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The synthesis of 4/5/6 polycyclic β-lactams by enyne metathesis and Diels−Alder reactions is described. Compared to the synthesis of 4/6/6 and 4/7/6 polycyclic β-lactams previously reported by our laboratory, formation of the strained 4/5/6 compounds requires alternative reaction conditions. Indeed, the synthesis of the 4/5 bicyclic diene 12 was more difficult than those of the 4/6 (13) and 4/7 (14) dienes. The strain of the 4/5 system could be observed by NMR spectroscopy and molecular modelling. Moreover, the reactivity of 4/5 diene 12 towards Diels−Alder cycloaddition was also different from that of the 4/6 (13) and 4/7 (14) dienes. Cycloadditions with 4/5 diene 12 therefore had to be performed in lithium perchlorate/diethyl ether (LPDE) or in an ionic liquid in order to proceed in good yields with various dienophiles. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

The versatile preparation of trisubstituted alkenes via selective Rh-catalyzed arylation of alkynes is described in water and in a water/toluene biphasic system. For hydrophobic alkyl alkynes, the reaction afforded either alkenes or dienes depending on the temperature and the solvent conditions. Aryl, heteroaryl, silylated and alkyl substituted alkynes reacted equally well with various boronic acids, leading regioselectively to functionalized alkenyl derivatives in high yields (65–99%). The mechanism was investigated in toluene/water mixture or water and involves a vinylrhodium complex. The efficient recycling of the Rh/m-TPPTC system is disclosed with excellent yield (92–96%) and purity of the alkene.

The photochemical cyclisation-dehydrogenation of the bis-styrylbenzene 3, where the terminal aryl moieties are connected by a suitable chiral tether derived from 1,3-pentanediol, led to a chiral, configurationally locked [5]helicene derivative. An X-ray diffraction study showed that an (S,S)-configuration of the chiral auxiliary induces a (P)-configuration of the helical framework.

An efficient preparation of N-methyl-O-tert-butylhydroxylamine hydrochloride has been settled, which allowed the synthesis of modified Weinreb amides. Nucleophilic addition of organolithium and Grignard reagents on these N-tert-butoxy-N-methylamides afforded efficiently the corresponding ketones and reduction with DIBAL furnished the corresponding aldehydes in good yields up to 97%.

Ru-SYNPHOS® and Ru-DIFLUORPHOS® catalysts were efficiently used for the synthesis of a wide variety of chiral p- hydroxy amides via asymmetric hydrogenation of the corresponding β-keto amides.

The new heterotopic atropisomeric diphosphine (R)-5,6-benzo-2,2′-bis(diphenylphosphino)-4′,5′,6′-trimethylbiphenyl has been prepared. The key step of this synthesis is a diastereoselective, intramolecular aryl–aryl coupling reaction via oxidation of a suitable, chiral diarylcuprate. The catalytic properties of the diphosphine in ruthenium promoted hydrogenations of model substrates and in rhodium promoted 1,4-additions of boronic acids to α,β-unsaturated ketones are fully comparable to those of reference ligands such as BINAP. This seems to indicate that C2-symmetry is not a structural prerequisite for atropisomeric chiral diphosphines to obtain high enantioselectivities in 1,4-addition reactions as well as in hydrogenation reactions.

[63995-70-0] C18H12Na3O9PS3 (MW 568.40) InChI = 1S/C18H15O9PS3.3Na/c19-29(20,21)16-7-1-4-13(10-16)28(14-5-2-8-17(11-14)30(22,23)24)15-6-3-9-18(12-15)31(25,26)27;;;/h1-12H,(H,19,20,21)(H,22,23,24)(H,25,26,27);;;/q;3*+1/p-3 InChIKey = MYAJTCUQMQREFZ-UHFFFAOYSA-K (the title reagent, among all the water-soluble ligands, is most widely used for carbon-carbon, carbon-hydrogen, and carbon-heteroatom formations3) Alternate Name: TPPTS, trisodium salt of 3,3′,3′′-phosphanetriylbenzenesulfonic acid, tris(3-sulfonatophenyl)phosphine sodium salt, triphenylphosphine-3,3′,3′′-trisulfonic acid trisodium salt. Solubility: soluble in H2O (1100 g/L). Form Supplied in: white powder. Analysis of Reagent Purity: TPPTS ligand is supplied in the presence of a variable amount of TPPTS oxide. 31P{1H} NMR (D2O, 200 MHz, 25 °C) δ = −4.8 ppm (δ = 34.2 ppm for oxide), 1H NMR (D2O, 200 MHz, 25 °C) δ = 7.86 (m, 3*2H), 7.54 (m, 3*2H) ppm (same signals at 8.14 and 7.78 ppm for oxide). Preparative Methods: TPPTS is synthesized by sulfonation of triphenylphosphine with oleum (i.e., concentrated H2SO4 and SO3). Various parameters (triphenylphosphine/oleum ratio,wt % of SO3, time, temperature, and agitation speed) have been studied and modified to suppress the formation of by-products such as phosphines with a low degree of sulfonation and phosphine oxides.1 One particularly attractive method employs orthoboric acid B(OH)3, concentrated H2SO4, and a controlled SO3 concentration and cleanly affords either disulfonated ligand (TPPDS) or TPPTS with negligible oxidation and no by-products.2 Purification: the purification of TPPTS is based on its higher solubility in water compared to mono- and disulfonated phosphines and lower solubility in methanol/water than the phosphine oxides. The resulting acid solution may be neutralized with NaOH, Na2SO4 is then separated by adding methanol, and an optimal purity is reached via repeated precipitation from water/methanol mixtures.1 Another process employs the extraction of the sulfonic acids with triisooctylamine in toluene followed by extraction with an aqueous NaOH solution, neutralization, and evaporation under vacuum.2 TPPTS oxide, present in variable amount in commercially available lot, may be eliminated by extraction with acetone/methanol/water (10:5:1).1b Handling, Storage, and Precautions: solid TPPTS is substantially stable to air, but bottles of TPPTS should be flushed with N2 or Ar and kept tightly closed for prolonged storage. TPPTS is slowly oxidized to the phosphine oxide in solution, therefore oxygen-free solvents are preferred.

This paper describes an efficient enantioselective conjugate addition of highly stable potassium trifluoro(organo)borates to α,β-unsaturated amides. This reaction, catalyzed by chiral rhodium(I) complexes affords Michael adducts with high yields and enantiomeric excesses up to 95%.

A formal synthesis of (−)-isoavenaciolide (1) by two different routes is reported. The first approach, leading to a key precursor 2 of (−)-isoavenaciolide (1), features the stereoselective construction of the three contiguous stereogenic centers by Evans diastereoselective reduction (d.e. = 80%) of β-hydroxy ketone 8. In the more efficient second approach, the nine-step sequence leading to the key precursor 2 involves sequential ruthenium-catalyzed hydrogenation reactions of β-keto ester 4 and β-hydroxy ketone 14 to form the two hydroxyl groups with an excellent control of the anti stereochemistry (d.e. = 99%). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

2-Bromo[5]helicene derivatives and substituted [7]helicenes have been prepared through a synthetic sequence relying on Heck-type and photocyclodehydrogenation reactions. This procedure provides a new, versatile and efficient approach to helicene derivatives. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Extracts from various organs of 25 plants of Brazilian traditional medicine were assayed with respect to their anti-bacterial activities against Escherichia coli, a susceptible strain of Staphylococcus aureus and two resistant strains of Staphylococcus aureus harbouring the efflux pumps NorA and MsrA. Amongst the 49 extracts studied, 14 presented anti-bacterial activity against Staphylococcus aureus, including the ethanolic extracts from the rhizome of Jatropha elliptica, from the stem barks of Schinus terebinthifolius and Erythrina mulungu, from the stems and leaves of Caesalpinia pyramidalis and Serjania lethalis, and from the stem bark and leaves of Lafoensia pacari. The classes of compounds present in the active extracts were determined as a preliminary step towards their bioactivity-guided separation. No extracts were active against Escherichia coli.

Two original chiral diphosphines, SYNPHOS and DIFLUORPHOS, have been synthesized on multigram scales. Their steric and electronic profiles have been established in comparison with the commonly used 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and 6,6′-dimethoxy-2,2′-bis(diphenylphosphino)-1,1′-biphenyl ligands. A screening study of the four ligands in Ru II -catalyzed asymmetric hydrogenation of prochiral ketones and olefins has been performed. It revealed that the stereoelectronic features of the ligand and the substrate deeply influenced the enantioselectivities obtained in asymmetric hydrogenation, SYNPHOS and DIFLUORPHOS being fully complementary in terms of enantioselectivity for this reaction.

The synthesis of new donor-acceptor acetylene-bridged compounds was realized via organophosphorus reactions and Sonogashira couplings. These systems exhibit high fluorescence quantum yields, and excitation induces very efficient charge redistribution in the molecules. [structure: see text]

Potassium trifluoro(organo)borates, highly stable organoboron derivatives, have recently emerged as promising alternatives to other organoboron reagents. These salts have shown interesting reactivity, not only through the intermediate formation of difluoroboranes, but also in transmetallation reactions with transition metals. In numerous reactions they have proven to be more reactive than boronic acids or esters. The preparation and reactivity of these ate complexes is discussed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

This Account covers the design of Ru catalysts and ligands. Two classes of chiral phosphine ligands are prepared: the electron-rich trans-2,4-substituted phosphetanes, readily available from optically pure 1,3-diol cyclic sulfates, and atropoisomeric ligands (SYNPHOS, MeO-NAPhePHOS, bearing heterotopic biaryl moieties, and a chiral water-soluble diguanidinium binaphthyl diphosphine, Digm-BINAP). Applications of these ligands to rhodium- and ruthenium-mediated hydrogenation of ketones and olefins have been reported with high enantioselectivities. The recognition abilities of Ru-SYNPHOS for a wide range of ketones is superior to those observed with BINAP, MeO-NAPhePHOS, and MeO-BIPHEP. Several biologically active compounds have been prepared through dynamic kinetic resolution. This work gives access to a number of highly active catalysts of the type [Ru(biphosphane)(H)(eta(6)-cot)]BF(4). These catalysts have demonstrated their utility in the enantioselective hydrogenation of the tetrasubstituted cyclopentenone "dehydrodione", which leads to the commercially important perfume component Paradisone (Firmenich).

Potassium organotrifluoroborates, highly stable organoboron derivatives, participate in asymmetric 1,4-additions to enones. This reaction, catalyzed by cationic rhodium(I) complexes chelated with binap, MeO-biphep or josiphos ligand, affords 1,4-adducts with high yields and enantioselectivities of up to 99%. Careful study of the reaction parameters shows the high sensitivity of the reaction to temperature, solvent and the amount of water cosolvent. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Rh-catalyzed C-C bond asymmetric formation under basic conditions in organoaqueous or alcoholic solvents has been described using the atropoisomeric water-soluble ligand (R)-DigmBINAP. The addition of phenylboronic acid to cyclohexenone has been efficiently optimized leading to quantitative yield and enantiomeric excesses up to 98% using 1-3 mol% catalyst. Easy product-catalyst separation has been found using ethylene glycol as the reaction solvent. Other α,β-unsaturated ketones and boronic acids could be engaged in the 1,4-addition. The mole fraction of the catalyst could be decreased to 0.005% with still acceptable ee. A TON of 13200 was obtained.

MeO-NAPhePHOS represents the first example of a new series of atropisomeric diphosphines bearing heterotopic biaryl moieties. The key step of its synthesis is the diastereoselective, intramolecular, Cu(I)-promoted coupling of 1-iodonaphthol and 2-iodo-3-methoxyphenol connected by a chiral tether. (R,R)-2,4-Pentanediol is used as the chiral auxiliary in this highly selective reaction that leads to a single enantiomer of the title diphosphine. In the Ru-promoted hydrogenations of carbonyl derivatives, NAPhePHOS affords enantioselectivity levels fully comparable to those of the C(2)-symmetrical analogues, BINAP and MeO-BIPHEP respectively, thus showing that the lack of C(2) symmetry is not detrimental to the catalytic properties of atropisomeric ligands in these hydrogenation reactions.

Smooth removal of the Allyloxycarbonyl (Alloc) moiety from allylic esters, carbamates and carbonates is carried out by Pd (O) catalyzed allyl transfer to diethylamine and thio derivatives as the accepting nucleophiles. The method has been successfully used for selective deprotection of secondary amines and base sensitive substrates.

[see reaction]. An efficient multigram-scale synthesis of optically pure Boc-(2S,3R,4S)-iso-dolaproine is reported using dynamic kinetic resolution (DKR). The catalytic asymmetric hydrogenation of ethyl (4S)-3-(2'-pyrrolidinyl)-3-oxo-2-methyl propanoate hydrochloride using in situ generated Ru[(S)-MeO-BIPHEP]Br2 catalyst affords the anti beta-hydroxy alpha-methyl ester quantitatively. The two new stereogenic centers are simultaneously controlled with high diastereoselectivity.

The first asymmetric synthesis of the (4S,5R)-5-carbomethoxy-4-hydroxy-Δ2-pyrazoline in four steps is described starting from the methyl 4,4-dimethoxy-3-oxobutanoate by sequential catalytic hydrogenation and electrophilic amination.

This review summarizes some recent work in the field of homogeneous ruthenium-catalyzed hydrogenation via dynamic kinetic resolution. The hydrogenation reaction of various α-substituted β-oxo ester...

Alkylations of the stable diethyl N-(diphenylmethylene)aminomethylphosphonate (1) under solid-liquid phase-transfer catalysis (PTC) with or without solvent to give N-(diphenylmethylene) aminomethylphosphonic esters 2 are described. Acidic hydrolysis of 2 afforded diethyl (1-aminoalkyl)phosphonates 3 in good yields

A highly efficient gold-catalyzed cycloisomerization reaction of bis-homopropargylic diols is described. The cyclizations are conducted in the presence of either AuI or AuIII catalysts in MeOH at room temperature in a very short time. The reaction conditions are compatible with functional groups, such as n-butyl, phenyl, allyl, benzyl, and alcohol groups, leading to original strained dioxabicyclo[2.2.1], -[2.2.2], or -[3.2.1] ketals in good to excellent yields.

Publisher Summary This chapter illustrates a smooth and efficient methodology for the cleavage of allyloxycarbonates, allylcarbamates and allyl carboxylates using Pd(OAc) 2 / TPPTS catalyst in aqueous medium. The free parent molecules are easily isolated from the reaction mixture by simple aqueous work-up and extraction; they are generally pure enough to be used in another step without any further purification. Moreover, the use of a two-phase system affords a valuable solution for the deprotection of secondary amines which are obtained without any N-allylated side product. In addition, in a biphasic medium the recycling of the active catalyst is particularly attractive from an industrial view point. Finally, chemo selective deprotection of bifunctional molecules containing differently substituted allylic groups was performed with high efficiency. Various applications of this technique are under investigation in our laboratory, especially in the field of peptide synthesis.

The Ru(II)-catalyzed hydrogenation of α-amino-β-keto esters as their hydrochloride salts affords preparation of the corresponding anti α-amino-β-hydroxy esters under mild conditions with high diastereoselectivities and enantioselectivities via dynamic kinetic resolution.

International audience; The enantioselective synthesis of (3S, 4S)-4-hydroxy-2, 3, 4, 5-tetrahydropyridazine-3-carboxylic acid 1 is described. The two stereogenic centers in anti relationship are obtained by sequential enantio and chemoselective hydrogenation of β-ketoester in presence of chiral ruthenium catalyst and diastereoselective amination of β-hydroxyester with di t-butylazodicarboxylate.

Allylcarboxy and Allyloxycarbonyl groups can be removed without affecting dimethylallylcarboxy and cinnamylcarboxy groups in the same molecule, using Pd(0) water soluble catalyst prepared in situ, with diethylamine as allyl scavenger. Homogeneous or biphasic media are suitable; the yields of deprotection are quantitative.

International audience; Enantiomerically pure anti N-Boc-α-hydrazino-β-hydroxyesters were obtained from the corresponding β-ketoesters by hydrogenation with chiral Ruthenium catalysts and electrophilic amination of the β-hydroxyester with di-tert-butylazodicarboxylate (DBAD).

International audience; Primary and secondary alkylboranes reacted rapidly at low temperature with Li or K t-butyl-N-tosyloxycarbamate (LiBTOC or KBTOC) to give the corresponding N-Boc protected primary amines in modest to good yields (16–81%).N-Boc primary amines were obtained from the reaction of alkylboranes with Lithium or Potassium salts of t-butyl-N-tosyloxycarbamate.

Alkylations of the stable diethyl N-(diphenylmethylene)aminomethylphosphonate (1) under solid-liquid phase-transfer catalysis (PTC) with or without solvent to give N-(diphenylmethylene) aminomethylphosphonic esters 2 are described. Acidic hydrolysis of 2 afforded diethyl (1-aminoalkyl)phosphonates 3 in good yields

Ruthenium complexes catalyze the oxidation of alcohols to the corresponding ketones or aldehydes when Ca(OCl)2 or NaIO4 are used as oxygen donors in the presence of water (5–10 equiv.). The reactions take place at room temperature affording products in yields of 45–80%.

The cover picture shows the X-ray crystal structures of ruthenium and rhodium complexes of chiral 1,1′-bis(phosphetano)ferrocenes. These diphosphanes rank among the ligands inducing excellent enantioselectivities in rhodium-promoted hydrogenations of prochiral olefins. X-ray crystal structures of their metal complexes afford information about their coordinating behaviour and preferred conformations in catalytically active species. Details are discussed in the article by A. Marinetti et al. on p. 2583 ff.

Reaction of the diastereomerically pure oxazaphospholidine 3 with alkyl halides was monitored by 1H, 13C, 31P NMR and clearly showed the formation of two phosphonium intermediates with the same diastereomeric ratio as that of the final products. Benzyl halides reacted with 3 yielding a mixture of the two epimers a and b which syncrystallized into a rare addition compound.