Synthesis of spiro[4.4]nonane-1,6-diols via the hydrogenation of spiro[4.4]nonane-1,6-dione: the profound effect of hydrogenating agents

The synthesis of spiro[4.4]nonane-1,6-diols via the catalytic as well as stoichiometric hydrogenation of spiro[4.4]nonane-1,6-dione was studied. Profound effects of the hydrogenation catalysts and reagents on the stereoselectivity of the products were observed. The choice of solvent also was found to have a significant influence on the product selectivity. The opening of a spiro-ring in the starting material was identified as a major side reaction in alcohol solvents. The absolute configuration of the trans, trans-diol was unambiguously determined by X-ray crystallography.     

Synthesis of Diphosphites from trans, trans-Spiro[4.4]nonane-1,6-diol and Their Application in Rh-catalyzed Asymmetric Hydroformylation of Styrene

Chiral diphosphite ligands were prepared by the reaction of (1R,5S,6R)-(trans, trans)-spiro[4.4]nonane-1,6-diol with chlorophosphites. The rhodium(Ⅰ) complexes containing these ligands were tested in the asymmetric hydroformylation of styrene and moderate enantioselectivity (up to 49% ee) was obtained. A pair of diastereomers 5a and 5b gave the opposite configuration of the product, which implies that the sense of enantioface selection is mainly dictated by the configuration of the terminal group on the ligand.     

A new chiral anthracene for the asymmetric Diels-Alder/retro-Diels-Alder sequence

(-)-(R)-9-(1,2-Dimethoxyethyl)anthracene (8) is successfully employed as a chiral template in the Diels-Alder/retro-Diels-Alder sequence for the preparation of alpha,beta-unsaturated lactams. The cycloadditions proceed with complete diastereoselectivity, and regioselectivity in subsequent transformations of the carbonyl groups is also excellent. Flash vacuum pyrolysis accomplishes the cycloreversion.     

Conversion of the enantiomers of spiro[4.4]nonane-1,6-diol into both epimeric carbaspironucleosides having natural C1' absolute configuration

[reaction: see text] The enantiomers of spiro[4.4]nonane-1,6-diol have been transformed by different reaction pathways into the two possible carbaspironucleoside epimers with natural C1' absolute stereochemistry.     

Promoter-dependent course of the Beckmann rearrangement of stereoisomeric spiro[4.4]nonane-1,6-dione monoximes

Activation of the Beckmann rearrangement of the enantiopure spirocyclic keto oximes (-)-9 and (-)-12 has been initiated with four acidic promoters. In two cases (PPE and PPSE), concerted 1,2 shift of the anti carbon operates exclusively. This is not the case with PPA or Eaton's reagent, although optical activity is fully maintained in these ring expansions as well.     

A practical new chiral controller for asymmetric Diels-Alder and alkylation reactions

[formula: see text] The enantiomerically pure hydroxy sulfones (+)- and (-)-2 have been prepared from 1,2-epoxycyclohexane by a simple and practical procedure. The acrylate esters of these alcohols undergo BCl3-catalyzed Diels-Alder reactions with a variety of dienes at -78 to -55 degrees C in CH2Cl2 or C7H8 with high dienophile face selectivity (Table 1). The chiral esters so formed are readily cleaved with recovery of the controllers (+)- or (-)-2. Esters of (+)- and (-)-2 can be converted to Z-potassium enolates and alkylated with high face selectivity.     

Design of a new and highly effective chiral auxiliary for Diels-Alder reaction of 1-aminodiene

A theoretical investigation of the facial selectivity of optically active oxazolidin-2-one-substituted dienes has been realized. This analysis enabled the development of (R)-4-phenyloxazolidin-2-thione as a very effective chiral auxiliary for cycloaddition of 1-aminodiene.     

新的手性β-亚磺酰亲双烯体用于不对称Diels-Alder反应

手征性cis-β-亚磺酰丙烯酸酯可从(1R, 2S, 3R)-3-巯基-1,7,7-三甲基二环[2.2.1]庚-2-醇制备, 它与环戊二烯的反应得Diels-Alder加成物, 并具有相当高的端基差向异构选择性。     

Optically active 1,2-bis(1-arylhydroxymethyl) ferrocene: a new, efficient chiral ligand for scandium-catalyzed asymmetric Diels-Alder reaction

[reaction: see text] The Sc(OTf)3/FERRODIOL (2) complex was prepared at -78 degrees C in CH2Cl2 in the presence of 2,6-lutidine and MS 4A. The chiral scandium Lewis acid-catalyzed asymmetric Diels-Alder reaction of cyclopentadiene (3) with 3-acyloxazolidin-2-ones (4) effectively produced the adduct (5) in a high yield with good selectivity, i.e., endo/exo = 90:10 up to 91% ee (endo).     

Diastereoface-discriminative metal coordination in asymmetric synthesis: D-pantolactone as practical chiral auxiliary for Lewis acid catalyzed Diels-Alder reactions

TiCl₄-catalyzed Diels-Alder additions of the acrylate of commercial D-pantolactone to cyclopentadiene, isoprene and butadiene proceed with very high diastereofacial selectivity. Practical and mechanistic aspects of these reactions are discussed.     

Synthesis and anticonvulsant activity of new fluorinated N-phenyl- and N-benzyl-2-azaspiro[4.4]nonane- and [4.5]decane-1,3-dione derivatives: Part III

A series of N-phenyl- and N-benzyl-2-azaspiro[4.4]nonane- and [4.5]decane-1,3-diones containing a fluoro or trifluoromethyl substituents at the aryl ring was synthesized and tested for their anticonvulsant activity in the maximal electroshock (MES) and subcutaneous metrazole (sc.Met) tests. Among them, the most active were N-benzyl derivatives with fluoro and trifluoromethyl substituents especially at position-2 of the aryl moiety. The introduction of the phenyl ring at the imide nitrogen atom resulted in less active compounds. The results obtained showed that incorporation of fluoro or trifluoromethyl substituents increased the anticonvulsant activity in comparison to respective chloro, methoxy or methyl analogues. Crystallographically obtained conformation for one active and two inactive derivatives with trifluoromethyl substituents at position-2 or -3 of phenyl ring were initially used for molecular electrostatic potentials (MEP) calculation. The MEP distribution at carbonyl oxygen atoms was different for active and inactive molecules.     

A new chiral sulfinyl-NH-pyridine ligand for Ir-catalyzed asymmetric transfer hydrogenation reaction

A new flexible C₁-symmetric tridentate ligand (S)-N-(2-(tert-butylsulfinyl)benzyl)-1-(pyridin-2-yl)methanamine sulfoxide (L1) was successfully prepared and utilized as a chiral ligand for Ir(I)-catalyzed ATH (asymmetric transfer hydrogenation) reactions. Without any cooperation of other chiral center, encouraging ee and conversion values have been achieved, which provide us a better understanding on these types of ligands and a new strategy to develop new high-efficiency chiral catalysts for asymmetric reaction.     

A simple,efficient, two-step synthesis of symmetric 2,7-dialkyl-1,6-dioxaspiro[4.4]nonanes

A two-step synthesis of symmetric 2,7-dialkyl-1,6-dioxaspiro[4.4]nonanes has been achieved by double Michael addition of nitromethane with two moles of enones on Amberlyst A21, followed by in situ reduction with sodium borohydride, then spontaneous spiroketalization of the obtained nitrodiol, by the Nef reaction under acidic conditions, affords the title compounds in good yields.     

Domino retro Diels-Alder/Diels-Alder reaction: an efficient protocol for the synthesis of highly functionalized bicyclo[2.2.2]octenones and bicyclo[2.2.2]octadienones

A novel and convenient approach, the domino retro Diels-Alder/Diels-Alder reaction sequence for highly stereo- and regioselective synthesis of various bicyclo[2.2.2]octenone and bicyclo[2.2.2]octadienone derivatives is presented. Thus, the masked o-benzoquinones (MOBs) 2a-e generated by the pyrolysis of the respective dimers 3a-e participated in this novel synthetic strategy with a variety of olefinic and acetylenic dienophiles at 220 degrees C to provide the title compounds in good to excellent yields.     

A new cationic,chiral catalyst for highly enantioselective Diels-Alder reactions

[reaction: see text] The Diels-Alder reaction of cyclopentadiene and 2-methacrolein is catalyzed by a chiral Lewis acid to form the exo adduct in 96% yield and 96% ee.     

A new non-natural chiral auxiliary: design, synthesis, and resolution of 1-mesitylethylamine and its application in the asymmetric aza-Diels–Alder reaction

1-Mesitylethylamine was designed as a new non-natural chiral auxiliary. Racemic 1-mesitylethylamine could be synthesized in two steps from mesityl cyanide and could be resolved via separation of diastereomeric carbamates derived from (−)-menthyl chloroformate, followed by reduction with DIBAL and acidic hydrolysis. Imines, prepared from enantiopure 1-mesitylethylamine and aromatic aldehydes, reacted with Danishefsky’s diene in the presence of a Lewis acid to give cycloaddition products, 4-pyridone derivatives, with high diastereoselectivity.     

A new, chiral aminoanthracene for the Diels-Alder/retro-Diels-Alder sequence in lactam and butenolide synthesis

9-(2-Phenylethyl)aminoanthracene has been prepared and used as a template in the Diels-Alder/retro-Diels-Alder sequence to produce α,β-butenolides and α,β-unsaturated lactams. In this sequence the aminoanthracene serves as a stereo- and regiocontrolling chaperone in guiding maleic anhydride or N-alkylmaleimides through transformations to the butenolide or lactam targets.     

Synthesis of new planar chiral [2.2]paracyclophane Schiff base ligands and their application in the asymmetric Henry reaction

A series of new planar and central chiral ligands based on [2.2]paracyclophane backbones were designed and prepared from enantiomerically pure 4-amino-13-bromo[2.2]paracyclophane and commercially available chiral amino alcohols. Their application in a copper-catalyzed asymmetric Henry reaction resulted in secondary alcohols with high yield and excellent selectivity for active aldehydes (up to 94% ee). This is a successful example of employing planar chiral [2.2]paracyclophane ligands in copper-catalyzed reaction.     

A novel and efficient chiral palladium-phosphinooxazolidine catalyst for the enantioselective Diels-Alder reaction

An efficient ruthenium-catalyzed transfer dehydrogenation of amines to imines was acheived under mild conditions using 2,6-dimethoxy benzoquinone (2) or cat. 2/MnO2 as oxidant.