Baran Group Meeting
Overview: 1987, vol. 109
– 8123 pages
– ~60 total synthesis papers
Publication record:
Barry Trost
E.J. Corey
Leo Paquette
Samuel Danishefsky
Phil Magnus
Clayton Heathcock
K.C. Nicolaou
Larry Overman
Stuart Schreiber
K. Barry Sharpless
Gilbert Stork
13
10
8
7
6
5
5
4
4
4
4
JACS: 1987 A Year in Review
Dane Holte
O O
Notable Isolation Papers:
Me
I
O
MeSSS
Me
O
S
O
Me
O
HO
MeO
OH
HO
OMe
OH
OMe
Et
N
H
O Me
HN
HO
O
H
N
OMe
H
O
O
O
MeO
Calichemicins, a Novel Family of Antitumor Antibotics.
1. Chemistry and Partial Structure of Calichemicin γ1I.
2. Chemistry and Structure of Calichemicin γ1I.
M.D. Lee, T.S. Dunne, M.M. Siegel, C.C. Chang, G.O. Morton,
and D.B. Borders, 3464–3466 and 3466–3468.
Key methodologies developed and/or refined:
structurally related to:
Esperamicins, a Novel Class of Potent Antitumor
Antibiotics.
2. Structure of Esperamicin X.
3. Structures of Esperamicins A1, A2, and A1a.
J. Golik, J. Clardy, G. Dubay, G, Groenwold, H. Kawaguchi,
M. Konishi, B. Krishnan, H. Ohkuma, K. Saitoh, and T.W.
Doyle, 3461–3462 and 3462–3464.
sBu
HO
Stereospecific Cross-Coupling of Vinyl Halides with Vinyl Tin Reagents
Catalyzed by Palladium. J.K. Stille and B.L. Groh, 813–817.
Me
MeO
Asymmetric Hydrogenation of β-Keto Carboxylic Esters. A Practical,
Purely Chemical Access to β-Hydroxy Esters in High Enantiomeric
Purity. R. Noyori, T. Ohkuma, M. Kitamura, H. Takaya, N. Sayo, H.
Kumobayashi, and S. Akutagawa, 5856–5858.
A Stable and Easily Prepared Catalyst for the Enantioselective
Reduction of Ketones. Applications to Multistep Syntheses. E.J. Corey,
R.K. Bakshi, S. Shibata, C-P. Chen, and V.K. Singh, 7925–7926.
O
Me
Palladium-Catalyzed Coupling of Aryl Triflates with Organostannanes.
A.M. Echavarren and J.K. Stille, 5478–5486.
Highly Enantioselective Borane Reduction of Ketones Catalyzed by
Chiral Oxazaborolidines. Mechanism and Synthetic Applications. E.J.
Corey, R.K. Bakshi, and S. Shibata, 5551–5553.
iPr
Me
OH
O
Me
iPr
O
N
Me
O
O
H
O
Me
O
O
N
O
NH
N
OMe N
Me
OMe
Me
Me
HN
O
N
S
The Isolation and Structure of a
Remarkable Marine Animal
OMe
Antineoplastic Constituent:
Structure of FK506: A Novel
Dolastatin 10. G.R. Pettit, Y.
Immunosuppressant Isolated from
Kamano, C.L. Herald, A.A. Tuinman,
Streptomyces. H. Tanaka, A. Kuroda, F.E. Boettner, H. Kizu, J.M. Schmidt,
H. Marusawa, H. Hatanaka, T. Kino, T. L. Baczynskyj, K.B. Tomer, R.J.
Goto, and M. Hashimoto, 5031–5033. Bonttems,
6883–6885.
OMe
JACS: 1987 A Year in Review
Baran Group Meeting
Syntheses that will be discussed today:
HO
Me NC
N H
Et
Me
Me
OCOMe
CN
CO2Me
Me
H
HO
N
H
OH
MeO
H
Me
Me
OH
Me
7,20-Diisocyanoadociane
(–)-Vindoline
Aphidicolin
OH
Me
HO
OH
O
O
Me
OH
OH
OH
OH
OH
Total Synthesis and Absolute Configuration of 7,20-Diisocyanoadociane.
E.J. Corey and P.A. Magriotis, 287–289.
Me
Me
Me
Pagodane
O
H
O
(CH2)2OTBMS
[4+2]
O
Me
OH
Me
OMe
N
O
Mitomycins
NH
Me
O
MeO
H
PhMe, 150 ºC
20 h (90%)
O
O
O
HO
O
CO2Me
BzO
TBMSO(H2C)2
H
N
H
(±)-Clavicipitic Acids
CN
MeO
Me
Me
Me
Me
Me
(±)-Laurenene
Me
O
H
N
H
N
Me
H
H
O
(±)-Cyanocycline A
PhMe, 185 ºC
36 h (54% + 36%
other diaster.)
Me NC
N
Me
O
H
H
O
MeO
H
OMe
Me Me
(–)-Steganone
(±)-2-Desoxystemodinone
Me
O
O
[4+2]
Ac
N
O
O
H
Me
iPr
O
O
Me
OH
O
O
O
1. PhSeSiMe3 (1.3 eq),
HO(CH2)2OH (xs), I2 (cat.)
2. mCPBA
3. Me2S, (iPr)2NH
Me
OH NH2
R
Me
CO2H
O
OCONH2
iPr
O
O
OH
Me
O
O
O
+
OH
O
Amphotericin B
Dane Holte
Me
CN
Me
H
H
Me
7,20-Diisocyanoadociane
O
O
OBz
Me
JACS: 1987 A Year in Review
Baran Group Meeting
Dane Holte
Stereocontrolled Construction of Key Building Blocks for the Total Synthesis of Amphoteronolide B and Amphotericin B. K.C. Nicolaou, R.A.
Daines, J. Uenishi, W.S. Li, D.P. Papahatjis, and T.K. Chakraborty, 2205–2208.
Total Synthesis of Amphoteronolide B. K.C. Nicolaou, R.A. Daines, and T.K. Chakraborty, 2208–2210.
Total Synthesis of Amphotericin B. K.C. Nicolaou, R.A. Daines, T.K. Chakraborty, and Y. Ogawa, 2821–2822.
macrolactonization
Me
HO
OH
OH
O
Me
O
OH
OH
OH
OH
OH
O
CO2H
Horner-WadsworthEmmons (HWE)
O
β-gylcoside
formation
O
O
O
HWE
BnO
OH
O
HO
OH
O
O
HWE
OBn
O
O
O
OH
HO
(+)-xylose
OBn
OBn
OH
OH
O
O
OH
HO
O
(MeO)2P
HO
OH
OR
O
OH
O
(–)-xylose
(EtO)2P
CO2Et
O
OH
Me
O
H
EtO
OEt
O
OH
(+)-diethyltartrate
BnO
O
H
RO
OBn
Me
O
OH
Me
O
O
RO
RO
CO2Me
(MeO)2P
O
OH NH2
OH
O
Me
O
OH
O
Me
Me
OH
MeO
OR
O
RO
OR
HO
OH
Me
Me
HO
HWE
HWE
O
Ph
acid-induced
THP formation
JACS: 1987 A Year in Review
Baran Group Meeting
Dane Holte
Stereocontrolled Total Synthesis of (±)-Cyanocycline A. T. Fukuyama,
L. Li, A.A. Laird, R.K. Frank, 1587–1589.
OBz
LDA, THF, -78 ºC; MeO
then ZnCl2 (1.5 M);
CO2tBu
Me
N
OH
then:
CO2tBu
MeO
Me
N
CO2Me
Me
OH
OMe OH
tBuO2C
H
Me
CO2PG
H
N
OBz
MeO
tBuO2C
OBz
(34% over
10 steps)
OMe O
H2N
CSA, quinoline,
PhH, reflux,
(85%)
H
O
OMe O
(77%)
OH
OBz
CH2OBz
MeO
NH
CO2PG
H
N
Me
MeO
CO2Me
HN
O
H
MeO
1. H2, Ra-Ni, Et3N
2. PhCH2OCH2CHO,
AcOH, MeOH
(66% over 2 steps)
OBz
HO
N
H
CO2PG
N
Me
MeO
then NaBH3CN
CO2Me
(64%)
mechanism?
HN
O
NOCl, -35 ºC;
H
MeO
H
CO2PG
N
Me
CO2Me
HN
MeO
O
H
(37% over
6 steps)
AcO
OAc
MeO
N
NCO2PG
Me
MeO
AcO
OAc
CN
H
H
HN
H
1. Lawesson's reagent MeO
mechanism?
Ar
S
O
S
P
S
P
S
AcO
OAc
CN
O
N
NCO2PG
Me
MeO
H
N
H
CN
MeO
N
, MeOH, 60ºC
(99%)
H
NCO2PG
Me
MeO
H
N
H
H
Ar
2. "Careful" Ra-Ni
(74% over 2 steps)
O
HO
O
CN
MeO
N
N
Me
O
H
N
H
O
H
H
(±)-Cyanocycline A
Me
(42% over
4 steps)
JACS: 1987 A Year in Review
Baran Group Meeting
HO
Enatioselective Total Synthesis of Aphidicolin. R.A.
Holton, R.M. Kennedy, H-B. Kim, M.E. Kraft, 1597–1600.
OH
Dane Holte
Synthesis of (–)-Vindoline. P.L. Feldman and H. Rapoport, 1603–1604.
Me
First 5 steps can be
done in one-pot, before
lunch:
1. LDA, PhMe, -78 ºC
2.
Tol
HO
O
OH
MeO2C
tBuOCl; then DBU (3 eq),
0 ºC, 20 min
(75% with one recycle)
O
S
Me
O
Me
-78 ºC to r.t.
TBSO
O
Me
O
O
3. vinyllithium (7 eq), 1 hr
4. HF/MeOH, 20 min
5. NaOMe, 0 ºC, 1.5 hr
(45% after chromatography)
Me
Me
O
O
O
Me
Me
Et
O
CO2Me
N
MeO
Total Synthesis of (±)-2-Desoxystemodinone. A Novel HydroxylAssisted, Intramolecular Ene Reaction. J.D. White and T.C Somers,
4424–4426.
OH
O
O
CO2Me
H OH
Me
N H
(–)-Vindoline
O
TBSO
Et
OCOMe
mechanism?
N
MeO
Me
O
S(O)Tol
N H
O
S(O)Tol
Me
Me
N
H Et
with vigor
HO
Me
N
MeO
Me
Me
S(O)Tol
OH
H
Me
Me
H
(Title withheld for your own good). P.J. Wagner and K. Nahm, 4404–4405.
(Title withheld for your own good). P.J. Wagner and K. Nahm, 6528–6530.
H
Me Me
Me
O
O
O
hv
mechanism?
O
H
Me
H
Me Me
"The pivotal role of the hydroxyl
substituent in this process was
verfied by its reductive removal..."
OH
CHO
PhMe, 110 ºC
16 h (94%)
H
Me
OH
OH
H
Me Me
JACS: 1987 A Year in Review
Baran Group Meeting
Palladium-Catalyzed Reactions in the Synthesis of 3- and 4-substituted
Indoles. 2. Total Synthesis of N-Acetal Methyl Ester of (±)-Clavicipitic
Acids. P.J. Harrington, L.S. Hegedus, and K.F. McDaniel, 4335–4336.
Br
1. Br2, hv, CCl4
2. PPh3
Me
Br
NO2 3. CH2O(g), Et3N
NHTs
OBz
OTMS
Me
O
SnCl4, -78 ºC
2. 3N HCl, r.t.
(98% overall)
N3
Me
CO2Me
PhMe, 110 ºC
2 hr (93%)
mechanism?
Ar
Ph
HClO4 (cat.)
5% Pd(OAc)2, NEt3
(60%)
N 2. I2
Ts
(97%)
N
Ts
N3
OMe
Br
I 1. Hg(OAc) ,
2
O
SEt
O
MeO
OMe
O
OH
N
OBz
MeO
Ph
O
OBz
H2N
O
O
SEt
O
Ar MeO
O
OH
Me
8% Pd(OAc)2, NEt3
P(o-tol)3 (83%)
Me
Me
O
O 1. EtS
NHAc
Br
N
Ts
Me Me
OBz
Ph
5% PdCl2(MeCN)2
benzoquinone
(80% over 3 steps)
Br
CO2Me
Ph
MeO
NO2
(80% overall)
NHAc
Total Synthesis of (±)-Mitomycins via Isomitomycin A. T. Fukuyama and
L. Yang, 7881–7882.
Br
1. Fe, AcOH
2. TsCl, py.
Dane Holte
Ac
N
O
40 ºC, 1 hr (87%)
N
Me
OMe
CO2Me
N
OMe
OH
NHAc
N
H
CO2Me
O
(±)-Clavicipitic Acid
N-Acetal Methyl Ester
N
Ts
O
OMe
H
N
O
Ac
N
MeO
CO2Me
NaBH4, hv
15% PdCl2(MeCN)2
(95%)
N
Ts
Na2CO3, -20 ºC
(74%)
Me
N
O
NH2
Al(OiPr)3, MeOH,
r.t. 2 d (91%)
mechanism?
O
OCONH2
R
OMe
N
Me
NH
O
R = OMe Mitomycin A
JACS: 1987 A Year in Review
Baran Group Meeting
Dane Holte
"Pagodane": The Efficient Synthesis of a Novel, Versatile Molecular Framework.
W. Fessner, G. Sedelmeier, P.R. Spurr, G. Rihs, and H. Prinzbach, 4626–4642.
Cl
Cl
Cl
O O
S
O
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
[4+2]
Cl
S Cl
Cl
Cl
Cl
O
Cl
Cl
Cl
Cl
PhMe, 110 ºC
Cl
H
Cl
H
Cl
-SO2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Li, tBuOH
85% overall
kg scale?!
Cl
Cl
Cl
Cl
Cl
Dytropic hydrogen transfer
O O
S
1.
O
O
Cl
O
O
O
254 nm hv
[4+2]
Pd/C (10 eq)
O
Cu2O, quinoline,
H2O, bipy.
1. B2H6, THF
2. NaOH, H2O2
150 ºC
3. CrO3, H2SO4
O
Na-K, tBuOH
Pagodane
(24% overall)
O
H
I
2. Pb(OAc)4,
CCl4, I2, hv
O
HO
O
OMe
OH
O
1. KOH, EtOH
I
2. Li, tBuOH
NaH
O
O
Cl
Cl
"an intimate mixture"
(ie. neat), 250 ºC,
sealed tube
[6+6]
O
[4+2]
H
H
Cl
hv, MeOH
Wolff rearr.
MeO2C
CO2Me
N2
O
AcOH; then
TsN3, NEt3
O
N2
See also, Platonic Hydrocarbons group meeting (Shenvi, 2006)
JACS: 1987 A Year in Review
Baran Group Meeting
Intramolecular Photocycloaddition. Cyclobutane Fragmentation: Total
Synthesis of (±)-Laurenene. M.T. Crimmins, and L.D. Gould, 6199–6200.
Me
Me
U filter,
>350 nm hv
Me
Me
O
Me
100 ºC
(87%)
Me
Me
O
Me
2. H2, Pd/C, EtOH
(80% overall)
Me
MeO
CO2Et
Me
H
H
Me
NaBH4,
CeCl3
Me
Me
H
Me
O
H
Me
H
Me
Me
H
Me
Me
R
R
O
O
OMe
H
Me
After asymmetric biaryl coupling,
there are 9 steps before closing
the 8-membered ring, with <10%
racimization.
O
Me
Me
MeO
O
O
MeO
H
OH
1. KH,
Bu3SnCH2I
Me
Me
H
2. nBuLi
(57%) Me
Me
mech?
various
alkylations
Me
OMe
OMe
O
MeO
OMe
(–)-Steganone
Synthesis of in-[34,10][7]Metacyclophane: Projection of an Aliphatic
Hydrogen toward the Center of an Aromatic Ring. R.A. Pascal, R.B.
Grossman, and D. Van Engen, 6878–6880.
Luche Me
(23%)
Me
N
MeO
N
Ph
O
MeO
(65%)
(7:1 mix. of diast.)
MeO
1. LiAlH4, Et2O
2. Swern Ox.
3. TsOH, PhH
(75% overall)
Me
Ph
OMe O
Me
Me
1. Na, NH3, -33 ºC
THF, reflux
MgBr
O
Me
OO
O
O
H
CO2Et
H
O
Me CO2Me
1. LiAlH4, Et2O
2. Swern Ox.
3. Ph3P=CHCO2Et
(89% overall)
Me
O
O
Me
O (27%)
An Asymmetric Synthesis of (–)-Steganone. Further Application of Chiral
Biaryl Synthesis. A. I. Meyers, J.R. Flisak, and R.A. Aitken, 5445–5452.
O
MeO2C
13 steps
Dane Holte
Me
Me
Me
Me
(±)-Laurenene
Crimmins, 6199–6200
1. TsCl, py.
2. LiEt3BH
(72% overall)
HO
JACS: 1987 A Year in Review
Baran Group Meeting
Comprehensive list of all total syntheses (*formal):
Me NC
HO H
Me
NH3
H
Me
CN
S
N
O
N
Me
CO2
H
Me
H
(+)-Thienamycin
Georg, 1129–1135
N
H
Me
O
O
HO
AcO
HO
AcO
HO
Me
Me
Me
Me
AcO
OH
MeO
Me
OH
OH
OH
O
Me
HO
Me
Me
O
Et
O
O
NH
O
OH
O
Et
Me
OH
OH
*Rifamycin S
Danishefsky, 862–867
Roush, 953–955
Me
MeO2C
Me
H
O
OH
CO2Me
Me
4-Methyl Juvenile Horomone
Ogura, 2853–2854
OH
OH
Me
H
Me
Me
Me
OH
Me
Me
Me
Me
Zincophorin
Danishefsky, 1572–1574
N
O
Me
H
Me
H
Et
OCOMe
CO2Me
H OH
Me
N
MeO
(±)-Bilobalide
Corey, 7534–7536
(–)-Vindoline
Rapoport, 1603–1604
HO2C
O
HN
O
H
N
Et
H
R = NH2 PDEI
R = Me PDEII
Magnus, 2711–2717
Boger, 2717–2727
Et
OH
HO
H NH3
Me
OH O
MeO
*Indanomycin
Danishefsky, 2082–2089
CO2
H
Acivicin
Whitney, 276–277
H
H
Me
Cl
N H
HN
MeO2C
Me
O
H
O
tBu
O
Aphidicolin
Holton, 1597–1600
OH
Et
N
Ph
O
O
Me
H
(±)-Cyanocycline A
Fukuyama, 1587–1589
O
HO
(+)-(9S)-Dihydroerythronolide
Stork, 1565–1567
O
O
OH
Me
O
N
Me
Me
O
Me
Me
OH
N
Me
OH
Me
OH
H
O
HO
OH
Me
O
O
O
H
CN
MeO
O
(+)-Phyllanthoside
Smith, 1269–1272
Smith, 1272–1274
CO2Me Et
HO
O
O
H
O
O
(±)-Catharanthine
Raucher, 442–446
7,20-Diisocyanoadociane
Corey, 287–289
Dane Holte
OH
O
Me
O
OH
OH
OH
OH
Amphoteronolide B, Amphotericin B
Nicolaou, 2205–2208
Nicolaou, 2208–2210
NIcolaou, 2821–2822
OH
O
O
CO2H
O
OH NH2
Me
OH
R
JACS: 1987 A Year in Review
Baran Group Meeting
Comprehensive list of all total syntheses (Cont'd):
MeO
O
N
MeO
HO
H
Me
OH
HO
O
HO
NH
OH
O
OH Me
Me
Me Me
Africanol
Paquette, 3025–3036
O
Me
OH
Me
H Me
OH
O
OH
O
O
Me
(±)-Grosshemin
Rigby, 3147–3149
H
(±)-Porantherine
Stevens, 4940–4948
O
O
O
O
OEt
OH
H
NH OH
NH2
O
MeO
OEt
HO
(–)-Specionin
Curran, 5280–5282
(+)-Actinobolin
Kozikowski, 5167–5175
O
MeO
O
O
H
O
Dactylol
Paquette, 3025–3036
Me
HO
d-(+)-Carbacyclin
Fuchs, 4755–4756
O
OH
H
HO
(±)-Cafestol
Corey, 4717–4718
H
Me
Me
N
C5H11
(–)-Punctatin A,
(+)-Punctatin D
(±)-3-Demethoxyerythratidinone *(+)-Showdomycin
Paquette, 3017–3024
Danishefsky, 917–918
O
Me
O
HO Me
O
HO2C
OH
OH
Me
Me
Dane Holte
OMe
(–)-Steganone
Meyers, 5446–5452
Me
Me
O
H
O
OH
Me
O
H
O
OMe
O
HO
OH
OH
O
H
Me
(±)-Granaticin
Yoshii, 3402–3408
Ac
N
HO2C
CO2H
O
(—)-N-Acetal-O-methylacosamine
Trost, 3792–3794
H
H
(±)-Clavicipitic Acid derivatives
Hegedus, 4335–4338
NH
Acromelic Acid A
Takano, 5523–5524
H
Me Me
(±)-2-Desoxystemodinone
White, 4424–4426
N
MeO
N
H
Me
HO
O
Me
O
d,l-Methynolide
Vedejs, 5878–5880
H
O
H
H
MeO2C
OH
Me
Et
OH
Me
Me
N
H
OH
HN
Me
O
HO
AcHN
CO2Me
O
CO2H
O
OMe
(±)- Reserpine
Martin, 6124–6134
N
H
O
Streptazolin
Overman, 6097–6107
Overman, 6017–6114
Overman, 6115–6118
N
OMe
OMe
OMe
O
N
H
H
H
H
MeO2C
(±)-α-Yohimbine
Martin, 6124–6134
OH
JACS: 1987 A Year in Review
Baran Group Meeting
Dane Holte
OMe
Comprehensive list of all total syntheses (Cont'd):
Me
O
H
H
Me
HO
O
O
O
(±)-Atractyligenin
Corey, 6187–6189
O
OH
O
O
O
Me
Me
Aplysiatoxin
Kishi, 6205–6207
H
O
Me
HO
HH
H
O
O
O
O
N
HN
NH2
N
N
Me
N
HO
HN
O
O
MeO
N
H
O
H
N
OH O
CC-1065
Kelly, 6837–6838
Me
O
O
O
OMe
Avermectin A1a
Danishefsky 8117–8119
Danishefsky 8119–8120
Me
OH
HN
O
Me
O
Me
Me
H
Me
Me
N
H
Me
Me
NH
OH
H
OH
O
OH
OH
Bu
OH
Me
O
Olivin
Roush, 7575–7577
Echinocandin D
Evans, 7151–7157
N
Pr
(+)-Pulmiliotoxin
(±)-Laurenene
OH Crimmins, 6199–6200 Schultz, 6493–6502
OMe OH
H
OH
N
H
H
NH
HO
*Ikarugamycin
Whitesell, 6403–6408
HN
Me
NH
Me
O
OH
O
(–)-5-Hexadecanolide
Taber, 7488–7494
Me
Me
H
O NH
O
O
O
HO2C
NH
H
Me
H
O
Calicimycin
Me
Boeckman, 7553–7555
O
Et
H Me
HO
R = OMe Mitomycin A
R = NH2 Mitomycin C
Fukuyama, 7881–7882
OH
O
N
O
O
OH
N
O
O
OMe
Me
Me
OMe
Me
OAc
OMe Br
O
O
O
OCONH2
R
O
O
*Forskolin
Ziegler, 8115–8116
Me
Me
Me
H
O
O
Me
NH
H
Me Me OH
CO2H
(+)-Gloesprone
Seebach, 6176–6177
Me
Me
OH
OH
C5H11
Me
O
OH
Me
HO
Me
Me
N
Et
H N
H
OMe
Et
N
H H
N
H H
(+)-Quebrachamine
Fuji, 7901–7903
(–)-Aspidospermidine
Fuji, 7901–7903
N
O
Et
(–)-Eburnamonine
Fuji, 7901–7903