indoline-2-thiones using benzyl alcohols

“…The BF 3 etherate-catalyzed C-benzylation using benzyl alcohols are known to proceed via a carbocation intermediate. 25 The involvement of benzyl carbocations appears most plausible in S-benzylation of indoline-2-thiones. The Lewis acid BF 3 etherate upon reaction with benzyl alcohol leads to the resonance-stabilized benzyl carbocation intermediate.…”