Nucleophilic 1.3 hydride

We ll defer a detailed discussion of the mechanisms of these reductions until Chapter 19. For the moment, we ll simply note that they involve the addition of a nucleophilic hydride ion ( H ) to the positively polarized, electrophilic carbon atom of the carbonyl group. The initial product is an afkoxide ion, which is protonated by addition of H 0+ in a second step to yield the alcohol product. 

Reduction to sulphides with nucleophilic hydride reagents. ... 

Nach einem SN2-Mechanismus reduzieren nucleophile Hydride (z.B. Lithiumal-anat1) unsymmetrisch substituierte Oxirane hauptsachlich an dem weniger substituierten Kohlenstoff-Atom unter Bildung der hoher substituierten Alkohole (normale Oxiran-Offnung reduktive Ringspaltung nach Markownikow) ... 

Lithium-triathyl-hydrido-borat in THF ist als stark nucleophiles Hydrid ein aus-gezeichnetes Mittel zur Demethylierung quartarer Trimethylammonium-Salze. 

The electrophilicity of alane is the basis for its selective reaction with the amide group. Alane is also useful for reducing azetidinones to azetidines. Most nucleophilic hydride reducing agents lead to ring-opened products. DiBAlH, A1H2C1, and A1HC12 can also reduce azetinones to azetidines.100... 

Such a protonated carbonyl should be more susceptible to nucleophilic hydride attack to give 26. Repetition of the process could then yield a metal carbene species and water ... 

Bimetallic activation of acetyl and alkoxyacetyl ligands — through formation of cationic P2 acyl complexes — to reaction with nucleophilic hydride donors was established. Cationic transition metal compounds possessing an accessible coordination site bind a neutral T -acyl ligand on another complex as a cationic P2 acyl system. These i2 3icyl systems activate the acyl ligand to reduction analogous to carbocation activation. Several examples of i2-acyl complexation have been reported previously. 

The nucleophilic addition of alcohols [130, 204-207], phenols [130], carboxylates [208], ammonia [130, 209], primary and secondary amines [41, 130, 205, 210, 211] and thiols [211-213] was used very early to convert several acceptor-substituted allenes 155 to products of type 158 and 159 (Scheme 7.25, Nu = OR, OAr, 02CR, NH2, NHR, NRR and SR). While the addition of alcohols, phenols and thiols is generally carried out in the presence of an auxiliary base, the reaction of allenyl ketones to give vinyl ethers of type 159 (Nu = OMe) is successful also by irradiation in pure methanol [214], Using widely varying reaction conditions, the addition of hydrogen halides (Nu= Cl, Br, I) to the allenes 155 leads to reaction products of type 158 [130, 215-220], Therefore, this transformation was also classified as a nucleophilic addition. Finally, the nucleophiles hydride (such as lithium aluminum hydride-aluminum trichloride) [211] and azide [221] could also be added to allenic esters to yield products of type 159. 

The [HRu3(CO)n] complex reacts with [CpRe(CO)2(NO)]+ only relatively slowly, and by a pathway which does not involve nucleophilic hydride attack (210). 

Nucleophilic hydride ion replaces selectively the fluorine at the C4 position in perfluoropyridine to give 4//-perfluoropyridine as the sole product from the reaction with lithium aluminum hydride.147 The same position is attacked with this complex hydride in 3-chloro-2,4,5,6-tet-rafluoropyridinc resulting in 3-chloro-2,5,6-trifluoropyridine (9).148... 

Wipf has shown that 4,4-disubstituted cyclohexanones undergo nucleophilic attack where the facial selectivity is determined by dipolar control. Thus, compounds of the type 23 underwent nucleophilic attack anti to the electronegative substituent at C(4), whereas the fluorinated analogue, 24, underwent attack syn to the oxygen, in accordance with the inversion of the dipole moment. They found that the logarithm of the experimentally observed facial selectivity for nucleophilic attack was correlated linearly (R = 0.998) with the calculated dipole moments. The facial selectivities were also shown to depend upon the nature of the nucleophile, hydride ions and alkynyl carbanions being essentially unselective. 

The reactions of complex metal hydrides occur by an attack of the nucleophilic hydride ion on an electrophilic center.1 Aromatic nitrogen heterocycles in which the nitrogen has contributed only one electron to the -system (1) are electrophilic as compared with benzene, and have been shown to undergo reduction by the active reducing agent, lithium aluminum hydride. The nitrogen heterocycles in which the heteroatom has contributed two electrons to the 77-system (2) are electron-rich as compared with benzene and usually do not undergo reaction by reduction with complex metal hydrides.2 A combination of these two structural features, as in oxazoles (3), usually induces sufficient electrophilicity to allow attack by the hydride ion and reduction. 

Nitriles (RCN) can be reduced to primary amines (RCH2HN2) with lithium aluminium hydride that provides the equivalent of a nucleophilic hydride ion. The reaction can be explained by the nucleophilic attack of two hydride ions ... 

On the basis of what we have already learned about the reactions of lithium aluminum hydride with aldehydes and ketones (Chapter 18) and the mechanisms presented so far in this chapter, we can readily predict the product that results when hydride reacts with a carboxylic acid derivative. Consider, for example, the reaction of ethyl benzoate with lithium aluminum hydride. As with all of the reactions in this chapter, this reaction begins with attack of the nucleophile, hydride ion, at the carbon of the carbonyl group, displacing the pi electrons onto the oxygen (see Figure 19.7). Next, these electrons help displace ethoxide from the tetrahedral intermediate. The product of this step is an aldehyde. But recall from Chapter 18 that aldehydes also react with lithium aluminum hydride. Therefore, the product, after workup with acid, is a primary alcohol. 

Following strategy 2 from Figure 6.32, chemoselective SN reactions of hydride-donors with carboxylic acid derivatives also succeed starting from carboxylic chlorides. For the reasons mentioned further above, weakly nucleophilic hydride donors are used for this purpose preferentially and should be added dropwise to the acylating agent in order to achieve success ... 

Thiazolylium and benzothiazolylium salts react normally with aqueous sodium borohy-dride yielding the corresponding thiazolidine or benzothiazoline. The mechanism and the stereochemistry of the reaction have been studied with thiazolylium salts chosen as models for thiamine, using borodeuteride/hydride and deuterium/protium oxide. The pathway described in Scheme 30 was suggested it involves the addition of a nucleophilic hydride at C-2 (50 -> 51), the addition of an electrophilic proton at C-5 (51 -> 52) and the addition of a second nucleophilic hydride at C-4 (52 — 53). 

Reactions in which complex metallic hydrides (LiAlH4, etc.) act as sources of nucleophilic hydride are of considerable synthetic value (Gaylord, 1956 Wiberg and Amberger, 1971). In the case of nitro-aromatics, some interesting hydride displacements [e.g. (38)] have... 

The vacant orbital is able to accept a lone pair of electrons from a Lewis base to give a neutral species or can combine with a nucleophile to form a negatively charged tetrahedral anion. Thcj reducing agent boran e-dimethyl sulfide is an example of the Lewis acid behaviour while the borohy-j dride anion would be the result of the imaginary reaction of borane with a nucleophile hydride. The vacant orbital makes borane a target for nucleophiles. 

The remaining thiol ester is more electrophilic than the acid and can be reduced by the nucleophilic hydride from NADPH. Just as in LiBH4 reductions of esters (Chapter 24), the reaction does not stop at the aldehyde level, and two molecules of NADPH are used to make the alcohol. This is... 

This [1 H+/2 e ] reduction is equivalent to a nucleophilic hydride addition to a NO ligand, a reaction that is analogous to the well-known formation of metal... 

In addition to the transfer reactions already discussed, propagating carbe-nium ions also react with nucleophilic hydride and methide anions. This reaction may be bimolecular, or it may occur by an intramolecular hydride shift to form a more stable carbenium ion. The activation energy of hydride transfer is usually higher than that of propagation, and therefore occurs only at elevated temperatures. Nevertheless, hydride transfer is the dominant reaction when a-methylstyrene is initiated by triphenylcarbenium ions. That is, steric hindrance prevents initiation by direct electrophilic addition of the carbenium ion to a-methylstyrene. Instead, it occurs by hydride transfer from monomer to yield triphenyl methane and the primary carbenium ion of a-methylstyrene [cf., Eq. (40)]. 

The mechanisin of alcohol oxidation with NAD has several analoge in laboratory chemistry A base removes the O-TC proton from the alcohol and Keaerates an allcoxide ion, which expels a hydride ion leaving group as in the Cannizzaro reaction tSection 19.13>> The nucleophilic hydride ion dacn adds to the Cs=C-C=N part of NAD in a conjugate addition reaction, much the same as water adds to the C=C-C=0 part of the tt,p-unsaturated acyl CoA in step 2. 

These compounds are nucleophihc at the noncoordinated sulfur, and undergo alkylation there with iodomethane or benzyl bromide to give initially (128) (which may be isolated as the PFe salt) and ultimately (129) (equation 28). They also react with electron-deficient alkynes, possibly by a dipolar mechanism, to afford cyclized iron carbene complex (130). Finally, compounds (129) are subject to attack by some nucleophiles hydride attack occurs initially at the metal, but ultimately gives ) -dithioester complexes, such as (131). ... 

The use of sulfur dioxide as the solvent and low temperatures allows efficient and clean formation of the a-chloro nitroso compound4 6. The primary adducts, containing nitroso, nitro, or oxime functions, can be reduced to chlorine-free amines or /i-chloro amines 8. Additionally, chlorine readily undergoes substitution by nucleophiles (hydrides, alcohols, amines, etc.), such that halogen-free and /i-functionalized nitroso and nitro compounds, which can further be reduced to amines, can be prepared by this route. Recently, the conversion of nitroso compounds (RNO) to amines (RNHEt) using a triethylborane/borane mixture has been described9 10, although not applied specifically to /i-chloro nitroso compounds. 

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