Asymmetric synthesis via acetal templates. 9. Further studies of the allylation reaction. Preparation of (−)-dihydromyoporone

A procedure has been developed for the high-yield coupling of chiral acetals 1 with allyltrimethylsilane (2, R′=H) as well as with methallyltrimethylsilane (2,R′=ME) to afford the hydroxy ethers 3 in which the new chiral center is formed highly enantioselectively. Homoallylic alcohols 4 of high ee are produced by removal of the chiral auxiliary.     

A new entry to asymmetric synthesis of optically active alpha,gamma-substituted gamma-butyrolactones, using a carbohydrate derived amide as both a chiral auxiliary and a proton source

A new entry for the asymmetric synthesis of optically active alpha,gamma-substituted gamma-butyrolactones was developed by using a carbohydrate-derived amide as both a chiral auxiliary and a proton source. Unlike the previously reported examples, the chiral auxiliary employed in this reaction also successfully functioned as a protonating agent. Excellent asymmetric induction could be achieved by this dual stereoselective control in the reaction process.     

Asymmetric Synthesis of Chiral Atropisomeric Bis‐Aryl Organophosphorus from Menthyl H‐Phosphinate

This review describes new methods for the synthesis of chiral monophosphine ligands with menthyl phenylphosphinate as a chiral auxiliary through asymmetric Suzuki‐Miyaura cross‐coupling reactions and asymmetric C–H functionalization. The chiral menthyl phenylphosphinate as a chiral auxiliary is easy to prepare and the menthyl group can easily be transformed into other functional groups, with the chiral center synchronously remaining. These methodologies provide highly efficient and practical strategies for the synthesis of novel axially chiral biaryl monophosphine oxides and their corresponding phosphines. Meanwhile, these reactions are easy to handle and exhibit wide scope for substrates with excellent diastereomeric ratios.     

New perspective for natural products synthesis: concise synthesis of (+)-sch 642305 by chiral auxiliary multiuse methodology

The synthesis of (+)-Sch 642305 is an example of chiral auxiliary multiuse methodology, which shows a new perspective for the synthesis of compounds with multiple asymmetric centers. Thus, (+)-Sch 642305 was concisely synthesized from the known compound. Every reaction is stereoselective, and the chiral nonracemic hydrobenzoin worked as chiral auxiliary for desymmetrization of diene, as a template for attaining regio- and stereoselective reactions, as an oxygen source at the C4-position, and as a protecting group of hydroxyl functions. Namely, the chiral auxiliary played a role in every step throughout the synthesis. Furthermore, the synthesis contains a new protocol for obtaining alpha'-alkylated enone compounds.     

Asymmetric Diels-Alder reactions with a chiral spirodione, (6S, 7S, 10R)-7-Isopropyl-10-methyl-1-oxaspiro[5.5]undec-3-ene-2,5-dione

The synthesis of the title spirodione, a new class of auxiliary based chiral synthon, using (−)-menthone having a unique carbon-carbon bond is described. Diels-Alder reactions were carried out with variety of dienes using the title auxiliary as a chiral dienophile in the presence of diethyl aluminium chloride as Lewis acid catalyst to afford the cycloadduct with good diastereoselectivity. The configurations of the chiral synthon and cycloadducts were determined by X-ray crystallography. Methodology for detachment of the chiral auxiliary from the cycloadducts has been developed.     

Chemoenzymatic synthesis and application of a new,easily chiral auxiliary for the synthesis of peptidomimetics via an Ugi reaction

A new chiral auxiliary derived from α-phenylethylamine, α-(2,4-dimethoxyphenyl)ethylamine is presented. It significantly expands upon the application of α-phenylethylamine derivatives used as chiral auxiliaries. A straightforward, chemoenzymatic synthesis of non-racemic α-(2,4-dimethoxyphenyl)ethylamine is described and the new chiral auxiliary applied to an asymmetric Ugi reaction. The mild conditions used for the cleavage of the auxiliary allowed to obtain chiral, non-racemic peptidomimetics possessing reactive α,β-unsaturated double bonds.     

Application of acyclic chiral auxiliaries on alkylation reactions

The application in alkylation reactions of an acyclic chiral auxiliary is described. The synthesis is straightforward from a chiral primary amine and a double acylation. A characteristic of this auxiliary is its modular design formed by an achiral part (acyl) and a chiral component (primary amine) so it can be tuned for different reactions without difficulty. The alkylation proceeds with excellent diastereoselectivity because the conformational flexibility of the enolate is restricted by the formation of a chelate and the allylic 1,3-strain.     

Preparation and Reactions of Amino Acid Ester Sulfones as New Remote Asymmetrical Induced Reagents

The development of chiral auxiliary-controlled asymmetric synthesis has been receiving increasing interest in recent yearsfi,2] Various chiral auxiliary reagents have been observed[3] and a lot of results showed that variation of the chiral auxiliary could influence asymmetric induction. Recently, it has been reported the reaction of the aminated sulfones as a remote chiral auxiliary with α,β-unsaturated carbonyl compounds.[4] Here we would like to report the preparation of amino acid ester sulfones as new remote asymmetrical induced reagents and their reactions with α,β-unsaturated esters.     

Synthesis of novel chiral spirodione, (6R,7R)-7-phenyl-1-oxaspiro[5.5]undec-3-ene-2,5-dione: application to the asymmetric Diels-Alder reaction with high π-facial selectivity

The synthesis of the title spirodione, a new class of auxiliary based chiral synthon using (−)-trans-2-phenylcyclohexanol and its application to the asymmetric Diels-Alder reaction are described. Methodology for detachment of the chiral auxiliary from the cycloadduct has been developed.     

Chiral induction in photochemical reactions. 14. : Linear free energy relationships as an instrument for the prediction of either de values or conformation energies of the auxiliary in the diastereoselective Paternò-Büchi reaction.

To value a stoichometric asymmetric synthesis it is important for a synthetic chemist to gain information about those structural elements of a chiral auxiliary which are responsible for high diastertomeric excesses in a particular reaction. Furtheron it is desirable to have detailed knowledge about the mechanism of the chirality transfer. In this paper an empirical relation is formulated for the correlation of structural variations of a chiral auxiliary and its influence of the diastereomeric excess in the photochemical oxetane formation in correspondance to the Ugi/Ruch concept. For this purpose we use a Linear Free Energy Relationship (LFER) which we have adjusted to reaction (2) in order to obtain quantitative information about the selectivity of this reaction on the basis of special parameters of the auxiliary applied.     

Synthesis of natural fragrant molecules cis-3-methyl-4-decanolide and aerangis lactone. General enantioselective routes to beta,gamma-cis-disubstituted gamma-lactones and gamma,delta-cis-disubstituted delta-lactones

General enantioselective routes to 3,4-cis-dialkyl substituted gamma-lactones and 4,5-cis-dialkyl substituted delta-lactones using TiCl(4)-mediated Evans asymmetric aldolization as the key step are reported. The syntheses are exemplified with two natural fragrant molecules, cis-3-methyl-4-decanolide (1) and aerangis lactone (2). The (R,R) steroegenic centers were established using (S)-phenylalanine-derived 2-oxazolidinone or thiazolidinethione as chiral auxiliary, whereas the (S,S) ones were constructed with auxiliary prepared from (R)-phenylglycine. NaBH(4)/CaCl(2)/THF in the presence of a small amount of EtOH was introduced as a new effective method for reductive cleavage of chiral oxazolidinone auxiliaries. Previously unknown, tricky concentration effects were observed during the monotosylation of diol 7 and BOM protection of Evans aldol 23.     

C(2)-Symmetric bis-sulfoxide: A novel chiral auxiliary for asymmetric desymmetrization of cyclic meso-1,2-diols

A new heterocyclic compound, C(2)-symmetric bis-sulfoxide 1, has been found to be an efficient chiral auxiliary for asymmetric desymmetrization of cyclic meso-1,2-diols via diastereoselective acetal fission. Both (R,R)- and (S,S)-1 are readily synthesized with high optical purity via asymmetric oxidation of 1, 5-benzodithiepan-3-one (2). After acetalization of meso-1,2-diols 6a-e and a mono-TMS ether 6f with this chiral auxiliary 1, the resulting acetals 7a-f were subjected to base-promoted acetal fission upon treatment with potassium hexamethyldisilazide (KHMDS) followed by acetylation or benzylation to give the desymmetrized diol derivatives 8a-f with high diastereoselectivity. The chiral auxiliary 1 is readily removed by acid-promoted hydrolysis and can be recovered without a loss in enantiomeric excess.     

Synthesis and evaluation of a new non-cross-linked polystyrene supported hydantoin chiral auxiliary for asymmetric aldol reactions

A new non-cross-linked polystyrene supported chiral hydantoin was prepared and it was shown to be a particularly effective chiral auxiliary for asymmetric aldol reactions, affording high yields and excellent diastereoselectivity. Furthermore, the recovery and recycling of the polymer-supported chiral auxiliary have been successfully achieved without an appreciable reduction in the yield or diastereoselectivity.     

Diastereoselective Ru-catalyzed cross-metathesis-dihydroxylation sequence. an efficient approach toward enantiomerically enriched syn-diols

Sequential catalysis has evolved as a powerful concept within the past years and allows the more efficient use of catalytically active expensive transition metals in organic synthesis. In this paper we present the stereoselective cross-metathesis-dihydroxylation of various olefins with chiral auxiliary substituted acrylamides. The chiral information (i.e., the auxiliary) introduced in the metathesis reactions allows for a stereoselective subsequent RuO4-catalyzed dihydroxylation. The sequence is concluded by an unusual kinetic resolution of the diastereomeric diols obtained in the oxidation reaction. As a consequence a variety of structurally diverse enantiomerically enriched diols are obtained. To the best of our knowledge the results summarized in this paper represent the first highly efficient diastereoselective RuO4-catalyzed oxidation.     

4 + 2] cycloadditions of nitroalkenes in water. Highly asymmetric synthesis of functionalized nitronates.

The [4 + 2] cycloadditions of (E)-2-aryl-1-cyano-1-nitroalkenes 1 with achiral and enantiopure vinyl ethers 2 and 3 carried out in sole water are reported. These reactions occur in a heterogeneous phase under mild conditions and are fast and highly stereoselective. By using (-)-N,N-dicyclohexyl-(1S)-isoborneol-10-sulfonamide as a chiral auxiliary, the cycloadditions are totally asymmetric. The face selectivity is discussed in terms of the shape of the chiral auxiliary and the reactive conformation of vinyl ether.     

Chiral relay: a novel strategy for the control and amplification of enantioselectivity in chiral Lewis acid promoted reactions

Chiral Lewis acid catalysis has emerged as one of the premiere method to control stereochemistry. Much effort has gone into the design of superior ligands with increasing steric extension to shield distant reactive sites. We report here an alternative and complementary approach based on a "chiral relay". This strategy focuses on the improved design of achiral templates which may relay and amplify the stereochemistry from ligands. The essence of this strategy is that the chiral Lewis acid would effectively convert an achiral template into a chiral non-racemic template. This approach combines the advantages of enantioselective catalysis (substoichiometric amount of the chiral inducer) with the ones of chiral auxiliary control (efficient and predictable stereocontrol).     

Development of new thiazole-based iridium catalysts and their applications in the asymmetric hydrogenation of trisubstituted olefins

New thiazole-based chiral N,P-ligands that are open-chain analogues of known cyclic thiazole ligands have been synthesized and evaluated in the iridium-catalyzed asymmetric hydrogenation of trisubstituted olefins. Chirality was introduced into the ligands through a highly diastereoselective alkylation using Oppolzer's camphorsultam as chiral auxiliary. In general, the new catalysts are as reactive and selective as their cyclic counterparts for the asymmetric hydrogenation of various trisubstituted olefins.     

Asymmetric diastereoselective thia-hetero-Diels–Alder reactions of dithioesters

Asymmetric thia-Diels–Alder reactions involving new dithioesters bearing a chiral auxiliary are described, with diastereoselectivities up to 78%. Double-stereodifferentiating experiments employing chiral substrates in the presence of a chiral Lewis acid catalyst have been also carried out and, in this case, a diastereomeric excess of 90% was reached. The absolute stereochemistry of cycloadducts resulting from dithiooxalates and carbonyloxazolidinone dithioesters was assigned based on an X-ray structure and chemical correlation. In order to rationalize the sense of the chiral induction, stereochemical models for Cu(II)/bis(oxazoline)/dithioester complexes are proposed.     

A novel design of a levoglucosenone derived chiral auxiliary

A two-step general approach to a new chiral auxiliary starting from levoglucosenone is reported. The compound is obtained by a [4+2] cycloaddition reaction with anthracene followed by a diastereoselective reduction of the C-2 keto function in high overall yield. The auxiliary has been used as chiral template in an asymmetric Diels-Alder reaction of the corresponding acrylic ester derivative with cyclopentadiene and shown to be efficient for asymmetric induction.     

Chiral Auxiliary Approach for Gold(I)-Catalyzed Cyclizations

Two different classes of stereoselective cyclizations have been developed using a chiral auxiliary approach with commercially available [JohnPhosAu(MeCN)SbF₆] as catalyst. First, a stereoselective cascade cyclization of 1,5-enynes was achieved using the Oppolzer camphorsultam as chiral auxiliary. In this case, a one-pot cyclization-hydrolysis sequence was developed to directly afford enantioenriched spirocyclic ketones. Then, the stereoselective alkoxycyclization of 1,6-enynes was mediated by an Evans-type oxazolidinone. A reduction-hydrolysis sequence was selected to remove the auxiliary to give enantioenriched β-tetralones. DFT studies confirmed that the steric clash between the chiral auxiliary and alkene accounts for the experimentally observed diastereoselective cyclization through the Si face.