Hydride nucleophile

Perfluoroisoquinoline, resembling isoquinoline itself, is most susceptible to hydride nucleophilic attack at Cl l//-perfluoroisoquinoline (11) results as the sole product from the reaction of lithium aluminum hydride with perfluoroisoquinoline.150... 

As mentioned above, appropriate hydride nucleophiles are capable of attacking coordinated CO [Eq. (3)]. This route to anionic formyl complexes was reported in 1976 by Casey, Gladysz, and Winter (29-34). All of the anionic formyl complexes in Table 1, including 22 [Eq. (4)], can be prepared by hydride attack on neutral metal carbonyl precursors. 

A straightforward example of this type of reaction is provided by the addition of hydride nucleophile (H -) to aldehydes and ketones. Recall from Section 10.7 that the organic chemist s sources of hydride nucleophile are lithium aluminum hydride and sodium borohydride. The reaction follows the basic conditions mechanism as illustrated by the following general equation using A1H4 as the nucleophile ... 

From the mechanism it can be seen that it takes two hydride nucleophiles to accomplish this reduction. Therefore, 1 mole of lithium aluminum hydride will reduce 2 moles of the ester. 

Q As usual, the hydride nucleophile attacks the carbonyl carbon and displaces the pi electrons onto the oxygen. 

The carbon-nitrogen double bond of the imine is attacked by the hydride nucleophile just like a carbon-oxygen double bond. 

Another method that can be used to prepare primary amines is the reduction of nitriles with lithium aluminum hydride. The mechanism for this reaction involves sequential addition of two hydride nucleophiles to the electrophilic carbon of the cyano group. The addition of water in the workup step supplies the two protons on the nitrogen in the product. An example follows ... 

The hydride nucleophile prefers to attack the carbonyl group of the borane complex IBBU2 from the top face following the Biirgi-Dunitz trajectory.3 The... 

Reduction of these C X a bonds is another example of nucleophilic substitution, in which LiAlHi serves as a source of a hydride nucleophile (H ). Because H" is a strong nucleophile, the reaction follows an Sn2 mechanism, illustrated for the one-step reduction of an alkyl halide in Mechanism 12.3. 

The iron cluster [Fe4S4(SPh)4] catalyzes the reduction of nitroarenes to arylamines. " A less hydridic nucleophile [HFe(CO)4] has also found application as a selective reducing agent for nitroarenes." Although [HFe(CO)4]"] is known to reduce aldehydes, ketones and acid halides," in THF solvent with tri-fluoroacetic acid, it selectively reduces nitrobenzenes to anilines in the presence of aldehyde and acid halide groups. 

Chiral Lewis acids combined with hydride sources like borohydride can reduce carbonyls to give one enantiomer selectively. The chiral Lewis acid complex with the carbonyl makes one face of the carbonyl more accessible to the hydride nucleophile. The chirality of the Lewis acid determines the chirality of the product. 

The role of metal ions as electrophilic catalysts is often underestimated. The formation of good ion-pair stabilization in the transition state in an anionic nucleophilic attack lowers the energy of the transition state. Even a powerful hydride nucleophile such as LiAlH4 will not add to a carbonyl if the lithium ion is kept from complexing with the carbonyl. 

Unsymmetrical ir-allyl-Pd complexes usually suffer attack of the hydride nucleophile at the less substituted position in an SN2-type reaction. However, the site selectivity of the process is controlled by steric and/or electronic effects. The reaction is strongly dependent on the structural features of the substrate and the reaction conditions. Opposite site selectivity is observed when the reduction occurs at the sterically more hindered position via a cationic intermediate (SN1-type). Very potent nucleophilic hydride sources, such as LiBHEt3 or LiAlH4, may rapidly attack intermediate it-ally 1 complexes at the less hindered terminal position to give the more substituted alkene, while less effective hydride-transfer reagents (NaBH3CN, NaBH4) attack the it-allyl systems at the site best able... 

The methoxide, methylsulfide, cyanide and hydride nucleophiles can be reacted with VI to yield VII, and that is the only attack on the diene that is observed . Emprical rules that predict the relative reactivity of different types of t-ligands are available . Although the stereochemistry of the addition to VI has not been determined, all the nucleophiles, including hydride, may add as external nucleophiles since complex VI is coordinatively saturated. The positive charge on the complex is also important. Both these properties... 

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