Alder-Ene ReactionEne Reaction

The four-electron system including an alkene π-bond and an allylic C-H σ-bondcan participate in a pericyclic reaction

The double bond shifts and new C-H and C-C σ-bonds are formed

The Alder-Ene Reaction requires higher temperatures because of the higheractivation energy of breaking the allylic C-H σ-bond.

While mechanistically different, the Ene reaction can produce a result similarto the Prins Reaction.

Mechanism of the Alder-Ene Reaction

Prins Reaction

The Prins Reaction is the acid-catalyzed of addition aldehydes to alkenes, andgives different products depending on the reaction conditions.

An excess of aldehyde acetals

When one equivalent of aldehyde is used and temperatures are > 70 °C diols orallylic alcohols may be isolated.

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Mechanism of the Prins Reaction

Appel Reaction

Appel Reaction

The reaction of triphenylphosphine and tetrahalomethanes (CCl4, CBr4) withalcohols is a ready method to convert an alcohol to the corresponding alkylhalide under mild conditions. The yields are normally high.

This reaction is somewhat similar to the Mitsunobu Reaction

Mechanism of the Appel Reaction1- activation of the triphenylphosphine by reaction with the tetrahalomethane2- Followed by attack of the alcohol oxygen at phosphorus to generate an

oxyphosphonium intermediate.

The oxygen is part of leaving group, and an SN2 displacement by halide takes place,proceeding with inversion of configuration if the carbon is asymmetric.

Mitsunobu Reaction

The Mitsunobu Reaction allows the conversion of primary and secondary alcohols toesters, phenyl ethers, thioethers

The nucleophile employed should be acidic, since one of the reagents (DEAD,diethylazodicarboxylate) must be protonated during the course of the reaction toprevent from side reactions.

Suitable nitrogen nucleophiles include phthalimide or hydrogen azide; subsequenthydrolysis (in the case of using phthalimide, see Gabriel Synthesis) or selectivereduction (in the case of azide formation, see Staudinger Reaction) makes thecorresponding amines accessible.

Mechanism of the Mitsunobu ReactionThe triphenylphosphine combines with DEAD to generate a phosphoniumintermediate that binds to the alcohol oxygen, activating it as a leaving group.Substitution by the carboxylate, mercapty completes the process.

The reaction proceeds with clean inversion, which makes the Mitsunobu Reactionwith secondary alcohols a powerful method for the inversion of stereogenic centersin natural product synthesis.

Side Reaction:

New protocols have been developed which allow better removal of side productsand/or the conversion of more basic nucleophiles.

Michaelis-Arbuzov Reaction

The reaction of a trialkyl phosphate with an alkyl halide to produce an alkylphosphonate.

This reaction sees extensive application in the preparation of phosphonateesters for use in the Horner-Emmons Reaction.

Mechanism of the Arbuzov Reaction

The first step involves nucleophilic attack by the phosphorus on the alkylhalide

Followed by the halide ion dealkylation of the resulting trialkoxyphosphoniumsalt

Arndt-Eistert Synthesis

Arndt-Eistert Synthesis

The Arndt-Eistert Synthesis allows the formation of homologated carboxylicacids by reaction of the activated carboxylic acids with diazomethane andsubsequent Wolff-Rearrangement of the intermediate diazoketones in thepresence of nucleophiles such as water, alcohols, or amines.

Mechanism of the Arndt-Eistert Synthesis

In the first step of this one-carbon homologation, the diazomethane carbon isacylated by an acid chloride to give an α-diazoketone.

Wolff-Rearrangement of the diazoketones to ketenes thermally (over therange between r.t. and 750°C, photochemically or by silver(I) catalysis.

nucleophiles such as water (to yield carboxylic acids), alcohols (to give esters)or amines (to give amides)

The method is widely used nowadays for the synthesis of β-amino acids.Peptides that contain β-amino acids feature a lower rate of metabolicdegradation and are therefore of interest for pharmaceutical applications.

Baeyer-Villiger Oxidation

Baeyer-Villiger Oxidation

The Baeyer-Villiger Oxidation is the oxidative cleavage of a carbon-carbonbond adjacent to a carbonyl, which converts ketones to esters and cyclicketones to lactones. The Baeyer-Villiger can be carried out with peracids, suchas MCBPA (metaChloroperoxybenzoic acid) or with hydrogen peroxide and aLewis acid.

Mechanism of the Baeyer-Villiger Oxidation

Baker-Venkataraman Rearrangement

Baker-Venkataraman Rearrangement

The base-induced transfer of the ester acyl group in an o-acylated phenolester, which leads to a 1,3-diketone.

This reaction is related to the Claisen Condensation, and proceeds through theformation of an enolate, followed by intramolecular acyl transfer.

Mechanism of the Baker-Venkataraman Rearrangement

Balz-Schiemann Reaction

Balz-Schiemann Reaction

The conversion of aryl amines to aryl fluorides via diazotisation andsubsequent thermal decomposition of the derived tetrafluoroborates orhexafluorophosphates. The decomposition may also be inducedphotochemically.

Mechanism of the Balz-Schiemann Reaction

Diazotisation.

The mechanism of the Balz-Schiemann reaction remains obscure. A possiblepathway is shown below:

Bamford-Stevens Reaction

Bamford-Stevens Reaction

Tosylhydrazones give alkenes upon treatment with strong bases.

Subsequent reaction with protic or aprotic solvents strongly influences theoutcome of the reaction.

This reaction may be used to effect the overall transformation of a ketone toan alkene.

Mechanism of the Bamford-Stevens Reaction

Carbenium ions are formed in protic solvents:

...and carbenes in aprotic solvents:

Barton Decarboxylation

Mechanism of the Barton Decarboxylation

The initiation of the Barton Decarboxylation ( Bu3Sn-H -> Bu3Sn. ) is effectedwith a radical initiator, the driving force for the reaction itself is the formationof the stable S-Sn bond.

Barton-McCombie ReactionBarton Deoxygenation

Mechanism of the Barton-McCombie Reaction

Initiation: Azobisisobutyronitrile (AIBN)

The catalytic cycle, in which low concentration of .SnBu3 effects the reaction:

Baylis-Hillman Reaction

This coupling of an activated alkene derivative with an aldehyde is catalyzedby a tertiary amine (for example: DABCO = 1,4-Diazabicyclo[2.2.2]octane).

Mechanism of the Baylis-Hillman Reaction

The addition of the amine catalyst to the activated alkene to form a stabilizednucleophilic anion. then adds to the aldehyde.