Recent Advances in the Synthesis of Isodon Diterpenoids and Schinortriterpenoids
- Corresponding author: Puno Pematenzin, punopematenzin@mail.kib.ac.cn
Citation:
Yan Bingchao, Hu Kun, Sun Handong, Puno Pematenzin. Recent Advances in the Synthesis of Isodon Diterpenoids and Schinortriterpenoids[J]. Chinese Journal of Organic Chemistry,
;2018, 38(9): 2259-2280.
doi:
10.6023/cjoc201806002
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Reagents and conditions: (a) (1) LDA, THF, -78 ℃, then allyl chlorformate; (2) ICH2CH2OTBDPS, CsCO3, CH3CN, 65% for 2 steps. (b) Pd2(dba)3, (S)-t-Bu-Phox, THF, 40 ℃, 82%, 87% ee. (c) DIBAL, toluene, then 5% HCl, MeOH, 78%. (d) (1) TBSOTf, Et3N; (2) Pd(OAc)2, O2, DMSO, 82%. (e) (1) (CH2OH)2, PPTS, benzene, reflux; (2) TBAF, THF; (3) TPAP, NMO, 58% overall. (f) (R)-2-methyl-CBS-oxazaborolidine, BH3•THF, toluene, -40 ℃, 90%. (g) NaH, THF, ClCON(Pr-i)2, 85%. (h) 9, s-BuLi, rac-TMCDA, -78 ℃, Et2O, then Ac2O, DMAP, 82%, gram scale. (i) (1) BF3•OEt2, -20 ℃, then aq. NaHCO3, 80%, gram scale; (2) (CH2OH)2, PPTs. (j) (1) K2CO3, MeOH; (2) IBX, DMSO; (3) DBU, THF, 70% overall. (k) (1) KHMDS, -78 ℃, TBSCl; (2) DDQ, MeCN, DTBMP; (3) 2 mol/L HCl, THF, 65%. (l) (1) t-BuOK, THF, -78 ℃, then (PhSeO)2O, 40%, 57% brsm; (2) 2 mol/L HCl, MeOH/THF, 50 ℃, 82%. (m) (1) NaBH4, -10 ℃, EtOH/CH2Cl2; (2) MsCl, DMAP, CH2Cl2, 55% for 2 steps; (3) LiAlH4, THF; (4) IBX, DMSO, 75% for 2 steps. (n) (1) t-BuOOH, Triton B; (2) (PhSe)2, NaBH4, 80%; (3) (1) Me4NBH(OAc)3; (4) Ac2O, DMAP, pyridine, 0 ℃, 60%.
Reagents and conditions: (a) (1) IBX, DMSO; (2) H2O2, NaOH, 85% for 2 steps. (b) (1) 18, NaOAc; (2) Pb(OAc)4, 65% for 2 steps. (c) (1) H2, SiO2, Lindlar cat.; (2) 20, n-BuLi, 80% for 2 steps, 21a:21b=2:1. (d) (1) PDC, SiO2; (2) NaBH4, EtOH, 84%, 21a:21b=3:1. (e) PhI(CF3CO2)2, K2CO3, HFIP, 0 ℃, 70%, gram scale. (f) (1) Dess-Martin, NaHCO3; (2) NaBH4, MeOH, 83% for 2 steps, dr=2.5:1 at C(12). (g) (1) Ac2O, DMAP; (2) NCS, TBACl, TEMPO, 85% for 2 steps. (h) cat. p-TsOH, 30 ℃. 78%. (i) (1) L-Selectride, -78 ℃; (2) methylene blue O2, hν, MeCN, trichloroisocyanuric acid, 55% for 2 steps. (j) PhI(OAc)2, TEMPO, 92%. (k) Me3SnOH, 96%. (l) LiOH, THF/H2O, 94%.
Reagents and conditions: (a) (1) LiHMDS, PhNTf2, THF, -78~0 ℃, 78%; (2) Pd(PPh3)4, CH2=CHSnnBu3, LiCl, THF, reflux, 92%. (b) (1) 28, BF3•Et2O, toluene, -30 ℃, 90%; (2) NaBH4, MeOH, 0 ℃, 78%. (c) (1) Ac2O, p-TsOH•H2O, toluene, 100 ℃; (2) NBS, AIBN, CCl4, reflux; then AgBF4, Et3N, DMSO, 23 ℃, 30, 19% for 2 steps, 31, 74% for 2 steps. (d) DMP, NaHCO3, CH2Cl2, 23 ℃, 73%. (e) Pd2(dba)3• CHCl3, PnBu3, HCOOH, Et3N, dioxane, reflux, 86%. (f) (1) LiOH•H2O, THF/H2O (V:V=1:1), 23 ℃, then HCl; (2) DMF, reflux; (3) p-TsOH•H2O, 2, 2-dimethoxypropane, 80 ℃, 79% for 3 steps. (g) (1) DIBAL-H, CH2Cl2, 0 ℃; (2) DMP, CH2Cl2, 0 ℃, 74% for 2 steps. (h) (1) SmI2, toluene, 0 ℃, 55%; (2) DMP, NaHCO3, CH2Cl2, 0~23 ℃, 86%. (i) (1) LiHDMS, TMSCl, THF, 0 ℃; (2) Eschenmoser salt, DMF, 50 ℃; (3) MeI/ether (V:V=1:5); then CH2Cl2, saturated aqueous K2CO3, 36, 47% (3 steps), 37, 40% (3 steps). (j) LiHDMS, TMSCl, 66%. (k) (1) m-CPBA, CH2Cl2, 0 ℃; (2) p-TsOH•H2O, MeOH, 0 ℃, 82% for 2 steps. (l) TBAF, 23 ℃, 90%. 39a:39b=1.5:1 in MeOH-d4. (m) (1) p-TsOH•H2O, 2, 2-dimethoxypropane, 23 ℃, 90%; (2) DMP, NaHCO3, CH2Cl2, 23 ℃, 85%. (n) (1) TMSOTf, Et3N, 60 ℃; (2) Pd(OAc)2, CH3CN, 23 ℃; (3) HCl, THF/H2O (V:V=1:1), 23 ℃, 54% overall. (o) DMP, NaHCO3, CH2Cl2, 23 ℃, 67%.
Reagents and conditions: (a) PCC, CH2Cl2; then 43, NaI, DBU, THF, then 1 mol/L HCl, 23 ℃, E only, 67% for 2 steps, decagram scales. (b) (1) TIPSOTf, Et3N, then 45, toluene, reflux, exo:endo=5:1. (c) NaBH4, THF/H2O, 58% for 2 steps in one-pot from 44. (d) (1) TBSOTf, Et3N; (2) DDQ, 80% for 2 steps, decagram scales. (e) Me2AlCl, LiBr, CH2Cl2, 23 ℃, 65%, decagram scales. (f) NaBH4, then MsCl, Et3N, 80%, decagram scales. (g) (1) TMSCl, NaI; then LiBHEt3. (2) MeLi, air, then thiourea, 57% for 2 steps, decagram scales. (h) Dess-Martin periodinate, then TBAF, 88%, decagram scales. (i) (1) SeO2, TBHP, 92%, decagram scales; (2) LAH, THF, 89%, decagram scales. (j) IBX, DMSO:THF (V:V=1:1), 80% decagram scales. (k) Jones reagent, 92%, gram scales. (l) TMSCl, NaI, HMDS, then Pd(OAc)2, 79% for 2 steps.
Reagents and conditions: (a) n-BuLi, THF, 15 ℃, then 55; TBAF, -50 ℃, 83%. (b) AIBN, Bu3SnH, toluene, 100 ℃, 70%. (c) LiAlH4, THF, 0~23 ℃, 89%. (d) Pb(OAc)4, AcOH, 0 ℃. (e) 60, NIS, CH2Cl2, -50~-20 ℃, 69% for 2 steps. (f) PhSH, Et3N, toluene, -50 ℃. (g) AIBN, Bu3SnH, 100 ℃, 89%. (h) (1) CrO3, H2SO4; (2) LiHMDS, TBSOTf, THF, -50 ℃, then LAH, 0 ℃, 61% for 2 steps. (i) (1) DMSO, (COCl)2, -78 ℃, then Et3N, 81%. (2) 65, t-BuOK, THF, 82%. (j) (1) HCl in MeOH, acetone, 76%; (2) AIBN, Bu3SnH, toluene, 100 ℃, 87%. (k) SmI2, Et3N, THF, 23 ℃. (l) (1) NaBH4, MeOH. (2) DMSO, (COCl)2, -78 ℃, then Et3N, 49% from 67. (m) (1) MeONa, MeOH; (2) SmI2, MeOH, -50 ℃, 70%. (n) BzCl, DMAP, Et3N, CH2Cl2, then TBSOTf, 79%. (o) MoO5•Py•HMPA, NaHMDS, THF, 77%. (p) H5IO6. (q) (1) LAH; (2) PCC, silica gel, CH2Cl2, 0~23 ℃, 34% for 3 steps. (r) (1) TBAF; (2) Ac2O, 72% for 2 steps; (3) SeO2, t-BuOOH; (4) MeONa, MeOH, 39%, for 2 steps. (s) (1) TBAF; (2) TMSCl, 85% for 2 steps; (3) SeO2, t-BuOOH; (4) DMP, NaHCO3, then HCl (aq.) for 2 steps.
Reagents and conditions: (a) O3, CH2Cl2/MeOH, 5 ℃, then Me2S, 23 ℃, 85%. (b) 30% H2O2, 10% NaOH/EtOH, 0 ℃, quant. (c) CH3ONHCH3•HCl, DIEA, COMU, DMF, 23 ℃, 62%. (d) (1) TMSCl, THF; (2) 3 mol/L MeMgBr, -78~23 ℃, 1 mol/L HCl, 52% for 2 steps. (e) 10% NaOH, MeOH, 23 ℃, quant.
Reagents and conditions: (a) (1) NaBH4, MeOH, 23 ℃, 77%; (2) MsCl, Et3N, CH2Cl2, 96%. (b) (1) DBU, CH2Cl2, 23 ℃, 80%; (2) LiAlH4, THF, 23 ℃, 95%. (c) (-)-DIPET, Ti(OiPr)4, TBHP, -30 ℃, 92% (99% ee). (d) DMP, CH2Cl2, 23 ℃, 92%. (e) n-BuLi, Et2O, 90% (dr=1.8:1). (f) Et2AlCl, 4 Å MS, THF, 40 ℃. (g) LiAlH4, THF, -78~23 ℃, 50% from 85, 87% ee. (h) pyridine, CH2Cl2, (Cl3CO)2CO, 85%. (i) (1) MOMCl, NaOH, TBAI, THF, 23 ℃; (2) K2CO3, MeOH, 92% for 2 steps. (j) (1) 2-(diethoxyphosphoryl)acetic acid, EDCI, DMAP, CH2Cl2, 23 ℃, 82%; (2) TsN3, DBU, 81%. (k) Rh2(OAc)4, PhH, 60%. (l) (1) t-BuOK, (HCHO)n, THF, 95%; (2) TFA, CH2Cl2, 90%. (m) Pb(OAc)4, AcOH, 0 ℃, then toluene, 145 ℃, 40%. (n) (1) NBS, (PhCO2)2, CCl4, reflux, 83%; (2) Bu3SnH, TEMPO, PhH, reflux, 80%. (o) (1) Zn, AcOH, THF, H2O, 70 ℃, 80%; (2) SmI2, THF, MeOH, 23 ℃, 60%. (p) Lindlar cat., MeOH, THF, 23 ℃, 90%. (q) DMP, CH2Cl2, 23 ℃, 78%. (r) DBU, toluene, 100 ℃, 55% (95% brsm).
Reagents and conditions: (a) (1) CuI•0.75DMS, 99, 100, TMSCH2C(MgBr)CH2, toluene/THF, -78 ℃, 80%, 99% ee. (b) LiTMP, THF, -78 ℃, then Davis oxaziridine, THF, DMPU, -78 ℃, then Ac2O, -78~0 ℃, 64%. (c) EtAlCl2, toluene, 0 ℃, 77%. (d) (1) NaH, Bu4NI, Me2SO4, DMF, 23 ℃, then aq. LiOH, 23 ℃. (2) Py•SO3, Et3N, DMSO, CH2Cl2, 0~23 ℃, 81 % for 2 steps. (e) i-PrMgCl•LiCl, 105, toluene, -78~0 ℃. (f) aq. TsOH, 0~85 ℃, 45% from 104. (g) NaHMDS, LaCl3•LiCl, THF, DMPU, CH2O(g), -45 ℃, 84%, 2:1 dr. (h) TFA, HC(OMe)3, MeOH, 60 ℃. (i) Zn(OTf)2, LiBH4, CH2Cl2, 23 ℃, 83% from 108, 3:1 dr. (j) TsOH, H2O, THF, 23 ℃, then DNBCl, DMAP, E3N, 23 ℃, 86%. (k) MsOH, HC(OMe)3, MeOH, 65 ℃. (I) ZnI2, TMSCN, 23 ℃, then aq. LiOH, then aq. HCl, 65 ℃, 82% from 111. (m) DMDO, acetone, 23 ℃. (n) InI3, MgI2, MeCN, 23 ℃, then DMP, 23 ℃. (o) aq. oxone, Bu4NHSO4, pH=7.4 buffer, 23 ℃, 76% overall.
Reagents and conditions: (a) (1) LAH, THF, 0 ℃; (2) Ac2O, pyridine, DMAP, CH2Cl2, 0 ℃, quant. for 2 steps. (b) SOCl2, pyridine, CH2Cl2, -78 ℃. (c) K2OsO4•H2O, NMO, then NaIO4, acetone/H2O, 23 ℃, 62% for 2 steps. (d) (1) MeLi, THF, -78 ℃; (2) Ac2O, Py, DMAP, 83% for 2 steps. (e) NOCl, Py, -40 ℃. (f) 450 W Hg lamp, acetone, 23 ℃, 43% from 120. (g) (1) Jones reagent, acetone, 0 ℃, 69%; (2) K2CO3, MeOH, 23 ℃, 95%. (h) (1) IBX, ethyl acetate, 80 ℃, 98%; (2) Ph3P=CH2, THF, 0 ℃, 83%. (i) 125, 2nd Grubbs cat., CH2Cl2, reflux, 73%. (n) Ph3P=CH2, THF, 0 ℃, 91%.
Reagents and conditions: (a) BF3•Et2O, CH2Cl2, -78~-30 ℃, 70%. (b) NaOH, MeOH, 75 ℃, 95%. (c) K2CO3, MeI, 23 ℃, 95%. (d) PTSA, toluene, 85 ℃, 75%. (e) KOH, MeI, 23 ℃, 85%.
Reagents and conditions: (a) (1) n-BuLi, HCO2Et, BF3•OEt2, -78 ℃; (2) TBSCl, imidazole, DMAP, CH2Cl2, 23 ℃, 47% from 130. (b) Au(PPH3)Cl, THF/EtOH, 91%. (c) (1) LDA, HCO2Et, THF, -78~23 ℃, 68%; (2) TsCl, NMI, LiOH, toluene, 77%. (d) 134, FeCl3, THF, 0 ℃, 78%. (e) HBr3•Py, -78 ℃, CH2Cl2/MeOH, 84%; (2) ClCH2CO2H, 23 ℃, CH2Cl2, 54% for 2 steps. (f) (1) Fe(acac)3, PhSiH3, EtOH/glycol, 60 ℃; (2) Py•HF, MeCN, 23 ℃, 45% for 2 steps. (g) (1) PhOC(S)Cl, pyridine, DMAP, CH2Cl2, 0 ℃, 81%; (2) AIBN, n-Bu3SnH, toluene, 110 ℃, 85%. (h) (1) DIBAL-H, CH2Cl2, -78 ℃, 89%; (2) MsCl, Et3N, 0 ℃, toluene, 81%. (i) K2OsO4•2H2O, NMO, NaIO4, Me2CO/H2O, 23 ℃, 82%; (2) DBU, toluene, 81 ℃, Me2CO, quant. (j) (1) 141, LiHMDS, CuI, THF, -90 ℃, 65%; (2) pyridine, 110 ℃, 91%. (k) MeLi, THF, -78 ℃, 96%. (l) (1) CrO3, HOAc, 23 ℃, 86%; (2) LiOH, THF, 70 ℃, 91%; (3) 145, CCl4/THF, 0 ℃, 47% (68% brsm). (m) (1) MOMCl, i-Pr2NEt, CH2Cl2, 0 ℃, quant.; (2) PdCl2(PhCN)2, CuI, Ph3As, 147, NMP, 120 ℃, 75% for 2 steps. (n) (1) Amberlyst-15, 80 ℃, THF/MeOH, 83%; (2) K2CO3, MeOH. (o) 143, toluene, 23 ℃, 81%, 10:1 dr. (p) (1) NaBH4, MeOH, -78~-65 ℃, 96%; (2) MgClO4, Ac2O, 75%.
Reagents and conditions: (a) t-BuOK, t-BuOH, reflux, 1 h, then 152, 23 ℃, 67%. (b) PhSeBr, LiHMDS, THF, -78 ℃, then, H2O2, CH2Cl2, 0 ℃, then TFA, 46%. (c) (1) NBS, CaCO3, dioxane, visible light, 75%; (2) PtO2, H2, MeOH, 23 ℃; (3) Ac2O/pyridine (V:V=1:1), 23 ℃, 86% for 2 steps. (d) LDA, THF, -78 ℃, PhSeBr, then H2O2, CH2Cl2, 0 ℃, 72%. (e) H2SO4, HCO2H, 23 ℃, 97%. (f) (1) LiAlH4, THF, 0 ℃; (2) TBSCl, imidazole, DMAP, CH2Cl2, 0~23 ℃, 96% for 2 steps. (g) (1) PhI(OAc)2, I2, cyclohexane, hν (250 W), 54%; (2) TBAF, THF, 23 ℃; (3) Ac2O, Et3N, DMAP, CH2Cl2, 0~23 ℃, 89% for 2 steps. (h) RuCl3•3H2O, NaIO4, MeCN/CCl4/pH 7 phosphate buffer (V:V:V=1:1:1), 23 ℃, 96%. (i) (1) K2CO3, MeOH, 40 ℃; (2) DMP NaHCO3, 23 ℃, 86% for 2 steps. (j) (1) 162, toluene, 120 ℃; (2) MePPh3Br, t-BuOK, THF, 0~23 ℃, 70% for 2 steps. (h) Er(fod)3, neat, 120 ℃, 64%, dr 2:1.
Reagents and conditions: (a) EDC, DMAP, CH2Cl2, 23 ℃, 98%. (b) 166, 60 W mercury lamps, MeCN/Me2CO (V:V=5:1), 23 ℃, 98%, 167a:167b:167c=5:2:0.2. (c) 1 mol/L LiOH/MeCN (V:V=1:1), 23 ℃, 95%. (d) 2-aminothioanisole, EDC, CH2Cl2, 23 ℃, 95%. (e) Pd(OAc)2, p-methoxy-iodobenzene, AgOAc, PhMe, 115 ℃, 82%. (f) NaOH, EtOH, 100 ℃, 85%. (g) 172, DCC, DMAP, CH2Cl2, 0~23 ℃, 85%.
Reagents and conditions: (a) Et2AlCl, CH2Cl2, 0 ℃, 65%. (b) (1) MeMgCl, 23 ℃, 78%; (2) KHMDS, O2, P(OMe)3, 75%; (3) TESOTf, 2, 6-lutidine, 23 ℃, 95%. (c) (1) CHBr3, t-BuOH, 23 ℃; (2) AgClO4•H2O, 23 ℃, 82% for 2 steps. (d) PdCl2/[P(o-tol)3]2, CuF2, 178, 85%. (e) (1) tBu-3-enylmagnesium bromide, THF, 0 ℃, 88%; (2) KHMDS, THF, -78 ℃, then MoOPH, -78 ℃, 62%; (3) BnOC(=NH)CCl3, Et2O, TfOH (cat.), 65%; (4) vinylmagnesium bromide, THF, 0 ℃, 77%. (f) Grubbs Ⅱ catalyst, MgBr2, CH2Cl2, 30 ℃, 65%. (g) KHMDS, but-2-ynoic pivalic anhydride, toluene, 0 ℃, 78%. (h) [Co2(CO)8], TMTU, PhH, 70 ℃, 74%. (i) (1) MeONa, MeOH, 23 ℃; (2) TMS-imidazole, CH2Cl2, 23 ℃, 91% for 2 steps. (j) (1) KHMDS, THF, -78 ℃, then MeI, -78 ℃, 88%; (2) DIBAL, CH2Cl2, -78 ℃; (3) DMP, NaHCO3, CH2Cl2, 23 ℃, 70% for 2 steps. (k) (1) Vinylmagnesium bromide, THF, -78 ℃, 88%; (2) TBAF, AcOH, THF, 23 ℃, 93%; (3) LiAlH2(OMe)2, THF, -78 ℃, 60%. (l) 187, Pd(OAc)2, CuCl2, CO, THF, 70 ℃, 78%. (m) (1) LiHMDS, THF, -78 ℃, then MeI, 80%; (2) lithium 2, 2, 6, 6-tetramethylpiperidin-1-ide, THF, -78 ℃, then NH4Cl aq., 76%; (n) Ac2O, Sc(OTf)3, CH3CN, 23 ℃, 92%. (o) (1) Pd(OH)2, H2, EtOAc, 23 ℃, 90%; (2) LiHMDS, THF, -78~0 ℃; (3) DMP, NaHCO3, CH2Cl2, 23 ℃, 60% for 2 steps.
Reagents and conditions: (a) (1) Hayashi ligand L1, TFA, toluene, -10 ℃, 88%, 98% ee; (2) AlMe3, MeMgBr, CH2Cl2, -78 ℃, 80%; (3) DMP, NaHCO3, CH2Cl2, 23 ℃, 93%. (b) (1) MeMgCl, THF, -78~-25 ℃, 84%; (2) KHMDS, THF, -78~0 ℃ followed by P(OMe)3, O2, 0 ℃, 90%; then TESCl, THF, 90%. (c) (1) KOt-Bu, CHBr3, petroleum ether, -20 ℃; (2) AgClO4•H2O, acetone, 23 ℃, 57% for 2 steps. (d) (1) ethynyltrimethylsilane, DIPA, Pd(PPh3)2Cl2, CuI, THF, 23 ℃, 88%; (2) (3-methylbut-3-en-1-yl)magnesium bromide, CeCl3, THF, 0 ℃, 81%. (e) (1) Co2(CO)8, Celite, toluene, reflux, 67%; (2) AgF, THF, MeOH, H2O, 80 ℃, 85%. (f) Pd(OH)2/C, H2, CH2Cl2, 23 ℃, 98%; (2) m-CPBA, CH2Cl2, 23 ℃, 73%, brsm. (g) (1) Ac2O, Et3N, CH2Cl2, 0 ℃, 91%; (2) LiHMDS, THF, -78~-40 ℃, 84%, brsm. (h) (1) Martin's sulfuran, CH2Cl2, 23 ℃, 83%; (2) Pd2dba3•CHCl3, n-Bu3P, HCOOH, DIPEA, dioxane, 45 ℃, 56% for 199a, 22% for 199b. (i) DBU, toluene, reflux, 41%. (j) TIPSOTf, Et3N, CH2Cl2, 0~23 ℃; then enolsilane 200, CAN, DTBP, CH3CN, -50~-30 ℃, 92%, dr 2.0:2.0:1.1:1.0. (k) 18-crown-6, KHMDS, HWE reagent 202, THF, -78 ℃, 60% for a mixture of epimer at C-20, dr 1.5:1. (l) OsO4, NMO, THF/H2O (V:V=1:1), 4 ℃, ca. 81%.
Reagents and conditions: (a) Cu(OTf)2, L2, 4Å MS, CH2Cl2, 0 ℃, 80%, 76% ee. (b) (1) EtSH, BuLi, THF, 0 ℃, 96%; (2) Pd2(dba)3, S-Phos, MeZnI, NMP/THF (V:V=1.5:1), 65 ℃, 80%. (c) (1) MeMgCl, THF, -40 ℃, then -20 ℃, 83%; (2) KHMDS, THF, -78 ℃; then P(OMe)3, O2, -78 ℃, 83%; (3) TESOTf, 2, 6-lutidine, CH2Cl2, 0 ℃, 94%; (4) CHBr3, t-BuOK, petroleum ether, -20 ℃; (5) AgClO4•H2O, CaCO3, acetone, 30 ℃, 66% for 2 steps; 177 was recrystallized with EtOAc/petroleum ether (V:V=1:6), 73%, > 99% ee. (d) Pd/C, H2 (101 kPa), MeOH/EtOAc (V:V=1:1), 23 ℃, 97%; (2) LiHMDS, PhNTf2, THF, -25 ℃, 89%. (e) (1) Sc(OTf)3, Ac2O, CH3CN, 96%; (2) LiHMDS, THF, 0 ℃, 93%; (3) Et3SiH, BF3•OEt2, 35 ℃, 65% (29% SM). (f) Pd(PPh3)4, Me3SnSnMe3, LiCl, THF, 60 ℃, 75%. (g) (1) 211, BH3•THF, THF, 0 ℃, 82%, > 99% ee; (2) Pd(PPh3)2Cl2, CuI, TMS-acetylene, toluene, 50 ℃, 99%. (h) 2-nitrophenol, EtC(OMe)3, 100 ℃, 90%, 7.5:1 dr at C-20. (i) aq. LiOH (1.0 mol/L)/THF (V:V=1:1), 60 ℃, 93%. (j) NIS, NaHCO3, CH3CN, 23 ℃, 52%. (k) (1) 208, Pd(PPh3)4, CuTC, NMP, 96%; (2) O2, DMSO, 145 ℃, 73%. (l) (1) LiAlH(Ot-Bu)3, THF, 5 ℃; (2) DAST, CH2Cl2, 22 ℃, 62% for 2 steps. (m) 217, BF3•OEt2, CH2Cl2, 23 ℃, 66%.
Reagents and conditions: (a) n-BuLi, 218, -78 ℃; then 219, -78~-10 ℃, 67%. (b) (1) TBSOTf, 2, 6-lutidine, CH2Cl2, 0~22 ℃, 75%; (2) [Pd(PPh3)4], Et3N, MeCN, 80 ℃, 91%. (c) (1) TBAF, THF, 23 ℃; then H2O2, KHCO3, MeOH, 23 ℃. (2) Et3SiH, ZnCl2, CH2Cl2, 23 ℃, then TBAF, THF, 22 ℃, 51% for 2 steps. (d) n-BuLi, 218, -78 ℃; then 223, -78~-10 ℃, 85%. (e) [CpCo(CO)2], PPh3, PhCl, MW (300 W), 150 ℃, 67%. (f) (1) TBAF, THF, 23 ℃; then H2O2, KHCO3, MeOH, 23 ℃, 84%; (2) Et3SiH, ZnCl2, CH2Cl2, 23 ℃, 77%. (g) (1) TBSCl, imidazole, DMAP, CH2Cl2, 23 ℃, 98%; (2) [CpCo(CO)2], PPh3 PhCl, MW (300 W), 150 ℃, 54%. (h) (1) OsO4, NMO, acetone/H2O (V:V=3:1), 23 ℃; (2) NaIO4/SiO2, CH2Cl2, 23 ℃, 85% for 2 steps. (i) ZnCl2, SOCl2, CDCl3, 23 ℃. (j) 228, ZnCl2, CH2Cl2, -30~23 ℃, 38%, 33% of C-23 epimer for 2 steps.
Reagents and conditions: (a) (1) ZnI2, P(OEt)3, 140 ℃, 94%; (2) O3, Me2S, -78 ℃, then K2CO3 aq., 55 ℃, 54%. (b) (1) LDA, 232, -78 ℃, 76%; (2) L-selectride, -78 ℃, 65%; (3) TMSCN, AlEt3; 80 ℃, then aq. NaOH, 84%. (c) (1) Co(acac)2, PhSiH3, O2, 86%; (2) aq. NaOH, 80 ℃, 88%. (d) (1) Ph3P=CH2, 91%; (2) KHMDS, Davis oxaziridine, then TESOTf, 69%; (3) O3, 96%; (4) LiHMDS, PhNTf2, 89%; (5) Sc(OTf)3, Ac2O, 96%. (e) (1) LiHMDS; (2) Et3SiH, BF2•OEt2, 60% for 2 steps. (f) (1) NBS, Benzoyl peroxide, 90%; (2) NaBH4, ArSeCN; (3) aq. H2O2, pyridine, 50% for 2 steps. (g) (1) I2, K2CO3, DMAP; (2) NaBH4, CeCl3•7H2O, 87% for 2 steps; (3) CuI, Et3N, Pd(PPh3)2Cl2, (trimethylsilyl)acetylene, 93%. (h) o-NO2C6H4OH, EtC(OMe)3, 180 ℃, 83%. (i) TBAF, 69% of 240, 22% of 241. (j) LiTMP, 87%. (k) (1) DIBAL-H, 99%; (2) DBU, LiCl, 29% of 243, 22% of C-23 epimoer 244. (l) TBS-OTf, Et3N, then TBAF, AcOH, 36%. (m) Pd(PPh3)4, CuI, LiCl, i-Pr2NEt, 89%. (n) H2, Lindlar cat., 60%. (o) 80 ℃; DDQ, 87%. (p) (3-AmO)Si-Me2H, 87%. (q) (1) 135 ℃; DDQ; (2) AgF, 73% for 2 steps.
Reagents and conditions: (a) (1) TPP, O2, hν, CCl4, -10 ℃, then thiourea, MeOH; (2) BzCl, Et3N, DMAP, CH2Cl2, 23 ℃, 73% for 2 steps. (b) [Pd(allyl)Cl]2, L3, K2CO3, MeOH, THF, 0 ℃; then DIPEA, 55 ℃, 70%. (c) (1) NaH, CH3I, DMF, 0 ℃, 90%, dr(C-13)=4:1; (2) NaBr, DMF, 180 ℃, 88%, dr(C-13)=1:1; (3) LDA, BrCH2CO2Bu-t, THF, -78 ℃; (4) TFA, CH2Cl2, 0~23 ℃, 93% for 2 steps. (d) EtMgBr, THF/Et2O (V:V=1:1), -78~23 ℃, 80%. (e) (1) O3, CH2Cl2/MeOH (V:V=1:1), -78 ℃, then Me2S, -78~23 ℃; (2) (Bn2NH2)- (OCOCF3), toluene, 63 ℃, 80% for 2 steps. (f) PPh3CHCO2Bu-t, toluene, 23 ℃, 54%. (g) (1) TFA, CH2Cl2, 0 ℃; (2) Br2, TFA, CDCl3/CCl4 (V:V=1:1), 23 ℃; (3) Et3N, DMF, 0~23 ℃, 76% for 3 steps; (4) [Pd(allyl)Cl]2, (Bu3Sn)2, LiCl, 1, 4-dioxane, 23 ℃, 49%. (h) (1) 30% H2O2, NaOH (aq.), MeOH, 0 ℃; (2) H2SO4, THF/H2O (V:V=5:1), reflux; (3) NaIO4, i-PrOH/H2O (V:V=1:1), 0~23 ℃; (4) I2, KI, NaHCO3, CH2Cl2/H2O (V:V=1:3), 0 ℃, 51% for 4 steps. (i) (1) NaBH4, MeOH, 0 ℃, 85%; (2) AIBN, Bu3SnH, toluene, 100 ℃, 90%; (3) PPh3, I2, imidazole, 0~23 ℃, THF, 84%. (j) (1) LDA, THF, -78 ℃, then 256, 86%, dr(C-19)=17:1; (2) CuCl2, EDC, toluene, 80 ℃, 83%. (k) CuI, Zn, Py/H2O (V:V=1:4), ultrasound, 23 ℃, 55%, 4% for C-10 epimer; (2) mCPBA, NaHCO3, CH2Cl2, -15 ℃, 51%. (l) (1) NaOMe, MeOH, 23 ℃; then NiCl2•6H2O, NaBH4, MeOH/THF (V:V=1:5), -15 ℃, 73%; (m) (1) ICl, THF, 23 ℃, 63%, dr(C-20)=1.5:1; (2) 261, AIBN, Bu3SnH, toluene, 4 Å MS, 100 ℃, 9% for schilancitrilactone B, 36% for schilancitrilactone C. TPP=5, 10, 15, 20-tetraphenyl-21H, 23H-porphine
Reagents and conditions: (a) (1) LDA, THF, -78 ℃, P(OMe)3, O2, 77%; (2) VO(acac)2, TBHP, CH2Cl2, 23 ℃, 97%. (b) (1) MeMgBr, THF, 0 ℃; (2) PDC, CH2Cl2, 23 ℃, 48% for 2 steps. (c) SmI2, THF, -78 ℃, 60%. (d) Py•HBr3, THF, 23 ℃, 81%, dr 7:1 at C-20. (e) 262, Ni(cod)2, dppm, 1, 4-dioxane, 60 ℃, 36% for schilancidilactone A (20S), 7% for schilancidilactone B (20R). (f) (1) LDA, THF, -78 ℃, then 256, 88% yield, dr(C-19)=9:1; (2) CuCl2, EDC, toluene, 80 ℃, 93%; (g) (1) CuI, Zn, pyridine/H2O, ultrasound, 56%, dr 7:1 at C-10; (2) LDA, THF, -78 ℃, P(OMe)3, O2, 64%, dr 2.7:1 at C-10; (3) Ac2O, Et3N, CH2Cl2, 93%. (h) (1) LDA, THF, -78 ℃, 82%; (2) Martin's sulfurane, CH2Cl2, 75%; (3) L-selectride, THF, -78 ℃, 87%. (i) (1) Co(acac)2, PhSiH3, O2, 1, 4-dioxane, 45% for 275, dr 1.3:1 at C-9; (2) Py•HBr3, THF, 23 ℃, 75%, dr 2:1 at C-20. (j) 261, Ni(cod)2, dppm, 1, 4-dioxane, 60 ℃, 10% for schilancitrilactone A, 40% for C-20-epimer.