Base-induced, addition elimination

The stereoselectivity of these reactions arises from a base-induced anti elimination after the migration. The elimination is induced by addition of methoxide to the boron, generating an anionic center. 

The proposed mechanism for a standard Heck reaction is depicted in Scheme 6.5. Generally, a haloalkene or haloarene undergoes oxidative addition to an in situ generated, coordinatively unsaturated 14-electron palladium(O) complex, but other substrates such as tosylates, triflates or diazonium salts can also be applied. Subsequent, sy -insertion into the C=C double bond of a complexed olefin yields a t7-(j -alkenyl) or (j- aryl)alkylpalladium complex. If no hydrogen atom in a pseudo cis-position relative to the palladium is present, an internal rotation step is required prior to syw-elimination of the olefin to afford the traws-olefin product and a palladium(II) hydride complex. The latter is restored to the initial Pd(0) species by base-induced reductive elimination.137"401... 

A traceless linker for anchoring secondary amines has been developed [123,124] and is referred to as the REM linker 21 (regenerated after cleavage, functionalized by Michael addition). Tertiary amines can be prepared on this support by conversion to a resin-bound quaternary ammonium salt followed by cleavage by base-induced Hofmann elimination [125]. The analogous vinyl sulfone resin 2m can also be used to anchor secondary amines and is stable to a greater range of reactants [126,127]. 

A serious limitation of VNS is connected with its mechanism, namely, conversion of intermediate ct adducts into the VNS products via bimolecular base-induced p-elimination. To cause the reaction, it is therefore necessary that these adducts be produced in a reasonable concentration. Indeed, low nucleophilic carbanions, such as dimethyl chloromalonate, do not react with moderately electrophilic nitrobenzene because of unfavorable equilibrium of the addition step, but react nicely with more electrophilic nitrothiazoles (Scheme 8) [34]. 

Amination of nitroarenes with hydroxylamine, known for over 100 years [43], proceeds undoubtedly according to the VNS mechanism. Modem aminating agents, such as 4-amino-1,2,4-triazole [44—46], sulfenamides [47, 48], and 0-methyl hydroxylamine [49, 50], are more versatile and efficient than hydroxylamine. 1,1,1-Trimethyl hydrazinium iodide proved to be particularly useful for this purpose [51-53]. Amination with this reagent proceeds via addition of the hydrazino moiety followed by a base-induced p-elimination of trimethylamine from the corresponding adducts. 

The VNS of hydrogen consists of the addition of a nucleophile bearing a leaving group X attached to the nucleophilic center to an electrophilic aromatic substrate followed by base-induced p-elimination of HX from the initially formed [Pg.222]

Carbenes are uncharged reactive intermediates of general formula CR2, in which carbon atom has a sextet of electrons. Depending on the nature of substituents R, they can behave as electrophilic or nucleophilic species, able to enter a variety of synthetically useful reactions. Perhaps the most important reaction of electrophilic carbenes is addition to C=C double bond giving cyclopropanes. Many electrophilic carbenes can be generated via the base-induced a-elimination process—abstraction of a proton from a carbon atom, connected with a halogen, followed by departure of the halogen anion from the initially formed a-halocarbanion (eq. 101). 

Bromination of dibutyl vinylboronate at low temperature readily affords a stable di-bromo derivative [2, 3]. Similarly, ( )-alkenylboronic acids or their catechol esters yield the corresponding substituted compound by stereospecific trans addition of bromine. Treatment with base induced anti elimination of the boronic group and the bromine ion. The final result of this sequence was the replacement of boron by bromine with inversion of olefin geometry in excellent yields and 99% stereochemical purities (Scheme 9.1) [4]. 

Vicarious nucleophilic substitution of hydrogen is described in several reviews [158, 159, 161]. The special character of vicarious nucleophilic substitution of hydrogen (VNSH) is that the nucleophile is a carbanion that must contain a leaving group X attached to the carbanionic centre. The first step is a fast reversible addition of carbanion to the nitroaromatic ring, followed by base-induced p-elimination of HX from the intermediate o-adduct 77. Protonation is then necessary to restore the aromaticity of the compound. Two equivalents of base must be used, the first to deprotonate the CH-acidic compound to form the carbanion the second is responsible for the HX elimination (Scheme 107) [168]. 

Relative reactivity of olefins with bromophenylcarbene generated either (1) by irradiation of 3-bromo-3-phenyldiazirine or (2) from base-induced a-elimination of a,a-dibromotoluene in the presence and in the absence of 18-crown-6 showed that addition of 18-crown-6 (via the complex of carbene with KCl/ KO-t-butanolate) as well as photolysis of diazirine afforded the free carbene. a-Ehmination normally proceeds via carbenoids (Scheme 3). 

The reaction of 3-methoxy-1,2,4-triazine 1-oxide 20 with the carbanion generated from chloromethyl phenyl sulfone proceeds as the vicarious nucleophilic substitution (VNS) of hydrogen (Scheme 1, path B) via addition of the carbanion at position 5 of the heterocycle. Following base-induced elimination of HCl and protonation, 3-methoxy-5-phenylsulfonyl-1,2,4-triazine 4-oxides 65 result (88LA627). 

Base-induced eliminative ring fission, in which both the double bond and the sulfone function take part, has been observed in thiete dioxides253. The reaction can be rationalized in terms of initial Michael-type addition to the double bond of the ring vinyl sulfone, followed by a reverse aldol condensation with ring opening. The isolation of the ether 270c in the treatment of 6c with potassium ethoxide (since the transformation 267 -> 268 is not possible in this case) is in agreement with the reaction mechanism outlined in equation 101253. 

Other examples of the ElcB pathway are benzyne formation from C6HsF (cf. p. 174), reversal of simple nucleophilic addition to 0=0, e.g. base-induced elimination of HCN from cyanohydrins (20 cf. p. 212),... 

The regioselective addition of nitryl iodide to alkenes, followed by base-induced elimination, gives nitroalkenes. Nitryl iodide is generally prepared by the reaction of AgN02 and iodine. 

Special cases of triafulvene formation were found in the base-induced reaction of the nitroso compound 91 with dimethyl fumarate85, in the thermolysis of tetra-fluorocyclopropene reported to give the perfluorinated triafulvenes 65/6668 and in the addition of bis(trifluoromethyl) ketene to bis (p-tolyl) cyclopropenone66 which gave rise to triafulvene 63 by elimination of C02 ... 

The vicarious nucleophilic substimtion of carbo- and hetero-cyclic nitroarene hydrogen by a hydroxyl group, on reaction with silylhydroperoxide anions, has been shown to proceed via nucleophilic addition of ROO followed by base induced elimination of ROH by an ii2-type mechanism the required orientation of the hydroxylation can be controlled by the conditions selected. ... 

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