Ring Synthesis by Annulation

A diastereoselective three-component reaction of 1,2-diamines 77, aromatic aldehydes 78, and 1,3-dicarbonyls 79 to fused 1,4-diazepanes 80 was reported independently by the groups of Kita [26] and Rodriguez [27]. The reaction went through the formation of an intermediate 81 bearing an imine and an enamino ester functionality, which 

METHOD a with CATALYST AND SOLVENT To a 50-mL, two-ncckcd, round-bottom flask flushed with Ar and equipped with a magnetic stirring bar and a reflux condenser were added 1,2-dichloroethane freshly distilled over CaCl2 (25 mL), commercially available nonactivated 4 A MS (6 g), p-ketoester, p-ketoamide 79 (or p-ketosulfone not shown) (1.28 mmol), aldehyde 78 (1.5 mmol), and diamine 77 (1.28 mmol). The heterogeneous mixture was stirred at reflux under Ar for 24 h. The solution was filtered through a short pad of Celite, which had been thoroughly washed with DCE. The solvent was evaporated under reduced pressure to afford the crude compound, which was purified by flash chromatography over silica gel. 

3 Cyclization via Prins-Type Reactions The intramolecular Prins reaction has been recognized as a powerful method to assemble six- and seven-membered rings from homoallylic alcohols and simple aldehydes under acid catalysis [28]. However, the competing 2-oxo-Cope rearrangement prior to cyclization could lead to a product with partial or total racemization when enantiomerieally enriched secondary alcohols are used [29]. Increasing the nueleophilicity of the alkene reagent 

4 Pericycttc Reactions Although a wide variety of ring-expansion processes through pericyclic cyclizations have been described, only a few cycloaddition methods were depicted for the direct generation of medium-ring heterocycles. The most attractive approaches were the [4-1-3] cycloaddition, the 1,3-dipolar cycloaddition of nitrone, and the type-2 intramolecular N-acylnitroso Diels-Alder reaction. 

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