Used for Allylic Substitutions

A vast majority of the allylic substitution reactions have been reported with palladium catalysts. However, complexes of other metals also catalyze allylic substitution reactions. In particular, complexes of molybdenum,tungsten, ruthenium, rhodium, and iridium have been shown to catalyze the reactions of a variety of carbon nucleo-pliiles. In addition, complexes of ruthenium, rhodium, and iridium catalyze the reactions of phenoxides, alkoxides, amines, and amine derivatives. The regioselectivity of the allylic substitution process witli these metals can often complement the regioselectivity of the reactions catalyzed by palladium complexes. The regioselectivity 

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Except for one recent example, all iridium-catalyzed allylic substitution reactions have been performed under an inert atmosphere with dry solvent and reagents. The iridium metalacycle is sensitive to protonation, which opens the metalacycle and results in the formation of a less-active complex containing a K -phosphoramidite ligand. A paper by Helmchen et al. addressed this issue [107]. Nearly all iridium catalysts used for allylic substitution consist of an iridium fragment chelated by COD. In the presence of a catalyst containing dibenzo[a,c]cyclooctatetraene (dbcot) in place of COD, allylic substimtion reactions occur in air with results that are comparable to those of reactions performed under an inert atmosphere (Scheme 35). 

Metals other than palladium and molybdenum can be used for allylic substitution reactions. For example, nickel in the presence of the oxazolinylferrocenylphosphine 9 provides good asymmetric induction for the reaction of a Grignard reagent with allylic electrophilic systems such as acetates.151... 

Various solvents have been used for allylic substitution reactions, largely depending on the nucleophile. Even water is a suitable solvent for allylic substitution reactions. For a discussion, see also 4.1.7. 

Catalysts lacking phosphorus ligands have also been used as catalysts for allylic substitutions. [lr(COD)Cl]2 itself, which contains a 7i-accepting diolefin ligand, catalyzes the alkylation of allylic acetates, but the formation of branched products was only favored when the substitution reaction was performed with branched allylic esters. Takemoto and coworkers later reported the etherification of branched allylic acetates and carbonates with oximes catalyzed by [lr(COD)Cl]2 without added ligand [47]. Finally, as discussed in Sect. 6, Carreira reported kinetic resolutions of branched allylic carbonates from reactions of phenol catalyzed by the combination of [lr(COE)2Cl]2 and a chiral diene ligand [48]. 

A = Br3, BrCl2, IC12) [Sket and Zupan, 1984], An ethylene-A-bromomaleimide copolymer has been used for bromine substitution at allylic and benzyl positions [Yaroslavsky et al., 1970],... 

A polyethylene glycol-polystyrene graft copolymer palladium catalyst has been used in allylic substitution reactions of allyl acetates with various nucleophiles in aqueous media.58 Another polymer-bound palladium catalyst 40 was developed and used in a Heck coupling of allylic alcohols with hypervalent iodonium salts to afford the substituted allylic alcohols as the sole products under mild conditions with high catalytic efficiency.59 The same polymer-bound palladium catalyst has also been used for Suzuki cross-coupling reactions.60... 

While a number of dendritic catalysts have been described, catalyst recyclization in most cases is an unsolved problem. Diaminopropyl-type dendrimers bearing Pd-phosphine complexes have been retained by ultra- or nanofiltration membranes, and the constructs have been used as catalysts for allylic substitution in a continuously operating chemzyme membrane reactor (CMR) (Brinkmann, 1999). Retention rates were found to be higher than 99.9%, resulting in a sixfold increase in the total turnover number (TTN) for the Pd catalyst. 

For example, POPAM dendrimers of 1,3-diaminopropane type have been used in membrane reactors as supports for palladium-phosphine complexes serving as catalysts for allylic substitution in a continuously operated chemical membrane reactor. Good recovery of the dendritic catalyst support is of advantage in the case of expensive catalyst components [9]. It is accomplished here by ultra-or nanofiltration (Fig. 8.2). 

Use of a chiral catalyst for allylic substitution reactions allows for desymmetrization reactions... 

Substitution reactions allow for the introduction or change of functional groups but rely on the prior formation of the stereogenic center. The approach can allow for the correction of stereochemistry. Reactions of epoxides, and analogous systems such as cyclic sulfates, allow for 1,2-functionality to be set up in a stereospecific manner. Reactions of this type have been key to the applications of asymmetric oxidations. The use of chiral ligands for allylic substitutions does allow for the introduction of a new stereogenic center. With efficient catalysts now identified, it is surely just a matter of time before this methodology is used at scale. 

Since its discovery by Tsuji [15,16] and catalytic expansion by Hata [17] and Atkins [18], allylic substitution has become the most popular palladium-catalyzed method for carbon-carbon bond formation along with crosscoupling reactions. However, the first report using NHC in this transformation only appeared recently [19]. An imidazolium salt with a bulky substituent on the nitrogen atoms, IPr HC1, was found to be a suitable ligand for allylic substitution with soft nucleophiles (Scheme 2). Pd2(dba)3 as palladium source and Cs2C03 as base completed the catalyst system. 

Kragl et al.100 described the retention of diaminopropyl-type metallodendrimers bearing palladium phosphine complexes on ultra- or nanofiltration membranes and their use as catalysts for allylic substitution in a continuously operating chemical membrane reactor. Their results demonstrated a viable procedure for catalyst recovery, because these metallodendrimers acting as catalyst supports offered an advantage in that the intrinsic viscosity of the solution is smaller, facilitating filtration. 

The lithium cuprates 39, prepared from a- and P-2-deoxy-D-glucopyranosyl-stannanes a- and P-38 are configurationally stable and provide the corresponding Michael addition products 40 on reaction with methyl vinyl ketone [Eq. (14)] [27]. The cuprates a-39 [28] and 41 [29] have been used by Kocienski et al. for allylic substitution at q -molybdenum complexes. 

A supported aqueous phase system (SAPC see Section 2.6) has also been developed for allylic substitution. Alkylation of (Ej-cinnamyl ethyl carbonate by ethyl acetoacetate or morpholine occurs in acetonitrile or benzonitrile using Pd(OAc)2-TPPTS supported on mesoporous or nonporous silica no leaching of the catalyst has been observed, allowing proper recycling of the catalyst [22-26]. Polyhydroxylated supports such as cellulose and chitosan have also been used successfully in this approach [27-29]. 

An early report of Bosnich and co-workers" describes that DiPAMP yields a racemic alkylated product but since then many mono- and bidentate P-ste-reogenic ligands have been used in the benchmark reaction for allylic substitution with very good results in some cases. Table 8.3 lists some the systems giving rise to good conversions and enantioselectivities. 

The regioselectivity of the allylic substitution process depends heavily on the identity of the metal and its coordination sphere. To bypass the issue of regioselectivity, most of the substrates used to demonstrate activity and enantioselectivity of catalysts for allylic substitution generate symmetrical allyl intermediates. However, many synthetic applications would require a regioselective substitution process involving unsymmetrical allyl intermediates. The regioselectivity of allylic substitution arises from the position of attack of the nucleophile on the allyl intermediate. 

Palladium bound to polymeric support has been employed for allylic substitution. Amphiphilic resins based on block PS-PEG-bearing phosphine residues (cf. Scheme 49) were used for allyhc substitution in aqueous media both in achiral and in enantios-elective reactions, hi the latter, MOP-type ligand has been tethered by a chiral link containing a residue of natural amino acid to the amphiphilic block-copolymer... 

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