Oxidative addition with inversion

However, a mechanistically interesting result which contradicts the expected anti addition -syn elimination mechanism of Pd-catalysed 1,4-elimination of allylic compounds has been reported. This is the elimination of the cyclic allylic carbonate 368 which afforded diene 371, but not diene 370, as expected from the anti addition-syn elimination mechanism. The selective formation of 371 is explained by oxidative addition with inversion to genearate 369, followed by elimination of the anti H of 369, namely anti elimination occurs [170]. 

As might be expected in analogy with Pd-catalyzed allylation, the overall inversion of configuration at the propargylic carbon center has been shown to be predominant - (Scheme 34). This is in accordance with a sequence consisting of oxidative addition with inversion, transmetallation, and reductive elimination with retention. 

Convincing evidence for oxidative addition by inversion has been presented by the reaction of chiral (5)-( )-3-acetoxy-l-phenyl-1-butene (4) with Pd(0)(dppe), followed by the treatment with NaBF4 to give optically active the TT-allylpalladium complex (l/ ,25,35) 5 with 81% stereoselectivity[19]. 

Dihydroxyiation of epoxides can be carried out with syn stereospecificity using OSO4 as the active oxidant. The reaction occurs by a cycioaddition mechanism. Epoxidation is aiso a stereospecific syn addition. Ring opening of epoxides by hydroiysis aiso ieads to diois. This is usuaiiy an anf/addition with inversion of configuration at the site of nucieophiiic attack, ieading to overaii anf/dihydroxyiation. 

For example, Mikolajczyk and Kielbasinski [172-175] studied the acylation of phosphine boranes 259 using CAL (Chirazyme ) lipase from Candida Antarctica and Lipase AK from Pseudomonas fluorescencs (Scheme 84). The best enantios-electivity was attained in the lipase AK-catalyzed acylation of 259 in cyclohexane solution with vinyl butyrate as an acyl donor (99% ee) for unreacted hydroxypho-sphinate 259 and 43% ee for the acylated product 260. The E-values were on the level of 15. The enzymatic resolution of alkoxy (hydroxymethyl)phenyl-phosphine boranes (/ /S)-261 was achieved by trans-esterification with vinyl acetate in the presence of CALB, Amano AK, Amano PS, Amano AH, and LPL in various solvents. The best enantioselectivity of imreacted alcohol 261 and acylated product 262 was attained in cyclohexane (37% ee, conversion 50%). Kielbasinski [176] recently reported some additional data, including theoretical calculations and more accurate chemical correlation, which proved that the borane reduction of acyclic phosphine oxides proceeded with inversion of configuration at the phosphoms center. On this basis, the stereochemistry of the enzymatic reaction was ultimately determined (Scheme 85). 

Furthermore, the catalytic allylation of malonate with optically active (S)-( )-3-acetoxy-l-phenyl-1-butene (4) yields the (S)-( )-malonates 7 and 8 in a ratio of 92 8. Thus overall retention is observed in the catalytic reaction[23]. The intermediate complex 6 is formed by inversion. Then in the catalytic reaction of (5 )-(Z)-3-acetoxy-l-phenyl-l-butene (9) with malonate, the oxidative addition generates the complex 10, which has the sterically disfavored anti form. Then the n-a ir rearrangement (rotation) of the complex 10 moves the Pd from front to the rear side to give the favored syn complex 6, which has the same configuration as that from the (5 )-( )-acetate 4. Finally the (S)-( )-mal-onates 7 and 8 are obtained in a ratio of 90 10. Thus the reaction of (Z)-acetate 9 proceeds by inversion, n-a-ir rearrangement and inversion of configuration accompanied by Z to isomerization[24]. 

Overall, the stereospecificity of this method is the same as that observed in per-oxy acid oxidation of alkenes. Substituents that are cis to each other in the alkene remain cis in the epoxide. This is because formation of the bromohydrin involves anti addition, and the ensuing intranolecular- nucleophilic substitution reaction takes place with inversion of configuration at the carbon that bear s the halide leaving group. 

For trisubstituted olefins, the nucleophile attacks predominantly at the less substituted end of the allyl moiety, e.g. to afford a 78 22 mixture of 13 and 14 (equation 7). Both the oxidative addition of palladium(O) and the subsequent nucleophilic attack occur with inversion of configuration to give the product of net retention7. The synthesis of the sex pheromone 15 of the Monarch butterfly has been accomplished by using bis[bis(l,2-diphenylphosphinoethane)]palladium as a catalyst as outlined in equation 87. A substitution of an allyl sulfone 16 by a stabilized carbon nucleophile, such as an alkynyl or vinyl system, proceeds regioselectively in the presence of a Lewis acid (equation 9)8. The... 

By studying the NMR spectra of the products, Jensen and co-workers were able to establish that the alkylation of (the presumed) [Co (DMG)2py] in methanol by cyclohexene oxide and by various substituted cyclohexyl bromides and tosylates occurred primarily with inversion of configuration at carbon i.e., by an 8 2 mechanism. A small amount of a second isomer, which must have been formed by another minor pathway, was observed in one case (95). Both the alkylation of [Co (DMG)2py] by asymmetric epoxides 129, 142) and the reduction of epoxides to alcohols by cobalt cyanide complexes 105, 103) show preferential formation of one isomer. In addition, the ratio of ketone to alcohol obtained in the reaction of epoxides with [Co(CN)5H] increases with pH and this has been ascribed to differing reactions with the hydride (reduction to alcohol) and Co(I) (isomerization to ketone) 103) (see also Section VII,C). 

Secondary bromides and tosylates react with inversion of stereochemistry, as in the classical SN2 substitution reaction.24 Alkyl iodides, however, lead to racemized product. Aryl and alkenyl halides are reactive, even though the direct displacement mechanism is not feasible. For these halides, the overall mechanism probably consists of two steps an oxidative addition to the metal, after which the oxidation state of the copper is +3, followed by combination of two of the groups from the copper. This process, which is very common for transition metal intermediates, is called reductive elimination. The [R 2Cu] species is linear and the oxidative addition takes place perpendicular to this moiety, generating a T-shaped structure. The reductive elimination occurs between adjacent R and R groups, accounting for the absence of R — R coupling product. 

The Tsuji-Trost reaction is the palladium-catalyzed allylation of nucleophiles [110-113]. In an application to the formation of an A-glycosidic bond, the reaction of 2,3-unsaturated hexopyranoside 97 and imidazole afforded A-glycopyranoside 99 regiospecifically at the anomeric center with retention of configuration [114], Therefore, the oxidative addition of allylic substrate 97 to Pd(0) forms the rc-allyl complex 98 with inversion of configuration, then nucleophilic attack by imidazole proceeds with a second inversion of configuration to give 99. 

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