AB8-16![]()
1-7![]()
12-20![]()
OOCO2MeIOOOPMBNOMeOOHOHOOMeBrOHOSiOTBSOOOMeOOMeNOMeOOHOSiOTBSOHOOMeHOHOSiOTBSOHOOMeHOHOSiOTBSOOOMeOOMeHOSiOTBSHOOOMeOOMeOHOSiOTBSOOOMeOOMeHOHOSiOTBSHOOOMeOOMeOHOSiOTBSOOOMeOOMeHOHHOSiOTBSOOOMeOOMeHOHHNOMeOOHOOOOPMBOHOOOPMBOONHPhOSiOTMSPhPh3P=CH2OOOPMBOROROHOSiOTBSOOOMeOOMeTiMeMeTotal Synthesis of Liangshanone
Huang, H.-X.; Mi, F.; Li, C.; He, H.; Wang, F.-P.; Liu, X.-Y.; Qin, Y.
Angew. Chem. Int. Ed. 2020, early view. 1) LDA/HPMA, 1; then 2; then LiAlH4;
then TBSCl, imidazole
2) DDQ
3) DMP, NaHCO3
4) 3, n-BuLi; then product of step 3
5) PhI(OAc)2, NaHCO3, MeOH;
then mesitylene, 180 °C
6) DMP, NaHCO3
7) NaBH(OMe)3, 7:1 d.r. 8) MeI, NaH
9) TBAF
10) DMP, NaHCO3
11) MeI, t-BuOK,
12) EtNH3Cl, Et3N, AcOH; then NaBH3CN
13) SmI2 (5.0 equiv), MeOH
14) TFA, O3; then PPh3; then t-BuNH2
15) NaClO2, NaH2PO4, 2-methyl-2-butene
16) NHPI, DIC, DMAP; then Zn, NiCl2•6H2O,
di-t-Bu-bipy, PhSiH3liangshanone4) Hint: inseperable diastereoisomers
in d.r. = 5:4solution to step 5-7:+liangshanone12316) Hint: NHPI = N-hydroxyphthalimide17) LDA, NCCO2Me,
18) Cs2CO3, MVK
19) LDA
20) LiAlH4
21) AZADO, DMAP, bpy, CuCl, open to air
22) TMSOTf (4.0 equiv.), Et3N;
then Ph3P=CHOMe
23) NaOH, MeOH
24) TfOH, 1:1.3 d.r.
25) Pd/C, H2, AcOH/EtOH
26) CH(OEt)3, p-TsOH, ethylene glycol
27) DMP, TFA
28) Petasis reagent
29) SeO2, t-BuOOH; then p-TsOH
30) DMP, TFA
31) NaBH(OMe)328) What is the molecular structure of
the Petasis reagent?
29) What stereselectivity do you expect?17) Hint: d.r of 5:4 carried through to
step 18 where product is isolated as
a single diastereomer.5-7) Rationalize the stereochemical
outcome and why step 6 & 7
are performed?a nearly 1:1:1:1 mixture
of racemates
and diastereomersdiastereoselective reduction
simplifies mixture to nearly a
1:1 mixture of racematesstep
6, 7step
6, 7step 5step 57) Hint: only one ketone reacts23) Hint: two transformations occurBonus:
To access a stereoselective synthesis of liangshanone which step do you need to modify? What strategy would you choose?Step 1; see the authors strategy belowBonus: Stereoselective Synthesis:pH 7 bufferJørgensen-Hayashi
catalyst+CH2O (aq)R = H, (92% ee)
R = TBSstep 2-598% ee
after recryst.mixturePetasis reagentsee below![]()
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