Ketones, 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>. 

RUTHENIUM-CATALYZED ALKYLATION OF AROMATIC KETONES WITH OLEFINS 8-[2-(TRIETHOXYSILYL)ETHYL]-l... 

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). 

In (C5Me5)Rh(C2H3SiMe3)2-catalyzed C-H/olefin coupling the effect of the coordination of the ketone carbonyl is different from that in the ruthenium-catalyzed reaction [10], In the rhodium-catalyzed reaction all C-H bonds on the aromatic ring are cleaved by the rhodium complex without coordination of the ketone carbonyl. Thus, C-H bond cleavage and addition of Rh-H to olefins proceed without coordination of the ketone carbonyl. After addition of the Rh-H species to the olefin, a coordinatively unsaturated Rh(aryl) (alkyl) species should be formed. Coordination of the ketone carbonyl group to the vacant site on the rhodium atom leads... 

The ruthenium-catalyzed addition of C-H bonds in aromatic ketones to olefins can be applied to a variety of ketones, for example acetophenones, naphthyl ketones, and heteroaromatic ketones. Representative examples are shown in the Table 1. Terminal olefins such as vinylsilanes, allylsilanes, styrenes, tert-butylethy-lene, and 1-hexene are applicable to this C-H/olefin coupling reaction. Some internal olefins, for example cyclopentene and norbornene are effective in this alkylation. The reaction of 2-acetonaphthone 1 provides the 1-alkylation product 2 selectively. Alkylations of heteroaromatic ketones such as acyl thiophenes 3, acyl furans, and acyl pyrroles proceed with high yields. In the reaction of di- and tri-substitued aromatic ketones such as 4, which have two different ortho positions, C-C bond formation occurs at the less congested ortho position. Interestingly, in the reaction of m-methoxy- and m-fluoroacetophenones C-C bond formation occurs at the congested ortho position (2 -position). 

On the other hand, unsaturated aldehydes and ketones were obtained using allylic alcohols as alkene components [68]. Similarly, allyl f-butyldimethylsilyl ether and N-allylamides gave silyl enol ethers [69] and enamides [70], respectively. The ruthenium-catalyzed alkene-alkyne coupling was successfully combined with the palladium-catalyzed intramolecular asymmetric allylic alkylation [71] to provide a novel one-pot heterocyclization method [72]. 

With regard to ruthenium complexes, in 1992 Moore and coworkers reported the ruthenium-catalyzed three-component coupling of pyridine, alkene, and carbon monoxide to produce 2-pyridyl alkyl ketone (Eq. 11.30) [73], This reaction involves ruthenium-catalyzed C-H bond activation followed by the insertion of CO and alkene to give the product. 

Having demonstrated the potential of artificial metalloenzymes for the reduction of V-protected dehydroaminoacids, we turned our attention towards organometallic-catalyzed reactions where the enantiodiscrimination step occurs without coordination of one of the reactants to the metal centre. We anticipated that incorporation of the metal complex within a protein enviromnent may steer the enantioselection without requiring transient coordination to the metal. In this context, we selected the palladium-catalyzed asymmetric allylic alkylation, the ruthenium-catalyzed transfer hydrogenation as well as the vanadyl-catalyzed sulfoxidation reaction. Indeed, these reactions are believed to proceed without prior coordination of the soft nucleophile, the prochiral ketone or the prochiral sulfide respectively. Figure 13.5. 

In addition to the above-mentioned reactions, Murai s group developed several other ruthenium-catalyzed carbonylations of arenes with similar reaction conditions (Scheme 6.19). Here, aza-heterocycle [58], 2-phenyloxazolines [59], iV-py-ridylindolines [60], A -arylpyrazoles [61, 62], and 2-phenylpyridines [63], were carbonylated into the corresponding products with Ru3(CO)i2 or Ru/C as the catalyst. Besides these novel carbonylation reactions, ruthenium-catalyzed de-carbonylative cleavage of alkyl phenyl ketones producing phenyl derivatives were also discovered by this group [64]. 

Beller reported a selective ruthenium-catalyzed synthesis of highly substituted pyrroles (e.g., 52). The sequence utihzes readily available starting materials benzylic ketone 49, amine 50 (ahphatic, aromatic, or ammonia), and vicinal diol 51.Tri-, tetra-, and pentasubstituted pyrroles can be easily prepared in moderate to high yields. A variety of aromatics, alkyl groups, and halogens are tolerated (13AG(I)597). 

With Ruthenium At the outset, the arylation of olefins using Ru catalysts was hampered by the formation of alkylated products, for example, the seminal work of Murai and coworkers [66] with Ru-catalyzed chelation-assisted C-H hond activation of aromatic ketones gave the alkylated products instead of the olefinic derivatives. 

Several related examples of transition metal-catalyzed addition of C-H bonds in ketones to olefins have been reported (Table 2) [11-14]. The alkylation of diterpenoid 6 with olefins giving 7 proceeds with the aid of Ru(H)2(CO)(PPh3)3 (A) or Ru(CO)2(PPh3)3 (B) as catalyst [11], Ruthenium complex C, Ru(H)2(H2)(CO) (PCy3)2, has catalytic activity in the reaction of benzophenone with ethylene at room temperature [12]. The alkylation of phenyl 3-pyridyl ketone 8 proceeds with A as catalyst [13], Alkylation occurs selectively at the pyridine ring. Application of this C-H/olefin coupling to polymer chemistry using ce,co-dienes such as 1,1,3,3-tetramethyl-l,3-divinyldisiloxane 11 has been reported [14]. 

Some progress has been made, particularly with the ruthenium complex-catalyzed transfer hydrogenation [56] For tert-butyl methyl ketone as the first purely aliphatic ketone the bench mark of 90 % ee has been crossed by application of the oxazolinylferrocenylphosphine 28 the transfer hydrogenation by isopropanol under reflux in the presence of sodium hydroxide resulted in 93 % ee (S)-3,3-dimethyl-butan-2-ol [57]. For alkyl aryl ketones 92-95 % ee is obtained with... 

Allyl alkyl carbonates, prepared from various alcohols except simple primary ones, are converted into aldehydes or ketones in the presence of a phosphine-free palladium catalyst. Acetonitrile as coordinating solvent is necessary for the success of this reaction. A mechanism via palladium alkoxides was proposed (Scheme 8). Ruthenium hydride complexes work similarly. A similar mechanism operates for the palladium-catalyzed decomposition of allylic carbonates. The reaction can be utilized for the mild deprotection of amines, e.g., for peptide synthesis shown in equation (20). 

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