Regioselectivity allylic substitution reactions

Depending on the substrate and the other reaction parameters, very higli re-gioselectivilies towards either a or y suhstilution can he obtained. In cetLain cases, the regioselectivity can easily he switclied between the two modes by changing the reaction conditions [11]. Compared to, for example, palladiumiO)-catalyzed allylic substitution reactions, the possibility of switching between S j2 and S j2 selectivity... 

Initial studies on the application of these catalysts to allylic substitution reactions showed that the arenethiolate moiety functions as an excellent nontransferable group, and that the regioselectivity can be completely reversed by suitable changes in the reaction parameters [33]. If the reaction between geranyl acetate and n-BuM gl was carried out inTHFat—30°C with fast addition of the Grignard reagent to the reaction mixture, complete a selectivity was obtained. Raising the tempera-... 

Evans and Nelson reexamined the rhodium-catalyzed allylic substitution reaction, in which they demonstrated that a triorganophosphite-modified Wilkinson s catalyst facilitates the allylic alkylation of secondary and tertiary aUyhc carbonates with excellent regioselectivity (Eq. 2). This work provided a convenient method for the construction of ternary and quaternary allylic products [11]. Additionally, they demonstrated that the modification of Wilkinson s catalyst with triorganophosphites serves to increase the re-... 

A new phosphoramidite ligand (1 Y = OMe), gives high enantioselectivities (92-99% ee) and regioselectivities (99% S 2 ) in iridium-catalysed allylic substitution reactions of carbonates and acetates with carbanion or primary amine nucleophiles.6 The new ligand also leads to a faster rate of reaction than other phosphoramidite ligands. 

Substrates derived from meso-cycloalkenediols such as 41 are a highly versatile starting materials for enantioselective allylic substitutions [15]. Regioselective displacement of one of the enantiotopic leaving groups by the chiral catalyst leads to a chiral allyl intermediate 42 which is attacked regioselectively at the ster-ically less hindered position to afford product 43 (Scheme 17). Products of this type can be converted to variety of useful compounds by a second allylic substitution reaction. 

Scheme 38 Allylic substitution reaction showing ligand-dependent regioselectivity...

Although Pd-N complexes sometimes have catalytic activities that are comparable to that of the Pd-P complexes,they often lead to significantly different reactivity profiles as exemplified by the Pd-catalyzed regioselective carbonylation (Scheme 9) or the selective activation of a switchable bisnucleophile (Scheme 10). Other examples can be found in the catalytic hydrogenation of alkenes, or the carbacyclization of enynes, as well as in cross-coupling and allylic substitution reactions. ... 

Most allylic substitution reactions have been conducted witti derivatives of allylic alcohols, such as acetates, phosphates, and carbonates. These reactions occur with allyl electrophiles displaying a wide structural variation. The allylic electrophiles can be cyclic or acyclic, substituted with aliphatic or aromatic groups, substituted at one or both termini, and substituted or unsubstituted at the central carbon. As discussed in more detail below, these substituents affect the regioselectivity of the substitution process. 

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... 

Hard nucleophiles (hNus) have not often been used in Irotalyzed allylic substitution reactions. Alexakis et al. [160] have investigated the use of arylzinc reagents as nonstabihzed nucleophilic partners. Despite different attempts to optimize the reaction conditions, the desired branched adducts were obtained only with moderate regioselectivities, but with good enantioselectivities. 

Further mechanistic insights were provided by Kunz et al. who found an evidence for an alternative isomerization pathway of Rh-allyl complexes. a-Allyl to o-allyl isomerization does not necessarily have to proceed via a 7t-allyl intermediate. A bimolecular pathway with an Sf 2 reaction of a second nucleophilic Rh complex can occur if the intermediate contains a terminal aUyl double bond. This finding can have important consequences for the regioselectivity of catalytic allylic substitution reactions. As the isomerization could proceed faster than the oxidative addition of the allylic substrate, some free catalyst could induce the isomerization by an 8)42 reaction (Scheme 12.90) [190]. 

Transition metal-catalyzed allylic substitution reactions with carbon nucleophiles are among the most important carbon-carbon bond formation methods in modem organic synthesis, because of their broad substrate scope under mild reaction conditions. In addition, they are applicable to enantioselective reactions, as well as exhibiting versatility towards the alkene functionality adjacent to the chiral centre for stereoselective derivatization. Tsuji-Trost allylic substitution, involving a (Ti-allyl) metal intermediate, has provided a particular advance in this regard [34, 35]. Most recently, Sawamura et al. [36, 37] have improved the regioselectivity of this reaction with unsymmetrically substituted allylic esters, and thus opened a new approach to sertraline. 

In 2008, Plietker and co vorkers reported an unprecedented dichotomy in allylic substitution reactions catalysed by NHC-Fe systems. Hence, with [Bu4N][Fe(CO)3(NO)] the regioselectivity of the addition of malonates onto ally carbonates could be controlled by simply changing the NHC and the base [eqn (7.5)]. Indeed, switching from SItBu to SIMes allowed for a remarkable inversion of the selectivity attributed to the possible intermediacy of a n-allyl complex instead of a o-allyl one when the steric pressure of the nitrogen substituents on the NHC was moved away from the metal centre. 

The allyl-substituted cyclopentadiene 122 was prepared by the reaction of cyclopentadiene anion with allylic acetates[83], Allyl chloride reacts with carbon nucleophiles without Pd catalyst, but sometimes Pd catalyst accelerates the reaction of allylic chlorides and gives higher selectivity. As an example, allylation of the anion of 6,6-dimethylfulvene 123 with allyl chloride proceeded regioselectively at the methyl group, yielding 124[84]. The uncatalyzed reaction was not selective. 

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