Formation of Polycyclic Lactones through a Ruthenium-Catalyzed Ring-Closing Metathesis/Hetero-Pauson–Khand Reaction Sequence

Abstract

Processes that form multiple carbon-carbon bonds in one operation can generate molecular complexity quickly and therefore be used to shorten syntheses of desirable molecules. We selected the hetero-Pauson-Khand (HPK) cycloaddition and ring-closing metathesis (RCM) as two unique carbon-carbon bond-forming reactions that could be united in a tandem ruthenium-catalyzed process. In doing so, complex polycyclic products can be obtained in one reaction vessel from acyclic precursors using a single ruthenium additive that can catalyze sequentially two mechanistically distinct transformations.

Development of an Enyne Metathesis/Isomerization/Diels–Alder One‐Pot Reaction for the Synthesis of a Novel Near‐Infrared (NIR) Dye Core

“…Experimentst op robe the substrate scope of the reaction are summarized in Ta ble 2. Substituents on the nitrogen, whichm ight influence the NIR absorption or fluorescencea nd will be discussed below,w ere not limited to benzyl, and these derivatives afforded the corresponding products in 16,65,37, and 27 %y ields, respectively (entries 2-5).…”

“…For example, by conversion of a Ru‐carbene into a Ru‐hydride in situ (Figure 1),9 olefin metathesis can be coupled with hydrogenation10 or isomerization 11. The tandem transformations catalyzed by ruthenium alkylidenes developed to date include olefin metathesis, followed by cyclopropanation,12 hydrovinylation,13 hydroarylation,14 the aza‐Michael reaction,15 the hetero‐Pauson‐Khand reaction,16 or oxidation 17…”

“…For example, by conversion of aR u-carbenei nto aR u-hydride in situ (Figure 1), [9] olefin metathesis can be coupled with hydrogenation [10] or isomerization. [11] The tandem transformations catalyzed by ruthenium alkylidenes developed to date include olefin metathesis, followed by cyclopropanation, [12] hydrovinylation, [13] hydroarylation, [14] the aza-Michael reaction, [15] the hetero-Pauson-Khand reaction, [16] or oxidation. [17] In our search for novel ande fficient Ru-catalyzedr eactions, [8c, 9, 17d, 18] we developed ao ne-potr ing-closing metathesis/oxidation and ao ne-pot ring-closing metathesis/1,3-dipolar cycloaddition to produce various2 -quinolones and isoindoloquinolines (Scheme 1), respectively,from N-allyl-2-alkynylaniline derivatives.…”

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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One‐Pot Ring‐Closing Metathesis/1,3‐Dipolar Cycloaddition through Assisted Tandem Ruthenium Catalysis: Synthesis of a Dye with Isoindolo[2,1‐a]quinoline Structure

“…For example, olefin metathesis can be combined with hydrogenation [3] or isomerization [4] by in situ conversion of a Ru-carbene into a Ru-hydride. [5] Ruthenium-alkylidene-catalyzed tandem transformations that were developed to date include olefin metathesis, followed by cyclopropanation, [6] hydrovinylation, [7] hydroarylation, [8] the aza-Michael reaction, [9] the hetero-Pauson-Khand reaction, [10] or oxidation. [11] On the other hand, [RuClCp*] and the "first generation" Grubbs metathesis complex A (Figure 1) catalyze an azidealkyne cycloaddition reaction to give 1,5-substituted triazoles, [12] and an intramolecular [3+2] cycloaddition of alk-5ynylidenecyclopropanes to give bicyclo[3.3.0]octane, [13] respectively.In our search for novel and efficient Ru-catalyzed reactions, [2c, 3, 11d, 14] we developed a one-pot ring-closing metathesis/oxidation methodology to produce various 2-quinolones from N-allyl-2-vinylaniline derivatives (Scheme 1).…”