Development of Isomerization and Cycloisomerization with Use of a Ruthenium Hydride with N-Heterocyclic Carbene and Its Application to the Synthesis of Heterocycles

Abstract

A pure ruthenium hydride complex with N-heterocyclic carbene (NHC) ligand was efficiently generated from the reaction of a second-generation Grubbs ruthenium catalyst with vinyloxytrimethylsilane and unambiguously characterized. This ruthenium hydride complex showed high catalytic activity for the selective isomerization of terminal olefin and for the cycloisomerization of 1,6-dienes. These reactions of N-allyl-o-vinylaniline lead to novel synthetic methods for heterocycles such as indoles and 3-methylene-2,3-dihydroindoles, which are useful synthons for bioactive natural products. These procedures address an important issue in diversity-oriented synthesis.

Improved Syntheses of Versatile Ruthenium Hydridocarbonyl Catalysts Containing Electron‐Rich Ancillary Ligands

“…[11,37] Clean, quantitative synthesis of 3b has been reported via cross-metathesis of 7b with vinyloxytrimethylsilane, followed by heating at 50 8C. [24] Routes to 3 from non-alkylidene precursors have centered on use of 2 as a precursor. 3 ) 3a was originally prepared by Yi, Nolan, and co-workers in ca.…”

“…[22,23] Analogous catalysts containing an N-heterocyclic carbene ligand (3, Figure 1), though less explored, are now beginning to see use in olefin hydrogenation and isomerization. [10,[24][25][26] In particular, 3a is implicated in the synthesis of saturated neoglycopolymers relevant to tissue engineering via tandem ROMP-hydrogenation, [10] while Arisawa, Nishida and co-workers have exploited the isomerization activity of 3b to develop new routes to indoles and related heterocycles via cycloisomerization of 1,6-dienes. [24] Prior routes to 2 and 3 require forcing conditions and/or prolonged reaction, and result in contamination by small amounts of side-products.…”

“…[10,[24][25][26] In particular, 3a is implicated in the synthesis of saturated neoglycopolymers relevant to tissue engineering via tandem ROMP-hydrogenation, [10] while Arisawa, Nishida and co-workers have exploited the isomerization activity of 3b to develop new routes to indoles and related heterocycles via cycloisomerization of 1,6-dienes. [24] Prior routes to 2 and 3 require forcing conditions and/or prolonged reaction, and result in contamination by small amounts of side-products. This is particularly problematic for use of the products in catalysis, as the batch-to-batch reproducibility of catalyst performance (and data) is undermined by the presence of contaminants in variable proportions.…”

Development of Environmentally Benign Organometallic Catalysis for Drug Discovery and Its Application

“…For more than ten years, we have been exploring a synthetic methodology for nitrogen-containing heterocycles using these ruthenium carbene catalysts and applying them to the synthesis of biologically active natural products. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Here, we describe our synthetic study of nitrogen-containing heterocycles using ring-closing metathesis (RCM), such as chiral bicyclic lactams, azacycloundecenes, axially chiral macrolactams, 1,2-dihydroquinolines and indoles, including the development of silyl-enol ether ene metathesis and selective isomerization of terminal olefin, and its application to the synthesis of the natural products, (Ϫ)-coniceine, (S)-pyrrolam A and angustureine.…”

One‐Pot Olefin Isomerization/Aliphatic Enamine Ring‐Closing Metathesis/Oxidation/1,3‐Dipolar Cycloaddition for the Synthesis of Isoindolo[1,2‐a]isoquinolines

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Abstract:N-Alkyl-N-(2-vinylbenzyl)prop-2-en-1-amine derivatives undergo ao ne-pot olefin isomerization/aliphatic enamine ring-closing metathesis (RCM)/oxidation/1,3-dipolar cycloaddition sequence with the ruthenium complex, Ru(CO)HCl(PPh 3 ) 3 ,asecond generation HoveydaGrubbs catalyst, and a1 ,3-dipolarophile.O verall, in as ingle operation the reactions equence converts simple benzylamine derivatives into isoindolo[1,2-a]isoquinolines with a p-conjugated four-ring system, throught hree unique ruthenium-catalyzed transformations.Keywords: cycloaddition;d omino reactions;h eterocycles;m etathesis; ruthenium Olefin metathesis using ruthenium carbenec atalysts (Figure 1) is one of the most importantc arbon-carbon doubleb ondf orming reactions,a nd has been used widelyi nt he preparation of functionalized organic compounds.[1] Over the past decade, Ru-catalyzed olefin metathesis followed by an on-metathesis [2] transformation is at ypical example of assisted tandem catalysis,a nd hasb een the subject of numerous publications.F or example,b yin situ conversion of aR u-carbene into aR u-hydride, [3] olefin metathesis can be coupled with hydrogenation [4] or isomerization.[5] Thet andem transformations catalyzed by ruthenium alkylidenes developedt od atei nclude olefin metathesis, followed by cyclopropanation, [6] hydrovinylation, [7] hydroarylation, [8] aza-Michael reaction, [9] hetero-Pauson-Khandr eaction, [10] and oxidation. [11] [RuClCp*] and "first generation"G rubbs metathesis complex A can catalyze an azide-alkyne cycloaddition reactiont og ive1 ,5-substituted triazoles [12] and intramolecular [3+ +2] cycloaddition of alk-5-ynylidenecyclopropanes to give bicyclo[3.3.0]octanes.

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