Mohammed Ali
Professor
Chemistry Department
Southeast Missouri State University
Research Interests
Major focus of my research program is Green Chemistry. We are pursuing research
aiming towards development of environmentally benign chemical processes. Some of
our current research interests are as follows:
I. Solid Supported Reagent
My group has developed a simple procedure for immobilizing inorganic reagents
on porous solid materials, such as, silica gel. Solid supported reagents/catalysts hold
promises to help reduce pollution and waste, improve product selection, and recycle
catalysts. Development of solid supported metal catalysts utilizing our procedure is in
progress. Students in my group are evaluating a number of solid supported reagents in
various synthetically important reactions. Solid supported ruthenium, chromium, and
lanthanide catalysts are among others we are currently investigating. So far, these
catalysts produced excellent results in various organic reactions. Some of our past and
current projects involving supported reagents are presented here.
[CAN], NaBrO3
O
R
R'
HS
SH
S
S
R
R'
Microwave
RSO2Na +
R'X
RSO2R'
Solvent free cond.
Synthesis 2007, 000
O
CrO3
Supported on silica gel
OH
N
R
O
R
R
Br N
R
R
Synth. Commun. 2006, 36, 1761
Pyridinium tribromide
R
R
R
Synth. Commun. 2006, 36, 1779
HO
R
R'
O
S
Synthesis, 2005, 1326.
OR
S
S
R
R'
OH
R
O
R
Synth. Commun., 1998, 2989
O
Synth. Commun. 2006, 36, 1751
R'
O
RSSR
RSH
Tetrahedron Letters 2002, 43, 6271
Synth. Commun., 2001, 1389
MMPP on Silica Gel
R
O
Jones Reagent on Silica Gel
H
OH
R
O
S
Br2
Hydrated Silica Gel
O
S
R
Synth. Commun. 2006, 36, 1769
R'
R
Jones Reagent on Silica Gel
R
R
CAN on Silica Gel
SH
P-TsOH
Silica gel
O
O
Hydrated Silica Gel
OR
Hydrated Silica Gel
S
S
O
S
R Synth. Commun., 2001, 3383 R
CAN on Silica Gel
R
Synth. Commun., 1998, 2969
(2 eq MMPP)
1
R
O
S
R
R
MMPP on Silica Gel
S
R
R
R
Sytnthesis 1997, 764
O
S
R
S
[RuCl3] and NaIO4 on Silica Gel
R
CH2Cl2 or DMC
(Project completed)
R
(1 eq MMPP)
R
O
S
R
O
[CrO3] + H5IO6
on silica gel
O
N Br
O
H
OH
Br
R
[P-TsOH]
O
Br
S
Br
N Br
N
R
R
O
R
R
O
O
N
Hydrated Silica Gel
R
R
O
S
Mg(ClO4)2
R'
R
SH
HO
O
S
S
R
R'
R
O
S R
Br2
Fluorous Phase
CH3CN + H2O
S R
S
Br2
Fluorous Phase
Anhydrous CH3CN
R
S
Br2
Fluorous Phase
R
R
R
O
S
R
Br
O
N Br
O
R
Br
R'
O
Catalyst
N
OH
[RuCl3] and NaIO4 on Silica Gel
SH
HS
S
S
R
R'
DMC
OH
R
S
CrO3 on Silica Gel
O
(Manuscript in preparation)
R
R
OH
CH2Cl2 or DMC
O
O
S
dry NaIO4
R
R
R
Hydrated silica gel
OH
R
O
O
OR
O
[RuCl3] and NaIO4 on Silica Gel
R
CrO3 on Silica Gel
R'
R'
OH
(Manuscript in preparation)
OR
CHO
R
S
H5IO6 on Silica Gel
R
(Manuscript in preparation)
N
R
OH
R
O
S
N
OH
H
R
N
Cl
+ Me I
CH2Cl2, heat
(Manuscript in preparation)
O
N Br
N
O
R-SH
R-S-S-R
(Manuscript in preparation)
II.
OH
+
O
R
R
R
Barbier Reaction
on Silica Gel
O
Br
CAN or (NH4)2S2O8
Supported on silica gel
Br
H
O
Solid Supported Reactions in Fluorous Solvent
2
C
N
Recently we became interested in combining solid supported reagents developed
in our laboratory with fluorous-organic bi-phase media. Fluorinated solvent or fluorous
media are organic solvents where fluorine atoms replaced hydrogens. Fluorous solvents
are extremely hydrophobic and chemically inert. Low toxicity, low volatility, and
thermal stability of fluorous solvents allow reactions in vigorous conditions. Fluorous
and organic solvents are immiscible at room temperature but are miscible at higher
temperature. Fluorous solvent, being heavier than organic solvents, when mixed with an
organic solvent sinks to the bottom. We are utilizing fluorous organic bi-phase media in
solid supported reagent methodology.
Performing reactions utilizing such a solidfluorous-organic tri-phase media is beneficial for the environment. We are at present
screening various solid supported reagents for solid-fluorous-organic triphase system.
A mixture of solid supported reagent, fluorous fluid, and an organic solvent
produce a solid-fluorous-organic tri-phase reaction media as shown in Fig 1. The
fluorous phase is located in between the solid supported reagent in the bottom and the
organic phase carrying the organic substrate at the top. The fluorous phase physically
separates the reagent from the substrate. Reaction mixtures is mechanically stirred or
heat is applied to the reaction mixture, if necessary, to perform the reaction.
Organic and Fluoro
monophase
Organic phase
Organic phase
Cool
Heat
Fluorous phase
Fluorous phase
Solid Supported
Reagent
Solid Supported
Reagent
A
B
Solid Supported
Reagent
C
Fig. 1 Principle of Solid-Fluorous-Organic Triphase Reaction
Upon heating, fluorous and organic phases become miscible, producing overall a
solid-liquid bi-phase system, Fig 1B, allowing the organic substrates in the liquid phase
to come into the contact of the reagent anchored on the solid support. The bi-phase
reaction media revert to tri-phase upon cooling, Fig 1C. At the end of the reaction, top
organic phase containing the reaction product is removed and the product is isolated by
evaporating the organic solvent under vacuum. Excess inorganic reagent and its byproducts remain attached to the solid support at the bottom of the reaction flask.
This procedure also allows to stop a reaction at any time by separating the
reagents from the organic substrates by turning the stirrer off or by cooling the reaction
mixture. Capability to control the progress of a reaction will be extremely useful for
reactions that require careful addition of reagents to prevent side reactions or highly
exothermic reactions.
III.
Construction of Small Strained Molecules
3
Numerous biologically as well as structurally interesting natural organic
compounds have cyclobutane ring incorporated in its structure. Examples include
grandisol, -pinene, nopinone, sterpurinol, acanthodoral, and trihydroxydecipiadiene.
CH3
H
OH
H
3-Sterpurinol
OH
O
OH
-pinene
(+) Grandisol
Nopinone
H
CHO
OH
Y
H
H
H
HO
Acanthodoral
OH
Trihydroxydecipiadiene
In addition to their presence in natural products, cyclobutane ring can serve as
building blocks for construction of complex organic molecules. The strain energy release
associated with the opening of cyclobutane ring offers possibilities for manipulations of
the cyclobutane ring to access molecules that are otherwise difficult to prepare. In this
regards cyclobutane ring can be regarded as a “pseudo functional group”.
We are developing procedures for construction of functionalized cyclobutane
rings utilizing [2+2] cycloaddition reactions promoted by solid supported lanthanide
catalysts. Lanthanide compounds, such as Yb(OTf)3, Sc(OTf)3, are very effective Lewis
acids at the same time they can tolerate water. As a result, they are good candidates for
supporting on solids using our procedure. Expensive lanthanide reagents supported on a
solid could be recovered and reused.
Our plans include synthesis of natural product acanthodoral utilizing [2+2]
cycloaddition reaction promoted by solid supported lanthanide reagent in the key step as
shown in Scheme-1.
Scheme-1
R'
+
O
O
R
Solid supported
lanthanide reagents
[2+2] Cycloaddition
4
R
R'
R
O
O
H
H
O
CH3
CH3
Supported reagent
[2 + 2] Cycloaddition
H
H
Acanthodoral
IV.
Ring Closing Metathesis (RCM) Reaction
We are developing synthetic procedures for nitrogen heterocyclic compounds
utilizing Ring Closing Metathesis (RCM) reaction.
For example, using 3Pyrazolidinones (1) as a common precursor we plan to prepare a wide variety of nitrogen
compounds, such as, azalactams (2), macrocyclic diamines (3), bicyclic hydrazines (4),
cyclic amines with pendant amino group (5), unsymmetrical N, N’-disubstituted amines
(6), among others. Some of these compounds are difficult to prepare by other known
procedures. Once established, we will utilize this protocol in the synthesis of nitrogen
containing natural products, such as, azatropane.
Scheme-2
R'
H
N
N
H
R
CO2Me
R
N
( )n
( )n
( )n
R
R
N
3
( )n
4
R'
H
O
O
CO2Me
NH
N
N
N
H
R
H
R
N
2
N
R
Azatropane
1
NHCO2Me
R
R'
V.
N
N
H
6
R
R
H
N
H
5
Fluorous Reagents
Among others, we are investigating fluorous Baylis-Hilman reaction as shown
below, Scheme-3. After unreacted aldehydes and organic base have been removed from
the reaction mixture by extracting the reaction mixture with a suitable organic solvent,
hydrolysis will produce the desired product. Recovered fluorous alcohol will be
recycled.
Scheme-3
5
O
RfCH2CH2 OH
RfCH2CH2 O
Cl
O
O
RfCH2CH2 O
+
+
H
O
Et3N
O
DABCO
THF
RfCH2CH2 O
OH
O
hydrolysis
OH
HO
+
RfCH2CH2 OH
6