Diastereospecific addition of organometallics to (S)-2-alkoxy-1-(1,3-dithian-2-yl)-1-propanones and its application to the synthesis of (−)-trachelantic acid

Nucleophilic addition of organometallics to (S)-2-alkoxy-1-(1,3-dithian-2-yl)-1-propanones afforded preferentially (1R,2S)-2-alkoxy-1-alkyl-1-(1,3-dithian-2-yl)-1-propanols. The utility of the present reaction was demonstrated in the synthesis of (2R,3S)-trachelanthic acid.     

Stereodivergent syntheses of anisomycin derivatives from D-tyrosine

[structures: see text] Enantiomerically pure 2-alkyl-3-acetoxy-4-iodopyrrolidines with all groups cis, and all adjacent groups trans (10 and 17), important precursors for the synthesis of pyrrolidinediols, have been prepared from D-tyrosine through regio- and diastereoselective reduction of a vinyl ketone and subsequent iodoamidation controlled by minimization of nonbonding steric interactions. Highly stereodivergent Woodward-Prevost methodology, applied to both iodopyrrolidines, yielded enantiomerically pure (2R,3R,4R)-, (2R,3R,4S)-, and (2R,3S,4R)-deacetylanisomycin (3, 4, and 5), each in excellent de. Incorporation of differential protection of the hydroxyl groups led to a one-pot synthesis of (2R,3R,4R)-anisomycin 2.     

Asymmetric synthesis of beta2-amino acids: 2-substituted-3-aminopropanoic acids from N-acryloyl SuperQuat derivatives

Conjugate addition of lithium dibenzylamide to (S)-N(3)-acryloyl-4-isopropyl-5,5-dimethyloxazolidin-2-one (derived from l-valine) and alkylation of the resultant lithium beta-amino enolate provides, after deprotection, a range of (S)-2-alkyl-3-aminopropanoic acids in good yield and high ee. Alternatively, via a complementary pathway, conjugate addition of a range of secondary lithium amides to (S)-N(3)-(2'-alkylacryloyl)-4-isopropyl-5,5-dimethyloxazolidin-2-ones, diastereoselective protonation with 2-pyridone, and subsequent deprotection furnishes a range of (R)-2-alkyl- and (R)-2-aryl-3-aminopropanoic acids in good yield and high ee. Additionally, the boron-mediated aldol reaction of beta-amino N-acyl oxazolidinones is a highly diastereoselective method for the synthesis of a range of beta-amino-beta'-hydroxy N-acyl oxazolidinones.     

Asymmetric synthesis of 2-alkyl- and 2-aryl-3-aminopropionic acids (beta2-amino acids) from (S)-N-acryloyl-5,5-dimethyloxazolidin-2-one SuperQuat derivatives

Conjugate addition of lithium amides to (S)-N-acryloyl- or (S)-N-2'-alkylacryloyloxazolidinones and alkylation or protonation of the resulting enolates with 2-pyridone respectively provides a highly stereoselective and product complementary route to a range of (R)- and (S)-2-alkyl-3-aminopropionic acids in good yield and in high ee.     

Synthesis of trans-(3S)-amino-(4R)-alkyl- and -(4S)-aryl-piperidines via ring-closing metathesis reaction

[reaction: see text] trans-(3S)-Amino piperidines bearing various alkyl and aryl substituents at the C-4 position were synthesized via a ring-closing metathesis reaction. The absolute stereochemistry was controlled using a protected D-serine as a starting material. Stereoselective hydrogenation of allylamines provided trans-(3S)-amino-(4R)-alkyl- and -(4S)-aryl-piperidines. This procedure presents the first method for the asymmetric synthesis of 4-substituted 3-amino piperidines.     

Dynamic kinetic resolution of racemic gamma-aryl-delta-oxoesters. Enantioselective synthesis of 3-arylpiperidines

Cyclodehydration of racemic gamma-aryl-delta-oxoesters with (R)- or (S)-phenylglycinol stereoselectively affords bicyclic delta-lactams, in a process that involves a dynamic kinetic resolution. Subsequent reduction of these lactams leads to enantiopure 3-arylpiperidines. Starting from racemic aldehyde esters, this short sequence has been applied to the synthesis of (R)-3-phenylpiperidine and the antipsychotic drug (-)-3-PPP (an (S)-3-arylpiperidine), whereas starting from racemic ketone esters enantiopure cis-2-alkyl-3-arylpiperidines are prepared.     

Highly enantioselective photocyclization of 1-alkyl-2-pyridones to beta-lactams in inclusion crystals with optically active host compounds

[reaction: see text] Upon photoirradiation of a 1:1 inclusion complex of (-)-3 and 2-alkyl-1-pyridone (1) (R = Et, n-Pr, i-Pr, n-Bu, i-Bu) in the solid state, optically active beta-lactams (2) of 91-99.5% ee were obtained in good yield.     

Diastereoselective hydroxylation of 6-substituted piperidin-2-ones. An efficient synthesis of (2S,5R)-5-hydroxylysine and related alpha-amino acids

The synthesis of (2S,5R)-5-hydroxy-6-oxo-1,2-piperidinedicarboxylates (5) and related (3S,6R)-3-hydroxy-6-alkyl-2-oxo-1-piperidinecarboxylates has been developed. The approach is based on the asymmetric hydroxylation of enolates generated from the corresponding N-protected-6-substituted piperidin-2-ones. The utility of 5a as a precursor in the synthesis of (2S,5R)-5-hydroxylysine (1), an amino acid unique to collagen and collagen-like proteins, has also been demonstrated. (2S)-6-oxo-1,2-piperidinedicarboxylates (6) required for hydroxylation studies were prepared in 38-74% yield, starting from conveniently protected aspartic acid as inexpensive chiral adduct. Hydroxylation of 6 to 5 proceeds in high yield and excellent diastereoselectivity by treatment of their Li-enolate with (+)-camphorsulfonyloxaziridine at -78 degrees C. Ring opening of di-tert-butyl (2S,5R)-6-oxo-1,2-piperidinedicarboxylate ((5R)-5a) under reductive conditions afforded the corresponding 1,2-diol (17) in 91%, which was further transformed to (2S,5R)-5-hydroxylysine in four steps (84%). 17 is also a versatile intermediate in the preparation of tert-butyl (2S,5R)-2-[(tert-butoxycarbonyl)amino]-5-hydroxy-6-iodohexanoate (3) and tert-butyl (2S)-2-[(tert-butoxycarbonyl)amino]-4-[(2R)-oxiranyl]butanoate (4), two amino acid derivatives used in the total synthesis of the bone collagen cross-link (+)-pyridinoline (2a).     

A general approach to (5S,6R)-6-alkyl-5-benzyloxy-2-piperidinones: application to the asymmetric syntheses of neurokinin substance P receptor antagonist (-)-L-733,061 and (-)-deoxocassine

A general approach to (5S,6R)-6-alkyl-5-benzyloxy-2-piperidinones based on the regio- and diastereoselective reductive alkylation of (S)-3-benzyloxyglutarimide 7 is described. This method opens an entrance to chiral nonracemic substituted 3-piperidinols. The versatility of the method is illustrated by the asymmetric syntheses of neurokinin substance P receptor antagonist L-733,061 (ent-1), (-)-deoxocassine (4), and an inhibitor of HIV proteases (5a).     

Synthesis of 1,1’-[methylenebis(oxy)]-bis[3-alkyl-3-(2-hydroxyethyl)triaz-1-ene 2-oxides]

Potential NO donors, 1,1’-[methylenebis(oxy)]bis[3-(2-hydroxyethyl)triaz-1-ene 2-oxides], were derived from 3-alkyl-3-(2-acetoxyethyl)-1-chloromethoxytriaz-1-ene 2-oxides and 3-alkyl-1-hydroxy-3-(2-hydroxyethyl)triaz-1-ene 2-oxide sodium salts.     

Reactions of 1-alkyl-1,2-diphospholes with 1,3-dipoles: diphenyldiazomethane and nitrones

The reaction of 1-alkyl-1,2-diphosphacyclopenta-2,4-dienes (1-alkyl-1,2-diphospholes) (1) with diphenyldiazomethane proceeds at room temperature via unstable [3+2] cycloadducts to form bicyclic phosphiranes (2). However, 1-alkyl-1,2-diphospholes (1) react with N,alpha-diphenylnitrone or N-tert-butyl-alpha-phenylnitrone depending on the temperature to give either dimers of 1-alkyl-1-oxo-1,2-diphospholes (5) or 1-alkyl-1,7-dioxo-6-azo-1,7-diphospha-bicyclo[3.2.0]hept-2-enes (7) - phosphorus analogues of β-lactams.     

Cyanoacetylene and Its Derivatives. 30. Reactions of 2,3-Dimercaptoquinoxaline with 3-Phenyl-2-propynonitrile and 4-Alkyl-4-hydroxy-2-alkynonitriles

The reaction of 2,3-dimercaptoquinoxaline with 3-phenyl-2-propynonitrile (~10 mass % KOH, 20-25°C, 5 h, dioxane) gave the S,S-diadduct (as with unsubstituted acetylene). 2,3-Dimercaptoquinoxaline reacted with 4-alkyl-4-hydroxy-2-alkynonitriles to give 2-cyanomethyl-2-(1-hydroxy-1-alkyl)-1,3-dioxolano[4,5-b]quinoxalines or 3-cyanomethylene-8-imino-2,2,6,6-tetramethyl-1,7-dioxa-4-thiaspiro[4.4]nonane.     

Diastereoselective fragmentation of chiral alpha-aminophosphonic acids/metal ion aggregates

Diastereomeric clusters of general formula [MAB(2)](+) and [MA(2)B](+) (M = Li(I), Na(I), Ag(I), Ni(II)-H, or Cu(II)-H; A = (R)-(-)- and (S)-(+)-(1-aminopropyl)phosphonic acid; B = (1R)-(-)- and (1S)-(+)-(1-aminohexyl)phosphonic acid) have been readily generated in the electrospray ionization (ESI) source of a triple-quadrupole mass spectrometer and their collision-induced dissociation (CID) investigated. CID of diastereomeric complexes, e.g. [MA(S)(B(S))(2)](+) and [MA(R)(B(S))(2)](+), leads to fragmentation patterns characterized by R(homo) = [MA(S)B(S)](+)/[M(B(S))(2)](+) and R(hetero) = [MA(R)B(S)](+)/[M(B(S))(2)](+) abundance ratios, which depend upon the relative stability of the diastereomeric [MA(S)B(S)](+) and [MA(R)B(S)](+) complexes in the gas phase. The chiral resolution factor R(chiral) = R(homo)/R(hetero) is found to depend not only on the nature of the M ion but also on that of the fragmenting species, whether [MAB(2)](+) or [MA(2)B](+). The origin of this behavior is discussed.     

Ruthenium complexes with chiral tetradentate imino-sulfoxide ligands

Treatment of 2-(methylsulfinyl)benzaldehyde (1) with ethylenediamine or (1R,2R)-(-)-1,2-diaminocyclohexane afforded N,N'-bis[2-(methylsulfinyl)benzylidene]ethylenediamine (L(1)) or (1R,2R)-N,N'-bis[2-(methylsulfinyl)benzylidene]-1,2-cyclohexanedia mine (L(2)), respectively. Lithiation of 2-bromobenzaldehyde diethylacetal with n-BuLi/TMEDA followed by reaction with (1R,2S,5R)-(-)-menthyl-(S)-p-toluenesulfinate afforded 2-(S)-(p-tolylsulfinyl)benzaldehyde diethyl acetal (2). Deprotection of 2 with pyridinium tosylate followed by condensation with ethylenediamine, (1R,2R)-(-)-diaminocyclohexane, or (S,S)-(+)-diaminocyclohexane afforded N,N'-bis[2-(S)-(p-tolylsulfinyl)benzylidene]ethylenediamine (L(3)), (1R,2R)-N,N'-bis[2-(S)-(p-tolylsulfinyl)benzylidene]-1,2-cyclohexanediamine ((R,R)-L(4)), or (S,S)-N,N'-bis[2-(S)-(p-tolylsulfinyl)benzylidene]-1,2-cyclohexanediamine ((S,S)-L(4)), respectively. Treatment of [Ru(PPh(3))(3)Cl(2)] with L afforded trans-[Ru(L)Cl(2)] [L = L(1) (3), L(2) (4), L(3) (5), (R,R)-L(4) ((R,R)-6), (S,S)-L(4) ((S,S)-6)]. The X-ray structures of (S(S),R(S))-4, (R,R)-6, and (S,S)-6 have been determined. The average Ru-N, Ru-S, and Ru-Cl distances in (S(S),R(S))-4 are 2.063, 2.2301, and 2.4039 A, respectively. The corresponding distances in (R,R)-6 are 2.071, 2.256, and 2.411 A, and those in (S,S)-6, 2.058, 2.2275, and 2.3831 A. Compound 3 exhibited a reversible Ru(III/II) couple at 0.56 V vs Cp(2)Fe(+/0) in CH(2)Cl(2). Treatment of 3 with AgNO(3) in water afforded the aqua compound trans-[Ru(L(1))Cl(H(2)O)][PF(6)] (7), which has been characterized by X-ray crystallography. The Ru-Cl, Ru-O, average Ru-N, and average Ru-S distances in 7 are 2.3733(6), 2.1469(16), 2.071, and 2.2442 A, respectively. Treatment of 3 with AgNO(3) followed by reaction with PPh(3) afforded [Ru(L(1))(PPh(3))(2)][PF(6)](2) (8). Treatment of [Os(PPh(3))(3)Cl(2)] with L(1) resulted in deoxygenation of one sulfoxide group of L(1) and formation of [Os(L(5))Cl(2)(PPh(3))] (9) (L(5) = N-[2-(methylsulfinyl)benzylidene]-N'-[2-(methylthio)benzylididene]ethylenediamine), which has been characterized by X-ray crystallography. The average Os-S(O), Os-N(trans to P), Os-N(trans to S), Os-P, and Os-Cl distances are 2.1931, 2.085, 2.175, 2.3641, and 2.4266 A, respectively.     

Resonance-stabilized 1,2,3-dithiazolo-1,2,3-dithiazolyls as neutral pi-radical conductors

Alkylation of the zwitterionic heterocycle 8-chloro-bis[1,2,3]dithiazolo[4,5-b:5',4'-e]pyridine (ClBP) with alkyl triflates affords 8-chloro-4-alkyl-4H-bis[1,2,3]dithiazolo[4,5-b:5',4'-e]pyridin-2-ium triflates [ClBPR][OTf] (R = Me, Et, Pr). Reduction of these salts with decamethylferrocene affords the corresponding ClBPR radicals as thermally stable crystalline solids. The radicals have been characterized in solution by cyclic voltammetry and EPR spectroscopy. Measured electrochemical cell potentials and computed (B3LYP/6-31G) gas-phase disproportionation enthalpies are consistent with a low on-site Coulombic barrier U to charge transfer in the solid state. The crystal structures of ClBPR (R = Me, Et, Pr) have been determined by X-ray crystallography (at 293 K). All three structures consist of slipped pi-stacks of undimerized radicals, with many close intermolecular S.S contacts. ClBPMe undergoes a phase transition at 93 K to a slightly modified slipped pi-stack arrangement, the structure of which has also been established crystallographically (at 25 K). Variable-temperature magnetic and conductivity measurements have been performed, and the results interpreted in light of extended Hückel band calculations. The room-temperature conductivities of ClBPR systems (sigma(RT) approximately 10(-)(5) to 10(-)(6) S cm(-)(1)), as well as the weak 1D ferromagnetism exhibited by ClBPMe, are interpreted in terms of weak intermolecular overlap along the pi-stacks. The latter is caused by slippage of the molecular plates, a feature necessitated by the steric size of the R and Cl groups on the pyridine ring.     

手性高效液相色谱拆分3-取代异吲哚-1-酮的研究

从伏牛花类植物中提取的生物碱Lennoxam ine^[1]、Nuevam ine和Chilenine,新研发的抗焦虑药Paz-inaclone^[2]和Pagoclone^[3]以及利尿、抗高血压药Chlortalidone^[4]等均含有光活性3-取代异吲哚-1-酮(2,3-二氢-1H -异吲哚-1-酮).这类化合物还是一类新型的不对称合成手性辅助基^[5].因此,光学纯的3-取代异吲哚-1-酮化合物在药物研发和不对称合成等领域具有应用前景.但有关它们的色谱拆分少见报道^[6,7].本文对15个外消旋3-取代异吲哚-1-酮样品进行高效液相色谱拆分研究,通过建立的手性色谱方法,不仅准确测定了相关产物的光学纯度,而且确认了N -取代邻苯二甲酰亚胺上手性辅助基在不对称合成过程^[8]中未发生消旋化.同时探讨了样品中3-位取代基对手性拆分的影响.     

Rhodium(III) complexes of 1-Alkyl-2-{(o-thioalkyl) phenylazo}imidazoles: synthesis,structure, spectral characterization,DNA binding study and DFT calculation

Transition Metal Chemistry - The Rh(III) complexes of 1-alkyl-2-{(o-thioalkyl)phenylazo}imidazole (SRaaiNR′, 1; R = R′= Me (a); R = Me, R′= Et...     

Asymmetric transformation of a double-stranded, dicopper(I) helicate containing achiral bis(bidentate) Schiff bases

Reactions of the bis(bidentate) Schiff-bases N,N'-bis(6-alkyl-2-pyridylmethylene)ethane-1,2-diamine (where alkyl = H, Me, iPr) (L) with tetrakis(acetonitrile)copper(I) hexafluorophosphate and silver(I) hexafluorophosphate afforded, respectively, the double-stranded, dinuclear metal helicates [T-4-(R,R)]-(+/-)-[M2L2](PF6)2 (M = Cu, Ag). The helicates were characterized by 1H and 13C NMR spectroscopy, conductivity, microanalysis, and single-crystal X-ray structure determinations on selected compounds. Intermolecular ligand exchange and intramolecular inversion rates for the complexes were investigated by 1H NMR spectroscopy. Reversible intermolecular ligand exchange between two differently substituted helicates followed first-order kinetics. The rate constants (k) and corresponding half-lives (t(1/2)) for ligand exchange for the dicopper(I) helicates were k = (1.6-1.8) x 10(-6) s(-1) (t(1/2) = 110-120 h) in acetone-d6, k = 4.9 x 10(-6) s(-1) (t(1/2) = 40 h) in dichloromethane-d2, and k > 2 x 10(-3) s(-1) (t(1/2) < 5 min) in acetonitrile-d3. Ligand exchange for the disilver(I) helicates occurred with k > 2 x 10(-3) s(-1) (t(1/2) < 5 min). Racemization of the dicopper(I) helicate by an intramolecular mechanism was investigated by determination of the coalescence temperature for the diastereotopic isopropyl-Me groups in the appropriate complex, and DeltaG() > 76 kJ mol(-1) was calculated for the process in acetone-d6, nitromethane-d3, and dichloromethane-d2 with DeltaG() = 75 kJ mol(-1) in acetonitrile-d3. Complete anion exchange of the hexafluorophosphate salt of a dicopper(I) helicate with the enantiomerically pure Delta-(-)-tris(catecholato)arsenate(V) ([As(cat)3]-) in the presence of Dabco gave the two diastereomers (R,R)-[Cu2L2][Delta-(-)-[As(cat)3]]2 and (S,S)-[Cu2L2][Delta-(-)-[As(cat)3]]2 in up to 54% diastereomeric excess, as determined by (1)H NMR spectroscopy. The diastereomerically and enantiomerically pure salt (R,R)-[Cu(2)L2][Delta-(-)-[As(cat)3]]2 crystallized from the solution in a typical second-order asymmetric transformation. The asymmetric transformation of the dicopper(I) helicate is the first synthesis of a diastereomerically and enantiomerically pure dicopper(I) helicate containing achiral ligands.     

Sesquiterpenoid derivatives from Ferula ferulaeoides [correction of ferulioides]. V

Nine novel prenyl-dihydrofurocoumarin-type sesquiterpenoid derivatives, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4-methyl-5- (4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo-[3,2-c]coumarin, and 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, were isolated from the roots of Ferula ferulaeoides [corrected]. The structures were established by comprehensive spectral analysis. The biosynthetic pathway leading to these prenyl-furocoumarin-type sesquiterpenoids is proposed based on their structures.     

A highly regio- and stereoselective nickel-catalyzed ring-opening reaction of alkyl- and allylzirconium reagents to 7-oxabenzonorbornadienes

[Reaction: see text]. An efficient method for the synthesis of cis-2-alkyl- or allyl-1,2-dihydronaphthalenes via a nickel-catalyzed highly regio- and stereoselective ring-opening addition of alkyl- or allylzirconium reagents to 7-oxabenzonorbornadienes is described. Treatment of 7-oxabenzonorbornadienes 1a-c with various alkylzirconium reagents 2a-j (Cp2ZrClCH2CH2R: R = tert-butyl, n-butyl, n-pentyl, -(CH2)3CH=C(CH3)2, -SiMe3, -CH2SiMe3, -(CH2)3Br, cyclopentyl, cyclohexyl, and benzyl) in the presence of NiBr2(dppe) and Zn powder in dry THF at 50 degrees C afforded the corresponding cis-2-alkyl-1,2-dihydronaphthalene derivatives 3a-m in good yields. In addition, allyl zirconium reagents 4a-c also underwent ring-opening reactions with 1a and 1c to give 5a-d in very good yields. The alkylative ring-opening products from 7-oxabenzonorbornadiene can be further converted to naphthalene derivatives 6a-c, via an acid-mediated dehydration, in good to excellent yields. A possible mechanism for the present catalytic reaction was proposed.