An efficient synthesis of valienamine via ring-closing metathesis

An efficient synthesis of valienamine is described. Valienamine was synthesized starting from commercially available 2,3,4,6-tetra-O-benzyl-D-glucose in nine steps, using ring-closing metathesis of (4S,5S,6S)-4,5,6-tribenzyloxy-7-(benzyloxymethyl)octa-1,7-dien-3-ol as a key step.     

An efficient synthesis of 3,4-dihydropyridone via a tandem olefin isomerization–ring-closing metathesis reaction

Novel 3,4-dihydropyridones were efficiently prepared via a tandem olefin isomerization–ring-closing metathesis reaction catalyzed by the second-generation Grubbs catalyst. The products were further functionalized at the 5-position, providing an interesting structural motif to be evaluated in medicinal chemistry.     

Facile chemoselective rhodium carbenoid N-H insertion reactions: synthesis of 3-arylamino- or 3-heteroarylpiperidin-2-ones

Rhodium(II) acetate catalyzed reactions of various substituted 3-diazopiperidin-2-ones with a range of aromatic amines, indoles, and benzotriazole yield exclusively the corresponding N-H insertion products despite competing C-H or O-H insertions. This strategy provides an example of a facile chemoselective N-H insertion reaction delivering a library of 3-arylamino and 3-heteroarylpiperidin-2-one derivatives in high yields.     

Solvent effects in a carbenoid N-H insertion route to triarylamines via 2-diazo-1,3-cyclohexanedione

The Rh-carbenoid derived from 2-diazo-1,3-cyclohexanedione inserts into the N-H bond of arylalkylamines and diarylamines. A solvent for this reactive carbenoid is suggested. The insertion products undergo a Pd-mediated aromatization to afford alkyldiarylamines and triarylamines.     

An efficient synthesis of fused tricycles with a benzene core via intramolecular double ring-closing enyne metathesis

A double enyne metathesis reaction has been developed for the efficient synthesis of tricyclic products with a benzene core in good yields. By this protocol, bisannulated benzenes with different ring sizes may be simultaneously constructed from the corresponding precursors in just ‘one shot’.     

Access to the core structure of aurisides by a ring-closing metathesis/transannular ketalisation sequence

A short access to the macrocyclic structure of aurisides has been achieved by combining a ring-closing metathesis leading first to a 14-membered ring and a subsequent transannular ketalisation to build the tetrahydropyran subunit.     

Preparation of nitrogen-containing heterocycles using ring-closing metathesis (RCM) and its application to natural product synthesis

Our synthetic study of nitrogen-containing heterocycles using ring-closing metathesis (RCM), such as chiral bicyclic lactams, azacycloundecenes, axially chiral macrolactams, 1,2-dihydroquinolines, 2-quinolinone and indoles, including a development of silyl-enol ether ene metathesis and isomerization of terminal olefins, are described. Their applications to natural product synthesis are also reported.     

Synthesis of cyclic sulfamoyl carbamates and ureas via ring-closing metathesis

Synthetic routes to a diverse set of cyclic sulfamoyl carbamates and ureas are reported. These routes utilize 3-component coupling, Mitsunobu alkylation, and ring-closing metathesis using the second-generation Grubbs catalyst to achieve the synthesis of the target S-heterocyclic compounds. Cyclic S-heterocycles ranging from 9- to 11-membered rings have been obtained.     

An efficient route to dimeric porphyrin-RGD peptide conjugates via olefin metathesis

We report the efficient use of cross-metathesis for the solid-phase synthesis of a porphyrin dimer containing as a spacer a pentapeptide moiety with RGD sequence. Such compound appears as a promising candidate for application in PDT.     

An efficient synthesis of oseltamivir phosphate (Tamiflu) via a metal-mediated domino reaction and ring-closing metathesis

An efficient synthesis of the influenza neuraminidase inhibitor prodrug oseltamivir phosphate (Tamiflu) from cheap, commercially available d-ribose is described. The main features of this approach comprise a metal (Zn, In)-mediated domino reaction and ring-closing olefin metathesis (RCM) of the resultant functionalized dienes to produce the Tamiflu skeleton. The synthesis described in this Letter represents a new and efficient transformation of a shikimic acid derivative into a 1,2-diamino compound which involved oxidation of an alcohol followed by reductive amination, regioselective ring opening of an amino pentylidene ketal and stereospecific nucleophilic replacement of a triflate with an azide.     

Synthesis of polycyclic benzofused nitrogen heterocycles via a tandem ynamide benzannulation/ring-closing metathesis strategy. Application in a formal total synthesis of (+)-FR900482

A two-stage "tandem strategy" for the synthesis of benzofused nitrogen heterocycles is described that is particularly useful for the construction of systems with a high level of substitution on the benzenoid ring. The first stage in the strategy involves a benzannulation based on the reaction of cyclobutenones with ynamides. This cascade process proceeds via a sequence of four pericyclic reactions and furnishes a multiply substituted aniline derivative which can bear a variety of functionalized substituents at the position ortho to the nitrogen. In the second stage of the tandem strategy, ring-closing metathesis generates the nitrogen heterocyclic ring. This two-step sequence provides efficient access to highly substituted dihydroquinolines, benzazepines, benzazocines, and related benzofused nitrogen heterocyclic systems. The application of this chemistry in a concise formal total synthesis of the anticancer agents (+)-FR900482 and (+)-FR66979 is described.     

Efficient synthesis of RGD-containing cyclic peptide-porphyrin conjugates by ring-closing metathesis on solid support

We report the efficient solid-phase synthesis of a new family of peptidic porphyrins containing a constrained RGD moiety obtained by ring-closing metathesis.     

Studies directed towards the stereoselective total synthesis of ilexlactone via a tandem ring-closing enyne metathesis protocol

Studies directed towards the stereoselective total synthesis of ilexlactone resulted in the synthesis of bicyclic systems 1a, 1b and ent-1a through tandem ring-closing enyne metathesis using Grubbs’ catalyst. The structures of synthetic 1a, 1b and ent-1a revealed that the proposed structure for ilexlactone is incorrect.     

N-Alkylation of diethyl acetamidomalonate: synthesis of constrained amino acid derivatives by ring-closing metathesis

An efficient method for N-alkylation of diethyl acetamidomalonate (DEAM) is reported. C-Alkenylation was achieved by treating the N-alkenylated DEAM with various electrophiles in the presence of Cs₂CO₃. RCM reactions of C- and N-alkenylated products gave cyclic amino acid derivatives in good yields.     

Solid-phase rhodium carbenoid N-H insertion reactions: the synthesis of a diverse array of indoles

A solid-phase synthesis of an array of indoles is reported. The key step in our approach involves a N-H insertion reaction of N-alkylanilines into a highly reactive polymer-bound rhodium carbenoid intermediate to yield the corresponding alpha-arylamino-beta-ketoester. These insertion products were then treated under acid-catalyzed cyclodehydration conditions to yield a series of polymer-bound indole esters, which were subsequently cleaved from the resin under Lewis acid-promoted amidation conditions to yield the desired indoles in good yields and with excellent purities.     

An efficient construction of bicyclic systems containing a seven-membered ring by tandem ring-closing metathesis reactions of dienynes

Various (5–7) and (6–7) bicyclic dienes bearing quaternary methyl group and ester functionality have been synthesized from acyclic dienynes by tandem ring-closing metathesis (RCM) reaction. Epoxidation of these conjugated dienes led to bicyclic vinyl oxiranes which undergo acid-catalyzed addition of alcohols to afford highly oxygenated compounds.     

Formal total synthesis of camptothecin via ring-closing metathesis strategy

A formal total synthesis of camptothecin 1 is presented. The key steps include construction of the D-ring of camptothecin featuring an efficient ring-closing metathesis (RCM) reaction and the subsequent Michael addition of nitropropane across the double bond of the dihydropyridone 3.     

An efficient synthesis of novel carbocyclic nucleosides with use of ring-closing metathesis from D-lactose

This paper describes an efficient synthetic route for various types of novel carbocyclic nucleosides. The required stereochemistry of the targeted nucleosides was successfully obtained with use of Grubbs cyclization and Trost allylic alkylation from the carbohydrate chiral template "D-lactose".     

Preparation of annulated nitrogen-containing heterocycles via a one-pot palladium-catalyzed alkylation/direct arylation sequence

[reaction: see text] A palladium-catalyzed/norbornene-mediated sequential coupling reaction involving an aromatic sp(2) C-H functionalization as the key step is described, in which an alkyl-aryl bond and an aryl-heteroaryl bond are formed in one pot. A variety of highly substituted six- and seven-membered annulated pyrroles and pyrazoles were synthesized in a one-step process in good yields from readily accessible N-bromoalkyl pyrroles or pyrazoles and aryl iodides.