Samarium(II)-promoted radical spirocyclization onto an aromatic ring

Samarium(II)-mediated spirocyclization onto an aromatic ring was achieved by the reaction of methyl 4-(4-oxoalkyl)benzoates with SmI(2) in the presence of i-PrOH and HMPA, yielding methyl 1-alkyl-1-hydroxyspiro[4.5]dec-6-ene-8-carboxylates in moderate to high yields. Utilizing this chemistry, spiro[3.5] and -[5.5] systems, and sterically congested spiro[4.5] systems, were easily synthesized. For the successful conversion, appropriate activation of the aromatic ring has proven to be extremely important: while an ester or amide functionality on the aromatic ring can promote the spirocyclization, a sulfonamide substituent causes ortho cyclization.     

Samarium(II) iodide reduction of isoxazolidines

SmI₂ was used as reducing agent for the N-O bond cleavage in isoxazolidines. The procedure revealed is general and particularly useful for the transformation of 5-spirocyclopropane isoxazolidines to the corresponding β-aminocyclopropanols, a troublesome transformation with other known reagents.     

Radical and palladium-catalyzed cyclizations to cyclobutenes: an entry to the BCD ring system of penitrem D

A novel approach toward the synthesis of the BCD ring system of penitrem D is described. The strategy capitalizes on the fast cyclization rates of aryl radicals into cyclobutenes and allows access to a variety of fused tricyclic structures. Radical/polar crossover reactions of precursors 24-29 promoted by samarium diiodide in the presence of HMPA and acetone allow access to the fully functionalized BCD ring system of penitrem D. The stereochemical implications of these processes are evaluated, and a Pd-mediated cyclization approach toward the penitrems is also introduced.     

Samarium(II)-mediated spirocyclization by intramolecular aryl radical addition onto an aromatic ring

Samarium(II)-mediated spirocyclization by intramolecular addition of aryl radicals onto an aromatic ring was achieved by the reaction of N-(2-iodophenyl)-N-alkylbenzamides with SmI2 in the presence of HMPA, yielding spirocyclic indolin-2-one derivatives. The ether congeners afford spirocyclic benzofuran derivatives in moderate yields by aryl radical addition onto a benzene ring without having an electron-withdrawing group. The reaction with other aryl groups such as naphthalene and indole rings is also described.     

Indium(I) iodide mediated efficient synthesis of selenoglycosides

A convenient odorless methodology has been developed for the preparation of selenoglycosides through indium(I) iodide mediated cleavage of diselenides and reaction with glycosyl bromides. The yields were excellent in all cases. Retention of the configuration at the anomeric center was observed in each case.     

Synthesis of the BCD ring system of azaspiracid: construction of the trispiro ring structure by the thioether approach

The synthesis of the BCD ring system of azaspiracid 1 has been attained. Construction of the stereochemistry of the C₁₃ position was successfully controlled by connection between the B ring and the C ring with a sulfur atom.     

An approach to the imine ring system of pinnatoxins

[reaction: see text] A concise stereoselective approach to the spirobicyclic imine fragment of pinnatoxins and pteriatoxins is described. The approach relies on a tandem reaction sequence involving consecutive sigmatropic rearrangements to build the quaternary chiral center at the core of the spirobicyclic ring system.     

A multi-scale approach to spin crossover in Fe(II) compounds

We report here for the first time a multi-scale study on the concept of spin-crossover compounds, which integrates improved density functionals, a polarizable force field and hybrid QM/MM calculations. This multi-scale setup is applied to the temperature dependence of spin states of a Fe(II) compound with trispyrazolylborate ligands that exhibits spin-crossover. Our study shows a transition temperature of around 290 K, which is in perfect agreement with experimental results. Moreover, based on our data we provide the origin of why spin transition occurs in this iron-compound: it results directly from spin-state changes in the iron-compound that lead to more favourable electrostatic interactions for the high-spin state.     

Samarium(II)-mediated reactions of gamma,delta-unsaturated ketones. Cyclization and fragmentation processes

[reaction: see text] On treatment with samarium(II) iodide, gamma,delta-unsaturated ketones undergo very different processes depending upon the nature of the reaction conditions. Employing samarium(II) iodide and MeOH, functionalized syn-cyclopentanol products are obtained stereoselectively. Mechanistic studies suggest that this cyclization occurs via a sequential reduction/intramolecular aldol reaction. With samarium(II) iodide and HMPA, products of a 4-exo-trig cyclization and of an interesting fragmentation reaction are observed.     

An intramolecular diels-alder approach to the galanthan ring system

A novel “phenylbutadiene + Δ²-pyrroline” intramolecular cycloaddition has been used to construct a functionalized galanthan.     

Sequenced reactions with samarium(II) iodide. Sequential intramolecular Reformatsky/nucleophilic acyl substitution reactions for the synthesis of medium-sized carbocycles

Samarium(II) iodide was used to access eight- and nine-membered carbocycles via a domino reaction comprised of a Reformatsky reaction followed by a nucleophilic acyl substitution reaction. This method represents a general and efficient approach to a variety of highly functionalized, stereodefined carbocycles.     

Stereochemistry of reactions in the 1,2-dimethylsilacyclopentane ring system. II. Stereoselective transformation

A number of stereoselective reactions of 1-substituted-1,2-dimethylsilacyclopentanes are described. Reactions of the silyl chloride (II) with ZnF₂ and with alcohols catalyzed by amines are stereoselective as a result of rapid isomerization of II. Alcoholysis of silicon hydride (I) catalyzed by transition metals is apparently an inversion reaction regardless of the nature of the catalyst, but can appear to be stereoselective because of isomerization of alkoxysilane product. Reduction of silyl fluoride (IV) by lithium aluminum hydride is nonstereoselective, a result which is proposed to arise through rapid isomerization of intermediates with expanded coordination.     

Tandem cyclization reactions of electron rich arylethylamino acid amides. An entry to the dihydroimidazoisoquinolin-3(2H)-one ring system

A straightforward route to the dihydroimidazo-isoquinolin-3(2H)-one ring system employing a tandem cyclization strategy under Bischler–Napieralski conditions is described.     

An efficient approach to designing and optimizing the analysis of Ni(II) by AdCSV in seawater

A highly sensitive voltammetric method was developed for the determination of nickel in seawater at nanomolar concentrations. The measurement is based on the differential pulse cathodic adsorptive stripping of Ni(II) complexed with pyridoxal salicyloylhydrazone at a hanging mercury drop electrode. Optimal conditions were found following a two-step study strategy based on a Plackett Burman design and subsequently a modified simplex method. They were: deposition potential −0.8 V; deposition time 120 s; differential pulse scan mode; pulse amplitude −0.07 V; pulse time 0.04 s; voltage step 0.017 V; time interval for voltage step 0.05 s; supporting electrolyte ammonium chloride/ammonia (0.08 M, pH = 8.9) and concentration of PSH 5.32 × 10⁻⁶ M. The response of the system was found to be linear in a range of Ni concentrations from 0 to 306.7 × 10⁻⁹ M. The detection limit was found to be 0.04 × 10⁻⁹ M of Ni(II). The precision of the method was 1.4% for 3.4 × 10⁻⁸ M of Ni(II) and 1.48% for the blank at a significance level of 95% (n = 9). The method was free from interferences of inorganic salts and trace metals at usual concentrations in seawater. The application to seawater was demonstrated by analysis of CRM 505 and LGC 6016 certified reference estuarine water and real seawater samples from Tangier Bay (Morocco).     

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.     

Sequenced reactions with samarium(II) iodide. Sequential intramolecular Barbier cyclization/Grob fragmentation for the synthesis of medium-sized carbocycles.

Samarium(II) iodide was used to access eight-, nine-, and ten-membered carbocycles via a domino reaction composed of a cyclization/fragmentation process. 2-(Iodoalkyl)-, 2-(iodomethyl)allyl-, and 2-(2-iodomethyl)benzyl-2-methyl-3-(methanesulfonyloxy)cycloalkanones were subjected to Barbier-type reductive coupling conditions. Intermediate cycloalkanedione derivatives were also treated under similar conditions, providing bicyclic hydroxy ketones with complete diastereoselectivity and high yields. This method represents a general and efficient approach to a variety of highly functionalized, stereodefined carbocycles.     

C-glycosides to fused polycyclic ethers. An efficient entry into the A-D ring system of gambierol

[reaction: see text]. This Letter describes our use of C-glycosides to synthesize the A-D ring system of the marine ladder toxin gambierol in 20 steps.     

Synthesis of vinylcyclopentanes via samarium(II) mediated tandem reactions

In the presence of either visible light or HMPA, SmI₂ reacts with some carbohydrate derived ω-iodoallylic alcohols, and their acetylated derivatives, to give vinylcyclopentanediol and vinylcyclopentanetriol derivatives.     

An efficient chemoenzymatic approach to (S)-gamma-fluoroleucine ethyl ester

[reaction: see text] An asymmetric synthesis of (S)-gamma-fluoroleucine ethyl ester 1 is described. The key transformation involves a lipase-catalyzed dynamic ring-opening of 2-(3-butenyl)azlactone 7b with EtOH to give amide ester (S)-6b in 84% enantiomeric excess. Removal of the N-pentenoyl group with N,N'-dibromodimethylhydantoin in the presence of trifluoroacetic acid afforded the titled compound, which was isolated as its hydrogen sulfate salt in 75% yield and >97% ee.