Trans attack

As observed with cyclohexanones, the diastereoselectivity of the addition reaction of trimeth-ylaluminum to 2-methylcyclopentanone depends on the stoichiometry of the reactants. Thus, addition of one equivalent of trimcthylaluminum proceeds via preferential tram attack whereas, due to the "compression effect , addition of an excess of the reagent leads to the formation of the equatorial alcohol via predominant attack from the cis side (Table 3)6. In contrast to the addition reactions with trimethylaluniinum, no reversal of the diastereoselectivity upon change of reagent stoichiometry was observed in the addition of triphenylaluminum to 2-methylcyclopentanone6. Even with an excess of the aluminum reagent trans attack predominates. However, the diastereoselectivity is lower than with the use of an equimolar amount of the reactants. 

Exclusive trims attack of the nucleophile is also observed with 2,3-epoxycyclopentanones 1559. In contrast to 2-alkyl- and 2-methoxy-substituted cyclopentanones, preferential trans attack to 2,3-epoxycyclopenlanones occurs with alkyl, ethenyl, and ethynyl nucleophiles. Thus, there is no assistance by the epoxidic oxygen for cis attack. Due to the geometry of the molecule, chelation-controlled cis attack is not possible39 60. 

In acyclic systems the 1,4-relative stereoselectivity was controlled by the stereochemistry of the diene. Thus, oxidation of (E,E)- and (E,Z)-2,4-hexadienes to their corresponding diacetates affords dl (>88% dl) and mesa (>95% me so) 2,5-diacetoxy-3-hexene, respectively. A mechanism involving a t vans-accto xy pal I adation of the conjugated diene to give an intermediate (rr-allyljpalladium complex, followed by either a cis or trans attack by acetate on the allyl group, has been suggested. The cis attack is explained by a cis migration from a (cr-allyl)palladium intermediate. The diacetoxylation reaction was applied to the preparation of a key intermediate for the synthesis of d/-shikimic acid, 3,... 

In another study,125 methyl 5-0-benzoyl-2,3-dideoxy-/8 D-g(t/cero-pent-2-enofuranoside (81) was treated with bromine in methanol in the presence of silver acetate and barium carbonate the two monobenzoates (shown as 84) of methyl 2-bromo-2-deoxy-j8-D-xylofurano-side were obtained. A rationalization for this reaction involves formation of an intermediate bromonium ion (82), produced by attack of Br on the less-hindered side of the double bond, which then undergoes trans-attack by the benzoate group at C-5 to give the benzoxonium intermediate (83) the monobenzoates (84) are obtained on processing of the reaction mixture with water. 

The stereoselectivity is explained by a change in the mode of acetate attack on the intermediate ir-allylpalladium complex. The coordination of acetate to palladium is effectively blocked by chloride ions, thus hindering cis-migration. As a result, path c is operative (Scheme 9.13). In the absence of chloride both cis and trans attacks (paths a and b) can occur depending on acetate concentration. 

Once complexed to palladium(II), the alkene is generally activated towards nucleophilic attack, with nucleophiles ranging from chloride to phenyllithium undergoing reaction. The reaction is, however, quite sensitive to conditions and displacement of the alkene by the nucleophile (path a) or oxidative destruction of the nucleophile can become an important competing reaction. Nucleophilic attack occurs predominately to exclusively at the more-substituted position of the alkene (the position best able to stabilize positive charge) and from the face opposite the metal (trans attack, path b) to produce a new carbon-nucleophile bond and a new carbon-metal bond. This newly formed a-alkylmetal complex (2) is... 

Nucleophilic addition to ir-allylpalladium complexes is known to take place widi a range of nucleophiles. and die mechanism and steieochonistry of diese reactions have been thoroughly investigated over die last few years. - For example, reaction with acetate anion occuis in the presence of benzoqui-none at room temperature in acetic acid solution by initial cis attack at the metal atom and subsequent migration. Alternatively, in die presence of chloride ions, a trans attack takes place to give the pr uct of opposite stereochemistry (Scheme 10). Intramolecular versions of the reaction are known. ... 

A different explanation is needed for numerous reported instances of olefins adding hydrogen halides almost entirely in the trans sense [8x, 82, 86]. This stereospecificity has been attributed to trans attack of the anion on a protonated intermediate variously represented as a r-complex" (4) or as a... 

Helmchen and co-workers [13] independently achieved similar results with catalysts of CAB 3 derived from valine (R = /-Pr). When R is 2,4,6-trimethylphenyl, the cycloaddition of crotonaldehyde and cyclopentadiene occurs with 72 % ee exo endo = 3 97) in the presence of 0.2 equiv. chiral catalyst. More recently, the same authors systematically investigated the influence of different experimental conditions on the enantioselectivity [15]. Improved enantioselectivity was obtained in THE or by addition of THE (ee up to 86 %). A transition-state model is proposed for prediction of the absolute configuration of the adducts (Eig. 2). In this model, the R group directs the R S02 group to the opposite side of the ring, where the latter group again participates in trans attack on boron. The conformation of the complexed enal has been determined to be s-cis, as has the coordination of carbonyl to boron syn to H. This model correctly predicts the outcome of all the examples studied. 

Substitution reactions of optically active metal complexes to yield reaction mixtures with some remaining optical activity usually owe this to the occurrence of optical retention reactions. Only five examples of optical inversion reactions have been reported, and all but one of these were discovered by Bailar 3) and his students. This is a somewhat surprising result because the types of rearrangements described above must also be involved in optical inversion reactions. In some of these cases the authors prefer to explain the mechanism of inversion on the basis of a trans-attack displacement 19, 33), One reason for this may be due to the erroneous assumption that a dissociation process could not provide a path... 

A recent study of the product distribution from cyclohexene in the presence of CuCl2 sheds some light of the stereochemical aspects of the reaction (114, 127). The products consisted of 1,2,- 1,3,- and 1,4-chloro- and diacetates plus the allylic and homoallylic acetates found in the absence of CuCl2. No enol acetate was detected. Only certain isomers were found. The diacetates were always the cis isomer, whereas the 1,3- and 1,4-chloroacetates were almost exclusively trans. The 1,2-chloroacetates were about in equal mixtures of cis and trans isomers. Also, deuterium-labeling studies indicated that acetoxypalladation was a trans process. Thus, the chloroacetates must be formed mainly by cis displacement of Pd(II) and diacetates by trans attack on the Pd(II)— carbon bond. For example, the scheme for formation of 1,2 and 1,3 products is shown in Eq. (99). 

The kinetics indicated that, in fact, the hydroxypalladation occurred by trans attack of water on the dimeric n complex 121) ... 

The formation of the cwdo-ir-allyl structure (XIX), can be explained by trans attack of alcohol followed by a thermally allowed conrotatory cyclization step (X = OR) 183) ... 

More recently, however, results with monooelfins indicate that trans addition can occur to both Pd(II) and Pt(II) n complexes. The first demonstration was the trans addition of amines to Pt(II) complexes 215), and more recently the trans attack of acetate on cyclohexene has been demonstrated (Section III, A, 2, a). However, cis attack can also occur such as the addition of phenylpalladium to cyclohexene (Section III, A, 4) or addition of PdCOOR to cyclic olefins (Section III, A, 3). Also, in the exchange studies (Section III, B, 1) the stereochemistry indicates that some nucleophiles can attack cis or trans. Thus chloride ion containing acetic acid can attack the Pd(II) olefin n complex from either inside or outside the coordination sphere. What are the factors involved The most important appears to be the ability of the nucleophile to coordinate to Pd(II). Thus, phenyl is covalently bonded to Pd(II) and is therefore always in the coordination sphere. Chloride is both inside the coordination sphere as well as outside the coordination sphere and can thus attack both cis and trans. Acetate is not complexed to Pd(II) in chloride-containing media, and thus can only attack trans. On the other hand, in chloride-free acetic acid, acetate is both inside and outside the coordination. Stereochemical results indicate that in this system acetate can attack in both a cis and trans fashion. 

Why, then, does water not attack the neutral aquo n complex, a route that is not consistent with the kinetics The answer could simply be that once the aquo tt complex is formed, the lower-energy route is to lose a proton to give the better nucleophile, hydroxyl, which then attacks the olefin from the coordination sphere. However, the important point is that in the light of recent studies, trans attack still does not appear likely. 

A trans attack, i.e., an attack of the acetoxy anion from the solution, is assumed [30] but a cis attack, i.e., a ligand insertion, cannot be excluded since trans attack has been proven with a cyclic olefin consisting of a rigid skeleton but this is not typical for linear olefins, and the above interpretation of the activation by sodium acetate [27] would make some sense with two coordinated acetate ligands of which one would be in a cis position relative to a coordinated olefin. 

The epoxides derived from 3-phenyl-5a-cholest-2-ene are hydrolysed by aqueous acids to give either cis- or rrans-2,3-diols, depending upon the reagent. The possibility of intervention of a stable benzylic cation at C-3 allows either cis- or trans-attack by water. Boron trifluoride converts the a-epoxide into 3a-phenyl-5a-cholestan-2-one, with concerted hydride migration (2 - 3j8). 

The / -hydroxycyclohexyl radical has been studied for its allylation reactions with allylstannane and the same preference for trans attack is found35. 

This reaction constitutes a special type of process in which a hydrogen atom and a nucleophile are added across the diene with formation of a carbon-hydrogen bond in the 1-position and a carbon-Nu bond in the 4-position. Some examples of such reactions are hydrosilylation [12-18], hydrostannation [19,20] animation [21,22], and addition of active methylene compounds [2la,23,24]. These reactions are initiated by an oxidative addition of H-Nu to the palladium(O) catalyst, which produces a palladium hydride species 1 where the nucleophile is coordinated to the metal (Scheme 8-1). The mechanism commonly accepted for these reactions involves insertion of the double bond into the palladium-hydride bond (hydride addition to the diene), which gives a (7r-allyl)palladium intermediate. Now depending on the nature of the nucleophile (Nu) the attack on the rr-allyl complex may occur either by external trans-attack (path A) or via a ds-migration from palladium to carbon (path B). 

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