Baran Lab Group Meeting
2007/12/15
JOC Year-in-Review, 1984
Statistics for J. Or g. Chem. 1984, Volume 49, Issues 1-26:
1313 Papers
14 Herbert C. Brown
8 Albert Padwa
8 Leo A. Paquette
7 Dale L. Boger
7 George A. Olah
...
4 Samuel J. Danishefsky
1 Elias J. Corey
Problems of the Day:
Ph
1
CO2 Me
Me
Sensitizer
Me
O
Me2 N
Me
Me
CO2 Me
Me
Ph Me
CO 2Me
(Major)
Δ
3
?
HO
CO2Me
Ph
CO2Me
+
Me
Me
Sensitizer
Me
(Minor)
CO2 Me
Ph
hν
?
Me
Ph
MeO 2C
OMe
O
O
Me OH OH
Ph
2
O
O
Me
hν
Δ
Syntheses discussed:
Y oshihir o Ishihar a
Ph
Me Me
Me
Cl
5-epi -Desosamine
Cyanobacterin
O
Me
CH2OH
OH
H
Me
R1
4
Me
Me
R1
Mechanism and side product?
Alternatively:
H
HOH2 C Me
OR
H
N
5
?
H
ROH
O
O
5 % HClO4
N
H
hν
NO 2
(± )-β-Chamigrene
H
R2
O
HO
(± )-Aphidicolin
O
hν
NO2
H
H
H
R2
O
H
NO 2
THF
(55 %)
O
N
CH2OH
Perhydropyrido[2,1,6-de]quinolizines
(Disclaimer: The proposed mechanism is neither discussed in the paper nor in the references,
and thus the answer given is merely an opinion/suggestion.)
1
Baran Lab Group Meeting
2007/12/15
JOC Year-in-Review, 1984
Synthesis of 5-epi-Desosamine via a Stereoselective Intramolecular N-Sulfinyl
Diels-Alder Cycloaddition
S. W. Remiszewski, R. R. Whittle and S. M. Weinreb*
J. Org. Chem. 1984, 49, 3243-3244
Y oshihir o Ishihar a
Total Synthesis and X-Ray Structure Determination of Cyanobacterin
T. -T. Jong, P. G. Williard* and J. P. Porwoll
J. Org. Chem. 1984, 49, 735-736
O
Cl
Me
1) BuLi,
then iPrCHO
Me
NaOH
s
Ph 3P CH3
Br
BuLi (2 eq)
NaOCN, TFA
O
(80 %)
then
then
Me ,
CHO
CHO
OH
O
Me
Me
(57 %)
O
O
SOCl2
S
N
O
py, 0 °C
(80 %)
O
H
O
Cl
Cl
O
H
O
Me
O
2) 3, then
SiO2 Separation
(72 %; 2 steps; dr 4:1)
O
1) PhMgBr
2) Piperidine,
EtOH, reflux
(90 %; 2 steps)
HO
H H
N
O
(HCHO)n
cat. TsOH, Δ
H
Me
O
Me
O
OH
(68 %; 2 steps)
Me
Me
NMe2 OH
1) TFA
2) O 3/SiO 2,
then Zn, AcOH
(70 %; 2 steps)
O
OMe
6-endo-dig
(~100 %)
O
???
Hg2+
O
Cl
LiAlH4
OH
Cl
O
O
N
O
OH
1) LDA, TMSCl
then excess LDA
Me
Ag+; 5-exo-dig (90 %)
OH
O
OMe
O
O
Me2N
Me OH OH
5-epi-Desosamine
O
Cl
O
Me
Me
O
2) H2, Pd/C
3) NaOH
O
HO
O
H
O
1) BCl3
HO
(EtO) 2P CH2CO2 Et
2) CH2Br 2, NaF
O
N
1) NaH,
O
O
O
Me
S
OMe
3
NH2
MeO
Me
2) MnO2
OMe
OMe
O
OMe
HO
Cl
Cyanobacterin
2
Baran Lab Group Meeting
2007/12/15
JOC Year-in-Review, 1984
CH2 TMS
Total Synthesis of (±)-Aphidicolin and (±)-β-Chamigrene
R. E. Ireland,* W. C. Dow, J. D. Godfrey and S. Thaisrivongs
J. Org. Chem. 1984, 49, 1001-1013
H
CH2 TMS
Me
Me
CO2Me
hν, O2, sens.
O
O
O
H
H
O
16
Me
(84 %)
H
O
H
O
O
2) TsOH,
Me2C(OMe) 2
3) TBAF
(92 %; 3 steps)
H
CH2TMS
O
Me
O
H
Me
O
O
2) NH2Cl
(~25 %; 2 steps)
H
O
Me
Me
Me
O
H
O
hν, MeOH
hν, Et2 O NaOMe
CH2TMS
Me
H
16
2) Et3 N, (HCHO) n,
PhSH, EtOH
(70 %; 2 steps)
O
H
Me
H
H
H
O
TMS Me
H
Me
H
Li, NH3
then TMSCl
(90 %)
H
O
CH2SPh
Me
Me
O
O
CO 2Me
Me
O
H
1) KH, then TMSCl,
then Pd(OAc) 2
H
O
O
(±)-β-Chamigrene
H
O
O
Me
H
O
CH2TMS
Me
H
N2
2) Li, MeNH2
3) PPTS, acetone
(82 %; 3 steps)
O
O
Me
1) BuLi, then
OH Me2NP(O)Cl2
H
O
O
1) BuLi, then
isoamyl nitrite,
then HCl
H
OTBS 1) OsO4
Me
O
Me
O
H
H
150 °C
CH2TMS
Me
2) TBSCl
(94%; 2 steps)
O
Me
O
1) DIBAL
H
Me
O
Me
2) Ph3P=CH2
(95 %; 2 steps)
H
H
H
1) DIBAL
O
O
H
O
CH2TMS
O
O
Me
SiO 2
O
(96 %; dr 2.6:1)
CH2TMS
CO2Me
Me
O
O
Hydroquinone, Δ
O
H
Me
O
Me
Y oshihir o Ishihar a
CH2OH
OH
H
1) MeLi, then
HCHO (g),
then AcOH
2) L-Selectride
3) HCl
(49 %; 3 steps)
Me
H
(±)-Aphidicolin
H
HO
HOH2C
H
Me
3
Baran Lab Group Meeting
2007/12/15
JOC Year-in-Review, 1984
H
Stereo- and Regioselective Total Synthesis of the Hydropyrido[2,1,6-d e]quinolizine Ladybug Defensive Alkaloids
R. H. Mueller,* M. E. Thompson, R. M. DiPardo
J. Org. Chem. 1984, 49, 2217-2231
H
1) H+ , KCN
N
2) SO 3/H2SO 4
(80 %; 2 steps)
H
H
H
N
N
H
H
H
H
Me
Y oshihir o Ishihar a
Hg(OAc) 2, EDTA
N
NH2
H
(71 %)
N
O
Me
O
N
H
H
H
H
N
1) H2, Pd/C
NH
Me
H
H
H
N
N
N
N
2) POCl 3, py
(24 %; 2 steps) H
H
H
H
H
H2, Pd/C
N
(~50 %)
H
Me
Me
O
H
H2 , Pd/C
190 °C
(97 %)
H
H
NH
N
RuO2 , NaIO4
B
H
H
TsOH
(68 %)
CrO 3
(79 %)
H
(67 %)
(dr ~92:8 !)
N
Me
H
BH3
CN
O
H
H
NH2
H
H
(35-45 %)
O
ClNH-ODNP
B
O
H
H
10
then H2O2 ,
NaOH
(69%)
H
OH
H
H
10
H
H
Overall idea:
?
NH3 , H2 , Pd/C
(80 %)
Hg(OAc) 2, EDTA
N
H
H
(83 %)
N
H
N
N
N
OH
N
O
O
Me
4
Baran Lab Group Meeting
2007/12/15
JOC Year-in-Review, 1984
Y oshihir o Ishihar a
3) LiBH4 reduction of olefins in the presence of esters: J. Org. Chem. 1984, 49,
3891-3898; 4822-4827
Herbert C. Brown (Purdue U.)
1) One-carbon extension into a carboxylic acid: J. Or g. Chem. 1984, 49, 892-898
R3B
1) LiC(OMe)Cl2
R3C
R2 BOR'
OH
2) H2O 2, NaOH
1) LiC(OMe)Cl2
H3 C-CH2 -(CH2 )9-CO2Et
R
R
J. Am. Chem. Soc. 1975, 95, 6876-6877
J. Am. Chem. Soc. 1971, 93, 2070-2071
H3C-CH2 -(CH2 )9 -CH2 OH
Slow reacti on
2) H2 O2, NaOH
O
2) H2 O2, NaOH
1) LiBH4 (2 eq)
H2C=CH-(CH2) 9-CO2 Et
1) LiBH4 (3 eq)
HO-CH2-CH2-(CH2) 9-CH2OH Fast reacti on
2) H2 O2, NaOH
Analogous reaction was unsuccessful with bis-boronic esters:
RB(OR')2
×
R
1) LiC(OMe)Cl2
RB(SR')2
O
2) H2 O2, NaOH
HO
Does not for m
via a boron-ate complex:
R'S
B
O
RB(SR')2
CCl2
R
Olefin-assisted ester reduction:
R1
H
2) H2 O2, NaOH HO
R2
B
HH
OR'
Deliberately add an ester to reduce olefins:
Also:
SR' Cl
Li
1) LiCCl3 , THF
H
O
R
1) LiCCl 3, THF
2) H2O, NaOH, Δ
2) Enantioselective allylation: J. Org. Chem. 1984, 49, 4089-4091
R
H
SR'
1) LiBH4 (3 eq),
EtOAc (1 eq) R
R
SR'
R
OH
2) H2 O2, NaOH
1) LiBH4 (3 eq),
EtOAc (1 eq) R
R
1) LiBH4 (3 eq),
EtOAc (1 eq) R
O
2) H2O2 , NaOH
I
2) I2 , NaOH
Me
Me
B
1) BH2Cl
Me
2)
Me
Me
MgBr
Me
β -carene
Me
4) Stereoselective cyclic ketone reductions: J. Org. Chem. 1984, 49, 2073-2074
Me
Me
9-BBN-H
HO
B
O
H
KH
K
B
O
B-Allyldiisocaranylborane
OH
RCHO
(72-80 %;
86-99 % ee)
O
Me
R
[H]
OH
[H]
(99:1 dr)
Me
Often better selectivities
than Selectrides!
5
Baran Lab Group Meeting
2007/12/15
JOC Year-in-Review, 1984
Y oshihir o Ishihar a
Leo A. Paquette (Ohio State U.)
Albert Padwa (Emory U.)
1) Methylene ketene equivalents in [2+2] cycloadditions: J. Or g. Chem. 1984, 49,
1317-1319
Generation of azomethine ylides from amides: J. Or g. Chem. 1984, 49, 3314-3322
O
"H C C
2
R
C O"
R
O
H2C
Cl
1) SOCl 2
C
H2 C
OH
2) NCS, SOCl2
O
H2C
Base
Cl
C
O
R
TMS
R
TMS
N
O
O
Vedejs J. Am. Chem. Soc. 1979,
101, 6452-6454
R
R'
Me3 O BF4
N
R'
CH2 N2
R'
R'
R
Huisgen J. Am. Chem. Soc. 1967,
89, 1753-1755
EWG
CsF
N
R
R'
TMS
N
EWG
R
TBAF
Cl
EWG
R'
R'
C O
H2 C
TMS
R
EWG
Cl
CH C
TMS
O
R
Δ
N
R
TMS
R'
CsF
N
R
OMe TMS
N
OMe
O
R
Cl
R
TBAF
Dale L. Boger (U. of Kansas)
TMS
R'
R'
Studies in pyrrole synthesis using tetrazines: J. Or g. Chem. 1984 , 49, 4405-4409
N
2) Trimethylsilyl cyclopropanes in synthesis: J. Org. Chem. 1984, 49, 3604-3609;
3610-3617; 3618-3621
TMS
Br
1) Mg
2) CH2 O
TMS
CH2 OH
CH2I2
TMS
EtZnI
CH2OH
N
R
N
N
R'
N
R
EDG
N
E
E
E
N
N
R
[Si]
Y
1) BuLi
SPh
SPh 2) TBSCl
TBS
Li
SPh Naphthalene
TMS
Y = -CH2Br,
-CH2 SR,
-P(O)R2 ,
etc.
R'
E = Ester
R'
N
N
H
N
1) Zn, AcOH
N
2) NaOH, Δ
R
R'
NH
R'
H
E
N
R
N
N
6
Baran Lab Group Meeting
2007/12/15
JOC Year-in-Review, 1984
Cycloaddition Reactions of Strained Ring Systems. Photochemistry of 1Phenyl-2-carbomethoxy-3,3-dimethylcyclopropene
A. Padwa* and G. D. Kennedy
J. Org. Chem. 1984, 49, 4344-4352
Me
O
Me2C
Ph
N2
N
Me
OMe
Me
N
Ph
+
CO2Me
Electronically excited triplet state generation via sensitized photolysis:
Ph
N
MeO2 C
1
CO 2Me
Me
Me
Sensitizer
hν
Me
hν
Me
Me
No sensitizer
Me
Me
Ph
•
Ph
+
Me
Me
CO 2Me
+
CO2Me
CO2Me
(30 %)
(49 %)
Ph
(20%)
Δ
2
O
NO2
H
Me
Ph
CO2Me
b
a
a breaks
C
H2
Me
MeO2 C
b breaks
Me
C
H2
-CO2 Me migration?
Ph migration
C-H insertion
AlCl3
(95 %)
Ph
(Minor)
CO2 Me
Ph
Me
Me Me
Me
H2O, Δ
(55 %)
NaOH
(68 %)
O
OH
K2 CO 3
O
NaBH4
R1
R1
O
NO 2
R2
O
R2
H+
NO2
NO2
4
Deprotection
involves light;
Mechanism?
C-H insertion
Me
Ph
Me
CO2Me
•
Me
CO 2Me
Me
Ph
Sensitizer
NO2
True wonders:
Me
CO2Me
Me
MeO 2C
Br
OH
Me
Ph
O
Ph
H
CO2Me
+
hν
?
Me
Antibacterial Benzisoxazolones. An Unusual Rearrangement Product from oNitrostyrene Oxide en Route to the Photolabile Carbonyl Protecting Group (oNitrophenyl)ethylene glycol
W. Wierenga,* A. W. Harrison, B. R. Evans and C. G. Chidester
J. Org. Chem. 1984, 49, 438-442
Mechanism: Excited singlet, generates a vinyl carbene
CO 2Me
Me
3
Br2
Ph
Me
Ph
Ph Me
CO 2Me
(Major)
?
Me
Electronically excited singlet state generation via direct photolysis:
CO2Me
Ph
CO2Me
(Pyrex-filtered)
Ph
Me
CO2 Me
Ph
Δ
Ph
Me
hν
N
Me
Y oshihir o Ishihar a
CO2 Me
Ph
O
KOH, dioxane
OH 18-crown-6
NO2
(73 %)
5
?
O
5 % HClO 4
NO2
THF
(55 %)
O
N
CH2OH
7