Like the meso epoxides the bromohydrin esters 4 serve as alkylating agents, yet provide access to the complementary set of product diastereomers compared to the direct use of meso epoxides. I the desymmetrization of meso epoxides is the most inves. Recent advances in catalytic enantioselective desymmetrization. Cooperative lewis acidonium salt catalysis as tool for the. Nonenzymatic catalytic enantioselective desymmetrization reactions long literature benoit cardinaldavid october 2009 introduction alcohol protection cyclic anhydride alcoholysis and alkylation oxidation reactions ring opening of epoxides and aziridines ring opening of bridged systems deprotonation reactions olefin metathesis. Us6580003b2 catalytic asymmetric desymmetrization of. In comparison, the use of bromide and iodide has been described in a single study so far. Salanvanadium catalyzed enantioselective desymmetrization of. Meso epoxides are necessarily a small subset of all possible epoxides. Molecules free fulltext applications of bolms ligand. Article views are the countercompliant sum of full text article downloads since november 2008 both pdf and html across all institutions and individuals. Desymmetrization through enantioselective catalysis. Studies on the use of peptide auxiliaries in the mesodesymmetrization of epoxides, and the kinetic resolution of secondary alcohols.
Read enantioselective desymmetrization of meso epoxides with anilines catalyzed by a niobium complex of a chiral multidentate binol derivative. Enantioselective desymmetrization of a phospholene meso. General ring opening of epoxides o r r desymmetrization of meso epoxides nuh, catalyst r r oh nu nu n3, nhr, or, ocor, sr, x, cn, r cat cr, zr, ti, ac, co o r kinetic resolutions of racemic epoxides. Asymmetric catalysis of epoxide ringopening reactions request. Desymmetrizations of mesoepoxides via nucleophilic ring opening reactions provide an attractive synthetic tool towards enantiopure. Furthermore, the resolution of terminal epoxides remained elusive. Based on the steric and electronic factors, the molecule 1 was designed with a rigid bicyclic skeleton possessing a pyridine moiety as one donor site and an ester group to introduce various other donor groups through simple functional group. The first example of salanvanadium catalyzed enantioselective ringopening of mesoepoxides has been reported, which furnished. Niwayama s 2000 highly efficient selective monohydrolysis of symmetric diesters. This is the first example of epoxide activation achieved using metal binol phosphates. While it is generally easily controlled on the laboratory scale, the toxic and potentially explosive nature of me 3sin 3 makes it a poor choice for industrial processes. Asymmetric catalysis, desymmetrization, meso epoxide, benzophenone imine, 1,2amino alcohol, scandium introduction the catalytic, enantioselective ringopening of meso epoxides is a valuable strategy for the asymmetric synthesis of 1,2difunctionalized fine chemicals.
The breakthrough of the organocatalyzed enantioselective desymmetrization of meso epoxides was the employment of chiral pyridine noxides as catalysts. Catalytic enantioselective desymmetrization of meso compounds in. Epoxide opening reactions recent advances and synthetic. Lithium binol phosphate catalyzed desymmetrization of meso.
Molecular recognition in the desymmetrization of meso epoxides with anilines is displayed by a lewis acid catalyst formed from niobiumv methoxide and a novel tetradentate binol derivative. The present invention also relates to catalysts for the aforementioned. A highly enantioselective method for desymmetrization of mesoepoxides using thiols is reported. To achieve an enantioselective symmetry breaking synthetic operation two enantiotopic functional groups must be differentiated this can be achieved by the use of. The enantioselective ringopening reaction of mesoepoxides with aryl thiols catalyzed by a chiral heterobimetallic tigasalen complex was realized, and the 1,2mercapto alcohols were obtained in good yields and moderate to high enantioselectivities up to 92% ee. Catalytic, enantioselective synthesis of bocprotected 1,2. The breakthrough of the organocatalyzed enantioselective desymmetrization of mesoepoxides was the employment of chiral pyridine noxides as catalysts. Enantioselective desymmetrization rr a b leading references. Enantioselective desymmetrization of mesoepoxides by. Carbonylative enantioselective mesodesymmetrization of cisepoxides to trans.
Asymmetric catalysis, desymmetrization, mesoepoxide, benzophenone imine, 1,2amino alcohol, scandium introduction the catalytic, enantioselective ringopening of mesoepoxides is a valuable strategy for the asymmetric synthesis of 1,2difunctionalized fine chemicals. This thesis describes the discovery of catalytic reactions that create carboncarbon bonds stereoselectively between substrates bearing an alkene and organoboronic acids reagents. Kinetic resolution of racemic epoxides by catalytic asymmetric ringopening meso epoxides are necessarily a small subset of all possible epoxides. A new catalytic reaction based on mechanistic insight. Cooperative lewis acidonium salt catalysis as tool for.
While it is generally easily controlled on the laboratory scale, the potentially explosive nature of me3sin3 makes it a poor choice for industrial processes. Enantioselective desymmetrization of mesoaziridines and mesoepoxides with various nucleophiles by organocatalysis has emerged as a cuttingedge approach in recent years. Antilla department of chemistry, university of south florida, 4202 east fowler avenue, tampa, florida 33620, united states, email. Jan 01, 2007 read enantioselective desymmetrization of meso epoxides with anilines catalyzed by a niobium complex of a chiral multidentate binol derivative. Onium salt catalysis as tool for the desymmetrization of mesoepoxides florian broghammer,a daniel brodbeck,a thorsten junge,a and rene peters a a. The present invention relates to methods for the synthesis of chiral nonracemic products, e. However, the enantioselective desymmetrization of mesoaziridines and meso epoxides catalyzed by small chiral organic molecules has only. Organocatalytic asymmetric reactions of epoxides wiley online. An unprecedented asymmetric desymmetrization of meso. Vanadium, ringopening, thiols, epoxides, enantioselectivity, asymmetric catalysis. Meso anhydrides divinyl carbinols and meso dienes achiral epoxides carboncarbon bond formation alcohol protection. Precursor to a coiii catalyst for the kinetic resolution of terminal epoxides with alcohols. The utility of a library of epoxide hydrolases in the synthesis of chiral 1,2diols via desymmetrization of a wide range of meso epoxides, including cyclic as well as acyclic alkyl and arylsubstituted substrates, is demonstrated.
Catalytic enantioselective desymmetrization of meso epoxides is an attractive method to prepare chiral alcohols1 because the meso epoxide substrates are readily available and the 1,2difunctionalized product structures with two adjacent chiral centers are very useful synthetic building blocks. Lithium binol phosphate catalyzed desymmetrization of mesoepoxides with aromatic thiols gajendrasingh ingle, michael g. General ring opening of epoxides o r r desymmetrization of mesoepoxides nuh, catalyst r r oh nu nu n3, nhr, or, ocor, sr, x, cn, r cat cr, zr, ti, ac, co o r kinetic resolutions of racemic epoxides. Nevertheless, the aminolysis of the epoxide ring provides access to chiral.
Implications for the use of diols in the desymmetrization of meso epoxides. Desymmetrization in stereochemistry is the modification of a molecule that results in the loss of one or more symmetry elements. Enantioselective desymmetrization of meso epoxides. Enzymatic desymmetrization johnson, tetrahedron, 1996, 3769 i. Isomerizations of this type are most often used to synthesize allylic alcohols, although other products are possible. Magnuson, tetrahedron, 1995, 2167 hodgson, tetrahedron, 1996, 14361 not covered here. In 2001, fu and colleagues demonstrated the utilization of selected chiral pyridine noxides in the enantioselective desymmetrization of meso epoxides. Basepromoted epoxide isomerization is the conversion of alkyl epoxides to ringopened products through the action of strong base.
Enantioselective ringopening reaction of mesoepoxides with arsh catalyzed by heterobimetallic tigasalen system. Request pdf organocatalytic asymmetric reactions of epoxides. Asymmetric ring opening of mesoepoxides catalyzed by the. Enantioselective desymmetrization of mesoepoxides with anilines catalyzed by polymeric and monomeric tiiv salen complexes article in chirality 231. The authors describe an enantioselective ring opening of meso epoxides. The desymmetrization of mesoepoxides by amines generally suffers from the noncompatibility of lewis basic amine and lewis acidic catalyst, because of their tendency to irreversibly coordinate to one another. Catalyst used in the kinetic resolution of racemic, terminal epoxides yielding a chiral diol and the unreacted enantiomer of the epoxide. A common application of this class of reactions involves the introduction of chirality. In the presence of trip, a range of mesoepoxides could undergo smooth ringope.
In 2001, fu and colleagues demonstrated the utilization of selected chiral pyridine noxides in the enantioselective desymmetrization of meso. Enantioselective ringopening reaction of mesoepoxides. Desymmetrization and dynamic kinetic resolution of substituted cyclohexanones. Desymmetrization of mesoepoxides using thiols thieme connect. However, the enantioselective desymmetrization of mesoaziridines and mesoepoxides catalyzed by small chiral organic molecules has only. The chiral r,rdiols were furnished with high ees and yields. A copper complex of a novel alicyclic chiral c 2symmetric piperazine allows the benzoylation of a series of cyclic and acyclic meso1,2diols to give optically active monobenzoates with high enantioselectivity. Epoxide hydrolasecatalyzed enantioselective synthesis of. Molecular recognition in the desymmetrization of meso epoxides with anilines is displayed by a lewis acid catalyst formed from niobiumv methoxide and a. University of cape town,faculty of science,department of chemistry, 2015 cited yyyy month dd. Desymmetrization of mesoepoxides by aromatic amines in water. Enantioselective desymmetrization of meso aziridines and meso epoxides with various nucleophiles by organocatalysis has emerged as a cuttingedge approach in recent years. I the desymmetrization of mesoepoxides is the most inves tigated approach to obtain enantioenriched 2functional ised alcohols.
In the presence of trip, a range of meso epoxides could undergo smooth ringopening reactions by aryl thiols with good efficiency and enantioselectivity. A copper complex of a novel alicyclic chiral c 2symmetric piperazine allows the benzoylation of a series of cyclic and acyclic meso 1,2diols to give optically active monobenzoates with high enantioselectivity. Studies on the use of peptide auxiliaries in the meso. Organic chemistry iayama organic chem curr res 9c e. Among the various catalysts reported for this type of reaction, lewis bases such as phosphoramides 9 and noxides6d, 10 have been reported to be effective catalysts for the ring opening of epoxides with tetrachlorosilane. Formally, such conversions required the loss of an improper axis of rotation mirror plane, center of inversion, rotationreflection axis. The first chiral bronsted acid catalyzed asymmetric nucleophilic ringopening reaction of meso epoxides is described. Asymmetric nucleophilic ring opening of mesoepoxides is a powerful method to synthesize chiral 1,2 functionalized. It was efficiently catalyzed by a chiral dy iii n,ndioxide complex through a thiolysiselimination sequence. The discovery, from nature, of a diverse set of microbial epoxide hydrolases is reported. Desymmetrization reactions of meso compounds through enantioselective catalysis are a powerful strategy for the synthesis of chiral molecules with multiple stereocenters. Organocatalyzed enantioselective desymmetrization of aziridines. The authors describe an enantioselective ring opening of mesoepoxides.
A highly enantioselective method for desymmetrization of meso epoxides using thiols is reported. A strong synergistic cooperation between different lewis acids in the system was exhibited in the catalytic process. Organic chemistry iayama organic chem curr res 9c e current. Acidcatalyzed enantioselective desymmetrization of mesoepoxides by 2. The hydrolytic kinetic resolution jacobsens catalyst. If you notice any publications incorrectly attributed to this author, please sign in and mark matches as correct or incorrect.
Recent advances in catalytic enantioselective desymmetrization reactions november 30, 2007 torsak luanphaisarnnont leading references. This remote stereocontrol strategy provides facile access to synthetically versatile cyclopentene derivatives bearing an. Chiral rhodiumi catalysts were found to react with various mesosymmetrical substrates, thereby resulting in enantioselective desymmetrization reactions. Enantioselective ringopening reaction of mesoepoxides with. Jan 29, 2007 read enantioselective desymmetrization of meso epoxides with anilines catalyzed by a niobium complex of a chiral multidentate binol derivative, angewandte chemie international edition on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. However, the enantioselective desymmetrization of mesoaziridines and meso epoxides catalyzed by small chiral organic molecules has only emerged in recent. The reaction has a broad scope in terms of epoxide substrates and aromatic. Broader applicability needs a wider range of substrates but these will all be chiral.
Request pdf asymmetric catalysis of epoxide ringopening reactions the. Enantioselective ring opening of mesoepoxides with thiols. This seminar will focus on the desymmetrization of meso compounds. Desymmetrization of cyclic mesoepoxides with silicon tetrachloride catalyzed by pindox, a chiral bipyridine mononoxide by a. I the desymmetrization of mesoepoxides is the most inves. View enhanced pdf access article on wiley online library html view download pdf for offline viewing.
Chiral pentacarboxycyclopentadienebased bronsted acid. Read enantioselective desymmetrization of meso epoxides with anilines catalyzed by a niobium complex of a chiral multidentate binol derivative, angewandte chemie international edition on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Nonenzymatic catalytic enantioselective desymmetrization reactions long literature benoit cardinaldavid october 2009 introduction alcohol protection cyclic anhydride alcoholysis and alkylation oxidation reactions ring opening of epoxides and aziridines ring opening of bridged systems deprotonation reactions olefin metathesis aldol reactions. Ogawa c, wang n, kobayashi s 2007 scandiumcatalyzed ringopening desymmetrization of mesoepoxides. Nonenzymatic catalytic enantioselective desymmetrization. These metrics are regularly updated to reflect usage leading up to the last few days. Chiral phosphoric acid catalyzed enantioselective desymmetrization of mesoepoxides by thiols. Enantioselective desymmetrization of mesoepoxides with. Enantioselective desymmetrization of mesonsulfonylaziridines with thiols. In a highly enantioselective method for desymmetrization of mesoepoxides with aromatic thiols, epoxide activation is achieved using metal binol phosphates. Desymmetrization of meso epoxides by aromatic amines in water. Studies on the use of peptide auxiliaries in the meso desymmetrization of epoxides, and the kinetic resolution of secondary alcohols. Desymmetrization of cyclic mesoepoxides with silicon. The asymmetric ring opening of mesoepoxides7, 8 is a versatile method for preparing optically active chlorohydrins.
Nov 07, 2014 a highly enantioselective method for desymmetrization of meso epoxides using thiols is reported. Mesoepoxides are necessarily a small subset of all possible epoxides. Since terminal epoxides are very cheap, a resolution process is viable. The first chiral bronsted acid catalyzed asymmetric nucleophilic ringopening reaction of mesoepoxides is described. However, the enantioselective desymmetrization of mesoaziridines and mesoepoxides catalyzed by small chiral organic molecules has only emerged in recent.
In the presence of trip, a range of mesoepoxides could undergo smooth ringopening reactions by aryl thiols with good efficiency and enantioselectivity. Organocatalyzed enantioselective desymmetrization of. These processes can be grouped into two categories. The reported products thus represent synthetic equivalents for enantioenriched trans epoxides for which only few protocols have been developed. Nov 12, 20 the first chiral bronsted acid catalyzed asymmetric nucleophilic ringopening reaction of mesoepoxides is described. Salanvanadium catalyzed enantioselective desymmetrization. Coates department of chemistry and chemical biology, baker laboratory, cornell university, ithaca, new york 148531. Lewis acidonium salt catalysis as tool for the desymmetrization of mesoepoxides. Enantioselective desymmetrization of meso epoxides with. Jul 18, 2005 the asymmetric ring opening of meso epoxides7, 8 is a versatile method for preparing optically active chlorohydrins.
Ogawa c, wang n, kobayashi s 2007 scandiumcatalyzed ringopening desymmetrization of meso epoxides. Hydroxyl sulfides are obtained in excellent yield and enantioselectivity for a broad scope of substrates. Niwayama s 2000 highly efficient selective monohydrolysis of symmetric. Pdf synthesis and evaluation of new 1,7dioxaspiro5.
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