Nucleophilic Substitution with Hydride Transfer

Reactions of this type occur fastest at C-2 in quinoline and at C-1 in isoquinolines. 

The immediate products of addition of alkyl and aryl Grignard reagents and alkyl- and aryllithiums are dihydro-quinolines and -isoquinolines and can be characterised as such, but can be oxidised to afford the C-substituted, re-aromatised heterocycles illustrated below is a 2-arylation of quinoline.  

Vicarious nucleophilic substitution (3.3.3) allows the introduction of substituents into nitroquinolines cyanomethyl and phenylsulfonyhnethyl groups, for example, can be introduced ortho to the nitro group, in 5-nitroquinolines at C-6 and in 6-nitroquinolines at C-5.  

Sodium amide reacts rapidly and completely with quinoline and isoquinoline, even at -45 °C, to give dihydro-adducts with initial amide attack at C-2 (main) and C-4 (minor) in quinoline, and C-1 in isoquinoline. The quinoline 2-adduct rearranges to the more stable 4-aminated adduct at higher temperatures. Oxidative trapping of the quinoline adducts provides 2- or 4-aminoquinoline isoquinoline reacts with potassium amide in liquid ammonia at room temperature to give 1-aminoisoquinoline.  

Oxidative aminations are possible at other quinoline and isoquinoline positions, even on the benzene ring, providing a nitro group is present to promote the nucleophilic addition  

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Triazasilatranes 179 and 180 react with various nucleophiles such as organometallic reagents (equation 176), metal alkoxides (equation 177) and amides (equations 178 and 179) to give the substitution products 172, 181-184 as well as hydride transfer products 169, 170. The relative ratios of these products depend on stereoelectronic factors, the nature of the nucleophilic reagents and the reaction conditions312. Thus, the reaction of triazasilatrane 180 with /i-butyllithiurn affords 181a, which is the product of substitution, while only 1-hydrotriazasilatrane (170) is formed from 180 and /e/t-butyllithiurn in a hydride transfer process. 

The nucleophilic addition of a hydride to the exocyclic double bond of fulvenes, using LiBEt3H as the hydride transfer reagent, resulted in the formation of the appropriately substituted lithium cyclopentadienide intermediates, which is insoluble under the reaction conditions chosen and can be isolated for purification purposes. Two equivalents of the substituted lithium cyclopentadienide undergo a transmetallation reaction when reacted with 1 mol equivalent of titanium tetrachloride in THF under reflux to give the appropriate non-bridged substituted titanocene dichloride in overall yields of up to 77% as seen in Scheme 2. 

As it was already discussed, these salts are easily formed by hydride transfer from the corresponding dioxolanes and triphenylmethylium salts but react differently with nucleophiles — exclusively by addition. Strong nucleophiles mostly form the kinetic product by substitution at C-2, weaker ones yield the thermodynamic products throu ring opening at 0-1—C-5 (0-3—C-4). These paths of the ambident reactivity, described in detail by Pittman and by Perst are shown below ... 

It is important to emphasize that three different types of reactions, i.e., electron transfer from (TPP)Co to Q (Eq. 13), Diels-Alder reaction of anthracenes with Q (Scheme 12) and hydride transfer from BNAH to Q (Scheme 14), have the common rate-determining step of Mg +-catalyzed electron transfer from these electron donors to Q. In each case, the relative catalytic dependence of A obs on [Mg ] is the same as indicated by Eq. 14, irrespective of different electron donors. The nucleophilic addition of a / ,/ -dimethyl-substituted ketene silyl acetal such as Me2C= C(OMe)OSiMe3 is also catalyzed by Mg + in MeCN [227, 228]. No reaction takes... 

With silyl-substituted oxiranes, dibal-H favors the primary alcohol and Bu 3A1H favors the secondary alcohol. These observations have been interpreted in terms of the timing of the hydride transfer to one of the oxirane carbons. dibal-H, which exists as a Lewis complex in donor media (R3N-A1H(Bu )2, or R20-A1H(Bu )2) acts as a nucleophilic hydride source, which preferentially attacks the least-hindered carbon. With Bu 3A1, complexation with the oxirane oxygen precedes isobutene elimination and the generation of the Al—H bond. A considerable carbocation character is acquired in the transition state, hence formation of the primary alcohol is favored. It is worthy of note that trialkylstannyl-substituted oxiranes are reduced with Red-Al invariably at the oxirane... 

A great variety of substituted enolates can be obtained by the addition of nucleophiles (XeMe) to enones (for X = trialkylsilyl, see Section D.4.3.). Reductive formation of these enolates (where X = hydrogen), however, can be achieved either by hydride transfer or by a two-electron reduction combined with proton abstraction from a suitable partner. Consecutive protonation produces the diastereomeric ketones. 

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