Aminoketones, ring closure

Hydroxy aldehydes or ketones normally exist in equilibrium with the corresponding 2-hydroxytetrahydrofurans, which afford 2,3-dihydrofurans on dehydration. Similarly, 7-aminoketones spontaneously yield pyrrolines. From a mechanistic viewpoint the-initial cyclizations may be regarded as being initiated by nucleophilic attack of the heteroatom upon the carbonyl group. While such reactions occur with facility, their synthetic applicability is largely determined by the accessibility of appropriate precursors. A selection of examples of this type of ring closure is provided in Scheme 12. 

As represented in Fig. 166, ring closure to y-piperidonc may occur, starting both from precursors 442 and aminoketones 443 with the suitable aldehyde. The synthesis of aconitine-type diterpene alkaloids" takes place similarly (Fig. 167), the only difference being the presence in the reactive site of an allylic carbon atom (446) instead of the alkyl group in a position to the carbonyl. 

Although a-aminoketones readily form imidazoles when they cyclize in the presence of formamide [48], preparative difficulties (see Sections 2,1.1, 2.2.1 and 4.1) point to alternative use of their precursors, a-oximinoketones, which can be reduced by dithionite or using catalytic methods in formamide at 70-100°C. Subsequent ring closure is achieved merely by raising the temperature to 180°C. 

Imidazoles can also be made by heating 4-tosyloxazolines in saturated methanolic ammonia or monoalkylamines. These reactions proceed through intermolecular condensation of a-aminoketones and amidines and intramolecular cyclization of a-ainidinoketones, respectively [49] (see Section 4.2). When A -unsubstituted 4-oxazolin-2-ones are added to isocyanates, the 2-oxo-4-oxazoline-3-carboxamide products cleave under the influence of strong acids and heat. Subsequent ring closure gives 4-imidazolin-... 

Cyclohexenone ring from -aminoketones Robinson-Mannich base procedure Ring closure... 

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