Protonation of Enamines

The preceding section described the preparation of enamines by mercuric acetate oxidation of tertiary amines. The initial product in these oxidations is the ternary iminium salt, which is converted to the enamine or mixture of enamines by reaetion with base. Thus iminium salts synthesized by methods other than the oxidation of tertiary amines or the protonation of enamines are potential enamine sources. 

Important for the hydrolysis is the observation (10) that protonation of enamines with hydrogen chloride does not immediately lead to immonium salts, but in most, if not all, cases first to the formation of the corresponding enammonium ions, which afterward rearrange more or less rapidly to the more stable immonium ions [Eq. (1)] ... 

Iminium salts can be made in a number of ways such as protonation of enamines (7), alkylation of aldimines and ketimines (5,9), cleavage of a covalent bond in a... 

A recent adaptation of the procedure employing perchlorate and fluoro-borate salts has been reported by Leonard and Paukstelis (J5). This report includes proof of structure by direct comparison to iminium salts prepared by protonation of enamines. The general reaction reported was that of a ketone or aldehyde with a secondary amine perchlorate to give iminium salts. A large structural variety of carbonyl compounds and several amine... 

The (3-carbon atom of an enamine is a nucleophilic site because of conjugation with the nitrogen atom. Protonation of enamines takes place at the (3-carbon, giving an iminium ion. 

The protonation of enamines usually follows the course shown in (37), i.e., N-protonation occurs first, followed in some instances by... 

If N-protonation of enamines would occur, their UV spectrum should be strongly shifted hypsochromically to an absorption close to that of the corresponding alkene. This may be inferred from the agreement of the UV absorption of styrene (232) Wmax = 248 nm, max = 15,000)334 with that of w-styryltrimethylammonium bromide344 (233) (Amax = 247 nm, max = 15,350). The UV absorption of the bicyclic orthogonal... 

In summary, the protonation of enamines at their carbon site is markedly dependent on such a dramatic resonance effect, so that slight structural alterations resulting in decreased conjugation are bound to markedly decrease the basicity of the carbon atom concerned and hence to favour protonation at the nitrogen site. 

Even though enammonium ions have been shown to be eventually transformed into iminium ions38-40, the steps that determine the protonation of enamines are highly sensitive to the reaction conditions, so that they can be accelerated or decelerated in order to preferentially direct the attack at the carbon or the nitrogen site of the enamine. 

Contrary to previous reports36-38 the stereoselectivity of deuteriation, and hence protonation, of enamines of cyclohexanone is low29. This means that the transition state is reactant-like since, if it were not, the transition state for equatorial protonation (attack from the a-face) would be destabilized by the non-bonded interactions associated... 

The overall bonding changes which occur upon hydrolysis of enamines are shown by equation 2. Experimental studies on the protonation of enamines revealed that enamine salts are formed prior to attachment of a nucleophilic moiety. That is, protonation of enamines occurs before attack by water or any other nucleophile8,9. As is the case for alkylation7 and acylation5fl,c, protonation can occur either on nitrogen or on the / -carbon (equation 3). 

The NH and C(2)H protons of enamines of general structures 3 have been deuteriated1 by dissolution of compounds 4-23 in excess of Me OD, followed by evaporation after some time and repetition of the (H/D) exchange procedure until the required degree of deuteriation is achieved. 

Nilsson and coworkers showed that addition of trifluoroacetic acid to enamines in dry pentane at 0 °C results initially in protonation at the carbon and proposed that the proton is transferred to the nitrogen atom by a bifunctional catalysis according to equation 19. They also showed that appropriate exchange resins can be used to favour selective protonation of enamines ". 

Stereoselective protonation of enamines of the following type yield immonium salts under kinetic control which are subsequently transformed by cleavage of the / -diketones into the keto acids 3133. 

Enantioselective Protonation of Enamines (Deracemization of Carbonyl Compounds)... 

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