Pinacolic deaminations

If such an amino group is located alpha to a hydroxyl group, then treatment with nitrous acid causes a reaction closely related to the pinacol rearrangement, pinacolic deamination ... 

Let us examine the stereochemistry of pinacolic deamination in some detail.. In this we shall see the operation of a factor we have not yet encountered in rearrangements conformational effects. More important, we shall get some idea of the methods used to attack problems like this. 

Figure 28.1. Pinacolic deamination of optically active labeled 2-amino-1,1-diphenyl-1-propanol.The most abundant conformer, II, of the dia-zonium ion yields cation 111. Cation III does two things (a) rearranges by back-side migration of Ph, and (b) rotates, in the easiest way possible, to form cation IV, which rearranges by front-side migration of Ph.

In pinacolic deamination we have a rather special situation, where reaction and rotation are of roughly comparable speeds, and hence both the populations and the reactivities of conformers affect the product ratio. Most interesting of all, perhaps, is the ingenuity that Collins used to show that this is so. 

Figure 28.2. Pinacolic deamination of diastereomeric 2-amino-l-anisyl-1-phenyl-1-propanols. In each case the most abundant conformer. Via or Vila, of the diazonium ion yields a cation in which an aryl group is in position for back-side migration via a trans transition state anisyl in lb, phenyl in VII6. Such rearrangement predominates. Some of each first-formed cation is converted through rotation into another cation, in which the other aryl group is in position for front-side migration via a trans transition state phenyl in Vic, anisyl in VIIc. Such rearrangement gives the minor product.

The pinacolic deamination of 2-amino-1,1 -diaryl-1 -propanols provides a convincing case for conformational control. Optically active 2-amino-l,l-diphenyl-l-propanoI 209) affords a-phenylpropiophenone (210) with 88% inversion plus 12% retention (76% inversion plus 24% racemization) at the terminus of phenyl migration 196K The diastereomer (211) of 2-amino-l-anisyl-l-phenyl-l-propanol reacts with preferential... 

For another classical problem of nucleophilic aliphatic substitution and rearrangement, namely pinacolic deaminations and rearrangements, the use of cyclohexane derivatives with a tert-hvXyX group instead of open-chain alkane derivatives was very helpful. The stereochemistry of these reactions was studied first by Bernstein and Whitmore (1939). Specific labeling with used first by Collins and his coworkers (Benjamin et al., 1957), helped significantly to elucidate the complex pathway of pinacolic deamination. Even summarizing the results would take far too much space here. 

In the case of the Tiffeneau-Demjanov rearrangement, the starting material is an aminomethylalkanol 5 thus after formation of the diazoalkane 6, the neighboring alcohol serves as an electron source to provide an electron push to satisfy the formed cation. In this sense, the Tiffeneau-Demjanov rearrangement resembles a pinacolic deamination process and provides a ketone 7. 

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