Advances in Catalytic Asymmetric Dearomatization

Abstract

Asymmetric catalysis has been recognized as the most enabling strategy for accessing chiral molecules in enantioenriched forms. Catalytic asymmetric dearomatization is an emerging and dynamic research subject in asymmetric catalysis, which has received considerable attention in recent years. The direct transformations from readily available aromatic feedstocks to structurally diverse three-dimensional polycyclic molecules make catalytic asymmetric dearomatization reactions of broad interest for both organic synthesis and medicinal chemistry. However, the inherent difficulty for the disruption of aromaticity demands a large energy input during the dearomatization process, which might be incompatible with the conditions generally required by asymmetric catalysis. In this Outlook, we will discuss representative strategies and examples of catalytic asymmetric dearomatization reactions of various aromatic compounds and try to convince readers that by overcoming the above obstacles, catalytic asymmetric dearomatization reactions could advance chemical sciences in many respects.

Enantioselective one-carbon expansion of aromatic rings by simultaneous formation and chromoselective irradiation of a transient coloured enolate

“…12 Recent progress in asymmetric photochemical reactions has mainly focused on [2 + 2] cycloadditions and [1,3]migration reactions; 13 much rarer are enantioselective [1,7]sigmatropic rearrangements. 14 Dearomatizing reactions are an important way of introducing complexity into cyclic systems, 15 and an alternative approach to the construction of cycloheptatrienes entails photochemical ring expansion of lithiated N-benzylbenzamides. 16 We previously noted (Scheme 1c) that dearomatized enolates undergo photochemical rearrangement to cycloheptatrienes on irradiation with a 500 W halogen lamp, but enantioselective variants of this reaction were limited to stereospecic transformations of chiral precursors.…”

Post-spin crossing dynamics determine the regioselectivity in open-shell singlet biradical recombination

“…Recently, we discovered an extraordinary regioselective intramolecular recombination of open-shell singlet biradical species. In line with our ongoing program on visible-light-induced dearomatization reactions, 9–11 we have developed an intramolecular [5 + 2] cycloaddition of indole-tethered vinylcyclopropanes (VCPs) (Fig. 1b).…”

Asymmetric Dearomative (3+2)-Cycloaddition Involving Nitro-Substituted Benzoheteroarenes under H-Bonding Catalysis

“…Catalytic asymmetric dearomatization (CADA) reactions constitute popular strategies for the synthesis of complex natural products, biologically active compounds, and pharmaceuticals from readily available aromatic molecules [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Despite their high synthetic potential, challenges related to the control of the regio- and stereo-selectivity of these processes, while overcoming the loss of aromaticity, still constitute an important issue.…”