Ruben Martinez EROS Volume V and VI Baran Group Meeting · 2015. 5. 21. · Ruben Martinez EROS...
Transcript of Ruben Martinez EROS Volume V and VI Baran Group Meeting · 2015. 5. 21. · Ruben Martinez EROS...
EROS Volume V and VIRuben MartinezBaran Group Meeting
01/24/15
Lithium Hexamethyldisilazide (LHMDS )
Cl OMeLHMDS
THF, 0 °C86%
(TMS)2N OMe
formally a CH2NH2 unit
1) RMgX, Et2O
2) HO-H2N R
Synthesis of primary amines
Org. React. 1949, 5, 413.50-92%
Br LHMDS (2 equiv.)
Et2O, -20 ºC
N(TMS)2Liuseful precursor to unsaturated
protected primary aminesTetrahedron 1992, 48, 6231.
SiMe2SiMe2
+
SiMe2
SiMe2
CH2
SiMe2
SiMe3
Pd(PPh3)2 O
O
O
1 mol%
PhH, reflux, 36h13%
J. Organomet. Chem. 1977, 131 , 147.
Disilane metathesis(Maleic anhydride)bis(triphenylphosphine)palladium
O
SPh2
LiBF4
O
99% J. Am. Chem. Soc. 1973, 95, 7862.
rearrangement of oxaspiropentanes to cyclobutanonesLithium Tetrafluoroborate
N
∗∗
Li
1) 1 atm 11COTHF, -78 °C2) R3SnCl
N∗∗
O SnR3
R1I, Pd(PPh3)4
THF, refluxN∗∗
O R1
Lithium PyrrolidideIntroduction of 11C for biological and clinical studies.
J. Chem. Soc., Perkin Trans. 1 1988, 569.
NMeMeMe I
11
PrSLi
HMPA, 50 °CNMe
Me11
Me
Lithium 1-PropanethiolateDemethylation of quaternary ammonium salts.
J. Org. Chem. 1973, 38, 1961.99%
Lithium Perchlorate[1,3]-Sigmatropic rearrangement
O
HO
HO
Me
Me
H
H3.0M LiClO4
Et2OHO
HO
Me
Me
H
H
O
90%
J. Am. Chem. Soc. 1991, 113, 5488.
N
N
EtCO2MeMe N
MeSMe
O
NEt
1) LiDMSO
2) TsOH
J. Org. Chem. 1985, 50, 961.
Lithium MethylsulfinylmethylideA key player in the total synthesis of vindoline
Top 10 EROS Reagents in 2013
SiMe3
Me2Si CH2
e-EROS gives detailed information on more than 4,500 reagents and catalysts, and every year more than 200 new or updated articles are added in order to keep the Database up-to-date.
Editor-in-ChiefProfessor Philip L. FuchsPurdue University
EROS Volume V and VIRuben MartinezBaran Group Meeting
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AcO
Me
O Me
HH
H
NAc
MeHO
HMe
H
AcO
I
O Me
HH
H
MeH
O
H
HgO, I2hν
cyclohexane, rt, 3d
Tetrahedron Lett. 1973, 4147.
AcO
Me
OH
H
Me R
H
H
HAcO
H
Me R
H
HO
HgO, I2hν
CCl4, reflux70%
50%
J. Am. Chem. Soc. 1964, 86, 1528.
Mercury(II) Oxide–IodineHydrogen Abstraction.
Mercury(II) Oxidetrans Diamination of alkenes
MeOH, HgO
HBF4, PhNH289%
NHPh
NHPhSynthesis 1981, 376.
BrHgO
Br280% Can. J. Chem. 1972, 50, 3109.
HO2C Br
CH2Br2HgO
Br280%
Bu3SnD, AIBN
93%
Synthesis 1976, 251.
Preparation of Alkyl Halides.
Ph
NNH2Ph
NNH2
HgO
PhH, refluxPhPh
Oxidation of hydrazones
Oxidations in Organic Chemistry; American Chemical Society: Washington, 1990.
MeMe
H2C
NMeMe
Me
H2C
Hg(NO3)2
MeCN
J. Org. Chem. 1982, 47, 4169.J. Chem. Soc., Chem. Commun. 1983, 384.
Mercury(II) Nitrate
I
I
I
I
F
F
F
IHgF2
70%J. Org. Chem. 1989, 54, 3796.
Mercury(II) FluorideMetathesis reactions
Mercuric Cyanide
Tetrahedron Lett. 2001, 42, 2077.
O
BrAcO
AcOOAc
N
HN NO2+
Hg(CN)2
MeNO2
81%
N
NO2N
OAcO
AcOOAc
N-Glycoside Formation.
Organometallics 1983, 2, 855.
Mercury (0)
Mercury selectively poisons heterogeneouscatalysts, particularly of the platinum group metals (PGM). This can be useful when ahomogeneous PGM catalyst decomposes with time to give the free metal; in such a case, Hg(0) can suppress the heterogeneouscomponent of the reaction. This can improve selectivity or givemechanistic information about which productsare attributable to which pathway.
Catalyst poison
AcO
Me
Me O
AcO
Me
Me SO
HSOH
BF3·OEt287%
J. Am. Chem. Soc. 1954, 76, 1945.
2-MercaptoethanolSteroidal ketone protection
D
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Methanesulfonyl ChlorideChlorination of allylic alcohols
OHR
R
MsCl, py
DMF, collidine83%
ClR
RJ. Org. Chem. 1971, 56, 3044.
Mild elimination of iodohydrins
O OI
HOOBn
MsCl, py
quench with Na2S2O3>99%
O O
OBn
Tetrahedron Lett. 1972, 107.
PhCONEt2 Ph
CONEt2OH
OH
AD-mix-βMeSO2NH2
t-BuOH, H2O, 0 °C96%
96% ee
Catalyst turnoverMethanesulfonamide
J. Org. Chem. 1992, 57, 2768Tetrahedron Lett. 1993, 34, 2079.
Me
Me
S MeOO
OH2N
O-(Mesitylsulfonyl)hydroxylamine
NPhBr
NN Ph
57%
OMSH
NaOHOMSH
Synthesis 1973, 159.J. Chem. Soc., Perkin Trans. 1 1977, 924.
NH2 transfer to nucleophiles
t-Bu
t-Bu t-Bu
H
Se
Me
Me
Me
B B
Me
Me
Me
TMSTMSLi
Angew. Chem., Int. Ed. Engl. 1988, 27, 961. Chem. Commun. 1986, 71.
Low-coordinate main group element derivativesMesityllithium
Allylic diazene rearrangementMesitylenesulfonylhydrazide
O
O
H
H
HO NCO2Me
OMeH
Me H
O
O
H
H
NCO2Me
OMeH
Me H1) MeAlCl2 -78 °C to -35 °C2) MSH, -78 °C to 0 °C
92%
J. Am. Chem. Soc. 1992, 114, 5898.
Mercury(II) Trifluoroacetate
HO HOO
MeMeHg(CF3CO2)2
Tetrahedron Lett. 1975, 2605.
HR H
OH
1) Hg(CF3CO2)2DCM, NaCl
2) LAH, THF
MeR
OH
OH
Acc. Chem. Res. 2003, 36, 766.
Cyclopropane Ring Openings
Oxymercuration
AcOOH
H H
Me
AcOO
H
β-fragmentation
HgO,I2hν
CCl4, 2 h, rt
J. Chem. Soc. (C) 1966, 937.Tetrahedron 1977, 33, 441.
Mercury(II) Oxide–Iodine cont.
Me
H
(E), 63%; (Z), 10%
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Molybdenum (VI) Fluorideoxygen to fluorine exchange
R R1
O MoF6BF3·OEt2
DCM, 20 ºC R R1
FF+ MoOF4
CF3 group installation
Br CF3Br CO2HMoF6
160 °C, 64 h89%
N CO2HHO2C
MoF6
200 °C, 45 h84%
N CF3F3Creactions must be run in a stainless steel autoclave
Tetrahedron 1971, 27, 3965.Tetrahedron 1975, 31, 391.
J. Fluorine Chem. 1979, 13 , 375.
J. Gen. Chem. USSR (Engl. Transl.) 1983, 53, 85.
Methyl Fluoride-Antimony (V) FluorideMeF/SbF5 is the most reactive methylating agent reported.
FF
FF F
F
FF
SO2ClF40-50%
MeF/SbF5
FF
FF F
F
FMe F
F
FF F
F
MeF
+
SO O
MeF/SbF5
SO2 SO OMe
CF3IMeF/SbF5
SO2CF3IMe
Can. J. Chem. 1984, 62, 69. Z. Naturforsch., Teil B 1991, 46b, 884.
Ot-Bu
Me t-Bu t-Bu Me
t-BuO
AlMe
Methylaluminum Bis(2,6-di-t-butyl-4-methyl)
MAD
Ph OMe+ Ph OEt
MAD
J. Am. Chem. Soc. 1990, 112 , 6115.
Ph OMe
AlR3
+Ph OEt
MeBBN
2) HOAc, -30 °C3) H2O2, NaOH
Li
OMe1)
THF, -30 °C
Me
OMe
1-Methoxyallenyllithium
Tetrahedron Lett. 1980, 21, 537.
OH
CH2
OMe O
OMe
O
O
6N HClt-BuOK
crown ether
t-BuOH, 4h, reflux74%
J. Am. Chem. Soc. 1978, 100 , 7746.
O
O
O
O
O
O
J. Am. Chem. Soc. 1980, 102 , 2134.
Helixanes: The first primary helical molecules: polyoxapolyspiroalkanones
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Chem. Lett. 1991, 641.
O
Ni(dpm)2 1 mol%i-PrCHO, O2
O
O
91% epoxidation of olefins also possible with same conditions
Ni(dpm)2Catalyst for oxidations
O
Me Me
H
N
O
Me Me
H
O
ONHAc
AcHN
O
NHOHNBu4IO4
0 ºC
Heterocycles 1989, 28, 147.
Nitrosocarbonylmethane
ClNO
NOH
hνH2SO4 NH
O
caprolactam4.5 billion kg produced annually.
HN
O
5n
533 °K
N2
Nylon 6
Nitrosyl ChlorideThe most important reagent in this GM
Fortschr. Chem. Forsch. 1967, 7, 559.
O2N
O2NO2N
O2N
HNO2
NO2
NO2
O2N
O2NO2N
O2N
NO2NO2
NO2
NO2
1) LiN(TMS)22) ClNO
3) O3
Angew. Chem., Int. Ed. 2000, 39, 401.
Needs more nitro!!!
OsO4–t-BuOOHoxidation TMS alkynes to α-keto esters
R TMSOsO4, TBHP
MeOH R
O
CO2Me60%
Tetrahedron Lett. 1986, 27, 1947.Oxalic AcidDecarboxylation of β-ketoesters
Chem. Soc., Chem. Commun. 1990, 1047.
NCO2Et
Me
OEtO2C
NCO2Et
Me
O(CO2H)2
H2O, dioxane81%
R
OF3C
OPd
OO t-Bu
PPT
PPT
Palladium tert-Butyl Peroxide Trifluoroacetateselective oxidation of terminal alkenes to methyl ketones
RO
internal alkenes form stableη3-allyl Pd complexesJ. Am. Chem. Soc. 1980, 102, 1047.
Phenyliodine(III) Bis(trifluoroacetate)Bond cleavage.
PIFACCl4, 20°C
OCOCF3
OCOCF3
(PIFA)
R
OR1 R
OR1
OH
PIFA, TFA
MeCN-H2O
J. Org. Chem. USSR (Engl. Transl.) 1981, 17, 1685.
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peptide
O
R
NH2 PhNCSpeptide
O
R
HN
HN
SPh
N NH
S
Ph
O R
HCl
MeNO2
OH-HO2C
R
NH2
Edman degradation of peptidesPhenyl Isothiocyanate
Acta Chem. Scand. 1950, 283.Fieser & Fieser 1967, 1, 844.Fieser & Fieser 1969, 2, 323.
The procedure, which is amenable to complexpeptides containing a variety of sensitive functionalities, has been applied tothe vancomycin group of antibiotics.
PhP
Cl
Se
Cl
Phenyl(seleno)phosphonic Dichloride
J. Chem. Soc., Chem. Commun. 1988, 1494.
NMe
O NMe
Se in xylene95 °C 96%
Oxygen–Selenium Exchange
PhenylthiomethyllithiumEpoxide Synthesis The overall yields for the three-step process are high and
compare favorably to the one-step methylene transfer accomplished by sulfur ylides, a reaction that is sometimeshindered by steric interference and proton abstraction.
Ph
O
Ph PhPhOPhSCH2Li 1) Me3OBF4
2) aq NaOHPhPh
HO SPh
88% 90%
Me
CHOPhSCH2Li
Me
OHSPh
1) Et3OBF4
2) NaH
Me
O
J. Am. Chem. Soc. 1973, 95, 3429.
Pure Appl. Chem. 1987, 59, 385.
P
N-t-Bu
N N
N
P P
PMe2N NMe2
NMe2
NMe2
NMe2
NMe2
NMe2
Me2NNMe2
Phosphazene Base P4-t-Bu
Alkylations of Carbanions
Angew. Chem., Int. Ed. Engl. 1987, 26, 1167.
Schwesinger's base
O O
t-Bu
MeMe
O
i-PrIP4-t-Bu
O O
t-Bu
Me Oi-Pr Me
45%
use of LDA or KHMDS gave only decomposition
OO
Me
P4-t-BuEtI O
O
Me EtEt68%
Schwesinger, R.; Hasenfratz, C. Unpublished results.
Chem. Ber. 1990, 124, 1837.
N
Ph O
BrBr1) PBr32) Br2
72%
Phosphorus(III) Bromide
Org. Synth., Coll. Vol. 1941, 1, 428.
Alkene Preparation.
OHHO
1) PBr3, CuBr2) Zn
J. Am. Chem. Soc. 1975, 97, 3252.
Org. Synth. 1989, 67, 210.
OEt
OTMS
PBr3
72%
66%
OEt
Br
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01/24/15
R
OC6H13
1) O3, DCM, -78 °C2) PI3
87%
R
OH
J. Chem. Soc., Perkin Trans. 1 1981, 1744.
An advantage over the traditional PPh3 reduction is the formation of water-soluble phosphorusbyproducts from PI3.
Phosphorus(III) Iodidereduction of ozonides
MeO
O
OO
Me
H H
MeMe
OO
O
Me
H H
Me
SEt
PPA, EtSH90 °C
Polyphosphoric AcidSelective epoxide opening
Chem. Pharm. Bull. 1967, 15, 887.
OH
OH
1) n-BuLi, THF2) K2WCl6, 65 °C
66% cis:trans = 73:27
Potassium Hexachlorotungstate(IV)
J. Chem. Soc., Chem. Commun. 1972, 370.
One pot conversion of 1,2-diols to alkenes
Potassium Monoperoxysulfate (Oxone)
Modification of Oxone: Since Oxone is a triple salt(2KHSO5·KHSO 4·K2SO4) only about 50% per mole is activeoxidant. A convenient method for the preparation of purifiedKHSO5·H2O on a large scale has been developed which allowsfor significant reduction in the amount of oxidizing agent neededfor a reaction.
H
O1 equiv Oxone
MeOH OMe
O
Tetrahedron 1998, 54, 401.83%
H
O1 equiv Oxone
DMF OH
O
97% Org. Lett. 2003, 5, 1031.
OH O
O4 equiv Oxone0.01 equiv OsO4
DMF, rt73%
Org. Lett. 2003, 5, 3089.
direct synthesis of lactones from alkenols
Potassium Monoperoxysulfate (Oxone)
Pyridinium Chlorochromate
OH
Me
2.5 equiv PCC
DCM, rt, 36 h
O
Me
Me
O
Me
Me
Me
70%
NaOH
EtOH
oxidative cationic cyclizationPCC
Tetrahedron Lett. 1978, 2461.
2-Pyrrolidone HydrotribromideSelective Bromination
OO
Br
PHTTHF N
O
O
N
O
O
BrPHTpyrrolidone
THF, reflux82%
O
O
PHTTHF96%
O
O
Can. J. Chem. 1969, 47, 706. Synthesis 1990, 59.
Bull. Chem. Soc. Jpn. 1986, 59, 3311.Eur. J. Org. Chem. 2002, 3429.
2KHSO5·KHSO4·K2SO4
EROS Volume V and VIRuben MartinezBaran Group Meeting
01/24/15
Rhodium(III) Chlorideselective reagent for the reduction of aromatic systems
HO2CNHCOMe
NaBH4, 2 equiv RhCl3
EtOH, 2 h, rt94%
Tetrahedron Lett. 1982, 23, 193.
HO2CNHCOMe
Ruthenium(III) ChlorideC–H Activation
O OO
EtRuCl3·3H2O
EtOH, 140 °CJ. Chem. Soc., Chem. Commun. 1986, 1255.75%
OHO
HO
ORuCl3, aq. CH3CO3H
MeCN, DCM, H2O, 0 to 20 °C58%
Tetrahedron Lett. 1998, 39, 7691.
Oxidation
Hydrogen Borrowing
CN MeO
OH
9.5 equiv
+ N
OMe
MeO
OMe
5 mol% RuCl3·H2O10 mol% dppf
PhMe, 150 °C 16 h84%
Chem. Lett. 2011, 40, 489.
Samarium(II) Iodide
O
MeMei-Pr
SePh O
O PMP
O
OPMP
Me
O
i-Pr
Me SmI2-HMPATHF, rt, 15 minthen PhSeBr
Reductive C-C cleavage of cyclobutane en route to (+)-guanacastepene A
50%J. Am. Chem. Soc., 2006, 128 , 7025.
NO
SEMN
Br Br
OTBS
CO2MeNHNHN
O
S
NO
SEMN
Br Br
OTBS
CO2MeNH2
NHHN
O
S
SmI2-MeOHTHF, rt, 15 min
79 %
J. Am. Chem. Soc., 2007, 129 , 12896.
N-N bond cleavage in a complex setting
Chem. Soc. Rev. 2013, 42, 9155.