Chiral heterocyclic β-enamino esters: convenient synthesis and diastereoselective reduction

The preparation of chiral pyrrolidine and piperidine β-enamino esters starting from ω-halogeno β-keto esters, their diastereoselective reduction and the subsequent cleavage of the chiral auxiliary are described.     

Diastereo- and enantioselective synthesis of N,O-nucleosides

The diastereo- and enantioselective synthesis of α- and β-3′-hydroxymethyl-N,O-nucleosides is described, based on the 1,3-dipolar cycloaddition of a N-glycosyl nitrone. Two approaches have been evaluated: the one-step procedure, which uses vinyl nucleobases, showed a better stereoselectivity towards β-nucleosides.     

Diastereo- and enantioselective total synthesis of stigmatellin A

Stigmatellin A (1) isolated from the myxobacterium Stigmatella aurantiaca is a powerful inhibitor of electron transport in mitochondria and chloroplasts. The first highly diastereo- and enantioselective total synthesis of this important natural product is described. Key steps in the synthesis are the alkylation of the SAMP-hydrazone (S)-13, a titanium mediated syn-diastereoselective aldol reaction, the anti-diastereoselective triacetoxyborohydride reduction of the aldol adduct (R,R,S)-16, formation of the chromone system via Baker Venkataraman rearrangement and exclusive (E) C=C double bond formation via Horner-Wadsworth-Emmons reaction.     

Divergent synthesis of pseudoenantiomers for ABC-ring moiety of steroids

Steroid family has various bioactivities and characteristic polycyclic structure. Although several synthetic methods have been reported, more efficient way is desired for medicinal chemistry. In this Letter, we synthesized pseudoenantiomers of tricyclic enones toward both enantiomers for ABC-ring moiety of steroids utilizing d-mannitol as a chiral source. The key steps are radical domino cyclization of polyalkenyl-β-keto ester into tricyclic keto ester and subsequent dealkoxycarbonylation.     

Diastereo- and enantioselective synthesis of alpha,beta-disubstituted gamma-nitro methyl sulfonates

A novel asymmetric synthesis of highly enantioenriched homotaurine precursors has been developed via diastereo-selective Michael addition of lithiated enantiopure sulfonates to nitroalkenes by using 1,2:5,6-di-O-isopropylidene-alpha-D-allofuranose as chiral auxiliary.     

A convenient synthesis of tetrazole, precursors of α-dialkylated α-amino acids, by reaction of trimethylsilyl azide with α-dialkylated β-ketoesters

The Schmidt rearrangement using trimethylsilyl azide with various α-dialkylated β-keto esters affords a convenient synthesis of tetrazole, precursors of α-dialkylated α-amino acids.     

Enantioselective preparation of C-ring fragment of cotylenin A via catalytic asymmetric intramolecular cyclopropanation of α-diazo β-keto ester

A synthetic pathway to the C-ring fragment of cotylenin A which emerged from our retrosynthetic analysis of cotylenin A is described. The catalytic asymmetric intramolecular cyclopropanation (CAIMCP) of the α-diazo-β-keto ester bearing 2,4,6-trimethylphenyl group as the ester part has been found to afford the crystalline product with high ee, which allowed to establish the approach to the C-ring fragment which required ten-pot operations. The developed approach would be beneficial to a large scale synthesis of the C-ring fragment for the total synthesis of cotylenin A.     

Solvent-free facile synthesis of novel α-tosyloxy β-keto sulfones using [hydroxy(tosyloxy)iodo]benzene

A facile, general and high yielding protocol for the synthesis of novel α-tosyloxy β-keto sulfones is described utilizing relatively non-toxic, [hydroxy(tosyloxy)iodo]benzene, under solvent-free conditions at room temperature.     

Diastereo- and enantioselective synthesis of orthogonally protected 2,4-diaminocyclopentanecarboxylates: a flip from beta-amino- to beta,gamma-diaminocarboxylates

Conformationally restricted, orthogonally protected 2,4-diaminocarboxylates with a cyclopentane skeleton were efficiently synthesized from beta-lactam 6, the syntheses involving strategies of diastereoselective epoxidation of the beta-lactam and the corresponding monoprotected amino esters with opposite selectivities followed by regioselective opening of the oxirane ring with sodium azide. The enantiomers were also prepared. This new class of compounds can be regarded not only as conformationally constrained beta,gamma-diamino acid derivatives but also as potential functionalized carbocyclic nucleoside precursors.     

Diastereo- and enantioselective synthesis of oxazine and oxazolidine derivatives with a chiral quaternary carbon center under multifunctional catalysis

An easy one-pot, multistep cascade reaction which could afford a series of substituted benzo[d]pyrido[2,1-b]oxazolidine and [1,3]oxazine derivatives in a highly enantio- (up to 98% ee) and diastereoselective (4:1 to >20:1 dr) manner with generally good to excellent yields (up to 99%) has been developed. This well designed strategy could be applied to a wide scope of substrates under mild conditions with simple operations.     

Enantio- and diastereoselective construction of vicinal quaternary and tertiary carbon centers by catalytic Michael reaction of α-substituted β-keto esters to cyclic enones

A catalytic enantio- and diastereoselective Michael reaction was achieved to construct vicinal quaternary and tertiary carbon centers in one step. Using 5 mol % of La(O-i-Pr)₃ and 10 mol % of a new N-linked-BINOL type ligand, the reaction of α-substituted β-keto esters to cyclic enones provided the corresponding Michael adducts in up to quantitative yield with a diastereomeric ratio up to 86/14 and enantiomeric excess up to 86% for the major isomer. An alternative catalyst preparation method using La(OTf)₃ instead of La(O-i-Pr)₃ was also examined.     

Regioselective addition of 1,3-dicarbonyl dianion to N-sulfonyl aldimines: an expedient route to N-sulfonyl piperidines and N-sulfonyl azetidines

A simple route for the synthesis of δ-amino-β-keto esters and δ-amino-β-diketones is reported. This involves regioselective addition of 1,3-dianions derived from ethyl acetoacetate and acetyl acetone to N-sulfonyl aldimines. The δ-amino-β-keto ester derivatives were further converted into the corresponding N-sulfonyl piperidines and N-sulfonyl azetidines.     

Diastereo- and enantioselective synthesis of densely functionalized cyclohexanones via double Michael addition of curcumins with nitroalkenes

The asymmetric double Michael additions of curcumins to nitroalkenes to afford highly functionalized cyclohexanones have been carried out for the first time. A combination of a dihydrocinchonine-thiourea organocatalyst and K₂CO₃ was found to be the most effective in obtaining the desired cyclohexanones in good yield, diastereoselectivity and enantioselectivity.     

Facile synthesis and properties of alkali-clearable azo disperse dye containing a carboxylic ester moiety

A yellow, alkali-clearable azo disperse dye containing a carboxylic ester moiety was readily synthesized from the reactant p-aminobenzoic acid by successive diazotization, coupling reaction, chlorination and esterification with ethanol. Then its molecular structure was characterized by FTIR,1H NMR,13 C NMR,mass spectrometry and elemental analysis. The synthesized dye and a similar control dye containing the acylamide moiety（I） were applied to dyeing poly（ethylene terephthalate） fabric and their washing and rubbing fastness properties with different post-treatment methods（reduction clearing and alkali clearing） were examined and compared. It is found that the ester-containing disperse dye shows good alkali-clear ability on poly（ethylene terephthalate） fabric and contaminates little to environment due to the absence of reductants, as well as low toxicity and easy recycling of the hydrolysates.     

Saponaceolides: Differential cytotoxicity and enantioselective synthesis of the right-hand lactone moiety

The enantioselective synthesis of the right-hand lactone moiety 5 of saponaceolide B, 2, is described. The mean graph profiles of 5 do not match the characteristic patterns of differential cytotoxicity of saponaceolides A, 1, and B, 2, in the NCI human disease-oriented tumor screening panel, pointing out the need of the entire saponaceolide structure for maintaining the specificity and potency of the antitumor activity. En route to 5 several useful chiral building blocks, such as compounds 6, 10, 19, 27, and 28 were prepared.     

Highly enantioselective synthesis of terutroban key intermediate via asymmetric hydrogenation

A chiral (R) key intermediate of the biologically active form of terutroban has been prepared by asymmetric hydrogenation. The catalysts are based on very easily accessible ruthenium complexes modified by chiral phosphorous ligands. The use of the chiral catASium^®T ligands family allowed us to realize this transformation efficiently in terms of yield and enantioselectivity (ee up to 92%) with high substrate/catalyst ratios.     

Diastereo- and enantioselective aldol reaction of granatanone (pseudopelletierine)

Granatanone (granatan-3-one, 9-methyl-9-azabicyclo[3.3.1]nonan-3-one, pseudopelletierine or pseudopelletrierin) undergoes deprotonation with lithium amides giving a lithium enolate, which reacts with aldehydes diastereoselectively giving exclusively exo isomers and anti/syn selectivity up to 98:2. Granatanone can be enantioselectively lithiated by chiral lithium amides and the resulting non-racemic enolate can be reacted with aldehydes giving aldols with enantiomeric excess up to 93% (99% ee after recrystallization). The absolute and relative configuration of the aldol products was determined by NMR spectroscopy and X-ray analysis.Granatanone; aldol reaction; asymmetric synthesis; enantioselective deprotonation; chiral lithium amide.     

Diastereo- and enantioselective intramolecular C(sp3)-H arylation for the synthesis of fused cyclopentanes

All C-H bonds are not equal: The intramolecular arylation of unactivated C(sp(3))-H bonds in the presence of a chiral Pd/binepine catalyst allows the synthesis of fused cyclopentanes efficiently and in an diastereo- and enantioselective manner (see scheme).     

Applications of chiral allenylzinc additions and Noyori asymmetric reductions to an enantioselective synthesis of a C3-C13 precursor of the polyketide phosphatase inhibitor cytostatin

A 12-step synthesis of a C3-C13 precursor of the protein phosphatase inhibitor cytostatin is described. Key stereocenters were introduced by a chiral allenylzinc addition and Noyori asymmetric-transfer hydrogenation.