TY - JOUR
T1 - Total Synthesis of Phenanthroquinolizidine Alkaloids Using a Building Block Strategy
AU - Jo, Young In
AU - Cheon, Cheol Hong
N1 - Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean Government (NRF-2018R1D1A1A02086110 and NRF-2014-011165, Center for New Directions in Organic Synthesis).
PY - 2019/9/20
Y1 - 2019/9/20
N2 - A concise and general strategy for the total synthesis of the phenanthroquinolizidine alkaloids has been developed. An iterative Suzuki-Miyaura coupling reaction between the requisite aryl boronic acid, 2-bromo-4,5-dimethoxyphenyl N-methyliminodiacetate (MIDA) boronate derived from boronic acid, and a suitable bromopyridine substrate bearing a homopropargyl alcohol at the 2-position generated the desired ortho-aza-terphenyl compounds. Hydrogenation of the triple bond followed by treatment with methanesulfonyl chloride afforded their corresponding tetrahydroquinolizinium ion intermediates, which were subsequently reacted with NaBH4 to provide the desired hexahydroquinolizine products. A final oxidative electrocyclization reaction gave the target phenanthroquinolizidine natural products. This synthetic approach only requires the use of three chromatographic separations throughout the entire synthesis.
AB - A concise and general strategy for the total synthesis of the phenanthroquinolizidine alkaloids has been developed. An iterative Suzuki-Miyaura coupling reaction between the requisite aryl boronic acid, 2-bromo-4,5-dimethoxyphenyl N-methyliminodiacetate (MIDA) boronate derived from boronic acid, and a suitable bromopyridine substrate bearing a homopropargyl alcohol at the 2-position generated the desired ortho-aza-terphenyl compounds. Hydrogenation of the triple bond followed by treatment with methanesulfonyl chloride afforded their corresponding tetrahydroquinolizinium ion intermediates, which were subsequently reacted with NaBH4 to provide the desired hexahydroquinolizine products. A final oxidative electrocyclization reaction gave the target phenanthroquinolizidine natural products. This synthetic approach only requires the use of three chromatographic separations throughout the entire synthesis.
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U2 - 10.1021/acs.joc.9b01768
DO - 10.1021/acs.joc.9b01768
M3 - Article
C2 - 31448609
AN - SCOPUS:85072509732
VL - 84
SP - 11902
EP - 11910
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
SN - 0022-3263
IS - 18
ER -