Enamines, alkylation rearrangement

A related enamine alkylation is seen in the rearrangement of an ethylene imine vinylogous amide, which was heated with sodium iodide in diglyme. The presumed internal enamine alkylation constitutes a critical step in an oxocrinane synthesis (265). Use of an ethylene imine urethane for alkylation of an enamine and formation of the hexahydroindole system has also been reported (266). 

In the reaction of 2-chlorocyclohexanone with a secondary amine (632) one encounters an intramolecular enamine alkylation analogous to the internal alkylations which constitute the critical step of some Favorskii rearrangements. 

In an enamine alkylation study, piperitone (8 X = H) gave, in addition to the expected dienamines, two rearranged dienamines via ring opening and reclosure hydrolysis yielded the o-menthenones (181Dauben s full paper (Vol. 7, p. 34) on... 

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,... 

The acid-catalyzed reaction of acetophenone with acyclic secondary amines results in the formation of the expected enamine and a rearrangement product. The latter product arises from the transfer of one of the amino N-alkyl groups to the cnamine s carbon to produce a ketimine (53a). 

The reaction of methyl propiolate (82) with acyclic enamines produces acyclic dienamines (100), as was the case with dimethyl acetylenedicarboxylate, and the treatment of the pyrrolidine enamines of cycloheptanone, cyclooctanone, cycloundecanone, and cyclododecanone with methyl propiolate results in ring enlargement products (100,101). When the enamines of cyclohexanone are allowed to react with methyl propiolate, rather anomalous products are formed (100). The pyrrolidine enamine of cyclopentanone forms stable 1,2-cycloaddition adduct 83 with methyl propiolate (82). Adduct 83 rearranges to the simple alkylation product 84 upon standing at room temperature, and heating 83 to about 90° causes ring expansion to 85 (97,100). 

Rearrangement of an enamine to a Sehiff s base through N- to C-alkyl migration was reported 729). These authors also found that enamines, rather than aminals, were formed from butyraldehyde and seeondary amines (730). Chloramines and aeetylenes reacted to give chloroenamine intermediates, which hydrolyzed on work-up of the reactions (731). 

The regioselectivity is an issue in substrates 141. With two alkyl substituents on the distal position, tetrahydropyridines 142 are the product. With only one alkyl substituent, the cyclic imine 143 was isolated for these rearrangement products it is unknown whether they stem from the enamine generated from a 5-endo-trig or 5-exo-digcydization (Scheme 15.44) [98]. 

Alkylation of enamines may lead to the formation of N-alkylated product, which on heating is converted to C-alkyl compound (This rearrangement is common with allylic halide, alkyl halide or a-haloacetic ester. 

The reaction of aliphatic and aromatic ketone oximes 97 with a dialkyl carbonate 98 in the presence of K2CO3 at 180-190 °C yields 3-alkyl-4,5-disubstituted-2(3//)-oxazolones 104 in 22-48% yields. Mechanistically, it is proposed that N-alkylation of the initially formed oxime O-carbonate 99 yields 100, which affords the enamine 101 in the presence of base. A [3,3] sigmatropic rearrangement ensues to produce 102, which then cyclizes to 104. In cases where 97 contains two methylene groups in proximity to the C=N bond, one of which is benzylic, the above reaction sequence is regioselective for the benzylic methylene group (Fig. 5.25 Table 5.6, Fig. 5.26). ... 

Opitz.G. (1961) Enamines. Vll. Course of the allyl- and propargyl-aUenyl rearrangements in the alkylation of enamines. Justus Liebigs Ann. Chem., 122—132. 

In the case of 21 the presence of an alkyl chain on the other side of the enamine group16 induces a H rearrangement in low-energy ions with loss of propylene, again followed by the loss of ketene (Scheme 15). 

Evidence for the two-step nature of the dihydropyran formation follows from the observation that both cis- and fraws-dibenzoylethene gave the same dihydropyran96, under conditions where cis-trans isomerism of the electrophilic alkene did not occur. On heating, the dihydropyrans rearrange into a mixture of the corresponding alkylated enamines (44 and 45) (Scheme 29). This is kinetically rather than thermodynamically controlled, since the equilibrium composition was obtained only after treatment with acid96, and can therefore be regarded as irreversible in an aprotic solvent (benzene) at 80°C. 

Similar results were obtained with enamines of acyclic ketones such as desoxybenzoin. Nitrostyrene gave only the less substituted mono-alkylated enamine and hence the / -nitro-a-phenylethyl ketone on hydrolysis117. Surprisingly 2-nitropropene gives mainly the tetrasubstituted cyclohexanone enamine106. A hexahydrobenzo-l,2-oxazine-7V-oxide (55) was isolated at low temperatures (in 80% yield) which rearranged at room temperature to a mixture of alkylated enamine isomers107 (Scheme 39). 

The reaction of enamines with acetylenic compounds has been the subject of intensive studies. In general, alkyl acetylenedicarboxylates and propiolates undergo initial cycloaddition (Chapter 18) to form cyclobutene derivatives. These cyclobutenes rearrange, in most cases spontaneously, to form products whose structures depend on the starting enamine and on the reaction conditions126-128 (Scheme 45). 

JV-Alkyl-JV-allyl enamines 128 (X = NR), like their carbon and oxygen counterparts 128 (X = CH2jO), can undergo [3,3]-sigmatropic rearrangement to form y,<5-unsaturated imines 129 (X = NR) (equation 27). This reaction has been defined as a 3-aza-Cope or the aliphatic amino-Claisen rearrangement8. 

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