Catalytic Electrophilic Alkylation of p‐Quinones through a Redox Chain Reaction

Abstract

Allylation and benzylation of p-quinones was achieved through an unusual redox chain reaction. Mechanistic studies suggest that the existence of trace hydroquinone initiates ar edoxc hain reaction that consists of aL ewis acid catalyzedF riedel-Crafts alkylation and as ubsequent redox equilibrium that regenerates hydroquinone.T he electrophiles could be various allylic and benzylic esters.T he addition of Hantzsche ster as an initiator improves the efficiency of the reaction.Quinone compounds participate in many naturally occurring electron-transfer processes owing to their unique redox properties. [1] Fore xamples,u biquinone (CoQ 10 )i sa sakey component of the aerobic cellular respiration process in most eukaryotic cells; [2] and plastoquinone and phylloquinone (Vitamin K) act as electron acceptors in photosynthesis in green leaves. [3] Many natural or synthetic quinone compounds thus exhibit potent biological activities as drug candidates for targeting relevant biochemical processes. [4] Thee lectronic properties of quinone derivatives have also attracted much attention from researchers working on functional materials. [5] Theb ulk of established chemical syntheses of quinones use af unctionalization-oxidation strategy.S ubstituents are first installed on hydroquinones,p henols,o rp henyl ethers through Friedel-Crafts reactions, [6] radical reactions, [7] and transition-metal-catalyzed coupling reactions, [8] and the resulting compounds are then oxidized to quinones. [9] Functionalized hydroquinone precursors can also be obtained through nucleophilic addition [10] and cycloaddition reaction [11] of simple quinones to substituted 2-cyclohexen-1,4-dione intermediates,w hich can then rearrange to hydroquinone and be oxidized. [12] Alternatively,L ipshutz [13] and Negishi [14] developed efficient syntheses of CoQ 10 based on metalcatalyzed cross-coupling between chloromethyl-CoQ 0 and organoaluminum or organozinc reagents.R ecently emerged direct quinone functionalization methods include radical CÀ Hf unctionalization with aryl boronic acids [15] and transitionmetal-catalyzed C À Hfunctionalization with broader varieties of coupling substituents. [16] However,benzylation of quinones remains challenging.H erein, we report am ild, one-step, redox-economical [17] catalytic allylation and benzylation of pquinones and the study of its unique mechanism, in which allyl and benzyl esters serve as the electrophiles and quinones are the formal "nucleophiles" (Scheme 1).

Few layer 2D pnictogens catalyze the alkylation of soft nucleophiles with esters

“…Nature makes use of alkyl phosphates, sulphonates, and esters as alkylating agents, under metal-free physiological conditions 10,11 . In contrast, synthetic methods generally employ energetically higher alkyl halides and alcohols as alkylating agents under very strong basic or acidic conditions (i.e., Williamson synthesis) 12 , and the synthetic alkylation protocols reported with poly-oxygenated compounds need expensive and toxic metal catalysts, such as the palladium-catalyzed Tsuji–Trost allylation reaction 13 , the Hantzsch ester-assisted hafnium-catalyzed alkylation of quinones 14 , and the gold-catalyzed alkylation with alkynylbenzoic acids 15 , among some others 16,17 . Thus, the discovery of a simple, metal-free, biomimetic alkylation reaction with readily available poly-oxygenated molecules 18 remains a challenge in organic synthesis and catalysis, furthermore attractive if selective and functional-group tolerant 19,20 .…”

Learning To Predict Reaction Conditions: Relationships between Solvent, Molecular Structure, and Catalyst

“…Since the labels are available, accuracy of the computer and chemist can be evaluated on this subset, while for the 9 unlabeled points, “accuracy” is much more qualitative and will be discussed in the subsequent paragraph. In the labeled subset the computer’s first solvent choice matched the label in 9 occurrences (via the kNN algorithm), giving correct predictions of dichloromethane 3 times, − water 3 times, − dichloroethane 1 time, and chloroform 2 times. , The second choice of the computer matched the Reaxys entry twice for dichloroethane and once for water. The chemists, however, performed at a lower success rate than the computer: an average of 2 matches per chemist was found with the 17 solvent labels.…”

Lewis Acid/Hexafluoroisopropanol: A Promoter System for Selective ortho-C-Alkylation of Anilines with Deactivated Styrene Derivatives and Unactivated Alkenes

“…Of note, quinoline and acridine are unreactive under our standard conditions. In the same vein, because the benzylation of quinone is challenging, 30 we used our strategy as a relay to access such type of products (6 in 86% yield) through the oxidation of 3ag in the presence of cerium ammonium nitrate (CAN). Moreover, the primary aniline 7 could be obtained by reduction of 3fa in 93% yield, 31 while it could not be accessed starting from 4-aminostyrene 1zc.…”