INTRAMOLECULAR DIELS–ALDER CYCLOADDITIONS OF cis -CYCLOHEXADIENEDIOLS DERIVED ENZYMATICALLY FROM (2-AZIDOETHYL)BENZENE. CONSTRUCTION OF HIGHLY FUNCTIONALIZED BRIDGED ISOQUINOLINE SYNTHONS Josef ZEZULA 1 , Tomáš HUDLICKÝ 2, * and Ion GHIVIRIGA 3,+ Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, U.S.A.; e-mail: 1 jzezula@chem.ufl.edu, 2 hudlicky@chem.ufl.edu, 3 ion@chem.ufl.edu Received March 30, 2001 Accepted June 4, 2001 (3a R,7a S)-4-(2-Azidoethyl)-2,2-dimethyl-3a,7a-dihydrobenzo[1,3]dioxole (22 ) was converted in two steps to trienes 23 and 24 , which upon heating underwent intramolecular Diels–Alder reactions to give mixtures of isomeric 11,11-dimethyl-5-oxo-10,12-dioxa-4-aza- tetracyclo[6.5.2.0 1,6 .0 9,13 ]pentadec-14-ene-7-carboxylates 25 , 26 and 27 , 28 , respectively. These products were separated and identified. For comparison, intermolecular Diels–Alder cycloaddition of diene 22 with maleic anhydride was carried out. Products of this reaction, 1-(2-azidoethyl)-4,4-dimethyl-3,5,10-trioxatetracyclo[5.5.2.0 2,6 .0 8,12 ]tetradec-13-ene-9,11- diones (29 and 30 ) were converted to methyl ester analogues of 31 and 32 in a two-step se- quence. The stereochemical outcome of these cycloadditions is discussed as well as their possible utilization in organic synthesis, especially in total synthesis of some alkaloids. Ke y w o rd s : Biotransformations; Diels–Alder reactions; Bridged octahydroisoquinolones; Mor- phine; Asymmetric synthesis; Isoquinoline alkaloids; Total syntheses; Chemoenzymatic syn- thesis. A recent review summarizes research in the area of chemoenzymatic syn- thesis originating in cis-cyclohexadienediols 1 . Gibson’s discovery of the re- markable enzymatic dearomatization 2 portrayed in Scheme 1 has led to the development of many applications of diol metabolites in asymmetric syn- thesis 3 . General methods of synthesis for inositols and their derivatives 4 , monosaccharides and their aza and pseudo analogs 5 , and oxygenated Amaryllidaceae alkaloids 6 have been developed in response to the availabil- ity of the optically pure diols 7 1 . Through continuing efforts of Gibson and Boyd, as well as through those of our own group, new metabolites have Collect. Czech. Chem. Commun. (Vol. 66) (2001) Intramolecular Diels–Alder Cycloadditions 1269 doi:10.1135/cccc20011269 + To whom inquiries regarding NMR structural work should be addressed.