Imine Anions Derived from 2° Allylic Amines

Abstract

The application of allylic carbanions to organic synthesis is extensive^2,3 and among the numerous variations are the generation and use of heteroallylic dianions. Noteworthy in this useful option is the ability of sulfide (?S^θ) to stabilize a developing adjacent carbanion,^4,5 while alkoxide (?0^θ) uniquely directs carbanion formation to a distal allylic position (Scheme I).^6,7 We now wish to report that under conditions typically used for hetero allylic dianion formation 2° allylic amides provide a third reaction pathway for this structural entity by isomerizing to the resonance-stabilized imine anions (Scheme I).^8,9 This overall conversion (presumably through an intermediate dianion) represents a heretofore unknown isomerization process that provides an alternative method for the generation of synthetically useful enolate equivalents.¹⁰     

Direct Stereoconvergent Allylation of Chiral Alkylcopper Nucleophiles with Racemic Allylic Phosphates

Copper-catalyzed stereoconvergent allylation of chiral sp³-hybridized carbon nucleophiles with a racemic mixture of acyclic secondary allylic phosphates is reported. In the presence of a copper-catalyst complexed with chiral BenzP* ligand, tandem coupling reaction of vinyl arenes, bis(pinacolato)diboron, and racemic allylic phosphates provided β-chiral alkylboronates possessing (E)-alkenyl moiety through a direct stereoconvergent allylic coupling with concomitant generation of a C(sp³)-stereogenic center. A range of vinyl (hetero)arenes and secondary allylic phosphates bearing 1°, 2°, 3° alkyl and phenyl α-substituents were suitable for the reaction, forming products with high enantioselectivities up to 95 % ee. Density functional theory calculations were conducted in detail to elucidate the origin of the observed regioselectivity of borylcupration and stereoconvergent (E)-olefin formation from racemic allylic phosphates.     

Asymmetric Cascade Reaction to Allylic Sulfonamides from Allylic Alcohols by Palladium(II)/Base‐Catalyzed Rearrangement of Allylic Carbamates

A regio‐ and enantioselective tandem reaction is reported capable of directly transforming readily accessible achiral allylic alcohols into chiral sulfonyl‐protected allylic amines. The reaction is catalyzed by the cooperative action of a chiral ferrocene palladacycle and a tertiary amine base and combines high step‐economy with operational simplicity (e.g. no need for inert‐gas atmosphere or catalyst activation). Mechanistic studies support a Pd^II‐catalyzed [3,3] rearrangement of allylic carbamates—generated in situ from the allylic alcohol and an isocyanate—as the key step, which is followed by a decarboxylation.     

Effets isotopiques du deutérium en RMN 13C,measure du marquage isotopique des alcools allylques.

Primary and secondary deuterium isotope effects on ¹³C NMR chemical shifts for trigonal carbons are reported for twelve allylic alcohols. The secondary DIECCS is used for an accurate measurement of the deuterium labeling of variously substituted allylic alcohols.     

Transition‐Metal‐Free Borylation of Allylic and Propargylic Alcohols

The base‐catalyzed allylic borylation of tertiary allylic alcohols allows the synthesis of 1,1‐disubstituted allyl boronates, in moderate to high yield. The unexpected tandem performance of the Lewis acid–base adduct, [Hbase]⁺[MeO‐B₂pin₂]^? favored the formation of 1,2,3‐triborylated species from the tertiary allylic alcohols and 1‐propargylic cyclohexanol at 90 °C.     

Nickel‐Catalyzed Reductive Allylation of Tertiary Alkyl Halides with Allylic Carbonates

The construction of all C(sp³) quaternary centers has been successfully achieved under Ni‐catalyzed cross‐electrophile coupling of allylic carbonates with unactivated tertiary alkyl halides. For allylic carbonates bearing C1 or C3 substituents, the reaction affords excellent regioselectivity through the addition of alkyl groups to the unsubstituted allylic carbon terminus. The allylic alkylation method also exhibits excellent functional‐group compatibility, and delivers the products with high E selectivity.     

A convenient procedure for smooth palladium-catalyzed allylic alkylation by sodium dimethyl malonate and cyclopentadienide. A new synthesis of allylic substituted cyclopentadienes.

The use of the Pd(dba)¹₂/dpe catalytic system in allylic alkylation allows sodium dimethyl malonate to react with allylic acetates at room temperature. According to this procedure, a novel synthesis of allylic substituted cyclopentadienes is described through the use of cyclopentadienide anion as a nucleophile.     

Reactions of Isatin Dimethyl Ketal and Its Ethyl Imino Ether with Methyllithium

Although allylic thiocyanates undergo a facile thermal (3,3) isomerization to form the more stable allylic isothiocyanates¹, this transformation has played a surprisingly minor role in organic synthesis. We have found that α,β-unsaturated esters (1) can be converted to α-isothiocyanatoacrylic esters (2) via an allylic (3,3) thiocyanate isomerization.     

The Reaction of Trialkylboranes with Allyl Phenyl Ether. Syntheses of 1-Alkenes and 1,5-Alkadienes

In the organoborane chemistry, the homologation reaction is one of the useful methods for the synthesis of organoboranes not available via hydroboration.¹⁾ The allylic boranes are known to be highly reactive and exhibit specific behaviors,²⁾ but with few exceptions,³) these are difficult to be prepared directly by the hydroboration reaction.⁵⁾ Previously, we reported that in the reaction of the dianion of phenoxyacetic acid with organoborane, the phenoxy group acts as a good leaving group.⁶⁾ This result suggested us a new homologation reaction converting a saturated organoborane to a allylic borane (1) by the treatment with the carbanion of allyl phenyl ether. Here we wish to report the synthesis of 1-alkenes (II) three-carbon-homologated from starting alkenes⁷⁾ and the regioselective synthesis of 1,5-dienes (III) using allylic borane intermediates (1) (eq. 1).     

DDQ-mediated direct oxidative coupling of amides with benzylic and allylic sp3 C–H bonds under metal-free conditions

A simple and efficient method for the direct oxidative coupling of amides with benzylic and allylic sp³ C–H bonds using DDQ as an oxidant is described. A range of amides including benzamide, benzyl carbamate, and substituted sulfonamides reacted efficiently with various benzylic and allylic substrates under metal free conditions to afford amidation products in good to excellent yields.     

Ir‐Catalysed Asymmetric Allylic Substitutions with Cyclometalated (Phosphoramidite)Ir Complexes—Resting States,Catalytically Active (π‐Allyl)Ir Complexes and Computational Exploration

Mechanistic aspects of allylic substitutions with iridium catalysts derived from phosphoramidites by cyclometalation were investigated. The determination of resting states by ³¹P NMR spectroscopy led to the conclusion that the cyclometalation process is reversible. A novel, one‐pot procedure for the preparation of (π‐ allyl)Ir complexes was developed, and these complexes were characterised by X‐ray crystal structure analyses and spectral data. They are fully active catalysts of the allylic substitution reaction. DFT calculations on the allyl complexes, transition states of the allylic substitution and product olefin complexes gave further mechanistic insight.     

Rhodium‐Catalyzed Enantioselective Intermolecular Hydroalkoxylation of Allenes and Alkynes with Alcohols: Synthesis of Branched Allylic Ethers

Regio‐ and enantioselective additions of alcohols to either terminal allenes or internal alkynes provides access to allylic ethers by using a Rh^I/diphenyl phosphate catalytic system. This method provides an atom‐economic way to obtain chiral aliphatic and aryl allylic ethers in moderate to good yield with good to excellent enantioselectivities.     

Metal-free oxidative C-C bond formation of active methylenic sp C-H bonds with benzylic sp C-H and allylic sp C-H bonds mediated by DDQ

An efficient and simple method for the oxidative coupling of benzylic and allylic sp³ C-H bonds with active methylenic sp³ C-H bonds under metal-free conditions was developed by employing 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as an oxidant. The reaction was shown to proceed smoothly for various 1,3-dicarbonyl compounds with a range of benzylic and allylic substrates in good to excellent yields.     

Selective Benzylic and Allylic Alkylation of Protic Nucleophiles with Sulfonamides through Double Lewis Acid Catalyzed Cleavage of sp3 Carbon–Nitrogen Bonds

The acid‐catalyzed benzylic and allylic alkylation of protic nucleophiles is fundamentally important for the formation of carbon? carbon and carbon? heteroatom bonds, and it is a formidable challenge for benzylic and allylic amine derivatives to be used as the alkylating agents. Herein we report a highly efficient benzylic and allylic alkylation of protic carbon and sulfur nucleophiles with sulfonamides through double Lewis acid catalyzed cleavage of sp³ carbon–nitrogen bonds at room temperature. In the presence of a catalytic amount of inexpensive ZnCl₂‐TMSCl (TMSCl: chlorotrimethylsilane), 1,3‐diketones, β‐keto esters, β‐keto amides, malononitrile, aromatic compounds, thiols, and thioacetic acid can couple with a broad range of tosyl‐activated benzylic and allylic amines to give diversely functionalized products in good to excellent yields and with high regioselectivity. Furthermore, the cross‐coupling reaction of 1,3‐dicarbonyl compounds with benzylic propargylic amine derivatives has been successfully applied to the one‐step synthesis of polysubstituted furans and benzofurans.     

PdII-Catalyzed stereospecific formation of tetrahydro- and 3,6-dihydro[2H]pyran rings: 1,3-chirality transfer by intramolecular oxypalladation reaction

The stereospecific synthesis of 2,6-disubstituted tetrahydropyran and 3,6-dihydro[2H]pyran is described. The Pd^II-catalyzed cyclization of the hydroxy nucleophile to the allylic alcohol takes place efficiently under mild conditions, with the stereogenic center on the secondary allylic alcohol transfers to a newly generated stereogenic center on pyran ring via a syn-S_N2′ type process.     

Evidence for involvement of cationic intermediate in epoxidation of chiral allylic alcohols and unfunctionalised alkenes catalysed by MnIII(quinazolinone) complexes

A pair of Mn^III(quinazolinone) complexes was prepared and evaluated in the catalytic epoxidation of the chiral allylic alcohols and unfunctionalised alkenes with iodosylbenzene. Epoxidation of chiral allylic alcohols with 1,3-allylic strain proceeded chemo- and diastereoselectively to give threo-epoxy alcohol (up to 99% d.r). Epoxidation of unfunctionalised alkenes by the proposed catalyst system proceeded nonselectively, as evidenced by the formation of isomerization and rearrangement products in the epoxidation of (Z)-stilbene. A three-step pathway involving a cationic intermediate is proposed for the formation of isomerization and rearrangement products. The fact that only products resulting from the cationic intermediate were detected in the oxidation of a mechanistic probe, (2-methoxy-3-vinylcyclopropyl)benzene, with Mn^III(quinazolinone) and PhIO substantiated the cationic oxygen transfer mechanism.     

Use of a bulky phosphine of weak σ-donicity with palladium as a versatile and highly-active catalytic system: allylation and arylation coupling reactions at 10-10 mol% catalyst loadings of ferrocenyl bis(difurylphosphine)/Pd

Carbon-carbon(sp²-sp² and sp¹-sp²) and carbon-nitrogen (nucleophilic allylation) coupling processes are promoted by a catalytic system containing [PdCl(η³-C₃H₅)]₂ with the new ferrocenyl bis(difurylphosphine) 1,1′-bis[di(5-methyl-2-furyl)phosphino]ferrocene, Fc[P(Fu^Me)₂]₂. Starting from aryl bromides or allylic acetates this versatile catalyst system may be used at low palladium loadings (10⁻¹-10⁻⁴ mol%) in some Heck, Suzuki, Sonogashira and allylic amination reactions to give cross-coupled products in excellent yield. Remarkably high activity is obtained in allylic substitution reactions, providing a significant impetus for the development of bulky phosphines possessing weak σ-donicity for this particular reaction.     

Diterpene Chemistry—VI : SeO2/H2O2 oxidations of exocyclic olefins

Unlike endocyclic olefins the major product from the SeO₂/H₂O₂ oxidation of exocyclic olefins is the same allylic alcohol as from the uncatalysed oxidation. Minor products derived from epoxide intermediates were investigated. The use of SeO₂ as an allylic oxidant for olefins has been extensively investigated, the functionality of the product being to a degree solvent dependent. Although the earlier mechanism of Guillemonat² is incorrect, his rules for the prediction of the position of oxidation still remain valid. A survey by Tratchenburg³ of the current position in SeO₂ oxidation postulates allylic oxidation as proceeding through the intermediacy of an oxaselenocyclobutane to a selenite ester which is solvated by competitive unimolecular (S_N1) and bimolecular (S_N2′) processes (Scheme 1).     

Intermolecular,Branch‐Selective,and Redox‐Neutral Cp*IrIII‐Catalyzed Allylic C−H Amidation

Herein, we report the redox‐neutral, intermolecular, and highly branch‐selective amidation of allylic C?H bonds enabled by Cp*Ir^III catalysis. A variety of readily available carboxylic acids were converted into the corresponding dioxazolones and efficiently coupled with terminal and internal olefins in high yields and selectivities. Mechanistic investigations support the formation of a nucleophilic Ir^III–allyl intermediate rather than the direct insertion of an Ir–nitrenoid species into the allylic C?H bond.     

Nickel‐Catalyzed Allylic Alkylation with Diarylmethane Pronucleophiles: Reaction Development and Mechanistic Insights

Palladium‐catalyzed allylic substitution reactions are among the most efficient methods to construct C?C bonds between sp³‐hybridized carbon atoms. In contrast, much less work has been done with nickel catalysts, perhaps because of the different mechanisms of the allylic substitution reactions. Palladium catalysts generally undergo substitution by a “soft”‐nucleophile pathway, wherein the nucleophile attacks the allyl group externally. Nickel catalysts are usually paired with “hard” nucleophiles, which attack the metal before C?C bond formation. Introduced herein is a rare nickel‐based catalyst which promotes substitution with diarylmethane pronucleophiles by the soft‐nucleophile pathway. Preliminary studies on the asymmetric allylic alkylation are promising.