Product tandem catalysis

The combination of cobalt with other metals like Pd increases the synthetic utility of this methodology. Thus, a concurrent tandem catalysis reaction of 102 and 103 using first an homogeneous chiral palladium complex, followed by the action of heterogeneous cobalt/C led to high enantioselective synthesis of PK products 104 (Scheme 30) [129]. 

Metal enolates have played a Umited role in the metal-catalyzed isomerization of al-kenes . As illustrated in a comprehensive review by Bouwman and coworkers, ruthenium complex Ru(acac)3 (51) has been used to isomerize a wide range of substituted double bonds, including aUylic alcohols (131), to the corresponding ketones (132) (equation 38) . The isomerization of aUylic alcohols affords products that have useful applications in natural product synthesis and in bulk chemical processes. An elegant review by Fogg and dos Santos shows how these complexes can be used in tandem catalysis, where an alkene is subjected to an initial isomerization followed by a hydroformylation reaction ... 

The synthetic synthesis of known chiral polymers mostly starts from optically pure monomers obtained form the chiral pool. The optically pure fermentation product L-lactic acid, for example, is the starting material for the synthesis of poly(L-lactide). However, converting a racemic or achiral monomer quantitatively into a homochiral polymer is less straightforward [3]. This is surprising considering the enormous potential of biocatalysis and tandem catalysis that has emerged in the past decades to prepare optically active intermediates [4]. 

Since the last decades, chemists have described a huge variety of multi-catalytic systems and cooperative effects [6]. First of all, it has been shown that cooperative effects can appear by combining two catalytic functions within the same molecule (bifunctional catalysis) [7] or in two separate molecules (cooperative dual catalysis) [8,9], Both can participate to the same catalytic cycle by activating together the same substrate (double-activation catalysis) or its own substrate. The two catalytic centers can also activate simultaneously different substrates in two directly coupled catalytic reactions for giving a product (synergistic catalysis) [10]. Tandem reactions have been also described [11, 12]. In that case, the two catalytic centers operate consecutively in two independent catalytic cycles, the second catalytic cycle using the product of the first one as an intermediate and converts it as final product. The second catalytic function may also not interact with the substrates but contributes to the stability of the active metal center and acts as redox partner (restorative catalysis) [8]. 

Tandem catalysis [1-10], which involves several catalytic cycles within the same medium to produce a desired product, is becoming increasingly important for the economic and environmental acceptability of the process. Copper salts are efficient catalysts in various transformations, including formation of carbon-carbon and carbon-nitrogen bonds [11-14], The author postulated they could play key parts in construction of complex nitrogen heterocycles with important biological activities through formation of multiple bonds [15-23]. 

Fig. 34) [83]. Initially they conducted a tandem enyne/alkene RCM reaction to generate the key tricyclic diene (131). However, they observed that the yield of this cascade reaction was low, presumably due to the further decomposition of the labile diene (131) under this condition. Therefore they decided to attempt a tandem catalysis sequence and selectively hydrogenate the less-substituted alkene moiety in situ after the metathesis. As a result, the desired tricyclic product (132) was produced in 52% yield over three transformations. 

In almost the same manner, tandem hydroformylation/aldol condensation aldol condensation of ketoolefins, such as p,y-unsaturated ketones, gives a single cyclization product under acid catalysis. Similar to the stepwise reaction, the in situ generated aldehyde preferentially acts as the electrophilic carbonyl component, while the ketone acts as the nucleophilic enol to form the five-membered ring product. Subsequent dehydration and hydrogenation of the resulting enone readily occurs under the reductive reaction conditions used (Scheme 30) [84],... 

The conjugate addition of organometallic reagents R M to an electron-deficient alkene under, for instance, copper catalysis conditions results in a stabilized car-banion that, upon protonation, affords the chiral yS-substituted product (Scheme 7.1, path a). Quenching of the anionic intermediate with an electrophile creates a disubstituted product with two new stereocenters (Scheme 1, path b). With a pro-chiral electrophile, such as an aldehyde, three new stereocenters can be formed in a tandem 1,4-addition-aldol process (Scheme 1, path c). 

Cascade Addition-Cyclization Reactions Given the importance of cascade reactions in modem chemical synthesis, the MacMillan group has proposed expansion of the realm of iminium catalysis to include the activation of tandem bond-forming processes, with a view toward the rapid constraction of natural products. In this context, the addition-cyclization of tryptamines with a,p-unsaturated aldehydes in the presence of imidazolidinone catalysts 11 or 15 has been accomplished to provide pyrroloindoline adducts in high yields and with excellent enantioselectivities (Scheme 11.3a). This transformation is successful... 

Novel aldol-type reactions under Cinchona-deriwed chiral thiourea catalysis was reported by Wang et al. [78]. In their report, a novel cascade Michael-aldol reaction was presented. The reaction involves a tandem reaction catalyzed via hydrogen-bonding with as little as 1 mol% catalyst loading to generate a product with three stereogenic centers (Scheme 28). hi the reaction of 2-mercaptobenzaldehyde 128 and a,P-unsatnrated oxazolidinone 129, the desired benzothiopyran 130 was formed smoothly in high yield and excellent stereoselectivity. 

The Lee group originated rhodium alkenylidene-mediated catalysis by combining acetylide/alkenylidene interconversion with known metal vinylidene functionalization reactions [31], Thus, the first all-intramolecular three-component coupling between alkyl iodides, alkynes, and olefins was realized (Scheme 9.17). Prior to their work, such tandem reaction sequences required several distinct chemical operations. The optimized reaction conditions are identical to those of their original two-component cycloisomerization of enynes (see Section 9.2.2, Equation 9.1) except for the addition of an external base (Et3N). Various substituted [4.3.0]-bicyclononene derivatives were synthesized under mild conditions. Oxacycles and azacycles were also formed. The use of DMF as a solvent proved essential reactions in THF afforded only enyne cycloisomerization products, leaving the alkyl iodide moiety intact. 

One of the major goals set for tandem ylide formation-cycloaddition chemistry has been the application of enantioselective catalysis to form one product in preference to all others. It appears that these transformations must involve a catalyst associated ylide for some degree of enantioselectivity to occur. Generally, if the free ylide forms without any catalyst association then enantioselectivity is highly unlikely. 

Silyl enolates are useful carbon nucleophiles in the asymmetric tandem Michael addition and lactonization (Scheme 3.3). Mukaiyama recently reported that cinchona-derived ammonium phenoxides act as activators (nucleophilic catalysis), to give highly stereocontrolled products [18-20]. In a typical PTC manner, most of the... 

The desymmetrization of dicarbonate 206 was initiated by the addition of one equivalent of N-(3-butenyl) nosylamide 207 under palladium catalysis in the presence of Trost s chiral diphosphine ligand 205. When the first allylic substitution was completed, the reaction was warmed and the resulting intermediate 208 was treated in situ with one equivalent of a second nosylamide 209. Product 210 resulting from this double substitution reaction was submitted to a tandem intramolecular ROM/RCM to furnish key precursor 211, which was engaged in the final cyc-lization step by the reduction of the double bonds, followed by the HCl-promoted domino deprotection of the acetal and aminal formation. 

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