JOC YEAR IN REVIEW 1972 - Scripps Research Institute · JOC YEAR IN REVIEW 1972 ALEXANDROS ZOGRAFOS...
23
JOC YEAR IN REVIEW 1972 ALEXANDROS ZOGRAFOS THE BARAN GROUP MEETING 08/20/2003
Transcript of JOC YEAR IN REVIEW 1972 - Scripps Research Institute · JOC YEAR IN REVIEW 1972 ALEXANDROS ZOGRAFOS...
JOC YEAR IN REVIEW 1972
ALEXANDROS ZOGRAFOS
THE BARAN GROUP MEETING08/20/2003
The difficult decisionSome statistics
!Number of articles 1225!!Full articles 480!More than 25 total synthesis! Isolation and characterization of 52
molecules!Several novel methods
Total synthesis
O
HO
OH
O
HO
Prostagladins
COOH
HOOC
HOOC
Cubane derivatives
HO
(-)-Patchouli alcohol
(-)-Seychellene
O
Jasmone
ON
OH
Dehydrojoubertiamine
O
O
O
O
O
HOH
Cinobufacin
O
OO
O
OH
OHHO
O
OH
H
H
Mirestrol
OHGuaiol
Total Synthesis of cis-JasmoneO
! Isolated from flower oils of Jasminum! Indispensable in the reproduction of jasmine
fragrance! Several preparations have been reported
First synthesis at 1952 by Harper! Two total synthesis in 1972.
Crombie, L.; Harper, S.; J. Chem Soc.; 1952, 869; Harper, S; Smith, J.; J. Chem. Soc.; 1955, 1512; Buchi, G.; Egger, B.; J. Org. Chem.; 1971, 36, 2021; Mc Murry, J.; Melton, J.; J. Am. Chem. Soc.; 1971, 93, 5309.
Two Efficient Methods for the Construction of cis-JasmoneBerkowitz, W.; J. Org. Chem., 1972, 37, 341; Grieco, P.; J. Org. Chem., 1972, 37, 2363.
O
Jasmone
ClCl
O
Cl
+Et3N, 00Chexanes
Cl
C
Cl
O
O
ClCl Zn,
Acetic acid
OH2O2Acetic acid
O O
Corey, E.; Tetr. Lett.,1970, 307.
DIBALToluene-780C
O OH
OHJonesReagent
ONaOH/H2O700C
O1.MeLi2.CrO3
O O
O
5150Cglass wool
O O
O
Cl
NaHBenzene
Berkowitz, W.;J. Org. Chem.1971, 36, 3787
-EtOH, CO
Ph3P=CHCH2CH3DMSO
cyclopropyloxopropanoate
HighlightsBaeyer-Villiger Ring Expansion
O H2O2acetic acid
O
O
O OH
OO O
O
H O O
A Thermal Two Carbon Ring-Expansion
O O
O
OC
O O
O
O O
O
H
Glasscatalysed
O O
O
OSiH H
OC
O+
EtOHSiHO
O
+ CO
-EtOH
Total Synthesis of Patchouli AlcoholHO
!A tricyclic sesquiterpene isolated from patchouli oil
!An important raw material for the composition of perfumes
!First total synthesis by Buchi at 1956
Buchi, G.; Erickson, R.; J. Am. Chem. Soc., 1956, 78, 1262; Buchi, G.; Erickson, R.; J. Am. Chem. Soc., 1961, 927; Buchi, G.; McLeod, W.; J. Am. Chem. Soc., 1962, 84, 3205; Buchi, G.; McLeod, W.; Padilla, O.; J. Am. Chem. Soc., 1964, 86, 4438.
A Synthetic Route to Racemic Patchouli AlcoholMirrington, R.; Schmalzl, K.; J. Org. Chem., 1972, 37, 2871
HO
(-)-Patchouli alcohol
+
O DielsAlder
O
O
O
OOH
O
O
O
O
O
O+
Both E and Zregioisomers
POClpyridine
AcClDMA
O
O
O
O
EtONa
Mirrington, R.;Tetr.Lett., 1969, 5017.
Li,NH3EtOH
OH
H+
OH
Ratio 4:1
TrClEt3NOTr
H1.B2H6, THF2.CrO3 pyridine
OTr
H
O
OTr
H
O
NaH, MeI
3 stepsI
H
O
Nasealed tube1000C
Danishefsky, D.; Chem.Commun., 1968, 1287.
BrZn
Highlights
O
O
OH
H H
OH
4 1
Li, NH3EtOH
O
O O
O
H
H
Proton attacks from the less hindered side
OH
O
O H+ O
Omaybe by carbocation
O
O
Baseelimination
AcCl
O
O
O
O
H:B
O
O
Both E and Zregioisomers
Assisted cleavage
Selective dehydration
Stereochemistry of the reduction
Synthesis Of Cubane Derivatives
HOOC
! Interesting molecular structure ! Original work by Eaton et al. at 1964 reporting
several derivatives of cubane skeleton! First synthesis of homocubane from 2-
cyclopentanone in less than 10% yield
A Facile Synthesis of HomocubanePaquette, L.; Ward, J.; J. Org. Chem., 1972, 37, 3569
HOOC
O
SeO2
H
OH
Jones Reagent
1.Br22.Et3N
OBr
hv
BrO
1.KOH
2.H3O
O
1.NBS, CCl42.Br2, pent-DCM
O
Br
Br
BrEt2NH, -200C
OBr
OBr
O
Brhv
O
Br1.KOH
2.H3O
O
BrHOOC
COOH
First synthesis of cubane derivatives
Favorskii type rearrangementSpontaneousdimerization
Eaton, P.; Cole, T.; J. Am. Chem. Soc., 1964, 86, 962
HighlightsSpontaneous cyclization of bromo-cyclopentanones
Favorskii type rearrangement
OBr
Br OO
Br
O
Br
O
Br OO
Br
O
Br
Br
Favorable intermediate
An intermolecular Diels-Alder Reaction
BrO
OHBr
OOH HOOC
-Br
Total Synthesis of Prostaglandins F1a and E1
OH
HO
O
OH
HO
Prostaglandin F1a
O
HO
O
OH
HO
Prostaglandin E1
! Prostaglandins are discovered by von Euler in 1932
! Carbocyclic oxygenated C-20 molecules are hormones that elicit an unusually diverse array of physiological response
! Several preparations have been reported
A New Method for the Preparation of ProstaglandinsSchaaf, T.; Corey, E.; J. Org. Chem., 1972, 37, 2921
O
HOOCH2Ph
O1.THP, TsOH2.DIBAL -780C
O
THPOOCH2Ph
OH OH
THPOOCH2Ph
O
OH
O
OHPh3P
DMSO, NaH
1.CH2N2, ether2.Ac2O, pyridine 500C3.H2, Pd/C 1atm 5%Acetic acid Ethanol
O
THPOOH
O
O
OCollinsReagent, DCM 00C
O
THPO
O
O
O
O
P(OMe)2
NaH, DME
O
THPO
O
O
O
O
O
NaBH4DME, 250C
O
THPO
O
O
O
HO
1.Acetic acid/H2O, 400C2.separation of epimers3.KOH, MeOH, THF, 250C
OH
HO
O
OH
HO
Prostaglandin F1a
O
HO
O
OH
HO
Prostaglandin E1
Corey, E.; J. Am. Chem. Soc., 1969, 91, 5675
Corey, E.; J. Am. Chem. Soc., 1968, 90, 3247
O
HighlightsSynthesis of Corey�s lactone
NaH, THF
BnOCH2Cl-550C
PhH2CO
Cu(BF4)2, 00C
CNCl
PhH2CO
CNCl
KOH, H2ODMSO
PhH2CO
O
mCPBANaHCO3DCM
O
PhH2CO
O
NaOH, H2O
CO2
HOO
HO OCH2Ph
KI3, NaHCO3H2O, 00C
OO
HO OCH2Ph
I
1.Ac2O, pyr.2.n-Bu3SnHAIBN, PhH
OO
AcO OCH2Ph
Novel Methods
! Thallium chemistry in organic synthesis! Novel etherification of alcohols! Palladium-Catalyzed Vinylic Hydrogen
Substitution (Heck reaction)
Novel Etherification of AlcoholsKashman Y.; J. Org. Chem., 1972, 37, 912
Dialkyl phosphites react with alcohols to give the correspondingether in the presence of catalytic amount of acid
O
HOP(OCH3)2
HO
R
R: C8H17
PH
OO
HOP(OCH3)2H+
O
RO:H
O POH
OH
ROH
+ O POH
OH
protonateddimethyl phospite -H+
ROCH3
Paladium-catalyzed Vinylic Hydrogen Substitution
Background before the discovery of Heck Reaction
RMX +H M'
M'XH
RR
+ HM'X
M: Hg, Sn, etc
example:HgOAc
+ Pd(OAc)2PdOAc
+ Hg(OAc)2
Easy to isolate
Transmetaletion
PdOAc HPdOAc
H
H+ +
H
HPdOAc
H
+ + +
HPdOAc HPdOAc β-elimination
Disadvantages
! There is often a problem obtaining the organomercury, lead or tin compounds
! Thick slurries of salts difficult to manipulate if the reaction is carried out catalytically in palladium
A New Method for the Arylation and Benzylation of Vinylic Hydrogen Heck R.; Nolley, J.; J. Org. Chem., 1972, 37, 2320
Mechanism of Heck Reaction
RX + Pd RPdX
RPdX +H
PdXH
R
HPdX
R�Use of a base is essential in order toneutralize the hydrogen halide from the reaction�Tolerate a number of functional groups�Iodides react rapidly. Benzyl halides are less reactive�Loss of stereochemistry. Both cis and trans products
Thalium Chemistry in Organic SynthesisBackground
! Thalium acetate was first described at 1903 by Meyer and Goldschmidt
! Among its applications are oxidative cleavage of cyclopropanes, the conversion of chalcones into isoflavones and the hydration of acetylenes
Year 1972
! Direct synthesis of allenic esters from β-ketoesters
! Oxidation of cyclohexanones to adipoins
A New Synthesis of Allenic EstersTaylor, E.; Robey, R.; McKillop, A.; J. Org. Chem., 1972, 37, 2797
O
R2
R1
R3
O
O R
R1, R2, R3=alkyl
H2N-NH2
NNH
R1
R2R3
O
TTNC C C
R1
R2
R3
OOMeOH
Mechanism
NNH
R1
R2R3
O HNNH
R1
R2R3
O
TTN
HNNH
R1
R2R3
O
HTl(NO3)2
-H2
HNNH
R1
R2R3
O
Tl(NO3)2TTNN
N
R1
R2R3
O
Tl(NO3)2
MeOH
C C CR1
R2
R3
OO
Oxidation of Cyclohexane to AdipoinsMcKillop, A.; Hund, J.; J. Org. Chem., 1972, 37, 3381
O OHHO OH
Tl YY
HO O
H+
O OH+HCOOH
OH-OHHO
OH
-H2O
OOH
McKillop, A. et al. J. Am. Chem. Soc., 1971, 93, 4919
