Solid‐Phase Synthesis of 2‐Alkenamides from Polystyrene‐Supported α‐Selenocarboxylic Acids

The polystyrene‐supported α‐selenoacetic acid and α‐selenopropionic acid were prepared and used for the synthesis of 2‐alkenamides from primary and secondary amines in good yields and high purities.     

Synthesis of α,β‐Unsaturated Ketones and Esters Using Polymer‐supported Selenium Bromide

Treatment of the polymer‐supported α‐phenylseleno ketones and esters prepared from polymer‐supported selenium bromide with ketone and ester enolates with hydrogen peroxide afford α,β‐unsaturated ketones and esters in good yields and high purities.     

Reactions of Polymer‐Supported α‐Selenoaldehydes with Grignard Regents. A Facile Solid‐Phase Stereoselective Synthesis of (E)‐1,2‐Disubstituted Ethenes

Polymer‐supported α‐selenoaldehydes easily obtained by reaction of polymer‐supported 4‐(phenylseleno)morpholine with aldehydes react with Grignard reagents to form polymer‐supported β‐hydroxyalkyl selenides, which were treated with thionyl chloride/triethylamine leading to (E)‐1,2‐disubstituted ethenes in good yields.     

Asymmetric Synthesis of Chiral α‐Substituted Mercaptoglycine Derivatives via α‐Sulfenylation of Ni(II) Complex of Glycine and S‐Substituted 4‐Methylbenzenesulfonothioate

The asymmetric α ‐sulfenylation of Ni(II ) complex of glycine with S ‐substituted 4‐methylbenzenesulfonothioate is reported. Due to the mild and simple reaction conditions, this asymmetric reaction is compatible with various functional groups.     

Oxidative acylation of α,α‐diarylallylic alcohols: Synthesis of 1,2,4‐triarylbutane‐1,4‐diones

A metal‐free mediated oxidative acylation of α,α‐diarylallylic alcohols with simple aromatic aldehydes for the synthesis of 1,2,4‐triphenylbutane‐1,4‐diones is presented. In the presence of TBPB (tert‐butyl peroxybenzoate), desired products were obtained in good to excellent yields for 28 examples. This protocol features high regioselectivity, wide functional group tolerance and atom economy.     

Nanomagnetic‐supported Sulfonic Acid: Simple and Rapid Method for the Synthesis of α,α′‐Bis‐(substituted‐benzylidene) Cycloalkanones

Nanomagnetic‐supported sulfonic acid is found to be a powerful and reusable heterogeneous catalyst for the rapid synthesis of α,α′‐bis‐(substituted‐benzylidene)cycloalkanones under conventional heating and solvent free conditions. High yield, simple work up and easy recovery of the catalyst are the most obvious advantages of this procedure.     

Facile Synthesis of Internal and C‐Terminal Peptide α‐Ketoamides with Fmoc‐Solid Phase Peptide Synthesis

We report a general and operationally simple method for the solid phase synthesis of α‐ketoamide peptides using standard Fmoc solid phase peptide synthesis. The method delivers deprotected peptide α‐ketoamides directly upon resin cleavage without any additional steps, and tolerates all side chain functional groups. A small collection of C‐terminal and internal α‐ketoamide peptides – including two reported protease inhibitors (HCV and SUB1) – were prepared in good yields. In addition, we demonstrate that our method serves as versatile platform for the convenient preparation of cyclic α‐ketoamide peptides, photocagged peptide α‐ketoamides, and fluorescently labeled peptides.     

Catalytic Asymmetric 1,2‐Addition of α‐Isothiocyanato Phosphonates: Synthesis of Chiral β‐Hydroxy‐ or β‐Amino‐Substituted α‐Amino Phosphonic Acid Derivatives

α‐Amino phosphonic acid derivatives are considered to be the most important structural analogues of α‐amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2‐addition reactions of α‐isothiocyanato phosphonate were developed. Through these processes, derivatives of β‐hydroxy‐α‐amino phosphonic acid and α,β‐diamino phosphonic acid, as well as highly functionalized phosphonate‐substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α‐phosphonic acid derivatives.     

Synthesis of α,α′‐Bis(Substituted Benzylidene)Cycloalkanones Catalyzed by Amino‐Functionalized Ionic Liquid

Condensation of aromatic aldehydes with cyclopentanone and cyclohexanone using amino‐functionalized ionic liquid, 1‐aminoethyl‐3‐methyl tetrafluoroborate as solvent and catalyst was successfully performed for preparation of α,α′‐bis(substituted benzylidene)cycloalkanones. The catalyst can be recovered and reused for at least three times without apparently lose of activity. The process is simple, environmentally benign and proceeds in excellent yields.     

Polymer‐Supported Hypervalent Iodine Reagent Mediated Synthesis of α‐Azidoketones

The reaction of aryl ketones with sodium azide using polymer‐supported bis(trifluoroacetoxyiodo)‐benzene (PSBTI) in the presence of trifluoroacetic acid (TFA) to prepare α‐azidoketones in one‐pot conditions is reported.     

Enantioselective Syntheses of Substituted γ‐Butyrolactones

The previously described chiral 2‐acyloxathianes 5 (Scheme I) are used in two different enantioselective syntheses of γ‐butyrolactones. In one synthesis, Grignard addition, cleavage and reduction to carbinols RR'C(OH)CH₂OH is followed by tosylation, malonate homologation, lactonization, and removal of the carbomethoxy group to give optically active γ‐lactones. A modification of this synthesis (Scheme I) leads to optically active α‐methylene‐γ‐lactones. In the second synthesis, reaction of a bromomagnesium enolate with ketones 5 leads to β‐hydroxyesters, which, by appropriate sequences of reduction and cleavage (Scheme II) are converted to optically active α‐ or β‐hydroxy‐γ‐lactones.     

Two‐Step Backbiting Reaction in the Ring‐Opening Polymerization of γ‐Acryloyloxy‐ε‐caprolactone Initiated with Aluminium Isopropoxide

γ‐Acryloyloxyethyl‐γ‐butyrolactone is formed as a byproduct when the polymerization of γ‐acryloyloxy‐ε‐caprolactone is initiated with aluminium isopropoxide in toluene. The extent of this side reaction decreases with decreasing temperature and is dependent on whether the reaction is stopped as soon as monomer conversion is complete or not. A two‐step backbiting mechanism is proposed for this intramolecular transesterification reaction.     

Tandem Benzylic Oxidation/Dihydroxylation of α‐Vinyl‐ and α‐Alkenylbenzyl Alcohols

A de novo tandem benzylic oxidative dihydroxylation of α‐vinyl‐ and α‐alkenylbenzyl alcohols has been developed to give α,β‐dihydroxypropiophenones (=2,3‐dihydroxy‐1‐phenylpropan‐1‐ones) and α,β‐dihydroxyalkyl phenones. This method was shown to be substrate‐selective and specific for the oxidation of benzylic alcohols.     

聚合物负载磺酸催化的三组分反应合成1-酰胺烷基-2-萘酚

聚合物负载磺酸，一种环境友好的固体酸催化剂，可以有效地催化2-萘酚、脲或酰胺和醛的三组分“一锅”反应生成1-酰胺烷基-2-萘酚。该方法得率高，操作简单。     

Preparation of the β2‐Homoselenocysteine Derivatives Fmoc‐(S)‐β2hSec(PMB)‐OH and Boc‐(S)‐β2hSec(PMB)‐OH for Solution and Solid‐Phase Peptide Synthesis

Fmoc‐β²hSer(^tBu)‐OH was converted to Fmoc‐β²hSec(PMB)‐OH in five steps. To avoid elimination of HSeR, the selenyl group was introduced in the second last step (Fmoc‐β²hSer(Ts)‐OAll→Fmoc‐β²hSec(PMB)‐OAll). In a similar way, the N‐Boc‐protected compound was prepared. With the β²hSe‐derivatives, 21 β²‐amino‐acid building blocks with proteinogenic side chains are now available for peptide synthesis.     

Secondary Amine‐Catalyzed Asymmetric γ‐Alkylation of α‐Branched Enals via Dienamine Activation

The direct and enantioselective γ‐alkylation of α‐substituted α,β‐unsaturated aldehydes proceeding under dienamine catalysis is described. We have found that the Seebach modification of the diphenyl‐prolinol silyl ether catalyst in combination with saccharin as an acidic additive promotes an S_N1 alkylation pathway, while ensuring complete γ‐site selectivity and a high stereocontrol. Theoretical and spectroscopic investigations have provided insights into the conformational behavior of the covalent dienamine intermediate derived from the condensation of 2‐methylpent‐2‐enal and the chiral amine. Implications for the mechanism of stereoinduction are discussed.     

Synthesis of Phenanthrene Derivatives through the Reaction of an α,α‐Dicyanoolefin with α,β‐Unsaturated Carbonyl Compounds

Phenanthrene derivatives were prepared by reacting an α,α‐dicyanoolefin with different α,β‐unsaturated carbonyl compounds resulting from Wittig reaction of ninhydrin and phosphanylidene or condensation of barbituric acid and an aldehyde. The easy procedure, mild and metal‐catalyst free, reaction conditions, good yields, and no need for chromatographic purifications are important features of this protocol. The structures of the product of type 3 and 5 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 1).     

Synthesis of new optically active α,α′,β‐trisubstituted‐β‐lactones as monomers for stereoregular biopolyesters

Various optically active (4R)‐alkyloxycarbonyl‐3,3‐dialkyl‐2‐oxetanones as monomers were synthesized from L‐(S)‐malic acid in six steps to prepare a new family of stereopolyesters for biomedical applications. The synthesis began with an esterification followed of a dialkylation in the aim to introduce hydrophobic groups as methyl or reactive group as allyl. Then, a saponification has permitted to obtain the corresponding diacids that reacted with appropriate alcohols to furnish different monoesters. The last and most important step was activation of hydroxyl group of monoesters with the asymmetric carbon configuration inversion according to the Mitsunobu reaction. Thus, this reaction has provided lactones from monoesters with 100% enantiomeric excess which was confirmed by ¹H NMR and by the synthesis of corresponding isotactic and semicrystalline homopolyesters. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2586–2597     

De Sign and Synthesis of 1,2,4‐Oxadiazole Derivatives as Non‐Steroidal 5α‐Reductase Inhibitors

The purpose of this study was to synthesize compounds in which the 1,2,4‐oxadiazole moiety replaced the amide bond of ONO3805 and to evaluate its 5α‐reductase inhibitory activity as a potential benign prostatic hyperplasia therapeutic target. Four 1,2,4‐oxadiazole derivatives, 1,2,8, and 20, were evaluated in vitro against 5α‐reductase of rat liver microsome. The prepared 1 and 2 possessed similar binding affinity (Ki) to that of ONO3805. Therefore, the use of 1,2,4‐oxadiazole ring as surrogate of the amide bond in ONO3805 has a successful result in this study. It leads not only to enhance chemical stability but also to maintain meaningful inhibitory activity. The butyric acid moiety of these inhibitors is considered to play an important role in mimicing the phosphoric acid portion of coenzyme‐NADPH in interacting with the active site of 5α‐reductase.