Enantiospecific Synthesis of Heterocycles from α-Amino Acids

Sardina, and F. Javier; Rapoport, Henry

doi:10.1021/cr9300348

Cited by 292 publications

(105 citation statements)

References 242 publications

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“…The cycloaddition of azomethine ylides with olefins affords highly functionalized pyrrolidines, which are structural motifs of biologically active natural products and pharmaceuticals. 119) Although many studies on the asymmetric [3ϩ2] cycloaddition of azamethine ylides using chiral Lewis acids as well as chiral organocatalysts have been reported, [120][121][122] there is only one report on the organocatalyzed version with nitroolefin and, furthermore, the level of asymmetric induction is still moderate (up to 63% ee). 123,124) To achieve a highly enantioselective [3ϩ2] cycloaddition of azomethine ylides with nitroolefins, we planned the one-pot stepwise synthesis of highly functionalized pyrrolidines 25 using thiourea-catalyzed Michael addition of a-amino malonate imine 24 into nitroolefin 4 via D and subsequent intramolecular aza-Henry reaction of the resulting intermediate E (Chart 6).…”

Section: Asymmetric Synthesis Of Multifunctionalized Pyrrolidinesmentioning

confidence: 99%

Development of Chiral Thiourea Catalysts and Its Application to Asymmetric Catalytic Reactions

2010

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We have developed several multifunctional thiourea catalysts bearing a tertiary amine or an 1,2-amino alcohol in expectation of their synchronous activation of a nucleophile and an electrophile through both acid-base and hydrogen-bonding interactions. From these studies, it was revealed that the weak acidity of thioureas compared with metallic Lewis acids could be overcome by this modification. The bifunctional aminothiourea could be used efficiently for a wide range of diastereoselective and enantioselective nucleophilic reactions such as Michael addition of 1,3-dicarbonyl compounds to nitroolefines, aza-Henry reaction of nitroalkanes to N-Boc imines, and hydrazination of cyclic b b-keto esters. We also discovered that multifunctional thiourea catalyst, bearing an 1,2-amino alcohol moiety, significantly accelerated the Petasis-type reaction of alkenylboronic acids to Nphenoxycarbonyl quinolinium salts, prepared from quinolines and phenyl chloroformate, to afford 1,2-addition products with high enantioselectivity (up to 97% ee). Furthermore, to expand the synthetic applicability of the thiourea-catalyzed asymmetric reactions, tandem organocatalyzed reactions were explored to establish the concise one-pot synthesis of chiral densely functionalized three-, five-, and six-membered compounds.

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Section: Asymmetric Synthesis Of Multifunctionalized Pyrrolidinesmentioning

confidence: 99%

Development of Chiral Thiourea Catalysts and Its Application to Asymmetric Catalytic Reactions

2010

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“…27,28 On the other hand, amino acids have emerged as important building blocks for the synthesis of a range of different compounds. [29][30][31] Moreover, the interest on the biological and medicinal properties of chalcogen amino acids has also been increasingly appreciated, mainly due to their antioxidant, 32 antitumor, 33 antimicrobial, 34 and antiviral 35 properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 1,3,4-oxadiazole derivatives from α-amino acid and acyl hydrazides under thermal heating or microwave irradiation conditions

Dornelles¹,

Rodrigues²,

Heck³

et al. 2015

Arkivoc

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“…5,6) Additionally, increasing utilities of unnatural amino acids as a key structural element have also been shown in fields of chemical biology and asymmetric transformation. [7][8][9][10][11] These contexts evoke much interest of synthetic chemists in asymmetric synthesis of the structural unit.…”

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confidence: 99%

A Convenient Method for Preparation of α-Imino Carboxylic Acid Derivatives and Application to the Asymmetric Synthesis of Unnatural α-Amino Acid Derivative

Inokuma

Jichu

Nishida

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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We describe herein a manganese(IV) oxide-mediated oxidation of N-p-methoxyphenyl (PMP)-protected glycine derivatives for the synthesis of α-imino carboxylic acid derivatives. Using this methodology, utilization of unstable glyoxic acid derivatives was avoided. Furthermore, using this methodology we synthesized novel α-imino carboxylic acid derivatives such as α-imino phenyl ester, perfluoroalkyl etsers, imides, and thioester. The asymmetric Mannich reaction of those novel imine derivatives with 1,3-dicarbonyl compound is also described, and the novel α-imino imide gave improved chemical yield and stereoselectivity compared with those obtained by the use of the conventional α-imino ester-type substrate.Key words α-imino carboxylic acid derivative; heterogeneous oxidant; asymmetric organocatalysis; thiourea; unnatural α-amino acid Unnatural α-amino acids are often seen in varieties of biologically active compounds, 1-4) including pharmaceutics, and have been used as indispensable chiral building blocks for the synthesis of such active compounds.5,6) Additionally, increasing utilities of unnatural amino acids as a key structural element have also been shown in fields of chemical biology and asymmetric transformation.7-11) These contexts evoke much interest of synthetic chemists in asymmetric synthesis of the structural unit.12,13) Enabling easy access to diverse α-amino acids only by changing nucleophiles employed, Mannich-type reaction of α-imino ester has been widely utilized for the asymmetric synthesis.14-20) Generally, condensation of glyoxalates and primary amines affords α-imino esters as the requisite substrate for Mannich-type reaction (Chart 1a); however, the glyoxalates are unstable, and suffer easy hydrolysis or polymerization at room temperature. Additionally, high susceptibility of the resulting α-imino ester to silica gel has forced us to directly use the imino esters for the Mannich reaction without purification, thereby leading to difficulty in maintaining the reaction outcome. In this context, cross-dehydrogenative coupling (CDC) has been investigated for the synthesis of α-functionalized amino acids 21-23) (Chart 1b). The CDC protocol features oxidative preparation of α-imino ester from glycinates with the use of the oxidants such as 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), CuOAc, Ru(bpy) 3 Cl 2 / light (or N-oxyl radical), or Cu(I)/molecular oxygen, followed by in situ Mannich reaction. Although the CDC protocol is free from the use of unstable glyoxalates, the in situ Mannich reaction has to be performed in the presence of the employed oxidant due to difficulty in achieving complete separation of the imino ester and oxidant, by which the use of the CDC remains within application to the coupling of oxidant-tolerant functional units. Here, we envisioned that the heterogeneous oxidation system enabling facile removal of insoluble oxidants by filtration allowed the imino ester to be readily obtained and subsequently subjected to Mannich reaction under oxidant-free conditions (Chart 1c).

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Enantiospecific Synthesis of Heterocycles from α-Amino Acids

Cited by 292 publications

References 242 publications

Development of Chiral Thiourea Catalysts and Its Application to Asymmetric Catalytic Reactions

Development of Chiral Thiourea Catalysts and Its Application to Asymmetric Catalytic Reactions

Synthesis of 1,3,4-oxadiazole derivatives from α-amino acid and acyl hydrazides under thermal heating or microwave irradiation conditions

A Convenient Method for Preparation of α-Imino Carboxylic Acid Derivatives and Application to the Asymmetric Synthesis of Unnatural α-Amino Acid Derivative

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