Direct Mannich Reaction Research Articles

Organocatalyticanti-Selective Direct Mannich Reaction

Several aldehydes (1) and α-amino esters (2) were transformed to the corresponding β-amino aldehydes in an anti-selective manner by using chiral amino sulfonamides (3) in low catalyst loadings (2 mol%). It turned out that the presence of the trifluoromethyl group on the sulfonamide moiety was necessary to achieve good yields as well as good anti/syn ratios and nearly complete enantioselectivity. For more sterically hindered aldehydes (e.g., R1 = i-Pr) higher catalyst loading (5 mol%) was required. No self-aldolization products were formed.

Proline-Catalyzed, Asymmetric Mannich Reactions in the Synthesis of a DPP-IV Inhibitor

[reaction: see text] A highly stereoselective L-proline-catalyzed, asymmetric direct Mannich reaction between a glyoxalate-derived imine and phenyl acetaldehyde was employed for the formation of a syn substituted beta-phenyl homoserine. This Mannich adduct was then readily elaborated to a functionalized beta-phenyl aspartic acid derivative through a series of mild and efficient transformations.

N-(2-Hydroxyacetyl)pyrrole as an Ester Surrogate in Asymmetric Mannich Reactions

N-(2-Hydroxyacetyl)pyrrole underwent a direct Mannich reaction with a variety of o-Ts aldimines to afford predominantly a syn-α-hydroxy-β-amino amide in good to excellent yield. Good diastereoselectivity and high enantionselectivity were achieved by using In(Oi-Pr)3 and (S,S)-linked BINOL as the catalyst system. Chiral aminoalcohols are important building blocks for many natural products and pharmaceuticals. As an ester equivalent, the N-acyl amide can be easily transformed to many common functional groups such as esters, alkyl amides, aldehydes.

Transition Metal Salt Catalyzed Direct Three‐Component Mannich Reactions of Aldehydes, Ketones, and Carbamates: Efficient Synthesis of N‐Protected β‐Aryl‐β‐Amino Ketone Compounds.

The transition metal salt-catalyzed direct three-component Mannich reactions of aryl aldehydes, aryl ketones, and carbamates are described. The RuCl3·xH2O-, AuCl3−PPh3-, and AuCl3-catalyzed direct Mannich reactions led to the synthesis of N-protected β-aryl-β-amino ketones, and the results create new possibilities for exploiting the transition metal salt-catalyzed direct Mannich reaction and facile synthesis of β-amino ketone libraries.

Transition Metal Salt-Catalyzed Direct Three-Component Mannich Reactions of Aldehydes, Ketones, and Carbamates: Efficient Synthesis of N-Protected β-Aryl-β-Amino Ketone Compounds

The transition metal salt-catalyzed direct three-component Mannich reactions of aryl aldehydes, aryl ketones, and carbamates are described. The RuCl(3).xH(2)O-, AuCl(3)-PPh(3)-, and AuCl(3)-catalyzed direct Mannich reactions led to the synthesis of N-protected beta-aryl-beta-amino ketones, and the results create new possibilities for exploiting the transition metal salt-catalyzed direct Mannich reaction and facile synthesis of beta-amino ketone libraries.

Catalytic Asymmetric Synthesis of a Nitrogen Analogue of Dialkyl Tartrate by Direct Mannich Reaction under Phase‐Transfer Conditions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Chiral Broensted Acid‐Catalyzed Direct Mannich Reactions via Electrophilic Activation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Catalytic asymmetric synthesis of a nitrogen analogue of dialkyl tartrate by direct mannich reaction under phase-transfer conditions.

[reaction: see text] Phase-transfer-catalyzed direct Mannich reaction of glycinate Schiff base 3 with alpha-imino ester 4 has been accomplished with high enantioselectivity by the utilization of N-spiro C(2)-symmetric chiral quaternary ammonium bromide 2 as a catalyst. This methodology enables the catalytic asymmetric synthesis of differentially protected 3-aminoaspartate, a nitrogen analogue of dialkyl tartrate. The product (syn-5) was converted into a precursor (6) of streptolidine lactam.

Chiral Brønsted acid-catalyzed direct Mannich reactions via electrophilic activation.

It was found that the phosphoric acid derivatives of general structure 1 serve as highly effective catalysts for the direct addition of acetyl acetone to N-Boc-protected arylimines. The beneficial effects of the 3,3'-bisaryl substituents of the catalysts on the enantioselectivity are greatly appreciated, and thus 1d functions as an excellent catalyst. The Brønsted acid-catalyzed direct Mannich reactions presented herein provide an attractive way to construct beta-aminoketones under extremely mild conditions. The stereochemical course of this reaction was established through the synthesis of Boc-(S)-phenylglycine methylester. The transformation thus demonstrated is applicable to a useful method for the synthesis of various phenylglycine derivatives.

Direct catalytic asymmetric mannich reactions of malonates and beta-keto esters.

The first catalytic asymmetric direct Mannich reaction of malonates and beta-keto esters has been developed. Malonates react with an activated N-tosyl-alpha-imino ester catalyzed by chiral tert-butyl-bisoxazoline/Cu(OTf)(2) to give the Mannich adducts in high yields and with up to 96% ee. These reactions create a chiral quaternary carbon center and it is demonstrated that this new direct Mannich reactions provides for example a new synthetic procedure for the formation of optically active beta-carboxylic ester alpha-amino acid derivatives. A series of different beta-keto esters with various ester substituents has been screened as substrates for the catalytic asymmetric direct Mannich reaction and it was found that the best results in terms of yield, diastereo- and enantioselectivity were obtained when tert-butyl esters of beta-keto esters were used as the substrate. The reaction of different beta-keto tert-butyl esters with the N-tosyl-alpha-imino ester gave the Mannich adducts in high yields, diastereo- and enantioselectivities (up to 95% ee) in the presence of chiral tert-butyl-bisoxazoline/Cu(OTf)(2) as the catalyst. To expand the synthetic utility of this direct Mannich reaction a diastereoselective decarboxylation reaction was developed for the Mannich adducts leading to a new synthetic approach to attractive optically active beta-keto alpha-amino acid derivatives. Based on the stereochemical outcome of the reactions, various approaches of the N-tosyl-alpha-imino ester to the chiral bisoxazoline/Cu(II)-substrate intermediate are discussed.

ChemInform Abstract: Catalytic Asymmetric Direct Mannich Reactions of Carbonyl Compounds with α‐Imino Esters.

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Catalytic Asymmetric Direct Mannich Reactions of Carbonyl Compounds withα-Imino Esters

Catalytic Asymmetric Direct Mannich Reactions of Carbonyl Compounds withα-Imino Esters

Catalytic Asymmetric Direct Mannich Reactions of Carbonyl Compounds with α-Imino Esters.

The development of a direct catalytic asymmetric Mannich reaction is shown and its potential demonstrated by the synthesis of optically active lactones via 4-hydroxyglutamic acid ester derivatives. The catalytic asymmetric Mannich reaction of carbonyl compounds with α-imino esters [Eq. (1); Ts = p-toluenesulfonyl] gives good yields and diastereoselectivities, as well as excellent enantioselectivities.

Organoarsen-verbindungen: XXXIII. Synthese und reaktionsverhalten der α-aminomethylphosphine und -arsine

α-Dialkylaminomethylphosphines and the corresponding arsines have been obtained by the following methods: (1) by direct Mannich reaction, (2) by reaction of secondary phosphines and arsines with bis(dimethylamino)methane, and (3) by reaction of methyleneammonium halides with secondary phosphines and arsines, silylphosphines and silylarsines, and alkali phosphides and alkali arsides, respectively. The compounds obtained show a similar reactivity as N, N-acetals. The aminomethyl group is transferred to H-acidic agents, the reaction with halides yields methylene ammonium halides and halophosphines or haloarsines, respectively. Reactivity towards methyl iodide is influenced by substituents at the phosphorus or arsenic atoms. In the case of the phosphorus compounds acetylphosphines are obtained by reaction with acetyl chloride, while the arsenic compounds add acetyl chloride to give ammonium salts.