Diastereoselective Conjugate Addition Research Articles

Diastereoselective Conjugate Addition of Cyanide to α,β-Unsaturated ­Oxazolidinones: Enantioselective Synthesis of ent-Pregabalin and Baclofen

Conjugate addition of cyanide to chiral α,β-unsaturated oxazolidinones catalyzed by samarium(III) isopropoxide proceeds with good diastereoselectivity. The addition products can be converted into the biologically active targets ent-pregabalin and baclofen.

Diastereoselective synthesis of aziridine esters via amino selanyl esters

A synthesis of aziridine esters based on the cyclisation of amino selanyl esters induced by the selanyl group activation was developed with either the Meerwein salt or NBS. Two asymmetric approaches are proposed: the diastereoselective reductions of α-selanyl β-iminoesters derived from α-oxoesters, which lead to cis chiral aziridine esters 6 and 6′ ; and the diastereoselective conjugate additions of a chiral amide to α,β-unsaturated esters providing trans chiral aziridine esters 6 and 6″ .

Regio‐ and Diastereoselective Conjugate Addition to 4,4‐Dimethylcyclohexadienones

AbstractConjugate addition of vinyl cuprate and dimethyl malonate to 4,4‐dimethylcyclohexa‐2,5‐dienones has allowed facile access to mono‐ and bis‐adducts in satisfactory yields. While the high diastereoselectivity of such processes to afford trans‐bis‐adducts was predictable, an unprecedented regioselectivity was observed with 2,4,4‐trimethylcyclohexa‐2,5‐dienone, with the first addition occurring exclusively at the C‐5 carbon atom (distal from the methyl group) and with the second addition of a bulky nucleophile such as dimethyl malonate even prevented. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Diastereoselective conjugate addition of 1-(α,β-unsaturated acyl)hydantoin with nucleophiles

A diastereomeric conjugate addition of dialkylaluminum chloride to 1-(α,β-unsaturated acyl)hydantoin provided the corresponding alkyl adduct with inducted chirality in the β-position. Treatment of 1-(α,β-unsaturated acyl)hydantoin with Gilman reagent in the presence of Lewis acid also gave the same product. In this reaction, diethylaluminum chloride was the most effective Lewis acid and the absolute configuration of the major adduct at the β-position of acyl group depended on the kinds of existing metals.

Syntheses of New Chiral Phosphane Ligands by Diastereoselective Conjugate Addition of Phosphides to Enantiomerically Pure Acceptor‐Substituted Olefins from the Chiral Pool

AbstractA variety of new chiral phosphanes were prepared by highly diastereoselective additions of phosphanes to α,β‐unsaturated carbonyl compounds and related acceptor‐substituted olefins derived from myrtenal as ex chiral pool source. Monophosphanes with astereogenic as well as stereogenic phosphorus are described. In addition diphosphanes were prepared by a highly diastereoselective double conjugate addition of a secondary diphosphane. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Asymmetric Synthesis of the cis‐ and trans‐Stereoisomers of 4‐Aminopyrrolidine‐3‐carboxylic Acid and 4‐Aminotetrahydrofuran‐3‐carboxylic Acid.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric Total Synthesis of Sperabillins B and D via Lithium Amide Conjugate Addition.

ChemInformVolume 36, Issue 5 Natural Products Asymmetric Total Synthesis of Sperabillins B and D via Lithium Amide Conjugate Addition. Stephen G. Davies, Stephen G. Davies Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorJane R. Haggitt, Jane R. Haggitt Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorOsamu Ichihara, Osamu Ichihara Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorRichard J. Kelly, Richard J. Kelly Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorMichael A. Leech, Michael A. Leech Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorAnne J. Price Mortimer, Anne J. Price Mortimer Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorPaul M. Roberts, Paul M. Roberts Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorAndrew D. Smith, Andrew D. Smith Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this author Stephen G. Davies, Stephen G. Davies Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorJane R. Haggitt, Jane R. Haggitt Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorOsamu Ichihara, Osamu Ichihara Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorRichard J. Kelly, Richard J. Kelly Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorMichael A. Leech, Michael A. Leech Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorAnne J. Price Mortimer, Anne J. Price Mortimer Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorPaul M. Roberts, Paul M. Roberts Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this authorAndrew D. Smith, Andrew D. Smith Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UKSearch for more papers by this author First published: 11 January 2005 https://doi.org/10.1002/chin.200505217Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume36, Issue5February 1, 2005 RelatedInformation

Stereoselective conjugate addition reactions of lithium amides to α,β-unsaturated chiral iron acyl complexes [(η 5-C 5H 5)Fe(CO)(PPh 3)(COCH [dbnd]CHR)

Conjugate addition of achiral lithium dimethylamide to the chiral iron cinnamoyl complexes ( S, E)- and ( S, Z)-[(η 5-C 5H 5)Fe(CO)(PPh 3)(COCH CHPh)] proceeds with high diastereoselectivity, with this protocol being used to establish unambiguously the absolute configuration of Winterstein’s acid (3- N, N-dimethylamino-3-phenylpropanoic acid) as ( R). The highly diastereoselective conjugate addition of lithium N-benzyl- N-trimethylsilylamide to a range of α,β-unsaturated iron acyl complexes, followed by in-situ elaboration of the derived enolate by either alkylation or aldol reactions is also demonstrated, facilitating the stereoselective synthesis of both cis- and trans-β-lactams. This methodology has been used to effect the formal asymmetric syntheses of (±)-olivanic acid and (±)-thienamycin. Addition of chiral lithium amides derived from primary and secondary amines to the iron crotonyl complex [(η 5-C 5H 5)Fe(CO)(PPh 3)(COCH CHMe)] indicates that lithium N-α-methylbenzylamide shows low levels of enantiorecognition, while lithium N-3,4-dimethoxybenzyl- N-α-methylbenzylamide and lithium N-benzyl- N-α-methylbenzylamide show high levels of enantiodiscrimination. The high level of observed enantiorecognition was used to facilitate a kinetic resolution of ( RS)-[(η 5-C 5H 5)Fe(CO)(PPh 3)(COCH CHMe)] with homochiral lithium ( R)- N-3,4-dimethoxybenzyl- N-α-methylbenzylamide. Further mechanistic studies show that conjugate additions of ( RS)-lithium N-benzyl- N-α-methylbenzylamide to either the ( RS)- or homochiral iron crotonyl complex show 2:1 stoicheiometry, while homochiral lithium N-benzyl- N-α-methylbenzylamide shows 1:1 stoicheiometry.

Efficient Synthesis of (.+‐.)‐γ‐Lycorane Employing Stereoselective Conjugate Addition to Nitroolefin.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly Diastereoselective Conjugate Additions of Monoorganocopper Reagents to Chiral Imides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Efficient synthesis of (±)-γ-lycorane employing stereoselective conjugate addition to nitroolefin

(±)-γ-Lycorane 3 was synthesized in 52% overall yield via seven steps from 5 by employing the highly stereoselective nitro-Michael cyclization of 5 to 9 and diastereoselective conjugate addition of aryllithium to a nitroolefin 10 as two key steps.

Highly Diastereoselective Conjugate Addition to Alkylidene Bis(sulfoxides): Asymmetric Synthesis of (+)‐erythro‐Roccellic Acid.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric synthesis of beta-amino esters by aza-Michael reaction of alpha,beta-unsaturated amides using (S,S)-(+)-pseudoephedrine as chiral auxiliary.

Chiral nonracemic beta-amino esters were prepared in good yields and enantioselectivities using the diastereoselective conjugate addition of nitrogen nucleophiles to alpha,beta-unsaturated amides derived from (S,S)-(+)-pseudoephedrine as the key step. In this way, several beta-amino amide adducts were prepared using different conjugate acceptors and two different lithium benzylamides as nucleophiles. These adducts were easily converted in only one step, into the final, highly enantioenriched beta-amino esters

Highly diastereoselective conjugate additions of monoorganocopper reagents to chiral imides

Stereoselective conjugate additions to chiral N-enoyl amides employing various monoorganocuprate reagents, Li[RCuI], are described. The presence of TMSI in the addition of Li[RCuI] in THF provided the highest stereoselectivities. Reversed major diastereomeric ratios were obtained employing Li[RCuI] in ether or conventional copper-promoted Grignard reagents. The results presented support the favored anti- s- cis conformation of the substrates using Li[RCuI]/TMSI in THF, while the copper-promoted Grignard reagents or the Li[RCuI] reagents in ether favor the opposite syn- s- cis conformation. Influence of lithium ions on the stereoselective conjugate addition of the monoorganocuprate reagent, Li[BuCuI], has been investigated and two different mechanistic pathways are presented. The results show that iodotrimethylsilane (TMSI) is crucial for the asymmetric conjugate addition of the copper reagent, but only in THF or when 12-crown-4 is used. The reaction is thought not to involve any halosilane in any critical steps in the organocopper mechanisms conducted in ether. The (CuI) 4(SMe 2) 3 complex precursor plays an instrumental role for the conjugate addition using monoorganocopper reagents.

Diastereoselective conjugate addition of Grignard reagents to a homochiral fumaramide derived from Oppolzer’s sultam

Conjugate addition of Grignard reagents to N, N ′-fumaroylbis[(2 R)-bornane-10,2-sultam] 1 occurred with moderate to high levels of diastereoselectivity. Diastereomeric excesses were estimated by analysis of the 1H NMR spectra of the succinamide mixtures and enantiomeric excesses from 19F NMR spectra of the bis Mosher esters of the diols produced by reductive cleavage of the succinamides. Saponification of the succinamides gave the corresponding ( R)-succinic acids with ees up to 92% showing that addition of the Grignard reagents takes place selectively on the re-face of 1 .

Asymmetric total synthesis of sperabillins B and D via lithium amide conjugate addition.

Diastereoselective conjugate addition of homochiral lithium (R)-N-allyl-N-alpha-methylbenzylamide to methyl (2E,5E)-hepatadienoate, followed by protecting group manipulation and subsequent iodocyclocarbamation allows a concise route to the core fragment, methyl (3R,5R,6R)-3,6-diamino-5-hydroxyheptanoate, of sperabillins B and D. Differentiation between the C-3 and C-6 primary amino groups of this core amino acid was readily achieved by treatment with acetone, giving the 5,6-isopropylidene and C-3-imine protected diamine, with subsequent regioselective acylation of the C-6-nitrogen facilitating the total synthesis of sperabillin D in 10.8% overall yield, and the first asymmetric synthesis of sperabillin B in 5.8% overall yield.

Asymmetric synthesis of the cis- and trans-stereoisomers of 4-aminopyrrolidine-3-carboxylic acid and 4-aminotetrahydrofuran-3-carboxylic acid

The diastereoselective conjugate addition of lithium (S)-N-benzyl-N-[small alpha]-methylbenzylamide has been successfully applied to the first asymmetric syntheses of cis-(3S,4R)- and trans-(3R,4R)-4-aminotetrahydrofuran-3-carboxylic acids (26% and 25% overall yield respectively, >98% d.e. and >97% e.e. in each case). Furthermore, the most efficient asymmetric synthesis to date of cis-(3R,4R)- and trans-(3R,4S)-4-aminopyrrolidine carboxylic acids is delineated: for cis-(3R,4R), four steps, >98% d.e., 52% overall yield; for trans-(3R,4S), five steps, >98% d.e., 50% overall yield.

SuperQuat N‐Acyl‐5,5‐dimethyloxazolidin‐2‐ones for the Asymmetric Synthesis of α‐Alkyl and β‐Alkyl Aldehydes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Diastereoselective Conjugate Addition to Chiral α,β‐Unsaturated Carbonyl Systems in Aqueous Media: An Enantioselective Entry to α‐ and γ‐Hydroxy Acids and α‐Amino Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly Diastereoselective Conjugate Addition to Alkylidene Bis(Sulfoxides): Asymmetric Synthesis of (+)‐erythro‐Roccellic Acid

Faciale Stereokontrolle ist möglich bei Additionen von Nucleophilen (Nu) an Alkylidenbis(sulfoxide): In Gegenwart geeigneter Lewis-Säuren (LA) erfolgt die Reaktion über Chelatkomplexe (B), was eine andere Konfiguration im Produkt zur Folge hat. Dies wurde zur Lösung eines Problems bei der ersten Totalsynthese von (+)-erythro-Roccellsäure genutzt. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2003/z52356_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.