Nucleophilic rearrangement mechanism

The rearrangement of cyclopropylcarbene to cyclobutene was studied theoretically using B3LYP at the 6-311G(d) level.58 The results show that the rearrangement of cyclopropylcarbene to cyclobutene is an electrophilic rearrangement, very different from the traditional mechanism of nucleophilic rearrangement for carbocations. 

The mechanism classification and the overall transformation classification are orthogonal to each other. For example, substitution reactions can occur by a polar acidic, polar basic, free-radical, pericyclic, or metal-catalyzed mechanism, and a reaction under polar basic conditions can produce an addition, a substitution, an elimination, or a rearrangement. Both classification schemes are important for determining the mechanism of a reaction, because knowing the class of mechanism and the overall transformation rales out certain mechanisms and suggests others. For example, under basic conditions, aromatic substitution reactions take place by one of three mechanisms nucleophilic addition-elimination, elimination-addition, or SrnL If you know the class of the overall transformation and the class of mechanism, your choices are narrowed considerably. 

Nucleophilic rearrangements formally occur in three steps. These steps may be illustrated by the rearrangement of a carbonium ion. A typical example is provided by the neopentyl system. It will be recalled that the SN2 mechanism at such a centre is slow, because of the steric hindrance caused by the /-butyl group in the (5-position. Furthermore, normal elimination is impossible, because there is no (5-hydrogen. 

A possible mechanism of this oxidative desulfurization is shown in as Fig. 6, namely, the central sulfur atom in the v-trithiane ring is oxidized to form sulfone, in which an intramolecular nucleophillic rearrangement takes place to give the 1,2-dithiolane ring and SO2. The intermediate, 5-hydroxy-l,2,3-trithiane in this reaction is a new v-trithiane compound. And, as we will mention later, it is a compound of importance as the base of insecticidal active derivatives. As there was no report on the crystal structure of v-trithiane, the stereochemical structure was investigated by X-ray analysis. ... 

Protonation of the alkene requires two curved arrows, as shown in the first step of the following mechanism. This leads to the more stable, secondary carbocation (rather than a primary carbocation). This secondary carbocation then undergoes a rearrangement, in which one of the carbon atoms of the ring migrates (as described in the problem statement). This is represented with one curved arrow that shows the formation of a more stable, tertiary carbocation. In the final step of the mechanism (nucleophilic attack), the carbocation is captured by a bromide ion. This step requires one curved arrow, going from the nucleophile (bromide) to the electrophile (the carbocation), as shown ... 

The rearrangement discovered by Kolosova et al. probably involves such reactivit (159). This reaction provides a good preparative method for various 5-amino-methylthiazoles (Scheme 43). No mechanism is proposed in the report, and it is not easy to understand how the C-5 enamine-like position competes with the very nucleophilic thiocarbonyl group of the formed A-4-thiazoline-2-thione. An alternative mechanism could start with ethanol addition at C-2. leading to the A-4-thiazoline (90) (Scheme 44). In this intermediate, C-5 nucleophilic reactivity would be favored bv the true enaminic structure. After alkylation on C-5,... 

Electrophilic attack on the sulfur atom of thiiranes by alkyl halides does not give thiiranium salts but rather products derived from attack of the halide ion on the intermediate cyclic salt (B-81MI50602). Treatment of a s-2,3-dimethylthiirane with methyl iodide yields cis-2-butene by two possible mechanisms (Scheme 31). A stereoselective isomerization of alkenes is accomplished by conversion to a thiirane of opposite stereochemistry followed by desulfurization by methyl iodide (75TL2709). Treatment of thiiranes with alkyl chlorides and bromides gives 2-chloro- or 2-bromo-ethyl sulfides (Scheme 32). Intramolecular alkylation of the sulfur atom of a thiirane may occur if the geometry is favorable the intermediate sulfonium ions are unstable to nucleophilic attack and rearrangement may occur (Scheme 33). 

Scheme 6 depicts a typical penicillin sulfoxide rearrangement (69JA1401). The mechanism probably involves an initial thermal formation of a sulfenic acid which is trapped by the acetic anhydride as the mixed sulfenic-acetic anhydride. Nucleophilic attack by the double bond on the sulfur leads to an episulfonium ion which, depending on the site of acetate attack, can afford either the penam (19) or the cepham (20). Product ratios are dependent on reaction conditions. For example, in another related study acetic anhydride gave predominantly the penam product, while chloroacetic anhydride gave the cepham product (7lJCS(O3540). The rearrangement can also be effected by acid in this case the principal products are the cepham (21) and the cephem (22 Scheme 7). Since these early studies a wide variety of reagents have been found to catalyze the conversion of a penicillin sulfoxide to the cepham/cephem ring system (e.g. 77JOC2887).

This mechanism explains the observed formation of the more highly substituted alcohol from unsymmetrical alkenes (Markownikoff s rule). A number of other points must be considered in order to provide a more complete picture of the mechanism. Is the protonation step reversible Is there a discrete carbocation intermediate, or does the nucleophile become involved before proton transfer is complete Can other reactions of the carbocation, such as rearrangement, compete with capture by water ... 

The mechanism of this reaction is not straightforward but the crucial step appears to be nucleophilic attack by water or OH" on the eoordinated ethene to give rr-bonded —CH2CH2OH which then rearranges and is eventually eliminated as MeCHO with loss of a proton. 

The mechanism of the indolization of aniline 5 with methylthio-2-propanone 6 is illustrated below. Aniline 5 reacts with f-BuOCl to provide A-chloroaniline 9. This chloroaniline 9 reacts with sulfide 6 to yield azasulfonium salt 10. Deprotonation of the carbon atom adjacent to the sulfur provides the ylide 11. Intramolecular attack of the nucleophilic portion of the ylide 11 in a Sommelet-Hauser type rearrangement produces 12. Proton transfer and re-aromatization leads to 13 after which intramolecular addition of the amine to the carbonyl function generates the carbinolamine 14. Dehydration of 14 by prototropic rearrangement eventually furnishes the indole 8. 

Arynes are intermediates in certain reactions of aromatic compounds, especially in some nucleophilic substitution reactions. They are generated by abstraction of atoms or atomic groups from adjacent positions in the nucleus and react as strong electrophiles and as dienophiles in fast addition reactions. An example of a reaction occurring via an aryne is the amination of o-chlorotoluene (1) with potassium amide in liquid ammonia. According to the mechanism given, the intermediate 3-methylbenzyne (2) is first formed and subsequent addition of ammonia to the triple bond yields o-amino-toluene (3) and m-aminotoluene (4). It was found that partial rearrangement of the ortho to the meta isomer actually occurs. 

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