Ruthenium cascade reactions

Abstract Ruthenium holds a prominent position among the efficient transition metals involved in catalytic processes. Molecular ruthenium catalysts are able to perform unique transformations based on a variety of reaction mechanisms. They arise from easy to make complexes with versatile catalytic properties, and are ideal precursors for the performance of successive chemical transformations and catalytic reactions. This review provides examples of catalytic cascade reactions and sequential transformations initiated by ruthenium precursors present from the outset of the reaction and involving a common mechanism, such as in alkene metathesis, or in which the compound formed during the first step is used as a substrate for the second ruthenium-catalyzed reaction. Multimetallic sequential catalytic transformations promoted by ruthenium complexes first, and then by another metal precursor will also be illustrated. 

In this review, we will focus on cascade and sequential catalytic transformations in which the first one is a ruthenium-catalyzed reaction. This will include ... 

A similar type of cascade reaction has been carried out with cyclic alkenes bearing only one olefinic side chain to obtain substituted heterocycles via ruthenium-catalyzed ring closing-ring opening metathesis (RCM-ROM) reactions. The preparation of enantiomerically pure cis- or trans-a,a -disubstituted piperidines has been achieved in the same yield for the two diastereoisomers [35] (Scheme 17). This reaction has also been used as a key step for the synthesis of natural products [36-39]. 

The analogous iridium formate complex was synthesized by Kaska and coworkers by reacting CO2 with a Ir(lll) dihydride complex. However, in this case, the formate complex proved to be unstable, undergoing disproportionation to form the hydrogen carbonate complex and the carbonyl dihydride, overall corresponding to the reverse water gas shift reaction CO2 -H H2 - CO-P H20[45j. Reduction of CO2 to the methanol level has since been effected using an aromatic nickel pincer complex and a cascade reaction involving a ruthenium pincer complex in one step [46]. 

Ruthenium-mediated regioselective intermolecular homo- and heterodimerization of substituted propiolates leads to 2H-pyran-2-one-5-carboxylates and 2H-pyran-2-one-6-carboxylates (140L652). 6-Aryl-2J-f-pyran-2-ones arise from a palladium-catalyzed oxidative aimulation of internal alkynes with acrylic acid with excellent regioselectivity and in high yields (140L2146). A one-pot isothiourea-promoted cascade reaction of (phenylthio) acetic acids with a,P-unsaturated trifluoromethyl arylke-tones provides 4-aryl-6-trifluoromethyl-2f/-pyran-2-ones (Scheme 42) (140L964). 

Conceptually similar palladium-catalyzed cascade reactions have been developed, involving molecular-queuing cycloaddition, cyclocondensation and Diels-Alder reactions [71], cydization-anion-capture-olefin metathesis [72], carbonylation-allene insertion [73], carbonylation/amination/Michael addition [74], sequential Petasis reaction/palladium-catalyzed process [75], supported allenes as substrates [76], and palladium-ruthenium catalysts [77]. 

Sabater S, MataJA, Peris E. Heterobimetalhc iridium—ruthenium assembhes through an ambidentate triazole-diyhdene hgand electrochemical properties and catalytic behavior in a cascade reaction. Organometallics. 2012 31 6450-6456. 

CASCADE REACTIONS CATALYZED BY RUTHENIUM, IRON, IRIDIUM, RHODIUM, AND COPPER... 

One important use for ruthenium catalysts is in cycloaddition reactions. A Ru-catalyzed cascade reaction of norbomadiene 12 with diynes 13, furnishing nor-bomene derivatives 14, was reported by Cheng et al. (Scheme 5.6) [13]. The process involves Ru-catalyzed [ 2+2)+2] cycloaddition and transfer hydrogenation. 

Significant progress has been made in the fields of ruthenium-, iron-, iridium-, rhodium-, and copper-catalyzed cascade reactions. Noticeably, these transition metal catalysts are critically important in numerous commercial chemical processes. Discoveries of new cascade processes along with improvements in the activity, selectivity, and scope of these catalysts could drastically reduce the environmental impact and increase the sustainability of chemical reactions. From the viewpoint of practical applications, iron and copper are the most abundant metals on Earth and, consequently, inexpensive and environmentally friendly. Moreover, many iron and copper salts and complexes are commercially available or are described in the literature. Due to these advantages, the development and applications of iron- and copper-catalyzed cascade reactions are becoming a thriving area of organic synthesis chemistry. 

Ruthenium-catalyzed cascade reactions in total synthesis... 

RUTHENIUM-CATALYZED CASCADE REACTIONS IN TOTAL SYNTHESIS... 

In the past decade, chemists have become more and more interested in ruthenium catalysts for organic synthesis, since ruthenium catalysts are able to perform specific new reactions with a large number of applications [54]. A variety of cascade reactions and sequential catalytic transformations have been developed based on this powerful catalyst system, which can promote several different types of reactions. 

A very powerful cascade reaction had been developed by Cho and Lee in their approach to the total synthesis of (3I ,9i ,10/ )-Panaxytriol 179 (Scheme 7.37) [81], which was isolated from Panax ginseng in 1983 [82]. The cascade sequence was initiated by relay metathesis, which is then followed by metallotropic [l,3]-shift and cross-metathesis. This approach has become an efficient way for the synthesis of natural products with highly unsaturated carbon skeletons. Treatment of 174 with Grubbs second-generation catalyst in CH Clj at 40 °C in the presence of 2.0 equiv of alkene 175 generated the expected prodnet 178 in 61% yield as a mixture of Z E-isomers. Surprisingly, ruthenium alkylidene 176 was isolated in 10% yield and could be converted to 178 upon treatment with 175. This confirms that complex 176 is a catalytically viable intermediate in the catalytic cycle. 

Recently, Dong et al. reported a multicatalytic cascade reaction combining Pd, acid, and Ru catalysis [11]. By coupling palladium-catalyzed oxidation, acid-catalyzed hydrolysis, and ruthenium-catalyzed reduction, the elusive anti-Markovnikov olefin hydration was formally achieved, affording primary alcohols from waters and aryl-substituted terminal alkenes (Scheme 9.8). 

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