Showing papers in "Tetrahedron-asymmetry in 2015"
TL;DR: In this article, the main processes for asymmetric transfer hydrogenation of ketones from 2008 up to today are considered, paying special attention to functionalized substrates, tandem reactions, processes under nonconventional conditions, supported catalysts, dynamic kinetic resolutions, the use of water as a green solvent, theoretical and experimental studies on reaction mechanisms, enzymatic processes, and finally applications to the total synthesis of biologically active organic molecules.
Abstract: In this review, we consider the main processes for the asymmetric transfer hydrogenation of ketones from 2008 up today. The most effective organometallic compounds (derived from Ru, Rh, Ir, Fe, Os, Ni, Co, and Re) and chiral ligands (derived from amino alcohols, diamines, sulfur- and phosphorus-containing compounds, as well as heterocyclic systems) will be shown paying special attention to functionalized substrates, tandem reactions, processes under non-conventional conditions, supported catalysts, dynamic kinetic resolutions, the use of water as a green solvent, theoretical and experimental studies on reaction mechanisms, enzymatic processes, and finally applications to the total synthesis of biologically active organic molecules.
183 citations
TL;DR: In this paper, the authors present the applications of enantioselective epoxidation of prochiral allylic alcohols, so called "Sharpless asymmetric epoxideidation" which is frequently referred as "kinetic resolution", which results in the corresponding 2,3-epoxy alcohols in high stereoselectivity as excellent starting materials for the synthesis of complex targets.
Abstract: This report presents the applications of enantioselective epoxidation of prochiral allylic alcohols, so called ‘Sharpless asymmetric epoxidation’, which is frequently referred as ‘kinetic resolution’. This reaction results in the corresponding 2,3-epoxy alcohols in high stereoselectivity as excellent starting materials for the synthesis of complex targets, such as naturally occurring biologically active molecules.
75 citations
TL;DR: This review highlights the advances in the use of isatin as starting material in various catalytic enantioselective strategies for the synthesis of 3,3-disubstituted oxindoles during the period from 2012 to 2014.
Abstract: 3,3-Disubstituted oxindoles with a stereogenic quaternary carbon center exist widely in various natural products and biologically active compounds. Various strategies have been developed for the synthesis of these enantiomerically enriched frameworks, among them the organo- or metal-catalyzed asymmetric addition of reagents to isatins is the most simple and straightforward method. This review highlights the advances in the use of isatin as starting material in various catalytic enantioselective strategies for the synthesis of 3,3-disubstituted oxindoles during the period from 2012 to 2014.
67 citations
TL;DR: The present review describes the chronological development of asymmetric organocatalyzed aldol reactions in aqueous media considering both ‘in water’ and ‘on water” concepts in each subsection.
Abstract: The aldol reaction is an excellent synthetic tool to construct β-hydroxy carbonyl skeletons. The asymmetric version of this reaction has been developed for the synthesis of enantiomerically enriched β-hydroxy carbonyl motifs, which can be extended toward the stereogenic construction of complex polyol architectures. l -Proline and other organic molecules are known to catalyze asymmetric direct aldol reactions in various solvents. Most asymmetric organocatalyzed direct aldol reactions occur in organic media, although some aldol reactions have been carried out in water, either as a co-solvent or additive. The development of highly diastereo- and enantioselective organocatalyzed direct aldol reactions between a wide variety of substrates in water without the contamination of any organic solvent is of great interest. Herein, we discuss organocatalysts based on l -proline, 4-hydroxy- l -proline, simple amino acids, enzymes etc., which have been so far applied in asymmetric aldol reactions in aqueous media. The present review describes the chronological development of asymmetric organocatalyzed aldol reactions in aqueous media considering both ‘in water’ and ‘on water’ concepts in each subsection.
43 citations
TL;DR: Enantioselective aldol reactions between ketones and aldehydes were shown to be catalysed by a variety of tert -butyl esters of peptides, with Pro-Glu(O t Bu)-O tBu proved to be the best, affording the product in good to excellent yields, diastereoselectivities and enantioselectedivities.
Abstract: Enantioselective aldol reactions between ketones and aldehydes were shown to be catalysed by a variety of tert -butyl esters of peptides. Amongst the peptides tested, Pro-Glu(O t Bu)-O t Bu proved to be the best, affording the product in good to excellent yields, diastereoselectivities and enantioselectivities.
37 citations
TL;DR: In this paper, the enantioselective oxidative coupling of 2-naphthols in water was established using dinuclear vanadium(V/IV) catalysis with O2 as the sole co-oxidant.
Abstract: The enantioselective oxidative coupling of 2-naphthols in water was established using dinuclear vanadium(V/IV) catalysis with O2 as the sole co-oxidant. In the vanadium-catalyzed reaction, the corresponding coupling products were obtained in good to excellent yields with up to 94% enantiomeric excess. In water, racemization of the coupling product was suppressed even at high temperature (70 °C).
27 citations
TL;DR: In this article, a chiral Bronsted acid catalyzed Friedel-Crafts reaction of terminal 1,1-diaryalkenes with indoles is described, which provides indole derivatives with acyclic all-carbon quaternary stereocenters in excellent yields and with excellent enantioselectivities.
Abstract: A chiral Bronsted acid catalyzed Friedel–Crafts reaction of terminal 1,1-diaryalkenes with indoles is described. This reaction provides indole derivatives with acyclic all-carbon quaternary stereocenters in excellent yields and with excellent enantioselectivities, and features high atom efficiency without the generation of side products.
25 citations
TL;DR: In this article, an efficient, one-pot, four-component procedure for the synthesis of a small library of novel chiral spiro-indenoquinoxaline pyrrolidines with high regio-, diastereo- and enantioselectivity (up to 99% ee), through a 1,3-dipolar cycloaddition reaction of azomethine ylides and an optically active cinnamoyl-crotonoyl oxazolidinone is described.
Abstract: An efficient, one-pot, four-component procedure for the synthesis of a small library of novel chiral spiro-indenoquinoxaline pyrrolidines and chiral spiro-indenoquinoxaline pyrrolizidines with high regio-, diastereo- (up to 96 dr), and enantioselectivity (up to 99% ee), through a 1,3-dipolar cycloaddition reaction of azomethine ylides and an optically active cinnamoyl–crotonoyl oxazolidinone is described. This methodology was very simple and was utilized to construct complex products from simple starting materials. The process was carried out in aqueous ethanol as an eco-friendly solvent and in the absence of any Lewis acids catalysts. The oxazolidinone chiral auxiliary was removed through a non-destructive protocol. The reaction mechanism is discussed on the basis of the assignment of the absolute configuration of the cycloadducts and using quantum mechanical calculations. The regio- and stereoselectivity were described on the basis of transition states’ stabilities and global and local reactivity indices of the reactants. The results of the theoretical calculations are in agreement with the experimental outcomes.
24 citations
TL;DR: In this paper, the bicyclic cores were prepared by a ruthenium-catalyzed ring-closing metathesis, followed by re-use of the catalyst in the subsequent syn-dihydroxylation in a one-pot procedure.
Abstract: Novel polyhydroxylated derivatives of quinolizidine and decahydropyrido[1,2-a]azepine were prepared starting from a common oxazolidinone. The bicyclic cores were prepared by a ruthenium-catalyzed ring-closing metathesis, followed by re-use of the catalyst in the subsequent syn-dihydroxylation in a one-pot procedure.
24 citations
TL;DR: In this article, a synthetic route leading to a series of new chiral catalysts containing the N-trityl-aziridine moiety and a primary and a secondary hydroxyl group as nucleophilic centers is described.
Abstract: A synthetic route leading to a series of new chiral catalysts containing the N-trityl-aziridine moiety and a primary and a secondary hydroxyl group as nucleophilic centers is described. All the new compounds have been tested as chiral catalysts in the enantioselective addition of diethylzinc and phenylethynylzinc to aryl and alkyl aldehydes, yielding the corresponding chiral alcohols in high chemical yields (up to 96%) and with excellent ee’s of ca. 90%. The influence of the stereogenic centers located at the carbon atom bonded with the hydroxyl moiety and on the carbon of the aziridine ring on the stereochemistry of the addition reactions is also discussed.
24 citations
TL;DR: In this article, the use of diethyl carbonate as a sustainable solvent for organocatalytic asymmetric transfer hydrogenations of 2-substituted quinolines using highly efficient chiral phosphoric acid catalysts with Hantzsch esters as a hydrogen source is reported for the first time.
Abstract: The use of diethyl carbonate as a sustainable solvent for organocatalytic asymmetric transfer hydrogenations of 2-substituted quinolines using highly efficient chiral phosphoric acid catalysts with Hantzsch esters as a hydrogen source is reported for the first time. The asymmetric transfer hydrogenation reaction in diethyl carbonate provides enantiomerically pure 1,2,3,4-tetrahydroquinolines with high yields and excellent enantioselectivities (up to 99% ee). These results clearly confirm that this green and sustainable solvent is an excellent replacement for organic solvents, which are harmful to the environment, and transition metal based catalysts are not required. The effects of different chiral phosphoric acids, solvents, catalyst loading, temperature effect, and reaction time on the conversion and enantioselectivity of desired product are discussed.
TL;DR: In this article, simple chiral triethylsilyl-amino alcohol organocatalysts containing a bulky triethyl silyl group on the oxygen atom at the γ-position were designed and synthesized as new organocATalysts for enantioselective Diels-Alder reactions of anthrones with maleimides to produce chiral hydroanthracene diels-alder adducts in up to 99% yield and with up to 94% ee.
Abstract: Simple chiral triethylsilyl-amino alcohol organocatalysts containing a bulky triethylsilyl group on the oxygen atom at the γ-position were designed and synthesized as new organocatalysts for enantioselective Diels–Alder reactions of anthrones with maleimides to produce chiral hydroanthracene Diels–Alder adducts in up to 99% yield and with up to 94% ee.
TL;DR: In this paper, 1,4-dihydropyridines were synthesized via catalytic enantioselective cyclization reactions of β,γ-unsaturated α-ketoesters, arylamines and acetylacetone for the first time.
Abstract: Penta-substituted 1,4-dihydropyridines were synthesized via catalytic enantioselective cyclization reactions of β,γ-unsaturated α-ketoesters, arylamines and acetylacetone for the first time. H 8 -BINOL-type chiral imidodiphosphoric acid 4c was a suitable catalyst and exhibited high catalytic and stereocontrolling abilities in these enone-type reactions. Under the optimized conditions, these 1,4-dihydropyridines were obtained with excellent enantioselectivities (up to 97% ee). In addition, the typical product 8ba was converted into the corresponding substituted piperidine with high yield (87%) and excellent enantioselectivity (95% ee) in a single-step reduction.
TL;DR: In this paper, the authors report experimental measurements of apparent equilibrium constants for several industrially relevant transamination reactions in a systematic manner to better understand the effect of amine acceptor and donor choice.
Abstract: In recent years biocatalytic transamination using ω-transaminase has become established as one of the most interesting routes to synthesize chiral amines with a high enantiomeric purity, especially in the pharmaceutical sector where the demand for such compounds is high. Nevertheless, one limitation for successful implementation and scale-up is that the thermodynamics of such conversions are frequently found unfavourable. Herein we report experimental measurements of apparent equilibrium constants for several industrially relevant transamination reactions in a systematic manner to better understand the effect of amine acceptor and donor choice. For example, we have found that ortho-substitution of acetophenone like molecules, had a significant impact on the thermodynamic equilibrium. Likewise, the effect of cyclic amine acceptors was evaluated and compared to similar non-cyclic structures. It was found that an aliphatic six membered ring was favourable and a conjugated bicyclic five membered ring structure, unfavourable. Finally, we evaluated and compared the use of five different donor molecules, and calculated their ΔGapp values. This is particularly important in the further implementation of such reactions because it may be used to help select suitable donor/acceptor combinations. The results presented here give guidance, with respect to thermodynamics, in order to further extend the application of biocatalytic transamination.
TL;DR: In this paper, a diastereomerically enriched oxazine intermediate was used to synthesize (+)-1-deoxynojirimycin and (2R,5R)-dihydroxymethyl-(3R,4R)dihyroxypyrrolidine [(+)-DMDP] by using 1,3-oxazine as a chiral building block and a nucleophilic addition to an aldehyde.
Abstract: Concise and stereocontrolled syntheses of (+)-1-deoxynojirimycin and (2R,5R)-dihydroxymethyl-(3R,4R)-dihydroxypyrrolidine [(+)-DMDP] were achieved via a diastereomerically enriched oxazine intermediate. The key strategies include the use of 1,3-oxazine as a chiral building block and diastereoselective nucleophilic addition to an aldehyde. Starting from readily available (R)-methyl 2-benzamido-3-((tert-butyldimethylsilyl)oxy)propanoate, (+)-1-deoxynojirimycin was synthesized in 11 steps and 26.2% overall yield while (+)-DMDP was synthesized in 11 steps and 27.1% overall yield, respectively.
TL;DR: In this article, four chiral amino alcohols with a sulfur substituent were synthesized from d -(+)-camphor and utilized as ligands in Cu(I)-catalyzed asymmetric Henry reactions between nitromethane and various aldehydes.
Abstract: Four chiral amino alcohols with a sulfur substituent were synthesized from d -(+)-camphor and utilized as ligands in Cu(I)-catalyzed asymmetric Henry reactions between nitromethane and various aldehydes. The reactions were carried out under mild conditions with excellent enantioselectivities and good yields without the exclusion of air or moisture. The highest enantioselectivity was observed (up to 96% ee) with ligand 3c in CH 3 NO 2 at 0 °C.
TL;DR: A series of 5- tert -butyl-2-(pyridine-2-yl)imidazolidine-4-ones have been prepared and their Cu(II) complexes studied as enantioselective catalysts of the asymmetric Henry reaction of various aldehydes with nitromethane as mentioned in this paper.
Abstract: A series of 5- tert -butyl-2-(pyridine-2-yl)imidazolidine-4-ones have been prepared and their Cu(II) complexes studied as enantioselective catalysts of the asymmetric Henry reaction of various aldehydes with nitromethane. It was found that these compounds were effective catalysts for this reaction, with enantiomeric excesses being as high as 97%. The enantioselectivities of individual derivatives were different and depended on the substituents attached to stereogenic centers and the configuration of imidazolidine-4-one cycle. High enantiomeric excesses were obtained irrespective of the solvent used. The most effective derivative was chosen for preparation of the key intermediate for Salmeterol medical drug and an enantiomeric excess of 92% was obtained.
TL;DR: In this article, aldol reactions between 4-nitrobenzaldehyde and cyclohexanone were catalysed by trans-4-hydroxyl group on (S )-prolinamide and (S)-1-phenylethylamine both influenced the ee of the predominant anti-aldol product.
Abstract: Direct asymmetric aldol reactions between 4-nitrobenzaldehyde and cyclohexanone were catalysed by trans -4-hydroxy-( S )-prolinamide (10 mol %) in the presence of CH 3 COOH (10 mol %) as the co-catalyst under solvent-free conditions at 15 °C. (2 S ,4 R )-4-Hydroxy- N -(( S )-1-phenylethyl)pyrrolidine-2-carboxamide 2 efficiently catalysed the asymmetric aldol reaction to afford the product in >99% yield and with 95% ee with an anti / syn ratio of 88:12 after 18 h. The additional trans -hydroxyl group on ( S )-prolinamide and ( S )-1-phenylethylamine both influenced the ee of the predominant anti aldol product. Different benzaldehyde derivatives with cyclohexanone gave the corresponding aldol products in 38–89% yields and with 56–94% ee with anti / syn (100:0–71:29). Catalyst 2 can be used up to 5 continuous cycles for asymmetric aldol reactions between 4-nitrobenzaldehyde and cyclohexanone with overall 91% yield and 86% yield of anti -product with anti / syn (98:2).
TL;DR: In this paper, the asymmetric synthesis of 3-alkyl-3-hydroxyindolin-2-ones via direct aldol reaction of isatin with ketones catalyzed by natural amino acid salts is described, in which the phenylalanine lithium salt was found to be the best catalyst.
Abstract: The asymmetric synthesis of 3-alkyl-3-hydroxyindolin-2-ones via direct aldol reaction of isatin with ketones catalyzed by natural amino acid salts is described, in which the phenylalanine lithium salt was found to be the best catalyst. This strategy was then applied to a variety of isatin and ketone substrates and the corresponding aldol products were obtained in excellent yields (up to 97%) with good to excellent enantioselectivities (up to 90%).
TL;DR: In this article, the enantiomeric excess of optically active promethazine was determined by a proton nuclear magnetic resonance (1H NMR) spectroscopic enantiodifferentiation method by means of (S)-(−)-1,1′-bi(2-naphthol) [(S)- (−)-BINOL] as a chiral solvating agent (CSA).
Abstract: The enantiomeric excess of optically active promethazine was determined for the first time by a proton nuclear magnetic resonance (1H NMR) spectroscopic enantiodifferentiation method by means of (S)-(−)-1,1′-bi(2-naphthol) [(S)-(−)-BINOL] as a chiral solvating agent (CSA), and additionally ascertained by HPLC measurements on Chiralcel® OJ chiral column. The results obtained for the enantiopurity of standard samples of promethazine were almost fully consistent with those established by chiral HPLC (quantitative to approximately 1% minor enantiomer). The developed method is simple, rapid, inexpensive, repeatable, sensitive, and very selective toward promethazine enantiomers, and may serve for its routine quantitative analysis.
TL;DR: Diastereoselective hydrophosphonylation of aldehydes with a chiral H -phosphonate with high asymmetric inductions led to the desired α-hydroxyphosphonic acids in very good yields and high enantiomeric purity as the ( R )-enantiomers.
Abstract: Diastereoselective hydrophosphonylation of aldehydes with a chiral H -phosphonate is described. High asymmetric inductions were obtained using a readily available TADDOL auxiliary. Subsequent, racemization-free removal of the chiral auxiliary led to the desired α-hydroxyphosphonic acids in very good yields and high enantiomeric purity as the ( R )-enantiomers.
TL;DR: In this paper, a simple, short, efficient, and concise approach for the synthesis of decytospolides A, B and partial synthesis of aspergillide A was achieved from d -mannitol.
Abstract: A simple, short, efficient, and concise approach for the synthesis of decytospolides A, B and partial synthesis of aspergillide A was achieved from d -mannitol. The key steps employed in this approach are a Barbier type allylation, an epoxide opening by Grignard reagent, a chelation controlled reduction, tandem or domino (olefin cross-metathesis/intramolecular oxa-conjugate cyclization by Hoveydas–Grubb’s 2nd generation and olefin cross-metathesis/S N 2 reaction with Grubb’s 2nd generation catalyst) processes.
TL;DR: The first catalytic asymmetric styrene hydroarylation reaction has been established via the enantioselective Friedel-Crafts alkylations of phenylhydrazones with o -hydroxyl styrenes under the catalysis of a chiral phosphoric acid as an organocatalyst, leading to the construction of a 1,1-diarylethane scaffold with high enanti-lectivity.
Abstract: The first catalytic asymmetric styrene hydroarylation reaction has been established via the enantioselective Friedel–Crafts alkylations of phenylhydrazones with o -hydroxyl styrenes under the catalysis of a chiral phosphoric acid as an organocatalyst, leading to the construction of a chiral 1,1-diarylethane scaffold with high enantioselectivity (up to 89% ee). The investigation on the activation mode suggested that the two reactants, o -hydroxyl styrenes and phenylhydrazones, were simultaneously activated by the catalyst via multiple hydrogen-bonds. The remote activation of the hydrazone functionality by a dual hydrogen-bonding interaction with the catalyst contributed greatly to the hydroarylation reaction of the o -hydroxyl styrenes.
TL;DR: In this article, a series of imidazolium moiety tagged planar chiral ferrocenyl oxazoline phosphine (FimiOAXP) ligands were designed and synthesised.
Abstract: A series of imidazolium moiety tagged planar chiral ferrocenyl oxazoline phosphine (FimiOAXP) ligands were designed and synthesised. In connection with their usefulness as ligands for asymmetric 1,3-dipolar cycloadditions of azomethine ylides with nitroalkenes, the catalysts were prepared in situ by treatment of copper(I) perchlorate and FimiOAXP. In the presence of a weak base, the pyrrolidine analogues were obtained in satisfactory yields and with excellent enantioselectivities (up to 99% ee). Through the experimental and computational outcomes, ion effect between the imidazolium moiety and azomethine ylide proved to be an essential factor for the excellent enantioselectivity. Moreover, with the benefit of the imidazolium moiety, the asymmetric 1,3-dipolar cycloaddition underwent in DCM/ionic liquids combined solvent for the first time. Taking advantage of the occasion, the catalyst could be recycled and reused for at least five times.
TL;DR: In this paper, a new set of enantiopure thiazolidine-based organocatalysts were prepared using a simple synthetic approach and successfully applied in the asymmetric direct aldol reaction between various cyclic ketones and aldehydes in a saturated aqueous medium.
Abstract: Taking l -aminoacids as starting materials, a new set of enantiopure thiazolidine-based organocatalysts were prepared using a simple synthetic approach and successfully applied in the asymmetric direct aldol reaction between various cyclic ketones and aldehydes in a saturated aqueous medium The aldol adducts were obtained with excellent enantioselectivity (up to >99% ee) and diastereoselectivity (dr >20:1)
TL;DR: In this paper, the influence of different solvents on the separation of valine enantiomers using β-cyclodextrin as a chiral selector was studied by means of a molecular mechanics and dynamics simulation.
Abstract: The influence of different solvents on the separation of valine enantiomers using β-cyclodextrin as a chiral selector was studied by means of a molecular mechanics and dynamics simulation. The interaction energy is modelled by the AMBER force field in which the polarity of organic modifiers is represented by different values of the dielectric constant e in the electrostatic contribution to energy, and also by different configurations of valine (non-polar or zwitterions). The regions with maximum chiral discrimination are determined by molecular mechanics, finding that the d -enantiomer is more stable outside the cavity than the l -enantiomer, for the different cases analysed. l -Val has more positions inside the cavity, where it is more stable except in vacuo and in non-polar solvents such as hydrocarbons, where the inner part of cyclodextrin is only slightly enantioselective and d -Val is more stable. Molecular dynamics simulations show that the most probable configuration of valine enantiomers is located outside the cavity in non-polar solvents with e = 1 or e = 2, in regions with low chiral discrimination. In solvents such as benzene, acetone, ethanol or water, the most probable configuration is near the centre of β-cyclodextrin, in favourably enantioselective positions where l -Val is more stable. The elution order depends on the polarity of solvents: l -Val is the first eluted enantiomer in all cases studied with the non-polar configuration and d -Val for zwitterions, independent of the value of the dielectric constant.
TL;DR: In this paper, the synthesis of new homochiral l -prolinamido-sulfonamides 1 -7 from enantiomerically pure (R, R )-11,12-diamino-9,10-dihydro-9-10-ethanoanthracene (R, R ) -8 is reported.
Abstract: The synthesis of new homochiral l -prolinamido-sulfonamides 1 – 7 from enantiomerically pure ( R , R )-11,12-diamino-9,10-dihydro-9,10-ethanoanthracene ( R , R )- 8 is reported. The l -prolinamido-sulfonamides 1 – 7 were tested as organocatalysts (10 mol %) in the aldol reaction of p - nitrobenzaldehyde and acetone in dichloromethane at room temperature in the presence of water (1 equiv) and acetic acid (20 mol %) giving good to high yields and enantioselectivities. Catalyst 4 (10 mol %) afforded the best results in the aldol reaction of acetone with p -substituted-benzaldehydes with electron withdrawing groups (i.e., nitro, cyano, bromo and chloro, up to 97% yield and 90% ee). The origin of the enantioselective induction was modeled using DFT methods. The estimated enantioselectivity for the model system is consistent with the experimental data.
TL;DR: In this article, the resolution of mandelic acid and its derivatives with free amino acids has been investigated and it was observed that the corresponding diastereomers were formed under either kinetic or thermodynamic control, which considerably influenced the purity of the enantiomeric mixtures obtained.
Abstract: The resolution of mandelic acid and its derivatives with free amino acids has been investigated. It was observed that the corresponding diastereomers were formed under either kinetic or thermodynamic control, which considerably influenced the purity of the enantiomeric mixtures obtained. It was found that in these particular resolutions, the eutectic composition of either the racemic compound or the resolving agent influenced the purity of the enantiomeric mixtures of the mandelic acid derivatives obtained after resolution.
TL;DR: Optically active isatin-derived N, O -aminals were obtained through the catalytic asymmetric addition of various alcohols to isatin derived N -Boc ketimines as discussed by the authors.
Abstract: Optically active isatin-derived N , O -aminals were obtained through the catalytic asymmetric addition of various alcohols to isatin-derived N -Boc ketimines. Using 2′-phenyl cinchonidine thiourea as the catalyst, adducts were obtained in 96% yield and with up to 92% ee.
TL;DR: In this article, a diastereoselective hydrophosphonylation of 2-azanorbornane aldehyde exo-1 with silylated phosphorus esters yielded the (S)-α-hydroxyphosphonic acid exO-3a.
Abstract: Highly diastereoselective hydrophosphonylation of 2-azanorbornane aldehyde exo-1 with silylated phosphorus esters yielded the (S)-α-hydroxyphosphonic acid exo-3a. The use of endo-2 gives the isomer with the opposite configuration at the new stereogenic center (R)-endo-4a. X-ray analysis revealed that exo-3a crystallizes in the orthorhombic space group P212121 with two crystallographically independent molecules, one zwitterionic and the other forming a salt with HBr.