Remarkable reactivity difference in oxygen-substituted versus non-oxygen-substituted bromoalkynes in Cu(I)-catalyzed cross-coupling reactions: total synthesis of (-)-S-18-hydroxyminquartynoic acid.
The conjugated tetraacetylenic natural product (S)-18-hydroxyminquartynoic acid (2) is synthesized in five linear steps and 17.7% overall yield from commercially available 1,2,5,6-O-diisopropylidene mannitol. The key step is a one-pot three-component Cadiot-Chodkiewicz reaction affording the tetrayne unit. The oxygen-substituted bromoalkyne 10 was found to react at a much faster rate than the non-oxygen-substituted bromoalkyne 6 in the key step. The undesired symmetric cross-coupling by 10 generates a symmetric tetrayne intermediate, which undergoes a nucleophilic addition by 1 equiv of ethylamine. This side reaction is suppressed by controlling the order and rate of addition of each component and by reducing the amount of ethylamine.
Gung
Benjamin W
BW
Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio 45056, USA. gungbw@muohio.edu
Kumi
Godwin
G
D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry; D001966:Bromine; D002384:Catalysis; D003300:Copper; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010100:Oxygen
C482286:(S)-18-hydroxyminquartynoic acid; D000480:Alkynes; D005231:Fatty Acids, Unsaturated; D003300:Copper; D010100:Oxygen; D001966:Bromine