Catalytic asymmetric synthesis of a new class of CyPHOX ligands

Four newly designed CyPHOX ligands with chiral cyclohexane scaffold replacing the previous planar aryl group of PHOX ligands, were efficiently prepared. The synthesis features a kinetically controlled asymmetric phos-Michael reactions of trisubstituted cyclic carboxylates, which is quite simple, reliable and scalable.     

固相不对称合成的一些进展

近年来,随着液相不对称合成方法在固相条件下的成功实现,固相不对称合成将成为构建手性小分子库和天然产物全合成的有力工具。本文综述了近年来通过底物手性诱导、手性辅助物诱导、手性试剂诱导和手性催化诱导的固相不对称合成的研究及应用,并探讨了其今后的发展方向。     

Divergent total synthesis of aspinolides B,E and J

Stereoselective total synthesis of aspinolides B, E and J, naturally occurring 10-membered lactones, were accomplished by divergent strategies starting from the commercially available 2,3-O-isopropylidene-d-ribose and methyl d-lactate. The synthesis features rapid access to the both key fragments from chiral pool and the formation of 10-membered ring lactones containing trans double bond employing cross-metathesis reaction (CM) and intramolecular Shiina macrolactonization.     

A general,enantioselective synthesis of 2-substituted thiomorpholines and thiomorpholine 1,1-dioxides

In the course of our drug discovery programs, we had need to access chiral, 2-substituted thiomorpholines and their oxidized congeners, thiomorpholine 1,1-dioxides. Here, we disclose a high-yielding, general protocol for the enantioselective synthesis of C2-functionalized thiomorpholines and thiomorpholine 1,1-dioxides.     

New perspective for natural products synthesis: concise synthesis of (+)-sch 642305 by chiral auxiliary multiuse methodology

The synthesis of (+)-Sch 642305 is an example of chiral auxiliary multiuse methodology, which shows a new perspective for the synthesis of compounds with multiple asymmetric centers. Thus, (+)-Sch 642305 was concisely synthesized from the known compound. Every reaction is stereoselective, and the chiral nonracemic hydrobenzoin worked as chiral auxiliary for desymmetrization of diene, as a template for attaining regio- and stereoselective reactions, as an oxygen source at the C4-position, and as a protecting group of hydroxyl functions. Namely, the chiral auxiliary played a role in every step throughout the synthesis. Furthermore, the synthesis contains a new protocol for obtaining alpha'-alkylated enone compounds.     

Stereoselective total synthesis of microcarpalide

A stereoselective total synthesis of microcarpalide using ring-closing metathesis (RCM) as a key step is reported. l-Ascorbic acid was used as a chiral pool material for the construction of the olefinic alcohol and an asymmetric aldol reaction provided the chiral precursor for the synthesis of olefinic acid.     

Practical synthesis of sultams via sulfonamide dianion alkylation: application to the synthesis of chiral sultams

[reaction: see text]. A practical synthesis of sultams was developed via intramolecular sulfonamide dianion alkylation. This method has been applied toward the synthesis of chiral sultams, which are synthetically valuable as chiral auxiliaries.     

Total synthesis of microcarpalide

A total synthesis of the natural product microcarpalide is described. Ring-closing metathesis of a dienic ester was used as the key step. Mannose was used as the chiral pool material for the construction of the olefinic-acid and a Sharpless asymmetric dihydroxylation reaction provided the chiral precursor for the synthesis of the olefinic-alcohol.     

Highly enantioselective synthesis of multifunctionalized allylic building blocks via oxazaborolidine-catalyzed borane reduction

A simple and convenient synthesis of optically active alkenyl β-hydroxy sulfides with high enantiomeric excess by CBS-oxazaborolidine-catalyzed borane reduction of the corresponding β-keto sulfides and its application to synthesis of chiral alkenic diols have been established.     

Formal total synthesis of (-)-oseltamivir phosphate

An asymmetric synthesis of chiral intermediate 3 for (-)-oseltamivir phosphate has been accomplished from chiral building block 1, which was prepared by catalytic asymmetric synthesis.     

The development for the synthesis of chiral acyclic nucleosides and their phosphonates

Acyclic nucleosides and their phosphonates possess significantly antiviral and cytostatic activities. For acyclic nucleosides and their phosphonates, the introduction of a chiral group to their side chain or the absolute configuration of the chiral atom could affect their biological activities obviously. Thus, the asymmetric synthesis of chiral acyclic nucleosides and their phosphonates has received continuous attention. The previous reports mainly focus on employing the chiral pool and chiral auxiliary methods for the synthesis of chiral acyclic nucleosides and their phosphonates. In contrast, the asymmetric catalysis methods for the synthesis of acyclic nucleosides and their phosphonates are still in the beginning. This digest paper will serve to highlight the significant progress that has been made in these areas.     

Phosphine-mediated enantioselective synthesis of carbocycles and heterocycles

Nucleophilic chiral phosphine catalysis has been prosperous in asymmetric synthesis over the past two decades. Various tunable chiral phosphines display excellent activity and selectivity in asymmetric transformations including acycloaddition reactions and cycloaddition reactions. Enantiomerically enriched cyclic compounds are ubiquitous in natural products and drug molecules. These phosphinecatalyzed reactions provide effective and extensive strategies for the synthesis of a series of complex cyclic compounds as well as the synthesis of chiral compounds which could be easily transformed to carbocycles and heterocycles. This minireview summarizes recent developments in this area and highlights meaningful breakthroughs.     

Intermolecular radical addition to N-acylhydrazones as a stereocontrol strategy for alkaloid synthesis: formal synthesis of quinine

Stereocontrolled Mn-mediated radical addition of alkyl iodides to chiral N-acylhydrazones enables strategic C-C bond disconnection of chiral amines. This strategy was examined in the context of a total synthesis of quinine, generating new findings of functional group compatibility leading to a revised strategy. Completion of a formal synthesis of quinine is presented, validating the application of Mn-mediated radical addition as a useful new C-C bond construction method for alkaloid synthesis. The Mn-mediated addition generates the chiral amine substructure of quinine with complete stereocontrol. Subsequent elaboration includes two successive ring closures to forge the azabicyclo[2.2.2]octane ring system of quincorine, linked to quinine through two known reactions.     

Stereoselective synthesis of 2,3,4-trisubstituted tetrahydrothiophenes

We describe an efficient new approach for the synthesis of highly substituted chiral tetrahydrothiophenes, based on the oxidation of a chiral furan substrate with singlet oxygen, followed by intramolecular hetero Michael addition.     

Total synthesis of aspidophytine

A total synthesis of aspidophytine was accomplished by employing a newly developed strategy for the enantiospecific syntheses of aspidosperma alkaloids. The key steps involve a novel ketene-lactonization reaction of a chiral vinyl sulfoxide (Marino annulation reaction) to set up the chiral quaternary carbon center, and a tandem Michael addition-alkylation reaction sequence to form the polycyclic core structure.     

Stereoselective total synthesis of almorexant

A highly stereoselective synthesis of almorexant has been achieved using (R)-tert-butanesulfinamide as a chiral source. The chiral tetrahydroisoquinoline core was constructed through allylation of chiral N-sulfinyl imine followed by ring closure of the secondary amide with a tethered halide. The chiral α-phenyl amide was introduced by means of S_N2 substitution of (S)-methyl 2-phenyl-2-(tosyloxy)acetate with chiral tetrahydroisoquinoline.     

Enantioselective synthesis of endohedral metallofullerenes

Endohedral metallofullerenes are promising materials in biomedical and material sciences. In particular, they are of interest as agents for magnetic resonance imaging (MRI), photovoltaic devices, and semimetallic components. The synthesis of chiral endofullerenes represents one step further in the potential use of these carbon allotropes; however, this step has not been addressed so far. In this regard, enantiopure endofullerenes are expected to open new avenues in fields in which chirality is a key issue. Here, the synthesis and characterization of the first chiral endohedral metallofullerenes, namely, chiral bis-adducts of La@C(72), are reported. Eight optically active isomers were obtained by enantioselective 1,3-dipolar cycloaddition of a N-metalated azomethine ylide onto a non-isolated-pentagon rule metallofullerene derivative, La@C(72)(C(6)H(3)Cl(2)), catalyzed by a copper chiral complex. The chiral bis-adducts of La@C(72), isolated by nonchiral HPLC, showed optical purities as high as 98% as revealed by the remarkable positive or negative Cotton effects observed in the circular dichroic spectra.     

A facile enantioselective synthesis of 2-(2-aminoethyl)allylsilanes, new synthons for piperidine synthesis

The synthesis of chiral (2-substituted-2-aminoethyl)allylsilanes by cerium mediated trimethylsilylmethylmagnesium chloride addition to the ester group of non racemic chiral β-aminoesters is described.     

Enantioselective total synthesis of (+)-tricycloclavulone

The first total synthesis of (+)-tricycloclavulone having a unique tricyclo[5,3,0,01,4]decane skeleton and six chiral centers was achieved in a highly stereoselective manner. It includes a catalytic enantioselective [2+2]-cycloaddition reaction using novel chiral copper catalyst, extremely effecting an intramolecular ester transfer reaction, and asymmetric reduction of the carbonyl group on the alpha-chain using Noyori's chiral ruthenium catalyst.     

Stereoselective synthesis of anamarine

A stereoselective synthesis of the naturally occurring, α,β-unsaturated lactone anamarine is described. The key step was a highly stereoselective aldol reaction of a protected erythrulose derivative with a chiral aldehyde. Another relevant step was an asymmetric aldehyde allylation with a chiral allylborane. The lactone ring was made by means of a ring-closing metathesis.