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An Efficient Access to Novel Enantiomerically Pure Steroidal δ‐Amino Acids
Author(s) -
Sünnemann Hans Wolf,
Hofmeister Anja,
Magull Jörg,
de Meijere Armin
Publication year - 2006
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200601076
Subject(s) - chemistry , stille reaction , yield (engineering) , denticity , catalysis , medicinal chemistry , organic chemistry , stereochemistry , materials science , crystal structure , metallurgy
Abstract 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 %).