Pd‐Catalyzed Selective Carbonylation of <i>gem</i>‐Difluoroalkenes: A Practical Synthesis of Difluoromethylated Esters

Liu, Jiawang; Yang, Ji; Ferretti, Francesco; Jackstell, Ralf; Beller, Matthias

doi:10.1002/anie.201813801

Cited by 64 publications

(31 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We hypothesized that these intermediates could be intercepted by CO 2 and would lead to an effective synthetic method for the preparation of α‐CF 3 carboxylic acids (path d). Although carboxylation reactions of stabilized sp 3 ‐hybridized carbanions are challenging due to facile decarboxylation of the carboxylate intermediate, we investigated and found a simple and straightforward procedure to prepare α‐CF 3 carboxylic acids through multicomponent fluorocarboxylation reactions between gem ‐difluoroalkenes, cesium fluoride, and CO 2 …”

Section: Methodsmentioning

confidence: 99%

Efficient Synthesis of α‐Trifluoromethyl Carboxylic Acids and Esters through Fluorocarboxylation of gem‐Difluoroalkenes

et al. 2019

View full text Add to dashboard Cite

A facile synthetic procedure for the preparation of α‐trifluoromethyl carboxylic acids and esters was achieved through multicomponent coupling reactions between gem‐difluoroalkenes, cesium fluoride, and carbon dioxide. The products were generated in moderate to excellent yields, and the synthetic utility of this method was demonstrated through the preparation of trifluoromethylated versions of popular nonsteroidal anti‐inflammatory drugs (NSAIDs).

show abstract

Section: Methodsmentioning

confidence: 99%

Efficient Synthesis of α‐Trifluoromethyl Carboxylic Acids and Esters through Fluorocarboxylation of gem‐Difluoroalkenes

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Pd‐based catalyst systems also promoted alkoxycarbonylations reactions to construct a series of α ‐difluoromethylated esters in high yields and excellent regioselectivities (Scheme ) . The use of aromatic gem ‐difluoroalkenes ( 242 ) afforded benzylic α ‐difluoromethylated esters ( 244 ), whereas the use of aliphatic gem ‐difluoroalkenes promoted a remote olefin functionalization through a cascade involving alkene isomerization to deliver distal‐substituted esters 244′ in high yield and selectivity.…”

Section: Generation Of Trifluoromethanesmentioning

confidence: 99%

Recent Advances in Transition Metal‐Catalyzed Functionalization of gem‐Difluoroalkenes

Koley

Altman

2020

Israel Journal of Chemistry

130

View full text Add to dashboard Cite

gem-Difluorinated alkenes are readily accessible building blocks that can undergo functionalization to provide a broad spectrum of fluorinated and non-fluorinated products. Herein, we review recent (since 2017) transition metalcatalyzed transformations of these specialized alkenes and summarize general reactivity patterns of these reactions. Many transition metal-catalyzed reactions undergo net CÀ F bond functionalization reactions to deliver monofluorinated products. These reactions typically proceed through β-fluoroalkylmetal intermediates that readily eliminate a βfluoride to deliver monofluoroalkene products. A second series of reactions exploit coinage metal fluorides to add F À to the gem-difluorinated alkene, and further functionalization delivers trifluoromethyl-containing products. In stark contrast, few transition metal-catalyzed reactions proceed in net "fluorine-retentive processes" to deliver difluoromethylenebased products. Reactions Proceeding via β-Fluoride Eliminationgem-Difluoroalkenes react with a variety of transition metalbased catalyst systems (e. g. Cu, Co, Mn, Pd, Ni, Ru, Rh) in net CÀ F functionalization reactions. These reactions typically proceed through a β-fluoroalkylmetal intermediate that readily undergoes β-fluoride elimination to form a new alkene based product (Scheme 1). At first, reaction of a substrate-ligated complex (1) to the gem-difluoroalkene 2, proceeds through a four-membered transition state 3 to generate the intermediate 4. This process involves the matching of the anionic ligand (Y) with the cationic α,α-difluorinated position of the alkene, which generates an intermediate metalalkyl bearnig two βfluoride atoms. Subsequent β-fluoride elimination generates [a] S.Scheme 3. Plausible mechanism for defluoroborylation of aliphatic gem-difluoroalkenes. Scheme 4. CÀ F Bond borylation of gem-difluoroalkenes. Scheme 5. Copper-catalyzed trans-selective monodefluoroborylation of various gem-difluoroalkenes. Scheme 6. CÀ F Bond borylation of gem-difluoroalkenes. Scheme 7. Copper-catalyzed tunable multi-borylation reactions of gem-difluoroalkenes. In parentheses the ratio of 22, 23 and 24 is reported. Scheme 8. Stereoselective defluorinative borylation and silylation of gem-difluoroalkenes. Scheme 9. a) Synthesis of fluorinated vinylsilanes from gem-difluoro/ polyfluoroalkenes. b) Cross-coupling reaction of 29 b and iodobenzene. Scheme 10. Nickel-catalyzed fluoroalkenylation of unactivated alkylbromides. rr = The regioisomeric ratio of the benzylic fluoroÀ alkenylation product to the other regioisomers. DMA = N,N-Dimethylacetamide. Scheme 14. Iron-catalyzed defluorinative cross-coupling of donor alkenes with gem-difluoroalkenes. Dibm = diisobutyrylmethane. Scheme 15. Nickel-catalyzed reductive aryl monofluoroalkenylation of alkenes. Scheme 16. Plausible mechanism for reductive aryl monofluoroalkenylation of gem-difluoroalkenes. Scheme 17. Nickel-catalyzed hydroalkenylation of alkynes through oxidative cyclization and β-fluoride elimination. Scheme 28. Ruthenium-catalyzed fluoroal...

show abstract

“…[1c, 4] In organic synthesis, gem-difluoro olefines are important intermediates with applications, for example, in carbonylation or carboxylation reaction of one of its CÀF bonds. [5] The efficient synthesis of gem-difluoro olefines has thus received broad attention in the past decades. Carbonyl compounds are traditional precursors for gem-difluoro olefination reactions, including the Wittig, [6] Horner-Wadsworth-Emmons, [7] and Julia-Kocienski reaction.…”

Section: Synthesis Of Gem-difluoro Olefins Through C à H Functionalizmentioning

confidence: 99%

Synthesis of gem‐Difluoro Olefins through C−H Functionalization and β‐fluoride Elimination Reactions

2020

View full text Add to dashboard Cite

A palladium catalyzed C−H functionalization and consecutive β‐fluoride elimination reaction between indole heterocycles and fluorinated diazoalkanes is reported. This approach provides for the first time a facile method for the rapid synthesis of gem‐difluoro olefins using fluorinated diazoalkanes under mild reaction conditions. Cyclopropanation products were obtained when N‐arylated rather than N‐alkylated indoles were applied in this reaction. Mechanistic studies reveal the importance of the β‐fluoride elimination step in this transformation. This method presents a new concept for the simple and direct transfer of a 1‐aryl‐(2,2‐difluorovinyl) group to access gem‐difluoro olefins.

show abstract

Pd‐Catalyzed Selective Carbonylation of gem‐Difluoroalkenes: A Practical Synthesis of Difluoromethylated Esters

Cited by 64 publications

References 84 publications

Efficient Synthesis of α‐Trifluoromethyl Carboxylic Acids and Esters through Fluorocarboxylation of gem‐Difluoroalkenes

Efficient Synthesis of α‐Trifluoromethyl Carboxylic Acids and Esters through Fluorocarboxylation of gem‐Difluoroalkenes

Recent Advances in Transition Metal‐Catalyzed Functionalization of gem‐Difluoroalkenes

Synthesis of gem‐Difluoro Olefins through C−H Functionalization and β‐fluoride Elimination Reactions

Contact Info

Product

Resources

About