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COOMeOHNOOOMeOHNOOOMeOOBnBrOOOHOOOOOOMeOOOOPArArPAr2PArArPAr2OOOMeOOOOOMeOHOOMeNSOONMeTsOOOOMeOHSOOPhPhFFFCF3FFFCF3PhPhFFFCF3FFFCF3OHONOHOOMeONOHOOMeOHNONClHPy•HClOOOOOOMeOOOOOMeRhOOOOMeOORhOOOOMeOOOOOMeOOBnO![]()
OOBnOOOMeDeconstructive Asymmetric Total Synthesis of Morphine-Family Alkaloid (-)-Thebainone A
Hou, S.-H.; Prichina, A. Y.; Dong, G.
Angew. Chem. Int. Ed. 2021, 60, 13057–13064.1) THF, n-BuLi, r.t., 16 h, then 1, then LiTMP
2) PCC
3) Pd(OH2)/C, H2
4) 2, DEAD, PPh3(-)-Thebainone A5) [Rh(COD)2]NTf2 (4 mol%), L3 (4.8 mol%)
o-difluorobenzene, 130 °C, 48 h6) LiAlH4
7) Ac2O, then 2 M HCl
8) BBr3
9) CH2N2, MeOH
10) TMSOCH2CH2OTMS, TMSOTf
then py, TsNHMe, Cs2CO3, then MeOH(R)-DTBM-segphos (L3)2(-)-Thebainone A6–1011) Martin’s sulfurane
12) sodium naphthalenide, then HCl
13) NaSEt
14) TFA, MeCN,
then Pd(TFA)2, DMSO, 80 °C1i) Li/NH3, t-BuOH
then NH4Cl
ii) ethylene glycol,
PPTS2Suggest a preparation for compound 2.Provide a mechanism for step 5.
HINT: The product of this key step contains four 6-membered rings.Please provide a mechanism for step 1.Draw the structure of Martin’s sulfurane?
Name 2 alternatives.Martin’s sulfurane - anti-eliminationalternatives
• Burgess - via Ei - syn elimination
• MsCl, NEt3 - E2“cut-and-sew”-reaction“selectivity (step 13) is likely due to more available s* orbital of the middle ether moiety, as its “flat” conformation is more disfavored due to sterics”14) developed by Tianning Diao and Shannon Stahl(-)-morphinecodeineSuggest a synthetic transformation toward codeine or morphine from an appropriate intermediate.14) Br2, AcOH
15) 2,4-DNPH
16) HCl
17) LAHM. Gates, G. Tschudi, J. Am. Chem. Soc. 1952, 74, 1109–1110;
M. Gates, G. Tschudi, J. Am. Chem. Soc. 1956, 78, 1380–1393.asymmetric
cut and sewmigratory
insertioncutsew**Mechanism of step 5Transformation to morphine(2+2) CAWhat is the pKa of TsNHMe?
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