Stereochemistry of nucleophilic attack

Upon treatment with oxygen and carbon nucleophiles, 18-electron ethylene-d2 complex of Pd gave alkyl complexes whose NMR analysis revealed the trans stereochemistry of the nucleophilic attack (Eq. 8.7) [38]. In the case of the reaction of 16-electron alkene complexes of Pd and Pt, both trans and cis attacks occurred depending on the nature of the nucleophile as well as the auxiliary ligand. The trans attack appears to dominate in the reaction of cyclic dialkene ligands (e. 

The cis hydroxymetallation was actually observed under certain conditions. Thus, R complex c 5-R(Me)(OH)(PPh3)2 reacted with dimethyl maleate in benzene to give a high yield of /1-hydroxyalkyl complex cis-Pt(Me)[CH(COOMe)CH(OH)(COOMe)](PPh3)2 of which X-ray structure determination unambiguously established occurrence of the cis addition of Pt and OH to the alkene (Eq. 8.11) [50]. Added free PPh3 did not retard the insertion 

Analogous reaction of Pt(Me)(OMe)(dppe) with CF2=CF2 in THF to give 6-methoxytetrafluoroethyl complex was proposed to involve migratory insertion step, without dissociation of OMe ion, though no direct stereochemical evidence has been provided [51], Apparent migratory insertion of alkenes to metal-hydroxo bond has also been observed in other metal complexes such as those of Ir [52]. 

Halometallation reaction of alkenes and alkynes is believed to be involved in 

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Figure 8.3 Stereochemistry of nucleophilic attack by HO- on the coordinated ethylene. /ratramolecular and i rarermolecular reactions should give cis and Irans orientations °f Pd-C and C-O bonds, respectively. D labeling helps to identify the stereochemistry of addition.

A detailed study of the specific rates of solvolysis of N,N,N, N -tetra-methyldiamidophosphorochloridate (80) (TMDAPC) with analysis in terms of the extended Grunwald-Winstein equation has been reported (Scheme 19). The stereochemistry of nucleophilic attack at tetracoordinate phosphorus was also discussed." The initial reaction of bis (2,4-dinitrophenyl) phosphate (BDNPP) (81) with hydroxylamine involves release of 1 mol 2,4-dinitrophen-oxide ion and formation of a phosphorylated hydroxylamine (82), which reacts readily with further NH2OH, giving the monoester (83). The intermediate (82) also breaks down by two other independent reactions one involves intramolecular displacement of aryloxide ion (83) and the other involves migration of the 2,4-dinitrophenyl group from O to N and formation of phosphorylated 2,4-dinitrophenylhydroxylamine (84) (Scheme 20)." ... 

Typical examples of the half sandwich type Cp complex are anionic zerovalent metal complexes of the type [CpM(CO)3]" and their binuclear derivatives [Cp2M2(CO)e] [12, 19]. Starting from the anion [CpM(CO)3] , a variety of complexes have been derived, including the neutral hydrides, CpMo(H)(CO)3, alkyls, CpM(R)(CO)3, [12] and the cationic allyl or diene complexes, [CpMo( n -C3H5)(NO)(CO)] [20, 21] or [CpMo(r -C4H5)(CO)2] [21, 22]. The stereochemistries of nucleophilic attack on the last two complexes have been extensively studied [23]. Permethylcyclopentadienyl of these complexes, e.g. (Ti -C5Me5)Mo(H)(CO)3 [24], have also been extensively reported. 

The stereochemistry of nucleophilic attack is consistently trans to the metal-alkene bond (Scheme 39, equation 19). Theregiochemistry of attack is normally at the alkene carbon bearing the most electron-donating (or least electron-withdrawing) group. For weakly electron-donating substituents, such as alkyl, the observed regioselection is modest for carbon-based nucleophiles. For amine and... 

One of the most useful aspects of Pd(0)-catalyzed allylic alkylation is the ability to take racemic mixtures of reactants and create preferred chirality in the product by the addition of a chiral ligand for the Pd metal. Draw the 17 -allylic complex created in the catalytic cycle of the following reactant with PdL. Describe why chirality in a ligand L would influence the stereochemistry of nucleophilic attack. 

The stereochemistry of nucleophilic attack at silicon shows ease of substitution to decrease in the order Br Cl>SR2 F >OMe>H, while ion pair dissociation controls the stereochemistry of RLi attack, and AlHi" reduction, of Si—O and Si—halogen compounds. The electronic character of the nucleophile influences... 

The product of nucleophilic attack can be anticipated by examining the lowest-unoccupied molecular orbital (LUMO) on protonated cyclopentene oxide. From which direction (top or bottom) would a nucleophile be more likely to approach each epoxide carbon in order to transfer electrons into this orbital Explain. Does one carbon contribute more to the LUMO, or is the orbital evenly spread out over both epoxide carbons Assuming that LUMO shape dictates product stereochemistry, predict which stereoisomers will be obtained, and their approximate relative amounts. Is the anticipated kinetic product also the thermodynamic product (Compare energies of 1,2-cyclopentanediol stereoisomers to tell.)... 

If the carbanion has even a short lifetime, 6 and 7 will assume the most favorable conformation before the attack of W. This is of course the same for both, and when W attacks, the same product will result from each. This will be one of two possible diastereomers, so the reaction will be stereoselective but since the cis and trans isomers do not give rise to different isomers, it will not be stereospecific. Unfortunately, this prediction has not been tested on open-chain alkenes. Except for Michael-type substrates, the stereochemistry of nucleophilic addition to double bonds has been studied only in cyclic systems, where only the cis isomer exists. In these cases, the reaction has been shown to be stereoselective with syn addition reported in some cases and anti addition in others." When the reaction is performed on a Michael-type substrate, C=C—Z, the hydrogen does not arrive at the carbon directly but only through a tautomeric equilibrium. The product naturally assumes the most thermodynamically stable configuration, without relation to the direction of original attack of Y. In one such case (the addition of EtOD and of Me3CSD to tra -MeCH=CHCOOEt) predominant anti addition was found there is evidence that the stereoselectivity here results from the final protonation of the enolate, and not from the initial attack. For obvious reasons, additions to triple bonds cannot be stereospecific. As with electrophilic additions, nucleophilic additions to triple bonds are usually stereoselective and anti, though syn addition and nonstereoselective addition have also been reported. 

The changes of stereochemistry in these systems are due to changes in the preferred direction of nucleophilic attack upon a carbocationic intermediate or a related ion pair. These results therefore indicate that the substrates or reaction intermediates have preferred orientations at the micellar surface. 

In the envisaged titanium oxo complex, the Ti atom is side-bound to the peroxy moiety (02H), consistent with all the spectroscopic results mentioned in Section III in Scheme 27, between the two O atoms that are side-bound to Ti4+, the O atom attached to both the Ti and H atoms is expected to be more electrophilic than the O atom attached to only the Ti atom and is likely to be the site of nucleophilic attack by the alkene double bond. The formation of the Ti-OH group (and not the titanyl, Ti=0, as proposed by Khouw et al. (221)) after the epoxidation and its subsequent condensation with Si-OH to regenerate the Ti-O-Si links had been observed (Section III.B) by FTIR spectroscopy by Lin and Frei (133). Because this is a concerted heterolytic cleavage of the 0-0 bond, high epoxide selectivity and retention of stereochemistry may be expected, as indeed has been observed experimentally (204). 

The nucleophilic attack of the water or hydroxide species takes place in an anti fashion i.e. the oxygen attacks from outside the palladium complex and the reaction is not an insertion of ethene into the palladium oxygen bond. This has been demonstrated in a model reaction by Backvall [4], The reaction studied was the Wacker reaction of dideuterio-ethene (cis and trans) in the presence of excess of LiCl, which is needed to form 2-chloroethanol as the product instead of ethanal. The latter product would not reveal the stereochemistry of the attack Note that all of the mechanistic work has been carried out, necessarily, on systems deviating in one aspect or another from the real catalytic one. The outcome depends strongly on the concentration of chloride ions [5],... 

The possibility of nucleophilic attack on different carbons in the resonance-stabilized carbocation facilitates another modification exploited by nature during terpenoid metabolism. This is a change in double-bond stereochemistry in the allylic system. The interconversions of geranyl diphosphate, linalyl diphosphate, and neryl diphosphate provide neat but satisfying examples of the chemistry of simple allylic carbocations. 

Electron transfer-induced nucleophilic addition to several otho cyclopropane compounds was also studied. The nucleophilic addition of methanol to quadricy-clane radical cation 8 produces the two methanol adducts 53 and 54. The stereochemistry of the methoxy groups in these structures identifies the preferred direction of nucleophilic attack upon the intermediate radical cations 8. Detailed NOE experiments delineate the structure of 53 and establish conclusively that the norbomene derivative 54 contains a 7-fl ri-methoxy group. The stereochemistry of both is compatible with stereospecific nucleophilic attack exclusively firom the exo-position. 7-Methylenequadricyclane also is attacked exclusively from the exo-face.These results can be explained via backside attack with inversion of configuration. 

Backwall and coworkers have extensively studied the stereochemistry of nucleophilic additions on 7r-alkenic and ir-allylic palladium(II) complexes. They concluded that nucleophiles which preferentially undergo a trans external attack are hard bases such as amines, water, alcohols, acetate and stabilized carbanions such as /3-diketonates. In contrast, soft bases are nonstabilized carbanions such as methyl or phenyl groups and undergo a cis internal nucleophilic attack at the coordinated substrate.398,399 The pseudocyclic alkylperoxypalladation procedure occurring in the ketonization of terminal alkenes by [RCC PdOOBu1], complexes (see Section 61.3.2.2.2)42 belongs to internal cis addition processes, as well as the oxidation of complexed alkenes by coordinated nitro ligands (vide in/ra).396,397... 

Loss of stereospecificity in the addition of soft carbon nucleophiles can occur if the rate of nucleophilic attack is slow, due, for example, to extreme steric bulk, e.g. NaCH(SChPh>2,167 of the nucleophile (equation 154). In this case, the initially displaced OAc has sufficient time to return and attack the ir-allyl complex. Acetate anions (vide infra) are capable of either ligand or metal addition, thus scrambling the stereochemistry of the starting allyl acetate. 

We believe (5.) that pseudorotations, or other ligand reorganisation processes, in TBP reaction intermediates are limited to the pairwise exchange of apical and equatorial ligands, with the constraint that P-X 0 remains equatorial. Thus if nucleophilic attack occurs opposite the eventual leaving group substitution occurs with inversion where this is not the case substitution occurs, after pseudorotation, with retention. When mixed stereochemistry is observed we believe it results from competitive attack opposite more than one substrate ligand. The factors that determine the direction of nucleophilic attack are not yet... 

Nucleophilic attack on other organic ligands on the complexes can compete with nucleophilic attack at CO. Phosphine substitution on the patent carbonyl does not alter the course of nucleophilic attack but may influence stereochemistry of the resulting phosphine-substituted metal acyl anion. 

The stereochemistry of nucleophilic vinylic substitution via the AdN-E mechanism ranges from retention of configuration to stereoconvergence. For SnV 1-type reactions, often partial inversion has been observed. The inversion has been attributed to nucleophilic attack on an ion pair intermediate.As illustrative examples, results of the acetolysis of the vinyl triflates la-c in the presence of sodium acetate are given in Scheme The fraction of inversion ranges from 40 to 80%, and is smaller the more stable the intermediate cation /3-alkyl substitution... 

The stereochemistry of addition in these reactions is of interest in that the two general mechanisms for nucleophilic attack lead to products of differing stereochemistries. If nucleophilic attack occurs initially at the metal center followed by transfer of the nucleophile to the olefinic ligand, then endo stereochemistry is expected with the M—C and Nuc—C bonds cis to one another ... 

The stereochemistry of nucleophilic addition is especially relevant to the mechanism of the Pd(II)-catalyzed conversion of ethylene and water to acetalydehyde. The mechanism originally proposed involved hydroxide attack at Pd followed by migration to coordinated ethylene ... 

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