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Journal of Organic Chemistry: 1974
A Brief Synopsis
-Mike DeMartino-Group Meeting: 10-29-2003
Overview
• Some general observations
• The “prime-time-players”…what were theydoing in JOC? (Thanks Dick Vitale, baby!)
• Some selected total syntheses
General Observations fromTitle Perusing
• Heterocyclic chemistry prevalent• Surprisingly little Tin/Palladium chemistry• Lots of Rearrangements:
– Thermal– Photolytic– Acid Catalyzed
• 13C spectroscopy a new thing in organic chemistry?!?• Not many total syntheses, mostly steroids• Sulfur chemistry very prevalent• A lot of degradation chemistry
E.J. Corey (Harvard)-Preparation of an optically active intermediate for the prostaglandins (p. 356)
OO
-A racemic route had previously been developed from (+/–) 1 to (+/–)-11-deoxyprostaglandins
1O
O
1
OH
OH
OLiOH (–)-1-(1naphthyl)ethylamine
3 recrystalizations
OH
OH
O• (–)-1-(1naphthyl)ethylamine
1. Removal of salt
2. 10 N HCl1
-g-Condensation of an allylic Phosphonium Ylide (p. 821)-Generally, allylic phosphorous ylides condense on the a carbon-Many geometric isomers usually obtained
CO2MeH
MePPhPh
•HBr
Hunig's Base
C5H11
Hexanal
O
O
CO2MeMe
C5H11
Generally, E/Z > 190-92 %
9-10%
+
E. J. Corey (p. 256)
Samuel Danishefsky (Univ. of Pitt)-A route to funtionalized heterocycles by homoconjugate addition (p. 1979)
-The use of a highly substituted cyclopropane as an electrophile (generated by reacting the olefin with dimethyl diazomalonate ine the presence of copper bronze)
CO2Me
CO2Me
NH2 NHCO2Me
CO2Me
CO2Me
N
O
O
Hydrazine
MeOH
-Showed in earlier work that mechanism goes through "Spiro-mode"
O
1. 10 % HCl
2.HCl, MeOH
NH CO2Me•HCl
NHH
ODesired pyrrolizidine
NHH
ODesired indolizidine
Samuel Danishefsky (Univ. of Pitt)-Furanoid systems by intramolecular homoconjugate addition (p. 2658)
CO2Me
CO2Me
O
O O NaH
PhH
-O-Alkylation was dominant pathway in all systems they tried in this paper
O
MeO2C
(CO2Me)2
CO2Me
CO2Me
O
O
O
NaH
PhHOR
DMSOO
(CO2Me)2OO
Geometry highly dependent on solvent and therefore solvation of reaction pathway
Gilbert Stork (Columbia)-Regiospecific Aldol condensations of the kinetic lithium enolates of methyl ketones (p. 3459)
-It had previously been difficult to trap the kinetic enolate with alkyl halides-So, used a more reactive electrophile to trap the enolate
O LiO LDA,
THF, –78°Butyraldehyde O OH
65% (90% Kinetic enolate)
O LiO LDA,
THF, –78°Benzaldehyde
Ph
O OH
75-80%
O LiO LDA,
THF, –78°Crotonaldehyde O OH
70%
Barry M. Trost (Wisconson, Madison)-Chemospecificity of allylic alkylations (p. 737)
-Use of cis and trans geranylacetone
-p-allyl complexes are remarkably stable
2Ethylene Gylcol
TsOH, PhH, Reflux
Conditions: PdCl2, NaCl, CuCl, NaOAc in AcOH
OO
PdCl/280%
Barry M. Trost (Wisconson, Madison)Alkylations
NaH
CH3SO2CH2CO2CH31, 2, or 3
H3CO2S CO2CH3 LiI, NaCN, DMF
130°C
H3CO2S
1. HOCH2CH2OH,TsOH, PhH, Reflux
2. Li, C2H5NH2, 0°C
3.H2O, HCl
Barry M. Trost (Wisconson, Madison)-Alkylation of Lactam Derivatives (p. 2475)
N N NO O LiO
MeMeMe
LDA, THF
–78°C
N N NOMe OMeLi
LDA, THF
–78°C
E+ E
OMeE+ E
1
2
-Both of the above examples proceeded with C-alkylation exclusively with alkyl halides, chlorosilanes.-For 1 (Stronger enolate), reaction with methyl vinyl ketone proceeds with 1,2 addition; for 2, (weaker reagent), reaction to MVK proceeded with conjugate additionThis selectivity is due to the less reactive reagent having its charge more delocalized in the transition state. To test this hypothesis, a controll exmeriment:
MVK
22hr,RTN OMe
Me
N OMe
O
Exclusively 1,4 addition, 29%
Barry M. Trost (Wisconson, Madison)-A convienent approach to Methyl 3-oxo-4-pentenoate (p. 2648)
-Not easily synthesized -The two main previous methods either ended with a final step of 7-12% (acid catalyzed elimination), or was based on a retro-Diels-Alder step (great yield, but requires special high-temp pyrolysis apparatus).-Utility seen as an "annelating agent" in the synthesis of terpenes and alkaloids
O
O
PhSHSPh OH
O 1. SOCl2
2.
TMSO
O
OMe
OLi SPh
O OTMS
O
OMeO H+
SPhO
OMeO
62-76 %
O
OMe
ONaHPhLi O
OMe
OPhSCH2I
63-80%
1
1Sodium
Metaperiodate SPhO
OMeOO
DO
OMe
O
Summary: 3-step route, 60-76% overall; 5-step route, 60-72% overall
R. F. Heck (Univ. of Delaware :-) )
NH2Br + ++CO
RR'
3N Pd(Br)2(PPh3)2
100°CR
O
NH
Possible Mechanism:
-Palladium caralyzed Amidation of aryl, heterocyclic, and vinylic halides (p. 3327)
R. F. Heck (Univ. of Delaware :-) )-Palladium caralyzed carboalkoxylation of aryl, benzyl, and vinylic halides (p. 3318)
Br + ++COR
R23N Pd(Br)2(PPh3)2
100°C R
O
O R2R1OH
Possible Mechanism:
• The following people did wonderful chemistry in JOC, ‘74,but time constraints cause their omission:– David Evans (UCLA)
• Useful Prostaglandin Intermediate (p. 3176)• Applications of trimethylsilyl cyanide (p. 914)
– Herbert C. Brown• New organoborane structures via alpha-bromination of borapolycyclanes (p. 861)• Synthesis of olefins: alpha-elimination of alpha-chloroboronic esters (p. 2817)• Synthesis of terminal acetylenes via treatment of lithium
ethynyltrialkylborates with Iodine (p. 731)– Herbert House
• Chemistry of Carbanions (p. 3102)• Electron transfer reactions: reduction of enones with Cr(II) compounds
(p. 1173), and of nonconjugated acetylenes (p. 747)– Robert E. Ireland
• Claisen rearrangement of N-Allylketene O,N-Acetals (p. 421)– And of course, many others…
(S)-Carlosic Acid
Blommer and Kappler, p. 113
Temple University
MeO2C
O O
O
t-BuOK
t-BuOHOCO2Me
HOO
OMeO2C
Br2
AcOH
O
HO
OMeO2C
Br
OHOMeMeO
O
O
OO
Et3N (cat), PhH80%
H2, Pd/C
AcOH O
HO
OMeO2C
Cl
O
TiCl4PhNO2
O
HO
OMeO2C
HCl
NaOH
O
HO
OHO2C
(S)-Carlosic Acid
Note: all yields in the synthesis were 70-80%, except the "key step," the cyclization
39%
Cassamedine
Cava and Libsch, p. 577
UPenn
O
O
OMeNH2 O
O
OH
OBr+
Known Compounds
O
O
OMe HN O
Br
O O
PhH, 2hr
76%
O
O
OMe
N
O O
Br
POCl3
CH3CN20 hr, 90%
O
O
OMe
N
O O
Br O
OEtEthylChloroformate
Et3N, 0°C90%
•HCl
O
O
OMe
N
OO
O
OEt
t-BuOKhn, 7hr
PhH, t-BuOH32%
O
O
OMe
N
OO
Me
LiAlH4, AlCl3Et2O, reflux
1.5 hr, 87%
O
O
OMe
N
OO
MeO
OO H
AcOH23%
Cassamedine
-An alkaloid isolated from Cassytha americana
The Sex Pheromone of the Pink Bollworm
Phillip E. Sonnet, p. 3793
U.S. Dept. of Agriculture, Maryland-Isolated from the Pectinophora gossypiella, the pink bollworm moth-Isolated as 1:1 mixture of geometric isomers
Cl OTHPLiH
OTHP
H
1. n-BuLi, THF
2. Cl(CH2)3Br, HEMPA, THF
53%
OTHPCl
84%
PPh3
84%
1. n-BuLi, THF/HMPA
2. Me(CH2)3CHO
OTHPPh3P
•HCl
OTHP
AcCl
AcOH58%
OAc
H2, Pd/BaSO4
Pentane, 84%OAc
NaNO2 (aq)HNO3 (aq)74%
OAc
H2, Pd/BaSO4
Pentane, 80%
OAc
The Sex Pheramone of the Pink Bollworm
The Sex Pheromone of the Pink Bollworm
Phillip E. Sonnet, p. 3793
U.S. Dept. of Agriculture, Maryland-Isolated from the Pectinophora gossypiella, the pink bollworm moth-Isolated as 1:1 mixture of geometric isomers
A Trail Pheromone of the Pharaoh Ant
Sonnet, Oliver, p. 2663
U.S. Dept. of Agriculture, Maryland-Isolated from the Monomorium pharaonis, the Pharaoh Ant-It was known that the pheromone had the general structure of 3-butyl-5-methoctahydroindolizine, but absolute stereochemistry of active pheromone was not elucidated-Synthesized all four stereoisomers because they were interested in the pheromone's utility as a pest control agent
N
C4H9
N
C4H9
N
C4H9
N
C4H9
H
H
H
H
A B C DA Trail Pheromone of the Pink Bollworm
N
C4H9
N
C4H9
N
C4H9
N
C4H9
H
H
H
H
N
1. BuLi
2.
C4H9
ON
OH
H2PtO2
NH OH
NaEtOH
NH OH
H
1. PhP3•Br22. Et3N
NBr–
C4H9
A B C D
1. PhP3•Br22. Et3N
1. PhP3•Br22. Et3N
A + B C + D A
H2PtO2
A Trail Pheromone of the Pink Bollworm
N
OH
OCH3H3CO
H3COCl–
Fagaronine Chloride
OCH3
OCH3
OCH3
Oi-Pr
NO2
Fagaronine Chloride
Stermitz, p. 3239
Colorado St. Univ., Fort Collins
NH2OCH3
Oi-Pr
NO2OCH3
OCH3
HNO3:HOAc1:1
HOAc
hn, 1hr
CH3CN:0.8N NaOH90%
NO2OCH3
OH
K2CO3i-PrBr
DMF, 92%
H2NNH2,EtOH
10% Pd/C100°C, 99%
BrH3CO
H3CO
PhH, 91%O
H
-Extremely active antileukemic alkaloid-Isolated from Faraga zanthoxyloides-Note: synthesis also proved structure
NBrH3CO
H3CO
Oi-Pr
OCH3
N
Oi-Pr
OCH3H3CO
H3CO1
1. Na, NH3(liq)
2. 13. NH4Cl, 24%
Dimethyl Sulfate,
PhNO2/Xylene180°C
N
OH
OCH3H3CO
H3CO
CH3OSO3–
8% NaCl(aq)
88%N
OH
OCH3H3CO
H3COCl–
Fagaronine Chloride
Fagaronine Chloride
Stermitz, p. 3239
Colorado St. Univ., Fort Collins
-Extremely active antileukemic alkaloid-Isolated from Faraga zanthoxyloides-Note: synthesis also proved structure
(+/–) 11-deoxyprostaglandin E2
Jonh Petterson, John Fried, p. 2506
Syntex, California
I C5H11
PreviousPreocedures
O OMe
C5H11
O OMe
LiCu
2
O1.
Et2O, -78°C
2. TMSCl, THF C5H11
O OMe
OTMS
1. Li, NH3(liq)Ferric Nitrate (trace)
Br CO2Me2.C5H11
OH
CO2MeO
(+/–) 11-deoxyprostaglandin E2
N
S
ArCO2H
O
HN H
OS
3-Arylcephalosporins
3-Arylcephalosporins
Firestone, Maciejewicz, Christensen, p. 3384
Merck Sharp and Dohme Research, New Jersey
S
H NH
Et2O3PO
O
OMe
+
Reported in 1973 by same the group
Cl Ar
O
K2CO3
Acetone N
S Ar
O
CO2CH2C6H4OMe
NaH
GlymePO3Et3
N
S
ArCO2CH2C6H4OMe
N3CH2COCl
Et3NN
S
ArCO2CH2C6H4OMe
O
N3H
H2
PtN
S
ArCO2CH2C6H4OMe
O
H2N H
N
S
ArCO2CH2C6H4OMe
O
N HO2N CHO
O2N
H+
H2ON
S
ArCO2CH2C6H4OMe
O
N H
O2N
Ar = C6H5 p-C6H4-CO2Me 4-thiazolyl
-Semisynthetic B-Lactam Antibiotics-High potency, acid stable, high degree of tolerance by man-Many modifications prior to this work
2,4-DNPHN
S
ArCO2CH2C6H4OMe
O
H2N HEt3N
S Cl
O N
S
ArCO2CH2C6H4OMe
O
HN H
OS
TFA
Anisole N
S
ArCO2H
O
HN H
OS
3-Arylcephalosporins
3-Arylcephalosporins
Firestone, Maciejewicz, Christensen, p. 3384
Merck Sharp and Dohme Research, New Jersey-Semisynthetic B-Lactam Antibiotics-High potency, acid stable, high degree of tolerance by man-Many modifications prior to this work