Tandem Claisen - Diels-Alder reactions in organic synthesis

The aromatic Claisen rearrangement and the Diels-Alder reaction have been widely used by synthetic chemists for the construction of natural products. A program was undertaken to explore the use of a novel sequential strategy that would incorporate the use of both the Claisen rearrangement and Diels-Alder reaction in one step. This strategy was applied towards the construction of the linear tetracyclic ring systems of the anthracycline and tetracycline antibiotics;The route was developed about the regiospecific Claisen rearrangement of 2-hydroxy-5-allyloxyacetophenone. Thermolysis of various 2-hydroxy-5-allyloxyacetophenone derivatives results in a Claisen rearrangement followed immediately by an intramolecular Diels-Alder cycloaddition to afford highly functionalized tri and tetracyclic linear ring systems. This tandem Claisen - Diels-Alder reaction is the first reported example of such a rearrangement where the diene component of the Diels-Alder reaction was not part of the aromatic ring upon which the Claisen rearrangement occurred. The Diels-Alder reaction involves the novel use of the enol form of (beta)-diketones as the diene component;The thermolysis precursors were synthesized using a modification of the Baker-Venkataraman reaction that incorporates an original 2 step sequence in just one reaction vessel. Use of a common intermediate from the tandem Claisen - Diels-Alder reaction affords an anthraquinone intermediate for the anthracyclines in just 4 steps from readily available starting materials in an overall yield of 14%. From the same intermediate a tetracycline intermediate can be formed in 2 steps