EROS Volume V and VI Ruben Martinez Baran Group Meeting 01/24/15 Lithium Hexamethyldisilazide (LHMDS ) Cl OMe LHMDS THF, 0 °C 86% (TMS) 2 N OMe formally a CH 2 NH 2 unit 1) RMgX, Et 2 O 2) HO - H 2 N R Synthesis of primary amines Org. React. 1949, 5, 413. 50-92% Br LHMDS (2 equiv.) Et 2 O, -20 ºC N(TMS) 2 Li useful precursor to unsaturated protected primary amines Tetrahedron 1992, 48, 6231. SiMe 2 SiMe 2 + SiMe 2 SiMe 2 CH 2 SiMe 2 SiMe 3 Pd(PPh 3 ) 2 O O O 1 mol% PhH, reflux, 36h 13% J. Organomet. Chem. 1977, 131 , 147. Disilane metathesis (Maleic anhydride)bis(triphenylphosphine)palladium O SPh 2 LiBF 4 O 99% J. Am. Chem. Soc. 1973, 95, 7862. rearrangement of oxaspiropentanes to cyclobutanones Lithium Tetrafluoroborate N ∗ Li 1) 1 atm 11 CO THF, -78 °C 2) R 3 SnCl N ∗ O SnR 3 R 1 I, Pd(PPh 3 ) 4 THF, reflux N ∗ O R 1 Lithium Pyrrolidide Introduction of 11 C for biological and clinical studies. J. Chem. Soc., Perkin Trans. 1 1988, 569. N Me Me Me I 11 PrSLi HMPA, 50 °C N Me Me 11 Me Lithium 1-Propanethiolate Demethylation of quaternary ammonium salts. J. Org. Chem. 1973, 38, 1961. 99% Lithium Perchlorate [1,3]-Sigmatropic rearrangement O HO HO Me Me H H 3.0M LiClO 4 Et 2 O HO HO Me Me H H O 90% J. Am. Chem. Soc. 1991, 113 , 5488. N N Et CO 2 Me Me N Me SMe O N Et 1) LiDMSO 2) TsOH J. Org. Chem. 1985, 50, 961. Lithium Methylsulfinylmethylide A key player in the total synthesis of vindoline Top 10 EROS Reagents in 2013 SiMe 3 Me 2 Si CH 2 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-Chief Professor Philip L. Fuchs Purdue University
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EROS Volume V and VIRuben MartinezBaran Group Meeting
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
01/24/15
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.
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
EROS Volume V and VIRuben MartinezBaran Group Meeting
01/24/15
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.
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
EROS Volume V and VIRuben MartinezBaran Group Meeting
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.