Radical borylation using N‐heterocyclic carbene (NHC)‐BH3 complexes as boryl radical precursors has emerged as an important synthetic tool for organoboron assembly. However, the majority of reported ...methods are limited to reaction modes involving carbo‐ and/or hydroboration of specific alkenes and alkynes. Moreover, the generation of NHC‐boryl radicals relies principally on hydrogen atom ion with the aid of radical initiators. A distinct radical generation method is reported, as well as the reaction pathways of NHC‐boryl radicals enabled by photoredox catalysis. NHC‐boryl radicals are generated via a single‐electron oxidation and subsequently undergo cross‐coupling with the in‐situ‐generated radical anions to yield gem‐difluoroallylboronates. A photoredox‐catalyzed radical arylboration reaction of alkenes was achieved using cyanoarenes as arylating components from which elaborated organoborons were accessed. Mechanistic studies verified the oxidative formation of NHC‐boryl radicals through a single‐electron‐transfer pathway.
NHC‐boryl radicals are generated by single‐electron oxidation of NHC‐BH3 complexes using a photoredox catalytic system. New reaction modes of NHC‐boryl radicals were determined for the facile synthesis of highly elaborated organoboron molecules. Key: N‐heterocyclic carbene (NHC), leaving group (LG).
Defluorinative functionalization of readily accessible trifluoromethyl groups constitutes an economical route to partially fluorinated molecules. However, the controllable replacement of one or two ...fluorine atoms while maintaining high chemoselectivity remains a formidable challenge. Here we describe a general strategy for sequential carbon-fluorine (C-F) bond functionalizations of trifluoroacetamides and trifluoroacetates. The reaction begins with the activation of a carbonyl oxygen atom by a 4-dimethylaminopyridine-boryl radical, followed by a spin-center shift to trigger the C-F bond scission. A chemoselectivity-controllable two-stage process enables sequential generation of difluoro- and monofluoroalkyl radicals, which are selectively functionalized with different radical traps to afford diverse fluorinated products. The reaction mechanism and the origin of chemoselectivity were established by experimental and computational approaches.
Organoboron compounds are highly valuable in synthetic chemistry. In particular, α-borylcarbonyl compounds have shown versatile synthetic applications, owing to fruitful chemistries of both the boryl ...and carbonyl moieties. However, the synthesis of these molecules still remains tedious and time-consuming. Here we report a straightforward and practical route to synthesize α-borylcarbonyl molecules based on a regioselective radical α-borylation of α,β-unsaturated carbonyl compounds. The reaction features unusual α-regioselectivity and high functional-group compatibility. Further synthetic applications of new α-borylated products were also demonstrated. DFT and kinetic studies implicated that the α-regioselectivity of β-aryl-α,β-unsaturated carbonyl compounds was determined by the thermodynamically more favorable radical α-addition step, whereas the formation of α-addition products from β-alkyl-α,β-unsaturated carbonyl compounds was driven by an energetically favored hydrogen atom transfer step. Given that α,β-unsaturated carbonyl compounds can be easily obtained in abundance and variety, this method enjoys great advantages in diverse and economical synthesis of valuable α-borylcarbonyl molecules.
A new and practical α‐monomethylation strategy using an amine‐borane/N,N‐dimethylformamide (R3N‐BH3/DMF) system as the methyl source was developed. This protocol has been found to be effective in the ...α‐monomethylation of arylacetonitriles and arylacetamides. Mechanistic studies revealed that the formyl group of DMF delivered the carbon and one hydrogen atoms of the methyl group, and R3N‐BH3 donated the remaining two hydrogen atoms. Such a unique reaction pathway enabled controllable assemblies of CDH2‐, CD2H‐, and CD3‐ units using Me2NH‐BH3/d7‐DMF, Me3N‐BD3/DMF and Me3N‐BD3/d7‐DMF systems, respectively. Further application of this method to the facile synthesis of anti‐inflammatory flurbiprofen and its varied deuterium‐labeled derivatives was demonstrated.
Selective monomethylation: An unprecedented and practical methylation protocol using a R3N‐BH3/DMF system as the methyl source has been developed for the selective α‐monomethylation of arylacetonitriles and arylacetamides. The formyl group of DMF delivers the carbon and one hydrogen atoms of the methyl group, and R3N‐BH3 donates the remaining two hydrogen atoms.
A method for the synthesis of amide‐containing molecules was developed using vinyl azides as an enamine‐type nucleophile towards carbon electrophiles, such as imines, aldehydes, and carbocations that ...were generated from alcohols in the presence of BF3⋅OEt2. After nucleophilic attack of the vinyl azide, a substituent of the resulting iminodiazonium ion intermediate migrates to form a nitrilium ion, which is hydrolyzed to afford the corresponding amide.
Nitrilium intermediate: A new method for amide synthesis employs vinyl azides as enamine‐type nucleophiles towards carbon electrophiles in the presence of BF3⋅OEt2. After nucleophilic attack of the vinyl azide, a substituent of the resulting iminodiazonium ion intermediate A migrates to form nitrilium ion B, which is hydrolyzed to afford the corresponding amide.
Radical cascade reactions are powerful tools to construct structurally complex molecules. However, the stereochemical control of acyclic radical intermediates remains a persistent challenge, due to ...the low differentiation between the two faces of these species. This hurdle further makes stereodivergent synthesis rather more difficult to be accomplished, in particular for intermediates resulted from complex cascades. Here we report an efficient strategy for stereoselective hydrogen atom transfer (HAT) to acyclic carbon radicals, which are generated via N-heterocyclic carbene (NHC)-boryl radicals triggered addition-translocation-cyclization cascades. A synergistic control by the NHC subunit and a thiol catalyst has proved effective for one facial HAT, while a ZnI
-chelation protocol allows for the preferential reaction to the opposite face. Such a stereoselectivity switch enables diastereodivergent construction of heterocycles tethering a boron-substituted stereocenter. Mechanistic studies suggest two complementary ways to tune HAT diastereoselectivity. The stereospecific conversions of the resulting boron-handled products to diverse functionalized molecules are demonstrated.
Cascade radical cyclization constitutes an atom‐ and step‐economic route for rapid assembly of polycyclic molecular skeletons. Although an array of redox‐active metal catalysts has recently shown ...robust applications in enabling various catalytic cascade radical processes, the use of free organic radical as the catalyst, which is capable of triggering strategically distinct cascades, has rarely been developed. Here, we disclosed that the benzimidazolium‐based N‐heterocyclic carbene (NHC)‐boryl radical is capable of catalyzing cascade cyclization reactions in both intra‐ and intermolecular pathways, assembling 5,5 fused bicyclic and 6,6,6 fused tricyclic molecules, respectively. The catalytic reactions start with the chemo‐ and regioselective addition of the boryl radical catalyst to a tethered alkene or alkyne moiety, followed by either an intramolecular formal 3+2 or an intermolecular 2+2+2 cycloaddition process to construct bicyclo3.3.0octane or tetrahydrophenanthridine skeletons, respectively. Eventually, a β‐elimination occurs to release the boryl radical catalyst, completing a catalytic cycle. High to excellent diastereoselectivity is achieved in both catalytic reactions under substrate control.
Benzimidazolium‐based N‐heterocyclic carbene (NHC)‐boryl radical catalyzes cascade cyclization reactions to construct polycyclic compounds both intra‐ and intermolecularly. This catalytic cascade radical reaction allows rapid construction of complex molecular architectures through the formation of two or three bonds in a single operation, respectively.
A synthetic method to construct boron-handled cyclic molecules was developed based on a radical borylation/cyclization cascade of 1,6-enynes. The process was initiated by the chemo- and ...regio-controlled addition of an N-heterocyclic carbene–boryl radical to an alkene or alkyne, followed by ring closure to afford boron-substituted cyclic skeletons. Further molecular transformations of the cyclic products to synthetically useful building blocks were also demonstrated.
Branched selectivity in asymmetric allylic C−H alkylation is enabled by using 2‐acylimidazoles as nucleophiles in the presence of a chiral phosphoramidite‐palladium catalyst. A wide range of terminal ...alkenes, including 1,4‐dienes and allylarenes, are nicely tolerated and provide chiral 2‐acylimidazoles in moderate to high yields and with high levels of regio‐, and enantio‐, and E/Z‐selectivities. Mechanistic studies using density‐functional theory calculations suggest a nucleophile‐coordination‐enabled inner‐sphere attack mode for the enantioselective carbon–carbon bond‐forming event.
Branching out: Palladium‐chiral phosphoramidite catalysis is used for an unprecedented branched‐selective asymmetric allylic C−H alkylation by using 2‐acylimidazoles as model coordinating nucleophiles. Density‐functional theory calculations suggest an unusual inner‐sphere mechanism for the carbon–carbon bond‐forming process.
Mono and dichloro‐substituted organic molecules are shown to possess significant roles in various fields, especially in medicinal chemistry. One approach to synthesizing these compounds involves the ...selective dechlorination of easily prepared trichloromethyl compounds. Nevertheless, developing a practical approach that allows selective mono‐ and dihydrodechlorination is a challenging task. Herein, we introduced a method for selective mono‐ and dihydrodechlorination of trichloroacetamides and acetates which was promoted by two different Lewis base‐boryl radicals. Accordingly, 4‐dimethylaminopyridine (DMAP)‐borane enabled mono‐substitution of chlorine atom by hydrogen while dihydro‐substitution of chlorine atoms was promoted by N‐heterocyclic carbene (NHC)‐boryl radical. Using deuterated Lewis base‐borane as deuterium atom source, mono‐ and dideuterodechlorination were also successfully took place. This protocol features broad substrate scope and operates under mild reaction conditions.
4‐Dimethylaminopyridine (DMAP)‐ and N‐heterocyclic carbene (NHC)‐boryl radicals were found to promote selective mono‐ or dihydrodechlorination of trichloroacetamides and acetates upon treatment with dilauroyl peroxide (DLP) as radical initiator and thiophenol as polarity reversal catalyst. Substituting the hydrogen atom donor, i. e. Lewis base‐borane, to its deuterated counterparts promoted mono‐ or dideuterodechlorination instead.
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