Synthesis of alpha,beta-unsaturated 4,5-disubstituted gamma-lactones via ring-closing metathesis catalyzed by the first-generation Grubbs' catalyst

[reaction: see text] 4-Methyl-5-alkyl-2(5H)-furanones have been prepared by ruthenium-catalyzed ring-closing metathesis of the suitable methallyl acrylates. Despite the electron deficiency of the conjugated double bond and of the gem-disubstitution of the allylic alkene moiety in the starting acrylates, the first-generation Grubbs' catalyst I proved to be an effective promoter for the ring closure, affording the expected butenolides in good to high yields.     

Diversity-oriented approach to spirocycles via ring-closing metathesis

We have demonstrated a simple and an efficient method for the synthesis of spirocycles starting with inexpensive and commercially available carbonyl compounds. Various spirocycles involving spiropropellane derivative have been assembled via ring-closing metathesis with the aid of Grubbs’ first generation catalyst.     

Efficient synthesis of 19-31 membered macrocyclic tetralactones via ring closing metathesis in ionic liquids

The ring closing metathesis reaction in the presence of Grubbs catalyst was demonstrated using several ionic liquids to synthesize a range of macrocyclic tetralactones having ring size of 19 to 31 membered with different spacers. The ionic liquid [mmim][PF₆] was found to be an excellent solvent and the recovery of the catalyst was demonstrated. X-ray analysis of a representative macrocyclic tetralactone was also reported.     

Stereoselectivity of macrocyclic ring-closing olefin metathesis

[reaction: see text] Macrocyclic ring-closing olefin metathesis using ruthenium catalyst 3 was performed to produce a 14-membered lactone. The E/Z ratio of lactone was high regardless of the R group (auxiliary) or the initial alkene stereochemistry. A kinetic study demonstrates that the high E/Z ratio is due to secondary metathesis reactions that isomerize the product to the thermodynamic E/Z ratio.     

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.     

Formal synthesis of valienamine using ring-closing metathesis

(1R,2S,3S,4R)-2,3,4-Tri-O-benzyl-5-(benzyloxymethyl)-cyclohex-5-ene-1,2,3,4-tetrol, a precursor of the α-glucosidase inhibitor, valienamine, was synthesised in eight steps from tetrabenzyl glucose. The key steps were the selective protection of an open-chain diol, and the formation of the cyclohexene ring by ring-closing metathesis with the trisubstituted olefin of valienamine correctly in place.     

Regio- and stereoselective hydrosilylation of terminal alkynes using Grubbs' first-generation olefin-metathesis catalyst

Grubbs' first-generation, Ru metathesis complex catalyses the hydrosilylation of terminal alkynes. The reaction exhibits an interesting selectivity profile that is dependent on the reaction concentration and more importantly on the silane employed.     

Synthesis of diverse macrocyclic peptidomimetics utilizing ring-closing metathesis and solid-phase synthesis

The synthesis of a range of highly functionalized peptidomimetic macrocycles has been accomplished using ring-closing metathesis and enyne tandem cross-metathesis-ring-closing metathesis reactions. This approach gives access to rigidified macrocycles modeled on the structures of cyclic peptides and designed to be biologically stable. The potential for peripheral functionalization of these templates has been demonstrated using Diels-Alder reactions, palladium(0) coupling reactions, and amide formation both in the solution phase and using polymer-supported syntheses.     

A convenient approach to cyclic enol phosphates via ring-closing metathesis

A strategy employing the second generation Grubbs catalyst in order to facilitate the generation of a variety of cyclic enol phosphates, including 2H-chromen-4-yl, 1,2-dihydroquinolin-4-yl, 2H-thiochromen-4-yl, 2H-thiochromen-4-yl 1,1-dioxide, and benzofuran-2-yl enol phosphate scaffolds is described. This work represents the first case of an olefin metathesis reaction in which one of the groups participating in the metathesis event is an enol phosphate moiety.     

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.     

Efficient synthesis of macrocyclic paracyclophanes by ring-closing metathesis dimerization and trimerization reactions

Ring-closing metathesis reactions of para-disubstituted aromatic substrates produced macrocyclic [n.n]-, and [n.n.n]paracyclophanes efficiently through dimerization and trimerization reactions. Sufficiently long alkyl chains allowed direct monocyclizations to yield [n]paracyclophanes. A small library of paracyclophanes were generated by the combinatorial cross-metathesis approach.     

Diversity-oriented synthesis of 13- to 18-membered macrolactams via ring-closing metathesis

An efficient build/couple/pair approach to diversity-oriented synthesis was employed to access several structurally complex macrolactams. In this paper, we describe the successful evaluation of ring-closing metathesis toward the systematic generation of skeletal diversity. By appropriately varying the nature and chain length of the alkenol fragment, a diverse collection of 13- to 18-membered macrolactams were obtained.     

Synthesis of coumarins by ring-closing metathesis using Grubbs’ catalyst

A novel generally applicable synthesis of coumarins from phenolic substrates utilizing ring-closing metathesis is described. This sequence involves O-allylation of phenols followed by ortho-Claisen rearrangement, subsequent based-induced isomerization affording 2-(1-propenyl)phenols, acylation with acryloyl chloride, and finally ring-closing metathesis (RCM) with Grubbs’ second generation catalyst.     

A ring-closing metathesis approach to a synthesis of the B ring of eleutherobin

A short and efficient RCM route is reported for the construction of the key nine-membered B ring of eleutherobin starting from the readily available 1,2,5,6-diisopropylidene-d-glucose.     

Formal synthesis of optically active ingenol via ring-closing olefin metathesis

The construction of strained carbon skeletons by ring-closing olefin metathesis (RCM) was investigated. With well-designed diene 4, RCM was found to be applicable to the formation of a highly strained inside-outside bicyclo[4.4.1]undecane skeleton of ingenol, a bioactive diterpenoid, and formal total synthesis of optically active ingenol (1) was achieved. The key features of this synthesis are construction of an A-ring by spirocyclization of the ketone with an allylic chloride unit, 26, and ring closure of a B-ring by olefin metathesis. Starting from Funk's keto ester 6, the key intermediate aldehyde 9 in Winkler's total synthesis was synthesized in eight steps in 12.5% overall yield. This strategy of direct cyclization of a strained inside-outside skeleton provided the first easy access to optically active ingenol.     

Cross metathesis on olefin-terminated monolayers on Si(111) using the Grubbs' catalyst

This paper reports the functionalization and patterning of olefin-terminated monolayers on Si(111) through cross metathesis. A simple, one-step synthesis of a diolefin--CH2=CH(CH2)9O(CH2)9CH=CH2--was developed from commercially available starting materials. Mixed partially olefin-terminated monolayers of this novel diolefin and 1-octadecene on hydrogen-terminated Si(111) were obtained. The olefins are raised above the rest of the monolayer and thus sterically accessible for further functionalization. Olefin-terminated monolayers were reacted with the Grubbs' first generation catalyst and olefins in solution that were terminated with fluorines, carboxylic acids, alcohols, aldehydes, and alkyl bromides. Characterization of these monolayers using X-ray photoelectron spectroscopy and horizontal attenuated total reflection infrared spectroscopy demonstrated that olefins on the surface had reacted via cross metathesis to expose fluorines, carboxylic acids, aldehydes, alcohols, and bromides. Through calibration experiments, we demonstrated a simple 1:1 correspondence between the ratio of olefins in solution used in the assembly and the final composition of the mixed monolayers. Finally, these monolayers on silicon were patterned on the micrometer-size scale by soft lithography using microfluidic channels patterned into poly(dimethylsiloxane) (PDMS) stamps. Micrometer-wide lines of polymer brushes were synthesized on these monolayers and characterized by scanning electron microscopy. In addition, olefin-terminated monolayers were patterned into micrometer-sized lines exposing carboxylic acids by cross metathesis with olefins in solution. This method of patterning is broadly applicable and can find applications in a variety of fields including the development of biosensors and nanoelectronics.     

A ring-closing metathesis approach to secosteroidal macrocycles

An efficient synthesis of secosteroidal macrocycles has been achieved via an oxidative ring-expansion/ring-opening sequence and a ring-closing metathesis reaction as the key steps.     

Control of olefin geometry in macrocyclic ring-closing metathesis using a removable silyl group

Introducing a silyl group at one of the internal olefin positions in diolefinic substrates results in E-selective olefin formation in macrocyclic ring-forming metathesis. The application of this method to a range of macrocyclic (E)-alkenylsiloxanes is described. Protodesilylation of alkenylsiloxane products yields novel Z-configured macrocycles.