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Volume 2, 2006
Contents
Foreword Pp. iv-vi
Editorial Pp.
1
Electrophilic Fluorination with Elemental Fluorine and Reagents
Derived from it Pp. 3
Shlomo Rozen
[Abstract]
The Chemistry of Interhalogen Monofluorides Pp.
43
Dale F. Shellhamer and Victor L. Heasley
[Abstract]
Fluorination Using Hypervalent Halogen Fluorides Pp.
49
Shoji Hara
[Abstract]
Application of Xenon Difluoride in Synthesis Pp.
61-
Barbara Zajc
[Abstract]
N-Fluoropyridinium Salts, Synthesis and Fluorination Chemistry
Pp. 159
Teruo Umemoto
[Abstract]
Onium-Poly Hydrogen Fluorides as Acid Catalysts, Ionic Liquids
and Fluorinating Agents in Organic Reactions Pp. 183
V. Prakash Reddy, G.K. Surya Prakash and George A. Olah
[Abstract]
N-Fluoro-1,4-Diazoniabicyclo[2.2.2]octane Dication Salts;
Efficient Fluorinating Agents and Functionalization Mediators for
Organic Compounds Pp. 213
Stojan Stavber and Marko Zupan
[Abstract]
α,α-Fluoroalkyl(Alkenyl)
Amino Reagents (FAR) - Recent Development Pp. 269
Viacheslav A. Petrov
[Abstract]
DAST and Deoxofluor Mediated Nucleophilic Fluorination Reactions
of Organic Compounds Pp. 291
Rajendra P. Singh, Dayal T. Meshri and Jean’ne M. Shreeve
[Abstract]
Synthetic Approaches to gem-Difluoromethylene Compounds
Pp. 327
V. Prakash Reddy, Meher Perambuduru and Ramesh Alleti
[Abstract]
Fluorinated Polycyclic Aromatic Hydrocarbons(PAHs) and Heterocyclic
Aromatic Hydrocarbons (Hetero-PAHs); Synthesis and Utility Pp.
353
Takao Okazaki and Kenneth K. Laali
[Abstract]
Fluorinated Carbohydrates Pp. 381
Martin Hein and Ralf Miethchen
[Abstract]
Enantioselective Electrophilic Fluorination: The Complete
Story Pp. 431
C. Audouard, J.-A. Ma and D. Cahard
[Abstract]
Synthesis of Chiral Fluorinated Materials via Biotransformation
Pp. 463
Tomoya Kitazume, Tomoko Matsuda and Kaoru Nakamura
[Abstract]
Recent Advances in the Chemistry of Fluorine- Containing
π-Allylmetal
and Allenylmetal Complexes Pp.491
Tsutomu Konno and Takashi Ishihara
[Abstract]
Synthetic Utility of Fluorinated β-Keto-Phosphonium
Salts, -Phosphonates and Related Compounds Pp. 523
Yanchang Shen
[Abstract]
Abstracts
[Back to top]
Foreward
Academic and industrial fluorine chemistry has experienced over
the past decade or so a shift in emphasis from research on highly
fluorinated materials to research on lightly fluorinated compounds.
This in large part is because of the significant commercial impact
of new fluorine-containing pharmaceuticals and agrochemicals coupled
with the overall optimism about opportunities for sustained growth
of fluorinated biologically active materials. More recently, a growing
concern about the environmental fate of some highly fluorinated
materials also has been a contributing factor. A consequence of
this change in emphasis is that many of the centers of specialized
excellence in traditional fluorine chemistry are much less prominent
today, or they have disappeared altogether. Witness, for example,
the dramatic change in industrial and academic fluorine chemistry
in the UK over the past couple decades, and the same trend is evident
in the US and Russia/CIS. It should come as no surprise, therefore,
that synthetic fluorine chemistry is increasingly being practiced
by chemists who would not consider themselves to be fluorine chemists.
These chemists are mainly interested in useful, practical methods
for introducing one or two fluorines, or a trifluoromethyl group,
at specific sites in a molecule. Commercially available fluorinating
agents or fluorinated starting materials and methods that do not
require specialized laboratory equipment or handling procedures
are of prime importance to these practitioners. This new volume
for the Advances in Organic Synthesis series edited by
Professor Kenneth Laali admirably fulfills most of these needs.
An obvious strength of this volume is that its sixteen chapters
were written by experts who either invented the various fluorinating
agents and methods or helped scope the chemistry and applications.
The coverage is intentionally not historical but rather contemporary
where most of the literature citations are less than ten years old.
This captures the modern developments and applications, but the
non-expert may find the need to refer to earlier literature for
a more comprehensive perspective.
The volume is a tour de force on electrophilic fluorinating agents
and their chemistry, leading off with selective fluorinations using
elemental fluorine and mainly acetyl hypofluorite, which is easily
and inexpensively generated from sodium acetate and fluorine. This
methodology more than any other covered in this volume does require
special care and equipment for handling elemental fluorine, but
this should not be a deterrent since reliably safe procedures have
been developed and published, for example, in Organic Syntheses.
The next two chapters cover the use of interhalogen monofluorides,
mainly BrF and IF generated in situ from the halogen and
elemental fluorine, and their hypervalent halogen fluoride counterparts
BrF3 and IF5, plus ArIF2, which
is the most stable class of hypervalent halogen fluorides. The following
chapter, the longest one with 97 pages and 262 references, is an
Organic Reactions style survey of contemporary reactions
of xenon difluoride. The diverse applications of XeF2
in synthesis are truly remarkable, although in most cases alternative
less-expensive fluorinating agents do as well or better. An exception
and an underutilized method is the “fluoro-Hunsdiecker”
reaction where XeF2 cleanly converts primary or tertiary
alkyl carboxylic acids to alkyl fluorides in good to excellent yields.
Olah’s pyridinium and dimethyl ether polyhydrogen fluorides,
Umemoto’s N-fluoropyridinium salts, and the N-fluoro-1,4-diazoniabicyclo[2.2.2]octane
dication salts (SelectfluorTM, AccufluorTM),
which are among today’s most popular and versatile reagents
for selective electrophilic fluorinations, are thoroughly reviewed
in the last three chapters on electrophilic agents. A particular
highlight of this volume is the complementary Chapter 13 that reviews
enantioselective electrophilic fluorinations employing various optically
active N-F sulfonamides and sultams, and N-fluoroamine salts of
cinchona alkaloids (generated by transfer fluorination of the alkaloids
with SelectfluorTM). Enantioselective fluorinations with
achiral N-F reagents catalyzed by chiral organometallic complexes
also are described. This is state-of-the art methodology for direct
chiral fluorinations, and although there remains room for improvement
in the observed ee’s, its importance to the increasing demand
for optically pure pharmaceuticals and agrochemicals cannot be overemphasized.
Recent developments in nucleophilic fluorinations of primarily
alcohols and carbonyl compounds and their derivatives mediated by
the classical FAR (fluoroalkyl or –alkenyl-amino reagents)
and DAST (diethylaminosulfur trifluoride) reagent and its modern
analog Deoxofluor®, are nicely reviewed in Chapters 8 and 9.
The former updates the use of the familiar Yarovenko-Raksha reagent,
CFHClCF2N(C2H5)2, and
Ishikawa’s reagent, CF3CFH CF2N(C2H5)2/CF3CF=CFN(C2H5)2,
and introduces a new, relatively inexpensive reagent CF2HCF2N(CH3)2
that is easily made from tetrafluoroethylene and dimethylamine.
Altho-ugh it is not commercially available yet, it promises to be
superior to the traditional FAR offerings.
The following chapters on the synthesis of gem-difluoromethylene
compounds, lightly fluorinated polycyclic aromatic hydrocarbons,
and fluorinated carbohydrates illustrate many useful applications
for several of the electrophilic and nucleophilic reagents from
the preceding chapters. These reviews describe and sometimes critically
compare the available options for introducing fluorine, but the
reader likely will have to consult the primary literature cited
to decide on the best choice to accomplish the desired transformation.
The chapter on synthesis of chiral fluorinated materials via
biotransformations is thematically rather out of place with the
rest of the volume since it does not deal with fluorination reactions
per se but rather covers enantioselective or diastereoselective
reactions of fluorinated molecules promoted by biocatalysts, including
lipase-catalyzed hydrolyses (kinetic resolutions) of fluorinated
esters to chiral alcohols, enantioselective acetylations of trifluoromethyl-containing
alcohols, and dead-cell promoted asymmetric reductions of trifluoromethylated
ketones. Nonetheless, these green processes represent very useful
methods for synthesizing chiral building blocks and products that
should be part of the modern chemist’s arsenal of synthetic
methods.
It is unrealistic to expect that this single volume can cover all
of the significant advances in synthetic fluorine chemistry. Although
Rupert’s reagent, (CH3)3SiCF3,
is briefly described in a couple of chapters, it along with other
nucleophilic trifluoromethylating reagents warrant more extensive
coverage. Absent are modern sources of truly anhydrous fluoride
ion, as well as the new mild reagents and procedures to generate
difluorcarbene for the synthesis of fluorinated cyclopropanes and
difluoromethyl ethers, for example. One would hope that Professor
Laali or an equally competent editor has plans for a second volume
that will include these omissions and update other advances in synthetic
organofluorine chemistry.
In summary, this book is a valuable addition to the repertoire
of modern synthetic organofluorine chemistry and an excellent source
of information for synthetic chemists interested in selective fluorination
methods and fluorinated building blocks.
Bruce E. Smart
Regional Editor
Journal of Fluorine Chemistry
DuPont Central Research & Development
Wilmington, DE
USA
[Back to top]
Editorial
I was first introduced to fluorine chemistry over 30 years ago
as a PhD student at Manchester University (with Robert Hazseldine).
My involvement and interest in organofluorine chemistry grew during
my postdoctoral years, in particular while in George Olah’s
laboratory. Over the years, my research activities and interests
branched out into other areas of mechanistic and synthetic chemistry,
but I continued to maintain serious interest in fluorine chemistry
and managed to keep some research activity going in the field whenever
possible. Today’s synthetic organofluorine chemists have at
their disposal a wide range of both electrophilic and nucleophilic
fluorinating agents whose reactivities/ selectivites may be tuned
to the task at hand. Further exciting new developments include the
synthesis and utility of chiral electrophilic fluorinating agents,
application of transition metal catalysis to enantioselective electrophilic
fluorination, biotransformations for synthesis of chiral fluorinated
materials, and the emergence of “tamed” fluorination
under “green” conditions. Whether by improving on the
more traditional reagents or by developing newer, more task-specific
agents, the repertoire of synthetic organofluorine chemistry has
greatly expanded during the last decade; and these advances are
bound to create greater diversity in terms of structural, physical,
and biological properties.
Early in 2004 I received an invitation from Dr. Atta-ur-Rahman,
Editor for “Advances in Organic Synthesis”,
to act as Executive Guest Editor for a volume within this series,
on a topic of my own choice. I had contemplated for some time to
edit and/or co-write a volume focusing on selected aspects of organofluorine
chemistry, with an emphasis on recent advances. The invitation signaled
an opportunity and created the impetus for me to begin the task
of getting the project off the ground. I have been most fortunate
that a large group of active scientists and leading researchers
in the field expressed interest in this project and agreed to contribute.
As editor, my goal has been to oversee the creation of a series
of focused and self-contained chapters that summarize and put into
perspective (preferably in a comparative fashion) the more recent
advances in the field. The collection should serve as a valuable
guiding source on the reactivity trends, efficacy, and scope which
are illustrated via examples. It is gratifying to see that the final
outcome far exceeded my initial expectations.
Comment on the Order of Chapters
In organizing this multi-authored volume, I felt it would be most
appropriate that the first four chapters deal with recent developments
involving the well established, older, reagents (such as elemental
fluorine, interhalogen monofluorides, hypervalent halogen mono-fluorides,
and xenon difluoride). The ensuing nine chapters delineate/describe/outline
the progress in synthetic fluorination chemistry involving the more
recently developed electrophilic and nucleophilic reagents (such
as N-fluoropyridinium, onium polyhydrogen fluorides, Selecfluor,
the chiral NF compounds, DAST and Deoxofluor), while the last three
chapters focus on enzymatic synthesis and the organometallic/heteroatom
chemistry aspects.+
Chapter Summaries:
The volume brings together sixteen contributions by experts from
seven countries:
Chapter 1. (by S. Rozen) describes the regio- and stereospecific
electrophilic fluorination of tertiary centers and double bonds
employing tamed F2, while also illustrating some new chemistry involving
acetyl hypofluorite.
Chapter 2. (by D. Shellhammer and V. Heasley) focuses on in situ
generation and the scope of fluorination involving interhalogen
monofluorides XF (X = Cl, Br, I).
Chapter 3. (by S. Hara) deals with the characteristic features
and representative reactions involving hypervalent halogen fluorides
BrF3, IF5 and ArIF2.
Chapter 4. (by B. Zajc) provides a comprehensive coverage of the
organofluorine chemistry of XeF2 with emphasis on the more recent
studies.
Chapter 5. (by T. Umemoto) summarizes the synthetic routes to a
variety of N-Fluoropyridinium salts with variable fluorinating power,
illustrating their synthetic scope.
Chapter 6. (by V.P. Reddy, G.K.S. Prakash and G.A. Olah) is devoted
to onium polyhydrogen fluorides and their fluorination chemistry.
Chapter 7. (by S. Stavber and M. Zupan) focuses on NF dication
salts as efficient electrophilic fluorinating agents as well as
functionalization mediators.
Chapter 8. (by V.A. Petrov) reviews the synthetic methods and utility
of “FAR” reagents.
Chapter 9. (by R.P. Singh, D.T. Meshri and J.M. Shreeve) is devoted
to nucleophilic fluorination with DAST and Deoxofluor.
Chapter 10. (by V.P. Reddy, M. Perambuduru and R. Alleti) reviews
the available methods for synthesis of gem-difluoromethylene compounds.
Chapter 11. (by T. Okazaki and K.K. Laali) focuses on the synthesis
and utility of fluorinated PAHs.
Chapter 12 (by M. Hein and R. Miethchen) provides a review of the
methods that have so far been used in carbohydrate chemistry to
synthesize fluorinated sugars and examines the utility of glycosyl
fluorides in chemical and enzymatic glycosylations.
Chapter 13. (by C. Audouard, J.-M. Ma and D. Cahard) reviews and
evaluates recent progress in enantioselective electrophilic fluorination.
Chapter 14. (by T. Kitazume, T. Matsuda and K. Nakamura) demonstrates
how chiral fluorinated compounds can by prepared enzymatically.
Chapter 15. (by T. Konno and T. Ishihara) is devoted to fluorinated
pi-allyl and pi-allenyl metal complexes and their chemistry.
Chapter 16. (by Y. Shen) concentrates on fluorinated beta-keto-phosphonium
salts and –phosphonates and their efficacy in synthesis.
Kenneth K. Laali (Executive Guest Editor)
Department of Chemistry
Kent State University
Kent
OH 44242
USA
E-mail: Klaali@kent.edu
[Back to top]
Electrophilic Fluorination with Elemental Fluorine and Reagents
Derived from it
Shlomo Rozen
Elemental fluorine is a highly reactive reagent which could destroy
almost any organic compound or perfluorinate it under controlled
conditions. However, under the right set of conditions, it may act
as an electrophile and as such, it can be a powerful electrophile
indeed. This chapter describes some regio- and stereospecific electrophilic
fluorination at saturated tertiary sp3 centers,
which are usually very unreactive and cannot participate in specific
organic reactions. It was concluded that the higher the hybridization
on p of these centers, the better is the outcome of the
reaction. In many cases, the substitution of such tertiary hydrogen
takes place in yields of 70% and more. Such fluorinations, which
were carried out on a wide variety of organic compounds, provide
an excellent opportunity for dehydrofluorination reactions to form
double bonds and hence are considered to enable functionalization
of “impossible sites” in organic molecules. Elemental
fluorine was also used for fluorination of double bonds, in a syn
mode, replacing the old and inefficient method of reacting olefins
with Pb(OAc)4 and HF. Acetyl hypofluorite is easily and
readily made from sodium acetate and F2. It proved to
be a very useful reagent for fluorination of activated aromatic
compounds, for addition across double bonds, in order to synthesize
biologically important fluorine containing derivatives, for constructing
α-fluoro
carbonyl and ether derivatives and for use in Positron Emitting
Tomography (PET).
[Back to top]
The Chemistry of Interhalogen Monofluorides
Dale F. Shellhamer and Victor L. Heasley
Interhalogen monofluorides (XF; X=Cl, Br or I) generated in
situ from hypohalites or N-halosuccinimides and a source of
fluoride ion are “sluggish” electrophiles. XF reagents
formed from F2 gas and a halogen source (ie: ClF3,
Br2, I2,) are very reactive electrophiles.
This wide range of reactivity allows the synthetic chemist to carry
out reactions on electron-rich or electron-deficient substrates.
Halofluorinations of alkenes, alkynes and electrophilic aromatic
substitution without catalyst are reviewed. Synthesis of geminal
difluorides from hydrazones is also presented.
[Back to top]
Fluorination Using Hypervalent Halogen Fluorides
Shoji Hara
Among various hypervalent halogen fluorides, BrF3, IF5,
and ArIF2 have been successfully used to introduce fluorine
atoms into molecules selectively. Characteristic features and representative
fluorination reactions involving these reagents are shown.
[Back to top]
Application of Xenon Difluoride in Synthesis
Barbara Zajc
Reactions of xenon difluoride (XeF2) with alkanes,
carbanions, alkenes and alkynes, aromatic and heteroaromatic compounds,
carbonyl derivatives, benzyl alcohols, organic iodo compounds, organosulfur,
selenium, tellurium, phosphorus, antimony, bismuth, silicon and
tin compounds are reviewed. Greater emphasis has been placed
on the synthetic details and utility. For each functional group,
the most recent papers describing the reactivity of XeF2
are discussed in more detail. Research progress achieved during
the period 1999-2004 is reviewed rather comprehensively. Also included
are the syntheses of compounds containing C-Xe(II) bond employing
xenon difluoride and its derivatives.
[Back to top]
N-Fluoropyridinium Salts, Synthesis and Fluorination
Chemistry
Teruo Umemoto
Synthesis of N-fluoropyridinium salts and their synthetic
application are discussed. Various types of stable N-fluoropyridinium
salts are synthesized from unsubstituted and substituted pyridines
and acids, their salts, silyl esters or Lewis acids by reaction
with F2 diluted with N2. The N-fluoropyridinium
salts are particularly useful as electrophilic fluorinating agents
toward organic compounds in terms of easy handling and variability
of fluorinating power and selectivity. This variability makes selective
fluorination of a wide range of organic compounds differing in reactivity
possible. Three classes of power- and selectivity-variable fluorinating
agents, non-counterion-bound N-fluoropyridinium salt series,
counterion-bound N-fluoropyridinium-sulfonate series, and
dimeric N,N’-difluorobipyridinium salt series, were
developed and successfully utilized for selective fluorinations
of various substrates. As another synthetic application, a novel
base-initiated reaction of N-fluoropyridinium salts producing
α-fluoropyridines
is discussed.
[Back to top]
Onium-Poly Hydrogen Fluorides as Acid Catalysts, Ionic Liquids
and Fluorinating Agents in Organic Reactions
V. Prakash Reddy, G.K. Surya Prakash and George A. Olah
Onium-poly hydrogen fluorides, the amine or ether complexes of
hydrogen fluoride, have been widely used as fluorinating agents
in organic synthesis. A variety of fluorination reactions involving
electrophilic additions to unsaturated compounds, nucleophilic substitutions,
desulfurative fluorinations, strained ring-opening fluorinations,
and deprotection of acetal, ketal and O-silyl ethers could be achieved
with these onium-poly hydrogen fluorides. Fluorination of alcohols
could be achieved under either SN1 or SN2
conditions, depending on the reagent choice and reaction conditions.
Deaminative fluorinations using these reagents provide convenient
access to chiral α-fluoro
acids. As strong Bronsted acids they can be used to catalyze the
electrophilic alkylation of alkanes with alkenes to give high-octane
gasoline-range hydrocarbons. They also serve as high dielectric
constant ionic liquid media. In addition, polymer-supported onium
polyhydrogen fluorides such as polyvinylpyridinium polyhydrogen
fluoride (PVPHF) have been developed as convenient alternative reagents,
which could be recovered and recycled for further use.
[Back to top]
N-Fluoro-1,4-Diazoniabicyclo[2.2.2]octane Dication Salts;
Efficient Fluorinating Agents and Functionalization Mediators for
Organic Compounds
Stojan Stavber and Marko Zupan
Fluorination of organic compounds using the most representative
reagents from the group of N-fluoro-1,4-diazoniabicyclo[2.2.2]octane
dication salts is reviewed. Data dealing with selective fluorofunctionalization
of aro-matics, alkenes, alkynes, saturated hydrocarbons, organometallics,
and organic molecules bearing nitrogen, sulfur, phosphorus, silicon
or carbonyl containing functional groups with SelectfluorTM
F-TEDA-BF4 1 (1-chloro-methyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane
bis(tetra-fluoroborate)), Ac-cufluorTM NFTh 2
(1-fluoro-4-hydroxy-1,4-diazoniabicyclo [2.2.2]octane bis(tetrafluoroborate))
or bis(NF)-TEDA-BF4 3 (1,4-difluoro-1,4-diazoniabi-cyclo[2.2.2]octane
bis (tetrafluoroborate)) are systematically collected and comparatively
evaluated. Fluorination of potentially bioactive organic mole-cules
(steroids, pyrimidine bases, glycols …) with the above mentioned
reagents is particularly emphasized. Functionalization of organic
compounds mediated by SelectfluorTMF-TEDA-BF4
is briefly reviewed.
[Back to top]
α,α-Fluoroalkyl(Alkenyl)
Amino Reagents (FAR) - Recent Development
Viacheslav A. Petrov
The review provides an update on the synthesis α-Fluoroalkyl
(alkenyl)Amino Reagents (FAR) and their application for conversion
of hydroxy- and carbonyl compounds into the corresponding fluorides.
The first part of the review contains data on the synthesis of
FAR by addition of secondary amines to fluoroolefins, halogen exchange
reactions, fluorination of carbonyl and thiocarbonyl compounds,
as well as via electron transfer reactions of polyfluorinated
bromoalkanes. The second section summarizes data on the physical
properties, handling and storage of FAR. The third section of the
review discusses the reactions of FAR with primary, secondary, tertiary,
and cyclic alcohols, as well as sugars, carbonyl and thiocarbonyl
compounds, and acids, which have been developed during the past
decade. Recent results on the chemical transformations of FAR other
than fluorination reactions are collected in the final section of
the review.
[Back to top]
DAST and Deoxofluor Mediated Nucleophilic Fluorination Reactions
of Organic Compounds
Rajendra P. Singh, Dayal T. Meshri and Jean’ne M. Shreeve
Organofluorine compounds have had a marked impact on medicinal
and agrochemical fields and the number of applications continues
to grow. These significant contributions arise from the unique changes
that occur in the physical and chemical properties of ordinary organic
compounds wrought by the presence of fluorine or a fluorine-containing
group. Among a large number of methods available to introduce fluorine
into organic compounds, the nucleophilic replacement of oxygen with
fluorine is one of the most practical ways. Although there are numerous
fluorinating reagents available, diethylaminosulfur trifluoride
(DAST) and bis(2-methoxyethyl)aminosulfur trifluoride (Deoxofluor)
often are the reagents of choice. Organic compounds containing oxygen
in hydroxyl and carbonyl groups are readily converted into their
corresponding fluorinated analogues by the introduction of one or
two fluorine atoms, respectively, through the use of these reagents.
In some cases, depending upon the compound and the reaction conditions,
a very useful nonfluorinated product can also be produced. Our interest
in applying various synthetic methods to incorporate fluorine or
a fluorinated group into a large variety of organic compounds encouraged
us to summarize the recent chemistry of DAST and Deoxofluor.
[Back to top]
Synthetic Approaches to gem-Difluoromethylene Compounds
V. Prakash Reddy, Meher Perambuduru and Ramesh Alleti
Organic compounds containing a gem-difluoromethylene group are
useful for a variety of applications in biological, pharmaceutical
and materials chemistry. Over the years a variety of synthetic protocols
for this class of compounds have been developed. They can be prepared
from their corresponding carbonyl compounds or through various derivatives
such as oximes and dithiolanes, electrophilic fluorinations of unsaturated
compounds and enolates, free-radical additions of halodifluoroalkanes
to olefins, and nucleophilic difluoromethylations of aldehydes and
ketones. Other approaches involve methods that utilize fluorinated
compounds as synthons. Enantioselective gem-difluorination
reactions have emerged employing chiral auxiliaries such as sulfinimines,
and chiral Lewis acid catalysts. This review focuses on the recent
developments in this area, emphasizing the synthetic methods that
can be conveniently carried out and are potentially broadly applicable.
[Back to top]
Fluorinated Polycyclic Aromatic Hydrocarbons(PAHs) and Heterocyclic
Aromatic Hydrocarbons (Hetero-PAHs); Synthesis and Utility
Takao Okazaki and Kenneth K. Laali
Fluorinated aromatic compounds are in high demand in a number of
fields including synthetic chemistry, molecular recognition/host-guest
chemistry, materials chemistry, as well in biology and pharmaceuticals.
Recent progress in the synthesis of fluorinated polycyclic hydrocarbons
and heterocyclic hydrocarbons is reviewed.
[Back to top]
Fluorinated Carbohydrates
Martin Hein and Ralf Miethchen
The review demonstrates how carbohydrate chemists exploit the
two fundamental strategies of organofluorine chemistry; (a) direct
introduction of fluorine atom(s) or fluorinated groups by appropriate
reagents in a late synthetic step, or (b) linking of fluorine-containing
“building blocks“ with various reactants (including
enantioselective approaches), in order to synthesize a wide variety
of fluorinated sugars. Numerous representative examples of these
strategies are provided and discussed. Also included are a number
of recommended experimental procedures (provided at the end of sections
1-3). In addition to reviewing various convenient fluorinating reagents
that have so far been applied to carbohydrate chemistry, the utility
of glycosyl fluorides in chemical and enzymatic glycosylations are
also examined.
[Back to top]
Enantioselective Electrophilic Fluorination: The Complete
Story
C. Audouard, J.-A. Ma and D. Cahard
Progress in the field of enantioselective electrophilic fluorination
during the past eighteen years resulting from fascinating research
conducted by twelve international groups is reviewed. Two complementary
strategies for the synthesis of enantiopure fluorine-containing
molecules currently define state-of-the-art in this area. The use
of chiral, non-racemic fluorinating agents is the most general approach
while catalytic methods using either transition-metal catalysts
or organocatalysts apply to specific substrates.
[Back to top]
Synthesis of Chiral Fluorinated Materials via Biotransformation
Tomoya Kitazume, Tomoko Matsuda and Kaoru Nakamura
Biotransformation of organofluorine materials into the optically
active functionalized fluorinated materials along with the discussion
on the effect of fluorine atom(s) during the enantioselective and/or
diastereoselective transformations is described. The ability of
microorganism to discriminate between enantiomers is very important
for the purpose of resolution and asymmetric synthesis. Also included
are discussions on recent developments in methodologies to control
enantioselectivities of catalytic reactions. Examples of practical
applications that involve reduction of various types of ketones
are also included.
[Back to top]
Recent Advances in the Chemistry of Fluorine- Containing
π-Allylmetal
and Allenylmetal Complexes
Tsutomu Konno and Takashi Ishihara
π-Allylmetal
complexes derived from α-fluoroalkylated
allyl mesylates react smoothly with various nucleophiles such as
stabilized carbanions, carboxylates, and amines at the carbon distal
to a fluoroalkyl group in a highly regioselective manner to give
the corresponding γ-products
in high to excellent yields. Treatment of the above fluorine-containing
π-allylmetal
complexes with hydride nucleophile gives the adducts derived from
the hydride attacking on the carbon attached to a fluoroalkyl group.
The γ-adducts,
obtained by the reaction of π-allylpalladium
complex with α-methoxy
acetate or N-protected glycine, undergo smooth Ireland-Claisen
rearrangement to give the corresponding multi-functionalized molecules
in high yields. On the other hand, the reaction of α-fluoroalkylated
propargylic mesylates with zinc reagents or stabilized carbanions
in the presence of palladium catalyst affords fluorine-containing
allene or furan derivatives respectively, in high yields, via
allenylpalladium complex.
[Back to top]
Synthetic Utility of Fluorinated β-Keto-Phosphonium
Salts, -Phosphonates and Related Compounds
Yanchang Shen
Sequential transformations have attracted much interest in recent
years because they provide simple and efficient entry into complex
compounds by including two or more steps in a single operation to
increase the complexity of the substrate, starting from commercially
available, relatively simple precursors. The new methodologies discussed
in this review chapter are based on sequential transformations and
possess high stereoselectivity. They include the synthetic utility
of fluorinated β-keto-phosphonium salts, “one-pot”
carbon-carbon double bond formation, ylide-ion formation resulting
from nucleophilic addition, stereocontrolled olefination method,
alkenylation based on elimination of triphenylarsine, reductive
olefination mediated by Ti(O-i-Pr)4 and Ph3P
and sequential transformation of organophosphorus compounds in organic
synthesis. The newly discussed methodologies are, therefore, potentially
useful in organic synthesis particularly in the medicinal and agricultural
chemistry for the synthesis of biologically active compounds.
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