Dibromomethane as one-carbon source in organic synthesis: total synthesis of (±)- and (−)-methylenolactocin

A general method was developed to construct monocyclic α-methylene-γ-butyrolactone moiety. The key step is to introduce the α-methylene group by the ozonolysis of mono-substituted alkenes followed by reacting with a preheated mixture of CH₂Br₂-Et₂NH. Application of this key step in the total synthesis of the (±)- and (−)-methylenolactocin was described.     

Titanocene(III) chloride mediated radical-induced one-pot synthesis of α-methylene-γ-butyrolactones

A simple and efficient methodology has been developed for the one-pot preparation of α-methylene-γ-butyrolactones by free-radical induced Barbier-type reaction of methyl 2-(bromomethyl)acrylate and aldehydes followed by in situ lactonization. The radical initiator titanocene(III) chloride (Cp₂TiCl) was easily generated in situ from commercially available Cp₂TiCl₂ and activated zinc dust in THF. Ketones remained unaffected under the reaction conditions.     

Dibromomethane as one-carbon source in organic synthesis: microwave-accelerated α-methylenation of ketones with dibromomethane and diethylamine

The reactivity of aryl alkyl ketone with a preheated mixture of dibromomethane and diethylamine is poor and gives an α-methylenation product in very low yield even under refluxing condition. It can be accelerated dramatically by microwave irradiation. Under microwave condition, the cyclic 1,3-dicarbonyls, aryl alkyl ketones, heteroaryl alkyl ketones and acyclic benzyl ketone give α-methylenation products in modest to good yields.     

Synthesis of homoallylic oxygenated α-methylene-γ-butyrolactones: a model for preparing biologically active natural lactones

In this Letter we describe a 12% overall yield synthesis of a model for homoallylic oxygenated α-methylene-γ-butyrolactones with relative stereochemistry defined by selective hydrogenation with Rh/Al₂O₃. The synthesis was realized in 9 steps involving simple reactions.     

Synthesis of enantiopure concave (+)-avenaciolide and (−)-canadensolide skeletons

Simultaneous regio- and chemoselective reduction of the carboxyl group of (2S,3S)-tetrahydro-3-hydroxy-5-oxo-2,3-furandicarboxylic acid (garcinia acid), isolated from plant sources in large amounts, has been carried out to reach the core concave bislactone structures of fungal metabolites (+)-avenaciolide and (−)-canadensolide in one and two steps, respectively.     

Vicinal dianions of diethyl α-aroylsuccinates: a general synthetic route to α-aroyl- and α-arylidene-γ-butyrolactones

Vicinal dianions derived from diethyl α-aroylsuccinates were found to react with carbonyl compounds β-regioselectively to afford α-aroyl-γ-butyrolactones, which were converted into α-arylidene-γ-butyrolactones by reduction with H₂/Pd-C followed by elimination employing methanesulfonyl chloride in pyridine. The method provides a general and convenient route to α-aroyl- and α-arylidene-γ-butyrolactones.     

Efficient assembly of α-methylene-γ-butyrolactones via a novel, tandem Claisen-ene rearrangement

A novel method for the rapid assembly of α-methylene-γ-butyrolactones, using a tandem Claisen-ene rearrangement as a key step, is presented. The importance of the structure of the Lewis acid promoters and the mechanism of action of Et₂AlSPh are discussed.     

Total synthesis of (±)-hyrtiazepine

The total synthesis of the azepinoindole alkaloid, (±)-hyrtiazepine, was achieved. Construction of the azepinoindole core structure was carried out by C-4 selective α-hydroxyalkylation of 5-hydroxyindole, introduction of serine at C-3 of the indole moiety, and intramolecular imination.     

Anodic cyanation of C-4 hydroxylated piperidines: total synthesis of (±)-alkaloid 241D

A stereospecific synthesis of dendrobates (±)-alkaloid 241D is described. Key steps in this approach involved the stepwise electrochemical synthesis of C-4 substituted α-aminonitriles and their alkylation with iodomethane and 1-bromononane, respectively. The N-aryl group was removed in the last step through a Birch dearomatization followed by the hydrolysis of the intermediate dienamines.     

Formal synthesis of (±)-brazilin and total synthesis of (±)-brazilane

A convergent synthesis towards (±)-brazilin and (±)-brazilane has been reported from 3,4-dimethoxy benzaldehyde in <15 reaction steps. Palladium(II)-catalysed intramolecular Friedel–Crafts cyclisation and Lewis acid supported intermolecular Friedel–Crafts alkylation reactions have been demonstrated. A tetracyclic substituted indane common key intermediate is employed to furnish the desired two molecules in good to excellent yield. Pd(OH)₂ has played a crucial role in the total synthesis of (±)-brazilane.     

Formal total synthesis of (±)-magellanine

Formal total synthesis of magellanine is described. Key features in the synthesis were stereoselective Ireland-Claisen rearrangement and intramolecular Pauson-Khand reaction of exo-cyclic enynes.     

Stereocontrolled total synthesis of (±)-pisiferol and (±)-pisiferal

The stereoselective total synthesis of (±)-pisiferol (1) and (±)-pisiferal (2) has been successfully accomplished using the trans-octahydrophenanthrene derivative 20 as a key intermediate. Intramolecular cyclisation of the diazoketone 15 followed by catalytic hydrogenation provided, stereoselectively, the keto-ester 17 which was converted into the acetate 20 through the intermediates 18 and 19.     

First total synthesis of(±)-sepicanin A

<正>A facile approach for the first total synthesis of naturally occurring geranylated flavanoids sepicanin A has been obtained with total yield 16%starting from 2,4,6-trihydroxyacetophenone after four steps.The key step was the protic acids(HCl or p-TsOH)-catalyzed benzopyrone formation in a protic polar solvent by deprotection and cycUzation of chalcone in one step.     

Formal total synthesis of (±)-cortistatin A

A second-generation synthesis of the pentacyclic core of the cortistatins, a family of rearranged steroidal alkaloids that have recently attracted much attention, is reported. The improved sequence provides access to significant quantities of this key compound, which enabled a formal total synthesis of (±)-cortistatin A by conversion to the key Nicolaou/Hirama dienone. It is anticipated that this new, robust route to the pentacyclic core will facilitate the total synthesis of a range of natural products in the cortistatin family, as well as the construction of key structural analogs to probe the promising biological activity of these important compounds.     

Formal total synthesis of (±)-martinellic acid

A concise formal total synthesis of the pyrrolo[3,2-c]quinoline containing natural product, martinellic acid, has been achieved from a pyrroloquinol-2-one through addition of a copper acetylide to an iminium ion. Global deprotection and alkyne reduction then provides the tricyclic triamine, which can be converted to martinelline and martinellic acid.     

A stereoselective total synthesis of (±)-tormesol

A general strategy for the synthesis of both trans/syn- and trans/anti-sphenolobane diterpenes has been developed, which utilizes an intramolecular ester enolate alkylation (IEEA) as a key step. A stereoselective total synthesis of (±)-tormesol (1), an unusual trans/syn-sphenolobane diterpene, was accomplished in 18 steps in 4.1% overall yield from readily available aldehyde 16.     

The total synthesis of (±)-arisugacin A

A 20-step total synthesis of (±)-arisugacin A with an overall yield of 2.1% is described here in detail. This synthesis features a formal [3+3] cycloaddition reaction of α,β-unsaturated iminium salts with 6-aryl-4-hydroxy-2-pyrones through a highly stereoselective 6π-electron electrocyclic ring-closure of 1-oxatriene. A strategic dihydroxylation-deoxygenation protocol leading to the desired angular C12a-OH was developed to serve as a critical step in leading to the final total syntheses of arisugacin A. This synthetic endeavor also led to an interesting and unexpected retro-aldol-aldol sequence in the AB-ring.     

Chiral vicinal diols as platforms for separable diastereomers in Johnson-Claisen rearrangement: a new short route to (−)-nor-canadensolide, (−)-canadensolide and (−)-sporothriolide

The chiral vicinal diols prepared by asymmetric dihydroxylation in high enantioselectivities provide an excellent platform for separable diastereomers in the Johnson-Claisen rearrangement. The separated syn-diastereomers were converted into the advanced γ-(lactone-lactol) intermediates (in six steps, 26-27% overall yields) for the synthesis of (−)-nor-canadensolide, (−)-canadensolide and (−)-sporothriolide.     

First total synthesis of (±)-adunctin B

The first total synthesis of (±)-adunctin B (1), a natural product isolated from Piper aduncum (Piperaceae) and having antibacterial activity, was achieved in 1.26% overall yield in 15 steps from 5,7-dimethoxycoumarin-3-carboxylate (8).