Review Article Organocatalysis: Key Trends in Green Synthetic Chemistry, Challenges, Scope ...

36 Pages·2015·2.91 MB·English

Hindawi Publishing Corporation
Journal of Catalysts
Volume 2014, Article ID 402860, 35 pages
http://dx.doi.org/10.1155/2014/402860
Review Article
Organocatalysis: Key Trends in Green Synthetic Chemistry,
Challenges, Scope towards Heterogenization, and Importance
from Research and Industrial Point of View
IsakRajjakShaikh1,2,3
1DepartmentofChemistry,ShriJagdishprasadJhabarmalTibrewalaUniversity,Vidyanagari,Jhunjhunu-ChuruRoad,
Chudela,JhunjhunuDistrict,Rajasthan333001,India
2RazakInstitutionofSkills,EducationandResearch(RISER),Shrinagar,NearRafaiyaMasjidandHanumanMandir,
Nanded,MaharashtraState431605,India
3PostGraduateandResearchCentre,DepartmentofChemistry,PoonaCollegeofArts,ScienceandCommerce,CampArea,
Pune411001,MaharashtraState,India
CorrespondenceshouldbeaddressedtoIsakRajjakShaikh;[email protected]
Received26September2013;Revised17December2013;Accepted23December2013;Published26March2014
AcademicEditor:SankaranarayanaPillaiShylesh
Copyright©2014IsakRajjakShaikh.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,
whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Thispaperpurportstoreviewcatalysis,particularlytheorganocatalysisanditsorigin,keytrends,challenges,examples,scope,
andimportance.Thedefinitionoforganocatalystcorrespondstoalowmolecularweightorganicmoleculewhichinstoichiometric
amountscatalyzesachemicalreaction.Inthisreview,theuseofthetermheterogenizedorganocatalystwillbeexclusivelyconfinedto
acatalyticsystemcontaininganorganicmoleculeimmobilizedontosomesortofsupportmaterialandisresponsibleforaccelerating
achemicalreaction.Firstly,abriefdescriptionofthefieldisprovidedputtingitinagreenandsustainableperspectiveofchemistry.
Next,researchfindingsontheuseoforganocatalystsonvariousinorganicsupportsincludingnano(porous)materials,nanoparticles,
silica,andzeolite/zeoliticmaterialsarescrutinizedinbrief.Thenfuturescope,researchdirections,andacademicandindustrial
applicationswillbeoutlined.Asuccinctaccountwillsummarizesomeoftheresearchanddevelopmentsinthefield.Thisreview
triestobringmanyoutstandingresearchestogetherandshowsthevitalityoftheorganocatalysisthroughseveralaspects.
1.Introduction present-daychemicalindustryistocontinueprovidingappli-
cations and socioeconomic benefits in an environmentally
In1987,theUnitedNationsCommissiononEnvironmentand friendlymanner.
Development(BrundtlandCommission)[1]defined“sustain- Over the last few decades, green chemistry has been
abledevelopment”asthedevelopmentthatmeetstheneeds recognizedasacultureandmethodologyforachievingsus-
of the present without compromising the ability of future tainabledevelopment[2].Greenchemistryischemistryable
generationstomeettheirownneeds.Twoofthekeyaspects topromoteinnovativetechnologiesthatreduceoreliminate
of sustainable development from an energy and chemical theuseorgenerationofhazardoussubstances.Anastasand
perspective are to develop more renewable forms of energy Warnerdefinedthe12principlesofgreenchemistry(Figure1)
and to reduce pollution. Chemistry during the twentieth [3]. Catalysis (including enzyme catalysis, heterogeneous
centurychangedthelivingstandardofhumanbeings.Among catalysis,andorganocatalysis,inparticular)isidentifiedtobe
the greatest achievements of chemistry are petrochemical attheheartofgreeningofchemistry[4]becausethisbranch
andpharmaceuticalindustries.Buttheseindustriesareoften of science is found to reduce the environmental impact of
blamed for polluting environment. The challenge for the chemicalprocesses[5].
2 JournalofCatalysts
esis
h
nt
y
my al s
no mic
e om eco us che
Prevent wast Maximize at Less hazardo
1() 2() 3()
(12) Minimize potential (4) Safer chemicals and products
for accidents
(11) Analyze in real time (5) Safety solvents and reaction conditions
to prevent pollution
(10) Design chemicals (6) Increase energy efficiency
and products to degrade after use
9() Use catalysts void chemical derivatives(protecting groups) Use renewable feedstocks
8) A 7()
(
Figure1:Inspiredbythe12principlesofgreenchemistry,from[3].
2.Catalysis:AMultidisciplinary
Transition state
AreaofChemistry
Catalyst is one of the few conceptual words that have
carriedoverbroadlyoutsidescientificlanguage.Catalysisis
a significant multidisciplinary area of chemistry. The term Catalysis
“catalysis” was first introduced in 1836 by Berzelius who
triedtoexplainspecialpowersofsomechemicalsubstances y Ea
g
capable ofinfluencingvariousdecompositionandchemical er
n
transformations. E
AccordingtoOstwald[6],“acatalystacceleratesachemi-
calreactionwithoutaffectingthepositionoftheequilibrium.”
A catalyst works by interacting with reactants, generating
intermediatesthatreacttogiveproducts.Itaffectstherateof A+B
approachtoequilibriumofareactionbutnotthepositionof C+D
theequilibrium(Figure2).Mostofthetimes,italsoprovides
subtlecontrolofchemicalconversions,increasingtherateof
adesiredreactionpathwaybutnottheratesofundesiredside Reaction coordinate
reactions(i.e.,theselectivityofachemicalprocess).
Catalysts are usually classified according to structure, Figure 2: Schematic illustration of the effect of a catalyst on the
composition, area of application, or state of aggregation. transformationofA+BintoC+D.
JournalofCatalysts 3
Accordingtothestateofaggregationinwhichthecatalysts fromnaturalgas/fuelstovariouscommodities[15,16].There
act, there are two main groups: homogeneous catalysts and are a variety of new challenges in creating alternative fuels,
heterogeneous catalysts. Homogeneous catalysts are well- reducing harmful by-products in manufacturing, cleaning
defined chemical compounds or coordination complexes, up the environment and preventing future pollution, deal-
which,togetherwiththereactants,aremolecularlydispersed ing with the causes of global warming, and creating safe
inthereactionmediumandcarryoutprocessesinauniform chemicalsandpharmaceuticals.Thus,catalystsareneededto
gas or liquid phase. Heterogeneous catalysis takes place meet these challenges of health, safety, and environmental,
between different phases. Generally the catalyst is in solid energy-related, and economic issues, but their complexity
state,andthereactantsaregasesorliquids.Theimmobilized and diversity demand an insight on the way catalysts are
catalysts obtained by attaching homogeneous catalysts to studied, designed, and used. This could come into reality
solidareinbetween.Insupportedcatalyststhecatalytically onlythroughtheapplicationofaninterdisciplinaryapproach
active substance is applied to a support material that has involving new methods for synthesizing and characteriz-
a large surface area and is usually porous. Arguments for ing molecular and material systems. Research in heteroge-
andagainstshallalwaysbemadewhilediscussingthemerits neous catalysis demands the cooperation of scientists from
and limitations of individual groups of catalysts for their analytical chemistry, solid-state chemistry, (nano)materials
respectiveapplicationsinindustries. chemistry,physicalchemistry,surfacescience,computational
and theoretical chemistry, reaction kinetics and mecha-
3.ApplicationofCatalysis nisms,reactionengineering,andso forth.Opportunitiesto
understand and predict how catalysts work at the atomic
Catalysis has played a pivotal role in the success of the scale are now appearing, made possible by breakthroughs
chemistryindustryinthetwentiethcentury.Morethan90% inthelastdecadeincomputation,measurementtechniques,
of chemical manufacturing processes in the world utilize characterization, spectroscopy, and imaging and especially
catalysts [7, 8]. Historically, the first industrially applied by new developments in surface-reactivity studies, model
catalytic process was for the hydrogenation of oils and fats catalyst design, and evaluation [16, 17]. Surface science and
toproducemargarineusingfinelydividednickelascatalyst. spectroscopy has its prominent role in analysing surface
Thus, heterogeneous catalysis was applied first industrially. reactionchemistryonthecatalyst[18,19].
The issue of metal leaching and the avoidance of trace Fermentation of sugar to ethanol and the conversion
catalyst residues are very important from environmental of ethanol to acetic acid catalyzed by enzymes were an
healthpointofview.Allthebasicrawmaterialsorbuilding exampleofcatalysisinantiquity.Offlate,enzymaticcatalysis
blocksforchemicalsaremanufacturedbyveryimportantset isconsideredasaseparatebranchof(biological)catalysis.Itis
of heterogeneous catalytic reactions (Table1) [8]. Although themostrecentbranchwidelyincludedinmanycommercial
catalystsarenotconsumedbythereactionitself,theymaybe applications [20, 21]. Enzymes are also highly active under
inhibited,deactivated,ordestroyedbysecondaryprocesses. mildconditionssuchastemperature,pressure,andpH,which
Thesolid-statecatalyticmaterialsarethemostimportanttype makethemeasiertoworkwithonasmallscale,butarealso
ofcatalysts. moreappealingonanindustrialscaleonacostandefficiency
Implementationof“clean”and“green”chemicaltechnol- basis. Another benefit is that reactions are preferentially
ogy in industries may help address the problem of envi- carriedoutinaqueousmediathereforeprovidinga“greener”
ronmental degradation besides producing useful chemicals route.Nottoforget,thedevelopmentofwaterbasedorganic
[9–12].Somecatalystsalsopresentimportanttechnologyin transformationsisalsoanareaofrapidlygrowingimportance
thepreventionofemissions,forexample,catalyticconverter inchemistry[22,23].
forautomobiles.Keepinginmindthefragileecosystemand The homogeneous catalysis prior to the recognition of
the importance of preserving the environment, the hetero- theeffectsofheterogeneouscatalystsstartedwiththeaction
geneous catalysts are tested in the pollution abatement [13, of nitrous oxides in the lead chamber process. Although
14] and to remove aqueous organic wastes, volatile organic the fundamental processes for refining petroleum and its
compound, and vehicular primary emissions such as CO, conversion to basic building blocks are based on heteroge-
unburnedhydrocarbon,NOx,andsoot. neous catalysts, many important value-added products are
Heterogeneous catalysis which takes place between dif- manufacturedbyhomogeneouscatalyticprocesses(Table2)
ferent phases has now grown into an important branch of [12]. Homogeneous catalysts have been well researched,
science[8–12,15].Excitingnewopportunitiesareemerging since their catalytic centers can be relatively easily defined
in this field based on nanotechnology approaches. Hence, and understood, but difficulties in separation and catalyst
research efforts are being directed to develop chemistry of regeneration prevent their wider use [12, 24–28]. The most
nanomaterials and their applications in catalysis for devel- widely used homogeneous catalysts are simple acids or
oping cost-effective, selective, energy sufficient, ecofriendly, bases which catalyze well-known reactions such as ester
and environmentally benign synthetic processes for indus- and amide hydrolysis or esterification. The market share of
tries. Though this involves a great scientific, economic, and homogeneous catalysts is estimated to be only ca. 10–15%.
technological challenge, it is essential to a sustainable and Many of the benefits of homogeneous catalysts, especially
healthywayoflife. highselectivity,arisefromtailoredmadecatalystsinvolving
The petroleum and fine chemical and pharmaceutical transition metals (or lanthanides) and appropriate ligands.
industries mostly rely on catalysts to produce everything Such catalysts are inexpensive enough that they can be
4 JournalofCatalysts
Table1:Listofsomeoftheindustriallyappliedreactionsandcatalysts.
Reaction Catalyst Inventor(Year)
Sulphuricacid(lead—chamberprocess) NO𝑥 Clement,Desormes(1806)
ChlorineproductionbyHCloxidation CuSO Deacon(1867)
4
NitricacidbyNH oxidation Pt,Rhnets Ostwald(1906)
3
Fathardening Ni Normann(1907)
Mittach,Haber,Bosch(1908);
Ammoniasynthesis(H +N ) Fe
2 2 Production1913BASF
Hydrogenationofcoaltohydrocarbons Fe,Mo,Sn Bergius(1913);Pier(1927)
MethanolsynthesisfromCo/H Zno/Cr O Mittach(1923)
2 2 3
HydrocarbonsfromCO/H (motorfuels) Fe,Co,Ni Fischer,Tropsch(1925)
2
Alkylationofolefinstogasoline AlCl Pines(1932)
3
Crackingofhydrocarbons Al O /SiO Houdry(1937)
2 3 2
Crackinginafluidizedbed Aluminosilicates Lewis,Gilliland(1939)
Ethylenepolymerizationatlowpressure Ticompounds Ziegler,Natta(1954)
Hydrogenation,isomerization,hydroformylation Rh-,Rucomplexes Wilkinson(1964)
Co/iodide BASF(1960);
Methanolcarbonylationtoaceticacid Rh/iodide MonsantoCo.(1966);
Iridium BPChemicalsLtd.(2000)
Asymmetrichydrogenation Rh/chiralphosphine Knowles(1974)
Three-waycatalyst Pt,Rh/monolith GeneralMotors(1974)
Methanolconversiontohydrocarbons Zeolites MobilChemicalCo.(1975)
Alpha-olefinsfromethylene Ni/chelatephosphine Shellcompany(1977)
Sharpless(epi)oxidation TI/ROOH/Tartarate May,Baker,Upjohn,ARCO(1981)
SelectiveoxidationswithH O TS-1(titaniumsilicate) Enichem(1983)
2 2
Hydroformylation Rh/phosphine Rhone-Poulene-Ruhrchemie(1984)
Polymerizationofolefins Zirconocene/MAO Sinn,Kaminsky(1985)
Selectivecatalyticreduction(SCR) V,W,Tioxides/monolith 1986
Table2:Differencesbetweenhomogeneouscatalystsandheteroge- on the other hand the progress of homogeneous catalysis
neouscatalysts. is also going on with fine chemicals [25, 33]. In spirit of
that, the beginning of this century saw the renaissance of
Homogeneouscatalysts Heterogeneouscatalysts
organocatalysispresentinganenvironmentaladvantageover
Samephaseasreactionmedium Solidphase
metalbasedcatalystsforstereoselectiveorasymmetricsyn-
Difficultseparation Easilyseparable theticmethodologies.Theabsenceofmetalinorganocatalyst
Norecyclability Recyclabilityandregeneration bringsanundeniableadvantageconsideringtheprinciplesof
Oftenhighratesofreaction Lowratesofreaction “greenchemistry”andtheeconomicpointofview(Tables3
Nodiffusioncontrol Diffusioncontrol and4).
Robusttopoisoning Poisoning,deactivation Understanding catalytic systems involve study of struc-
ture, state, and composition of catalysts and the phase in
Highselectivity Lowselectivity
whichtheyperform.And,forthis,oneneedstounderstand
Shortlife Longcatalyticlife
chemistryofmoleculesandmaterialsusefulascatalystsand
Mildconditions Energy-consumingprocess
orcatalystcarriers.
Wellunderstoodmechanism Poormechanisticunderstanding
4.MaterialsforCatalysis
neutralized, easily separated from organic materials, and
disposedof.Thiscontributestothehugequantityofaqueous Thediversityofresearchfieldconnectedtothechemistryof
saltwastegeneratedbyindustry.Organometalliccatalystsare materials is significant for their applications in many areas
currentlywidelyusedinindustry,butthesearchforimproved includingadsorption,catalysis,electrochemistry,andsurface
efficiencies,enantioselectivities,orrecyclingisstillamatter science. Nanoparticles [34], metal oxide, and mixed metal
ofintenseresearches[29–33].Itistruethathomogeneously oxides[35–38]preparedbysimplemethodsareusefulcata-
catalyzedprocessessuchashydroformylation,carbonylation, lysts.Researchinvolvingmetal-organicframeworks[39,40],
oxidation, hydrogenation, metathesis, and hydrocyanation mesoporoussilica[41–43],microporousoropen-framework
contribute with millions of tons to the bulk chemicals, but inorganic[44–46],and/ormesoporemodified[47]materials
JournalofCatalysts 5
Table3:Comparisonamongorganometalliccatalysts,enzymecatalysts,andorganocatalysts.
Organometalliccatalyst Enzymecatalyst Organocatalyst
Robust;inexpensive;readilyavailable;nontoxic;inerttoward
Widesubstratescope;highcatalytic Limitedsubstratescope;high
moistureandoxygen;methodespeciallyattractiveforthe
activity;involvingtediousprocess; selectivityandcatalyticactivity;
preparationofcompoundthatdonottoleratemetalcontamination
potentialheavymetalpollution usuallysingleenantiomer
(pharmaceuticalproducts)
Table4:Advantagesanddisadvantagesoforganocatalysts. ofthesestructureshavebeenappliedinindustrialprocesses
to any significant extent. Yet one can account for relatively
Advantages Disadvantages few applications to the huge number of new materials
Easypreparationoravailability Highcatalystloading introduced.NotableexamplesarethereportedusesofSAPOs
Easyhandling;inerttowardsmoisture in lube dewaxing and in natural gas to olefin technologies
Relativelyprematurefield
(water)andair(oxygen) andMCM-22inaromaticsalkylation.Thezeolitestructures
Easyscale-up with large-pore/bimodal porosity and tunable acidity can
bearemarkablebenefitforcatalyticprocessesinindustries.
Nometalcontamination
Withinindustrialcatalysis,thereareconstantinnovationand
Easyscreening
changingapproachestoprovisionofselective,economically
Usefulincomplex(steric)reactions
viable,andenvironmentallybenignprocesses.
Recently, enormous growth in the chemical diversity of
inorganic materials with transition-metal incorporation in
new compositional domains has also been explored due
has steadily increased following the widespread utility of
to their potential application in adsorption and catalysis.
aluminosilicate zeolites [48–51], titanosilicates [52, 53], and
Inorganicpolymers,transitionmetalphosphates,andmetal-
aluminiumphosphates[54,55].
organicframeworks[39,40]withnovelcatalytic,electronic,
In industries, research endeavours are mainly devoted
magnetic, and unique structural properties are particularly
towards the study and development of zeolites or zeolitic
promising candidates [60–64]. The mesoporous structure
materials with several attractive features such as cat-
withstrongaciditycanbearemarkablebenefitforcatalytic
alytic active site(s), large surface area, zeolitic pore walls,
reactionsinvolvinglargeorganicmolecules,inwhichdiffu-
and pore size control. The synthesis and characteriza-
sionconstraintsand/oradsorptionofreactantmoleculesonto
tion of the crystalline aluminosilicate materials with tun-
the strong acid sites are the main concern. A lot has been
able meso-/microporosity and their strong acidity have
reportedaboutthepathwaystodevelopmesostructuredsilica
potentially important technological implications for shape-
[65].Intermsofsurfacefunctionalization,theperformance
selectivecatalyticreactions,ionexchange,andadsorptionof
of mesoporous silica has been polished by several methods
organiccompounds[56–58].Theporediameterscanbefinely
such as metal incorporation [66], metal deposition [67],
chosen, tuned, and utilized for exhibiting shape-selective
grafting by organic functional groups [68], and immobiliz-
catalysis depending on the molecular shape/size of organic
ing metal complex [69]. New approaches to synthesis and
reactant and product. The widespread interest has been
characterizationofbimodal,thatis,micro-mesoporousand
developed in the zeolitic science towards the development
or meso-macroporous materials might assist us in under-
and discovery of zeolites with desired characteristics since
standing the phenomena of diffusion, confinement effects,
conventional zeolites lack fine tuning of their properties to
selectivity,andsoforth[47].
acid/baseandredoxorbifunctionalormultifunctionalprop-
erties.Organicfunctionalizationaddsnewcatalyticfunctions
tozeolites[59]. 5.Organocatalysis:ANovel
Zeolites are microporous crystalline aluminosilicates SyntheticPhilosophy
with unique properties used for many processes. Zeolites
possess acid sites that are associated with the tetrahedral The term “organocatalyst” is a concatenation of the words
aluminium atoms in their framework, and therefore, the “organic”and“catalyst.”Thedefinitioncorrespondstoalow
amount of acidity depends on the aluminium content of molecularweightorganicmoleculewhichinsubstoichiomet-
the zeolite. Zeolite acid catalysts have wide application in ricamountscatalyzesachemicalreaction.Theorganocatalyst
industrialprocesses.TheintroductionofY-zeolitestoreplace could be achiral or chiral and could be composed of C,
amorphous silica-alumina in fluidized catalytic cracking H, N, S, and P. Organocatalysis has several advantages not
(FCC)andinhydrocrackingprocessesintheearly1960’swas onlybecauseofitssyntheticrangebutalsofortheeconomic
a breakthrough application in acid catalysis. With the ever reasons. The absence of metal in organocatalyst brings an
increasingresearcheffortsinthisarealeadingtodiscoveries undeniable advantage considering both the principles of
of new structures and modification schemes by academic “greenchemistry”andtheeconomicpointofview(Figure3).
and industrial laboratories, the potential of solid acids has Nowadays organocatalysis is one of the hot research
evolved tremendously. However, with the exception of the topics in advanced organic chemistry. It is a novel syn-
ZSM-5,Mordenite,andtosomeextentBetazeolite,veryfew theticphilosophyandmostlyanalternativetotheprevalent
6 JournalofCatalysts
∙∙
N O
N
CO2H
N N
H H
N
L-Proline DMAP MacMillan’s catalyst
HO N
NH2 O
OH
N
Quinine
Nobin
Figure3:Fewfamousexamplesoforganocatalysts:L-proline,DMAP,quinine,andMacMillan’scatalyst.
transition metal catalysis. Organocatalysts are often based (iii)Price/Availability:Lowcost;alkaloids,naturalamino
onnontoxicorganiccompoundsoriginatingfrombiological acids,L-proline,tartaricacid,andsoforthareeasily
materials. Organocatalysts can be Lewis bases, Lewis acids, availableandareeconomicallyattractive.
Brønstedbases,andBrønstedacids.Mostoftheorganocatal-
(iv)Recyclingissues:immobilizationofthecatalystisthe
ysisreportedsofarareexplainedbyLewisbasemechanism.
simplestwaytorecoverit.
TheLewisbasemechanismcanbesimplifiedasfollows.
(v)Some of the examples include bioderived and
Step I: Lewis base, for example, cinchona alkaloid, biodegradableorganocatalysts.
initiates catalysis via a nucleophilic addition to, or (vi)Organocatalystsworkatmildreactionconditions.
deprotonationof,thesubstrate.
(vii)Sometimes the final products of reactions contain
StepII:thechiralintermediateundergoesreaction. highlevelsofmetalcontaminationderivedfromcat-
alyst degradation phenomena, which pose a serious
Step III: separation of product(s) from the catalyst
drawbackifthemetalistoxicforpharmaceuticaland
occurs.
food industries. Absence of transition-metal brings
StepIV:regenerationofthecatalystanditsavailability organocatalysisattheheartofgreeningchemistry.
foranewcatalyticcycleoccurs.
Organocatalysiscanbecategorizedintoourdifferenttypes
Therearemanyorganocatalyticreactionsthatneedasecond asfollows.
mechanism to explain the catalytic cycle involved. This is
Type-I:activationofthereactionbasedonthenucle-
calledbifunctionalorganocatalysisinwhichtheorganocata-
ophilic/electrophilicpropertiesofthecatalystisdone
lystpossessesnotonlyaLewisbase(nitrogenorphosphorus
(Scheme1).
atom)butalsoaBrønstedacidicsite.Thereisalottobedone
inredoxcatalysisandinexploitationofthesynergeticeffectof
differentcatalyticactivesiteswithinoneorganiccompound Type-II:organicmoleculesformreactiveintermedi-
ormaterial. ates. The chiral catalyst is consumed in the reaction
Someadvantagesoforganocatalystsincludethefollowing. andrequiresregenerationinparallelcatalyticcycleas
itisreportedinScheme2.
(i)Reactionsperformedbyorganocatalystshavepoten-
tialapplicationinlargescaleproductioninindustries.
Type-III: phase transfer reactions occur. The chiral
(ii)Scope: organic reactions occur which are not in catalystformsahost-guestcomplexwiththesubstrate
practiceandnotpossiblebyotherformsofcatalysts, andshuttlesbetweenthestandardorganicsolventand
forexample,asymmetricsyntheticprocesses. asecondphase.
JournalofCatalysts 7
CO2H
N O
O
H
3mol% L-proline
O DMF,20∘C,20h
O 100%
O
OH
Scheme1:HajosandParrish[70].
O
O
O
O O
O
R2 R2 O
30mol% catalyst
R1 R3 30%H2O2(3equivalent) R1 R3
CH3CN–K2CO3
Scheme2:ShuandShi[71].
Catalytic enantioselective enolate alkylation evidencesthatprovetheirpivotalroleinsynthesisofbuilding
(Scheme3)occurs blocksforlife.L-AlanineandL-isovalinecapableofcatalyzing
certain C–C bond formation reactions had been found on
meteorites[81].
Type-IV: molecular-cavity-accelerated asymmetric Anasymmetrictransformationwithanorganicmolecule
transformations occur in which the catalyst may was published in 1912 by Bredig and Fiske [82]. Pracejus
selectfromcompetingsubstrates,dependingonsize applied cinchona alkaloids in the asymmetric conversion
andstructurecriteria(Scheme4). of ketenes to (S)-methyl hydratropate [83, 84]. An initial
researchbyYamada&Otaniwasimportant,too[85].Thesev-
entiesbroughtanothermilestone;HajosandParrishreported
6.DiscoveryandtheHistoryof aL-prolinecatalyzedRobinsonannulationinexcellentenan-
Organocatalysis tioselectivities [70, 86, 87]. Eder et al. reported organocat-
alytic aldol reactions in good enantioselectivities [88]. To
Liebig’s synthesis of oxamide from dicyan and water is the summarize,in1970s,HajosandParrishand,independently,
firstorganocatalyticreactionreported[74].Acetaldehydewas Eder, Sauer, and Wiechert published a series of papers and
further identified to behave as the then-named “ferment,” patentsinvolvingsuchorganocatalytictransformations.The
now called as enzyme. Dakin in 1909 demonstrated that in asymmetric synthesis of enediones, useful building blocks
a Knoevenagel type condensation between aldehydes and innaturalproducttotalsyntheses,wasachieved.(S)-Proline
carboxylicacidsoresterswithactivemethylenegroups,the inducedtheformationof(S)-enediones.
amine catalysts could be mediated by amino acids [75]. Two mechanisms [89] were proposed: (1) involving the
Langenbeck is remembered for developing enamine type formationofa carbinolamineintermediate, followed by the
reactions and the application of simple amino acids and displacement of the proline moiety by nucleophilic attack
smalloligopeptidesascatalysts[76–78].Naturalproducts,in of the enol from the side chain ketone; (2) involving an
particular, strychnine, brucine, and cinchona alkaloids and enaminiumintermediateactingasanucleophileintheC–C
amino acids (including short oligopeptides), were among bondformationwithconcomitantNH⋅⋅⋅Ohydrogentrans-
the first organic catalysts tested [79, 80]. Though the field fer. Wynberg firstly published various 1,2 and 1,4 additions
of small-molecule catalysts seems very simple, there are catalyzedbycinchonabifunctionalorganocatalysis[90–92].
8 JournalofCatalysts
−
Br
+
H N
O
O
N
O Ph Ot-Bu
Chiral quaternary ammonium catalyst Ph O
N CsOH·H2O 10mol% catalyst
Ph Ot-Bu CH2Cl2 −78∘C,24h O O
Ph BrH2C O
O 81% 96% ee
O
Scheme3:Coreyetal.[72].
O
N HO
HN
O OH
O
O O HO OH
H
O
Nu
BOCHN
BOCHN NO2 (1) Polymer +
(2) Nu
NO2
Scheme4:Sellergrenetal.[73].
Alltheseresearchendeavourswerenotcarefullylookedinto practical,andbroadlyapplicablemethodologicalapproachin
tillListetal.reportedin2000prolinecatalyzedaldolreaction thecatalyticasymmetricsynthesis.
ingoodenantiomericexcesses[93,94].
Asymmetriccatalysisconstitutesoneofthemostimpor-
7.SomeExamplesandDevelopmentsin
tant subjects in synthetic organic chemistry. Asymmetric
CatalystStructuralVariants
synthesisachievingatomeconomyisachallengefororganic
synthesisandhomogeneouscatalysisusingmetalcomplexes
Followingarethefamousexamplesoforganocatalysts.
leadstheway.Buttheapplicationofsuchmethodologiesin
chemical industry is rather limited due to the high cost of
chiralligandsandnoblemetalsusedinsuchtransformations. 7.1.ProlineandDerivatives. TheprolinecatalyzedRobinson
Moreover, the pharmaceutical entities and food industry annulationwas oneoftheearliestexamples ofanenantios-
productsdonottolerateacontamination,ofeventraces,of elective reaction using an organic catalyst [85]. This amino
any such metals for that matter. Synthesis of chiral drugs acid contains both a nucleophilic secondary amino group
has a major financial impact in pharmaceutical industries and a carboxylic acid moiety functioning as a Brønsted
onaglobalscale.Differentenantiomersordiastereomersof acid. The availabilityof proline in both enantiomericforms
a molecule often have different biological activity. Most of brings advantages over enzymatic methods. Arguably, the
the drugs might be soon sold as single enantiomers in the firstexampleofprolinecatalyzedasymmetricaldolreaction
coming years. There is a huge demand for organocatalysts isreportedbyHajosandParrish[70,86,87].TheWieland-
leading to 100% yield, 100% ee, of the desired product. The Miescher ketone is a useful synthetic building block for
needfromchemicalindustry,especiallypharmaceutical,for which a classical asymmetric procedure using (S)-proline
reliable asymmetric transformations of molecular skeletons waspublishedfortyyearsago[88].Itisquitesignificantthat
is higher than ever. Therefore, asymmetric organocatalysis thefirstefficientorganocatalyzedasymmetricreactionswere
is in a process of attaining maturity into a very powerful, describedbyHajos&Parrish[86,87]andbyEderetal.[88],
JournalofCatalysts 9
both teams from pharmaceutical companies (Hoffmann- Heterogenized Proline. An explosion of research articles in
la-Roche and Schering). The asymmetric synthesis of the theareaofhomogeneousorganocatalysisoccurredwithinthe
Wieland-Miescher ketone is also based on proline and lastdecadeorso.Inadditiontotheinitialprolinecatalyzed
anotherearlyapplicationwasoneofthetransformationsin reactions,theword“organocatalysis”coversnowadaysmany
thetotalsynthesisoferythromycinbyWoodwardetal.[95]. otherwell-knownorganocatalystsandorganicreactions.Pro-
Proline is recognized as a versatile organocatalyst of these lineimmobilizedontosomesortofinorganicsupportpaves
times(Scheme5). the way towards heterogenization of other organocatalysts
Infact,therenewalofprolinecatalyzedtransformations [151–153]. A simple and efficient synthesis of polystyrene-
in early 2000 by D. W. C. MacMillan, Carlos F. Barbas III, supportedprolineandprolinamideisreported.Polystyrene-
andBenjaminListsawtherenaissanceoftheconceptandit supported proline catalyzes the asymmetric aldol reaction
wasthestartingpointoftheword“organocatalysis.”Professor between cyclohexanone and substituted benzaldehydes in
Ahrendtgroupreportedthefirstenantioselectiveorganocat- water. Highyields, diastereoselectivities,andee valueshave
alytic Diels-Alder reaction [96]. Proline was identified as beenobserved.Theversatilityofthisresinwasalsoconfirmed
an effective organocatalyst for asymmetric aldol reaction byselenenylationofaldehydes.Bothprolineandprolinamide
[97]. The catalytic asymmetric 𝛼-alkylation of aldehydes resins gave high yields. Recycling studies showed that the
was reported by Vignola and List [98]. This transformation proline resin performs as better heterogeneous organocat-
hadbeenaccomplishedwiththehelpofcovalentlyattached alyst as compared to the prolinamide resin [153]. An aldol
auxiliaries.𝛼-MethylL-prolineexhibitshigherenantioselec- reaction catalyzed by proline functionalized silica gel was
tivities and improved reaction rates when compared to L- investigated in continuous flow microreactors by reaction-
proline. In recent years, proline, especially L-proline, has progress kinetic analysis and nonlinear chromatography
been used to catalyze essential transformations used in the [154].
fine chemical and pharmaceutical industries, such as the Though the research community advocates asymmetric
directasymmetricaldolreactions[99–107],Diels-Alderreac- synthesis for industrial application, organocatalysts have
tions, Michael reactions [108–115], Mannich reaction [116– beenseldomappliedinindustry,duetoinsufficientefficiency
122],Multicomponentreactions[123,124],and𝛼-amination and the difficulties in catalyst separation and recycling
[125], 𝛼-aminoxylation [126–128], 𝛼-oxyaldehyde dimer- [155–161]. The concept of heterogenizing organocatalyst on
ization [100], 𝛼-functionalization of carbonyl compounds supports combines the advantages of both homogeneous
[129], and 𝛼-alkylation of aldehydes [130]. Organocat- organocatalysis and heterogeneous recycling. Though this
alytic cyclopropanation reactions were typically performed might seem simple and present opportunities in indus-
using catalyst-bound ylides. However, Kunz and MacMil- trial chemical processes, the research in heterogeneous
lan demonstrated that activation of olefin substrates using organocatalysis demands a multidisciplinary approach by
catalytic(S)-(−)-indoline-2-carboxylic acid is a viable route identifying catalytic activity upon bonding organocatalyst
for the formation of highly enantioenriched cyclopropanes covalentlytothesupport;understandingnoncovalentinter-
[131]. action as structure-reactivity and conformation deciding
factor;takingintoconsiderationthecharacteristicproperties
Prof. K. A. Jørgensen has made an important
of the supports, confinement effects, if any, and so forth.
breakthrough in asymmetric synthesis by developing (R)-
and (S)-𝛼,𝛼-bis[3,5-bis(trifluoromethyl)phenyl]-2-pyrroli- Somerecentexampleswillbedescribedontheapplications
of supported proline as organocatalysts for their preindus-
dinemethanol trimethylsilyl ether as excellent chiral organ-
ocatalysts in the direct organocatalytic 𝛼-functionaliza- trialization study. The latter half of this review, in general,
ironsoutthedetaileddiscussiononkeytrendswithexamples,
tion of aldehydes. Diarylprolinol silyl ether reagents were
scope,challenges,and“green”applicationsofheterogeneous
found to catalyze C–C, C–N, C–O, C–S, and C–Hal bond
organocatalysts.
forming reactions [132–138]. Cascade or domino reactions
swiftlyconstructcomplexbiologicallyimportantcompounds
andminimizewasteandalsothelaboratoryoperations[139].
7.2. Other Amino Acids. Barbas and coworkers found the
Enders’ group developed proline derived organocatalyst for
proteinogenic amino acid tryptophan (Figure4) to be an
achemo-,diastereo-,andenantioselectivethree-component excellentorganocatalystfortheMannichreactionofhydrox-
domino reaction to yield tetrasubstituted cyclohexene yacetonewithavarietyofiminesperformedinDMFleading
carbaldehydes [140]. The four stereogenic centers are the desired anti-amino alcohols in excellent diastereoselec-
generated in three consecutive C–C bond formations, that tivities (up to >19:1) and enantioselectivities (90–98% ee).
is,Michael/Michael/aldolcondensationwithhighdiastereo- Similarly, t-butyl protected threonine catalyzed the aldol
andcompleteenantiocontrol.Thesynthesisofpolyfunctional reactionofhydroxyacetoneandvariousaldehydesinNMPto
cyclohexenebuildingblocksinvolvingprolinecatalyticsteps givethecorrespondingsyn-aldoladductsinhighyieldsand
isreportedinthisdominoreaction. good to excellent enantio- and diastereoselectivities [162].
Thoughthissegmentofourreviewisdedicatedtoproline Zhao et al. reported [163] the development of an amino
as an important class of organocatalysts, it would also be a acidbasedsmallmoleculecapableofpromotingasymmetric
goodplacetoacknowledgetheresearchcontributionsfrom monosilylation of meso-1,2-diols. Furthermore, the catalyst
professorAhrendtetal.tothefieldoforganocatalysis[96,99, can be recycled with equal efficiency. Three-component
100,103,127,131,141–150]. reaction involving condensation of aldehyde, 1,3-carbonyl
10 JournalofCatalysts
O CO2Bn
N CO2Bn
H N
H
Ph
O
H
NO2
H O OH
O
N H
H
OH
O
O
NHPh
1 2
R R
Scheme5
O with catalysis. Useful asymmetric heterodomino reactions
for the highly diastereoselective synthesis of symmetri-
cal and nonsymmetrical synthons of benzoannelated cen-
OH tropolyquinaneswerereported[173,174].
In recent years, trials are being made by using amino
H2N acids, especially L-proline, to catalyze essential transforma-
N tionsinthefinechemicalandpharmaceuticalindustries.The
H
interestinthisfieldhasthusincreasedspectacularlyinthelast
Figure4:L-Tryptophan. few years. However, organocatalytic methods often require
catalystloadingsashighas30mol%fortheachievementof
high conversions in reasonable reaction times [175]. Some
critics suggest that low turnover numbers might limit the
compound, and (thio)urea is known as Biginelli reaction. potential uses of organocatalysis for industrial applications.
Various organocatalysts such as tartaric acid, oxalic acid, Processdevelopmentandscale-uparebeingtestedforseveral
citricacid,andlacticacidwerefoundeffectiveinproducing organocatalytic reactions confirming organocatalysis as a
Biginelliproducts[164–172]. valuable tool for industrial scale solutions. Scientists are
Because of the “privileged” green nature of this field, reporting novel organocatalytic systems in various reputed
it has become an obligation for scientific community and international research journals and those catalysts exhibit
academic institutions to be mindful and teach this branch various valuable functions derived from a variety of struc-
ofcatalysistostudentsandalsokeepitasadrivingforcein tural,ionic/electronic,andchemicalproperties.Broadvariety
the generation and dissemination of knowledge in pursuit ofefficientsyntheseswillcontributetoanincreasingnumber
of efficient synthetic methodologies and processes using of organocatalytic large scale reactions in the future. The
organocatalysts.Thesynthesisofnewchiralbuildingblocks organocatalysts shall be used in various fields, especially in
or complex molecular structures involving organocatalytic asymmetricorganicsynthesis.
step(s) is being reported almost every day in scientific
literature.Asitisnotpossibleheretodiscussallthecatalysts 7.3.AmineandChiralVicinalDiamines. Prolineandpyrro-
individually in detail, the author decides to present salient lidine derivatives, commonly known as Hayashi-Jørgensen
developmentsinorganocatalysisandalliedresearchareas. catalysts, in the form of ferrocenyl pyrrolidine, are applied
Synthesis of prochiral cyclohexanones by amine cat- asorganocatalystwhereintheferrocenemoietycontrolsthe
alyzedself-Diels-Alderreactionsof𝛼,𝛽-unsaturatedketones conformational space and a simple alkyl group effectively
in water brought coupled the concept of green chemistry coversafaceofthederivedenamine(Figure5)[180].