Palladium-catalyzed allylic substitution regioselectivity

Vinyloxazolidin-2-ones 224 were used as substrates for palladium catalyzed allylic substitutions showing an unexpected regioselectivity towards the branched product 226. This effect was rationalised on the basis of an hydrogen bond interaction<03JA5115>. 

Allylic substitutions are among the most important carbon-carbon bond-forming reactions in organic synthesis. Palladium-catalyzed allylic substitutions and their asymmetric version have been extensively studied and widely used in a variety of total syntheses [78]. The palladium catalysis mostly requires soft nucleophiles such as malonate carbanions to achieve high stereo- and regioselectivity. 

The factors that control regioselectivity of palladium-catalyzed allylic substitutions have been the subject of numerous studies. Experiments that reveal the effects of both symmetric and unsymmetric ancillary ligands on this regioselectivity have been reported, along with experiments that have revealed effects of the type of nucleophile and the effects of basic additives. The following section describes some of this work on palladium-catalyzed processes. 

Depending on the substrate and the other reaction parameters, very high re-gioselectivities towards either a or y substitution can be obtained. In certain cases, the regioselectivity can easily be switched between the two modes by changing the reaction conditions [11]. Compared to, for example, palladium(0)-catalyzed allylic substitution reactions, the possibility of switching between Sn2 and Sn2 selectivity... 

The stereospecificity of the palladium-catalyzed nucleophilic substitution of cyclic allylic substrates is addressed in the following diagram and in Table 3. Allyl chloride and carbonate derivatives arc included in these examples for the sake of comparison. The substrates listed form meso-n-a ]y complexes avoiding regioselectivity problems. Furthermore, the n--allyl complexes involved cannot isomerize through n-a-n rearrangement. 

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... 

AUylic substitution catalyzed by copper is a transformation that is related to ally-lie substitutions catalyzed by other transition metals discussed previously in this chapter, but several features of copper-catalyzed allylations make them worth differentiating. First, copper-catalyzed allylic substitutions are conducted with different types of nucleophiles tiian most allylic substitutions catalyzed by other metals. Second, the regioselectivity of the copper-catalyzed reactions is typically different from that of reactions catalyzed by complexes of other metals, particularly of reactions catalyzed by complexes of palladium. Thus, this last section of tiie chapter describes studies on allylic substitution catalyzed by copper, witii an emphasis on enantioselective examples. 

Although dramatic progress has been made in the enantio-control of palladium-catalyzed allylic alkylation, the lack of re-giocontrol is often a problem in the case of monosubstituted allylic substrates. The use of ferrocene-based ligands afforded the chiral-substituted derivative in good regioselectivity and in 94% ee (eq 60). ... 

Kawatsura M, Hrrakawa T, Tanaka T, Dceda D, Hayase S, Itoh T. Regioselective synthesis of trifluoromethyl group substituted allylic amines via palladium-catalyzed allylic amination. Tetrahedron Lett. 2008 49 2450-2453. 

A-Alkylhydroxylamines react with substituted allyl acetates (e.g. 15, equation 11) in palladium catalyzed addition-elimination reactions giving the corresponding A-alkyl, A-allylhydroxylamines 16. The reaction proceeds with high regioselectivity but complete racemization. A similar reaction with 0-acyl hydroxamic acids has been carried out using allylic a-alkoxycarbonyloxyphosphonates. ... 

The palladium-catalyzed decarboxylative coupling of allyl 2-(benzo[c(jthiazol-2-yl)acetates 118 provides a facile approach to 2-(but-3-enyl)benzo[c(jthiazoles 122 <07JA4138>. The reaction is initiated by nucleophilic attack of Pd(0) on the allyl ester to give Pd-7t-allyl complex 119, which undergoes nucleophilic attack at the less substituted allylic carbon from the benzothiazole nitrogen to produce 120. Decarboxylative dearomatization leads to intermediate 121, and a subsequent aza-Cope rearrangement driven by rearomatization affords the final product 122 and accounts for the unusual regioselectivity. This appears to be the first report of a tandem allylation/aza-Cope reaction driven by decarboxylative dearomatization/ rearomatization. 

Allylic and dienyl sulfones have been prepared by conjugate addition to 1,3-dienes ". Phenylsulfonyhnercuration of conjugated dienes gives mercury adducts which can be treated with base to afford phenylsulfonyldienes. 2-(Phenylsulfonyl)-l,3-dienes can be stereo- and regioselectively functionalized via Michael addition of nucleophiles to give allylic sulfones. A key intermediate in the synthesis of a Monarch butterfly pheromone 4 was prepared by BackvaU and Juntunen by alkylation and subsequent palladium-catalyzed substitution of the allylic sulfone formed by Michael addition of dimethyl malonate to 2-(phenylsulfonyl)-l,3-butadiene (equation 10). 

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. ... 

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