SmI2 In THF Research Articles

Secondary Amides as Hydrogen Atom Transfer Promoters for Reactions of Samarium Diiodide.

Two secondary amides (N-methylacetamide and 2-pyrrolidinone) were used as additives with SmI2 in THF to estimate the extent of N-H bond weakening upon coordination. Mechanistic and synthetic studies demonstrate significant bond-weakening, providing a reagent system capable of reducing a range of substrates through formal hydrogen atom transfer.

SmI2-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B.

The synthesis and reactivity of indole derivatives substituted in the benzene section was studied. Starting materials 4- and 6-iodoindole were conveniently prepared via the Batcho–Leimgruber route and purified by sublimation. Novel vicinally indolyl-substituted cyclopentanols with unexpected cis-configuration were formed by SmI2-mediated reductive dimerization of a 4-(indol-6-yl)butenone, obtained by Heck reaction. The two indolyl units appear to chelate Sm(II)/(III) leading to a gauche-type arrangement at the newly formed bond between the two β-carbons. Through a sequence of Sonogashira cross coupling and Meyer–Schuster rearrangement 6-prenoylindole was synthesized and reductively dimerized to a cyclopentane in a [3 + 2] cycloaddition by treatment with SmI2 in THF. From 4-iodoindole, the natural product indiacen B from the myxobacterium Sandaracinus amylolyticus was synthesized for the first time, confirming its antimicrobial activity. The E-configuration of the chloroalkene moiety of indiacen B was confirmed by X-ray analysis.

Reversed Electron Apportionment in Mesolytic Cleavage: The Reduction of Benzyl Halides by SmI2.

The paradigm that the cleavage of the radical anion of benzyl halides occurs in such a way that the negative charge ends up on the departing halide leaving behind a benzyl radical is well rooted in chemistry. By studying the kinetics of the reaction of substituted benzylbromides and chlorides with SmI2 in THF it was found that substrates para-substituted with electron-withdrawing groups (CN and CO2 Me), which are capable of forming hydrogen bonds with a proton donor and coordinating to samarium cation, react in a reversed electron apportionment mode. Namely, the halide departs as a radical. This conclusion is based on the found convex Hammett plots, element effects, proton donor effects, and the effect of tosylate (OTs) as a leaving group. The latter does not tend to tolerate radical character on the oxygen atom. In the presence of a proton donor, the tolyl derivatives were the sole product, whereas in its absence, the coupling dimer was obtained by a SN 2 reaction of the benzyl anion on the neutral substrate. The data also suggest that for the para-CN and CO2 Me derivatives in the presence of a proton donor, the first electron transfer is coupled with the proton transfer.

Pinacol Approach to the Eunicellane Skeleton

AbstractA short route to a partially aromatic version of the eunicellane skeleton, which occurs in cytostatic marine diterpenoids, was developed. The key step is the pinacol cyclization of a p‐cymene‐derived C20 keto aldehyde to form the 10‐membered ring of the [8.4.0] bicycle. We observed different reactivities upon employment of the SmI2/THF or TiCl3/Zn–Cu/DME reagent system. Upon treatment with SmI2 in THF, the arylalkynes cyclized to novel [4.2.0] cyclohexylidene benzocyclobutanols, whereas the corresponding arylalkenes reacted to the desired [8.4.0] system. Under McMurry conditions, the alkynes afforded the [8.4.0] system, and this represents the first de novo synthesis of the complete eunicellane skeleton with a benzene partial structure.

The Effect of Replacing Carbon by Nitrogen in Reductions with SmI2: Reduction of Azobenzene

The reduction of azobenzene by SmI(2) in THF to give hydrazobenzene was investigated. The kinetics are first order in the substrate and first order in SmI(2). The kinetic order in MeOH is ca. 0.56, and in TFE it is ca. 0.2. The fractional order in the proton donors is interpreted as being a result of their acting in two opposing manners. In one the proton donor enhances the reaction by protonation of the radical anion, and in the other it slows the reaction by binding to the lone pair electrons of the nitrogen in the azobenzene. This hampers the fast inner-sphere electron-transfer mode. Experiments conducted in the presence of low concentrations of HMPA show rate enhancement suggesting that the SmI(2), which is partly coordinated to HMPA molecules, has some free sites to bind to the substrate. When more HMPA is added, it prevents the fast inner-sphere mechanism and the rate decreases. In this system, the increase in the reduction potential of SmI(2) caused by HMPA is similar to the rate enhancement by an inner sphere mechanism. In general, the replacement of a skeletal carbon by a nitrogen atom causes a significant rate enhancement.

ChemInform Abstract: Some Features of an SmI2-(Me2N)3P-THF System. Transformation of Esters into Dimethylamides.

Smil-intermediates generated upon addition of (Me2N)3P to a solution of SmI2 in THF exhibit the properties of a single-electron reducing agent and an N-nucleophile. In particular,N,N-dimethylamides are formed from esters.

Reduction of Benzophenones with SmI2. Post Electron Transfer Processes

The kinetics of the reaction of several substituted benzophenones with SmI(2) in THF was studied by using stopped flow spectrometry. The electron transfer takes place during the dead time of mixing and for most derivatives it is nearly quantitative. In the presence of an excess of substrate and in the absence of proton donors the dimerization reaction to pinacol is second order in the radical anion and has a negative order in SmI(2). Similarly, in reactions in the presence of excess SmI(2), the reaction shows negative order in the concentration of the substrate. It is concluded that the radical anions exist as a mixture of monomeric ion pairs and Streitwieser dimers. In the presence of trifluoroethanol, protonation of the Streitwieser dimer occurs with a rate constant an order of magnitude larger than that of the monomer.

Biogenetic-Like Cyclization of Denudatenone A to Dolabellane-Type Diterpenoids Induced by Samarium(II) Iodide: A Ketyl-Olefin Radical Coupling Reaction Forming Five-Membered Carbocycles

Denudatenone A was treated with SmI2 in THF with or without the additives to form dolabellane-type diterpenoids as a result of 5-exo-trig mode of cyclization. The cyclized products were effectively obtained when water or HMPA was added. This constitutes the biogenetic-type transformation of vibsane to dolabellane diterpenoids.

Mechanistic Impact of Water Addition to SmI2: Consequences in the Ground and Transition State

The mechanistic impact of water addition to SmI2 on the ground state and rate-limiting transition state structures in the reduction of benzyl bromide was determined using UV-vis spectroscopy, cyclic voltammetry, vapor pressure osmommetry, and stopped-flow spectrophotometric studies. The results obtained from these studies show that, upon addition of water, SmI2 in THF (or DME) becomes partially water-solvated by displacing metal-coordinated solvent. Further addition of water displaces remaining bound solvent and induces a monomer-dimer equilibrium of the SmI2-water complex. Concomitant with this process, a thermodynamically more powerful reductant is created. Rate studies on the reduction of benzyl bromide by SmI2-water are consistent with reaction occurring through a dimeric transition state with the assembly of the activated complex requiring an equivalent of water at low concentrations but not at higher concentrations. The mechanistic complexity of the SmI2-water system shows that simple empirical models describing the role of water in SmI2-mediated reductions are likely to contain a high degree of uncertainty.

Synthesis of Novel Binuclear Samarium Thiolate Complexes [(THF)3I2Sm(μ‐SAr)]2 (Ar=Ph, 4‐Me2NC6H4) and Crystal Structure of [(THF) 3I2Sm(μ‐S‐4‐Me2NC6H4)]2

Abstract Reactions of SmI2 in THF with ArSSAr produced two binuclear samarium thiolate complexes [(THF)3I2‐ Sm(μ‐SAr)]2 [Ar=Ph (1), 4‐Me2NC6H4 (2)] in high yields. The structure of 2 was characterized by single crystal X‐ray crystallography. The crystal of 2 belongs to the triclinic system with space group $ P {\bar 1} $ and a=0.95705(13) nm, b=1.22287(14) nm, c=1.26450(14) nm, α=64.194(11)°, B=78.491(13)°, γ=76.176(12)°, V=1.2860(3) nm3, Z=1, μ=4.783 mm−1, Dc=1.964 Mg/m3, M=1521.19, S=1.046, R1=0.0358, wR2=0.0910. X‐ray analysis revealed that 2 is a thiolate‐bridged dimer in which each Sm atom adopts a distorted pentagonal bipyramidal coordination geometry.

Samarium diiodide mediated regeneration of 1,2-benzene diamine and preparation of benzimidazolin-2-ones from 2,1,3-benzothiadiazoles

On treatment with SmI2 in THF and in the presence of methanol, 2,1,3-benzothiadiazoles underwent reductive N–S bond cleavage leading to 1,2-benzenediamines in high yields. Without methanol but in the presence of triphosgene, benzimidazolin-2-ones were obtained in moderate yields under mild conditions.

Very Rapid Preparation of SmI2 by Sonic Treatment of Iodoform and Metallic Samarium.

A very rapid preparation of SmI2 by sonication of a mixture of metallic samarium and iodoform in THF is described. To prove the synthetic applications of the obtained SmI2 several high-yielding reactions were carried out. Preliminary results for the generation of SmI2 in THF by sonication from diiodomethane, 1,2-diiodoethane, or iodine are also described. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Very Rapid Preparation of SmI2 by Sonic Treatment of Iodoform and Metallic Samarium

AbstractA very rapid preparation of SmI2 by sonication of a mixture of metallic samarium and iodoform in THF is described. To prove the synthetic applications of the obtained SmI2 several high‐yielding reactions were carried out. Preliminary results for the generation of SmI2 in THF by sonication from diiodomethane, 1,2‐diiodoethane, or iodine are also described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Synthesis of a homoleptic Sm(ii) bis(phosphinimino)methanide

Reaction of two molar equivalents of [KN(SiMe3)2] and a mixture of [CH2(Ph2PNC6H2-Me3-2,4,6)2] and SmI2 in THF resulted in the formation of a stable homoleptic samarium dialkyl without additional solvent coordination.

Samarium diiodide-promoted sequential coupling-aldol-reduction reactions of ferrocene-substituted enones

Abstract On treatment with SmI2 in THF, 1-ferrocenyl-3-phenyl-2-propen-1-one and its related ferrocene-substituted enones underwent cyclodimerizations to give aldols (2a–g) with 3,4-trans configuration. Further reduction by using increased amounts of SmI2 produced the corresponding diols. The stereoselectivity in this study was comparable with that in the SmI2-promoted cyclodimerization of chalcones, but in contrast to that in the SmI2-promoted cyclization-aldol reaction of 1,1’-dicinnamoylferrocenes. The thienyl- and furyl-substituted enones 5a and 5b could be visualized as an extended system of conjugated ketones, so that the SmI2-mediated coupling reactions occurred preferably by linkages of β-carbons with thiophene or furan rings, giving compounds 8a,b and 9a,b.

Some features of an SmI2−(Me2N)3P—THF system. Transformation of esters into dimethylamides

Smil-intermediates generated upon addition of (Me2N)3P to a solution of SmI2 in THF exhibit the properties of a single-electron reducing agent and an N-nucleophile. In particular,N,N-dimethylamides are formed from esters.

The First Synthesis of Herbicidin B. Stereoselective Construction of the Tricyclic Undecose Moiety by a Conformational Restriction Strategy Using Steric Repulsion between Adjacent Bulky Silyl Protecting Groups on a Pyranose Ring

The first total synthesis of the nucleoside antibiotic herbicidin B (1b) was achieved, where a novel aldol-type C-glycosidation reaction promoted by samarium diiodide (SmI2) was used as a key step. Treatment of methyl 3,4-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-1-phenylthio-2-ulos-β-d-glucuronate (13) with SmI2 in THF regioselectively gave the corresponding 1-enolate, which was readily trapped with 1-β-d-xylosyladenine 5‘-aldehyde derivative 7 to afford the product 19a,b as an anomeric mixture. Dehydration of the 5‘-hydroxyl in 19a,b with using Burgess's inner salt gave the enone 20, which was subsequently hydrogenated to give undeculofuranuronyl adenine derivative 21. Deprotection of 21 gave a tricyclic sugar nucleoside, 23. However, it was an epimer of herbicidin B at the 6‘-position. Construction of the desired 6‘-α-configuration was achieved by using a conformational restriction strategy based on repulsion between adjacent bulky protecting groups on the pyranose ring. Thus, when methyl 3-O-tert-butyldimethylsilyl-4-O-tert-butyldiphenylsilyl-1-phenylthio-2-ulos-d-glucuronate (29c), the conformation of which was restricted in an unusual 1C4-like conformation, was used as a precursor for ulose 1-enolate in the SmI2-promoted aldol reaction with 7, the desired 6‘-α-aldol product 30c was predominantly obtained. Compound 30c was dehydrated, followed by hydrogenation of the alkenyl bond and then deprotection to form an internal ketal linkage between the 3‘- and 7‘-positions, which spontaneously gave herbicidin B.

Structure and Energetics of the Samarium Diiodide-HMPA Complex in Tetrahydrofuran.

The role of HMPA as a ligand for SmI2 and the stoichiometry and energetics of formation for the SmI2-HMPA complex in THF were investigated employing UV-vis spectroscopy, isothermal titration calorimetry (ITC), and vapor pressure osmometry (VPO). The aggregation number for SmI2 in THF was found to be 0.98 ± 0.09 over the entire concentration range studied (6.71-84.0 mM), indicating that SmI2 is monomeric. The UV-vis data suggest that four HMPA ligands coordinate to SmI2, and this was supported by ITC experiments. The combined results are consistent with [SmI2(HMPA)4] being the reductant responsible for the unique reactivity exhibited by SmI2-HMPA cosolvent combinations.

ヨウ化サマリウムを用いたカルバニオンの発生とその反応

Reduction of aryl and vinyl radicals to the corresponding organosamarium species by SmI2 can be attained by using benzene-HMPA as a solvent system. Thus, SmI2-mediated Barbier- and Grignardtype coupling reactions between ketones and aryl, vinyl, or alkynyl iodides proceed via organosamarium species in benzene-HMPA. Reductive dehalogenation of 1, 1-dihaloalkenes by SmI2 in benzene-HMPA generates alkylidenecarbenes, which undergo either 1, 5-C-H insertion giving cyclopentenes or 1, 2-shift giving alkynes. On the other hand, SmI2 was found to be useful to effect 2, 3-rearrangement under mild conditions. Metalated ethers undergoing Wittig rearrangement are regioselectively generated by either an intramolecular 1, 5-hydrogen transfer of a vinyl radical, generated by a single electron transfer from SmI2 to γ-haloallyl ethers, or a net two-electron reduction of diallyl acetals with the liberation of an allyloxy samarium by SmI2 in acetonitrile. 2, 3-Rearrangement of allylic sulfonium ylides can be effected by the reaction of allylic sulfides with samarium carbenoid, generated from CH2I2 and SmI2 in THF.

Reductive deamination of α-amino carbonyl compounds by means of samarium iodide

Reaction of α-amino carbonyl compounds with SmI2 in THF–HMPA in the presence of a proton source afforded the deamination products, where the fragmentation occurred between the nitrogen and the carbon α to the carbonyl group.