An efficient access to novel enantiomerically pure steroidal delta-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 6pi-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 delta-amino acid 9 a and the delta-amino acid derivatives 9 b, c in good yields (76-86 %).
Sünnemann
Hans Wolf
HW
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany.
Hofmeister
Anja
A
Magull
Jörg
J
de Meijere
Armin
A
D000475:Alkenes / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D002070:Butadienes / Q000737:chemistry; D002384:Catalysis; D003432:Cross-Linking Reagents / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry; D008698:Mesylates / Q000737:chemistry; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism; D013256:Steroids / Q000737:chemistry*; D017971:Tin Compounds / Q000737:chemistry
D000475:Alkenes; D000596:Amino Acids; D001643:Bridged Bicyclo Compounds; D002070:Butadienes; D003432:Cross-Linking Reagents; D006571:Heterocyclic Compounds; D008698:Mesylates; D009942:Organometallic Compounds; D013256:Steroids; D017971:Tin Compounds; C031525:stannane; D010165:Palladium; C012077:trifluoromethanesulfonic acid