JACS Year in Review: 1989
Baran GM
1989 - Year of the Snake
(+)-Ophiobolin C, Kishi, 2735
"deep, say little and possess great wisdom"
- Random Facts: Nobel Prize Chemistry Sidney Altman, Thomas R. Cech
George H.W. Bush as 41st President of USA
Exxon Valdez oil spill
Soviet War in Afghan.
Romanian Revolution
THPO
N
H2N
N
S
N
OH
N
N
H2N
N
N
OMe H2N
(77%)
OtBuNC
N
N
N
2. LiBF4, MeCN
3. NaOAc, tBuOH
(89%)
Fiesselmann
NC
N
H2N
N
NH2
OMe
OMe
NH
SMe
S
Cl
NMe2
"Isolationofaverysmallamountof
this material from large quantities of
urine"and"Hewas,however,
rated by extreme difficulties in
obtaining sufficient amounts"
NH2
N
OtBu
N
N
H
H
more recent synthesis
Woerpel, JACS 2002,
124, 11342
NH2
OMe
S
OtBu
O
For comparison of 5-8-5 system:
see JOC 1985, 50, 3541;
JOC 1987, 52, 4634.
THPO
TMS
S
OtBu
NMe2
TBDPSO
NC
N
N
N
O
NMe2
TMS
OtBu
TBDPSO
OH
TBSO
3 steps
(52%)
CHO
I
SMe
S
1. xylene, THPO HO2C
230 oC
OBn
2. H+
(72%, 6:1) PO
PO
O
O
Brook
1. CH2N2
Claisen
2. LAH; 3. MsCl
TBS
R=(CH2)3OBn R
4. LAH; 5. H2/PtO2
(57%)
6. H2, Pd(OH)2
7. PvCl/pyr
8. TBAF
THPO
1. Swern
2.
TMS
OPv
OPv
Li
1. tBuONO
MeCN, CuBr2
2. NaSMe
(52%)
SMe
Peduncularine, Hiemstra, Speckamp, 2588
HO
HH
O
OH
CN 1.
HS
N
H
OHC
Total Syntheses (by page number)
(±)-Urothione, Taylor, Reiter, 285
O
SMe
NC
N
OH
HN
Klement Foo
TBDPSO
O
(85%)
HO
OTBS
HO
OPv
CrCl2, cat. NiCl2
DMSO/DMS, rt
H
OPv
TBDPSO
(73%, single d)
NHK
O
(±)-Ceroplastol I, Boeckman Jr., 2737
CO2H 6 steps
CO2H
(S)-malic acid
HO
EtO
O
N
iPr
1. HCO2H
2. NH3/MeOH
(87%)
HO
N
O
CH2OH
OEE
O
O
O
Past synthesis: Kato, JCS CC 1988, 354.
4 steps
MeO2C
H
OMOM
O
JOC 1980, 45, 752
6:1
Page 1
JACS Year in Review: 1989
Baran GM
OEE
MeO2C
O
O
H
H
OMOM
MeO2C
OMOM Na, NH3/THF
tBuOH; NaBrO3
(NH4)2Ce(NO3)6 cat.
then CrO3 acetone;
CH2N2 excess (45%)
CO2Me
KN(TMS)3
E
then LiI,
collidine, Δ
(76%)
Dieckman
O
H
O
(–)-Picrotoxin, Yoshikoshi, 3728
CHO
O
O
OO
OH
NBS OHC
O
(89%)
MeO2C
NaOMe
MeOH
(73%)
O
H
O
OH
2 steps
OMe
Klement Foo
1. MeLi
2. Ac2O, pyr
DMAP
(91%)
Br
Br
Other synthesis:
Corey, JACS 1979,
101, 5841
O
O
AcO
H
OMs
O Na[PhSeB(OEt3)]
EtOH
(92%)
AcO
NBS
(88%)
O
1. Zn(Cu)
NH4Cl (88%)
OAc
2. Jones
O
O
TL 1987, 28, 4293
OH
O
OAc
OAc
Br
(±)-Oxosilphiperfol-6-ene, Kakiuchi, 3707
AlCl3
(93%)
O
OTMS
Other syntheses: Paquette,
JACS 1984, 106, 6690;
Snider, JOC 1994, 59,
5419; Rawal, OL 2000, 2,
2711.
3 Steps
(63%)
MeO
AcO
O
O
1. H2O2, NaOH/MeOH
2. N2H4.H2O, AcOH
3. PCC (51% overall)
Wharton
a
O
O
O
4 steps
(32%)
O
4 steps
(76%)
O
Cargill
O
O in this paper
O
C4H9
(±)-silphiperfol-6-ene
O
Os2O4
OH
O pyr then
O
AcO
H2S
(86%)
O
Br
O
3 steps
Br
(–)-Perhydrohistrionicotoxin, Winkler, 4852
C5H11
C5H11
O
HN
HN
6 steps HN
O
OH
b
6 steps
O
OH
3 steps
OH
O
O
1. NaBH4
2. NaH
(60%)
C5H11
hv
HN
O
O (95%)
Br
Other syntheses:
Keck, JOC 1982, 47, 3590; Corey,
JACS 1975, 97, 430; Evans, JACS
1982, 104, 3695
(–)-picrotoxin
O
OO
O
O
(–)-picrotin
C5H11
HN
O
O
O
O
O
O
Page 2
JACS Year in Review: 1989
Baran GM
Pseudopterosins A & E, Corey, 5472
1. DIBAL-H
2. Ph3P=C(Me)SEt
3. Swern
4. HgCl2
5. NaOMe, MeOHO
(40%)
H
H
O
O
OSugar
H
H
KH-HMPA
TBSCl
(97%)
1. 2-butynal
TMSOTf
2. PCC
(61%) TBSO
KH
O
(70%)
O
1. (PhSe)2O,
(Me3Si)2NH
2. HClO4, H+
(56%)
H
H
O
OH
OH
(±)-Dactylol, Feldman, 6457
K
1.
O
OH
PhO2S
[6π+2π]
O
hv
(41%)
2. LiCH2SO2Ph
(31%)
OH
H2,
Pd/C
OH
HO
LAH
(73%)
(89%)
H
OMe OH
H
isolable
OH
O
O
OH
OH
NHAr
OMe OTBS
1. MeI
K
CO
2
3
O
O
2. H+
(63%)
OH Hoffmann
OH
O
NHAr
O
H H
(50%)
O
11:1
PhC(Me2)O2Li
1. 3.6N HCl
CO2Me
2. Bu3P,
HO
DEAD
(28-31%)
H
H
O
OH
OH
Pd2(dba)3
(allyl-O)2CO
Δ, 55%
∗
H
O
OH
E
H
O
O H
H
15% of cis-syn-cis
14% of regioisomer
Study towards:
Kinsella, JOC 1990,
55, 105.
O O
H
Salcomine,
O2, MeCN
(72%)
OH
OMe CHO
OH
MeOH
CaCO3
NO23 d, 95%
Bradsher
cycloaddition
Cl
BCl3 (77%)
(–)-Echinosporin, Smith III, 8039
H
O
O
O
HO
O
CONH2
O
O
H
O
H
H
O
OH
O2N
O
O
O
OH
O
H
O
H
O
OMe O
TL 1988, 29, 3423
H
N
OH
O
OH
O
HO
(–)-Cryptosporin, Gupta, Franck, 7668
OH O
OMe
Me
O
H
OH
Klement Foo
HO E
H
CONH2 SO3, pyr
DMSO
O
(46%)
OH
H
HO E
H H
NH4OH,
OH
MeOH
CONH2 (86%)
O
O
H
OH
OH
via fragmented diketone
Page 3
JACS Year in Review: 1989
Baran GM
(–)-Aspochalasin B, Trost, 8281
OH E
E
17 steps for required oxidation
O level and 3 more side chain Cs.
BHT,Δ
O
N
H
N
H
NHCbz
(33-40%)
H
N
H
OH
O
O
O
O
O
(Unexpected) Outcomes in Methodology
Sworin, 1815
O
OH
H
OH
O
N
H
RCM to the rescue!!!
Methodology: Invention and Study
2 steps
1. (EtO)2C=CHCO2Et,
PPTS,
OCO2Me
2. KOH; reflux; CH2N2,
O
OEt 3. BuLi-DIBAL-Hl; PCC
SO
Ph
2
4. [CH2=C(OEt)]CuLi;
O
ClCO2Me; (10%)
O SO2Ph
OH
Cl
O
[3,3]
Δ
Cl
Paquette, Schreiber, 2331
H
N
H
via:
H
Pd(PPh3)4
via syn π-allyl
dppp, reflux
Pd complex
(49%)
CH3CO3H,
K2CO3; PPTS
O
OEt (62%)
O SO2Ph
Klement Foo
BnNMe3F
O
N
H
O
O
SO2Ph
OH (53%)
H
OH
KHMDS
4 d (50%)
NP
OH
OMe
O
KH
(40%)
O
via:
H
O
H
OMe
ThD
single diastereomer
(±)-Pleuromutilin, Boeckman Jr., 8284
OTs
OH
1.Me2CuLi,
HMPA
2. (CH2=CH)MgBr
(80%)
O
O
O
O
OH
MeO
Hayashi, Ito, 3426
OH
KH Δ
(99%)
Anionic
Oxy-Cope
O
HB
Ar
H2O2
O
cat. [Rh(cod)2]BF4 NaOH
(+)-BINAP
Ar
OH
ee 82-96%
except at RT 57-76%
-complements normal hydroboration regioselectivity
-only applicable to Rh cat. with 3o phosphine L and net + charge on Rh
Page 4
JACS Year in Review: 1989
Baran GM
Trost, 4430 via: OPd+
Pd2(dba)3.CHCl3
PPh3,
O
AcO
Moore, 975
O
R1
O
TMS
Δ
R2
O
O
O
O
more hindered
Rozen, 8325
F2, MeCN
0 oC
H
Ph
R
R= alkyl, Ph
aldehydes
E/Z-olefins (at will)
ketones
1. BMS
R
O
2. MeOH
Ph
3. H2O2/OH
(50%)
N
H
Ph
R
1. 9-BBN
2. MeOH
Ph
Me
MeOH RH2N
Ph
H
B
Me
OMe
O
O
O
R
OEt
R
O
E
R2
O
R
Bn
R
H
O
Me
O
Me
OH O
O
O
MeO
Padwa, 6451
H
O Rh2OAc4
N
N
E
E
O
R
N2
O
R
If an R group
replaces H, the 5,5,5
system does not form
Few variations of alkyne
O
O
O
Isoarnebifuranone
Me
R
O
Bn
O
cis
H
elim.
B(OR)2
E
R1
O E
R
O
R2
O
O
Bn R
Bn R
R
O
R1
O
R1
E
R
MeO
R
(81%)
trans
elim.
OE
R2
R
R
R2
Selectivity between 5 or 6membered ring is dependent
on R. Radical stabilizing
groups favor cyclopentadione.
Electrophile E affects outcome
=>bicycle can form
In the next paper:
Ph
E selectivity:
O
R2N
R
N
H
H
H O 2
rotate Ph
H
B(OR)2 2 2 H
B(OR)2
R2N H
Ph
Me
Ph
Me
Z selectivity:
R2N
H
H
B
R1
R
R2
OE
Example
OH
(Interesting) Selectivity Issues in Methodology
O
R1
O
O
O
H
H
(80%)
Brown, 384
R
Klement Foo
O
nanaomycin D
O
O O
E
(<10%)
N
E
R
(90%)
H
O
E
N
N
E
H+
O
R
E
E
R
O
E
E
N
R
Page 5
O
JACS Year in Review: 1989
Baran GM
R1
R2
R3
ZnBr
Yamamoto, 366: Inverse polarity
Kanematsu, 5312
O
Klement Foo
tBuOK
tBuOH
Δ
0.5-1 h R
α
O
[4+2]
R1
2
R3
O
R1
O
ZnBr
[2+2]
R2
R3
R2
R3
[3,3]
R1
R
O
S-trans
"Counter-intuitive"-chemistry in Methodology:
R1
O
TMS
O
O
OMe
Anti-Bredt lactams
possible due to amide
tBuO
N ability to assume
Td geometry
Rh2OAc4
H
N
(50%)
H
O
R
O
OTMS
Cl
Other Methodology:
Bailey, 765
tBuLi
I -78 oC
Li
Li
NH
MeOH
I
2 steps
-unprecedented in 1989
-deoxygenated solvents needed
O
Schwartz, 3069
RO2C
HO
NH
N2
O
R1
CO2H
R2
O
O=VCl3 O
-2HCl
R1
-Limited substrates
-Stoichiometric in V
V
73-81%
60% for CO2
Cl
O
R2
Li
TMEDA
to RT
Li E+
O
O
TMSCl
O
Williams, 1073: "Anti-Bredt lactam"
1. Na/NH3
OH O
PPh3.
2. O3/Me2S HO2C
DEAD
then Jones
NHOMe
(85%)
(64%)
N
O
-Few examples of Nu: other alternatives are
geranyl zinc bromide and benzyl zinc bromide
-Electrophile is limited to D2O, I2, MeI, alkyliodides
TMSCl as E+:
O
R3
O
E+ R
O
ZnBr
O
R2
O
Ni cat. R
R2
R3
S-cis
Depends
on R1
R1
O
β
E
Δ
-CO2
O
Examples
R2
R1
R1
R2
Ph
73-95%
Page 6
JACS Year in Review: 1989
Baran GM
Brown, 1754
1. NaOtBu
∗
R
2. BrCH2CO2Et
1. NaOtBu
2. ClCH2CN
∗
R BR2
(9-BBN)
∗
R
∗
1. NaOtBu
R
2. BrCH2C(O)R'
Examples of R:
CN
Et
CO2Me
CO2Me
2. CH2N2
(81%)
-ortho-lithiation not suitable with methyl ester
-double ortho-lithiation not common
-not limited to aromatic systems
CONiPr
Et
CONEt2
1. CO2, Δ
E
xs. (TMP)2Mg
2. CH2N2
CONEt2
E
CONEt2
E
CONEt2
(87%)
-Buchwald Zr chemistry: Pages 776 and 2870 (see Maimone GM)
-Pd cat. cross-coupling: Negishi, 3089; 3336; 3454; 8018
-SmI2 promoted reductive couping: Molander, 8236
-TFDO oxidation: Curci, 6749
-Diels-Alder related: eg. Corey 5493
-Sharpless Dihydroxylation related
-Trost Pd-TMM related: eg. 7487.
-Nicolaou Brevetoxin B related: eg. 5321, 5330, 5335...
-Stryker's reagent-conjugate reduction, 8818.
-Aldol related
CONiPr
N
-possible on cubanes
E
Pearson, 6778
cf.
R
H
R
RO
Fe(CO)3
O
Nu
R
Nu
R
Nu
[InMo(CO)3]2
AgBF4
1. Li/NH3
2. conc HCl
Δ
1:3
-nucleophile has to
be soft. GR just
deprotonates
[Mo]
O
H
R
N
H
H
OH
O
OMe
H
E
O
OH
(±)-trichodermol,
Pearson, 1499
HO
H
N
N
O
PF6-
then
alkylation
Total Syntheses (not covered)
CONiPr
Fe(CO)3
O
NOPF6
NEt3
Methodologies (not covered)
CONiPr
RO
O
-Nucleophiles can be lithium enolates or Grignard reagents
-dienes in 7-membered rings shown
-symmetrical dienes shown only
-high yields for nucleophlic attack
Eaton, 8016
1. CO2
xs. (TMP)2Mg
CO2H air
KOH
Nu
H
R'
H
[Mo]
CO2Me
O
99% ee
CO2Me
[Mo]
[Mo]
CO2Et
Klement Foo
E
triquinocene,
Cook, 2169
E
N
N
H H
(+)-koumine,
Magnus, 786
PhO2S
3
H
O N
N
Pr
Pr
H
E
(±)-pumiliotoxin C,
OMe
Balasubramanian, 3363
Page 7
JACS Year in Review: 1989
Baran GM
Klement Foo
Total Syntheses (not covered) cont'd
OH
HO
NH
H
O
NH2
OH
OH
N
N
NH
Huperzine A,
Kozikowski, 4116
Et
OH O
Pancratistatin,
Danishefsky, 4829
O
O
Vallesamidine,
Heathcock, 1528
O
N
H
O
O
N
NH
N
N
H
O
(+)-croomine, Williams,
1923
Daphnilactone A,
Heathcock, 1530
(±)-Suaveoline,
Cook, 7504
and many more...
Interesting Structures
Large molecular bowl,
Pascal Jr., 6846
Cyclophane hosts,
Whitlock Jr., 692
[4]Radialene system,
Iyoda, 3761
Page 8