Cox and simpkins, asymmetric synthesis using homochiral lithium amide bases, tetrahedron. The often complex nature of these compounds makes their implementation towards the synthesis of natural products or pharmaceutical targets a challenging yet rewarding endeavour. Full text of organolithiums in enantioselective synthesis. The principal enabling force in the development of organolithium chemistry is the. Enantioselective catalytic lithiation using a chiral. Catalytic enantioselective miniscitype addition to. An aryloxy group is a weak director of metallation, but in preliminary studies we were able to deprotonate and methylate the hindered diaryl ether 6 by treatment with nbuli in ether at 0 c with or without. Corey and laszlo kurti, enantioselective chemical synthesis offers an authoritative and comprehensive overview of the fields progress. Sep 10, 2019 a new synthetic route to nalkyl2acylazetidines was developed through a highly stereoselective addition of organolithiums to nalkyl2oxazolinylazetidines followed by acidic hydrolysis of the resulting oxazolidine intermediates. Catalytically enantioselective synthesis of acyclic. Inter and intramolecular enantioselective carbolithiation. The synthesis of chiral structures is one of the key areas of the chemical sciences. These forms are structurally identical, yet they are mirror images of each other. Enantioselective formal synthesis of palmerolide a.
The approach entails the merger of several catalytic processes and is expected to facilitate the preparation of bioactive organic molecules. Most of the molecules on earth are chiral, such as amino acids and carbohydrates. Written by worldrenowned and bestselling experts, nobel laureate e. Strategies for enantioselective synthesis the direct enantioselective synthesis of quaternary centers is one of the enduring challenges of organic synthesis.
This volume is the first dedicated to a comprehensive coverage of this important area. Organolithium compounds, strong bases and nucleophiles, gained outstanding importance as key intermediates and powerful reagents in organic synthesis, such as the formation of chiral 2substituted piperidines. Sep 10, 2019 stereo and enantioselective addition of organolithiums to 2oxazolinylazetidines as a synthetic route to 2acylazetidines article pdf available in frontiers in chemistry 7 september 2019. A catalytic approach for enantioselective synthesis of. Diaryl ethers carrying carbamoyloxymethyl groups may be desymmetrised enantio and diastereoselectively by the use of the secbuli. Dynamics and catalytic resolution of selected chiral. The reactions link carbon radicals to the carbon centers adjacent to nitrogen in pyridine rings. Dynamics and catalytic resolution of selected chiral organolithiums.
Pdf sustainable asymmetric organolithium chemistry. Pdf stereo and enantioselective addition of organolithiums. Enantioselective synthesis by lithiation adjacent to nitrogen and electrophile incorporatio. Journal of the american chemical society 2008, 16, 55305541.
Mar, 2011 organolithiums are the prototypical nucleophilic reagent, but the direct use of them as nucleophiles in catalytic asymmetric synthesis has been problematic. Catalytic asymmetric carboncarbon bond formation via. Boron trifluoride etherateassisted ring opening of. Paralleling the surge of interest in methods for asymmetric synthesis, the use of. Functionalized organolithium reagents in the synthesis of. An example is the merck and dupont synthesis of efavirenz, a potent hiv reverse transcriptase. Pdf enantioselective synthesis by lithiation adjacent to oxygen and. Enantioselective addition of organolithiums to co groups and. Organolithiums in enantioselective synthesis book, 2003. Paralleling the surge of interest in methods for asymmetric synthesis, the use of organolithiums in enantioselective synthesis has witnessed spectacular advances in a. Moving to the 6methyl analogue 11 gave products that were expected to be atropisomeric 10, because they have four substituents ortho to the ether linkage, one of them tertiary.
Herrera 1,2, 1 laboratory of asymmetric synthesis, department of organic chemistry, institute of synthetic chemistry and homogeneous catalysis isqch, university of. Stereo and enantioselective addition of organolithiums to 2oxazolinylazetidines as a synthetic route to 2acylazetidines article pdf available in frontiers in chemistry 7. Jan 06, 2004 read organolithiums in enantioselective synthesis. Organolithiums preparation and reactivity lithiumhalogen exchange is an equilibrium process, and the position of the equilibrium varies with the stability of the carbanion intermediate. In nature, many molecules exist in two different forms, referred to as enantiomers. Diastereo and enantioselective synthesis of atropisomeric ethers by benzylic lithiation. The methods involve the generation of enantiomerically enriched configurationally stable organolithiums by deprotonation of. Enantioselective organocascade catalysis yong huang, abbas m.
The selected targets for this investigation using chiral organolithiums, 2,3dehydropyridones and chiral tertiary alcohols, are important building blocks for enantioselective synthesis. The configuration of the chiral ligands was approved by applying advanced nmr experiments. Organolithiums are the prototypical nucleophilic reagent, but the direct use of them as nucleophiles in catalytic asymmetric synthesis has been problematic. Full text of organolithiums in enantioselective synthesis see other formats.
Macmillan division of chemistry and chemical engineering, california institute of technology, pasadena, california 91125 received august 14, 2005. Enantioselective synthesis of nsubstituted quaternary carbon stereogenic centers by zrcatalyzed additions of dialkylzinc reagents to aryl, alkyl, and trifluoroalkylsubstituted ketoimines. Synthesis and reactions of lithiated monocyclic azoles containing two or more heteroatoms. Synthesis of chiral protected cyclohexyl derivatives for the enantio and. The development of methods for the regioselective synthesis of organolithiums has replaced their image of. An exciting and growing field is the use of organolithiums in enantioselective synthesis. Enantioselective alphadeprotonation of achiral epoxides 1, 21, and 26 using organolithiums in the presence of sparteine 2 and subsequent electrophile trapping gives access to enantioenriched. This reactivity is widely applied in the industrial syntheses of pharmaceutical compounds. Enantioselective synthesis is an important means by which enantiopure chiral molecules may be. Organolithiums are key reagents and intermediates in organic synthesis.
By employing chiral sulfoxide phosphine sopcu and pdcl 2 dppf complexes as catalysts, the 1,4. Chiral, nonracemic ligands and additives implement enantioselective additions of organolithiums to co functions of carbonyl compounds i. This volume, number 23 in the tetrahedron organic chemistry series, presents organolithium chemistry from the perspective of a synthetic organic chemist, drawing from the synthetic literature to present a unified overview of how organolithiums can be used to make molecules. Tertiary amines through desymmetrization of 2substituted 2nitro1,3diols. Some new insight and applications in enantioselective synthesis. Key strategies in the synthesis include the oxidative furan ringopening of a chiral furyl carbinol for the installation of the 1,4dienol core and a jung nonaldolaldol reaction for the dienamide core. Stent enantioselective addition of organolithiums to co groups and ethers bernd goldfuss enantioselective conjugate addition and 1,2addition to c. Practicality ultimately begins and ends with cost efficiency, and catalysis is generally a good place to start. Enantioselective synthesis of substituted pyrrolidines by. Stereoselective preparation of organometallic reagents. Matrix presented enantioselective synthesis of attenols a and b was accomplished by using diastereoselective hydroboration, lindlar reduction, and acidcatalyzed acetal formation. Organolithiums in enantioselective synthesis springerlink.
Therefore, since the discovery by schlenk and holtz, lithiation chemistry has grown into a well established technique also receiving. Sorganolithium species was enhanced by using a less coordinating solvent and short reaction times. The formation of carboncarbon bonds represents a key step in the synthesis of many organic. Regioselective synthesis of organolithiums by deprotonation. Moving to the 6methyl analogue 11 gave products that were expected to be atropisomeric 10, because they have four substituents ortho to the ether linkage, one of them. This study revealed an unusual reactivity of the cn bond of the oxazoline group when reacted with organolithiums in a nonpolar solvent such as toluene. Enantioselective addition of organolithiums to co groups. Organolithium chemistry occupies a central position in the selective construction of cc. Eames, recent developments in enantioselective deprotonation mediated by substoichiometric quantities of chiral bases, eur. Overview of organolithiumligand combinations and lithium amides for enantioselective processes david m. A new synthetic route to nalkyl2acylazetidines was developed through a highly stereoselective addition of organolithiums to nalkyl2oxazolinylazetidines followed by acidic hydrolysis of the resulting oxazolidine intermediates. Sparteinemediated asymmetric deprotonative lithiation has emerged as a powerful synthetic tool to generate chiral carbanions, thanks to the pioneering work by hoppe and hense 1 and beak et al.
Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. Organolithium organometallic reagents sigmaaldrich. Carbamatedirected benzylic lithiation for the diastereo and. Synthesis of s2,2dimethyl1,1binaphthalene 11 from sbinol 5. Some new insight and applications in enantioselective. Asymmetric cyclization of achiral olefinic organolithiums. Enantioselective synthesis by lithiation adjacent to nitrogen and electrophile incorporation, in organolithiums in enantioselective synthesis hodgson dm.
Beak chemistry, which involves enantioselective generation of organolithiums in the presence of. Journal of the american chemical society 2000, 122 28, 67896790. Stereo and enantioselective addition of organolithiums to. Organolithiums in enantioselective synthesis topics in organometallic chemistry softcover reprint of the original 1st ed. Substituted styrene derivatives also undergo efficient enantioselective carbolithiation in the presence of chiral diamines, when there are electrondonating groups e. Paralleling the surge of interest in methods for asymmetric synthesis, the use of organolithiums in enantioselective synthesis has witnessed spectacular advances in. Asymmetric synthesis and transition metalcatalyzed cross.
To make the radicals, they prepared derivatives of. Enantioselective catalytic lithiation using a chiral binaphthyl derivative as electron carrier. Organolithium reagents can also perform enantioselective nucleophilic addition to carbonyl and its derivatives, often in the presence of chiral ligands. The lithiation reaction of 2chloro1phenylpropane employing binaphthyl derivative 11 as electron carrier, in thf at room temperature, produced the corresponding organolithium. Hoppe, universitat munster outline asymmetric deprotonation of alkyl carbamates synthesis of slaframine asymmetric deprotonation of allyl carbamates. Purchase enantioselective chemical synthesis 1st edition.
Shop organolithium compounds for organic synthesis. Jun 27, 2000 enantioselective synthesis of 3substituted indolines by asymmetric intramolecular carbolithiation in the presence of. As part of a larger study on the amenability of chiral organolithiums to a catalytic dynamic resolution, ntrimethylallyl2lithiopyrrolidine, nboc2lithiopiperidine, and the ethylene ketal of nboc2lithio4oxopiperidine were selected. Catalytic enantioselective addition of organolithium reagents to aldehydes. Organolithium chemistry occupies a central position in the selective construction of cc bonds in both simple and complex molecules. New methodologies for the catalytic enantioselective addition. This barcode number lets you verify that youre getting exactly the right version or edition of a book. Organolithiums in enantioselective synthesis ebook, 2003. Organolithiums in enantioselective synthesis, advanced. Socalled minisci reactions have been used for decades in pharmaceutical and agrochemical synthesis to make carboncarbon bonds.
Lim, enantioselective synthesis by lithiation adjacent to nitrogen and electrophile incorporation, organolithiums in enantioselective synthesis, 10. Paralleling the surge of interest in methods for asymmetric synthesis, the use of organolithiums in enantioselective synthesis has witnessed spectacular advances in a little over a decade. Organolithiums in enantioselective synthesis david m. Enantioselective formal synthesis of palmerolide a organic. Stereo and enantioselective addition of organolithiums to 2. Jonathan clayden has succeeded in conveying this knowledge with succinct commentaries supported by appropriate examples. The direct enantioselective synthesis of quaternary centers is one of the enduring challenges of organic synthesis.
Boron trifluoride etherateassisted ring opening of ethylene. Some new insight and applications in enantioselective synthesis ischia advanced school of organic chemistry iasoc 2004 september 18 23, ischia porto napoli, italy d. Carbamatedirected benzylic lithiation for the diastereo. Catalytic asymmetric carboncarbon bond formation via allylic.
Cucatalyzed enantioselective allylic alkylation with organolithium. Apr 01, 2005 organolithiums in enantioselective synthesis organolithiums in enantioselective synthesis majewski, marek 20050401 00. Stereoselective preparation and stereochemical behaviour of. Enantioselective synthesis of multisubstituted allenes by. Clear chapter headings and subjectauthor indexes make finding information easy, and the volume will be a useful addition to library reference collections. Asymmetric synthesis of tertiary alcohols and thiols via. Organocatalytic enantioselective henry reactions yolanda alvarezcasao 1, eugenia marqueslopez 1 and raquel p. Selectivity for synthesis is recommended for every chemist who wishes to become thoroughly acquainted with the potential of organolithium chemistry. A protecting groupfree strategy is presented for diastereo and enantioselective routes that can be used to prepare a wide variety of zhomoallylic alcohols with significantly higher efficiency than is otherwise feasible. Enantioselective synthesis of 3substituted indolines by asymmetric intramolecular carbolithiation in the presence of.
Enantioselective synthesis of attenols a and b keio. Remarkably, for extremely reactive organolithium compounds, which are among the most broadly used reagents in chemical synthesis, a general. Organolithiums in enantioselective synthesis organolithiums in enantioselective synthesis majewski, marek 20050401 00. Stereochemistry of bruices organic chemistry before embarking on comprehending this summary. The cdr of nboc2lithiopiperidine using our newly discovered ligands was applied to the. Enantioselective formal synthesis of macrolactone palmerolide a, a polyketide marine natural product, is described. Organolithiums in enantioselective synthesis topics in.
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