Ruthenium cyclization with alkynes

The final cyclization manifold has been realized with a different ruthenium catalyst (Scheme 22). The cationic [Cp Ru(MeCN)3]PF6 induces exclusive endo-dig cyclization of both homopropargylic and bis-homopropargylic alcohols.29 73 The clean reaction to form a seven-membered ring is noteworthy for several reasons intramolecular exo-dig cyclization with bis-homopropargylic alcohols is not well established, the platinum-catalyzed case has been reported to be problematic,80 and the selectivity for seven-membered ring formation over the exo-dig cyclization to form a six-membered ring is likely not thermodynamic. The endo-dig cyclization manifold was thus significant evidence that a re-examination of alkyne hydrosilylation mechanisms is necessary (see Section 10.17.2). 

Terminal alkynals (113) of appropriate length (n = 1, 2) and substitution [X = C(C02-Me)2, C(CH2OR)2, NTs, and others] have been cyclized with decarbonylation to cycloalkenes (114), using a ruthenium(I) catalyst.348 In some cases, cycloisomerization to give conjugated aldehyde occurred. Both processes are believed to involve catalytic ruthenium vinylidenes. 

Reactions with aikynes may aiso result in the formation of cyclized products. Thus a ruthenium-catalysed reaction with aromatic amides has been used to give isoquinoline derivatives. On the basis of values of the kinetic isotope effect, A h/ d> proposed that the rate-determining step is a concerted acetate-assisted metalation-deprotonation process to yield the intermediate (30), followed by aikyne insertion and ring closure. The reaction of arylketones with alkynes may yield indenols when catalysed by rhodium cyclopentadienyl in the presence of silver and copper salts. The reaction proceeds regioselectively, so that reaction of acetophenone with 1-phenyl-1-propene... 

Another example of ruthenium(II)-catalysed double inserticm of alkynes into C-H and O-H bonds was reported by Lee. The C-H bond oxidative cyclizations of phosphonic acid monoesters or phosphinic acids with alkynes lead to a wide range of phosphaisocoumarins with excellent yields up to 97%. The catalyst was prepared from [RuCl2(p-cymene)]2/KPF6, with 1 equiv. of Ag2C03 and of AgOAc in t-BuOH, under aerobic conditions [(Eq. 101)] [194]. 

Scheme 7.7 Proposed mechanism for ruthenium-catalyzed cyclization of amines with alkynes.

Aryl and heteroaryl amidines underwent oxidative C-H bond functionalization with alkynes with the aid of ruthenium catalysis [48]. In the presence of [RuCl2(p-cymene)]2/KPF5 as catalyst, the cyclization reactions led to the formation of a variety of 1-iminoisoindolines with high site selectivity, regioselectivity, and... 

ROM-RCM of cycloalkene-yne 119 having a substituent at the 3-position of the cycloalkene would give a polymer because ruthenium carbene complex XVlll generated in this reaction could react with the starting alkyne. If this reaction is carried out under ethylene gas, the cyclized compound 120 should be formed by the reaction of XVlll with ethylene [Eq. (6.88)]. On the basis of this idea, ROM-RCM-CM of cycloalkene-yne 119 was carried out under ethylene gas " ... 

Besides enyne metathesis [66] (see also the chapter Recent Advances in Alkenes Metathesis in this volume), which generally produces 1-vinylcyclo-alkenes, ruthenium-catalyzed enyne cycloisomerization can proceed by two major pathways via hydrometallation or a ruthenacycle intermediate. The RuClH(CO)(PPh3)3 complex catalyzed the cyclization of 1,5- and 1,6-enynes with an electron-withdrawing group on the alkene to give cyclized 1,3-dienes, dialkylidenecyclopentanes (for n=2), or alkylidenecyclopentenes (for n= 1) [69,70] (Eq. 51). Hydroruthenation of the alkyne can give two vinylruthenium complexes which can undergo intramolecular alkene insertion into the Ru-C bond. 

The same research group has also developed the ruthenium-catalyzed inter-molecular addition of carboxylic acids to carbon-carbon triple bonds [4]. When a-hydroxy acids 3 were employed with terminal alkynes, 1,3-dioxolan-4-ones 5 were synthesized via cyclization of enol ester intermediates 4 (Eq. 2) [5]. 

Ruthenium vinylidene 826 derived from terminal alkyne 825 with RuChl -cymenelPPhs undergoes 6rt-electro-cyclization to afford benzothiophene 827 (Scheme 125) <1996JA11319>. Pt-catalyzed double cyclization of diynes 828 gives polycyclic benzodithiophenes 829 <2005TL8153>. 

The [2 -I- 2] cycloaddition of an alkene and an alkyne is a valuable route leading to cyclobutene derivatives. The ruthenium(0)-catalyzed [2 -1- 2] cycloaddition of a strained cycloalkene, norbornene 40, vith highly electron-deficient DMAD afforded the cyclobutene 74 (Scheme 4.28) [62]. As expected, the reaction took place at the exo face of 40 via the ruthenacyclopentene intermediate 75, that ivas formed by the oxidative cyclization of DMAD and norbornene. In addition to the parent 40, various norbornene derivatives can also be used as alkene components. When the Ru" precatalyst 17 ivas employed, electronically neutral alkynes participated in the [2 -1- 2] cycloaddition with norbornene and its derivatives [63]. A similar [2 -1- 2] cycloaddi-... 

Ruthenium-catalyzed carbonylations of allylic compounds [62] were described in Chapter 11. Here, ruthenium-catalyzed carbonylative cyclization of allylic carbonates with alkenes, not alkynes, which offers a new route to cyclopentenones is revealed [63]. Treatment of allyl methyl carbonate with 2-norbornene in the presence of 2.5 mol% [RuCl2(CO)3]2 and 10 mol% Et3N in THE at 120°C for 5 h under 3 atm of carbon monoxide gave the corresponding cyclopentenone, exo-4-methyltri-cyclo[5.2.1.0 ]dec-4-en-3-one, in 80% yield with high stereoselectivity exo 100%) (Eq. 5.37). 

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