Nucleophiles incoming

Thermal Substitution.—Carbonyl substitutions in Group VI metal carbonyls occur predominantly by dissociative pathways, associative pathways also contributing when the more nucleophilic incoming ligands are considered. The kinetics of the reaction of [W(CO)3(CS)(phen)] with ligands L (phosphines or phosphites) to give [W(CO)3(CS)L(phen)] show first- and second-order terms... 

Carbon is partially bonded to both the incoming nucleophile and the departing halide at the transition state Progress is made toward the transition state as the nucleophile begins to share a pair of its electrons with carbon and the halide ion leaves taking with it the pair of electrons m its bond to carbon... 

The S l mechanism, ia which the substituent leaves before the incoming nucleophile attacks, is less frequentiy encountered, although it is known to occur... 

Substitution reactions by the ionization mechanism proceed very slowly on a-halo derivatives of ketones, aldehydes, acids, esters, nitriles, and related compounds. As discussed on p. 284, such substituents destabilize a carbocation intermediate. Substitution by the direct displacement mechanism, however, proceed especially readily in these systems. Table S.IS indicates some representative relative rate accelerations. Steric effects be responsible for part of the observed acceleration, since an sfp- caibon, such as in a carbonyl group, will provide less steric resistance to tiie incoming nucleophile than an alkyl group. The major effect is believed to be electronic. The adjacent n-LUMO of the carbonyl group can interact with the electnai density that is built up at the pentacoordinate carbon. This can be described in resonance terminology as a contribution flom an enolate-like stmeture to tiie transition state. In MO terminology,.the low-lying LUMO has a... 

The mechanism of the Sfs2 reaction. The reaction takes place in a single step when the incoming nucleophile approaches from a direction 180° away from the leaving halide ion, thereby inverting the stereochemistry at carbon. 

The first SN2 reaction variable to look at is the structure of the substrate. Because the S, j2 transition state involves partial bond formation between the incoming nucleophile and the alkyl halide carbon atom, it seems reasonable that a hindered, bulky substrate should prevent easy approach of the nucleophile, making bond formation difficult. In other words, the transition state for reaction of a sterically hindered alkvl halide, whose carbon atom is "shielded" from approach of the incoming nucleophile, is higher in energy... 

Although nor shown in the preceding reactivity order, vinylic halides (R2C=CRX) and aryl halides are unreactive toward Sn2 reaction. This lack of reactivity is probably due to steric factors, because the incoming nucleophile... 

A further improvement of the theory of 1,2-asymmetric induction was introduced by Felkin15. Neither Cram s open-chain model nor the Karabatsos model is able to explain why the stereoselectivity increases when either the incoming nucleophile R2e or the substituent at the carbonyl group (R1) increases in bulk. To explain these experimental observations the following assumptions are made for the Felkin model ... 

A polar substituent, such as chlorine, stabilizes the transition states in which the incoming nucleophile and the polar group are remote (Figure 6, L = Cl). 

The high importance of the steric interaction of the incoming nucleophile with the axial groups at C-3 and C-5 of the cyclohexanone is impressively demonstrated by addition reactions to 3,3,5-trimethylcyclohexanone (14). The presence of an axial methyl substituent intensifies the steric interaction in such a way that the nucleophile is forced to enter the carbonyl group exclusively from the less hindered equatorial side6,7,21. Exclusive formation of the axial... 

In accord with the Felkin-Anh model, a-chiral ketones react more diastereoselectively than the corresponding aldehydes. Increasing steric demand of the acyl substituent increases the Cram selectivity. Due to the size of the acyl substituent, the incoming nucleophile is pushed towards the stereogenic center and therefore the diastereoface selection becomes more effective (see also Section 1.3.1.1.). Thus, addition of methyllithium to 4-methyl-4-phenyl-3-hexanonc (15) proceeds with higher diastercoselectivity than the addition of ethyllithium to 3-methyl-3-phenyl-2-pen-tanone (14)32. 

In the general case, an incoming nucleophile would be expected to be favoured by (i) a high basicity consistent with ( ) a high polarizability, and the metal complex to favour its approach if (in) it contains electron-acceptive, or B class ligands. An interpretation of the available data may be essayed on these lines. The infrared data upon Ni(CO)4 are consistent with a weakening of the C-O bond , and it would be of interest to examine the solvent effect upon the Ni-C bond. 

It is interesting to note that the oxidation of sulphoxides by peracids is faster in alkaline than in acidic solution. This is in contrast to the oxidation of sulphides and amines with the same reagents " . The oxidation rate of ortho-substituted aryl alkyl sulphoxides with aromatic peracids is less than the corresponding meta- and para-substituted species due to steric hindrance of the incoming peracid anion nucleophiles . Steric bulk in the alkyl group also has some effect . Such hindrance is not nearly so important in the oxidation reaction carried out under acidic conditions . 

At the second stage of chlorine substitution in the tetramers there is a greater statistical probability for the incoming nucleophile to attack the phosphorus adjacent to =P(C1)(NHR), viz. P4 or P8, rather than the remote phosphorus, viz. P6 (Fig. 9). However, this statistical effect is countered by the electron releasing effect of the substituent already present on P2, which tends to deactivate P2 as well as P4 and P8 towards further nucleophilic substitution. It is observed that reactive amines such as dimethylamine (94) or ethylamine (95) react with N4P4C18 and... 

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