Baran Group Meeting
JACS Year in Review: 1993
Select Natural Products Isolated
Volume 115
12642 Pages
2323 Papers
~ 70 Total Synthesis Papers
OH
H
O
O
H
H
H
H
H
O
H
H
H H
O
O
O
H
George A. Olah 7 (0)
Larry E. Overman 6 (6)
E. J. Corey 6 (3)
Leo A. Paquette 5 (3)
Richard A. Lerner 5 (0)
Paul A. Grieco 4 (3)
Amos B. Smith III 4 (1)
K. Barry Sharpless 4 (0)
N
N
OH N
H
N
N
Cl
H2N
OH
Gambierol
Yasumoto, 361
Also see Maitotoxin
Yasumoto, 2060
HO
H2N
HN
Nobel Prize in Chemistry awarded to Kary B. Mullis and Michael
Smith for "contributions to the development of methods within DNAbased chemistry", with half to Dr. Kary B. Mullis, La Jolla, California,
U.S.A., for "his invention of the polymerase chain reaction (PCR)
method", and half to Professor Michael Smith, University of British
Columbia, Vancouver, Canada, for "his fundamental contributions to
the establishment of oligonucleotide-based, site-directed
mutagenesis and its development for protein studies".
O
O H
HO
Publication Record:
Arnold L. Rheingold 19 (0)
Stuart L. Schreiber 11 (4)
K. C. Nicolaou 9 (6)
Barry M. Trost 9 (1)
Ken N. Houk 9 (0)
Dale L. Boger 8 (7)
Sam Danishefsky 8 (5)
Robert H. Grubbs 7 (0)
Brandon Rosen
O
O
O
O
O
H
O
H
NH2
OSugar
Palau'amine (original structure)
Scheuer, 3376
See: ACIE 2007, 2320
OH
Polycavernoside A
Yasumoto, 1147
O
OH
O
OH
OH
O
OH
OH
HO
OH
H
Most Cited Paper is "Synthesis and Characterization of Nearly
Monodisperse CdE (E = S, Se, Te) Semiconductor Nanocrystallites"
with 4341 citations
N
O
CO2Me
Xanthoquinodins
Omura, 8558
N
O
HO
CO2H
O
O
HN
NH
O
Papers with 0 Citations: 17
HO
Xesticyclamine A (original structure)
Crews, 10436
See: Tet. Lett. 1994, 4719
Balanol
Kulanthaivel and Clardy, 6452
O
Events of Note:
Bill Clinton becomes POTUS (January 20)
ATF begins siege of Branch Davidian in Waco, TX (February 28)
Janet Reno becomes first female Attorney General (March 11)
University of Michigan loses to UNC in NCAA Championship (April 5)
Andrew Wiles presents proof of Fermat's Last Theorem (June 24)
NASA loses contact with Mars Observer (August 21)
Oslo Accords signed in Washington, DC (September 13)
Benazir Bhutto is first elected woman in Pakistan (October 19)
Maastricht Treaty takes effect (November 1)
NAFTA signed into law (December 8)
MeS
HO
OH
O
OH
OH
OH
OH
O
O
OH
OH
OMe O
OH
O
OH
OH
OH
OH
OH
OH
Quinolidomicin A1
Seto, 3014
OH
Page 1
JACS Year in Review: 1993
Baran Group Meeting
Total Syntheses Covered
H
Brandon Rosen
Methodologies Covered
OH
OH
O
O
H
HO
OH
H
O
O
H
Muscone
Oppolzer, 1593
OH
H
HO2C
Miroestrol
Corey, 9327
Syntheses and Activities of New Single-Component, Ruthenium-Based
Olefin Metathesis Catalysts
Grubbs, 9858
531 Citations
OBz
Scopadulcic Acid B
Overman, 2042
H
N
O
O
OH
N
OMe O
H
H
O
H
O
OH
O
H
Magellanine
Overman, 2992
Paquette, 4377
OMe
O
OH
Asymmetric Alkene Aziridinations with Readily Available Chiral DiimineBased Catalysts
Jacobsen, 5326
395 Citations
OMe
OH
O
HO
H
OH
Rapamycin
Nicolaou, 4419
Schreiber, 7906
Danishefsky, 9345
CO2Me
O
N
O
H
HO
H
H
O
O
O
O
Bruceantin
Grieco, 5841
O
O
Porantheridine
Comins, 8851
H
Preparation and use of C2-Symmetric Bis(phospholanes): Production of
Amino Acid Derivatives via Highly Enantioselective Hydrogenation
Reactions
Burk, 10125
528 Citations
Catalytic Ring-Closing Metathesis of Functionalized Dienes by a
Ruthenium Carbene Complex
Grubbs, 9856
430 Citations
O
H
1-Hydroxy-7-azabenzotriazole. An Efficient Peptide Coupling Additive
Carpino, 4397
928 Citations
H
Bis(oxazoline)-Copper Complexes as Chiral Catalysts for the
Enantioselective Aziridination of Olefins
Evans, 5328
385 Citations
Catalytic Asymmetric Allylation of Aldehydes
Keck, 8467
357 Citations
N
7,8-Epoxy-4-basmen-6-one
Myers, 7926
H
N
O
H
H
O
Strychnine
Overman, 9293
H
H
HO
OH
Clavularane
Williams, 11654
Page 2
JACS Year in Review: 1993
Baran Group Meeting
Miroestrol
Corey, 9327
Scopadulcic Acid B
Overman, 2042
CHO 1. Dabco,
acrylonitrile
MeO
OH
CO2H
SnBu3
7 steps
I
I
2. NaOH, ∆
77%
MeO
O
TIPSO
CHO
1. KSF clay
I
H
OH
80-85% yield
10-14 g scale
H
iBu2AlCl
H
O
O
HO2C
2. Add to Et2Zn,
1% (+)-DAIB
75%
O
HO
N
Et
L
H
OBz
Magellanine
Overman, 2992
O
Zn
75% yield
92% e.e
H
H
LiCH(SMe)2, 0 °C
O
Me2N
HO
O
"...the best illustration to date of the power
of intramolecular Heck cyclizations to solve
formidable problems in complex molecule
synthesis."
Scopadulcic Acid B
1. Cy2BH, 0 °C
H
O
H
Zn
5 steps
O
OTIPS
Et
10
6 steps
O
Muscone
Oppolzer, 1593
O
H
HO
OH
76%
TIPSO
OH
Miroestrol
OMe
H
TIPSO
3 steps
O
H
NC
4 steps
OH
O
OH
O
OMe
OTIPS
OH
H
3 steps, then
Pd(OAc)2, PPh3
MeCN, 80 °C
O
Pd(PPh3)4
80%
HO
OTBS
Mechanism?
Br
Br
OMe
H
O
OH
MeO OMe
O
2. PhH, ∆;
PPTS, rt
99%
OTBS
5 steps
2. PhI(OAc)2
59%
Br
1. TMSOTf, 0 °C
OTIPS
O
O
O
6 steps
O
+
H
Brandon Rosen
Name Reaction?
(+)-DAIB
H
5 steps
O
then Cu(OTf)2,
(iPr)2NEt, 50 °C
70%
MeS
H
CH(OMe)2
Mechanism?
Et2Zn, ClCH2I
91%
TESO
SnCl4, -78 °C
57%
Name?
Bn
O
N
HO
N
H
1. Swern
2. Li/NH3, -78 °C
82%
4 steps
O
H
H
H
H
1. OsO4, NaIO4
O
H
OH
H
OMe
O
H
2. BnNH2, NaBH3CN
60%
H
OMe
H
Muscone
H
Magellanine
H
Page 3
JACS Year in Review: 1993
Baran Group Meeting
Brandon Rosen
Magellanine
Paquette, 4377
O
H
H
SnBu3
1. MsCl, Et3N
S
OEt
2.
HO
S
HO
MeO2C
O
EtO
O
H
Bu3Sn
CN
9 steps
S
H
OMOM
H S
CO2Et
(iPr)2NEt
Pd(MeCN)2Cl2
0.003 M
MOMO
H
H
O
O
OH
N
OMe O
H
CO2Et
H
28%
30% rsm
30% iodostannane
OH
O
2. NaH, MeI
O
N
O
H
H
H
H
H
OH
O
OH
O
OMe
OH
Rapamycin
H
OH
OMOM
MOMO
H
O
OMe
H
6 steps
O
OMe
OMe
N
O
I
H
N
H
I
O
O
OH
OMe O
O
1. NaBH4, CoCl2
O
H
Magellanine
4 steps
70%
Rapamycin
Nicolaou, 4419
TMS
HO
I
O
O
OH
Ph
I
O
I
OPMB
N
PMBO
O
TIPSO
OH
OMe OTIPS
OH
O
CHO
N
H
O
OPMB
I
OTBS O
Ph
O
N
HN
CO2H
H
OTES OTIPS
OMe
OTBDPS
N
OMe O
O
OPMB
OMe
OH
HO
O
I
OTESO
H
HOBt, DIPC
I
95%
I
H
O
O
OTES OTIPS
O
O
OMe
OMe
OMe
H
OMe
OTBDPS
TES
OTBDPS
See: J. Chem. Soc. Chem. Commun. 1993, 617 and 619
and Classics in Total Synthesis I, Chapter 31.
Page 4
JACS Year in Review: 1993
Baran Group Meeting
Brandon Rosen
Bruceantin
Grieco, 5841
TBDMS
OTDMS
O
O
CO2Me
6 steps
H
O
H
O
OH
O
O
CO2Me
1. NBS
OH
O
CO2Me
2. DMF, ∆
78%
H
H
O
O
OH
N
OMe O
CO2Me
H
3 steps
O
O
30%
O
H
OH
O
O
O
OMe
PMBO
O
MOMO
MOM
O
1. OsO4
2.
OH
I+ O
O
O
F3C CF3
MOM
O
MOMO
O
CO2Me
H
O
H
6 steps
H
OAloc
O
H
H
OTBS
4 steps
OTBS
40%
BocN
CO2Me
OMe
O
H
HO
H
H
O
OTIPS
OMe
O
OH
O
OMe
Rapamycin
O
H
O
O
O
O
7 steps
O
H
O
MOMO
H
H
HO
OH
O
CO2Me
H
ODEIPS
OH
OMe
MOM
N
OMe O
H
O
9 steps
OAloc
TBSO
O
O
OTBSOMe
PMBO
ODEIPS
H
OAloc
O
O
H
MeO
O
OMe
OMe
OTIPS
Bruceantin
5 steps
Rapamycin
Schreiber, 7906
Name reaction?
R
R
BocN
OTBS PMBO
ODEIPS
SO2Ph
OH
H
OMe
3 steps
OTBS PMBO
ODEIPS
O
OH
OHC
H
OMe
See: JOC 1992, 57, 7906.
OTIPS
OMe
O
H
Sm
BocN
O
BocN
L
H
SmI2
95%
OMe
O
42%
H
OTBS PMBO
ODEIPS
OH
O
O
H
OMe
OTIPS
OMe
OTIPS
Page 5
JACS Year in Review: 1993
Baran Group Meeting
7,8-Epoxy-4-basmen-6-one
Myers, 7926
Strychnine
Overman, 9293
O
CO2Me
O
(EtO)2P
H
3 steps
3 steps
H
85%
OH
Brandon Rosen
Cl
CO2Et
H
OH
40%
7 steps
1. MeOCOCl
O
AcO
2. tBuOCH2COCH2CO2Et
Pd2(dba)3, PPh3
88%
AcO
OtBu
6 steps
N
OTIPS
O
O
11 steps
H
H
H
OTIPS
Pd2(dba)3, Ph3As
CO, LiCl, NMP
80%
OtBu
O
51%
O
N
I
R2N
O
hυ
H
O
3 steps
F3C
N
Me3Sn
OtBu
H
Mechanism?
OtBu
7,8-Epoxy-4-basmen-6-one
NHTFA
(CH2O)n,
Na2SO4
O
NaH, PhH
Porantheridine
Comins, 8851
R2N
NH
then KOH, EtOH/H2O
OtBu
98%
HO
O
OMe
Ph
N+
O
Cl-
TIPS
89% yield
84% e.e
O
O
5 steps
N
N
Aux*
O
O
O
O
1. Zn, H2SO4
2. Na2CO3
O
Porantheridine
1. H2, Pd/C
2. KOH, EtOH
O
O
O
N
DIBAL, -78 °C
N
H H
O
76%
CO2Me
O
O
OH
N
OtBu
O
N
N
O
N
OH
OTf
N
H
N
2. HCl, MeOH, ∆
70%
CO2Me
2. Comins'
Reagent
NTf2
Comins' Reagent
OH
1. LDA, then NCCO2Me
N
H
2. NaOMe
80%
1. LDA
N
1. TsOH
N
N
O
O
Cl
N
Mechanism?
O
OZnCl
TIPS
NR2
O
HO
H
OH
H
N
Ac2O, NaOAc, HOAc
65%
N
H H
HO
N
O
O
H
O
O
H
Strychnine
Page 6
JACS Year in Review: 1993
Baran Group Meeting
Brandon Rosen
Rapamycin
Danishefsky, 9345
OTBS
OTBS
OH
CHO
OMe
OMe Ph(O)S
O
O
H
N
LDA, THF, -78 °C
Ph
S
O
O
H
H
O
O
OH
H
7 steps
OtBu
2. TiCl3(OiPr)
O
O
N
1. DMP
N
OMe O
57%
O
O
O
O
3. HF•pyr
H
OH
OMe
OtBu
OMe
8%
OMe
O
OTIPS
OMe
See: J. Org. Chem. 1991, 56, 5826 and 5834.
H
O
O
OH
N
OMe O
H
O
O
O
H
OMe
OH
O
OH
OMe
Harrison, D. E. et. al. Nature, 460, 392 - 396 (2009).
Rapamycin
Clavularane
Williams, 11654
O
HO
7 steps
CO2H
TBSO
5 steps
10 steps
H
H
H
HO
OH
HO
then aq. HF
96%
H
H
-78 °C
38% (+ isomers)
HO
OH
3 steps
O
H
2. NaHMDS,
then H+, then NaOH
82%
NC
H
CSA
OH
1. EtOCH=CH2
TMSCN, 18-crown-6, KCN
OHC
HO
MEMO
Cl
Cl
TBSO
O
O
H
Clavularane
Page 7
JACS Year in Review: 1993
Baran Group Meeting
1-Hydroxy-7-azabenzotriazole. An Efficient Peptide Coupling Additive
Carpino, 4397
N
"Initial examination of [HOAt] was inspired by the consideration
that it incorporates within a single molecule both key elements of a
1:1 mixture of HOBt and a tertiary amine which is of greater
catalytic activity than HOBt itself in couplings involving esters."
N
N
N
N
N
"When BOC-Aib-OH is coupled to H-Aib-OMe in the presence of
HOBt, reaction is incomplete after 24 h (ca. 35% of the HOBt ester
remains unreacted), whereas with HOAt a theoretical yield of the
dipeptide is obtained."
N
OH
OH
HOBt
HOAt
Brandon Rosen
Catalytic Ring-Closing Metathesis of Functionalized Dienes by a
Ruthenium Carbene Complex
Grubbs, 9856
Ph
O
Ph
PCy3
Cl
Ru
Cl
Cl
Ph
PCy3
Cl
Boc
N
O
93%
Ph
Cl
Cl
Cl
2 PR3
PPh3
Ru
Ph
O
PR3
Ru
NC
NC
Ph
Cl
Cl
PR3
Ru
Ph
Preparation and use of C2-Symmetric Bis(phospholanes): Production of
Amino Acid Derivatives via Highly Enantioselective Hydrogenation
Reactions
Burk, 10125
R
R
P
OH
R
R
NHC(O)R'
H2
R
Cl
Cl
CO2R''
NHC(O)R'
Cl
PhI=NTs, CuOTf
CO2Ph
Ph
O
"...no single asymmetric
hydrogenation catalyst has yet been
developed and shown to provide
directly a wide range of amino acid
derivatives with very high
enantioselectivies (> 99% ee)."
Ph
75% yield
> 98% ee
Ts
N H
Ph
H
O
CO2Ph
67% yield
97% ee
N
Ph
Catalytic Asymmetric Allylation of Aldehydes
Keck, 8467
R = Me, Et, n-Pr, i-Pr
DuPHOS Ligands
cat*
N
N
P
2 steps
N
Bis(oxazoline)-Copper Complexes as Chiral Catalysts for the
Enantioselective Aziridination of Olefins
Evans, 5328
R
CO2R''
NTs
Cl
"Complexes 2a,b represent the first examples of a new generation of robust, well-defined, singlecomponent catalysts for the metathesis of acyclic olefin. Even with the present level of activity,
the remarkable functional tolerance of 2a,b makes these catalysts very attractive for the
synthesis of a variety of useful substrates."
R
O
PhI=NTs, CuOTf
Ph
PR3
R = Cy or iPr
R3P
OH
Boc
N
+
PPh3
R
Ph
PCy3
Asymmetric Alkene Aziridinations with Readily Available Chiral
Diimine-Based Catalysts
Jacobsen, 5326
Ph
Cl
Ru
88 - 93%
air, undistilled solvent
"Again in this case the use of HOAt or HATU lowers the extent of
racemization to less than 1-2%."
Syntheses and Activities of New Single-Component, Ruthenium-Based
Olefin Metathesis Catalysts
Grubbs, 9858
PCy3
O
Ph
OH
1. 10 mol% BINOL/Ti(Oi-Pr)4
H
2. allyltributylstannane
Ph
98% yield
92% ee
> 99% ee
Page 8
JACS Year in Review: 1993
Baran Group Meeting
Additional Syntheses Not Covered Today
HO
O
Additional Syntheses Not Covered Today
OH
N
H
O
O
N
H
OH
Muamvatin
Paterson, 1608
N
OH
O
O
O
OH
N
Br
OH
Dehydrotubifoline
Rawal, 3030
Paeoniflorigenin
Corey, 8871
OH
OH
NCS
OH
OH
Mycoticin A
Schreiber, 3360
O
NH
NH
Hapalindole Q
Albizati, 3499
AcHN
CO2H HO
O
S
i-Pr
O
N
O
NMe
N
N
H
CO2Me
Pseudotabersonine
Grieco, 1164
H
O
O
N
H
OH
H
H
Paraherquamide B
Williams, 9323
OH
11
Cl
O
O
O
HO
H
O
H
OH
O
Erythrodiol
Corey, 8871
OH
OH
H
Isolaurepinnacin
Overman, 9305
HO
OH
O
HO
H
OH
Echitamidine
Bonjoch/Bosch, 2064
O
BzO
O
HO
HO
CO2Me
Brandon Rosen
H
O
N
O
O
10
O
Lactacystin
Omura/Smith, 5302
Solamin
Keinan, 4891
HN
O
O
O
O
S
N
MeHN
ON
S
OMe
OMe
Dynemicin A Methyl Ester
Schreiber, 10378
N
N
H
S+
H
N
O
O
MeO
OH
Lankacidin C
Kende, 9842
S
O
N
MeO2C
O
HO
O
MeO
1-Deoxylycorine
Schultz, 7904
HO
S
HO
N
S
N
O
OH
HO
O
O
O
H
O
H
Tantazole B
Fukuyama, 8449
HO
Leinamycin
Fukuyama, 8451
Morphine
Overman, 11028
OCONH2
OH
N
S
OH
OH
Discodermolide
Schreiber, 12621
Page 9