Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Merging Visible-Light Photoredox and Chiral Phosphate Catalysis for Asymmetric Friedel−Crafts Reaction with in Situ Generation of N‑Acyl Imines Meng-Lan Shen, Yang Shen, and Pu-Sheng Wang* Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei 230026, China
Org. Lett. Downloaded from pubs.acs.org by IDAHO STATE UNIV on 04/12/19. For personal use only.
S Supporting Information *
ABSTRACT: In the presence of visible-light photoredox and chiral phosphate catalysts, a novel asymmetric Friedel−Crafts reaction of indoles and readily accessible α-amino acid derived redox-active esters is established to afford enantioenriched 1indolyl-1-alkylamine derivatives in moderate to high yields and with high levels of enantioselectivities. This method not only shows a mild and efficient alternative for the in situ generation of N-acyl imines but also indicates the feasibility of a multicatalyst system for asymmetric photoredox catalysis.
N-Acyl imines are valuable building blocks to access versatile nitrogen-containing compounds.1 Asymmetric transformation of these compounds represents one of the fundamental issues in chiral Brønsted acid or transition-metal catalysis and hold great synthetic value.2 In particular, N-acyl aliphatic imines can easily isomerize to the corresponding N-acyl enamines; hence, considerable efforts have been devoted to the development of stable N-acyl imine precursors.1c Among them, conventionally employed precursors are α-amidosulfones3 (Scheme 1a).
mild and convenient methods to generate N-acyl imines is still of great significance in organic synthesis. In recent decades, multicatalysis has shown great potential to create unprecedented transformations.5 For example, visiblelight photoredox6 and chiral Brønsted acid combined catalysis7 are capable of generating α-aminoalkyl radicals8 for a variety of radical-mediated functionalizations.7h−j,l,m Inspired by these pioneering works, we hypothesized that α-aminoalkyl radicals,7h,m,9 generated from α-amino acids derived redoxactive esters (RAEs), might be oxidized by the corresponding oxidative photocatalyst to afford N-acyl imines. As such, these RAEs can be regard as novel N-acyl imine equivalents.10 Moreover, the employment of chiral phosphate co-catalysis may be able to capture the unstable N-acyl imines,11 providing opportunities to access new asymmetric photoredox transformations12 (Scheme 1b). Herein, we describe a novel asymmetric Friedel−Crafts reaction of indoles13 with in situ generation of N-acyl imines from α-amino acids derived RAEs by merging visible light photoredox and chiral phosphate catalysis. Our initial investigation was focused on the reaction of indole 1a and alanine-derived N-(acyloxy)phthalimide14 2a in the presence of 1 mol % Ru(bpy)3(PF6)2 (5a) and 5 mol % chiral phosphoric acid15 4a in MeCN under blue LED light (Table 1, entry 1). To our delight, the desired product 3aa was afforded in moderate yield and enantioselectivity. Then a variety of iridium photoredox catalysts16 were evaluated (entries 2−4), including Ir(ppy)3 (5b), [Ir(ppy)2(dtbbpy)](PF6) (5c), and [Ir(dF(CF3)ppy)2(dtbbpy)](PF6) (5d), and 5d turned out to be the best photoredox catalyst in terms of catalytic efficiency and control of enantioselectivity. Inspired by Ishihara’s work of chiral metal phosphate catalysis on Mannich-type reactions,2c,17 a variety of alkali and alkaline
Scheme 1. Conventional Protocols for the Synthesis of NAcylimines
These can be obtained from aldehydes, amides, and sodium benzosulfonate and easily converted into N-acylimines in the presence of bases or Lewis acids. Other stable and easily handled precursors are N-Boc aminals, which were first reported by Maruoka and co-workers.4 Although these precursors have been widely used,3b,c,4b the development of © XXXX American Chemical Society
Received: February 1, 2019
A
DOI: 10.1021/acs.orglett.9b00442 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Table 1. Optimization of Reaction Conditionsa
Scheme 2. Scope with Respect to indolesa
entry
photocatalyst 5
4
yield (%)
ee (%)
1 2 3 4 5 6 7 8b 9c 10d 11 12 13e
Ru(bpy)3(PF6)2 Ir(ppy)3 [Ir(ppy)2(dtbbpy)](PF6) [Ir(dF(CF3)ppy)2(dtbbpy)](PF6) [Ir(dF(CF3)ppy)2(dtbbpy)](PF6) [Ir(dF(CF3)ppy)2(dtbbpy)](PF6) [Ir(dF(CF3)ppy)2(dtbbpy)](PF6) [Ir(dF(CF3)ppy)2(dtbbpy)](PF6) [Ir(dF(CF3)ppy)2(dtbbpy)](PF6) [Ir(dF(CF3)ppy)2(dtbbpy)](PF6)
4a 4a 4a 4a 4b 4c 4d 4e 4f 4b 4b
54 85 91 93 85 56 41 89 94
