Burns_Apr_05

CO2H Me Me O Me H Me H O H (±)-Perovskone H Me OH (–)-Chlorothricolide O HO O O O
Me
Me
H Me Me
O
Me
(+)-Epoxydictymene
Natural products discussed in part or full:
TESO Me O 1. Ti(Oi-Pr)4 t-BuOOH 2. TBS protection 93% (3 steps) Me
OTES Me OH
Me 1. HOCH2CCl3, H+, 60% 2. (MeO)2SO2, K2CO3, 91%
OTf TESO O H HO Me Me O OTCE OMe 1. Piperidine, NaCNBH3 Me N Me O OTCE OMe Me 1.05 eq. TBAF then A, –20° - RT O Me Me O OTCE OMe Me TBSO Me OCO2Et O 1. LDA, THF (+)-camphorsulfonyl oxaziridine 2. 20 eq. Red-Al -78 °C – RT 3. phosgene, pyr. 82%
3
Me TBSO O 91% overall
Me O H O +
TESO Me TBSO
Me O O H O SiO2
TESO Me TBSO O KOt-Bu; AcOH
R O SmI2 R=H (enol taut.)
6 : 1 ratio
R=OH
O HO MeO
Me
O
1. Red-Al 2. Cl2CO, pyr. 88%
OMe
(±)-Thielocin A1b
(±)-Papuamine
O Ph Ph OH NH O O
AcO
Hale Waihona Puke Baidu
O OH Me
O Me O Me O Me Me OH OH OH OH OH (–)-Roxaticin O HO OH Ph Me CO2H CO2H O OH O CO2H O OH OAc Ph Me
OBOM Me
H OH OBz OAc
O
O
O
LAH, 92% O Ph Ph OH NH O Me O OH O Ph O (–)-Taxol AcO O OH Me
AcO Me TBSO
O OBOM Me
1. LAH, 78% 2. TFA, H2O 3. DCM, 5% NaOH (70%)
H OH OBz OAc
O
H
O OAc O H H O N RaNi, H2 69% N O S S O N
N
3
(+)-Xestospongin A
Baran Group Meeting
T. Fukuyama, 3125, (–)-Hapalindole G, 3125
O O Cl Me Me O O N2 O OMe Cu(II) 60% Me
JACS 1994
W. Oppolzer, 3139
∆ HOHN Me CO2Me Ph O H O Me HOHN HO Me Ph HOHN Cl Me 1. DIBAL; NaBH4, EtOH 2. Zn-Cu 3. Jones [O] (67%) Me H Cl Me Br O O Me Ph H Ph O N H O N H Me H HO 80°, 81% Ph N 80°, 81% Me N Me HO N
OBOM Me OTMS O
1. BOMCl, Hünig's base 2. LDA, TMSCl 3. m-CPBA 79%
TESO Me TBSO O O O
OH Me
H
H
O O Me Me Me O HO
Me OH Me
Me
Me O O
Me
OTBS
O Me
O
O
O
O
O Me
Me Me
Me Me
O HO MeO Me Me Me O O MeO Me Me Me O O Me O OH Me OH O Me Me Me O O OMe Me Me Me (±)-Fredericamycin A Me O OH OMe HN HO O O HO O O OH H H H H H H H N H N H H O
H
OH
T. R. Hoye, 2617, (+)-Xestospongin A
Cl OMe OMe Cl O H H2N HO S DCM, 5% NaOH S OH CN MeO OMe Cl 42% HO NC S N O S Cl TFA S H O OAc CN OAc H2O 99% MeO OMe
N. Z. Burns 4/27/05
Stepwise-radical or concerted process? n
1. Me MeO Me
n
OH 2. ArSO2N3, DBU (95%)
Ph H
H Cl Me
O I
1. LiCl, CSA, DMF, 140° 2. LDA, CBr4 (56%)
1. KOt-Bu, -78° – 0°; (PhSeO)2O , 0° 2. KOt-Bu, -78 °C 3. Ac2O, DMAP ?% mechanism?
TESO O Me TBSO OBOM Me Me 1. HF•pyr, CH3CN, 0 °C 2. PhLi, -78 °C TBSO 3. TPAP, NMO 85% O 1. +S(NEt2)3 Me3Si-F2 (TASF) 2. a) LiHMDS, THF TESO Ph b) NBz O 3. HF•pyr. 4. H2, Pd/C, EtOH, reflux 87%
1
Baran Group Meeting
R. N. Young, 759, (±)-Thielocin A1b
Me 1. Zn-Hg/HCl, EtOH, ∆ 2. TMS(CH2)2ONa, ∆ 3. TBDPSCl (50%) Me TBDPSO Me O OTMSE 1. PhI(OAc)2, AcOH OH 2. LiOH, 12-crown-4 THF/H2O (40%) HO Me HO
TESO Me TBSO O O O
Me O H O
1. O3 2. KMnO4, KH2PO4 3. CH2N2 93%
H O
(±)-Thielocin A1b
2
(+ 8% of C3 epimer from purification)
Baran Group Meeting
JACS 1994
S. D. Rychnovsky, 1753, (–)-Roxaticin
Me H
Complete diastereocontrol
Me HO I
O
LDA, Ti(OiPr)4 Me 68% O
1. Ac2O, Pyr, 60° 2. DBU, PhH, ∆ 3. TFA/MsOH (10:1) (88%) Cl Me Me H O 1. Pd, CO 2. DPPA, Et3N, allyl alcohol (72%) Me Me Me H O Cl Me Li Cl Me Me Me H H O O NAlloc MeO 1. NaBH4 2. Ms2O, Pyr 3. LiN3 (72%) Cl Me Me H NH (–)-Hapalindole G pdct. H NC Cl Me 1. Na/Hg; HCO2H, Me Ac2O, Pyr 2. COCl2, Et3N (76%) Me H NH H N3 Me MeO
OH O Ph O
H
OAc
(+)-Zaragozic Acid C
(–)-Taxol
Cl H O N Me Me H H
Me HO HO
OH O OH OBz (–)-Paeoniflorin O O O
N
O H
NC
Me
NH (+)-Xestospongin A (–)-Hapalindole G
OH
N. Z. Burns 4/27/05
OH Me Me OH TESCl, pyr.
O H HO
Me
O OEt OH
1. HOCH2CCl3, H+ 2. (MeO)2SO2, K2CO3 3. Et3SiH, TFA, (52%)
Me Me HO Me
O OTCE OMe B
1. (i-Pr)2NMgBr, THF; O H 2. phosgene, pyr; EtOH 75% Me HO
Me Me
TESO Me TBSO O O O
OBOM Me 1. MsCl, pyr 2. OsO4 65%
TESO Me TBSO O O O
OBOM Me 1. DBU, 105° H OH OMs OH 2. Ac2O, pyr. (62%)
OH OH OH OH OH (–)-Roxaticin
TESO Me TBSO
Me O O OH 1. Swern 2. LiTMP, -10 °C 86% mechanism? Me O O
2. TBSCl, NaH TBSO 3. MeOTf (78%)
95% TESO O HO MeO Me Me Me O O Me Me O O O 1. TFAA, B 2. Cd, DMF/AcOH 3. 0.5 N NaOH (41%) O Me O Me Me O OH OMe 1. (Imid)2CO, 95% O 2. TBAF, DMF, 81% 3. Cl2CHOCH3 TMSEO 4. B, Et3N (87%) 5. Cd, DMF/AcOH 82% Me O Me Me O OTCE O OH Me OH OMe Me LiTMP, Davis oxaziridine -40 °C 88% Me O O Me MeO Me Me Me O O Me O OH Me OH O Me Me Me O O OMe Me Me Me O OH OMe TBSO OH O TESO Me Me
TESO Me OH Me CO2Me OH OMe 1. TsOH, 2. PhSK, DMF 86 °C 3. acid work-up 92% Me Me Me OMe O O OTBS O Me O Me OBn O O Me OtBu NC O Me O O O Me Br 2 eq. O O Br Me Me LiNEt2 63% O Me O Br
Baran Group Meeting
JACS Year in Review 1994
Me Me O
N. Z. Burns 4/27/05
This survey of the Journal of the American Chemical Society in the year 1994 (volume 116) is not meant to be comprehensive by any means. A strong emphasis has been placed on total synthesis from this year as opposed to pure methodology. It was an exciting 12 months for natural product synthesis as two daunting targets, taxol and zaragozic acid, both succumbed to their first construction in a laboratory. In addition, many extremely creative solutions to nature's many other synthetic challenges posed as of 1994 were revealed. In this handout a small fraction of that is presented. Enjoy! Me
N. Z. Burns 4/27/05
TESO Me TBSO O O O
Me O CO Me 2 H O LDA, THF 93%
CN O O O
Me
TBSO O O O
H
O Me
Me Me
Me Me
Me CN
1. LiNEt2, 91% 2. LIDBB, 63%
TESO 1. MeMgBr 2. Burgess (60%) Me TBSO O O O
JACS 1994
R. A. Holton, 1597, 1599, (–)-Taxol
Me O OTMSE O Me A O (+)-patchino Me 1. t-BuLi, hexane reflux Me 2. Ti(Oi-Pr)4 t-BuOOH (98%) Me O OH Me BF3•OEt2, -80 °C (75% conv.) 93%