Samarium Enolate Research Articles

Stereoselective Cascade Cyclizations with Samarium Diiodide to Tetracyclic Indolines: Precursors of Fluorostrychnines and Brucine.

A series of γ-indolylketones with fluorine, cyano or alkoxy substituents at the benzene moiety was prepared and subjected to samarium diiodide-promoted cyclization reactions. The desired dearomatizing ketyl cascade reaction forming two new rings proceeded in all cases with high diastereoselectivity, but with differing product distribution. In most cases, the desired annulated tetracyclic compounds were obtained in moderate to good yields, but as second product tetracyclic spirolactones were isolated in up to 29 % yield. The reaction rate was influenced by the substituents at the benzene moiety of the substrate as expected, with electron-accepting groups accelerating and electron-donating groups decelerating the cyclization process. In case of a difluoro-substituted γ-indolylketone a partial defluorination was observed. The intermediate samarium enolate of the tetracyclic products could be trapped by adding reactive alkylating agents as electrophiles delivering products with quarternary carbons. In the case of a dimethoxy-substituted tetracyclic cyclization product a subsequent reductive amination stereoselectively provided a pentacyclic compound that was subsequently N-protected and subjected to a regioselective elimination. The obtained functionalized pentacyclic product should be convertible into the alkaloid brucine by four well-established steps. Overall, the presented report shows that functionalized tetracyclic compounds with different substituents are rapidly available with the samarium diiodide cascade cyclization as crucial step. Hence, analogues of the landmark alkaloid strychnine, for example, with specific fluorine substitutions, should be easily accessible.

Cyclopentane Formation from Flexible Precursors Using Samarium(II) Reagents

Three efficient methods for five‐membered ring carbocycle synthesis have been developed from simple starting materials using samarium(II) reagents. A Reformatsky aldol reaction proceeded efficiently with samarium(II) iodide using lithium bromide as an additive. A new intramolecular alkylation of a samarium enolate was realized with a pendant sulfonate ester leaving group. Pinacol cyclization of a simple diketone was also demonstrated giving a diol product in high stereoselectivity. A promising lead result has been established demonstrating enantioselectivity in a chiral ligand controlled Reformatsky aldol reaction.

Samarium-mediated intramolecular cross-couplings of an α,β-unsaturated N-acylpyrrole

The first example of an α,β-unsaturated N-acylpyrrole undergoing a SmI2-mediated cyclization is reported. In contrast to other unsaturated units, the intermediate samarium enolate readily engages in aldol-type reactions, necessitating careful control of the reaction conditions.

ChemInform Abstract: Synthesis and Synthetic Applications of Samarium Enolates of Unmasked Amides: Efficient Synthesis of 3‐Aminoamides and 3‐Amino‐2‐chloroamides.

AbstractIn situ prepared samarium acetamide and chloroacetamide enolates react with the aldimines to yield the target compounds.

ChemInform Abstract: Samarium(II) Iodide Promoted Radical Ring Opening Reactions of Cyclopropyl Ketones.

Radical ring opening reactions of cyclopropyl ketones mediated by samarium(II) iodide-induced single electron transfer have permitted the elaboration of a tandem rearrangement cyclisation strategy. The resultant samarium enolates may be effectively quenched on oxygen or carbon by electrophiles.

Synthesis and Synthetic Applications of Samarium Enolates of Unmasked Amides: Efficient Synthesis of 3-Aminoamides and 3-Amino-2-chloroamides

Unprotected samarium acetamide and chloroacetamide enolates were prepared by treatment of iodoacetamide and dichloroacetamide with SmI2. The addition of these samarium-based enolates to aldimines was efficiently performed affording 3-aminoamides and 3-amino-2-chloroamides in high yields. A mechanism is proposed to explain the synthesis and reactivity of samarium enolates of primary amides.

ChemInform Abstract: Preparation of a Fluorous Chiral BINOL Derivative and Application to an Asymmetric Protonation Reaction.

Fluorous Chiral Proton Source (R,S)-FDHPEB resulted in a higher enantioselectivity (95% ee) than that of the original nonfluorous (R,S)-DHPEB (87% ee) in an enantioselective protonation of a samarium enolate. (R,S)-FDHPEB was easily recovered by a simple filtration through a fluorous reverse phase silica gel and was recyclable.

Highly Diastereoselective Samarium Diiodide Induced Ketyl Cyclisations of Indole and Pyrrole Derivatives – Scope and Limitations

AbstractHere we summarise our results for SmI2‐induced 5‐exo‐trig to 8‐exo‐trig reductive cyclisations of suitably substituted indole and pyrrole derivatives. All precursors were easily prepared by simple N‐alkylation or N‐acylation of indole and pyrrole derivatives with the corresponding iodo alkanones, acid chlorides or lactones. The SmI2‐induced cyclisations in most cases provided tri‐ and tetracyclic derivatives, even in the absence of HMPA, in good to very good yields and with excellent diastereoselectivities. Extensive investigations of the reaction conditions revealed that in the presence of different proton sources SmI2‐induced cyclisations afforded mainly one major type of diastereomer (thermodynamic control), so the formation of three or four stereogenic centres is controlled in one step. The mechanism of the SmI2‐induced ketyl coupling is discussed in more detail on the basis of these observations and two possible mechanistic pathways are compared. The assumed intermediate samarium enolates were also trapped with allyl iodide, furnishing interesting polycyclic N‐heterocycles bearing newly formed quaternary centres as single diastereomers.

ChemInform Abstract: The Addition Reaction of Samarium Enolates and 2‐Haloenolates Derived from Esters, and Amides to Imides. Totally Stereoselective Synthesis of Enantiopure 3,4‐Diamino Esters or Amides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The Addition Reaction of Samarium Enolates and 2-Haloenolates Derived from Esters, and Amides to Imines. Totally Stereoselective Synthesis of Enantiopure 3,4-Diamino Esters or Amides

The addition reaction of samarium enolates and 2-haloenolates derived from esters and amides to imines takes place in an efficient manner. A novel protocol to perform the addition reaction of samarium enolates derived from esters or amides to chiral 2-aminoimines, with total stereoselectivity and without racemization, is also reported. The use of samarium enolates in place of other classic metallic enolates (lithium, magnesium, etc.) could be a valuable alternative to obtain enantiopure 3,4-diamino esters or amides, when enolates of low basicity are necessary.

ChemInform Abstract: The Use of Samarium Enolates, a Novel Alternative in the Addition Reactions to Imines. Synthesis of 3‐Amino Esters, Amides and Enantiopure 3,4‐Diamino Esters.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Samarium Enolates and Their Application in Organic Synthesis

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The Use of Samarium Enolates, A Novel Alternative in the Addition Reactions to Imines. Synthesis of 3‐Amino Esters, Amides and Enantiopure 3,4‐Diamino Esters

Abstractmagnified imageAn efficient reaction of tosylimines with a range of samarium enolates (derived from esters, and amides) is reported. The reaction with the α‐dibenzylamino‐N‐tert‐butanesulfinimine derived from chiral phenylalaninal afforded the corresponding enantiopure 3,4‐diamino ester with very high diastereoselectivity.

ChemInform Abstract: Samarium(II)—Mediated Linker Cleavage—Cyclization in Fluorous Synthesis: Reactions of Samarium Enolates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Samarium diiodide-promoted electrophilic amination of ketone enolates: efficient synthesis of quaternary carbon-containing α-aminated ketones

An efficient and practical electrophilic amination method that allows the preparation of useful quaternary carbon-containing α-aminoketones was developed. The reaction proceeds regiospecifically via a samarium enolate intermediate at room temperature in the presence of mild reducing agent SmI 2. Unlike the most reported lithium enolate cases, this new amination method does not require the use of strong base such as BuLi or LDA.

Samarium(II)−Mediated Linker Cleavage−Cyclization in Fluorous Synthesis: Reactions of Samarium Enolates

SmI2 has been used to cleave a sulfur linker and trigger cyclizations in strategies for the traceless fluorous synthesis of N-heterocycles. The studies give further insights into the reactivity of samarium enolates.

Use of samarium diiodide in the field of asymmetric synthesis

Samarium diiodide may be a useful reagent in a step of an asymmetric synthesis process. It can release a blocking group in mild conditions, as described in several examples. SmI2 has been used as electron donor in many C–C bond formations in presence of a chiral auxiliary. It can also generate samarium enolates which were subjected to asymmetric protonation. The examples selected in this review of SmI2 methodology concern only the cases where the chiral auxiliary is not retained in the final product.

Highly Substituted Dihydroindole Derivatives by Intermolecular Couplings of Samarium Ketyls and Indoles

Samarium diiodide promoted intermolecular reductive couplings of ketones and aldehydes to 3-methoxycarbonyl-substituted indole derivatives afforded dihydroindoles in good yields and with excellent diastereoselectivities. Trapping of the intermediate samarium enolate with allyl iodide furnished tricyclic lactones with good efficacy, thus demonstrating the potential of this method for the construction of structurally complex indole derivatives by a three-component protocol.

Synthesis of star-shaped poly(ε-caprolactone) by samarium-based tetrafunctional initiator and its dilute-solution properties

An in situ–generated tetrafunctional samarium enolate from the reduction of 1,1,1,1-tetra(2-bromoisobutyryloxymethyl)methane with divalent samarium complexes [Sm(PPh2)2 and SmI2] in tetrahydrofuran has proven to initiate the ring-opening polymerization of ϵ-caprolactone (CL) giving star-shaped aliphatic polyesters. The polymerization proceeded with quantitative conversions at room temperature in 2 h and exhibited good controllability of the molecular weight of polymer. The resulting four-armed poly(ϵ-caprolactone) (PCL) was fractionated, and the dilute-solution properties of the fractions were studied in tetrahydrofuran and toluene at 30°C. The Mark–Houwink relations for these solvents were [η] = 2.73 × 10−2Mw0.74 and [η] = 1.97 × 10−2Mw0.75, respectively. In addition, the unperturbed dimensions of the star-shaped PCL systems were also evaluated, and a significant solvent effect was observed. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 175–182, 2006

Solid‐supported synthesis of well‐defined polymethacrylate with samarium(III) enolate immobilized on polystyrene beads through an acetal‐type linker

A solid-supported samarium enolate, designed to have an acetal-type linker, initiated the polymerization of methyl methacrylate (MMA) in a living anionic fashion. The linker was selectively cleaved at the acetal structure by a treatment with a weak acid, and this produced well-defined poly(MMA).