二卤环丙烷偶联

No abstract available

ConspectusTransition-metal-catalyzed reductive coupling of electrophiles has emerged as a powerful tool for the construction of molecules. While major achievements have been made in the field of cross-couplings between organic halides and pseudohalides, an increasing number of reports demonstrates reactions involving more readily available, low-cost, and stable, but unreactive electrophiles. This account summarizes the recent results in our laboratory focusing on this topic. These findings typically include deoxygenative C-C coupling of alcohols, reductive alkylation of alkenyl acetates, reductive C-Si coupling of chlorosilanes, and reductive C-Ge coupling of chlorogermanes.The reductive deoxygenative coupling of alcohols with electrophiles is synthetically appealing, but the potential of this chemistry remains to be disclosed. Our initial study focused on the reaction of allylic alcohols and aryl bromides by the combination of nickel and Lewis acid catalysis. This method offers a selectivity that is opposite to that of the classic Tsuji-Trost reactions. Further investigation on the reaction of benzylic alcohols led to the foundation of a dynamic kinetic cross-coupling strategy with applications in the nickel-catalyzed reductive arylation of benzylic alcohols and cobalt-catalyzed enantiospecific reductive alkenylation of allylic alcohols. The titanium catalysis was later established to produce carbon radicals directly from unactivated tertiary alcohols via C-OH cleavage. The development of their coupling reactions with carbon fragments delivers new methods for the construction of all-carbon quaternary centers. These reactions have shown high selectivity for the functionalization of tertiary alcohols, leaving primary and secondary alcohols intact. Alkenyl acetates are inexpensive, stable, and environmentally friendly and are considered the most attractive alkenyl reagents. The development of reductive alkylation of alkenyl acetates with benzyl ammoniums and alkyl bromides offers mild approaches for the conversion of ketones into aliphatic alkenes.Extensive studies in this field have enabled us to extend the cross-electrophile coupling from carbon to silicon and germanium chemistry. These reactions harness the ready availability of chlorosilanes and chlorogermanes but suffer from the challenge of their low reactivity toward transition metals. Under reductive nickel catalysis, a broad range of alkenyl and aryl electrophiles couple well with vinyl- and hydrochlorosilanes. The use of alkyl halides as coupling partners led to the formation of functionalized alkylsilanes. The C-Ge coupling seems less substrate-dependent, and various common chlorogermanes couple well with aryl, alkenyl, and alkyl electrophiles. In general, functionalities such as Grignard-sensitive groups (e.g., acid, amide, alcohol, ketone, and ester), acid-sensitive groups (e.g., ketal and THP protection), alkyl fluoride and chloride, aryl bromide, alkyl tosylate and mesylate, silyl ether, and amine are tolerated. These methods provide new access to organosilicon and organogermanium compounds, some of which are challenging to obtain otherwise.

Nickel-catalyzed reductive cross-coupling reactions have emerged as powerful methods to join two electrophiles. These reactions have proven particularly useful for the coupling of sec-alkyl electrophiles to form stereogenic centers; however, the development of enantioselective variants remains challenging. In this Perspective, we summarize the progress that has been made toward Ni-catalyzed enantioselective reductive cross-coupling reactions.

The union of photoredox and nickel catalysis has resulted in a renaissance in radical chemistry as well as in the use of nickel-catalyzed transformations, specifically for carbon-carbon bond formation. Collectively, these advances address the longstanding challenge of late-stage cross-coupling of functionalized alkyl fragments. Empowered by the notion that photocatalytically generated alkyl radicals readily undergo capture by Ni complexes, wholly new feedstocks for cross-coupling have been realized. Herein, we highlight recent developments in several types of alkyl cross-couplings that are accessible exclusively through this approach.

We report an efficient palladium-catalyzed ring-opening defluorinative Hiyama cross-coupling of gem-difluorocyclopropanes with structurally diverse (hetero)arylsilanes through C-C bond activation and C-F bond cleavage. This regioselective ring-opening defluorinative Hiyama cross-coupling features a broad substrate scope with excellent functional group compatibility, affording a diverse variety of linear 2-fluoroallylic scaffolds in good yields with high Z-selectivity.

This study introduces an efficacious palladium-catalyzed method for the regioselective and stereoselective cross-coupling of gem-difluorinated cyclopropanes with an array of gem-diborylalkanes under mild reaction conditions. The innovative methodology facilitates the synthesis of 2-fluoroallylic gem-diboronic esters with exceptional Z-stereo- and chemo-selectivity. Notably, this protocol extended to the ligand-modulated regio- and stereoselectivity divergence cross-coupling of 1,1-difluoro-2-vinylcyclopropane as a reaction partner. Furthermore, we explore further transformations of the fluorinated gem-diboronates, encompassing the oxidation to form ketone and hydrogenation to generate mono-fluorinated alkylated gem-diboronate.

A palladium-catalyzed cascade coupling/retro-Claisen reaction of CF3-substituted β-diketones with readily available gem-difluorocyclopropanes has been developed. This methodology allows for the expedient synthesis of γ-fluorinated γ,δ-unsaturated ketones in a one-pot procedure with a broad scope and good to excellent yields.

No abstract available

No abstract available

We herein report the development of a novel Pd/Ni dual-catalyzed ring-opening functionalization of gem-difluorinated cyclopropanes (gem-F2CPs) with azaaryl acetates. This bimetallic catalytic strategy streamlines the diversity-oriented synthesis (DOS) of α-quaternary 2-fluoroallylic azaaryl acetates with features of a broad scope and excellent functional group tolerance, which enables the efficient late-stage transformation of natural product-derived gem-F2CPs. The resulting α-quaternary azaaryl acetates could serve as a valuable platform to prepare other different fluoroallylic azaaryl scaffolds.

This study presents a novel method for the regioselective coupling of gem-difluorinated cyclopropanes with gem-diborylmethane, utilizing a Pd-catalyst system. This innovative approach enables the synthesis of 2-fluoroalkenyl monoboronate scaffolds with high Z-selectivity. The resulting products undergo further transformations, including oxidation, Suzuki cross-coupling, and trifluoroborylation, all of which are achieved with good yields. This work introduces a valuable synthetic pathway to access important fluorinated compounds for various applications in organic chemistry.

The construction of all-carbon quaternary centers in small-ring systems is important but challenging in organic synthesis. Herein, by taking gem-difluorocyclopropyl bromides (DFCBs) as a type of general and versatile building block, we developed a practical method for building all-carbon quaternary centers in gem-difluorinated cyclopropanes (DFCs). The reaction relies on the involvement of a gem-difluorocyclopropyl radical intermediate, which can couple with a wide range of nucleophiles under copper catalysis.

gem-Difluorinated cyclopropanes have attracted wide research interest in organic synthesis due to their high reactivity. Herein, we report a Lewis acid-catalyzed cross-coupling reaction of mono- and disubstituted gem-difluorinated cyclopropanes with nucleophiles. The formation of a fluoroallyl cation species triggered via the Lewis acid-assisted activation of the C-F bond is proposed in this transformation. The cation species is then trapped by the nucleophiles, including electron-rich arenes and allylsilanes, to deliver a series of fluoroallylic products in good yields. The reaction provides an alternative mode for using gem-difluorinated cyclopropanes as fluoroallyl surrogates.

The control of linear/branched selectivity is one of the major focuses in transition-metal catalyzed allyl–allyl cross-coupling reactions, in which bond connection occurs at the terminal site of both the allyl fragments forming different types of 1,5-dienes. Herein, terminal/internal regioselectivity is investigated and found to be switchable in allyl–allyl cross-coupling reactions between gem-difluorinated cyclopropanes and allylboronates. The controlled terminal/internal regioselectivity arises from the fine-tuning of the rhodium catalytic system. Fluorinated 1,3-dienes, 1,4-dienes and 1,5-dienes are therefore produced in good yields with respectively isomerized terminal, internal, and terminal regioselectivity.

In this paper, we describe a new type of cross-coupling between simple diazo and vinyldiazo compounds that gives access to unusual allyldiazo products. Blue light discriminates two diazo compounds towards free carbene formation, triggering sequential cyclopropenation, (3+2) cycloaddition and ring opening rearrangement processes. This strategy involves an overall reshuffle of diazo functionality and olefinic carbons of vinyldiazo compounds with an extrusion of nitrogen. Mechanistic studies including a 15N-labelling experiment demonstrate that the diazo functionality of allyldiazo products derives from simple diazo compounds, while vinyldiazo reagents are selectively decomposed via energy transfer with thioxanthone photocatalyst. The obtained allyldiazo compounds can be efficiently converted into synthetically useful structures such as 1,3-dienes, gem-difluoro-1,4-diene, hydrazine, dihydropyrazole, pyridazine, and bicyclobutane.

Monofluoroalkene scaffolds are frequently found in various functional molecules. Herein, we report a Pd-IHept-catalyzed (NHC = N-heterocyclic carbene) defluorinative functionalization approach for the synthesis of monofluoroalkenes from gem-difluorocyclopropanes and malonates. The flexible yet sterically hindered N,N'-bis(2,6-di(4-heptyl)phenyl)imidazol-2-ylidene ligand plays a key role in ensuring the high reaction efficiency. In addition, sterically hindered 1,1- and 1,2-disubstituted gem-difluorocyclopropanes could also be used in this transformation.

Functionalized monofluoroalkenes (3‐arylated and 5‐oxygenated 1‐aryloxy‐2‐fluoro‐1‐alkenes) are synthesized via selective activation of the CF bonds in 2‐aryloxy‐1,1‐difluorocyclopropanes that are readily prepared from aryl vinyl ethers. Treatment of these difluorocyclopropanes with Me2AlCl promotes fluoride abstraction followed by cyclopropane ring opening to generate α,β‐unsaturated oxocarbenium ions. These cations are subsequently trapped with nucleophiles, such as arenes and silyl enol ethers (Friedel–Crafts‐ and aldol‐type reactions), to provide functionalized 2‐fluoro‐1‐alkenes. Because of the instability of vinyl cations, further fluoride abstraction is suppressed, resulting in completely selective CF bond activation.

Monofluoroalkene-based dipeptide bioisosteres were synthesized via (I) difluorocyclopropane ring opening and (II) S N 2′-type defluorination. (2,2-Difluorocyclopropyl)methyl acetates were treated with acetonitrile in the presence of trifluoromethanesulfonic acid (triflic acid, TfOH). Elimination of acetic acid resulted in regioselective cleavage of the C–C bond distal to the CF 2 moiety (ring opening), and then a Ritter-type N-terminal introduction afforded N -(2,2-difluorohomoallyl)acetamides. The obtained difluoroacetamides underwent allylic substitution of bromine for fluorine in an AlBr 3 /CuBr system to generate 3-fluoroallylic bromides, whose substitution with n -Bu 4 NCN facilitated C-terminal introduction. Conversion of the cyano group into a carbamoyl group afforded the desired monofluoroalkene-based dipeptide bioisosteres.

Abstract A bromotropone corresponding to the agylcone of the glycosylated sesquiterpenoid natural product liriosmaside A has been prepared over ten steps and in a fully regio‐controlled manner through the gem‐dibromocyclopropane‐mediated ring‐expansion of a readily accessible decalenone. A Pd[0]‐mediated glucosylation reaction applied to this bromotropone afforded a product mixture from which an enantiomerically pure cross‐coupling product could be obtained and its structure confirmed through single‐crystal X‐ray analysis of a derivative. Various (unsuccessful) attempts are described to selectively acylate the last compound and thereby install the 3‐hydroxy‐3‐methylglutaric acid or HMGA‐containing side chain of the title natural product. A literature survey of other natural products embodying the HMGA motif suggest that liriosmaside A and its co‐metabolite liriosmaside B could be S‐configured at C3”. The evaluation of the glucosylated tropone in a series of anti‐bacterial, anti‐fungal and cytotoxicity assays reveals that it is inactive in all of these and so emphasizing the prospect that this and related troponoids, including the natural products liriosmaside A and B, can serve as useful models for new anti‐viral agents.

A ligand-controlled palladium-catalyzed three-component reaction of o-bromobenzaldehyde, N-tosylhydrazone, and methanol is described. This reaction uses readily available compounds as starting materials while displaying a broad substrate scope and good functional group compatibility.

Efficient construction of optically pure molecules from readily available starting materials in a simple manner is an on-going goal in asymmetric synthesis. As a straightforward route, transition-metal catalyzed enantioconvergent coupling between widely available secondary alkyl electrophiles and organometallic nucleophiles has emerged as a powerful strategy to construct chiral center(s). However, the scope of racemic secondary alkylmetallic nucleophiles for this coupling remains limited in specific substrates due to the difficulties in stereoselective formation of the key alkylmetal in-termediates. Here, we report an enantiodivergent strategy to efficiently achieve an array of synthetically useful chiral cyclopropanes, including chiral fluoroalkylated cyclopropanes and enantiomerically enriched cyclopropanes with chiral side chains, from racemic cyclopropylzinc reagents. This strategy relies on a one-pot, two-step enantiodivergent relay coupling (EDRC) process of the racemic cis-cyclopropylzinc reagents with two different electrophiles, which involves kinetic resolution of racemic cis-cyclopropylzinc reagents through a nickel-catalyzed enantioselective coupling with alkyl electrophiles, followed by a stereospecific relay coupling of the remaining enantiomeric cyclopropylzinc reagent with various electrophiles, to produce two types of functionalized chiral cyclopropanes with opposite configuration on the cyclopropane ring. These chiral cyclopropanes are versatile synthons for diverse transformations, rendering this strategy effective to structurally diversified molecules of medicinal interests.

No abstract available

No abstract available