EROS Volume V and VI
Ruben Martinez
Baran Group Meeting
01/24/15
Top 10 EROS Reagents in 2013 Lithium Perchlorate
[1,3]-Sigmatropic rearrangement
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.
O
O
Me
Editor-in-Chief
Professor Philip L. Fuchs
Purdue University
H
Me
HO
Me
3.0M LiClO 4
Me
Et 2O
90%
H
H
HO
HO
H
HO
J. Am. Chem. Soc. 1991, 113, 5488.
Lithium 1-Propanethiolate
Demethylation of quaternary ammonium salts.
Me
Me
N
Me I
PrSLi
Me
N
Me
HMPA, 50 °C
99%
11
11
Me
J. Org. Chem. 1973, 38, 1961.
Lithium Pyrrolidide
Introduction of 11 C for biological and clinical studies.
∗
Lithium Hexamethyldisilazide (LHMDS )
Synthesis of primary amines
Cl
OMe
LHMDS
THF, 0 °C
86%
(TMS) 2N
OMe
N
Li
1) RMgX, Et 2O
2) HO 50-92%
formally a CH 2NH 2 unit
H 2N
LHMDS (2 equiv.)
Et 2O, -20 ºC
N(TMS) 2
Li
useful precursor to unsaturated
protected primary amines
Tetrahedron 1992, 48, 6231.
Lithium Methylsulfinylmethylide
A key player in the total synthesis of vindoline
N
N
N
Et
Me CO 2Me
1) LiDMSO
N
Me
SMe
N
∗
THF, reflux
O
R1
J. Chem. Soc., Perkin Trans. 1 1988, 569.
SnR3
SPh2
LiBF 4
99%
J. Am. Chem. Soc. 1973, 95, 7862.
(Maleic anhydride)bis(triphenylphosphine)palladium
Disilane metathesis
O
Pd(PPh 3) 2
SiMe2
+
SiMe2
SiMe3
SiMe2
CH 2
J. Org. Chem. 1985, 50, 961.
∗
Lithium Tetrafluoroborate
rearrangement of oxaspiropentanes to cyclobutanones
O
O
Et
O
2) TsOH
R1I, Pd(PPh 3) 4
N
O
R
Org. React. 1949, 5, 413.
Br
1) 1 atm 11 CO
THF, -78 °C
2) R 3SnCl
O
O
PhH, reflux, 36h
13%
1 mol%
SiMe3
SiMe2
SiMe2
Me 2Si CH 2
J. Organomet. Chem. 1977, 131 , 147.
EROS Volume V and VI
Ruben Martinez
2-Mercaptoethanol
Steroidal ketone protection
Mercury(II) Oxide
trans Diamination of alkenes
Me O
HS
Me
Me O
OH
AcO
HBF 4, PhNH 2
89%
NO 2
+
AcO
MeNO 2
81%
AcO
N
AcO
OAc
I
HgF 2
70%
N
Me
Ph
Mercury(II) Oxide–Iodine
Hydrogen Abstraction.
Me R
Me R
Me
H
HgO, I 2
hν
H
H
CCl 4, reflux
70%
OH
H
O
H
AcO
H
J. Am. Chem. Soc. 1964, 86, 1528.
F
F
Hg(NO 3) 2
Ph
PhH, reflux
Oxidations in Organic Chemistry; American Chemical Society: Washington, 1990.
O
AcO
I
HgO
NNH 2
F
I
D
Synthesis 1976, 251.
NNH 2
Ph
H
I
Mercury(II) Nitrate
Me Me
H 2C
Ph
Tetrahedron Lett. 2001, 42, 2077.
I
93%
Br
Oxidation of hydrazones
OAc
Mercury(II) Fluoride
Metathesis reactions
Bu 3SnD, AIBN
Br 2
80%
HO 2C
N
Hg(CN) 2
Can. J. Chem. 1972, 50, 3109.
CH 2Br 2
HgO
Mercuric Cyanide
N-Glycoside Formation.
O 2N
Br
Br 2
80%
Mercury (0)
Catalyst poison
Mercury selectively poisons heterogeneouscatalysts, particularly
of the platinum group metals (PGM). This can be useful when a
homogeneous PGM catalyst decomposes with time to give the
free metal; in such a case, Hg(0) can suppress the heterogeneous
component of the reaction. This can improve selectivity or give
mechanistic information about which products
are attributable to which pathway.
Organometallics 1983, 2, 855.
O
Synthesis 1981, 376.
HgO
J. Am. Chem. Soc. 1954, 76, 1945.
H
N
NHPh
Preparation of Alkyl Halides.
AcO
Br
NHPh
MeOH, HgO
S
Me
BF 3·OEt 2
87%
AcO
Baran Group Meeting
01/24/15
J. Org. Chem. 1989, 54, 3796.
N
Me
Me
Me Me Ac
H
H
N
O
Me
H
H
H
HO
Me Me
H
O
HgO, I 2
hν
Me cyclohexane, rt, 3d
I
H
H
O
H
H
50%
MeCN
H 2C
J. Org. Chem. 1982, 47, 4169.
AcO
J. Chem. Soc., Chem. Commun. 1983, 384.
AcO
Tetrahedron Lett. 1973, 4147.
EROS Volume V and VI
Ruben Martinez
Mercury(II) Oxide–Iodine cont.
O-(Mesitylsulfonyl)hydroxylamine
β-fragmentation
Me
H
AcO
HgO,I 2
hν
H
CCl 4, 2 h, rt
OH
Baran Group Meeting
01/24/15
H
H
(E), 63%; (Z), 10%
O
J. Chem. Soc. (C) 1966, 937.
Tetrahedron 1977, 33, 441.
Me
AcO
Me
O
O S
H 2N
O
Me
Me
OMSH
NH 2 transfer to nucleophiles
Mercury(II) Trifluoroacetate
Oxymercuration
N
Me
Me
NaOH
OMSH
Br
Ph
57%
Synthesis 1973, 159.
J. Chem. Soc., Perkin Trans. 1 1977, 924.
Hg(CF 3CO 2) 2
HO
HO
O Tetrahedron Lett. 1975, 2605.
Methanesulfonamide
Catalyst turnover
Cyclopropane Ring Openings
R
H
H
1) Hg(CF 3CO 2) 2
DCM, NaCl
OH
2) LAH, THF
OH
O
HO
CO 2Me
HN
92%
OMe
H
O
Me
H
O
Me
B
Me
Li
B
Me
TMS
TMS
Angew. Chem., Int. Ed. Engl. 1988, 27, 961.
OH
96% ee
J. Org. Chem. 1992, 57, 2768
Tetrahedron Lett. 1993, 34, 2079.
Methanesulfonyl Chloride
Chlorination of allylic alcohols
CO 2Me
HN
R
H
OMe
H
O
J. Am. Chem. Soc. 1992, 114, 5898.
Mesityllithium
Low-coordinate main group element derivatives
Me
Me Me
CONEt 2
Ph
Acc. Chem. Res. 2003, 36, 766.
1) MeAlCl 2 -78 °C to -35 °C
2) MSH, -78 °C to 0 °C
H
OH
AD-mix-β
MeSO 2NH 2
t-BuOH, H 2O, 0 °C
96%
OH
Mesitylenesulfonylhydrazide
Allylic diazene rearrangement
Me
H
CONEt 2
Ph
Me
R
N Ph
N
OH
MsCl, py
DMF, collidine
83%
R
R
Cl
R
J. Org. Chem. 1971, 56, 3044.
Mild elimination of iodohydrins
t-Bu Se
H
t-Bu
t-Bu
Chem. Commun. 1986, 71.
I
O
O
O
O
MsCl, py
HO
OBn
quench with Na 2S2O3
>99%
OBn
Tetrahedron Lett. 1972, 107.
EROS Volume V and VI
Ruben Martinez
1-Methoxyallenyllithium
Methyl Fluoride-Antimony (V) Fluoride
MeF/SbF 5 is the most reactive methylating agent reported.
OMe
1)
Me
Me
Li
THF, -30 °C
BBN
F
OMe
2) HOAc, -30 °C
3) H 2O 2, NaOH
Tetrahedron Lett. 1980, 21, 537.
O
t-BuOK
crown ether
F
F
F
F
MeF/SbF 5
SO2ClF
40-50%
F
Me
F
F
F
F
+
F
F
F
F
Me
F
F
F
F
F
O
6N HCl
t-BuOH, 4h, reflux
CH 2
74%
F
F
F
OH OMe
Baran Group Meeting
01/24/15
OMe
MeF/SbF 5
O
J. Am. Chem. Soc. 1978, 100 , 7746.
S
CF3I
S
SO2
O
OMe
O
Can. J. Chem. 1984, 62, 69.
O
MeF/SbF 5
SO2
CF3IMe
Z. Naturforsch., Teil B 1991, 46b, 884.
Helixanes: The first primary helical molecules: polyoxapolyspiroalkanones
O
O
O
Molybdenum (VI) Fluoride
oxygen to fluorine exchange
O
O
O
O
J. Am. Chem. Soc. 1980, 102 , 2134.
R
Me
Br
O
Al
Me
t-Bu t-Bu
DCM, 20 ºC
CO 2H
MoF 6
OMe
+
Ph
OEt
+
R1
MoOF 4
Br
CF3
160 °C, 64 h
89%
J. Fluorine Chem. 1979, 13 , 375.
Me
MAD
Ph
F
CF 3 group installation
t-Bu
O
F
R
Tetrahedron 1971, 27, 3965.
Tetrahedron 1975, 31, 391.
Methylaluminum Bis(2,6-di-t-butyl-4-methyl)
t-Bu
R1
MoF 6
BF 3·OEt 2
MoF 6
MAD
HO 2C
Ph
OMe
+
Ph
OEt
AlR3
J. Am. Chem. Soc. 1990, 112 , 6115.
N
CO 2H
200 °C, 45 h
84%
F 3C
N
CF3
reactions must be run
in a stainless steel autoclave
J. Gen. Chem. USSR (Engl. Transl.) 1983, 53, 85.
EROS Volume V and VI
Ruben Martinez
Ni(dpm) 2
Catalyst for oxidations
OsO 4–t-BuOOH
oxidation TMS alkynes to α-keto esters
O
O
O
Ni(dpm) 2 1 mol%
i-PrCHO, O 2
91%
epoxidation of olefins also possible with same conditions
Chem. Lett. 1991, 641.
O
Me
Me
NHOH
N
O
R
MeOH
60%
CO 2Me
Tetrahedron Lett. 1986, 27, 1947.
H 2SO 4
O
(CO 2H) 2
Me
N
CO 2Et
Me
N
CO 2Et
H 2O, dioxane
81%
Chem. Soc., Chem. Commun. 1990, 1047.
Palladium tert-Butyl Peroxide Trifluoroacetate
selective oxidation of terminal alkenes to methyl ketones
O
NOH
O
EtO 2C
Me
Nitrosyl Chloride
The most important reagent in this GM
hν
O
OsO 4, TBHP
TMS
O
NHAc
O
H O
AcHN
Heterocycles 1989, 28, 147.
NBu 4IO 4
0 ºC
H
ClNO
R
Oxalic Acid
Decarboxylation of β-ketoesters
Nitrosocarbonylmethane
Me
Baran Group Meeting
01/24/15
O
NH
533 °K
F 3C
H
N
5
N2
n
caprolactam
Nylon 6
4.5 billion kg produced annually.
Fortschr. Chem. Forsch. 1967, 7, 559.
O
O
Pd
O
O t-Bu
PPT
PPT
R
R
O
J. Am. Chem. Soc. 1980, 102, 1047.
internal alkenes form stableη3-allyl Pd complexes
(PIFA)
Phenyliodine(III) Bis(trifluoroacetate)
Bond cleavage.
OCOCF3
PIFA
Needs more nitro!!!
O 2N
O 2N
O 2N
O 2N
H
NO 2
NO 2
NO 2
OCOCF3
CCl 4, 20°C
1) LiN(TMS) 2
2) ClNO
3) O3
NO 2
NO 2
O 2N
O 2N
O 2N
O 2N
NO 2
NO 2
Angew. Chem., Int. Ed. 2000, 39, 401.
J. Org. Chem. USSR (Engl. Transl.) 1981, 17, 1685.
O
O
R
R1
PIFA, TFA
MeCN-H 2O
R
R1
OH
EROS Volume V and VI
Ruben Martinez
Phenyl Isothiocyanate
Edman degradation of peptides
The procedure, which is amenable to complex
peptides containing a variety of sensitive
functionalities, has
been
applied
to
the vancomycin group of antibiotics.
O
O
NH 2
peptide
PhNCS
H
N
peptide
R
R
H
N
HO 2C
Ph N
OH-
NH 2
O
t-Bu
Ph
S
O
NH
O
N
Me
Ph
Ph
PhSCH 2Li
Acta Chem. Scand. 1950, 283.
Fieser & Fieser 1967, 1, 844.
Fieser & Fieser 1969, 2, 323.
CHO
PhSCH 2Li
P
N
P NMe 2
NMe 2
N
Me 2N P NMe 2
NMe 2
t-Bu
O
45%
O
O
Me
O
Chem. Ber. 1990, 124, 1837.
i-Pr Me
O
O
P 4-t-Bu
EtI
O
Et
Et
use of LDA or KHMDS gave only decomposition
Schwesinger, R.; Hasenfratz, C. Unpublished results.
68%
Me
O
Me
Phosphorus(III) Bromide
Se
N
Me
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 sometimes
hindered by steric interference and proton abstraction.
HO
Ph
SPh
Ph
88%
Me
N
MeNO 2
R
Me
OH
O
2) NaH
Pure Appl. Chem. 1987, 59, 385.
Org. Synth., Coll. Vol. 1941, 1, 428.
66%
J. Am. Chem. Soc. 1975, 97, 3252.
OEt
O
Br
1) PBr 3, CuBr
2) Zn
Ph
2) aq NaOH
90%
J. Am. Chem. Soc. 1973, 95, 3429.
Me
Br
72%
Alkene Preparation.
HO
OH
O
Ph
1) Me 3OBF 4
1) Et 3OBF 4
SPh
1) PBr 3
2) Br 2
N
Ph
O
Me 2N P
Me
HCl
J. Chem. Soc., Chem. Commun. 1988, 1494.
Phenylthiomethyllithium
Epoxide Synthesis
N-t-Bu NMe 2
NMe 2
P 4-t-Bu
i-PrI
O
Me
Phenyl(seleno)phosphonic Dichloride
Oxygen–Selenium Exchange
Se
P
Ph
Cl
Cl
in xylene
95 °C
96%
Phosphazene Base P 4-t-Bu
Schwesinger's base
Alkylations of Carbanions
NMe 2
Angew. Chem., Int. Ed. Engl. 1987, 26, 1167.
S
R
Baran Group Meeting
01/24/15
OTMS
PBr 3
OEt
72%
Br
Org. Synth. 1989, 67, 210.
EROS Volume V and VI
Ruben Martinez
Phosphorus(III) Iodide
reduction of ozonides
R
An advantage over the traditional PPh3 reduction
is the formation of water-soluble phosphorus
byproducts from PI3.
1) O3, DCM, -78 °C
2) PI 3
O
Potassium Monoperoxysulfate (Oxone)
O
H
Me
H
O
H
O
O
H
OH
DMF
97%
Org. Lett. 2003, 5, 1031.
direct synthesis of lactones from alkenols
Me
Me
O
PPA, EtSH
O
OH
O
H
H
SEt
Chem. Pharm. Bull. 1967, 15, 887.
Potassium Hexachlorotungstate(IV)
One pot conversion of 1,2-diols to alkenes
O
4 equiv Oxone
0.01 equiv OsO 4
O
DMF, rt
73%
Me
90 °C
O
OH
O
1 equiv Oxone
H
O
OH
Tetrahedron 1998, 54, 401.
83%
Polyphosphoric Acid
Selective epoxide opening
O
OMe
MeOH
J. Chem. Soc., Perkin Trans. 1 1981, 1744.
Me
Me
O
1 equiv Oxone
R
87%
C6H13
Baran Group Meeting
01/24/15
Pyridinium Chlorochromate
Org. Lett. 2003, 5, 3089.
PCC
oxidative cationic cyclization
O
O
OH
2.5 equiv PCC
DCM, rt, 36 h
Me
Me
Me
Me
NaOH
Me
EtOH
Me
70%
Tetrahedron Lett. 1978, 2461.
1) n-BuLi, THF
2) K 2WCl6, 65 °C
66%
cis:trans = 73:27
J. Chem. Soc., Chem. Commun. 1972, 370.
2-Pyrrolidone Hydrotribromide
Selective Bromination
O
Modification of Oxone: Since Oxone is a triple salt
(2KHSO 5·KHSO 4·K 2SO 4 ) only about 50% per mole is active
oxidant. A convenient method for the preparation of purified
KHSO5·H2O on a large scale has been developed which allows
for significant reduction in the amount of oxidizing agent needed
for a reaction.
Eur. J. Org. Chem. 2002, 3429.
PHT
THF
Potassium Monoperoxysulfate (Oxone)
2KHSO5·KHSO 4·K 2SO 4
O
O
Br
Can. J. Chem. 1969, 47, 706.
O
O
PHT
THF
96%
O
PHT
pyrrolidone
Br
THF, reflux
82%
N
O
Synthesis 1990, 59.
N
O
O
O
Bull. Chem. Soc. Jpn. 1986, 59, 3311.
EROS Volume V and VI
Ruben Martinez
Baran Group Meeting
01/24/15
Samarium(II) Iodide
Rhodium(III) Chloride
selective reagent for the reduction of aromatic systems
HO 2C
HO 2C
NHCOMe
NHCOMe
NaBH 4, 2 equiv RhCl 3
EtOH, 2 h, rt
94%
Tetrahedron Lett. 1982, 23, 193.
Ruthenium(III) Chloride
C–H Activation
O
RuCl 3·3H 2O
O
O
Et
EtOH, 140 °C
Chem. Soc. Rev. 2013, 42, 9155.
J. Chem. Soc., Chem. Commun. 1986, 1255.
75%
Oxidation
O
Reductive C-C cleavage of cyclobutane en route to (+)-guanacastepene A
O
RuCl 3, aq. CH 3CO 3H
MeCN, DCM, H 2O, 0 to 20 °C
58%
PMP
O
HO
O
O
Me
HO
Tetrahedron Lett. 1998, 39, 7691.
i-Pr
PMP
O
Me
O
SmI2-HMPA
THF, rt, 15 min
then PhSeBr
50%
O
SePh
i-Pr Me
Me
J. Am. Chem. Soc., 2006, 128 , 7025.
Hydrogen Borrowing
N-N bond cleavage in a complex setting
OMe
Br
SEMN
OH
+
CN
MeO
9.5 equiv
5 mol% RuCl 3·H 2O
10 mol% dppf
PhMe, 150 °C 16 h
84%
MeO
N
O
OMe
O
N
N
S
NH
CO 2Me
Br
SEMN
OTBS
HN
Chem. Lett. 2011, 40, 489.
Br
Br
SmI2-MeOH
THF, rt, 15 min
79 %
O
OTBS
O
N
HN
CO Me
NH NH 2
2
S
J. Am. Chem. Soc., 2007, 129 , 12896.