Dibromomethane as one-carbon source in organic synthesis: total synthesis of (±)-canadensolide

A diastereoselective total synthesis of (±)-canadensolide is described. The key step is to introduce the α-methylene group by the ozonolysis of mono-substituted alkenes followed by reaction with a preheated mixture of CH₂Br₂-Et₂NH.     

Practical synthesis of adenosine 3′,5′-cyclic monophosphorodithioate

Adenosine 3′,5′-cyclic monophosphorodithioate (cAMPS₂), which has two exocyclic sulfurs directly attached to phosphorus, was synthesized from adenosine phosphoramidite by intramolecular cyclization employing the phosphotriester method as a key step.     

Stereoselective formal synthesis of (−)-centrolobine

Stereoselective formal synthesis of (−)-centrolobine was achieved from naturally occurring l-(+)-tartaric acid, employing a facile FeCl₃ mediated stereoselective formation of a tetrahydropyran as the key step.     

Thermal 1,3-proton shift reaction and its application for operationally convenient and improved synthesis of α-(trifluoromethyl)benzylamine

This paper describes a synthesis of α-(trifluoromethyl)benzylamine via a novel base-free biomimetic reductive amination of α,α,α-trifluoroacetophenone with benzylamine. When the corresponding imine, derived from α,α,α-trifluoroacetophenone and benzylamine was heated at 200 °C under N₂ for 1 day, the thermal 1,3-proton shift reaction took place giving rise to the N-(benzylidene)-α-(trifluoromethyl)benzylamine in quantitative yield. This thermal 1,3-proton shift reaction was used a key step in the development of new and substantially simplified, practical and operationally convenient procedure for preparation of the target α-(trifluoromethyl)benzylamine on large scale.     

Controlled synthesis of AB2 amphiphilic triarm star-shaped block copolymers by ring-opening polymerization

This paper describes the synthesis of a novel amphiphilic AB₂ triarm star-shaped copolymer with A = non-toxic and biocompatible hydrophilic poly(ethylene oxide) (PEO) and B = biodegradable and hydrophobic poly(ε-caprolactone) (PCL). A series of AB₂ triarm star-shaped copolymers with different molecular-weights for the PCL block were successfully synthesized by a three-step procedure. α-Methoxy-ω-epoxy-poly(ethylene oxide) (PEO-epoxide) was first synthesized by the nucleophilic substitution of α-methoxy-ω-hydroxy-poly(ethylene oxide) (MPEO) on epichlorohydrin. In a second step, the α-methoxy-ω,ω′-dihydroxy-poly(ethylene oxide) (PEO(OH)₂) macroinitiator was prepared by the selective hydrolysis of the ω-epoxy end-group of the PEO-epoxide chain. Finally, PEO(OH)₂ was used as a macroinitiator for the ring-opening polymerization (ROP) of ε-caprolactone (εCL) catalyzed by tin octoaote (Sn(Oct)₂). PEO-epoxide, PEO(OH)₂ and the AB₂ triarm star-shaped copolymers were assessed by ¹H NMR spectroscopy, size exclusion chromatography (SEC) and MALDI-TOF. The behavior of the AB₂ triarm star-shaped copolymer in aqueous solution was studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM).     

Chemo-enzymatic short-step total synthesis of symbioramide

A concise synthesis of symbioramide, a marine-origin ceramide from a common starting material, methyl (±)-trans-2,3-epoxyoctadecanoate, in a convergent manner was achieved. The key step is the direct lipase-catalyzed coupling reaction between methyl (2R,3E)-2-hydroxy-3-octadecenoate and non-protected (±)-erythro-dihydrosphingosine, giving natural (2S,3R,2′R)-symbioramide and its (2R,3S,2′R)-isomer in 38% and 37% yield, respectively. The optically active β,γ-unsaturated α-hydroxyester was prepared by Mg(ClO₄)₂-mediated isomerization of epoxide and the subsequent lipase PS-catalyzed kinetic resolution.     

The stereoselective total synthesis of (−)-cleistenolide

The stereoselective total synthesis of (−)-cleistenolide is described employing the Barbier allylation, MacMillan α-hydroxylation, Stille-Gennari olefination, and CeCl₃·7H₂O mediated lactonization as key steps.     

Gold-mediated synthesis of α-ionone

A simple and convenient synthesis of α-ionone, an important component of flowers and fragrances, is reported. The key step in the formation of the α,β-unsaturated ketone moiety involves an NHC-Au^I catalyzed Meyer-Schuster-like rearrangement of readily prepared propargylic esters. The complex [{Au(IPr)}₂(μ-OH)][BF₄] proved to be the most efficient catalyst leading to α-ionone in 70% yield from a propargylic benzoate. This optimized procedure represents a valuable and attractive alternative to classical methods leading to α,β-unsaturated ketones, such as the Wittig or aldol reactions.     

Asymmetric synthesis of (−)-codonopsinine

The asymmetric synthesis of (−)-codonopsinine was achieved in 7 steps (from commercially available tert-butyl crotonate) in 5% overall yield and >99:1 dr. The key step in this synthesis involved ring-closing iodoamination of a functionalised homoallylic amine, which occurred with concomitant N-debenzylation, to give a 3-iodopyrrolidine that was elaborated to (−)-codonopsinine.     

Asymmetric syntheses of diarylheptanoid natural products (−)-centrolobine and (−)-de-O-methylcentrolobine via hetero-Diels-Alder reaction catalyzed by dirhodium(II) tetrakis[(R)-3-(benzene-fused-phthalimido)-2-piperidinonate]

Catalytic asymmetric syntheses of (−)-centrolobine and (−)-de-O-methylcentrolobine have been achieved, incorporating a hetero-Diels-Alder (HDA) reaction between 4-aryl-2-silyloxy-1,3-butadienes and phenylpropargyl aldehyde derivatives as a key step. The HDA reaction using dirhodium(II) tetrakis[(R)-3-(benzene-fused-phthalimido)-2-piperidinonate], Rh₂(R-BPTPI)₄, as a chiral Lewis acid catalyst provides exclusively cis-2,6-disubstituted tetrahydropyran-4-ones in up to 93% ee.     

A One Pot Synthesis of Dehydrohedione (DHH) from a Hedione® Precursor

Dehydrohedione (DHH) 1a was obtained via a one pot, three step, domino procedure in 54% overall yield from 2a , by treatment with CuBr₂, in MeOH at 65 °C. We demonstrated that the direct transformation of malonate derivative 2a into DHH 1a under CuX₂ Kochi's conditions goes preferentially through the pathway involving intermediates 2b / 2c and 7a , rather than 3a / 3b or 8a / 8b , essentially via α‐halogenation/dehydrohalogenation of the ketone moiety, both mediated by CuX₂, while in‐situ decarbomethoxylation is promoted by the resulting CuX in refluxing MeOH.     

Efficient synthesis and biological activity of enantiomeric pairs of thiolactomycin and its 3-demethyl derivative

The title total synthesis was achieved by employing deconjugative asymmetric α-sulfenylation of the chiral 3-(α,β,γ,δ-unsaturated acyl)oxazolidin-2-one with a 3,3-dimethoxypropyl methanethiosulfonate as a key step. From the biological activity assay carried out using the title compounds, it appeared evident that in vitro antibacterial and mammalian type I FAS inhibitory activity can be cleanly separated by changing not only the substituent at the C₃-position but also the absolute configuration at the C₅-position, and that unnatural (S)-(−)-3-demethylthiolactomycin and its congeners might be usable as selective mammalian type I FAS inhibitors.     

Two-step cathodic synthesis of poly(para-phenylenevinylene)

The electrochemical behavior of a film, which consists of intermediate products of the α,α,α′,α′-tetrabromo-para-xylol (TBX) reduction and is deposited on a glassy-carbon electrode from 5 × 10^?2 M TBX solutions, is studied in 0.1 M Bu₄NBF₄ solution in DMFA by cycling the potential from 0 to ?1.4 V with respect to an aqueous saturated calomel electrode. When the potential is cycled from 0 to ?2.1 V in a cell filled with the supporting electrolyte, the film, which is assumed to have the (-BrHC-C₆H₄-CHBr-)_n composition, can be reduced to form poly(para-phenylenevilylene) (PPV). This film exhibits redox activity in the cathodic range in solutions of Bu₄NBF₄ in DMFA and in both cathodic and anodic ranges in solutions of Bu₄NBF₄ in AN. It is observed for the first time that, if the cathodic limit of the potential cycling range is extended to ?2.5 V, the cathodic doping of PPV at potentials below ?2 V disappears and a new reversible redox process takes place at more negative potentials.     

A concise synthesis of 3′-α-fluoro-2′,3′-dideoxyguanosine (FddG) via 3′-α-selective fluorination of 8,2′-thioanhydronucleoside

The antiviral nucleoside 3′-α-fluoro-2′,3′-dideoxyguanosine (FddG) was synthesized via 3′-α-selective fluorination of 8,2′-thioanhydronucleoside as the key step. Desulfurization of 3′-α-fluoro-3′-deoxy-8,2′-thioanhydronucleoside could be achieved by the treatment with Raney Ni in toluene. This method provides a concise route to 3′-α-fluoro-2′,3′-dideoxynucleosides that avoids the use of explosive and expensive SF₄-related fluorinating reagents.     

Stereoselective total synthesis of decarestrictine O

The stereoselective total synthesis of decarestrictine O, a polyketide natural product is described. The synthesis involves MacMillan α-hydroxylation, C₁-Wittig olefination, hydrolytic kinetic resolution and ring closing metathesis (RCM) as key steps. Improved efficiency was achieved by using the DIBAL mediated reductive transformation of trans-dimethyl l-tartrate acetonide into ε-hydroxy α,β-unsaturated ester in a single step.     

Theoretical prediction on the synthesis of 2,3‐dihydropyridines through Co(III)‐catalysed reaction of unsaturated oximes with alkenes

Cobalt‐based catalysts can replace the homologous group‐9 rhodium‐based ones. Herein, we used density functional theory (DFT) calculations to predict the synthesis of 2,3‐dihydropyridines using α,β‐unsaturated oxime pivalates and alkenes catalysed by [Cp*CoOAc]⁺ instead of [Cp*RhOAc]⁺. The catalytic cycle involves reversible acetate‐assisted metalation‐deprotonation, migratory insertion of alkenes, and reductive elimination/N‐O cleavage. The migratory insertion of alkenes was determined to be the rate‐determining step, and the reaction is irreversible due to the strongly exergonic reductive elimination/N? O cleavage. When using the CF₃‐substituted Cp*Co(III) catalyst, the apparent activation energy indicates that the title reaction can proceed at higher temperatures. Electron‐withdrawing substituent groups on Cp* facilitate the reaction. In contrast, substituting phenyl with the electron‐deficient p‐CF₃‐phenyl at the 2‐position of α,β‐unsaturated oxime pivalate hinders the reaction, and so does the use of polarized alkenes with electron‐withdrawing substituent groups     

Synthesis of substituted pyrrolidines and piperidines from endocyclic enamine derivatives. Synthesis of (±)-laburnamine

Functionalization of the α- and β-positions of readily available endocyclic enamine derivatives provides a convenient method for the formation of substituted pyrrolidines and piperidines. α-Alkoxy-β-iodopyrrolidines are formed by the electrophilic addition of iodine to the endocyclic enamine double bond of an N-substituted 2-pyrroline, and nucleophillic attack by an alcohol on the intermediate iodonium ion. The resultant α-alkoxy-β-iodopyrrolidines can be used in radical cyclization reactions to give bicyclic hemiaminal compounds, which can be further elaborated using N-acyliminium chemistry to form α,β-cis-dialkylsubstituted pyrrolidines. A strategy for the incorporation of amino functionality at the β-position was also established by using iodoamination of the enamine double bond, followed by migration of the amine functionality through an aziridination/methanolysis protocol. An alternative method uses an azidomethoxylation protocol using ceric ammonium nitrate (CAN) in the presence of NaN₃ and methanol. Formation and trapping of the N-acyliminium ions derived from these substrates, afforded the 3-carbamate and 3-azido-2-substituted products with good diastereoselectivity, with the preferential formation of the trans and cis stereoisomers, respectively. Using the sequential iodoamination, aziridination in methanol and N-acyliminium transformation, trans-3-NHCO₂Me-2-allyl-pyrrolidine was prepared, which was used as the key precursor in a synthesis of the natural 1-amidopyrrolizidine alkaloid, (±)-laburnamine.     

A rapid,highly efficient,and general protocol for the synthesis of functionalized triarylmethanes: a straightforward access for the synthesis of (−)-tatarinoid C

A rapid, efficient, and convenient synthesis of functionalized triarylmethane is described by the Friedel–Crafts alkylation of methoxybenzenes with a variety of aldehydes in the presence of BF₃·OEt₂. The generality of the method is demonstrated by screening a variety of di- or tri-substituted arenes as well as substituted aromatic, heteroaromatic, and aliphatic aldehydes. (−)-Tatarinoid C is synthesized in a single step following the same protocol.     

The synthesis and reactivity of polysilylacetylenes: Diels—Alder reactions to give bis (silyl) benzenes

Six bis(silyl)acetylenes (XMe²Si? C?C? SiMe₂X) with the following varied silicon substituents X were prepared: 1 (Me, Me); 2 (H, H); 3 (C1, H); 4 (CI, CI); 5 (MeO, H); 6 (MeO, MeO). While 1 and 2 may be prepared by the reaction of dilithio- or bis(bromomagnesium)-acetylide with the appropriate chlorosilane, similar reactions designed to give 3–6 yielded oligomers, XMe₂Si? (? C?C? SiMe₂)_n? X, 7, X=CI, MeO, as the major products, indicating that the acetylenic functionality on silicon activates the chlorosilane towards nucleophilic substitution. Compounds 3 and 4 were prepared by free radical chlorination of 2. Methanolysis of 3 and 4 gave quantitative yields of 5 and 6 respectively. Compounds 1–6 undergo a Diels–Alder reaction with α-pyrone to produce, after loss of carbon dioxide, bis(silyl)-substituted benzene derivatives. The order of reactivity has been determined to be: 4=6>3=5>1>2, indicating that chloro or alkoxy substituents favor the cycloaddition with 2- pyrone. The adducts formed by compounds 3–6 undergo an unusually facile hydrolysis or elimination to give 1,1,3,3-tetramethyl-1,3-disila-2-oxaindane.     

An expedient synthesis of ellipticine via Suzuki-Miyaura coupling

A simple and efficient total synthesis of ellipticine was developed via the Suzuki-Miyaura coupling of sterically sensitive 2-hydroxybenzeneboronic acid with a multifunctional aryl halide using Pd(OAc)₂ as a catalyst and Cu(OAc)₂·H₂O as an additive in DMSO/H₂O as a key step followed by double N-arylation and cyclization.