Reactivity patterns with nucleophiles

Specific alterations of the relative reactivity due to hydrogen bonding in the transition state or to a cyclic transition state or to electrostatic attraction in quaternary compounds or protonated azines are included below (cf. also Sections II, B, 3 II, B, 5 II, C and II, F). A-Protonation is often reflected in an increase in JS and therefore the relative reactivity can vary with the significance of JS in controlling the reaction rate. Variation can also result from rate determination by the second stage of the SjjAr2 mechanism or from the intervention of thermodynamic control of product formation. Variation in the rate and in the reactivity pattern of polyazanaph-thalenes will result when nucleophilic substitution [Eq. (10)] occurs only on a covalent adduct (408) of the substrate rather than on its aromatic form (400). This covalent addition is prevented by any 4-... 

The familiar pattern of 2-amination with sodamide ( — 33°, 90% yield) occurs also with 1,5-naphthyridine. Greater reactivity at the 2-position is attributed, as before, to a cyclic transition state with electrophilic attack at a ring-nitrogen concomitant with nucleophilic attack adjacent to the cationic center thus formed. 

As mentioned earlier, metal complexation not only allows isolation of the QM derivatives but can also dramatically modify their reactivity patterns.29o-QMs are important intermediates in numerous synthetic and biological processes, in which the exocyclic carbon exhibits an electrophilic character.30-33 In contrast, a metal-stabilized o-QM can react as a base or nucleophile (Scheme 3.16).29 For instance, protonation of the Ir-T 4-QM complex 24 by one equivalent of HBF4 gave the initial oxo-dienyl complex 25, while in the presence of an excess of acid the dicationic complex 26 was obtained. Reaction of 24 with I2 led to the formation of new oxo-dienyl complex 27, instead of the expected oxidation of the complex and elimination of the free o-QM. Such reactivity of the exocyclic methylene group can be compared with the reactivity of electron-rich enol acetates or enol silyl ethers, which undergo electrophilic iodination.34... 

As can be seen from Table 2 rates of reaction of nucleophiles with phenyl benzenethiolsulfinate vary markedly with nucleophile structure (Kice and Liu, 1979). The particular reactivity pattern observed will be discussed later in Section 8 in conjunction with data on the reactivity of the same nucleophiles toward phenyl benzenethiolsulfonate, PhS02SPh. Of significance at present is the fact that PhS is much more reactive than nucleophiles such as OH- or CH30. In the alkaline hydrolysis of PhS(0)SPh (Oae et al., 1977b Kice and Rogers, 1974a) this means that the thiophenoxide liberated by the initial attack of OH- on PhS(0)SPh (28) will rapidly react with a second molecule of thiolsulfinate to form disulfide and sulfenate ion (29). 

We will defer consideration of the particular pattern of nucleophile reactivity observed until Section 9. There we will compare it with what is found for the same group of nucleophiles reacting with (a) an aryl rr-disulfone ArS02S02Ar, a substitution that involves the same leaving group as in (139) but which takes place at a sulfonyl ( S02) rather than a sulfinyl ( S=0) sulfur, and (b) an aryl thiolsulfonate, ArSSOzAr, a substitution where ArSO is displaced from a sulfenyl ( S) sulfur. 

Rogne (1970) has measured the reactivity of some of the same nucleophiles toward benzenesulfonyl chloride in water at 25°. When log km for reaction of these nucleophiles with PhSOjCl is plotted vs. the log values for the same nucleophiles from Table 10, one obtains a good straight line relationship with a slope of about 0.8. This shows that the reactivity pattern observed with PhSOjSOjPh and shown in Table 10 is representative of what will be observed generally in nucleophilic substitution at the sulfonyl sulfur of reactive sulfonyl substrates. 

Related reactivity patterns have been described for the in situ formed complexes [RuCl(=C=C=C=C=CPh2)( 7 -C6Me6)(PR3)][PF6] (PR3 = PMej, PMe2Ph, PMePhj) [359, 360], [RuCl(=C=C=C=C=CPh2) K (Af,P,P,P)-N(CH2CH2PPh2)3 ] [PFg] [362], or frans-[RuCl(=C=C=C=C=CPh2)(dppm)2][PF6] [169, 216, 363], which readily add alcohols and amines (used as solvents) across the Cy=Cs bond. However, in the former case a competitive nucleophilic addition across the C -Cp double bond was also observed with methanol. 

The anion 7 is quite nucleophilic and undergoes exclusive C-alkylation upon reaction with electrophiles including chlorotrimethylsilane °. These reactivity patterns have led to the suggestion that enolates of iron-acyl complexes may be considered to behave similarly to the organic dianion 910- u. 

Trifluoromethyl iodide is a poor substrate for SN2 reactions [28], The increased donativity of the methylene carbon as rendered by the fluorine atoms is reflected in its reluctance to enter a bonding relationship with a nucleophile. Similar reactivity patterns are known for chloromethyl phenyl sulfone [28] and chloromethyltrimethyl-silane. In these latter compounds the reactive center is directly linked to an acceptor group. 

In contrast to the [Ni(TMC)]+ complex, [NikOEiBC)]" shows reactivity patterns for R and X of methyl > primary > secondary > tertiary and I > Br > Cl. This is consistent with the rate-determining step being SN2-type nucleophilic attack at R—X by [Ni (OEiBC)] to generate NiIIl-alkyl species (147, 148). 

This reactivity pattern is rather rare but is seen in the condensation of carbon nucleophiles such as nitromethane with arylidene isocyanides (equation 74) (79JHC(S)lll). The isocyanides are obtained by condensing aromatic aldehydes with tosylmethyl isocyanide. 

Ketones and aldehydes can be converted into a number of nucleophilic molecules with similar reactivity patterns. 

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