Allylic derivatives leaving groups

Allylic acetoxy groups can be substituted by amines in the presence of Pd(0) catalysts. At substituted cyclohexene derivatives the diastereoselectivity depends largely on the structure of the palladium catalyst. Polymer-bound palladium often leads to amination at the same face as the aoetoxy leaving group with regioselective attack at the sterically less hindered site of the intermediate ri -allyl complex (B.M. Trost, 1978). 

Dienes and allylarcncs can be prepared by the Pd-catalyzcd coupling of allylic compounds with hard carbon nucleophiles derived from alkenyl and aryl compounds of main group metals. Allylic compounds with various leaving groups can be used. Some of them are unreactive with soft nucleophiles, but... 

Scli ir 6.34. Leaving group and reagent dependence of allylic cubctitution in ao/clic derivative 161. 

The reaction works well with primary alkyl halides, especially with allylic and benzylic halides, as well as other alkyl derivatives with good leaving groups. Secondary alkyl halides give poor yields. Tertiary alkyl halides react under the usual reaction conditions by elimination of HX only. Nitriles from tertiary alkyl halides can however be obtained by reaction with trimethylsilyl cyanide 4 ... 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

Scheme 7. The simplest type of enantioselective allylic alkylation which occurs on treatment of an allylic substrate with a metal derivative, together with a stabilized nucleophile (R = H, alkyl or aryl X" = leaving group [M] = metal catalyst Nu" = nucleophile L = coordinating atom).

It should be noted that Trost s DPPBA-derived ligand 21 possesses considerable utility in many other situations of allylic substitution, for example with substrates which are cyclic or which possess enantiotopic leaving groups, or with prochiral nucleophiles.1171... 

Recently the use of allylic halide (see compound 96, Scheme 34) or sulfonate for the introduction of a malonyl residue at C-2 of pyranose derivatives using tetrakis(triphenyl-phosphine)palladium complex has been reported [132]. In this case, the malonyl chain is introduced anti to the leaving group at the 7-position. 

The first example of Pd-catalyzed enantioselective allylation to be reported was the reaction of l-(l -acetoxyethyl)cyclopentene and the sodium salt of methyl benzenesulfonylacetate in the presence of 10 mol % of a DIOP-Pd complex, which led to the condensation product in 46% ee (Scheme 85) (200). This reaction used a racemic starting material, but the enantioselection was not a result of kinetic resolution of the starting material, because the chemical yield was above 80%. However, in certain cases, the selectivity is controlled at the stage of the initial oxidative addition to a Pd(0) species. In a related reaction, a BINAP-Pd(0) complex exhibits excellent enantioselectivity the chiral efficiency is affected by the nature of the leaving group of the allylic derivatives (Scheme 85) (201). It has been suggested that this asymmetric induction is the result of the chiral Pd catalyst choosing between two reactive conformations of the allylic substrate. 

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