Transition-metal-catalyzed reactions allylic substitution

In addition to the applications reported in detail above, a number of other transition metal-catalyzed reactions in ionic liquids have been carried out with some success in recent years, illustrating the broad versatility of the methodology. Butadiene telomerization [34], olefin metathesis [110], carbonylation [111], allylic alkylation [112] and substitution [113], and Trost-Tsuji-coupling [114] are other examples of high value for synthetic chemists. 

Asymmetric synthesis of tricyclic nitro ergoline synthon (up to 70% ee) is accomplished by intramolecular cyclization of nitro compound Pd(0)-catalyzed complexes with classical C2 symmetry diphosphanes.94 Palladium complexes of 4,5-dihydrooxazoles are better chiral ligands to promote asymmetric allylic alkylation than classical catalysts. For example, allylic substitution with nitromethane gives enantioselectivity exceeding 99% ee (Eq. 5.62).95 Phosphi-noxazolines can induce very high enatioselectivity in other transition metal-catalyzed reactions.96 Diastereo- and enantioselective allylation of substituted nitroalkanes has also been reported.9513... 

Fischer-type carbenes can also be modified via transition metal catalyzed reactions. Fischer chromium aminocarbene complexes can be used as nucleophiles in palladium-catalyzed allyUc substitution reactions with aUylic acetates and carbonates, alFording the corresponding allyl-substituted aminocarbenes. For example, reaction of the Uthiated carbene (15) gives (16) in good yield (Scheme 25). ... 

A similar triarylphosphane was introduced by Leitner for the performance of transition metal catalyzed reactions in supercritical CO2 [24]. Recently, this phosphane was used for palladium catalyzed substitutions of allylic substrates in perfluorinated solvents under fluorous biphase conditions [25], Therefore, the reaction of cinnamyl methylcarbonate (36) with several nucleophiles (Nu-... 

Much effort has been devoted to developing catalysts that control the enantioselectiv-ity of these substitution reactions, as well as the regioselectivity of reactions that proceed through unsymmetrical allylic intermediates. A majority of this effort has been spent on developing palladium complexes as catalysts. Increasingly, however, complexes of molybdenum, tungsten, ruthenium, rhodium, and iridium have been studied as catalysts for enantioselective and regioselective processes. In parallel with these studies of allylic substitution catalyzed by complexes of transition metals, studies on allylic substitution catalyzed by complexes of copper have been conducted. These reactions often occur to form products of Sj 2 substitution. As catalylic allylic substitution has been developed, this process has been applied in many different ways to the synthesis of natural products. ... 

Transition metal catalyzed reactions, providing a formal Alder-Ene product, have a unique mechanism and selectivity when compared to the traditional Alder-Ene reaction product. There has been a debate in explaining the initial step, whether a 7t-allyl complex was formed from the ene reaction components, or merely complexation of each reacting component and metallocycle formation. For the Ru-catalyzed reaction, Trost and coworkers reported that the below description rationalized the observed selectivity. Coordination followed by carbocyclization provides either 110 or 111. Carbometallations normally prefer to attaeh at the less substituted terminus of the alkyne, favoring initial formation of 109 leading to 111. However, steric effects between the two bonding carbons may disfavor such a mode and therefore 108 may be preferred due to steric effects which would form carbocycle 110. So, as R increases in size, one would expect that more... 

The use of polymer-supported Ugands for transition-metal-catalyzed reactions has widely been exploited, including asymmetric examples. However, there are relatively few examples of polymer-supported enantiomerically pure ligands being used in aUylic substitution reactions (Scheme 16). Hayashi s MOP ligands have been attached to a resin support, to provide palladium catalysts such as complex 82.[ i Up to 84% was obtained in allylic substitution reactions. 

Multicomponent sequential transition-metal-catalyzed reactions were accomplished by the group of Muller. Their approach involves cycloisomerizations or combinations of a Heck reaction and an insertion or allylic substitution reaction, yielding an intermediate from which by P-H-elimination an aldehyde is generated, which reacts with an amine to give an imine, which in turn is reduced or otherwise modified. This conceptually challenging approach allows the experimentally remarkably facile generation of a variety of compounds of interest in medicinal chemistry. 

Transition metal-catalyzed allylic substitution with phenols and alcohols represents a fundamentally important cross-coupling reaction for the construction of allylic ethers, which are ubiquitous in a variety of biologically important molecules [44, 45]. While phenols have proven efficient nucleophiles for a variety of intermolecular allylic etherification reactions, alcohols have proven much more challenging nucleophiles, primarily due to their hard, more basic character. This is exemphfied with secondary and tertiary alcohols, and has undoubtedly limited the synthetic utihty of this transformation. 

For lead references on other transition metal-catalyzed allylic substitution reactions, see (a) Cobalt Bhatia, B. Reddy, M.M. Iqbal, J. Tetrahedron Lett. 1993, 34, 6301. 

With respect to the large number of unsaturated diazo and diazocarbonyl compounds that have recently been used for intramolecular transition metal catalyzed cyclopropanation reactions (6-8), it is remarkable that 1,3-dipolar cycloadditions with retention of the azo moiety have only been occasionally observed. This finding is probably due to the fact that these [3 + 2]-cycloaddition reactions require thermal activation while the catalytic reactions are carried out at ambient temperature. /V-Allyl carboxamides appear to be rather amenable to intramolecular cycloaddition. Compounds 254-256 (Scheme 8.61) cyclize intra-molecularly even at room temperature. The faster reaction of 254c (310) and diethoxyphosphoryl-substituted diazoamides 255 (311) as compared with diazoacetamides 254a (312) (x1/2 25 h at 22 °C) and 254b (310), points to a LUMO (dipole) — HOMO(dipolarophile) controlled process. The A -pyrazolines expected... 

When propargyl allyl ethers are subjected to transition metal-catalyzed enyne cyclization reactions, 3-alkylidene-substituted tetrahydrofurans are usually formed. A useful variation of this scheme is the Pd(0)-catalyzed tandem enyne cyclization/Suzuki coupling reaction with various arylboronic acids (Equation 90) <2005JOC1712>. The stereoselectivity of this reaction is explained by invoking a chairlike transition state. 

The transition metal-catalyzed allylation of carbon nucleophiles was a widely used method until Grieco and Pearson discovered LPDE-mediated allylic substitutions in 1992. Grieco investigated substitution reactions of cyclic allyl alcohols with silyl ketene acetals such as Si-1 by use of LPDE solution [95]. The concentration of LPDE seems to be important. For example, the use of 2.0 M LPDE resulted in formation of silyl ether 88 with 86 and 87 in the ratio 2 6.4 1. In contrast, 3.0 m LPDE afforded an excellent yield (90 %) of 86 and 87 (5.8 1), and the less hindered side of the allylic unit is alkylated regioselectively. It is of interest to note that this chemistry is also applicable to cyclopropyl carbinol 89 (Sch. 44). 

Besides the transition-metal-catalyzed asymmetric addition reactions to prochiral olefins, the substitution reaction of a carbon nucleophile to allylic esters has been investigated using a variety of chiral transition-metal catalysts. Using the aforementioned sugar diphosphites... 

In general, the catalytic cycle for the transition-metal catalyzed allylic substitution reactions involves initial attack of the metal at the double bond followed by oxidative insertion into the antiperiplanar C-0 bond to afford the Ti-allyl system. At this point, depending on whether soft or hard nucleophiles are used, however, the alkylation reaction proceeds through distinctly different pathways (Scheme 10). With soft nucleophiles, where Pd is often the metal center of choice. 

Transition metal-catalyzed allylic substitutions or, as these reactions are also called, allylic alkylations or allylations , Eq. (1), are highly versatile reactions that have become part of the standard repertoire of modern organic synthesis [ 1,... 

The concept of C2-symmetric ligands has widely been recognized as an ideal design of asymmetric ligands, which include DIOP, chiraphos, and BINAP. These ligands have been applied to a variety of transition metal-catalyzed asymmetric reactions and have been fairly successful. However, this situation is not always applied to rr-allylpalla-dium-mediated asymmetric allylic substitutions. In the reaction, which has been the most frequently examined asymmetric reaction catalyzed by 7r-allylpalladium complexes, two factors need to be controlled for the sake of high stereoselectivity. One is... 

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