Electrophilic Capture Research Articles

Multicomponent Reactions (MCRs) with o-Quinone Methides.

This article presents a comprehensive overview of multicomponent reactions (MCRs) that proceed via ortho-quinone methide intermediates (o-QM) generated in the reaction medium. Examples of applications involving these highly reactive intermediates in organic synthesis and biological processes (e. g., biosynthetic pathways, prodrug cleavage and electrophilic capture of biological nucleophiles) are also described. QMs are often generated by eliminative processes of phenol derivatives or by photochemical reactions, including reversible generation in photochromic substances. This class of compounds can undergo various reaction types, including nucleophilic attack at the methide carbon, with subsequent rearomatization, and react with electron-rich dienophiles in inverse-electron demand hetero-Diels-Alder reactions. Its versatile reactivity has been explored in the context of cascade reactions for the construction of several classes of substances, including complex natural products.

Solvent choice and kinetic isotope effects (KIEs) dramatically alter regioselectivity in the directed ortho metalation (DoM) of 1,5-dichloro-2,4-dimethoxybenzene.

The regioselective formation of the 6-lithio derivative of 1,5-dichloro-2,4-dimethoxybenzene (i.e., 12) by directed ortho metalation (DoM) with nBuLi in THF is described. Although literature reports suggest direct deprotonation at C6, a series of time-course and labelling studies has revealed that deprotonation rather occurs exclusively at C3 followed by isomerization of the anion to C6. By contrast, when DoM was performed in Et2 O, deprotonation again occurred selectively at C3, but now no isomerization occurs, and electrophilic capture produces the regioisomer of that produced in THF. In these labeling studies, it has been found that deuterium has an enormous kinetic isotope effect (KIE) that suppresses not only the original DoM reaction at C3 when deuterium is present there, but also suppresses isomerization to C6 when the label is at that site. Remarkably, this "protecting-group" role of the deuterium is unique to THF; in ether, full deprotonation of the deuterium at C3 was observed.

Chiral Fluorinated α‐Sulfonyl Carbanions: Enantioselective Synthesis and Electrophilic Capture, Racemization Dynamics, and Structure

Enantiomerically pure triflones R(1) CH(R(2) )SO2 CF3 have been synthesized starting from the corresponding chiral alcohols via thiols and trifluoromethylsulfanes. Key steps of the syntheses of the sulfanes are the photochemical trifluoromethylation of the thiols with CF3 Hal (Hal=halide) or substitution of alkoxyphosphinediamines with CF3 SSCF3 . The deprotonation of RCH(Me)SO2 CF3 (R=CH2 Ph, iHex) with nBuLi with the formation of salts [RC(Me)SO2 CF3 ]Li and their electrophilic capture both occurred with high enantioselectivities. Displacement of the SO2 CF3 group of (S)-MeOCH2 C(Me)(CH2 Ph)SO2 CF3 (95 % ee) by an ethyl group through the reaction with AlEt3 gave alkane MeOCH2 C(Me)(CH2 Ph)Et of 96 % ee. Racemization of salts [R(1) C(R(2) )SO2 CF3 ]Li follows first-order kinetics and is mainly an enthalpic process with small negative activation entropy as revealed by polarimetry and dynamic NMR (DNMR) spectroscopy. This is in accordance with a Cα S bond rotation as the rate-determining step. Lithium α-(S)-trifluoromethyl- and α-(S)-nonafluorobutylsulfonyl carbanion salts have a much higher racemization barrier than the corresponding α-(S)-tert-butylsulfonyl carbanion salts. Whereas [PhCH2 C(Me)SO2 tBu]Li/DMPU (DMPU = dimethylpropylurea) has a half-life of racemization at -105 °C of 2.4 h, that of [PhCH2 C(Me)SO2 CF3 ]Li at -78 °C is 30 d. DNMR spectroscopy of amides (PhCH2 )2 NSO2 CF3 and (PhCH2 )N(Ph)SO2 CF3 gave NS rotational barriers that seem to be distinctly higher than those of nonfluorinated sulfonamides. NMR spectroscopy of [PhCH2 C(Ph)SO2 R]M (M=Li, K, NBu4 ; R=CF3 , tBu) shows for both salts a confinement of the negative charge mainly to the Cα atom and a significant benzylic stabilization that is weaker in the trifluoromethylsulfonyl carbanion. According to crystal structure analyses, the carbanions of salts {[PhCH2 C(Ph)SO2 CF3 ]Li⋅L}2 (L=2 THF, tetramethylethylenediamine (TMEDA)) and [PhCH2 C(Ph)SO2 CF3 ]NBu4 have the typical chiral Cα S conformation of α-sulfonyl carbanions, planar Cα atoms, and short Cα S bonds. Ab initio calculations of [MeC(Ph)SO2 tBu](-) and [MeC(Ph)SO2 CF3 ](-) showed for the fluorinated carbanion stronger nC →σ* SCF 3 and nO →σ* SCF 3 interactions and a weaker benzylic stabilization. According to natural bond orbital (NBO) calculations of [R(1) C(R(2) )SO2 R](-) (R=tBu, CF3 ) the nC →σ*SR interaction is much stronger for R=CF3 . Ab initio calculations gave for [MeC(Ph)SO2 tBu]Li⋅2 Me2 O an O,Li,Cα contact ion pair (CIP) and for [MeC(Ph)SO2 CF3 ]Li⋅2 Me2 O an O,Li,O CIP. According to cryoscopy, [PhCH2 C(Ph)SO2 CF3 ]Li, [iHexC(Me)SO2 CF3 ]Li, and [PhCH2 C(Ph)SO2 CF3 ]NBu4 predominantly form monomers in tetrahydrofuran (THF) at -108 °C. The NMR spectroscopic data of salts [R(1) (R(2) )SO2 R(3) ]Li (R(3) =tBu, CF3 ) indicate that the dominating monomeric CIPs are devoid of Cα Li bonds.

A Highly Stereoselective TMSOTf-Mediated Catalytic Carbocupration of Alkynoates

The TMSOTf-mediated catalytic carbocupration of ynoates has been investigated. It has been shown that catalyst loadings as low as 5 mol % readily allow for high yields and diastereoselectivities for a series of aromatic Grignard reagents. In addition, we have been successful in vicinally functionalizing 1a via initial TMSOTf-mediated catalytic carbocupration followed by a secondary electrophilic capture of the TMS allenoate intermediate.

Carbolithiation of Simple Terminal and Strained Internal Alkenes by the Naphthalene and the Biphenyl Dianion: New Modes of Reactivity of Highly Reduced Organic Species in Solution

AbstractDianions derived from arenes of high reduction potential (biphenyl, naphthalene) and Li(s) can carbometallate propene, isobutene or norbornene among other alkenes, in an intermolecular fashion. This reaction runs at room temperature to afford partially dearomatized alkylated aryl anions that are susceptible to further functionalization by electrophilic capture. This form of reactivity, typical of the arene dianion, deviates from the specific alkali metal‐like reactivity displayed by these complexes, affording regio‐ and in many cases stereo‐controlled products. DFT calculations help to figure out the regiochemical outcome of this reaction, where some of the most inexpensive organic starting materials are involved. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Studies of the Generation and Pericyclic Behavior of Cyclic Pentadienyl Carbanions. Alkylation Reactions as an Efficient Route to Functionalized cis-Bicyclo[3.3.0]octenes

Carbolithiation has been studied with alkyllithium reagents in a series of six- through nine-membered 3-methylene-1,4-cycloalkadienes, efficiently producing the corresponding cyclic pentadienyl carbanions. These pentadienyl anions display unique reactivity, depending on ring size. Cyclooctadienyl anions readily undergo disrotatory electrocyclization to cis-bicyclo[3.3.0]octenyl systems, which are trapped with a variety of electrophiles to stereoselectively provide functionalized cis-bicyclo[3.3.0]octenes. The carbolithiation and electrocyclization processes are examined using low-temperature (1)H NMR experiments. An expedient synthesis of a linear triquinane illustrates this methodology. Electrocyclization of the corresponding cyclononadienyl anion requires unusually high temperatures (120 degrees C), and computational studies provide insights into this change in reactivity. Cycloheptadienyl and cyclohexadienyl anions, generated via carbolithiation, provide functionalized cycloheptadienes and cyclohexadienes upon electrophilic capture. Trapping experiments reveal that the cycloheptadienyl anions are transformed to heptatrienyl anions. A series of experiments have been designed to explore evidence for the feasibility of equilibration of open and closed anionic systems, and these studies report the first isolation of a cis-bicyclo[3.1.0]hexene derived from electrocyclization of a cyclohexadienyl carbanion.

Reactivity in the upper limits of the reduction potential in solution: arene dianion intermolecular carbolithiation of alkenes

Lithium salts of dianions derived from arenes of high reduction potential (biphenyl, naphthalene) can carbometallate terminal alkenes (propene, isobutene) in an intermolecular fashion, affording partially dearomatized alkylated aryl anions, which are susceptible to further functionalization by electrophilic capture. This form of reactivity, specific of the arene dianion, deviates from the typical alkali metal-like reactivity displayed by these complexes, affording in most cases regio- and stereocontrolled products. Simple semiempirical calculations (PM3) help predicting the regiochemical outcome of this reaction, where some of the most inexpensive organic starting materials are involved.

SmI2-mediated sequential radical cyclization/anionic capture of aryl iodides on solid support

Aryl radicals were generated by SmI2 on solid support, cyclized on to CC bond, and reduced to their organosamarium anionic species followed by electrophilic capture. However, the capture reaction was substrate-dependant in solution and on solid support. In some examples, results from solid phase reactions were equal or better to the corresponding solution reactions.

Polyannulated glycopyranosides via radical-mediated tandem reactions. Stereoselective synthesis of 6·5·6 dioxatricycles via 5-exo-trig, 6-endo-dig mode — III

A series of C-silylated enynols, e.g. 6-methyl-l-trimethylsilyl-hept-5-en-l-yn-4-ol (rac-A) was prepared and submitted to N-iodosuccinimide mediated iodoalkoxylation of tri-O-acetylglycal Thanks to the presence of the silyl group the resulting diastereomeric glycosides (S)A1 and (R)A1 were readily separated. Triethylborane/oxygen/ethyl iodide promoted iodine transfer afforded doubly annulated glycosides in a 5-exo-trigonal, 6-endo-digonal cascade. The required re-protection of the three acetoxy groups was carried out orthogonally. The newly installed iodocyclohexene moiety served as site for further functionalization, which was accomplished by metal-halogen exchange followed by electrophilic capture or by reduction/epoxidation.

Synthesis of Vinylallenes by Conjugate 1,6‐, 1,8‐, 1,10‐ and 1,12‐Addition Reactions of Organocuprates with Acetylenic Michael Acceptors and Their Use as Dienes in Intermolecular Diels‐Alder Reactions

AbstractVarious vinylallenes were synthesized by conjugate cuprate additions to acetylenic Michael acceptors. Thus, 1,6‐addition reactions with 2‐en‐4‐ynoates 1, 3, and 5a, respectively, furnished vinylallenes 2, 4, and 7 after regioselective electrophilic capture of the allenyl enolates formed. Likewise, 1,8‐addition to 2,4‐dien‐6‐ynoates 8a and 10 gave the vinylallenes 9 and 11, whereas the 1,10‐addition of Me2CuLi to 2,4,6‐trien‐8‐ynoate 12 provided allene 13, and the analogous 1,12‐addition to 2,4,6,8‐tetraen‐10‐ynoate 14 furnished the polyene 15. These vinylallenes are valuable dienophiles in regio‐ and stereoselective Diels‐Alder reactions, as evidenced by the formation of the cycloaddition products 16–24. In the presence of Lewis acids, vinylallene 4a presumably rearranges to a cyclopentadiene derivative which then forms the cycloadducts 25 and 26.

Synthesis of Allenes by 1,6‐Addition of Organocuprates to Acceptor‐Substituted Enynes: Scope and Limitations

AbstractAcyclic acceptor‐substituted conjugated enynes bearing sulfonyl sulfinyl, sulfonate, nitro, amide, cyano, and oxazolidino groups at the double bond were synthesized and the regioselectivity of their reaction with organocuprates was examined. All Michael acceptors except enynes with nitro and amide functions underwent 1,6‐additions, and the allenyl enolates thus formed were trapped with electrophiles in order to obtain the corresponding allenes. A qualitative reactivity scale for these reactions was established. The dependence of the regioselectivity of both the cuprate addition and the subsequent electrophilic capture on the acceptor group and the substitution pattern of the allenyl enolate were studied. Cyclic 2‐en‐4‐ynoates with endocyclic double bonds were synthesized and treated with organocuprates to afford an exocyclic allene in one case.

Isodicyclopentadienes and related molecules. 57. Stereocontrolled synthesis of sterically crowded titanocenes of high enantiomeric purity by electrophilic capture of C-silylated ligands with configurational inversion

Isodicyclopentadienes and related molecules. 57. Stereocontrolled synthesis of sterically crowded titanocenes of high enantiomeric purity by electrophilic capture of C-silylated ligands with configurational inversion

Impact of substituent modifications on the atropselectivity characteristics of an anionic oxy-Cope ring expansion

The phenomenon of atropisomerism is critically examined in the tricyclic E, syn, up enolates derived from anionic oxy-Cope rearrangement of 1-vinyl-2-cyclohexenyl-7,7-dimethyl-exo-norbornan-2-ols, as well as the ketones derived from their protonation and methylation. In all cases studied, the [3,3] sigmatropic shift proceeds with 100% stereoselectivity via the endo-chair transition-state option. The E and syn stereochemistry is established during chirality transfer at this stage. The «oxygen-up» conformation stems directly from the structural features inherent in the starting alcohols. In the unsubstituted example and with certain substitution pattrerns in the original cyclohexene ring, the E, syn, up enolates are seen to be thermodynamically unstable relative to their E, syn, down atropisomers, such that products results exclusively by electrophilic capture of the latter. By suitable substitution, the barrier to this preequilibrium can be sufficiently heightened so that products resulting from the E, syn, up species can be obtained

Direct lithiation of chalcogenachromones, -flavones, and -pyranones. The interconversion and electrophilic capture of ring-opened and ring-closed anions

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirect lithiation of chalcogenachromones, -flavones, and -pyranones. The interconversion and electrophilic capture of ring-opened and ring-closed anionsMichael R. Detty and Lynda W. McGarryCite this: J. Org. Chem. 1988, 53, 6, 1203–1207Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March 1988https://doi.org/10.1021/jo00241a015RIGHTS & PERMISSIONSArticle Views316Altmetric-Citations28LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (636 KB) Get e-Alerts Get e-Alerts

Enamines from iodine oxidation of trialkylamines. 1. Electrophilic capture by cationic heterocyclic rings

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnamines from iodine oxidation of trialkylamines. 1. Electrophilic capture by cationic heterocyclic ringsDonald H. Wadsworth, Michael R. Detty, Bruce J. Murray, Charles H. Weidner, and Neil F. HaleyCite this: J. Org. Chem. 1984, 49, 15, 2676–2681Publication Date (Print):July 1, 1984Publication History Published online1 May 2002Published inissue 1 July 1984https://doi.org/10.1021/jo00189a004RIGHTS & PERMISSIONSArticle Views530Altmetric-Citations27LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (773 KB) Get e-Alerts Get e-Alerts