Asymmetric Synthesis of α-Amino Phosphonic Acids Employing the Condensation of Nitrones with Phosphite Derivatives

Abstract

Chiral α-amino phosphonic acid derivatives were synthesized by condensing an enantiomerically homogeneous diazasilyl phosphite with a series of prochiral nitrones. The reactions proceed under mild conditions with moderate to high enantioselectivities and good yields.     

Facile Asymmetric Synthesis of α-Amino Acids Employing Chiral Ligand-Mediated Asymmetric Addition Reactions of Phenyllithium with Imines

A three-step methodology involving an external chiral ligand-mediated asymmetric addition of phenyllithium to an anisidine imine, oxidative removal of N-PMP group, and finally oxidative conversion of the phenyl group to a carboxyl group provides a facile synthesis of optically pure α-amino acid derivatives bearing a bulky α-substituent.     

Asymmetric Synthesis of Chiral Trifluoromethyl Containing Heterocyclic Amino Acids

An operationally convenient, asymmetric synthesis of chiral trifluoromethyl containing heterocyclic amino acids has been developed via Michael addition reaction of chiral equivalent of Ni(II)‐complex of glycine and β ‐trifluoromethylated‐α ,β ‐unsaturated ketones. The simplicity of the experimental procedures and high stereochemical outcome of the presented method render these heterocyclic amino acids readily available for systematic medicinal chemistry studies and de novo peptide design.     

Chiral Sulfinimines in Asymmetric Synthesis of Enantiomeric Aminophosphonic Acids

Abstract

Aminophosphonic acids have become important in different fields of chemistry, medicine and agriculture. In this review article, we highlight a new strategy developed in the author's laboratory of asymmetric synthesis of enantiomeric aminophosphonic acid that users chiral sulfinimines as reagents. A key reaction in the synthesis of enantiopure α-, β- and γ-aminophosphonic acids is a highly or fully diastereoselective addition of trivalent phosphorus nucleophiles and α-phosphonate carbanions to enantiopure sulfinimines. The steric course of these addition reactions is rationalized. The usefulness of the sulfinimine methodology is demonstrated by the synthesis of biologically active enantiopure 2-amino-3-phosphonopropanoic acid (AP3), 2-amino-4-phosphonobutanoic acid (AP4) and phosphoemeriamine.     

Asymmetric Synthesis of Unnatural Amino Acids and Tamsulosin Chiral Intermediate

An efficient and enantioselective hydrogenation of N-acetylamino phenyl acrylic acids was successfully developed by using ruthenium catalyst. This methodology is important in the field of pharmaceuticals and provides a new process for the preparation of unnatural amino acids and tamsulosin chiral intermediate.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.]     

手性辅基法不对称合成特殊结构α-氨基酸——甘氨酸等当体途径

特殊结构的α-氨基酸对于生命过程研究和生物医药开发有重要意义. 不对称合成α-氨基酸的方法学中, 手性辅基方法是较多研究和应用的领域. 介绍了该方法近二十年来的发展, 对近十年的甘氨酸等当体合成策略做了详尽述评.     

手性双噁唑啉配体在不对称合成中的应用

双噁唑啉手性配体已广泛用于不对称Henry反应、环丙烷化反应、Aldol反应、烷基化反应、环加成反应中,并表现出很高的对映选择性和催化活性,成为最有用的手性配体之一。文章综述了近10年来双噁唑啉手性配体及高分子受载手性双噁唑啉在不对称合成中的研究进展。     

手性助剂控制的不对称Michael加成立体选择性研究

手性助剂控制的不对称反应是不对称合成的主要方法之一.采用不同空间位阻Evans手性助剂对呋喃基丙烯酸进行立体选择性控制,通过不同空间位阻的格氏试剂对Michael受体1进行不对称1,4-Michael加成反应研究,合成了一系列新的Michael加成产物2a～2h.研究结果表明手性助剂及格氏试剂的空间位阻是影响反应立体选择性的主要因素.当手性助剂及格氏试剂的取代基为芳基时,产物的de值都大于95%,而取代基为烷基、苄基及脂环基时,产物的de值则低于70%.     

Chiral Alkoxy Side Chains from (-)-Amino Acids in Mediating Asymmetric Synthesis of Tricarbonyl(cyclohexadienyl)iron Complexes

The asymmetric induction in the complexation reaction of (S)-1-methyl-2-(5-methyl-cyclohexa-1,4-dienylmethyloxy)-pyrrolidine 5 and (S)-2-(2-N,N-dimethylamino-1-propanoxy)-5-methylcyclohexa-1,4-diene 6 having heteroatom adjacent the stereogenic center has been investigated. The diastereoselectivity was determined directly from the diastereotopic peaks in the ¹H NMR or by chemical correlation with 9 . The conversion of η-1,4-complexes 7a and 8a to 9 proceeded with high retention of configuration while that of the η-2,5-Fe(CO)₃ complexes 7b and 8b undergoes considerable racemization.     

Determination of the Absolute Configuration of Amines and alpha-Amino Acids by (1)H NMR of (R)-O-Aryllactic Acid Amides

(R)-O-Aryllactic acid (ROAL) amides derived from alpha-chiral primary amines and alpha-amino acid esters show different chemical shifts in (1)H NMR spectroscopy (300 MHz) depending on their configuration. Molecular mechanics, semiempirical calculations, and (1)H NMR studies suggest that, in solution, these amides prefer an ap-Z conformation with the C(alpha)OAr and C=O groups close to anti-periplanar as in the case of mandelic acid amides. The proposed conformational preference is different from that of the ROAL esters (C(alpha)H and C=O groups in a syn-periplanar conformation). The conformational model for ROAL amides allows the absolute configuration assignment of primary amines and alpha-amino acid esters according to the relative position of the aryl group and the substituents on the amine moiety, and also their enantiomeric composition.     

Catalytic Asymmetric Conjugate Addition of a Borylalkyl Copper Complex for Chiral Organoboronate Synthesis

We report the catalytic enantioselective conjugate addition of a borylalkyl copper nucleophile generated in situ from a 1,1‐diborylmethane derivative to α,β‐unsaturated diesters. In the presence of a chiral N‐heterocyclic carbene (NHC)–copper catalyst, this method facilitated the enantioselective incorporation of a CH₂Bpin moiety at the β‐position of the diesters to yield β‐chiral alkyl boronates in up to 86 % yield with high enantioselectivity. The alkylboron moiety in the resulting chiral diester products was converted into various functional groups by organic transformation of the C?B bond.     

Synthesis and Asymmetric Enantioselective Addition of Chiral Polybinaphthyl and Polybinaphthol I.igands

Four chiral polymers P-1, P-2, P-3 and P-4 were synthesized by the polymerization of （S）-2,2＇-dioctoxy-1,1＇- binaphthyl-6,6＇-boronic acid （S-M-3） with （S）-6,6＇-dibromo-1,1＇-binaphthol （S-M-1）, （R）-6,6＇-dibromo-1,1＇- binaphthol （R-M-1）, （S）-3,3＇-diiodo-1,1＇-binaphthol （S-M-2） and （R）-3,3＇-diiodo-1,1＇-binaphthol （R-M-2） under Pd-catalyzed Suzuki reaction, respectively. All four polymers can show good solubility in some common solvents due to the nonplanarity of the polymers in the main chain backbone and flexible alkyl groups in the side chain. The analysis results indicate that specific rotation and circular dichroism （CD） spectral signals of the alternative S-S chiral polymers P-1 and P-3 are larger than those of S-R chiral polymers P-2 and P-4, but their UV-Vis and fluorescence spectra are almost similar. The results of asymmetric enantioselectivity of four polymers for diethylzinc addition to benzaldehyde indicate that catalytically active center is （R） or （S）-1, 1＇-binaphthol moieties.     

C2轴对称樟脑磺酰胺基醇配体催化环己烯乙炔对酮的不对称加成反应

应用C2轴对称的樟脑磺酰胺基醇配体和Cu(OTf)2催化带官能团的环己烯乙炔对酮的不对称加成反应. 芳香酮、脂肪酮和杂环酮都适用于此体系, 并且在室温下最高e.e.值约为89%, 其中脂肪酮首次被应用于此反应, 极大地扩展了底物的范围. 研究结果表明, 脂肪酮的立体位阻对反应的对映选择性起着至关重要的作用.