SmI2-coupling reaction of chiral non-racemic α-bromo-α′-sulfinyl ketones with imines: synthesis of enantiomerically pure 2-methyl-3-amino-1-ol moieties

Chiral non-racemic α-bromo-α′-sulfinyl ketones were shown to react with imines in the presence of SmI₂ to give the corresponding 1,3-aminoketo derivatives with good syn-diastereoselectivity. Further reduction of these adducts either with DIBAL-H only or with DIBAL-H in the presence of Yb(OTf)₃ afforded syn- and anti-2-methyl-3-amino-1-ol moieties, respectively, in good yields and diastereoselectivities.     

Bifunctional‐Thiourea‐Catalyzed Diastereo‐ and Enantioselective Aza‐Henry Reaction

Bifunctional thiourea 1 a catalyzes aza‐Henry reaction of nitroalkanes with N‐Boc‐imines to give syn‐β‐nitroamines with good to high diastereo‐ and enantioselectivity. Apart from the catalyst, the reaction requires no additional reagents such as a Lewis acid or a Lewis base. The N‐protecting groups of the imines have a determining effect on the chirality of the products, that is, the reaction of N‐Boc‐imines gives R adducts as major products, whereas the same reaction of N‐phosphonoylimines furnishes the corresponding S adducts. Various types of nitroalkanes bearing aryl, alcohol, ether, and ester groups can be used as nucleophiles, providing access to a wide range of useful chiral building blocks in good yield and high enantiomeric excess. Synthetic versatility of the addition products is demonstrated by the transformation to chiral piperidine derivatives such as CP‐99,994.     

Synthetic study of solanoeclepin A: Cyclobutane cyclization via SmI2-additive-mediated reaction and D ring functionalization

The construction of tricyclo[5.2.1.0^1,6]decene skeleton was achieved by cyclobutane ring formation via improved radical reaction using SmI₂-H₂O-HFIP and SmI₂-LiCl conditions in good yields. Those additives were studied to increase the reactivity of SmI₂. Two interesting reactions via neighboring group participations are described for introducing the C4 oxygen functionality by the assistance of C6 substituent in a regioselective manner.     

A Novel Method for the Synthesis of α,β‐Unsaturated Amides Mediated by Samarium Diiodide

Promoted by Samarium diiodide (SmI₂), α,β‐unsaturated amides were formed from nitrogen anions (formed in situ by the reduction of nitro compounds) and α,β‐unsaturated esters. This reaction contrasts with the conjugate addition between amines and α,β‐unsaturated esters promoted by samarium triiodide (SmI₃) and provides an alternative attractive way to obtain α,β‐unsaturated amides using SmI₂.     

Solvent‐free cyanosilylation of aldehydes catalyzed by SmI2

A novel method to obtain racemic cyanohydrin silylethers by reaction of trimethylsilyl cyanide with a variety of aldehydes promoted by catalysis of SmI₂ is reported. The corresponding cyanosilylethers were obtained in high yields (up to 99%) in solvent‐ free conditions at room temperature within a relatively short time using 0.01–0.5 mol% catalyst loadings. Copyright © 2007 John Wiley & Sons, Ltd.     

Some unusual reactivities in the SmI2-mediated reductive coupling of acrylamides and acrylates with imides

A serendipitous discovery of some intra-molecular enolate addition reactions following a SmI₂-mediated reductive cross-coupling between imides and electron-deficient olefins leading to some novel compounds was investigated to determine the generality of the protocol and the possible mechanistic pathways involved. This provided a Z-selective synthesis of γ-ketoenediamides in good yields, albeit as of now the substrate scope remains limited. It was also shown that the seemingly similar acrylate substrates can behave differently compared to the corresponding acrylamides in their SmI₂-mediated reductive cross-coupling reaction with imides, and it was argued that these diverging reactivities are dominated by the ability of the acrylates to coordinate the samarium metal centre.     

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

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.

     

Synthetic studies toward longeracemine: a SmI2-mediated spirocyclization and rearrangement cascade to construct the 2-azabicyclo[2.2.1]heptane framework

Longeracemine, a member of the Daphniphyllum family of alkaloids contains a novel carbon framework featuring a highly functionalized 2-azabicyclo[2.2.1]heptane core as part of an overall 5/6/5/5/6/5 skeleton. A synthetic intermediate containing the core of longeracemine has been efficiently prepared by employing a stereoselective SmI₂-mediated cascade reaction to advance a 7-azabicyclo[2.2.1]heptadiene to a 2-azabicyclo[2.2.1]heptene that is functionally poised for conversion to the natural product.

A synthetic intermediate containing the core of longeracemine, that is functionally poised for conversion to the natural product, has been efficiently prepared by employing a stereoselective SmI₂-mediated cascade reaction.     

A Facile Synthetic Route to α-Selenoketones Promoted by SmI2 OR SmI3

α—Arylseleno or α—alkylselenoketones were synthesized by reactions of α—haloketones with RSeBr mediated by SmI₂ or SmI₃     

Synthesis of Novel 1,2,4‐oxadiazoline Derivatives Containing Quinoline Moiety by 1,3‐Dipolar Cycloaddition

A series of novel 1,2,4‐oxadiazoline derivatives containing 2‐(1,2,4‐triazol‐1‐yl)quinoline were synthesized by the reaction of imines with benzohydroximinoyl chlorides in the presence of Et₃N via 1,3‐diplolar cycloaddition reaction. The structures of the target compounds were confirmed by IR, ¹H NMR, MS, elemental, and X‐ray crystallographic analysis.     

Rate Study of Proton Catalyzed SmI2 Reduction of 2‐Heptanone and 1,2‐Epoxydecane

Rate constants directly measured from the GC‐analyzed method for SmI₂ reduction of 2‐heptanone and 1,2‐epoxydecane in the presence of various proton sources were obtained. Water exhibits much stronger catalytic effect than methanol and t‐butanol. Dependence of reaction rates on concentration of SmI₂ and temperature were studied.     

Generation and metathesis of azomethine imines in reaction of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with het(aryl)methylidenemalononitriles

A new metathesis reaction of azomethine imines is found. Catalytic or thermal diaziridine ring opening of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes leads to azomethine imines reacting further with het(aryl)methylidenemalononitriles to give in situ new azomethine imines inaccessible by common synthetic methods. New azomethine imines are detected as pyrazolines formed via a 1,4-H shift and trapped by the [3+2] cycloaddition with various dipolarophiles to yield 1,5-diazabicyclo[3.3.0]octane derivatives bearing pharmacophoric heterocycles, e.g. furan, nitrofuran, thiophene, and indole. The best results are achieved in the Et₂O·BF₃-catalyzed reactions in ionic liquids.     

On the Role of Pre‐ and Post‐Electron‐Transfer Steps in the SmI2/Amine/H2O‐Mediated Reduction of Esters: New Mechanistic Insights and Kinetic Studies

The mechanism of the SmI₂‐mediated reduction of unactivated esters has been studied using a combination of kinetic, radical clocks and reactivity experiments. The kinetic data indicate that all reaction components (SmI₂, amine, H₂O) are involved in the rate equation and that electron transfer is facilitated by Brønsted base assisted deprotonation of water in the transition state. The use of validated cyclopropyl‐containing radical clocks demonstrates that the reaction occurs via fast, reversible first electron transfer, and that the electron transfer from simple Sm(II) complexes to aliphatic esters is rapid. Notably, the mechanistic details presented herein indicate that complexation between SmI₂, H₂O and amines affords a new class of structurally diverse, thermodynamically powerful reductants for efficient electron transfer to carboxylic acid derivatives as an attractive alternative to the classical hydride‐mediated reductions and as a source of acyl‐radical equivalents for C?C bond forming processes.     

Samarium diiodide as coupling agent between aldehydes and organic halides for the synthesis of homoallylic and homobenzylic alcohols

Many aliphatic aldehydes are transformed into secondary alcohols by reaction with allyl halides or benzylic halides in presence of SmI₂.     

Nickel‐Catalyzed Synthesis of N‐Aryl‐1,2‐dihydropyridines by [2+2+2] Cycloaddition of Imines with Alkynes through T‐Shaped 14‐Electron Aza‐Nickelacycle Key Intermediates

Despite there being a straightforward approach for the synthesis of 1,2‐dihydropyridines, the transition‐metal‐catalyzed [2+2+2] cycloaddition reaction of imines with alkynes has been achieved only with imines containing an N‐sulfonyl or ‐pyridyl group. Considering the importance of 1,2‐dihydropyridines as useful intermediates in the preparation of a wide range of valuable organic molecules, it would be very worthwhile to provide novel strategies to expand the scope of imines. Herein we report a successful expansion of the scope of imines in nickel‐catalyzed [2+2+2] cycloaddition reactions with alkynes. In the presence of a nickel(0)/PCy₃ catalyst, a reaction with N‐benzylidene‐P,P‐diphenylphosphinic amide was developed. Moreover, an application of N‐aryl imines to the reaction was also achieved by adopting N‐heterocyclic carbene ligands. The isolation of an (η²‐N‐aryl imine)nickel(0) complex containing a 14‐electron nickel(0) center and a T‐shaped 14‐electron five‐membered aza‐nickelacycle is shown. These would be considered as key intermediates of the reaction. The structure of these complexes was unambiguously determined by NMR spectroscopy and X‐ray analyses.     

Synthesis of N6-phosphorylated sydnone imines and their functionalization via 4-Li derivatives. Novel bicyclic sydnone imines

The highly efficient gram-scale method for preparation of up to date hardly available N₆-phosphorylated sydnone imines based on the reaction of sydnone imine hydrochlorides with substituted phosphinate or phosphonate acids chlorides in the presence of a base was elaborated. A possibility of straight deprotonation of sydnone imines with n-BuLi followed by the reaction 4-Li-derivatives thus obtained with electrophiles was demonstrated. Novel representatives of bicyclic sydnone imines fused via 4,5-edge of the oxadiazolium ring were obtained. Also sydnone imines containing both phosphorus and sulfur functionalities were obtained with high yields.     

Comparative study of TmI2, SmI2, and SmI2/HMPA in the cross-coupling reactions of 2-acetylthiophene and thiophene-2-carboxylate with carbonyl compounds

The cross-coupling reactions of acetylthiophene or ethyl thiophene-2-carboxylate with aldehydes or ketones were achieved in a regioselective manner by using thulium diiodide in THF solution. Similar coupling reactions were also realized by using samarium diiodide together with excess amounts of hexamethylphosphoramide (HMPA). However, ethyl thiophene-2-carboxylate was inert in SmI₂/THF solution, and acetylthiophene was simply reduced to thienylethanol by SmI₂ in the absence of HMPA.     

Addition of Me3SiCN to trifluoromethyl derivates of N‐(pyridylmethylidene) anilines catalyzed by Lewis acids

A series of novel Shiff bases (1a–h) was synthesized by condensation of pyridinecarboxaldehydes (1–4) with 3‐ and 4‐trifluoromethylanilines (5, 6) in the presence of molecular sieves (4 Å). It was found that AlCl₃ and AlBr₃ catalyzed the addition of Me₃SiCN to the C?N bond of the imines obtained, whereas the other Lewis acids studied (YCl₃, LaCl₃, ZnI₂) were not active. The reactivity of the imines in the title reaction, on the whole, correlated with their basicity. Besides the addition giving the expected α‐amino nitriles (2a,b,d–f,h), an unusual reaction leading to unsaturated nitriles (3a–h) was observed. The structures of saturated and unsaturated products 2d and 3c were determined by X‐ray diffraction. Copyright © 2001 John Wiley & Sons, Ltd.     

A stereoselective cyclisation cascade mediated by SmI2–H2O: synthetic studies towards stolonidiol

A cascade reaction involving sequential conjugate reduction, stereoselective aldol cyclisation and chemoselective lactone reduction mediated by SmI₂–H₂O provides access to a cyclopentanol bearing two vicinal quaternary stereocentres with good stereocontrol. The functionalised cyclopentanol product has been converted to a key intermediate in ongoing asymmetric studies towards stolonidiol.     

Formal synthesis of (−)-oleocanthal by means of a SmI2-promoted intramolecular coupling of bromoalkyne with α,β-unsaturated ester

A novel approach to the synthesis of (?)-oleocanthal starting from d-ribose, in which a SmI₂-promoted intramolecular coupling of bromoalkyne with α,β-unsaturated ester is a key step, has been developed.