Substitution reactions ruthenium-catalyzed alkylation

The synthesis of 5- -methylene tetrahydropyrans 378 can be accomplished by a regioselective ruthenium catalyzed C-C coupling reaction of prop-2-yn-l-ols 379 and allylic alcohol (Equation 156) <1999JOC3524>. A ruthenium catalyzed alkylative cycloetherification reaction between allene 380 and vinyl ketones furnishes 2-substituted tetrahydropyrans 381 in high yield (Equation 157) <1999JA10842>. 

In the course of a study on creation of a library of a great number of hetaryl ketones and related derivatives, Szewczyk et al. <2001AGE216> elaborated a ruthenium-catalyzed transformation of heterocycles with activated C-H bond by reaction with olefins and carbon monoxide. Thus, 253 gave 254, albeit in very poor yield. Synthetically, the more straightforward iron-catalyzed transformation was described by Fiirstner et al. <2002JA13856>. These authors reacted 255 with a Grignard reagent in the presence of Fe(acac)3 to afford the 7-alkyl-substituted derivative 256 in reasonable yield (acac = acetylacetonate). 

The successful use of neopentyl bromide as electrophile raled out the possibility that the reaction occurs via a Friedel-Crafts reaction or a simple nucleophibc substitution. In addition, when 1-hexene was employed instead of the alkyl halide, only traces of the desired product were obtained, suggesting that a mechanism involving initial -elimination of HX from the alkyl halide, along with a subsequent ruthenium-catalyzed hydroarylation (part 4), is not operative. 

Enantioselective allylic substitutions catalyzed by transition-metal complexes are a powerful method for constructing complex organic molecules [4f,55]. Palladium-based catalysts have often given excellent results. To expand the scope of the reaction, a new enantioselective allylic alkylation catalyzed by planar-chiral ruthenium complexes was developed [56]. For example, the reaction of l,3-diphenyl-2-propenyl ethyl carbonate with sodium dimethyl malonate in the presence of 5 mol% of a planar chiral (S)-ruthenium complex (Figure 5.3) at 20 °C for 6 h in THE resulted in the formation of the corresponding chiral allylic alkylated product of dimethyl 2-((2 )(lS)-l,3-diphenylprop-2-enyl)propane-l,3-dioate in 99% yield vsdth 96% e.e. (Eq. 5.33). 

Ruthenium(ll)-catalyzed cycloaddition reactions of Y-sulfonylimines 1308 with methyl isocyanoacetate 1309 gave /ra r-2-imidazolines 1310 stereoselectively in 75-90% yields under neutral, mild conditions [R = phenyl, substituted phenyl, 2-furyl, lrans-PhCH=CH, tert-Bu R = tosyl, PI1SO2] (Scheme 333) < 1997JOG1799>. In contrast, the same reaction catalyzed by 1 mol% AuCl(( -HexNG) provides 4-methoxycarbonyl-5-alkyl-2-imidazolines 1321 with over 98% -selectivity (Scheme 333) <1996TL4969>. 

Aromatic hydrocarbons, such as benzene add to alkenes using a ruthenium catalyst a catalytic mixture of AuCVAgSbFs, or a rhodium catalyst, and ruthenium complexes catalyze the addition of heteroaromatic compounds, such as pyridine, to alkynes. Such alkylation reactions are clearly reminiscent of the Friedel-Crafts reaction (11-11). Palladium catalysts can also be used to for the addition of aromatic compounds to alkynes, and rhodium catalysts for addition to alkenes (with microwave irradiation). " Note that vinyhdene cyclopropanes react with furans and a palladium catalyst to give aUylically substituted furans. ... 

Previous reports on the reaction of vinyl-substituted silanes [9] and silsesquioxane [15] with vinyl alkyl ediers catalyzed by ruthenium complexes containing or generating Ru-H and/or Ru-Si bonds show that the process proceeds according to the nonmetallacarbene mechanism as in SC and yields (usually in 5-fold excess of alkene) l-silyl-2-alkoxy-ethenes with a high preference for the jF-isomer (Eq. 1). 

Several other mechanistically distinct metal-catalyzed dearomatization procedures have been reported, and almost all involve phenol or naphthol derivatives undergoing dearomatization via intramolecular transformations. Intramolecular Pd- and Rh-catalyzed C4-arylation and alkylation of /)ara-substituted phenols has been used to construct compounds of general structure 82 (Fig. 15.1) [86]. These reactions rely on generation of electrophilic aryl or alkyl o-metal complex intermediates that participate in tandem C4 metalation-reductive elimination with an attached phenol. Ruthenium- and Pt-catalyzed reactions of naphthalenes and alkynes deliver spirocyclic products such as 83 [87, 88]. An asymmetric intramolecular naphthalene dearomatization catalyzed by Pd(0)-phosphine complexes has been used to prepare carbazole derivatives 84 in good enantiomeric excess from l-(AI-2-bromophenyl)aminonaphthalene precursors [89]. 

Metal carbenes generated from the reaction of paUadium or ruthenium catalysts with a-diazo esters have also been found to be electrophilic enough to undergo electrophilic aromatic substitution with pyrrole. The Ru-catalyzed reaction leads to a 2-alkylated pyrrole upon rearomatization. In contrast, the Pd car-bene, in combination with a phosphoric acid cocatalysL generates an intermediate enolate, which subsequently combines with an imine electrophile to furnish a three-component adduct with good enantioselectivity and moderate S37i/a -selectivity (eq 6). 

Originally, the pyridine construction reaction was based on cobalt catalysis and restricted to the use of acetonitrile or alkyl nitriles as one of the cycloaddition partners. However, recent advancements in this area have led to the development of certain ruthenium or rhodium catalysts, allowing the use of methylcyanoformate as an electron-deficient nitrile component in crossed [2 - - 2 - - 2]-cycloaddition reactions [39]. From the point of view of applications, the use of methylcyanoformate in transition-metal-catalyzed pyridine formation reaction is quite beneficial because the ester moiety might serve as a functional group for further manipulations. It might also serve as a protective group of the cyanide moiety, because cyanide itself cannot be used in this reaction. These considerations led to the design of a quite flexible approach to substituted 3-(130)- and y-carbolines (131) based on transition-metal-catalyzed [2 -f 2 -I- 2] cycloaddition reactions between functionalized yne-ynamides (129) and methylcyanoformate (Scheme 7.28) [40]. 

Under conditions of C-H/N-H bond functionalization, aryl-, heteroaryl-, and alkenyl-substituted IH-pyrazoles underwent oxidative annulation with aryl and alkyl alkynes in high chemo- and regioselectivity in the presence of Ru(II)/AgSbFg catalyst (Eq. (7.28)) [36]. Aryl alkynes particularly bearing electron-donating substituents are more reactive in the present reaction system. A cationic ruthenium(II)-catalyzed reversible C-H bond metalation step was observed in the H/D exchange experiments. 

Murai et al. have reported that dihydridocarbonyl/> /5(tiiphenylphosphine)ruthenium (Ru) catalyzes the addition of the ortho C-H bonds of acetophenone across the C-C double bonds of olefins such as trimethylvinylsilane to yield ortho alkyl substituted acetophenones (7-3). We have shown that this reaction can be applied to achieve step-growth copolymerization (cooligomerization) of aromatic ketones and a,co-dienes. For example, reaction of divinyldimethylsilane and acetophenone catalyzed by Ru at 150°C yields copoly(3,3-dimethyl-3-sila-1,5-pentanylene/2-aceto-1,3-phenylene), =... 

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