Rearrangements to an Electrophilic Carbon

Our start is to check for any decent proton transfer reactions. Protonating the alcohol with HBr has a favorable which greatly improves the 

Now is the time to choose which of our two rearrangements to electrophilic carbon route to use. The Dn crosscheck passes, the p aHL of the leaving group is below zero, the carbocation is tertiary, and the solvent is polar. We can proceed with the Dn step. 

From the product, we see that a methyl has migrated migrating the hydroxyl would just give the same connectivity as the reactant. The carbocation produced from the methyl migration is more stable than the one we started with because it is now resonance-stabilized by the lone pair on oxygen. 

The rearrangement produces the protonated product, which is deprotonated by the strongest base in solution neutral water. 

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Elimination reactions (Figure 5.7) often result in the formation of carbon-carbon double bonds, isomerizations involve intramolecular shifts of hydrogen atoms to change the position of a double bond, as in the aldose-ketose isomerization involving an enediolate anion intermediate, while rearrangements break and reform carbon-carbon bonds, as illustrated for the side-chain displacement involved in the biosynthesis of the branched chain amino acids valine and isoleucine. Finally, we have reactions that involve generation of resonance-stabilized nucleophilic carbanions (enolate anions), followed by their addition to an electrophilic carbon (such as the carbonyl carbon atoms... 

Whenever an SN1 reaction is encountered, it is important to examine the carbocation tor the possibility of rearrangement. Rearrangement will occur if the carbon adjacent to the electrophilic carbon is bonded to more carbon groups than the electrophilic carbon In such cases, at least part of the product results from the carbocation formed by migration of a hydrogen or an alkyl group from the adjacent C to the electrophilic C. 

Because of their reactivity, it is frequently difficult to decide whether a free carbene has been generated or whether an electrophilic carbon undergoes a synchronous reaction. It is generally accepted that a free carbene is an intermediate in the Wolff rearrangement, in which a diazoketone rearranges to a highly reactive ketene. The versatile ketene intermediate then reacts to... 

As mentioned in previous sections, carbocation intermediates are subject to rearrangement to a more stable ion (sec. 2.7.B.iii). If the cation were stabilized in some manner, rearrangement would be much less likely, as when a heteroatom is attached to the electrophilic carbon. An example is the oxygen stabilized cation (3041 generated by reaction of a ketone with an acid catalyst. The electrons on the heteroatom are donated to the positive center leading to resonance stabilization (this is called back donation). Such a cation is usually... 

Mechanism 28.2 illustrates some of the key steps of the Edman degradation. The nucleophilic N-terminal NH2 group adds to the electrophilic carbon of phenyl isothiocyanate to form an A-phenylthiourea, the product of nucleophilic addition (Part [1]). Intramolecular cyclization followed by elimination results in cleavage of the terminal amide bond in Part [2] to form a new peptide with one fewer amino acid. A sulfur heterocycle, called a thiazolinone, is also formed, which rearranges by a multistep pathway (Part [3]) to form an A-phenylthiohydantoin. The R group in this product identifies the amino acid located at the N-terminal end. 

Ozonation ofAlkenes. The most common ozone reaction involves the cleavage of olefinic carbon—carbon double bonds. Electrophilic attack by ozone on carbon—carbon double bonds is concerted and stereospecific (54). The modified three-step Criegee mechanism involves a 1,3-dipolar cycloaddition of ozone to an olefinic double bond via a transitory TT-complex (3) to form an initial unstable ozonide, a 1,2,3-trioxolane or molozonide (4), where R is hydrogen or alkyl. The molozonide rearranges via a 1,3-cycloreversion to a carbonyl fragment (5) and a peroxidic dipolar ion or zwitterion (6). 

Similarly, in the acetoxycarbene series, 87-OAc rearranges to 88-OAc with kc = 8.5 x 106 s-1, 265 times faster than 17-OAc ring expands to 23-OAc (3.2 x 104 s-1).81 These rapid and dominant phenyl carbon 1,2-C shifts of 87 to 88 (bond a), rather than benzyl carbon (bond b) 1,2-C shifts to 89, are attributed to tz orbital mediation by the phenyl group in effect an electrophilic attack of the carbenic carbon on the aromatic ring. Ab initio calculations support this view.114... 

Pathway 2 of Scheme 9 corresponds to one of the most interesting developments in the Beckmann rearrangement chemistry. By trapping of the electrophilic intermediate with a nucleophile (Nu ) other than water, an imine derivative 227 is produced that may be used for further transformations. Carbon or heteroatom nucleophiles have been used to trap the nitrilium intermediate. Reducing agents promote the amine formation. More than one nucleophile may be added (for example, two different Grignard reagents can be introduced at the electrophilic carbon atom). Some of the most used transformations are condensed in Scheme 11. 

Thus, a-sulfinyl lithium carbanion of 1-chloroethyl p-tolyl sulfoxide was reacted with 1,4-cyclohexanedione mono ethylene ketal (195) to afford the adduct (196) in quantitative yield. The adduct was treated with ferf-butylmagnesium chloride (magnesium alkoxide was initially formed) followed by isopropylmagnesium chloride to result in the formation of magnesium /3-oxido carbenoid 197. The /3-oxido carbenoid rearrangement then takes place to give one-carbon expanded magnesium enolate 198. Finally, an electrophile was... 

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