Tandem metal-catalyzed processes

Me3SiCN is a convenient, reactive cyanide donor in transition metal-catalyzed processes. The Pd-catalyzed reaction of aryl iodides with Me3SiCN is useful for the synthesis of aryl cyanides.257 Me3SiCN works also as an effective co-catalyst for the Pd-catalyzed cyanation of aryl iodides with KCN.258 Allylic acetates, carbonates, and the related compounds undergo the Pd-catalyzed cyanation with Me3SiCN.259-261 The tandem cyclization-cyanation reaction of 2-bromo-l,6-heptadienes with Me3SiCN proceeds under catalysis by an Ni complex (Equation (68)).262... 

Sequential transition-metal-catalyzed processes are dominated by palladium-17], rhodium- [8], and ruthenium- [9] catalyzed sequences. With respect to Fogg s and de Santos classification, only cyclizing metal-catalyzed one-pot processes [1] in the sense of auto and assisted tandem catalysis will be discussed and highlighted in this overview. 

A masked allylic boron unit can be revealed through a transition-metal-catalyzed borylation reaction. For example, a one-pot borylation/allylation tandem process based on the borylation of various ketone-containing allylic acetates has been developed. The intramolecular allylboration step is very slow in DMSO, which is the usual solvent for these borylations of allylic acetates (see Eq. 33). The use of a non-coordinating solvent like toluene is more suitable for the overall process provided that an arsine or phosphine ligand is added to stabilize the active Pd(0) species during the borylation reaction. With cyclic ketones such as 136, the intramolecular allylation provides cis-fused bicyclic products in agreement with the involvement of the usual chairlike transition structure, 137 (Eq. 102). 

However, the latter type of metal-catalyzed cascade reactions turns out to be even more challenging since issues of selectivity and efficiency are crucially dependent on the particular catalyst structure. This type can either be performed in a parallel or sequential fashion [16,21], Whereas parallel catalysis is significantly more difficult to develop, sequential catalysis offers the possibility of altering reaction conditions and additives from step to step in the sense of bi- or multicatalytic one-pot processes, assisted tandem catalysis, or auto tandem catalysis [1]. Therefore, a demanding goal is the development of one-catalyst multireaction sequences that set the stage for new reactions in diversity-oriented syntheses of complex molecular structures (for reviews on diversity-oriented syntheses see [27-33]). 

Tandem carbonyl ylide generation from the reaction of metallo carbenoids with carbonyl continues to be of great interest both mechanistically and synthetically. Effective carbonyl ylide formation in transition metal catalyzed reactions of diazo compounds depends on the catalyst, the diazo species, the nature of the interacting carbonyl group and competition with other processes. The many structurally diverse and highly successful examples of tetrahydrofuran formation cited in this mini-review clearly indicate that the tandem cyclization/cycloaddition cascade of metallo carbenoids has evolved as an important strategy in both carbo- and heterocyclic synthesis. 

Transition-metal catalyzed tandem hydrosilylation/cyclization of dienes is a well known process, hi order to render this reaction environmentally benign, Studer developed metal-free conditions using a silylated cyclohexadi-ene reagent 114 (Scheme 33) [108-110]. Thereby, the silyl radical released upon rearomatization of radical intermediate 115 reacts with a diene to form a /1-silyl radical 116, which undergoes cyclization into 117. Reduction of 117 with cyclohexadiene 114 affords again 115, as well as 118, thus allowing for... 

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 ... 

Other metal-mediated reactions of azide reagents to terminal alkynes have also been reported. Indium(ll) triflate catalyzed tandem azidation/l,3-dipolar cycloaddition of various (o,(o-dialkoxyalkynes 134 with trimethylsilyl azide yielded fused 1,2,3-triazoles 135 <05TL8639>. A new ruthenium-catalyzed process for the regioselective synthesis of 1,5-disubstituted-1,2,3-triazoles has been developed <05JA15998>. 

In synthesis of complex molecules, well-designed synthetic strategies involving transition metal catalyzed intra- or intermolecular processes can lead to short cuts to target molecules by so-called tandem or domino reactions [148]. Further progress is expected in the field to accomplish efficient synthesis. 

Trost, B.M. and Shi, Y. (1992) Cycloisomerizalion for atom economy. Polycycle construction via tandem transition metal catalyzed electrocychc processes. J. Am. Chem. Soc., 114, 791-2. 

In 2000, Fiirstner et al. reported platinum-catalyzed reaction of alkynyl allyl ethers 1 to tetrahydrofuran derivatives 2 (Scheme 27.1) [2]. After this pioneering work, the TT-acidic metal-catalyzed tandem carbon-heteroatom bond formation/1,3-migration reaction became a powerful synthetic method of polysubstituted heteroarenes, since the aromatization process often drives the migration of various carbon functional groups involving cleavage of a carbon-heteroatom bond. 

Another synthetic application starting with functionalized alkynes is the tandem addition-cyclization process. Such processes in the presence of radical initiators have been reported. The first metal-catalyzed version is exemplified by the following experiments [22] thus, when 1,6-heptadiyne is treated with HP(0)(0Me)2 in the presence of Pd(OAc)2 and dppben [l,2-bis(diphenylphosphino)benzene] at 130 C, cyclized product 8 is formed in 76% yield (Scheme 17). N, A -dipropargyl-p-tosylamide reacts similarly, but the major product is pyrrole derivative 9 due to extensive double bond isomerization. Extensimi to //-phosphinate and sec-phosphine oxide is also... 

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