Stereoselective synthesis of (1R,2S)-2-amino-1,3-diols from (R)-cyanohydrins

Vinyl substituted (1R,2S)-amino alcohols 5 were obtained by addition of vinyl magnesium bromide to the corresponding cyanohydrin O-trimethylsilyl ethers (R)-2. The O- and N-protected vinyl amino alcohols 6 were ozonized at −78°C in methanol yielding (1R,2S)-2-amino-1,3-diols7 in high enantiomeric and diastereomeric excesses. For purification, compounds 7 in some cases were acetylated to give the derivatives (1R,2S)-8. Racemic 6a was converted by oxidative ozonolysis at −78°C in methanolic NaOH solution to the corresponding methyl N-acetyl-β-hydroxy propanoate 9a. The configuration of (1R,2S)-8a was confirmed by x-ray crystallographic analysis.     

A convenient stereoselective synthesis of (R)-(−)-denopamine and (R)-(−)-salmeterol

β-Adrenoreceptor agonists (R)-(−)-denopamine (R)-1 and (R)-(−)-salmeterol (R)-2 have been prepared in good overall yield and high enantioselectivity through a biotransformative pathway.     

(R)-Binaphthoxy diiodide lanthanides

The synthesis and characterization of novel enantiopure binaphthoxy-diiodo lanthanides [(R)-2-(1-naphthol)-1′-naphthoxide)LnI₂(THF)₃] (Ln=Sm (4a), Yb (4b), La (4c)) are described. These complexes have been prepared by reacting the mono potassium salt of (R)-binaphthol with the corresponding lanthanide triiodides and were characterized by elemental analysis, IR and NMR spectroscopies. Recrystallization of 4c from THF–hexane led to monocrystals of [(R)-2-(1-naphthol)-1′-naphthoxide)]-diiodolanthane-tetrakistetrahydrofurane] (4c*). Complex 4c* crystallizes in the orthorhombic space group, P2₁2₁2₁ with cell parameters a=13.086(1) Å, b=15.496(1) Å, c=18.854(1) Å, V=3823.2(6) ų, and Z=4.     

Studies on the synthesis of biphenylneolignans. Part 1: Enantioselective synthesis of (S,S)- and (R,R)-2,2′-dimethoxy-4-(3-hydroxy-1-propenyl)-4′-(1,2,3-trihydroxypropyl)diphenyl ether

Two erythro-isomers of 2,2′-dimethoxy-4-(3-hydroxy-1-propenyl)-4′-(1,2,3-trihydroxypropyl)diphenyl ether, (7′S, 8′S)-9 and (7′R, 8′R)-9, were synthesized in seven steps, in which an improved method for the synthesis of the key intermediate 3 was developed. The absolute configuration of the target molecules was also confirmed.     

Reactions and X-ray crystal structure of (3-cyano-2,4-pentanedionato-N)pentaamminecobalt(III) perchlorate chloride dihydrate

The pentaamminecobalt(III) complex with the 3-cyano-2,4-pentanedionate anion coordinated through the nitrile nitrogen has been characterized by X-ray crystallography. The crystals of [(NH₃)₅CoNCacac](Cl)(ClO₄)·2H₂O are triclinic, space group P , a = 10.245(2) Å, b = 14.071(4) Å, c = 6.971(2) Å, = 90.03(3)°, β = 109.86(2)°, γ = 108.91(2)°, V= 887.1 ų, Z = 2, D_c = 1.64 g cm⁻³, F(000) = 456, Mo-K radiation, λ = 0.71069 Å, μ(Mo-K) = 12.7 cm⁻¹. The structure was determined by the heavy-atom method, and refined by block-diagonal least-squares calculations, R = 0.0537, R_w = 0.0607, for 2499 observed reflections. Principal dimensions are: Co---N(NH₃) trans to NCacac⁻ 1.940(5), other Co---N(NH₃) 1.967(2), Co---N(NCacac⁻) 1.911(5) Å. The pendant acac moiety is best described in terms of a delocalized bond network with, for example, C---C distances in the range 1.44–1.52(1) Å. Several reactions involving this free acac group are also described including the preparation and characterization of the dimeric species pentaamminecobalt(III) - μ - (3 - cyano - 2,4 - pentanedionato) - bis(propylenediamine) cobalt(III) perchlorate.     

Asymmetric Synthesis via Acetal Templates. 14. Preparation of Enantiomerically Pure (3S,4S)- and (3S,4R)-Statine Derivatives

Several (3S,4S)- and (3S,4R)-statine derivatives have been prepared by attack of nucleophiles on crystalline, epimeric N-BOC-lactams 7a and 7b. The key step in the synthesis of the lactams was the TiCl₄-catalyzed coupling reactions of acetals derived from (R)-1,3-butanediol with allyltrimethylsilane.

Several enantiometrically pure (3S,4S- and (3S, 4R)-statine derivatives were made by sodium cyanide-catalyzed reaction of nucleophiles with the lactams 3a and 3b which were synthesized by the scheme 1 → 2 → 3.     

Asymmetric hydroboration of [E]- and [Z]-2-methoxy-2-butenes. Synthesis of (−)-[2R,3R]-butane-2,3-diol in >97% ee

Asymmetric hydroboration of [E]- and [Z]-2-methoxy-2-butene, using (−)-diisopinocampheylborane at −25°C in THF solvent, followed by oxidation using H₂O₂/NaOH, gave (−)-[2R,3R]- and (+)-[2R,3S]-3-methoxy-2-butanols in >97 and 90% ee, respectively. (−)-[2R,3R]-3-Methoxy-2-butanol was converted to (−)-[2R,3R]-butane-2,3-diol (>97% ee, in an overall yield of 65%).     

Asymmetric syntheses of protected (2S,3S,4S)-3-hydroxy-4-methylproline and 4′-tert-butoxyamido-2′-deoxythymidine

Described herein is a versatile approach to (i) (2S,3S,4S)-3-hydroxy-4-methylproline 3, a constituent of echinocandins and related oligopeptide antibiotics; (ii) (2S,3S)-3-hydroxyproline 1; (iii) (2R,3S)-3-hydroxyprolinol 5, and (iv) 4′-tert-butoxyamido-2′-deoxythymidine 6b. The method features a stepwise regio- and diastereoselective reductive furylation of the protected (3S,4S)-4-methylmalimide 10, (S)-malimide 9, and a chemoselective oxidative transformation of the furyl group to the carboxyl group as the key steps.     

Phenylbis(2- pyridyl)phosphine: P- vs. N,N′-coordination in carbonylmolybdenum-(O) and -(II) complexes

The first carbonyl molybdenum-(O) and -(II) complexes with phenylbis(2-pyridyl)phosphine (PPhpy₂) have been synthesized. PPhpy₂ reacts with [Mo(CO)₅(NCMe)] to give [Mo(CO)₅(PPhpy₂-P)]. With [Mo(CO)₄(NBD)] (NBD = norbornadiene) it gives [Mo(CO)₄(PPhpy₂-P)₂] when a 2 : 1 ratio is used, or [MO(CO)₄(py₂PhP---N,N′)] for a 1 : 1 ratio. Decarbonylation of any of these pyridylphosphine complexes leads to an oligomer of formula {MO(CO)₃(μ-PPhpy₂)}_n, which is also obtained after heating [MO(CO)₆] in solution with an equimolar amount of PPhpy₂. The oligomer undergoes oxidative addition by iodine or allylbromide to give [MoI₂(CO)₃(py₂PhP---N,N′)], or [MoBr(η³-CH₂CHCH₂)(CO)₂(py₂PhP---N,N′)], respectively. These complexes are also obtained by addition of equimolar amounts of PPhpy₂ to solutions of [MoI₂(CO)₃(NCMe)₂] and MoBr(η³-CH₂CH CH₂)(CO)₂(NCMe)₂, respectively. The ligand tends to act as a P-donor towards molybdenum(O) substrates, and as a chelating N,N′-donor in molybdenum (II) complexes.     

A thermochemical investigation of guest-host interactions in labile Werner clathrates of the [Ni(4-EtPy)4(NCS)2]·G type (G = Methyl derivatives of benzene)

The stoichiometry of thermal decomposition has been studied for (I): [Ni(4-EtPy)₄(NCS)₂] as a host complex as well as for its clathrates [Ni(4-EtPy)₄(NCS)₂]·G where guest molecule G - toluene, (II): T, (III): o-xylene (o-X) and (IV): p-xylene (p-X). The loss of volatile components proceeds in three steps (−2L, −1L, −1L) for I and in four steps (−G, −2L, −1L, −1L) for II, III and IV. DSC and X-ray powder measurements indicated a phase transition in all compounds under study. However, this process is overlapped by the escape of G in II and III. The differences in enthalpy changes are associated with different guest-host interactions in the particular clathrates.     

Synthesis of 1,1′-methylenedi[(1R,1′R,3R,3′R,5R,5′R)-8-oxabicyclo[3.2.1]oct-6-en-3-ol] and derivatives: precursors of long-chain polyketides

Racemic 1,1′-methylene[(1RS,1′RS,3RS,3′RS,5RS,5′RS)-8-oxabicyclo[3.2.1]oct-6-en-3-ol] ((±)-6) derived from 2,2′-methylenedifuran has been resolved kinetically with Candida cyclindracea lipase-catalysed transesterification giving 1,1′-methylenedi[(1R,1′R,3R,3′R,5R,5′R)-8-oxabicyclo[3.2.1]oct-6-en-3-ol] (−)-6 (30% yield, 98% ee) and 1,1′-methylenedi[(1S,1′S,3S,3′S,5S,5′S)-8-oxabicyclo[3.2.1]oct-6-en-3-yl] diacetate (+)-8, (40% yield, 98% ee). These compounds have been converted into 1,1′-methylenedi[(4S,4′S,6S,6′S)- and (4R,4′R,6R,6′R)-cyclohept-1-en-4,6-diyl] derivatives.     

Enzymatic production of (3S,4R)-(−)-4-(4′-fluorophenyl)-6-oxo-piperidin-3-carboxylic acid using a commercial preparation from Candida antarctica A: the role of a contaminant esterase

The enantioselective hydrolysis of (3RS,4RS)-trans-4-(4′-fluorophenyl)-6-oxo-piperidin-3-ethyl carboxylate (±)-2 was effected using a commercial preparation of lipase from C. antarctica A (CAL-A). We found that the hydrolytic activity of the lipase (immobilized on a number of very different supports) with this substrate was negligible. However, a contaminant esterase with Mw of 52 KDa from this commercial preparation exhibited much higher activity with (±)-2. This enzyme was purified and immobilized on PEI-coated support and the resulting enzyme preparation was highly enantioselective in the hydrolysis of (±)-2 (E >100), hydrolyzing only the (3S,4R)-(−)-3, which is a useful intermediate for the synthesis of pharmaceutically important (−)-paroxetine. Optimization of the reaction system was performed using a racemic mixture with a substrate concentration of 50 mM. This enzyme preparation was used in three reaction cycles and maintained its catalytic properties.     

Catalytic and structural studies of Rh complexes of (−)-(2S,4S)-2,4-bis(diphenylphosphino)pentane. Asymmetric hydrogenation of acetophenonebenzylimine and acetophenone

Rhodium(I) complexes formed by (−)-(2S,4S)-2,4-bis(diphenylphosphino)pentane (BDPP) are efficient catalysts for the hydrogenation of acetophenone and acetophenonebenzylimine. The composition of the solvent mixture and the reaction temperature have a marked influenced on the enantioselectivity. These effects are thought to be related to the enhanced conformational flexibility of six-membered rings when simple substrates without functional groups are coordinated to the rhodium. X-ray crystallographic studies reveal that in [Rh((S,S)-BDPP)NBD]⁺ (1) the ligand is in a chair conformation, and that in [Rh((S,S)-BDPP)COD]⁺ (2) the chelate ring is in a δ-skew conformation. Studies of Rh((S,S)-BDPP)(NBD)Cl (3) in solution indicate a trigonal bipyramidal structure with a chair conformation of the ring in aromatic solvents and a conformationally labile ring in methanol.     

Structural, spectral and thermal studies of N-2-(4-picolyl)- and N-2-(6-picolyl)-N′-(2-chlorophenyl)thioureas and N-2-(6-picolyl)-N′-(2-bromophenyl)thiourea

N-2-(4-picolyl)-N′-2-chlorophenylthiourea, 4PicTu2Cl, monoclinic, P2₁/c, a=10.068(5), b=11.715(2), β=96.88(4)°, and Z=4; N-2-(6-picolyl)-N′-2-chlorophenylthiourea, 6PicTu2Cl, triclinic, P-1, a=7.4250(8), b=7.5690(16), c=12.664(3) Å, =105.706(17), β=103.181(13), γ=90.063(13)°, V=665.6(2) ų and Z=2 and N-2-(6-picolyl)-N′-2-bromophenylthiourea, 6PicTu2Br, triclinic, P-1, a=7.512(4), b=7.535(6), c=12.575(4) Å, a=103.14(3), β=105.67(3), γ=90.28(4)°, V=665.7(2) ų and Z=2. The intramolecular hydrogen bonding between N′H and the pyridine nitrogen and intermolecular hydrogen bonding involving the thione sulfur and the NH hydrogen, as well as the planarity of the molecules, are affected by the position of the methyl substituent on the pyridine ring. The enthalpies of fusion and melting points of these thioureas are also affected. ¹H NMR studies in CDCl₃ show the NH′ hydrogen resonance considerably downfield from other resonances in their spectra.     

Coordination geometry of chromium(VI) species. The first example of cis-bridging chromate ions in helically structured catena(μ-CrO4-O,O′)[Ni(HIm)3H2O]

Nickel(II) chromate complex with imidazole (HIm) was isolated from the [Ni²⁺–HIm–CrO₄²⁻] system in various experimental conditions, i.e. reagent molar ratios and nickel(II) salts. The catena(μ-CrO₄-O,O′)[Ni(HIm)₃H₂O] (1) crystallizes in monoclinic crystal system—space group P2₁/n with cell parameters: a=11.784(2), b=8.899(2), c=13.934(3) (Å), β=95.19(3) (°). The unit cell contains two independent helixes, left- and right-handed, stabilized by intrahelical and interhelical hydrogen bonds (HB) and π–π interactions. The cis coordination of the CrO₄²⁻ anions and the HB systems appeared to be the main determinants of the helical architecture. To the best of our knowledge the cis-chromate coordination was observed for the first time. The cis coordination causes the distortion of the nickel octahedron, which was analysed by 4 K single crystal electronic spectra with D_4h symmetry approximation (gaussian resolution and crystal field parameters). This symmetry was also confirmed with the polarised electronic spectra. The magnetic properties of the complex suggest the occurrence of weak intrachain antiferromagnetic interactions between the magnetic Ni^II center. The computational DFT studies of complex 1 assuming three possible isomers mer[(HIm)₃]–cis[(CrO₄²⁻)₂], mer–trans and fac–cis suggested that the main contribution to the stability of 1 might have interhelical and intrahelical hydrogen bonds.     

Rhenium(I) methoxo carbonyl complexes containing tetraphosphine or triphosphine ligands; facile separation and X-ray crystallographic studies of d/l- and meso-[{Re2(μ-OMe)2(CO)6}2(μ,μ′-1,1,4,7,10,10-hexaphenyl-1,4,7,10-tetra-phosphadecane)]

Reaction of the activated mixture of Re₂(CO)_10, Me₃NO and MeOH with a 1:1 mixture of rac (d/l)- and meso-1,1,4,7,10,10-hexaphenyl-1,4,7,10-tetraphosphadecane (hptpd) yields a mixture of (d/l)- and meso-[{Re₂(μ-OMe)₂(CO)₆}₂(μ,μ′-hptpd)] 1. The diastereomers can be easily separated by selective dissolution of d/l-1 in benzene, and give clearly distinguishable ¹H- and ³¹P-NMR spectra. The fluxional behavior of d/l-1 in solution has been studied by variable-temperature ¹H- and ³¹P-{¹H}-NMR spectroscopy. The crystal structures of both d/l- and meso-1 have been determined. Both molecules consist of two {Re₂(μ-OMe)₂(CO)₆} moieties which are bridged by the two P---CH₂---CH₂---P moieties of the hptpd ligand. Whilst the molecules of meso-1 possess crystallographic i-symmetry, those of d/l-1 do not have any crystallographic symmetry. These diastereomers therefore give clearly distinguishable Raman spectra in the solid state. Reaction of tris[2-(diphenylphosphino)ethyl]phosphine (tdppep) with the activated mixture affords the complex [{Re₂(μ-OMe)₂(CO)₆}(μ,η²-tdppep)] 2, and the analogous reaction involving bis[2-diphenylphospinoethyl)phenylphosphine (triphos) gives [{Re₂(μ-OMe)₂(CO)₆}(μ,μ′,η³-triphos){Re₂(CO)₉}] 3 and [{Re₂(μ-OMe)₂(CO)₆}(μ,η²-triphos)] 4.     

Indenyl complexes of ruthenium(II) containing optically active diphosphines. X-ray structures of (S,S)-(η-C9H7)-Ru{Ph2PCH(CH3)CH(CH3)PPh2}Cl and of its η-C5H5 analogue

The optically active indenyl complexes ((η⁵-C₉H₇)Ru(L---L)Cl (where L---L is either (S,S)-1,2-dimethyl-1,2-ethanediylbis(diphenylphosphine) (chiraphos) or (R,R)-1,2-cyclopentanediylbis(diphenylphosphine) (cypenphos)) have been synthesized and spectroscopically characterized and compared with the corresponding cyclopentadienyl complexes. Reaction of the new complexes with 2-e-donors give cationic adducts in which the pentahaptocoordination of the indenyl ligand is maintained. The crystal structures of (S,S)-(η⁵-C₉H₇)Ru{Ph₂PCH(CH₃)CH(CH₃)PPh₂}Cl (1) and (S,S)-η⁵-C₅H₅Ru{Ph₂PCH(CH₃)CH(CH₃)PPh₂}Cl (3) have been determined.     

(R)-bis-Binaphthoxy iodo lanthanides as catalysts for Diels–Alder reactions

[(R)-1,1′bi-2,2′-Naphthoxy]LnI(THF)₂ (Ln: Yb, Sm, La) 5 have been prepared by reaction of the bispotassium salt of (R)-binaphthol with lanthanide triiodides, and characterized. They are active catalysts for Diels–Alder reactions although with low asymmetric inductions. The lanthanum iodo bisbinaphthoxide gives a slightly higher enantiomeric excess than the two other complexes.     

New chiral P-ligands: P-amino- and P-cycloalkoxy dibenzo[c.e][1,2]oxaphosphorines

The reaction of racemic chloro-dibenzo[c.e][1,2]oxaphosphorine with (S)-(−)--methyl-benzylamine and (1R,2S,5R)-(−)-menthol led to a mixture of optically active diastereomers of the corresponding phosphonous derivatives. The isomers were separated in a diastereomeric excess of 71–93% at the phosphonic oxide and/or at the phosphonous borane stage. The P(III) boranes are suitable precursors of the P-ligands. The absolute P-configuration in one of the menthyl phosphonates isolated was determined by single crystal X-ray analysis.     

The synthesis and x-ray structure of (N,N-dimethyldithiocarbamato)(n-butyl)diphenyltin(IV)

(N,N-Dimethyldithiocarbamato)(n-butyl)diphenyltin(IV), n-BuPh₂SnS₂NMe₂, crystallizes in the monoclinic space group P2₁/n with a 9.772(5), b 9.895(4), c 21.418(9) Å, β 95.81(3)⁰, V 2060 ų Z = 4, μ 14.4 cm⁻¹ The structure was determined by the heavy-atom technique from 3103 independent reflections measured at room temperature on an Enraf-Nonius four-circle CAD-4 diffractometer using monochromatized Mo-K radiation and refined to a final R value of 5.8%. The tin atom is essentially four-coordinated with a weak fifth tin-sulphur bond (Sn---S(2) 3.079(1) Å) considerably longer than the other (Sn---S(1) 2.466(1) Å). A comparison with the complex n-BuPhSn(C1)S₂CNEt₂ (Sn---S(1) 2.454(1) Å; Sn---S(2) 2.764(1) Å) suggests that enhanced steric factors are responsible for the preferential monodentate behaviour of the dithiocarbamate ligand in the title complex.