Green Approaches To Asymmetric Catalytic Synthesis

155 Pages·2011·2.5 MB·English

by  Angela Patti (auth.)

SpringerBriefs in Molecular Science
Green Chemistry for Sustainability
Series Editor
Sanjay K. Sharma
For furthervolumes:
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Angela Patti
Green Approaches To
Asymmetric Catalytic
Synthesis
123
Angela Patti
National Research CouncilofItaly
Instituteof BiomolecularChemistry
Via PaoloGaifami 18
95126Catania
Italy
e-mail: [email protected]
ISSN 2191-5407 e-ISSN 2191-5415
ISBN 978-94-007-1453-3 e-ISBN978-94-007-1454-0
DOI 10.1007/978-94-007-1454-0
SpringerDordrechtHeidelbergLondonNewYork
(cid:2)AngelaPatti2011
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Preface
The importance of chirality in molecular recognition processes and the biological
activityofmanychiralpharmaceuticaldrugsandagrochemicalsisnowadayswell
acceptedandthereisacontinuousneedforsyntheticmethodsleadingtosingleor
enrichedenantiomers. Chiralcompounds alsofindapplication inthe development
of specific sensors for biological molecules and new materials with peculiar
properties related with ordered spatial arrangements.
Hystorically, nature has been the main source of chirality and many synthetic
processesreliedoncompoundsfrom‘‘chiralpool’’asstartingmaterials,resolving
agents for the separation of enantiomers from their racemate, or chiral auxiliaries
indiastereoselectivesynthesis.Inthelast20yearsasymmetriccatalyticreactions,
basedontheabilityofnonnaturalchiralcompoundsinsub-stoichiometricloading
topromotethe synthesisofasingleenantiomer inlarge amount throughselective
chiral multiplication effect, have became largely predominant exerting a tremen-
dous impact on the production of chiral compounds from achiral molecules. The
relevanceofthisapproach hasbeen acknowledgedbytheNobelprize awardedto
Sharpless, Noyori and Knowles for their fundamental research in this field. Most
catalysts are complexes of chiral ligands with transition metals and fine tuning of
sterical and electronic properties of the ligands has provided in many cases high
levelsofstereoselectivity,evenatverylowcatalystloading,suitableforindustrial
scale-up.
At the beginning of the 90s, the increasedattentionto the protection of human
and environmental health led to the development of ‘‘green chemistry’’, which
gives central emphasis to the design of new chemicals and processes aimed to
reduce or eliminate the use and generation of hazardous substances. This goal
could be achieved with a substantial modification of all the aspects of a chemical
processfromthemoreobvioususeofrenewablesourcesorwasteminimisationto
conceptualchangesinsyntheticreactionsinordertomaximizeatomeconomyand
limit derivatization steps whenever possible. Fundamental approaches of research
in this field are well summarised in the ‘‘twelve principles of Green chemistry’’
and, in this context, catalysis is a milestone in that it is often compatible with the
v
vi Preface
useoflesstoxicreagents,reductioninenergyrequirements,highproductivityand
simplification of separation procedures.
Since the effects of chiral drugs or agrochemicals in most cases reside on a
singleenantiomerwhiletheotherisinactiveordisplaysantagonistand/oradverse
effects,thereisanincreasingdemandofformulationscontainingstereochemically
pure active ingredients that beneficially allow reduced total administered dose,
enhancedtherapeuticwindoworactivityandsuppressionoftherisksassociatedto
the‘‘inactive’’enantiomer.Inthiscontext,asymmetriccatalysishasgatheredakey
role in organic synthesis and much research has been focused on its advance in a
more sustainable direction.
Considerable efforts have been carried out for structural optimization of the
catalysts, since asymmetric induction is directly related with their chemical, ste-
reochemical,electronicandsteric properties.Intransition-metalcatalysis,besides
the most investigated C -symmetrical ligands, unsymmetrically disubstituted or
2
monodentate ligands and bifunctional catalysts have been also explored in con-
junction with the use of less toxic and/or less expensive metals, leading to an
expanded portfolio of effective asymmetric reactions today available. Simulta-
neously, the first report ten years ago of a proline-catalysed direct asymmetric
aldol reaction opened the door to ‘‘organocatalysis’’ that has emerged as a pow-
erful methodology, complementary to biocatalytic and metal-transition catalysis,
with attractive features in high operational simplicity, low cost and toxicity of
catalysts and the possibility to perform several reactions through different acti-
vation modes.
In the search for more benign alternatives to organic solvents, many of which
are volatile, flammable and harmful for human and environmental health, water,
ionic liquids and fluorinated solvents have been largely investigated and biphasic
liquid-liquid systems based on these non conventional reaction media have
allowed the selective recover and recycle of chiral catalysts, providing that they
were suitably labeled with ionic or fluorous substituents in order to increase their
phase-affinity. In a complementary recycle strategy, a variety of active catalysts
havebeenimmobilizedonmacromolecularsupportsandrecoveredbysolid–liquid
separations. The productivity of some asymmetric reactions has been markedly
improved through the application of microwave irradiation as non-conventional
heating source or the development of continuous-flow reactors, which have pro-
videdmoreprolongedcatalystlife,reductionofsolventwasteandsimplificationof
workup procedures. As concerns the design of new synthetic strategies, enantio-
selective cascade reactions represent an emerging and exciting research field for
theirpotentialintheconstructionofcomplexmoleculesfromsimpleprecursorsin
a single process, thus avoiding the costly protection/ deprotection steps and
purification of intermediates.
Herein is presented a general overview of the approaches currentlyapplied for
‘‘green’’ optimization of the different factors contributing to the overall efficiency
of an asymmetric catalytic process together with selected examples taken from
seminal references in the field and the past five-year literature. Rather than a
comprehensivediscussionofeachargumentthistextoffersaconcisemanualofthe
Preface vii
fundamental concepts with the aim to stimulate the interest of readers in new
opportunities offered to chemists for synthetic buildup of stereochemical and
molecular complexity, preserving at the same time human and environmental
resources.

Acknowledgements
GratefulthanksareduetoProf.MarioPiattelliforhelpfulsuggestionsandrevision
of manuscript, to Mr. Agatino Renda for technical assistance and to Dr.ssa Sonia
Pedotti for continuous and fruitful research collaboration.
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