Ketyl-olefin Coupling Research Articles

Visible-Light-Antenna Ligand-Enabled Samarium-Catalyzed Reductive Transformations.

Although divalent Sm reagents are some of the most important single-electron transfer reagents for reductive transformations, their catalytic applications are challenging. In this study, a bidentate phosphine oxide ligand substituted with 9,10-diphenylanthracene as a visible-light antenna was designed for Sm-catalyzed reduction reactions under mild reaction conditions. Pinacol coupling of aryl ketones and aldehydes was developed with 1 mol % of Sm catalyst and organic amine (DIPEA) as a sacrificial mild reductant. Mechanistic studies suggest that the visible-light-antenna ligand coordinates to Sm(III) and reduces Sm(III) to Sm(II) under visible-light irradiation. The catalytic system is also applicable for cross-pinacol coupling and other single-electron reductive transformations, including aza-pinacol coupling, flavone dimerization, C-O bond cleavage, C-C ring-opening of cyclopropane, ketyl-olefin coupling, and cross-coupling of the ketyl radical with the α-amino radical.

Data for Catalytic Defluorinative Ketyl-Olefin Coupling by Halogen-Atom Transfer

Data for Catalytic Defluorinative Ketyl-Olefin Coupling by Halogen-Atom Transfer

Data for Catalytic Defluorinative Ketyl-Olefin Coupling by Halogen-Atom Transfer

Data for Catalytic Defluorinative Ketyl-Olefin Coupling by Halogen-Atom Transfer

Iron-Catalyzed Allylic Defluorinative Ketone Olefin Coupling.

In this protocol, we demonstrate our discovery that iron is able to efficiently catalyze the reductive allylic defluorinative ketyl olefin coupling reaction between α-trifluoromethyl alkenes and unactivated ketones. This operationally simple cross-electrophile reaction circumvents the use of pre-generated organometallics and allows for the synthesis of diverse functional-group-rich tertiary gem-difluorohomoallylic alcohols through a polarity-reversed strategy. Preliminary mechanistic studies support a mechanism that proceeds through a ketyl formation/olefin insertion/β-fluoro elimination sequence.

Catalytic defluorinative ketyl-olefin coupling by halogen-atom transfer.

Ketyl–olefin coupling reactions stand as one of the fundamental chemical transformations in synthetic chemistry and have been widely employed in the generation of complex molecular architectures and natural product synthesis. However, catalytic ketyl–olefin coupling, until the recent development of photoredox chemistry and electrosynthesis through single-electron transfer mechanisms, has remained largely undeveloped. Herein, we describe a new approach to achieve catalytic ketyl–olefin coupling reactions by a halogen-atom transfer mechanism, which provides innovative and efficient access to various gem-difluorohomoallylic alcohols under mild conditions with broad substrate scope. Preliminary mechanistic experimental and computational studies demonstrate that this radical-to-polar crossover transformation could be achieved by sequentially orchestrated Lewis acid activation, halogen-atom transfer, radical addition, single-electron reduction and β-fluoro elimination.

Chromium-Catalyzed Allylic Defluorinative Ketyl Olefin Coupling

Herein we report a chromium-catalyzed allylic defluorinative ketyl olefin coupling between aldehydes and α-trifluoromethyl alkenes, which provides novel and efficient access to diverse gem-difluorohomoallylic alcohols. Remarkably, the high chemoselectivity of this reaction enables the conversion of the formyl moiety in the presence of various easily reducible functionalities including ketone, organohalides, aziridine, sulfone, alkyne, and unactivated alkene. The utility of this method is demonstrated by various simple derivatizations of the attached hydroxyl group of the coupling products. The preliminary mechanistic investigations suggest a reaction pathway with a rate-limiting C-C forming step followed by facile β-fluoro elimination.

Photoredox-Catalyzed Ketyl-Olefin Coupling for the Synthesis of Substituted Chromanols.

A visible light photoredox-catalyzed aldehyde olefin cyclization is reported. The method represents a formal hydroacylation of alkenes and alkynes and provides chromanol derivatives in good yields. The protocol takes advantage of the double role played by trialkylamines (NR3) which act as (i) electron donors for reducing the catalyst and (ii) proton donors to activate the substrate via a proton-coupled electron transfer.

ChemInform Abstract: Proton‐Coupled Electron Transfer in Organic Synthesis: Novel Homolytic Bond Activations and Catalytic Asymmetric Reactions with Free Radicals

AbstractReview: [28 refs.

Proton-Coupled Electron Transfer in Organic Synthesis: Novel Homolytic Bond Activations and Catalytic Asymmetric Reactions with Free Radicals

Proton-coupled electron transfers (PCET) are unconventional redox processes in which an electron and proton are exchanged together in a concerted elementary step. While these mechanisms are recognized to play a central role in biological redox catalysis, their applications in synthetic organic chemistry have yet to be widely established. In this Account, we highlight two recent examples from our group outlining the use of concerted PCET as a platform for the development of catalytic and enantioselective reactions of neutral ketyl radicals. Central to this work was the recognition that PCET provides a mechanism for independent proton and electron donors to function jointly as a formal hydrogen atom donor competent to activate organic π systems that are energetically inaccessible using conventional H-atom transfer technologies. In addition, we found that neutral ketyls formed in the PCET event are remarkably strong hydrogen-bond donors and remain strongly associated to the conjugate base of the proton donor following the PCET event. When chiral proton donors are used, these successor H-bond complexes provide a basis for asymmetric induction in subsequent reactions of the ketyl radical. 1 Introduction 2 Concerted PCET and Effective Bond Strengths 3 Concerted PCET Activation of Ketones: A Catalytic Protocol for Ketyl–Olefin Coupling and Mechanistic Investigations 4 Enantioselective PCET Catalysis: Development of Catalytic Asymmetric Aza-pinacol Cyclizations 5 Conclusions

Catalytic Ketyl-Olefin Cyclizations Enabled by Proton-Coupled Electron Transfer

Concerted proton-coupled electron transfer is a key mechanism of substrate activation in biological redox catalysis. However, its applications in organic synthesis remain largely unexplored. Herein, we report the development of a new catalytic protocol for ketyl-olefin coupling and present evidence to support concerted proton-coupled electron transfer being the operative mechanism of ketyl formation. Notably, reaction outcomes were correctly predicted by a simple thermodynamic formalism relating the oxidation potentials and pKa values of specific Brønsted acid/reductant combinations to their capacity to act jointly as a formal hydrogen atom donor.

A convenient pathway to Sm(ii)-mediated chemistry in acetonitrile

In this communication we show that the instability of samarium diiodide (SmI(2)) in acetonitrile is a consequence of ionization of the reductant in this solvent. Samarium triflate (Sm(OTf)(2)) is exceptionally stable in acetonitrile for periods over six months and can be used with appropriate additives to initiate a ketyl-olefin coupling reaction in high yield.

Ketyl−Allene Cyclizations Promoted by Samarium(II) Iodide

[reaction: see text] Samarium(II) iodide has proven to be an effective reagent for intramolecular reductive coupling reactions. Previous investigations of intramolecular ketyl-olefin coupling reactions provided carbocycles in excellent yield and good diastereoselectivity. This method has been extended to ketyl cyclizations with allenes. Substrates leading to both carbocycles and heterocycles in a selective manner are explored.

Total Synthesis of (+)‐Isoschizandrin Utilizing a Samarium(II) Iodide Promoted 8‐Endo Ketyl—Olefin Cyclization.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Total synthesis of (+)-isoschizandrin utilizing a samarium(II) iodide-promoted 8-endo ketyl-olefin cyclization.

The 13-step synthesis of (+)-isoschizandrin reported herein features a samarium(II) iodide-promoted 8-endo ketyl-olefin coupling to assemble the eight-membered ring present in the target concomitantly with the required functionality and stereochemistry. In constructing (+)-isoschizandrin as a single atropisomer, the synthesis utilizes a kinetic resolution of a seven-membered lactone using a CBS-oxazaborolidine.

Stereoselective Cyclization of cis-Decalin Skeleton of Vinigrol via Ketyl-Olefin Coupling Promoted by Samarium(II) Iodide

The cis-decalin ring system of vinigrol, a unique tricyclic diterpene isolated as a novel antihypertensive compound from a culture broth of Virgaria nigra, was synthesized featuring a ketyl-olefin coupling annulation reaction induced by SmI2.

The unexpected formation of bicyclo[2.2.1]heptane derivatives by Lewis acid-catalyzed transannular double cyclization

Attempted synthesis of the cyclooctanoid skeleton of taxane molecules, by an intramolecular Lewis acid catalyzed Hosomi–Sakurai cyclization of the allylsilane with the aldehyde moiety in 17, unexpectedly led to the formation of bicyclo[2.2.1]heptane derivatives 18 and 19a. Since the formation of spiro compounds by allylsilane terminated domino reaction has no precedent in literature, we extended the reaction conditions to unactivated olefins. Spontaneous aromatization accompanied by bicyclic ring formation was observed in these cases. Bicyclo[2.2.1]heptane derivative 11 was also formed in high yield by an intramolecular SmI2 mediated ketyl–olefin coupling of aldehyde in the hydroxysulfone 10.

Sequenced reactions with samarium(II) iodide. Intermolecular ketyl-olefin coupling/intramolecular nucleophilic acyl substitution for the preparation of six-, seven-, and eight-membered carbocycles

A samarium(II) iodide-promoted sequence consisting of an intermolecular ketyl-olefin coupling followed by an intramolecular nucleophilic acyl substitution is described. This process leads to functionalized six- to eight-membered monocyclic and bicyclic ring systems in moderate to good yields.

Sequential Ketyl-Olefin Coupling/beta-Elimination Reactions Mediated by Samarium(II) Iodide.

Samarium(II) iodide (SmI(2)) has been employed in an intramolecular sequential ketyl-olefin coupling/beta-elimination reaction. The overall process results in the net addition of an alkenyl species to a ketone carbonyl. This novel protocol for the intramolecular delivery of an alkenyl moiety avoids the basic reaction conditions typical of nucleophilic additions that are mediated by alkenylmagnesium halides and alkenyllithium reagents. A high degree of stereocontrol is imparted in the SmI(2)-mediated process as a result of the excellent facial selectivity conveyed in the initial ketyl-olefin coupling reaction. The relative asymmetric induction engendered in these addition reactions is complementary to more traditional nucleophilic addition reactions in that the alkenyl group is directed to the carbonyl center by an attached tether.

Sequenced Reactions with Samarium(II) Iodide. Sequential Nucleophilic Acyl Substitution/Ketyl Olefin Coupling Reactions for the Preparation of Oxygen Heterocycles.

Samarium(II) iodide has been employed to promote a sequential intramolecular nucleophilic acyl substitution/intramolecular ketyl olefin coupling cyclization sequence to provide bicyclic, tricyclic, and spiro-fused oxygen heterocycles in excellent yield and with high diastereoselectivity.