Enantiospecific Trifluoromethyl‐Radical‐Induced Three‐Component Coupling of Boronic Esters with Furans

Abstract

In the presence of trifluoromethylsulfonium reagents, boronate complexes derived from 2‐lithio furan and non‐racemic secondary and tertiary alkyl or aryl boronic esters undergo deborylative three‐component coupling to give the corresponding 2,5‐disubstituted furans with excellent levels of enantiospecificity. The process proceeds via the reaction of boronate complexes with a trifluoromethyl radical, which triggers 1,2‐metallate rearrangement upon single‐electron oxidation. Alternative electrophiles can also be used in place of trifluoromethylsulfonium reagents to effect similar three‐component coupling reactions.

Enantiospecific Three‐Component Alkylation of Furan and Indole

“…3 , Scheme a) . Furthermore, inspired by the intriguing reactivity of unsaturated boronate complexes, we showed that nucleophilic furyl‐derived boronate complexes 2 react with electrophiles in an enantiospecific three‐component coupling reaction (leading to 4 , Scheme a) . Key to the success of this process was the use of highly activated electrophiles, such as the Umemoto trifleoromethylating agent or carbocationic species.…”

“…[3] Furthermore,i nspired by the intriguing reactivity of unsaturated boronate complexes, [4] we showed that nucleophilic furyl-derived boronate complexes 2 react with electrophilesi na n enantiospecific three-componentc oupling reaction (leading to 4,S cheme1a). [5] Key to the success of this process was the use of highly activated electrophiles, such as the Umemoto trifleoromethylating agent [6] or carbocationic species. Interestingly, the trifluoromethylation reaction was found to proceed through as elf-initiated radical chain mechanism.I ndependently,S tudera nd our group have shown that electrophilic radicals add to vinyl boronate complexes 5 (Scheme 1b).…”

“…However,i nc ontrol experiments we found that neither light nor the photocatalyst were required for the transformation. Furthermore, addition of the radicalinhibitor 1,1-diphenylethylene [7a] had no effect on the reaction outcome (see Supporting Information-3.5 for details), ruling out ap ossible electrontransfer initiated radicalc hain process [5] and supportingapolar S N 2-like pathway.T he nucleophilic reactivity of indole-derived borates generated from difficult-to-handle trialkyl boranes has been described, [18] however the difficulties in accessing enantioenriched chiral boranes has prevented the use of this methodology for the synthesis of chiral compounds in enantioenriched form. Surprisingly,r eactions of boronates derived from stable boronic esters are rare with only as ingle reportv ery recently disclosed by Ready et al (with p-allyl palladium complexes).…”

DFT Study on the Gold(I)‐Catalyzed Dehydrogenative Heterocyclization of 2‐(1‐Alkynyl)‐2‐alken‐1‐ones to form 2,3‐Furan‐Fused Carbocycles: Effects of Additives C5H5NO vs. PhNO

“…Furans can not only be used as key structural units in a number of biological active natural products, pharmaceuticals, and agrochemicals, but can also act as important precursors in the synthesis of acyclic, carbocyclic, and heterocyclic compounds . Owing to the reasons above, the substituted furans have played a crucial role in catalytic synthesis reactions in recent decades.…”

Synthesis of α‐Chiral Ketones and Chiral Alkanes Using Radical Polar Crossover Reactions of Vinyl Boron Ate Complexes

“…[4] Aggarwal et al further demonstrated that boron ate complexes of enantioenriched alkylboronic esters and furan-2-yllithium undergo stereospecific 1,2-metalate rearrangements in the reaction with the trifluoromethyl radical. [5] Importantly,s uch chiral secondary boronic esters are readily accessed by hydroboration, [6] by the Matteson approach, [7] and by reaction of boronic esters with Hoppese nantioselectively lithiated carbamates. [8] We considered using in situ generated vinyl boron ate complexes VI,derived from enantioenriched boronic esters V and vinyllithium, in ar adical polar crossover reaction with various alkyl iodides and report herein that this key transformation followed by oxidation offers anew route to a-chiral ketones.S uch chiral moieties are widespread in natural products and the development of synthetic routes to access enantioenriched a,a-disubstituted ketones is therefore of great importance.A lthough many protocols for auxiliarycontrolled asymmetric enolate reactions have been developed over the last decades, [9] the direct asymmetric alkylation of ketones is still highly challenging [10] and mostly transitionmetal catalysts are required.…”