Glyoxylate Imines Research Articles

Asymmetric synthesis of piperidines using the nitro-Mannich reaction☆

Abstract A method for the synthesis of functionalized piperidines containing 3 contiguous stereocentres in the 2-,3- and 4- positions uses a diastereoselective nitro-Mannich to control stereochemistry. The nitro-Mannich reaction between a β-aryl/heteroaryl substituted nitroalkanes and glyoxylate imine provides β-nitro-amines with good selectivity (70:30 to >95:5) for the syn, anti-diastereoisomers. Reductive cyclisation with BF3.OEt2 and Et3SiH gave, after purification, stereochemically pure piperidines in 19–57% yield for ten examples with different 4-aryl/heteroaryl substituents.

Transformation of Racemic Azlactones into Enantioenriched Dihydropyrroles and Lactones Enabled by Hydrogen‐Bond Organocatalysis

Azlactones, a potent building block for the synthesis of complex molecules, have been explored in an organocatalytic Mannich reaction with protected imines. In this study, azlactones containing a propargyl substituent were employed for the first time in organocatalysis so far. The catalytically active species responsible for high enantioselectivity with substrate containing such a small linear substituent is assembled in situ from a bifunctional thiourea, prone to dimerization, and an organic acid, as evidenced by DOSY NMR. The resulting α,β‐diamino acid derivatives were subjected to further derivatization: as an example, gold‐catalyzed intramolecular hydroamination of alkynes gave chiral spirocyclic dihydropyrrole. Alternatively, related squaramide catalyst enabled a Mannich reaction of azlactones with N‐aryl or alkyl glyoxylate imines. Reduction of these adducts gave access to 2,3‐diaminobutyrolactones or 2,3‐diamino‐1,4‐diol with a tertiary and a quaternary stereocenter.

Catalytic Asymmetric Mannich Reaction with N-Carbamoyl Imine Surrogates of Formaldehyde and Glyoxylate.

N,O-acetals (NOAcs) were developed as bench stable surrogates for N-carbamoyl, (Boc, Cbz and Fmoc) formaldehyde and glyoxylate imines in asymmetric Mannich reactions. The NOAcs can be directly utilized in the chiral primary amine catalyzed Mannich reactions of both acyclic and cyclic β-ketocarbonyls with high yields and excellent stereoselectivity. The current reaction offers a straightforward approach in the asymmetric synthesis of α- or β-amino carbonyls bearing chiral quaternary centers in a practical and highly stereocontrolled manner.

Catalytic Asymmetric Mannich Reaction with N‐Carbamoyl Imine Surrogates of Formaldehyde and Glyoxylate

AbstractN,O‐acetals (NOAcs) were developed as bench stable surrogates for N‐carbamoyl, (Boc, Cbz and Fmoc) formaldehyde and glyoxylate imines in asymmetric Mannich reactions. The NOAcs can be directly utilized in the chiral primary amine catalyzed Mannich reactions of both acyclic and cyclic β‐ketocarbonyls with high yields and excellent stereoselectivity. The current reaction offers a straightforward approach in the asymmetric synthesis of α‐ or β‐amino carbonyls bearing chiral quaternary centers in a practical and highly stereocontrolled manner.

ChemInform Abstract: Asymmetric Synthesis of Tetrahydropyridines via a Broensted Acid Catalyzed Aza‐Diels—Alder Reaction.

AbstractProtected glyoxylate imine reacts with various aryl substituted 2‐silyloxy‐1,3‐butadienes, and depending on the functionalization of the aryl ring tetrahydropyridines are obtained.

Asymmetric Synthesis of Tetrahydropyridines via a Brønsted Acid Catalyzed Aza-Diels–Alder Reaction

The asymmetric synthesis of tetrahydropyridines employing a normal electron-demanding aza-Diels–Alder reaction has been developed. The [4+2] cycloaddition of ethyl glyoxylate imine with aryl-substituted 2-silyloxy-1,3-butadienes is catalyzed by 5 mol% of a BINOL-derived phosphoric acid and in general leads to good yields and ee values with good to excellent diastereoselectivities. The cycloadducts can be further converted into the corresponding piperidinones, which are important pipecolic acid derivatives.

ChemInform Abstract: Asymmetric Synthesis and Catalytic Activity of 3‐Methyl‐β‐proline in Enantioselective anti‐Mannich‐Type Reactions.

AbstractChiral β‐prolines are synthesized and used as organocatalysts in the anti‐selective Mannich‐type reaction of ketones/aldehydes with ethyl glyoxylate imine.

Asymmetric Synthesis and Catalytic Activity of 3-Methyl-β-proline in Enantioselective anti-Mannich-type Reactions

Enantiomerically pure 3-methyl-β-proline was synthesized using an asymmetric phase-transfer-catalyzed alkylation of a cyanopropanoate to establish the all-carbon stereogenic center. The catalytic activity of 3-methyl-β-proline in the Mannich-type reaction between a glyoxylate imine and ketones/aldehydes was subsequently investigated. The catalyst was designed and found to be more soluble in nonpolar organic solvents relative to the unsubstituted β-proline catalyst, and as a result allowed for added flexibility during optimization efforts. This work culminated in the development of a highly anti-diastereo- and enantioselective process employing low catalyst loading.

ChemInform Abstract: Enantioselective Intermolecular Carbon—Carbon Bond Formation of Glyoxylate Imines with Allylstannanes Catalyzed by tropos BIPHEP—Gold(I) Complexes with Au—Au Interactions.

AbstractThe present study reveals the advantage of tropos BIPHEP—gold(I) complexes with intramolecular Au—Au interactions compared to the structurally similar atropos BINAP—gold complexes without the Au—Au interaction.

Aza‐Diels–Alder reaction between cyclopentadiene and protonated N‐phenylethyliminoacetates of 8‐phenylmenthol and 8‐phenylneomenthol: a density functional theory study

The cycloaddition between glyoxylate imines possessing two chiral auxiliaries, N‐(R)‐ or N‐(S)‐1‐phenylethyl and 8‐phenylmenthyl or 8‐phenylneomenthyl, and cyclopentadiene is described. Computational calculations using density functional theory with the Becke, three‐parameter, Lee–Yang–Parr functional and the 6‐31G(d) basis set were performed to better understand the highly diastereoselective mechanism and the exo‐selectivity observed experimentally for these ionic aza‐Diels–Alder reactions. Copyright © 2011 John Wiley & Sons, Ltd.

Enantioselective Intermolecular Carbon–Carbon Bond Formation of Glyoxylate Imines with Allylstannanes Catalyzed by tropos BIPHEP–Gold(I) Complexes with Au–Au Interactions

The present study reveals the advantage of tropos BIPHEP—gold(I) complexes with intramolecular Au—Au interactions compared to the structurally similar atropos BINAP—gold complexes without the Au—Au interaction.

Highly diastereoselective synthesis of 2-azabicyclo[2.2.1]hept-5-ene derivatives: Bronsted acid catalyzed aza-Diels–Alder reaction between cyclopentadiene and imino-acetates with two chiral auxiliaries

The cycloaddition between protonated glyoxylate imines possessing two chiral auxiliaries, N-( S)- or N-( R)-1-phenylethyl and (−)-8-phenylmenthyl or (+)-8-phenylneomenthyl, and cyclopentadiene is described. The absolute configuration of all adducts formed was unequivocally assigned through NMR, specific optical rotation, and X-ray data of appropriated derivatives. Experimental results confirm the highly exo-selectivity for these aza-Diels–Alder reactions, single adducts being obtained from combinations of (8PM)-( R-PEA) and (8PNM)-( S-PEA).

ChemInform Abstract: The Study of Friedel—Crafts Alkylation Reaction of Thiophenes with Glyoxylate Imine Catalyzed by Fe(III): An Easy Access to α‐Aminoesters.

ChemInformVolume 42, Issue 25 Heterocyclic Compounds ChemInform Abstract: The Study of Friedel—Crafts Alkylation Reaction of Thiophenes with Glyoxylate Imine Catalyzed by Fe(III): An Easy Access to α-Aminoesters. Zhong Huang, Zhong Huang State Key Lab. Chem. Resour. Eng., Beijing Univ. Chem. Technol., Beijing 100029, Peop. Rep. ChinaSearch for more papers by this authorJingchang Zhang, Jingchang Zhang State Key Lab. Chem. Resour. Eng., Beijing Univ. Chem. Technol., Beijing 100029, Peop. Rep. ChinaSearch for more papers by this authorNai-Xing Wang, Nai-Xing Wang State Key Lab. Chem. Resour. Eng., Beijing Univ. Chem. Technol., Beijing 100029, Peop. Rep. ChinaSearch for more papers by this author Zhong Huang, Zhong Huang State Key Lab. Chem. Resour. Eng., Beijing Univ. Chem. Technol., Beijing 100029, Peop. Rep. ChinaSearch for more papers by this authorJingchang Zhang, Jingchang Zhang State Key Lab. Chem. Resour. Eng., Beijing Univ. Chem. Technol., Beijing 100029, Peop. Rep. ChinaSearch for more papers by this authorNai-Xing Wang, Nai-Xing Wang State Key Lab. Chem. Resour. Eng., Beijing Univ. Chem. Technol., Beijing 100029, Peop. Rep. ChinaSearch for more papers by this author First published: 26 May 2011 https://doi.org/10.1002/chin.201125101Read 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. Volume42, Issue25June 21, 2011 RelatedInformation

The study of Friedel–Crafts alkylation reaction of thiophenes with glyoxylate imine catalyzed by Fe(III): an easy access to α-aminoesters

A Friedel–Crafts alkylation reaction of thiophenes with glyoxylate imine was developed to give α-aminoesters. In the presence of FeCl 3·6H 2O as the catalyst, various α-aminoesters were prepared with moderate to high yields (up to 95%) except for some special substrates.

ChemInform Abstract: Enantioselective Organocatalytic Synthesis of Arylglycines via Friedel—Crafts Alkylation of Arenes with a Glyoxylate Imine.

AbstractThe enantioselective organocatalytic synthesis of the arylglycines (III) is reported to proceed with good to excellent yields (60‐89%) and enantioselectivities (68‐96%).

Povarov Reaction of Glyoxylate Imines Derived from 12-Aminodehydroabietic Acid

Glyoxylate and arylglyoxal imines based on 12-aminodehydroabietic acid undergo hetero-Diels—Alder (Povarov) reaction with ethyl vinyl ether, cyclopentadiene, and indene to give, respectively, methyl (8aR,9R,12aS)-3-aroyl-5-isopropyl–9,12a-dimethyl–7,8,8a,9,10,11,12,12a-octahydronaphtho[1,2-f]quinoline-9-carboxylates, methyl (7R,10aS,10dR,13aS)-1-aroyl–3-isopropyl–7,10a-dimethyl–2,5,6,6a,7,8,9,10,10a,10d,13,13a-dodecahydro-1H-naphtho[1,2-f]cyclopenta[c]quinoline-7-carboxylates, and methyl (6aS,11bS,11eS,15R,15aR)-6-aroyl–4-isopropyl–11e,15-dimethyl–2,5,6,6a,7,11b,11e,12,13,14,15,15a-1H-dodecahydroindeno[2,1-c]-naphtho[1,2-f]quinoline-15-carboxylates.

Enantioselective Organocatalytic Synthesis of Arylglycines via Friedel–Crafts Alkylation of Arenes with a Glyoxylate Imine

AbstractThe enantioselective organocatalytic synthesis of arylglycines has been developed employing 1 mol% of an enantiopure N‐triflyl phosphoramide Brønsted acid as organocatalyst. Various differently substituted phenylglycine derivatives can be synthesized in good to excellent yields and enantiomeric excesses based on a Friedel–Crafts alkylation of electron‐rich arenes with a glyoxylate imine. A novel protocol for the deprotection of the N‐tert‐butylsulfonyl (Bus) group has also been developed.

A Solid‐Supported Organocatalyst for Highly Stereoselective, Batch, and Continuous‐Flow Mannich Reactions

The fast and highly stereoselective Mannich reaction of aldehydes and ketones with the N-(p-methoxyphenyl) ethyl glyoxylate imine catalyzed by polystyrene resins functionalized with (2S,4R)-hydroxyproline is reported. The effect of the nature of the linker connecting proline with the polymeric backbone has been studied, and a 1,2,3-triazole linker constructed from azidomethyl polystyrene and O-propargyl hydroxyproline turns out to be optimal for catalytic activity and enantioselectivity. With aldehyde donors, fast reactions leading to complete conversion in 1-3 h are recorded in DMF. With ketone donors, the reactions tend to be slower, but can be efficiently accelerated (six-membered ring cycloalkanones) by low-power microwave irradiation. This approach, which greatly facilitates product isolation since the catalyst is removed by simple filtration, has allowed the implementation of the reactions of aldehyde substrates in a continuous-flow, single-pass system. In this manner, the continuous synthesis of the enantiomerically and diastereomerically pure adducts (syn/anti>97:3; ee>99 %) has been achieved at room temperature with residence times of 6.0 min. This methodology has allowed for the preparation of up to 7.8 mmol of the desired Mannich adduct through the use of 0.46 mmol of catalytic resin (5.9 mol %), in a greatly simplified experimental protocol that avoids purification steps.

Enantioselective synthesis of (3-indolyl)glycine derivatives via asymmetric Friedel–Crafts reaction between indoles and glyoxylate imines

Chiral phosphoric acid-catalyzed enantioselective Friedel–Crafts reaction of indoles with ethyl glyoxylate imines was developed. With 10 mol % of the catalyst, the Friedel–Crafts reactions between a wide range of indoles and imines have been carried out, affording optically active (3-indolyl)glycine derivatives with excellent yields and high enantioselectivities (up to 87% ee).

3-Trifluoromethanesulfonamido-pyrrolidine: A General Organocatalyst for anti-Selective Mannich Reactions

Mannich-type reactions of a glyoxylate imine with carbonyl compounds catalyzed by 3-trifluoromethanesulfonamidopyrrolidine proceed with high yields and anti-stereoselectivity. The catalyst is easily prepared and the transformation appears to be quite general accommodating aldehydes or ketones.