BÀI TẬP -BÀI GIẢI TỔNG HỢP HÓA HỮU CƠ LUYỆN THI HSG QUỐC GIA (tập 2 2021)

BÀI TẬP TỔNG HỢP HÓA HỮU CƠ LUYỆN THI HSG QUỐC GIA (tập 2 2021)BÀI TẬP TỔNG HỢP HÓA HỮU CƠ CHUYÊN NGÀNH HÓA HỌC (tập 2 2021)BÀI TẬP TỔNG HỢP HÓA HỮU CƠ GIÁO VIÊN HÓA HỌC (tập 2 2021)BÀI TẬP TỔNG HỢP HÓA HỮU CƠ BỒI DƯỠNG HỌC SINH GIỎI (tập 2 2021)

BÀI TẬP TỔNG HỢP HÓA HỮU CƠ LUYỆN THI HSG QUỐC GIA (tập 2) Thạc sĩ Phạm Công Nhân TAXOL Fukuyama Group - Group Meeting Problems 01/09/2002 Li Me O TMSO MeO THF –78 °C; TMSCl (1.5 eq); 25 °C; HCl aq H H 0.1 eq PhSH 0.1 eq PhSNa C16H20O2 Me O O THF reflux 12 hr H O MeN O MeO Cl O lutidine 1) MeAlCl2, CHCl3 2) NaBH4, MeOH, 63% (2 steps) toluene 68% 3) MsCl, Et3N, 94% 4) t-BuOK, THF, reflux, 86% MeO CrCl2 (8 eq) TMSCl (6 eq) H2O (1 eq) O R1CHO NMe + R2 N N R1 O R2 THF 25 °C, 24 h Ph OEt O OEt Ph benzene reflux H 67% O HN TESO Ar CO2Me 1) Boc2O, DMAP Et3N, CH2Cl2 Ar-C7H8NO 2) TBAF, THF-H2O 3) DMSO, H2O, 130 °C 1) Me3SiOK toluene, 70 °C; aq NH4Cl 2) Pb(OAc)4 t-BuOH, 50 °C Cl Ar = N NHBoc Ar O Fukuyama Group - Group Meeting Problems 01/16/2002 O PhSH aq HCHO Et3N O Me EtOH O 1) Li/NH3 THF, t-BuOH; TMSCl, Et3N O Me4NBH(OAc)3 H MeCN-AcOH –40 °C 2) Sc(OTf)3 aq HCHO THF HO O Me Me OH SmI2 (0.1 eq) Ph OH Ph O H Ph Ph OH (4.0 eq) O Ph PhMe, 80 °C, hr 95% O O Ph DNs N 1) cyclopentadiene, NaIO4, MeOH, H2O 2) DNsCl, pyridine, CH2Cl2 NH2 O NHOH 3) Pd(PPh3)4, THF, ∆ N O OH + n-Bu Ph MeOTf 2,6-di-t-Bu-pyridine CH2Cl2, °C; 1) MS 4Å CH2Cl2 OHC 2) Oxone®, NaHCO3 MeCN-H2O 54% NH2 A O n-Bu aq NaHCO3 55%, >98% ee Cr(CO)5 benzene N Ph reflux Ph O OHC N Fukuyama Group - Group Meeting Problems 01/23/2002 O CO2Me N2 O O CO Me O Rh2(OAc)4 (1 mol%) CH2Cl2 reflux, 54% O O NO2 NO hν + ROH OR CHO OAc OAc Hg(OTf)2 1.2 eq tetramethylurea H O CH3CN r.t., 5.5 h; NaCl HO ArCO2 Ar = p-nitrophenyl HgCl 22% Ph TMS DMAD (2.0 eq) TMS Et2O –78 °C to rt 16 hr 79% N A C26H35NO8Si2 TMS n-Bu N TMS N TMS (1.0 eq) TMS O n-Bu MeO2C Et2O –78 °C to rt 24 hr 33% MeO Ph Ph N3 CO2Me OMe 1) benzene, 80 °C N O 2) PhCHO, DABCO (1.5 eq) Ph CO2Me CO2Me Ph O TMS N TMS Fukuyama Group - Group Meeting Problems 01/30/2002 AlCl3 (2.0 eq) SiMe3 N OH CH2Cl2 –10 to °C 84% NO2 O O OH POCl3, 50 °C NMe CHO MeO 86% OMe MeO N Me Cl O O O Pd(dba)2, dppp CO (6 atm) DMF N H NO2 74% CN CN NC i-PrNH2, hυ NH3, CH3CN-H2O MeO NHi-Pr MeO O OTIPS Me N PMP O PMP = p-C6H4OMe 1) ClTi(Oi-Pr)3, c-C5H9MgCl THF, rt, 90% 2) SiO2, CF3CH2OH, rt; P(OEt)3, rt, 68% H OH H TIPSO H stereoisomers Fukuyama Group - Group Meeting Problems 11/06/2002 Br Bu2Mg (0.52 eq) n-BuLi (1.1 eq) DMF (~2.0 eq) –20 °C; THF –20 °C; –20 °C; 2N HCl OH O COOH CHO N3 O 1) hν CHCl3, rt, h 2) PPh3 toluene, reflux, h CO2Me N 3) methyl propiolate toluene 140 °C, 12 h CO2Me + N N N H 1) HCl, MeOH reflux, 44% O CO2Me C23H26N2O5 2) ClCO2Me, Na2CO3 CH2Cl2, rt, 84% OH N 3) NaBH4, CeCl3 MeOH, 88% 4) MsCl, Et3N, DMAP CH2Cl2, 91% 5) Et3N, EtOH, H2O 60 °C, 83% N MeO2C CO2Me 1) MOMCl, i-Pr2NEt A 2) cat t-BuOK 3) n-BuLi Br Br Li-morpholineamide (2 eq) –78 °C, h; isobutyraldehyde reflux, h THF, 71% Br HO A, –78 °C, 2.5 h; O Br HCl/EtOH, °C THF, 75% OMe N O 1) I2 (1.5 eq) collidine (1.5 eq) CH2Cl2, rt 84% (95:5) 2) NaN3, DMF 3) SnCl2, H2O; OMe Boc2O, Na2CO3 83% (2 steps) Amino acid derivative 1) I2, EtOH-H2O 78% 2) Zn, THF 3) CH2N2 87% (2 steps) NHBoc CO2Me Fukuyama Group - Group Meeting Problems 11/13/2002 Ph N O Rh2(OAc)4 (1 mol%) N H dichloroethane 130 °C Ph O Ph note: stereoselective H DMF, MeTi(Oi-Pr)3 c-HexMgBr C11H19N decaline, 220 °C, h 90% THF, rt, 14 h 63% 3) triisopropylbenzene reflux, h, 80% 1) NaNHNH2 ether-THF, °C, h N 2) CN HO O O OH HO O O OH N MgSO4, EtOH, rt, 12 h (68% in steps) O NO2 O S NH2 O O2N CN Cl Et3N, THF reflux, 24 hr 76% MeO MeO O MeO O Me O Br R Me OTIPS MeLi (1 eq) THF, –100 °C; MeO A TFAA, –78 °C; PhNH2, –15 °C 1) n-BuLi, THF, –78 °C; A, –78 °C; oxalic acid, H2O, rt 2) toluene, 110 °C; air, rt R= Me MeO O R Me OTIPS O OTBS Me Me O N NMe2 Fukuyama Group - Group Meeting Problems 11/20/2002 OMe OMe Hg(OTf)2, THF rt, 30 min; H N H NaBH4, MeOH °C to rt, 14 h N3 47% (α:β = 2:1) 1) O 3) NOClgas pyridine, –20 °C; , hν quant reflux 85% in steps hν, pentane 2) n-BuLi 71% O 4) TsOH benzene O O H H 1) aq NaOH PhH, reflux, hr; 3) MCPBA, CH2Cl2 –78 °C, 30 66% (2 steps) H O CH2N2, Et2O 65-70% 2) tryptamine, MS4A Et2O, reflux, 24 hr CO2Me N 4) hν MeCN, quartz tube hr, 60% O N H H O O N3 O BF3•OEt2 CO2Me SiMe2Ph "tetrahydrofuran" CH2Cl2 –50 °C N3 SbCl5 CH2Cl2 –50 °C HO CO2Me Me Bu 1) NH2OH•HCl Py-EtOH Bu O 2) NaBH3CN MeOH, pH 3-4 N toluene, reflux O Fukuyama Group - Group Meeting Problems 11/27/2002 NaH; cat CuCl acryloyl chloride A HN toluene, rt, 23 h 56% S O2 O O H NO2 1) A, PhNCO Et3N, benzene rt, 48 h, 70% 3) LAH, ether rt, 20 h, 97% 4) NH2OSO3H (2 eq) 2) xs MeMgBr, THF –78 °C, 45 min; rt, 90 min, 72% aq NaOH, CH2Cl2 °C, 75 min, 54% 5) cat TsOH, benzene 60 °C, 48 h, 61% O O Ph NO2 N (4 eq) ,PhH; H Py H N CH3COCl PhCHO (1 eq) 90% O O (2 eq) NC hexane 90% CN O N 48% HBF4 OMe O Me OH O OMe MeNO2 91% N2 Hept H Sit-BuMe2 · Hept NOBF4, CH3CN, –30 °C; Me N O Br2, CCl4 Me 72% Br OMe CO2Me 1) cat Ti(Oi-Pr)4 EtMgBr (2 eq) 95% 2) TMSOTf 2,6-lutidine CH2Cl2, 88% H TiCl4 n-Bu3SnH cat AIBN CH2Cl2 –40 °C benzene reflux H 71% 95% MeO Br O OMe Fukuyama Group - Group Meeting Problems 12/04/2002 OAc SMe N O OH Me2S SMe BF4 OMe reflux bycyclic compound O N toluene O O O Ph O Ph Ph2S2, AIBN Ph PhCl, hν, reflux 52% Ph CpW(CO)3 O O TfOH OEt Tungsten-contained ethyl ester EtOH-CH2Cl2 OEt O 1) (CO2H)2, 75% O 2) NOBF4, LiCl CH3CN, 47% H 65% COOH HgCl2 O LiPdCl3, CH3CN, ºC to rt; A CHCl K2CO3, reflux 59% 23% Cl (CH2O)n, AlCl3 (0.5 eq) R R R' O CH2Cl2, rt, h; H2O 62% R' O Fukuyama Group - Group Meeting Problems 12/18/2002 O N2 1) TIPSOTf, i-Pr2NEt Et2O-Hex °C to rt TMSCHN2 CH2Cl2-Hex, rt; A Cr(CO)5 1) MeO OMe MeO OMe 1) TFA THF-H2O 85% 98% MeO O SiO2, rt 2) hυ benzene Sii-Pr3 O NHt-Bu Tricyclic compound O 2) MeOH 100 °C 92% 2) t-BuNC THF 85% MeO S O2 Cl N NaCH2S(O)CH3 NO2 Bu CHO THF-DMSO rt Pd(PPh3)4 (1 mol%) Bu N THF, rt Cl 85% O MeHN O 1) NCS, Et2O 2) cat CuCl, CuCl2 aq AcOH-THF Me N 3) aq HCl, MeOH 4) toluene, reflux O OMe Fukuyama Group - Group Meeting Problems 12/25/2002 MeO N MeO 1) Bu3SnTMS, CsF DMF, rt 2) PPA, 60 ºC 40 h, 66% MeO H N MeO h, 85% OHC I PPA=polyphosphic acid O N Cl O NaN3 (ca eq) O O MeCN/H2O (3:1) rt, 97% 1) BuLi ether, –20 °C; N S Me SiMe3 S MeO CH2Br 2) MeOTf benzene, °C 96% Me Me 3) CsF DMSO, rt; aqNaOH, 68% CH2SMe MeO 58% N3 HO H HO O OH Bn2NH, AcOH Pd(OH)2/C, H2 EtOH, 40 °C MeOH HO HO OH O O (TMS)3SiH Me AIBN H N3 H H N NH NH2 OH ... ClCH2CH2Cl reflux, 48 h 66% 2) pH 13 O Br 1) FeCl3 2) AcONa N N H Me Ph C12H24O2Si Et2O N Cl CO2Me Me 3) DIBAL, CH2Cl2 –10 °C 4) Tf2O, 2, 6-lutidine CH2Cl2, –78 °C toluene reflux O 1) BnNH2, Pd2(dba)3,... CH2Cl2 rt, 15 hr, 52% N MeO2C Cl 1) Li S 2) HgCl2, H2O Cl O N CHO CO2Me Fukuyama Group - Group Meeting Problems 03 /20 /20 02 OTIPS Cp2TiCl2; MeMgBr, Br2 (2 eq) MgBr 2) Pd-C, HCO2NH4, MeOH reflux... NaIO4, MeOH, H2O 2) DNsCl, pyridine, CH2Cl2 NH2 O NHOH 3) Pd(PPh3)4, THF, ∆ N O OH + n-Bu Ph MeOTf 2, 6-di-t-Bu-pyridine CH2Cl2, °C; 1) MS 4Å CH2Cl2 OHC 2) Oxone®, NaHCO3 MeCN-H2O 54% NH2 A O n-Bu