Catalytic Enantioselective Boryl and Silyl Substitution with Trifluoromethyl Alkenes: Scope, Utility, and Mechanistic Nuances of Cu–F β-Elimination

Journal of the American Chemical Society, Год журнала: 2019, Номер 141(50), С. 19917 - 19934

Опубликована: Дек. 6, 2019

Catalytic enantioselective methods are introduced that allow access to a variety of allyl boronates and silanes contain difluoroalkene unit; the resulting products may be used for preparation organofluorine compounds in high enantiomeric purity. Furthermore, number key mechanistic aspects transformations have been investigated analyzed. Thus, first, an NHC–Cu-catalyzed method boryl substitution with F3C-substituted alkenes is introduced. These processes, unlike previously reported strategies, applicable alkyl as well aryl substituted substrates, afford bearing moiety (up 98% yield 95:5 er). Second, corresponding silyl substitutions, first cases their kind, presented 94% 97:3 Third, experimental computational (DFT) investigations described shed light on catalytic processes. Evidence (X-ray structures Cu–alkyl intermediates kinetic studies) put forth illustrating initial Cu–boryl Cu–silyl addition significantly faster than ensuing Cu–F elimination, latter step can facilitated by either mild Lewis acid (e.g., Li or Na cation) nucleophilic promoter alkoxide). findings together DFT studies demonstrate β-elimination probably proceeds anti-stereochemistry. Representative ways through which new understanding rationalize disclosed findings, improve transformation, develop diastereo- provided. For example, explanation provided regarding why bisphosphine–Cu complexes do not efficiently promote substitutions aryl-substituted but facile, how size ligand impact regioselectivity efficiency.

Язык: Английский

---

Synthesis of gem-Difluoroalkenes via Nickel-Catalyzed Reductive C–F and C–O Bond Cleavage

ACS Catalysis, Год журнала: 2018, Номер 9(1), С. 775 - 780

Опубликована: Дек. 21, 2018

By merging C–O and C–F bond cleavage in cross-electrophile coupling, we developed a method for efficient synthesis of gem-difluoroalkenes with an alkoxy-substituent on the homoallylic position using easily accessible acetals as coupling partners α-trifluoromethyl alkenes. Remarkably, this Ni-catalyzed allylic defluorinative cross-coupling reaction demonstrates high tolerance wide range sensitive functional groups proves to be applicable late-stage functionalization structurally complex compounds.

Язык: Английский

---

Synthesis of gem-Difluoroalkenes by Merging Ni-Catalyzed C–F and C–C Bond Activation in Cross-Electrophile Coupling

Organic Letters, Год журнала: 2019, Номер 21(8), С. 2723 - 2730

Опубликована: Март 29, 2019

By merging C–F and C–C bond activation in the cross-electrophile coupling, we developed an efficient cyanide-free synthesis of diverse functional-group-rich cyano-substituted gem-difluoroalkenes using cyclobutanone oxime esters trifluoromethyl alkenes as precursors. Notably, this Ni-catalyzed reaction is bestowed with broad substrate scope, low catalyst loading, complete regioselectivities, high tolerance a wide range sensitive functional groups. Preliminary mechanistic studies indicate that iminyl radical-initiated cleavage involved pathway.

Язык: Английский

---

Reductive Allylic Defluorinative Cross-Coupling Enabled by Ni/Ti Cooperative Catalysis

Organic Letters, Год журнала: 2019, Номер 21(20), С. 8316 - 8322

Опубликована: Окт. 1, 2019

Unactivated alkyl chlorides are abundant building blocks in organic synthesis, but they have been rarely engaged cross-electrophile coupling. Herein, we report a Ni/Ti-cocatalyzed reductive allylic defluorinative cross-coupling between trifluoromethyl alkenes and unactivated bromides, enabling the efficient preparation of diverse functional-group-rich gem-difluoroalkenes. Notably, synthesis gem-difluoroalkene analogues azaperone, haloperidol, benperidol was also accomplished using our method as key step.

Язык: Английский

---

Catalytic asymmetric synthesis of monofluoroalkenes and gem-difluoroalkenes: advances and perspectives

Organic Chemistry Frontiers, Год журнала: 2021, Номер 8(10), С. 2315 - 2327

Опубликована: Янв. 1, 2021

The latest achievements in the catalytic asymmetric synthesis of both monofluoro- and gem-difluoroalkenes are discussed.

Язык: Английский

---

Access to Divergent Fluorinated Enynes and Arenes via Palladium-Catalyzed Ring-Opening Alkynylation of gem-Difluorinated Cyclopropanes

Organic Letters, Год журнала: 2020, Номер 22(4), С. 1414 - 1419

Опубликована: Фев. 3, 2020

Herein, we describe a palladium-catalyzed alkynylation of gem-difluorinated cyclopropanes via C–C bond activation/C–F cleavage, followed by C–C(sp) coupling. The new approach proceeds with broad substrate scope under mild reaction conditions, whereas both 1,1-disubstituted and complex-molecule-modified react smoothly high stereoselectivity. developed method provides efficient convenient ways access to diversity important fluorinated enynes arenes slightly modification the conditions.

Язык: Английский

---

gem ‐Difluoromethylene Alkyne‐Enabled Diverse C−H Functionalization and Application to the on‐DNA Synthesis of Difluorinated Isocoumarins

Angewandte Chemie International Edition, Год журнала: 2020, Номер 60(4), С. 1959 - 1966

Опубликована: Окт. 6, 2020

Using gem-difluoromethylene alkynes as effectors, unprecedented diverse C-H activation/[4+2] annulations of simple benzoic acids are reported. The chemodivergent reaction outcomes well-tuned by Rh/Ir-catalyzed system; in the RhIII catalysis, 3-alkenyl-1H-isochromen-1-one and 3,4-dialkylideneisochroman-1-one skeletons afforded a solvent-dependent manner whereas difluoromethylene-substituted 1H-isochromen-1-ones generated under IrIII -catalyzed system. Mechanistic studies revealed that unusually double β-F eliminations fluorine effect-induced regioselective reductive elimination independently involved to enable distinct modes for divergent product formations. Besides, synthetic application both derivatization obtained diene products on-DNA synthesis DNA-tagged difluorinated isocoumarin have been demonstrated, which manifested great potential utility developed protocols.

Язык: Английский

---

Reductive quenching-initiated catalyst-controlled divergent alkylation of α-CF3-olefins

Chem Catalysis, Год журнала: 2022, Номер 2(6), С. 1380 - 1393

Опубликована: Апрель 21, 2022

Gem-difluoroalkenes and trifluoromethyl alkanes are pervasive in biologically active molecules. Photo-catalyzed alkylation of α-CF3-olefins provides a straightforward approach to access these scaffolds; however, such strategy is often hampered, gem-difluoroalkenes usually formed instead under reductive quenching-initiated photoredox conditions. It both mechanistically synthetically appealing if simple change the catalyst can chemo-selectively lead either type products. Here, we show visible-light-induced photo-catalyst for preparing from α-CF3-olefins. The chemo-selectivity reactions arises judicious choice rather than modification substrate structures. A wide variety substrates bearing an assortment functional groups (62 examples) compatible with this strategy. use HFIP as additive promotes formation probably via facilitation hydrogen atom transfer step O-H but not α-C-H bond.

Язык: Английский

---

Multiple-fold C–F bond functionalization for the synthesis of (hetero)cyclic compounds: fluorine as a detachable chemical handle

Organic Chemistry Frontiers, Год журнала: 2022, Номер 9(7), С. 2013 - 2055

Опубликована: Янв. 1, 2022

We highlighted the recent advances in field of multiple-fold C–F bond functionalization for synthesis (hetero)cyclic compounds.

Язык: Английский

---

Nickel-Catalyzed anti-Markovnikov Hydroalkylation of Trifluoromethylalkenes

ACS Catalysis, Год журнала: 2022, Номер 12(15), С. 9410 - 9417

Опубликована: Июль 18, 2022

Transition-metal-catalyzed difunctionalization of olefins constitutes a fertile synthetic platform for rapid access to complex molecules from bulk chemicals. However, substrates featuring fluoroalkyl substituents are rarely employed because facile β-fluoride elimination pathways. Herein, we report hydroalkylation trifluoromethylalkenes with alkyl halides under nickel catalysis that enables the construction 1,1,1-trifluoropropane derivatives. The common pathway is suppressed by identifying competent proton donor favors protonolysis process. Also, unactivated alkenes could be readily as when using Ni/hydrosilane catalytic system.

Язык: Английский

---