Hydride ion addition

As well as the above addition and elimination sequences, metal-catalyzed nucleophilic addition can occur. Examples include the zinc(II)-catalyzed hydride ion addition in the reduction of the formyl group of the phenanthroline aldehyde (49)91 and the copper(II)-catalyzed ring opening of 2-pyridyloxirane (50)92 (equations 22 and 23). 

Reduction of the cation (M = W) with NaBH4 affords a yellow oil identified as the isopropyl complex (C5H6)W(CO)3[CH(CH3)2] with none of the w-propyl isomer present. A hydride ion addition corresponding to that with the analogous iron complex (255) is postulated. 

Hydride ion addition to certain /zs-CsH5 compounds produces cyclo-pentadiene olefin complexes (equations 24-A-l, 24-A-2) addition to arene complexes gives A5-cyclohexadienyls (24-A-3) ... 

Fig. 4.1. Increase in the Stt overlap and rehybridization of the n MO of formaldehyde in the course of the hydride-ion addition reaction according to the calculations in Ref. [5]. B, D, and F correspond to geometry configurations in Fig. 1.18...

However, the possibility of a hydride mechanism is not excluded. Irradiation of [6-27] may homolytically cleave the metal-carbon bond to form a 7r-allyl complex [6-28]. Hydride ion addition to the 7r-complex [6-29] gives an isopropyl complex, C5H5Fe(CO)3—CH(CH3)2 This process is designated as a n-a rearrangement. Analogous 7r-allyl and olefin complexes of molybdenum and of tungsten are known. 

Cationic rings are readily reduced by complex hydrides under relatively mild conditions. Thus isoxazolium salts with sodium borohydride give the 2,5-dihydro derivatives (217) in ethanol, but yield the 2,3-dihydro compound (218) in MeCN/H20 (74CPB70). Pyrazolyl anions are reduced by borohydride to pyrazolines and pyrazolidines. Thiazolyl ions are reduced to 1,2-dihydrothiazoles by lithium aluminum hydride and to tetrahydrothiazoles by sodium borohydride. The tetrahydro compound is probably formed via (219), which results from proton addition to the dihydro derivative (220) containing an enamine function. 1,3-Dithiolylium salts easily add hydride ion from sodium borohydride (Scheme 20) (80AHC(27)151). 

The 3-substituents in 3-nitro- and 3-phenylsulfonyl-2-isoxazolines were displaced by a variety of nucleophiles including thiolate, cyanide and azide ions, ammonia, hydride ions and alkoxides. The reaction is pictured as an addition-elimination sequence (Scheme 54) (72MI41605, 79JA1319, 78JOC2020). 

Addition of hydride ion from the catalyst gives the adsorbed dianion (15). The reaction is completed and product stereochemistry determined by protonation of these species from the solution prior to or concurrent with desorption. With the heteroannular enolate, (13a), both cis and trans adsorption can occur with nearly equal facility. When an angular methyl group is present trans adsorption (14b) predominates. Protonation of the latter species from the solution gives the cis product. Since the heteroannular enolate is formed by the reaction of A" -3-keto steroids with strong base " this mechanism satisfactorily accounts for the almost exclusive formation of the isomer on hydrogenation of these steroids in basic media. The optimum concentration of hydroxide ion in this reaction is about two to three times that of the substrate. 

The formation of 88 is postulated to be occurring by the nucleophilic attack of a hydride ion (47), abstracted from the secondary amine, on the a-carbon atom of the iminium salt (89). The resulting carbonium ion (90) then loses a proton to give the imine (91), which could not be separated because of its instability (4H). In the case of 2-methyIhexamethylenimine, however, the corresponding dehydro compound /l -2-methylazacyclo-heptene (92) was isolated. The hydride addition to the iminium ion occurs from the less hindered exo side. 

The reaction has been applied to more complex enamines 13) and to dienamines 19). The reduction may be rationalized by initial protonation at the enamine carbon and subsequent decarboxylation of formate ion and addition of the hydride ion to the iminium cation. This mechanism has been given support by the reaction of the enamine (205) with deuterated formic acid 143) to give the corresponding amines. The formation of 206 on reaction with DCOOH clearly indicates that protonation at the enamine carbon is the initial step. 

This method has been used for the reduction of l-methyl-2-alkyl-.d -pyrrolinium and l-methyl-2-alkyl-.d -piperideinium salts by Lukes et al. (42,249-251) and for the reduction of more complex bases containing the dehydroquinolizidine skeleton by Leonard et al. (252). The formic add reduction may be satisfactorily explained by addition of a hydride ion, or an equivalent particle formed from the formate anion, to the -carbon atom of the enamine (253), as shown in Scheme 13. 

In addition to the effects of a cyclic transition state, of lone-pair repulsions, and of rate of removal of hydride ion mentioned above, the position of nucleophilic substitution can be altered by a) hydrogen... 

It is eommon knowledge that the reaetion is a two-step proeess, whieh ineludes the addition of a nueleophile at an unsubstituted earbon of an arene or hetarene followed by the aromatization of the intermediate cr -adduet (94MT). Elimination of the hydride ion seems to be an improbable step eompared to the elimination of a nueleofuge X from sueh cr -adduets. Thus the aromatization of a (T -adduet is the key step for the whole reaetion, and it ean proeeed by several general paths, as shown in Seheme 1. 

Evidence in support of a carbocation mechanism for electrophilic additions comes from the observation that structural rearrangements often take place during reaction. Rearrangements occur by shift of either a hydride ion, H (a hydride shift), or an alkyl anion, R-, from a carbon atom to the adjacent positively charged carbon. The result is isomerization of a less stable carbocation to a more stable one. 

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. 

As with the reduction of carbonyl compounds discussed in the previous section, we ll defer a detailed treatment of the mechanism of Grignard reactions until Chapter 19. For the moment, it s sufficient to note that Grignard reagents act as nucleophilic carbon anions, or carbanions ( R ), and that the addition of a Grignard reagent to a carbonyl compound is analogous to the addition of hydride ion. The intermediate is an alkoxide ion, which is protonated by addition of F O"1 in a second step. 

Figure 19.7 Mechanism of carbonyl-group reduction by nucleophilic addition of "hydride ion" from NaBH4 or LiAIH4.

The Cannizzaro reaction takes place by nucleophilic addition of OH- to an aldehyde to give a tetrahedral intermediate, which expels hydride ion as a leaving group and is thereby oxidized. A second aldehyde molecule accepts the hydride ion in another nucleophilic addition step and is thereby reduced. Benzaldehyde, for instance, yields benzyl alcohol plus benzoic acid when heated with aqueous NaOH. 

Reduction Conversion of Nitriles into Amines Reduction of a nitrile with LiAIH4 gives a primary amine, RNH . The reaction occurs by nucleophilic addition of hydride ion to the polar C=N bond, yielding an imine anion, which still contains a C=N bond and therefore undergoes a second nucleophilic addition of hydride to give a dianion. Both monoanion and dianion intermediates are undoubtedly stabilized by Lewis acid-base complexafion to an aluminum species, facilitating the second addition that would otherwise be difficult Protonation of the dianion by addition of water in a subsequent step gives the amine. 

The reaction is similar to the reduction of a nitrile to an amine, except that only one nucleophilic addition occurs rather than two, and the attacking nucleophile is a carbanion (R ) rather than a hydride ion. For example ... 

Amide reduction occurs by nucleophilic addition of hydride ion to the amicle carbonyl group, followed by expulsion of the oxygen atom as an alumi-nate anion leaving group to give an iminium ion intermediate. The intermediate iminium ion is then further reduced by JL1AIH4 to yield the amine. 

Reductive animations also occur in various biological pathways, fn the biosynthesis of the amino acid proline, for instance, glutamate 5-semjaldehyde undergoes internal imine formation to give 1-pyrrolinium 5-carboxylate, which is then reduced by nucleophilic addition of hydride ion to the C=N bond. 

Subsequent dehydration of /3-hydroxybutyryl ACP by an ElcB reaction in step 7 yields trans-ciotonyl ACP, and the carbon-carbon double bond of crotonyl ACP is reduced by NADPH in step 8 to yield butyryl ACP. The doublebond reduction occurs by conjugate addition of a hydride ion from NADPH to the /S carbon of fraus-crotonyl ACP. In vertebrates, the reduction occurs by an overall syn addition, but other organisms carry out similar chemistry with different stereochemistry. 

When the hydride ion of lithium alanate is used as nucleophile, cyclohexa-2,4-dien-l-ol is obtained as a labile addition product which eliminates water on standing to give benzene.12 The reaction of an oxepin derivative that possesses a hexamethylene bridge across C3-C6 with sodium methoxide gives an addition product 5 in which the seven-membered heterocyclic system is retained.213 214... 

Xu and Li (1989) investigated H — CIDNP spectra of fifteen substituted benzene-diazonium ions during reduction with NaBH4. The spectra are consistent with a mechanism in which the first step is the addition of a hydride ion to the diazonium ion. The diazene formed (Ar - N2 - H) is assumed to dimerize and disproportionate into a radical pair [Ar-N-NH2 N = N — Ar] which loses one equivalent of N2 yielding [Ar—N —NH2 Ar] and recombines to give the diarylhydrazine. A proportion of the aryl radicals escape and form the hydro-de-diazoniation product. 

The addition of monomer to the latter anion leads to the polymer, In this procedure the reaction of sec-BuLi with the C = 0 group is prevented, and due to the very low concentration of the reactive CH2C(CH3) (CO OCH3), Li+ their disproportionation, presumably involving hydride ion transfer, is minimized also. All these factors contribute to the cleanness of polymerization. 

As is the case for cationic polymerisation, anionic polymerisation can terminate by only one mechanism, that is by proton transfer to give a terminally unsaturated polymer. However, proton transfer to initiator is rare - in the example just quoted, it would involve the formation of the unstable species NaH containing hydride ions. Instead proton transfer has to occur to some kind of impurity which is capable for forming a more stable product. This leads to the interesting situation that where that monomer has been rigorously purified, termination cannot occur. Instead reaction continues until all of the monomer has been consumed but leaves the anionic centre intact. Addition of extra monomer causes further polymerisation to take place. The potentially reactive materials that result from anionic initiation are known as living polymers. 

Neither methyl nor ethyl fluoride gave the corresponding cations when treated with SbFs. At low temperatures, methyl fluoride gave chiefly the methylated sulfur dioxide salt, (CH3OSO) ShF while ethyl fluoride rapidly formed the rert-butyl and ferf-hexyl cations by addition of the initially formed ethyl cation to ethylene molecules also formed ° At room temperature, methyl fluoride also gave the tert-butyl cation. In accord with the stability order, hydride ion is abstracted from alkanes by super acid most readily from tertiary and least readily from primary positions. 

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