An Efficient Access to Novel Enantiomerically Pure Steroidal δ‐Amino Acids

A highly chemoselective sequence of Stille and Heck couplings on the heterocyclic bromoenol triflates 2 a – c with the bicycloalkenylstannanes cis‐ 3 and trans‐ 3 furnished the intermediate bromobutadienes 4 a – c in good yields ranging from 73–94 %. A modified Heck coupling protocol employing the palladacycle 8 and an additional bidentate ligand such as 1,4‐bis(diphenylphosphinyl)butane allowed a significant reduction in catalyst loading while still obtaining the heterocyclic 1,3,5‐hexatrienes 5 a – c in good yields (71–94 %). The unsymmetrically substituted 1,3,5‐hexatrienes 5 a – c in solution underwent 6π‐electrocyclizations following an optimized microwave‐heating protocol to yield the steroidal tetracycles cis ‐ 7 a – c and trans‐ 7 b (59–69 %). Tetracycles cis‐ 7 a – c are the products of a subsequent 1,5‐hydrogen shift to the thermodynamically more stable, more highly substituted diene units. Removal of the tert‐ butyl groups provided the novel steroidal δ‐amino acid 9 a and the δ‐amino acid derivatives 9 b ,  c in good yields (76–86 %).