Baran Group Meeting
Basic Statistics:
Volume number: 105
Number of Pages: 7800
Total Synthesis Papers: ~40
Publication Record:
Paquette
15 (6 tot. syn.)
Trost
15 (2 tot. syn.)
Yamamoto
8 (0 tot. syn.)
Vollhardt
6 (1 tot. syn.)
Mangus
5 (3 tot. syn.)
Overman
5 (2 tot. syn.)
Ohno
4 (3 tot. syn.)
Danishefsky 3 (1 tot. syn.)
Marshall
3 (1 tot. syn.)
Whitesides
3 (0 tot. syn.)
Van Tamelen 2 (2 tot. syn.)
JACS: 1983 Year in Review
Historical Events:
-Reagan signs legislation that makes the
third monday in January Dr. Martin Luther
King Day.
-Challenger makes its second flight. Sally
K. Ride is the first woman in space.
- People Magazine's most intriguing
people for 1983 were: Debra Winger, Mr.
T., Joan Rivers, Matthew Brodrick,
Michael Jackson, & Jennifer Beals
-Michael Jackson performs the
"moonwalk" for the first time before a live
audience.
-The last DeLoreans were produced.
-John Williams wins grammy for Best
Instrumental Composition for "Flying" (the
Theme From E.T.)
Emily Cherney
OCH3
Isolation Chemistry:
N
Incorrect structural reassignment of Carzinophilin (a.k.a.
OCH3
Azinomycin A)
J. Am. Chem. Soc. 1983, 105, 6311
O
OH
O
O
O
O
OH
OH N
H3CO
N
O
N
O
OH
O
H
O
O
H
H3C
AcO
N
N
O
(incorrect
reassignment)
HO
(Correct structural reassignment)
1st Total Synthesis: ACIEE (2001) 1736
H3CO
O
O
N
O
Isolation Chemistry:
previously incorrect
assignment
N
O
O
O
Halenaquinone
J. Am. Chem. Soc. 1983, 105, 6177
1st Total Synthesis
J. Org. Chem. 1988, 8483
N
O
Amphimidine
J. Am. Chem. Soc. 1983, 105, 4835
1st Total Synthesis
J. Am. Chem. Soc. 1988, 4051
HN
O
N
O
HN
O
O
NH
OH
Caesalpinine A
J. Am. Chem. Soc. 1983, 105, 4441
OH
O
O
HO
O
Sesbanimide
J. Am. Chem. Soc. 1983, 105, 3739
1st Total Synthesis
Tetrahedron 1988, 44, 4721
OH
O
Betaenones
J. Am. Chem. Soc. 1983, 105, 2907
H
Correct Structural reassignment of vancomycin
J. Am. Chem. Soc. 1983, 105, 6915
HO
O
H
OH
JACS: 1983 Year in Review
Baran Group Meeting
Syntheses Discussed
H
CO2Me
H
O
O
O
(±)-quadrone
O
Br
HO
O
O
H
N
(±)-gephyrotoxin
(+)-compactin
O
OH
OH
O
eucannabinolide
H3C
R3
O
R1
(±)-verrucarol R1=H; R2,R3=OH
(±)-anguidine R1=OH; R2,R3=OAc
OH
H
O
H
HO O
(±)-coriolin
O
H
O
HO2C
O
H
pentalenene
"nearly
quant.
yield"
O
MOM
O
"Total Synthesis of Qinghaosu" Schmid, Hofheinz; 624-625
(See Maimone 2005 Classic Terpene Syntheses group meeting)
H
1) 1O2, methylene
blue, MeOH, !78 °C
H
2) HCOOH, 0 °C
(30%)
O
(±)-hirsutic acid C
isocomene
MOM 2 steps
Constitutes formal total synthesis: three steps from quadrone based on
Danishefsky's synthesis J. Am. Chem. Soc. 1980, 102, 4262
via:
H
(±)-silphinene
(100%)
alcohol
NaH, PhH, "
O
OH
H
MOM
tamyl
49%
H
HO2C
O
CO2H
O
O
R2
O
O
(31%)
OH
1) BBr3
2) Jones [O]
H
HO
O
Qinghaosu
(a.k.a. artemesinin)
O
H
O
MOM
H
H
H
(59%)
HgO, H2SO4,
MeOH!H2O
O
H
H
AcO
MOM
O
O
O
1. HCO2H;
NaOH
2. PCC
H
Al, !78 °C
O
O
(±)-plumericin
O
H
O
H
"A Short Step Entry to (±)-Quadrone" Takeda, Shimono, and Yoshii; 563-568
(See Guerrero 2004 Quadrone group meeting)
H
H
Emily Cherney
H
CH3
HOO
O
O
HO2C
H
CH3
O
H
O
O
O
H
O
Qinghaosu
(a.k.a. artemesinin)
JACS: 1983 Year in Review
Baran Group Meeting
Emily Cherney
"Biomimetic Approach to Plumericin"
Trost, Balkovec, Mao; 6755-6757
"Synthesis of the Cytotoxic Germacranolide Eucannabinolide"
Still, Murata, Revial, Yoshihara; 625-627
OBOM
O
1) PhSeK!LiBr
1) LiAlH4
OBOM
2) H2O2
2) mCPBA
3) Jones [O]
3) BOMCl, Hünig's
O
(70%)
(53%)
KOH, DMSO
H
H
H
S+Ph2BF4O
LiNEt2
(82%)
2 steps
O
H
HO
H
O
(+)-carvone
MsO
Bu3Sn
Bu3SnMgCl;
MsCl
O
(58%)
OMe
OMe
K2CO3,
DMSO
OMe
OMe
(96%)
(88%)
Bu3Sn
OMe
(1.3 eq) OMe
H
nBuLi,
(82%) THF,
!70 °C
dry MeOH,
K2CO3
BOMO
rt, 25 hours
H
O
(72%)
2 steps
H
(1:1 dr)
H
O
H
(>15:1 dr)
OMe
OMe
equlilbrated
with DBU
H
Ac2O, DMAP,
Hünig's;
"distill through
quartz tube 500 °C"
OH
O
BOMO
H
O
8 steps
O
O
OH
H
CO2Me
H
H
O
O
O
O
O
O
O
O
CCl3COCl (50 eq)
2,6-tBu pyridine (5 eq)
H
Mg(OMe)2,
MeOH, THF
!45 °C
(±)-Plumericin
Eucannabinolide
O
(85%)
BOMO
O
H
O
(90%)
O
H
O
O
OH
H
NaIO4;
NaOAc
(89%)
OMe
OMe
1) NaBH
(24%) 2) cat. K 4CO
5 steps 3) Collins2 [O]3
O
O
AcO
H
H
O
H
2) H2O2, Ti(OiPr)4,
Hünig's, Et2O, !30 °C
H
OH
mCPBA,
!78 °C to 0 °C;
PhSe
MVE
O
(65%)
O
AcO
O
O
H
O
OH
(>6:1 dr)
1) oxalic acid,
SiO2, CH2Cl2
BOMO
OH
O
KHMDS (5 eq),
DME, 85 °C,
BOMO
14 hours
OMe
OMe
H
5 steps
PhSeBr,
Et3N,
!40°C
COCCl3
H
O
(90%)
O
O
O
JACS: 1983 Year in Review
Baran Group Meeting
"Total Synthesis of the Hypocholesterolemic Agent Compactin"
Hsu, Wang, Latimer, Sih; 593-601
O
OH
OBn
1) NaH, BnCl
H
H
H
2) PhSeBr,
SePh
A. pullulans
AcOH, KOAc
O
(33%)
H
H
OH
1) O
O
O
O
(71%)
5 steps
O
O
OBn
H
Pd/C, H2,
pyridine
PhSLiCu
;
O
O
1) NaOH
2) H2O2, "
3) Jones [O]
TrO
HO
O
H
OBn
MeO2C
O
H
OH
H
HO
O
O
H
MeO
(56%)
H
OH
CO2Me
OH
1) O
H
5 steps
H
A
CO2H
H
O
OMe ; O
NaH, nBuLi
O
H
HO
MeO
OMe
1) KH, Tol., "
O
2) (s)-Me-butyric
anhydride
H
(44%)
20 steps
OMe
O
H
O
(40 %)
H CH
O
H
3
O
H
O
HO
O
H
(+)!Compactin
23 steps
(+)!Compactin
O
O
O
(59%)
OMe
SPh
2) Zn(BH4)2
TsOH, PhH
MeO
5 steps
1) MsCl, pyr.; DBU
2) AcOH, THF, H2O
3) PCC
H
(63%)
H
OH
H
1) TsCl, pyr.
OMe 2) NaI, MEK, "
3) PhSO2CH2CO2Me,
DMSO,
O
(78%) Me2SO-Na+
H
4) Na(Hg),
MeOH,
Na2HPO4
OMe
Tol., BHT (0.4 eq),
3 eq. A
125 °C, sealed tube
(70%)
O
PhS
O
O
O
MeO
O CO2Me
H
(64%)
1) (2-Me butyric)2O, O
DMAP
2) KOH, EtOH
OMe
O
1) TosylHNNH2; LDA
(62%) 2) Li, NH
3
O
(70%)
MeO
OBn
H
2) Et3N, MsCl
O 3) DBU
H
OBn
1) LiAlH4, !10 °C
OMe 2) NaH, MeI
MeO
3) Na, NH3, !78 °C
H
HCHO
(78%)
O
H
OBn
OBn
H
"Total Synthesis of the Hypocholesterolemic Agent (+)!Compactin"
Grieco, Zelle, Lis, Finn; 1403-1404
OAc
H
OBn
Emily Cherney
O
O
H
1) 10% HCl, THF
2) Ag2CO3, PhH, "
3) BBr3
(22%)
JACS: 1983 Year in Review
Baran Group Meeting
"Total Synthesis of (±)!Verrucarol"
Roush, D' Ambra; 1058-1060
methyl acrylate
BF3•Et2O, DCM,
CH3
!78 °C
TMS
(78%)
MeO
O
TMS
CH3
OMe
OAc
4 eq.
O
O
O
mCPBA
HO
(95%)
O
O
OH
OH
O
O
O
(82%)
Br
20 Steps
1) CH(N(CH3)2)3
2) AcOH, NaOAc,
O
H 2O
TBDMSO
O
O
O
TBDMSO
; Hünig's
H
(95%)
OBz
O
O
(98%)
OBz
O
O
O
O
1) LDA (2 eq)
CH3 2) MsCl, imid., DMF
O
3) MeLi, THF, !78 °C
O
OH
1) NBS
2) Ac2O, pyr.
O
TBDMSO
O
1) Jones [O]
2) Wittig
OBz
O
O
O
O
xs. LiAlH4,
DME, "
HO
O
AcO
O
HO
OH
H
(29%)
CH3
O
O
TBDMSO
OBz
O
HO
OH
1) KOH, MeOH
2) BzCl
Br
CH3
O
1) Ac2O, pyr.
OH 2) 2M NH OH
4
O
TBDMSO
CH3
OH
O
CH3
(±)!Verrucarol
TsOH
OH
(90%)
24 Steps
OH
OH
O
O
CH3
O
OH
O
TBDMSO
OAc
O
TBDMSO
CH3
O
(63%)
OH
Zn/Ag
5:1 THF!EtOH
OTBDMS
O
HO
CH3
Br
O
CO2Me
O
5 steps
S. cervisiae
(70%)
6 steps
(65%)
O
O
O
O
O
OAc
O
OH
O
MeO2C
2) LDA (1.2 eq),
O
O
!78 °C to !20° C;
gaseous HCHO
!20 °C to rt, 24 h
(56%)
Toluene, BHT,
140 °C
(57%)
1) LiAlH4, DME, "
HO
2) PPTS, PhH, "
3) 1 N HCl
HO
O
O
DCM, NaHCO3,
23 °C, 50 h ,
42-51%
mechanism?
HO
1) TsOH,
Benzene, " HO
O
"Total Synthesis of the Trichothecene Mycotoxin Anguidine"
Brooks, Grothaus, Maziyasni; 4472-4473
NO2
O 2N
(4-6 equiv)
MeO2C
Emily Cherney
OAc
6 steps
CH3
AcO
OH
OH
CH3
OAc
O
CH3
OH Anguidine
Baran Group Meeting
JACS: 1983 Year in Review
Emily Cherney
"Total Syntheses of (±)!Gephyrotoxin and (±)!Dihydrogephyrotoxin"
"An Efficient Total Synthesis of (±)!Gephyrotoxin"
Hart, Kanai; 1255-1263
Overman, Lesuisse, Hashimoto; 5373-5379
OH
1) LiAlH4, !70°C
O
O
HO
OMOM
MOMO
H
2) Succinimide,
P
O
O
O
H
H
MeO
DEAD, PPh3
O3; NaBH4
O
OMe
H
O
O
CHO
H
H
(51%)
(80%)
O
n
N
O
BuLi
NH
O
N
N
OBn
O
O
OBn
H
O
1) PBu3;
TFA,
H2 (2 eq),
4
Steps
NCSeAr Ar=
O
(76%)
o-NO2Ph
ex. LiAlH4, Et2O, (92%) Pd/C;
1N NaOH, CHCl3
!19 °C;
2) H2O2
O
H
O
H
H
MOMO
H
1) iBu2AlH
Cl3C
O
Cl MOMO
H
H
O
O
O
O
H
H
2)
HCO
H
, PMP
O
2
H
H
N
(85%)
N
(63%)
N
N
N
H
H
O
(>12:1
dr)
O
O
O
O
CCl3
1) NaOH
(71%) 2) NaH, CS2, MeI
1) 10% aq. HClO4
3) Bu3SnH
(75%) 2) OHC-CH P+Ph Br-,
2
3
OTBDPS
nBuLi
MOMO
1) Lawesson's
1) disiamylborane;
2)
H2O2
MOMO
CHO
H
H
H
Br
COOEt
CH(OMe)2
H
1) PPTsS, MeOH
2) TBDPS
H
iPrOH, H O
3) Et3N, PPh3
protection
2)
KOH,
2
H
H
H
H
H
H
(80%)
N
N
N
(73%)
(96%)
N
N
H
mechanism?
H H
50
psi
H
,
O
2
O
O
CCl3
1) 1N HCl;
Pt/Al2O3
CO2Et
CO2Et
NaOMe;
EtOAc:Hex
(46%)
NaBH4
(92%)
1:1
(±)!Gephyrotoxin
(±)!Gephyrotoxin
2) TBDPSCl,
1) Bu4N+F1) 24% HBr in DME
Et3N, DMAP
TBDPSO
MOMO
H
H
2) Swern
H
2) Swern
H
3) tBuLi,
3) tBuLi,
TBDMS
TIPS
H
H
TMS
TIPS
N
N
N
N
4)
DIBAL
4) Bu4N+FH
H
17 Steps
21 Steps
H
H
+
5) Bu4N F
(27%)
(>24:1 dr)
HO
HO
(20%)
TBDPSO
CO2Et
JACS: 1983 Year in Review
Baran Group Meeting
"A Stereoselective Total Synthesis of (±)-Hirsutic Acid C"
Greene, Luche, Deprés; 2435-2439
1)
, H2SO4
CO2H
H3C CO2tBu CCl3COCl, POCl3; HO2C
Zn-Cu, TFA
2) LDA, CH3I
(80%)
(60%)
"Stereoselectivity of Intramoledular Dicobalt Ocatcarbonyl Alkene-Alkyne
Cyclization: Short Synthedid of (±)-Coriolin"
Exon, Magnus; 2477-2478
CH3
+
OTBS 1) PhCH2 NEt3Cl ,
KF•2H2O, THF, !
2) nBuLi, MeI
O
Li
H
TMS ;
TBSCl
H
H
(86%)
Cl
O
Emily Cherney
CH3
TMS
Cl
1) 3 eq Li(CH3)2Cu;
CH3I
2) CH2N2
1) CCl3COCl, POCl3
Zn-Cu; CH2N2
H3C
2) Zn, AcOH
MeO2C
H
CH3 1) NaBH4
2) Cr(ClO4)2,
H2NCH2CH2NH2
(42%)
4 steps
H
(65%)
H3C
TBSO
1) Wacker [O]
t
t
2) KO Bu, BuOH
(47%)
H
H 3C
H
H3C
H
O
H
mechanism? (50%)
(±)-hirsutic Acid C
H3C
HO2C
O
H
15 Steps
1) H2O2, NaOH
2) NaBH4
(73%)
t
O KO Bu, DME, TBSO
20 °C, 2h
Constituted formal
total synthesis
7 steps to coriolin
O
HO H3C
H
1) LiHMDS;
HCO2CH3
2) HCHO,
K2CO3
HH3C
CH3
O
H
O
mCPBA; DBU
(34%)
2 steps
TBSO
HF/pyr.
H3C
H
O
(±)-coriolin
O
HO
H3C
H3C
HO2C
H3C
H
H3C
H
H
H
OH
O
1) H2, 10% Pd/C
2) allylation "standard TBSO
conditions"
H
H3C
H
TBSO
HO2C
H3C
H
H3C
H
(50%)
mechanism?
H3C
(58%)
O
MeO2C
MeO2C
H
Co2•(CO)8, CO,
heptane, 110 °C
H Cl CH3
1) PdCl2, Pd(OAc)2
O 2) AlBr3,
S
H 3C
H
OTBS
H3C
H
O O
H
OH
H
OH
O
H
OH
18 Steps
Note: see Gallagher 2004 group meeting on
coriolin for completion of synthesis:
Trost, J. Am. Chem. Soc. 1981 103, 7380
JACS: 1983 Year in Review
Baran Group Meeting
"Triquinane Sesquiterpenes. An Iterative, highly Stereocontrolled
Synthesis of (±) Silphinene"
Paquette, Leone-Bay; 7352-7358
"Total Synthesis of (±)-Pentalenene, the Least Oxidized Neutral
Triquinane Metabolite of Streptomyces griseochromogenes"
Paquette, Annis; 7358-7363
1) Cl2CHCOCl,
1) TsOH, H2O,
Et3N, pentane
THF
OH Cl
OH ClCl
OTES 2) CH3OH, HCl;
Cl 2) CH2N2
TsOH
O
1)
O
O
BrMg
O
CuBr•Me2S
2) HCl, aq acetone
(79%)
H
OH 1) CH3SO2Cl,
Et3N, DCM
2) DBU, DCM
O
(76%)
H
O
1)
OH
O BrMg
O
CuBr•Me2S
1) TolOCCl
O
pyr., THF
2) 200 °C, 25 torr
H
1) CH3Li
2) PCC,
Celite
O
1) O3, (CH3)2S
2) TsOH,
HO
H
(57%)
BF3•Et2O
DCM, rt, ON
H
1) Na, NH3
2) PPTs, H2O
acetone
Cl
CH3
(quant.)
O
H
H
O
H
CH3
O
O
Cl
OH
(quant.) 1) CH3Li
2) TsOH, PhH
CH3CO3H,
NaHCO3
CHCl3,
Zn,
AcOH
1) Li(3-butene)2Cu
2) CH3MgBr
Cl
OH
OHC
CH3
OH
H
O
(95%)
H
H
(83%)
H2NNH2,
K2CO3,
diethylene
glycol, !
1) LDA; PhSeCl;
H2O2
2) Li(CH3)2Cu
O
1) LDA; PhSeCl;
H2O2
2) (PPh3)3RhCl
TESH
H3C
CH3
H
H
H
H2NNH2,
K2CO3,
triethylene glycol, !
18 steps
CH3
H
O
CH3
H3C
(±) silphinene
1) SnCl4, PhH
2) PCC
H
O
15 steps
O
H
(43%)
5 steps
2) HCl, H2O, THF
(84%)
OMe
OH
H
H
(70%)
S
Emily Cherney
H
(±)-pentalenene
JACS: 1983 Year in Review
Baran Group Meeting
"Direct Stereocontrolled Synthesis of Isocomene"
Wenkert, Arrhenius; 2030-2033
1) CH3CHI2,
Zn(Et)2
OMe
1) KOEt
2) H2CrO4,
2) LiAlH4
pyr.•AcOH
O
(53%)
O
(93%)
HO
(7:1 dr)
(94%)
1) NaOH, MeOH
2) NaH, O
1) CH3Li
2) 30% H2SO4,
hexane
(80%)
S
O
MeO
"Palladium-Catalyzed Stereocontrolled Cyclization of 1,3-Diene
Monoepoxides" Takashi Takahashi, Hideaki Kataoka, and Jiro Tsuji, 147-149
"Wittig Olefination via Reaction of Fluorine-Containing Phosphoranium Salts
and F-Acyl Fluorides. A New Approach to Fluoroolefin Synthesis'" Donald
Burton and Daryl G. Cox; 650-651
1) LDA;
TMSI
2) CH2I2,
Zn(Et)2
OMe
"Stereochemistry of Transmetalation in the Palladium-Catalyzed Coupling of
Acid Chlorides and Organotins" Jeff W. Labadie and J. K. Stille; 669-670
MORE: 6129-6137, 7173-7175, 7175-7176
"Palladium-Catalyzed Acylation of Unsaturated Halides by
Anions of Enol Ethers" Charles E. Russell and Louis S. Hegedus; 943-949
"Stereocontrol in Homogeneous Catalytic Hydrogenation via Hydroxyl Group
Coordination" Gilbert Stork and Daniel E. Kahne, 1072-3
TMSO
MeO
(91%)
"Hydroalumination of l-(Trimethylsilyl)-l,3-diynes. Syntheses of
Stereodefined Enynes and Dienes" Joseph Miller and George Zweifel; 13831384
"Titanium-Induced Cyclization of Keto Esters: A New Method of
Cycloalkanone Synthesis" John E. McMurry* and Dennis D. Miller; 1660-1661
1) CH3SCH2Li
2) CH3I, NO2CH3
NaH
"Synthetic Applications of Titanocene Methylene Complexes: Selective
Formation of Ketone Enolates and Their Reactions" John R. Stille and Robert
H. Grubbs; 1664-1665
(62%)
(92%)
S+I- OH
O
Methods Papers:
O
MeO
OMe
OMe
Emily Cherney
"Palladium-Mediated Cycloaddition Approach to Cyclopentanoids.
Introduction and Initial Studies" Barry M. Trost and Dominic M. T. Chan; 23152325
O
LiI, THF (91%)
"Vanadium( V) Peroxo Complexes. New Versatile Biomimetic Reagents for
Epoxidation of Olefins and Hydroxylation of Alkanes and Aromatic
Hydrocarbons" Hubert Mimoun, et. al. ; 3101
1) LiAlH4
2) nBuLi, TMEDA,
O
Cl P
N(CH3)2
Cl
then, (CH3)2NH
Li,
EtNH2,
THF
(±)-isocomene
17 Steps
O
N(CH3)2
P
N(CH3)2
O
"Activation of Methane by Iridium Complexes" Graham, et. al.; 7190-7191
"Enantionselective Carbocyclization: A Facile Route to Chiral
Cyclopentanes" Taber, Raman; 5935-5937
O
"A Titanium Vinylidene Route to Substituted Allenes" Buchwald, Grubbs; 54905491
JACS: 1983 Year in Review
Baran Group Meeting
Emily Cherney
On A Lighter Note....
Suggested Reading...
The 1st Synthesis of: "18[(2,6)pyridino6coronand-6]: 'Sexipyridine' "
Newkone, Lee; 5956-5957
"Total Synthesis of Dodecahedrane"
Paquette, Ternansky, Balogh, Kentgen; 5446-5450
(See Shenvi 2006 Platonic Hydrocarbons GM)
SeO2, AcOH
24h, Δ
H3C
N
N
CH3
OHC
1)
O
N
N
N
nBuLi,
Br
Br
THF,
3
days,
45
°C
O
2) NBS, aq THF,
MeOH
N
N
CHO
N
S
S
N
S
N
S
O
H3C
N H
CH2(CH2SH)2,
TsOH, Toluene, Δ
H
O
OH
OH
N H
H
(±)-aspidospermidine
HO
H
CH3
HO
N
H
(±)-kopsanone
(±)-aphidicoline
H
N H
N
O
O
N
N
H2NOH•HCl, AcOH
Δ, 24 hours
N
O
N
N
N
N
N
O
O
O
OH
O
(+)-tryptoquivaline G
R3 OH
OH
R1
N
"Synthesis and Characterization of [7]Circulene"
Yamamoto, Harada, Nakazaki; 7171-7172
OH
O
O
OH OR2
duanomycinones
O
O
O
CO2H
(±)-frenolicin
BrBr
BrBr
(CH3)3O+BF4-
SH
Br
SH Cs2CO3, DMF
Br
1)
2) NaH
S
BrBr
BrBr
S
H3CS
1) mCPBA
2) 300 °C,
0.001 mm
1) trace I2, hν
2) nBuLi, DMF
3) LiAlH4, TiCl3
SCH3
[7]circulene