59557-05-0

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Ethynylbenziodoxol(on)e (EBX) cyclic hypervalent iodine reagents are now established reagents for the alkynylation of radicals and nucleophiles, yet they present limited possibilities for further structure and reactivity modification. Herein, the first synthesis is reported for the corresponding ethynylbenziodazolone (EBZ) reagents, in which the oxygen atom in the iodoheterocycle is replaced by a nitrogen atom. The substituent on the nitrogen enables further fine-tuning of the reagent structure and reactivity. EBZ reagents are obtained easily from the corresponding benzamides by using a one-step procedure, and display reactivity comparable to that of EBX reagents. In particular, they are applied in an asymmetric copper-catalyzed oxyalkynylation of diazo compounds, which proceeds in high yield and enantioselectivity for a broad range of substituents on the diazo compounds and the alkyne.

We describe here an operationally simple and straightforward synthesis method for a series of diverse 4,5-disubstituted 1,2,3-thiadiazoles via the nucleophilic addition of α-diazo carbonyl compounds to carbon disulfide. This method features using abundant and inexpensive carbon disulfide under mild reaction conditions.

Enantioselective catalytic methods allowing the addition of both a nucleophile and an electrophile onto diazo compounds give a fast access into important building blocks. Herein, we report the highly enantioselective oxyalkynylation of diazo compounds usi

The direct carboxylation of the ipso-C(sp2)-H bond of a diazo compound with carbon dioxide under mild reaction conditions is described. This method is transition-metal-free, uses a weak base, and proceeds at ambient temperature under atmospheric pressure in carbon dioxide. The carboxylation exhibits high reactivity and is amenable to subsequent diversification. A series of unsymmetrical 1,3-diester/keto/amide diazo compounds are obtained with moderate to excellent yields (up to 99%) with good functional group compatibility.

In the presence of sodium acetate, the reaction between 2,2,6-trimethyl-4H-1,3-dioxin-4-one and secondary or tertiary alcohols (including chiral ones) or primary or secondary amines could be carried out in refluxing tetrahydrofuran, under much milder conditions than those described in the literature. In these new conditions, side products normally observed using the traditional protocol were avoided, and-keto esters and-ketoamides were normally obtained in quantitative yields.

The present invention provides a cooling component or sensate component which has further strong cooling intensity and is excellent in the persistency or refresh-feeling and cool-feeling, a sensate composition comprising the same, and various products comprising the sensate composition. The present invention relates to, as a cooling component or sensate component, (3R)-1-menthyl 3-hydroxybutyrate represented by the following formula (I):

An efficient and practical method has been manifested for the diversity-oriented synthesis of quinolines via Friedlaender annulation reaction for the generation of a wide range of structurally interesting and pharmacologically significant compounds by using eerie ammonium, nitrate as a catalyst (10 mol %) at ambient temperature in 45 min, A variety of functional groups are introduced at various positions of the quinoline moiety, and further the diversity of the core skeleton was expanded at R1 and R 2 positions by the synthesis of various hybrids. Initial screening of the compounds for cytotoxicity against a series of cancer cell lines showed promising results.

The present invention provides a cooling component or sensate component which does not have undesirable stimulus feeling, bitterness and the like and is excellent in the persistence of refresh-feeling and cool-feeling, a sensate composition which comprise

Intermolecular O-H insertion reactions of rhodium carbenoids generated from chiral diazoacetoacetates are less efficient and less stereoselective than the reactions of those generated from the corresponding phenyldiazoacetates. Nevertheless, when the diazoacetoacetate is connected to a phenolic moiety through a 2,4-pentanediol tether, the carbenoid generated shows a high potential in both efficiency and stereoselectivity during the intramolecular O-H insertion reaction to give a cyclic ether in up to 88% diastereomeric excess (de) in quantitative yield. The de value depends on the structure of the tether, but is independent of the catalyst employed. The isomerization of the cyclic ether has been studied under the conditions of equilibrium and kinetic protonation of the corresponding enolate. The similarity between the de values obtained by insertion and those obtained under equilibrium suggests that the rhodium catalyst is eliminated during the early stages of the O-H insertion reaction and that proton transfer, which determines the stereoselectivity, occurs after the elimination of the rhodium metal, independent of the stereochemistry of the initial addition. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

An efficient and environmentally benign boric acid catalyzed protocol for the transesterification of ethyl acetoacetate with a variety of primary and secondary alcohols in good to excellent yields is described. The versatility of this transformation is demonstrated with problematic substrates such as propargyl alcohol and allyl alcohol, which are known to undergo Carroll rearrangement during transesterification.

The use is described of a compound of the formula (I) or (ent-I) or a blend consisting of two, three or more compounds of the formula (I) or (ent-I) (a) as a cooling substance for non-therapeutic purposes or (b) for the production of a medicament, wherein in each of the formulae (I) and (ent-I) R1, R2, R3, R4 and R5 mutually independently in each case mean hydrogen or a linear, branched or cyclic, saturated or unsaturated hydrocarbon residue having 1 to 4 carbon atoms.

Treatment of methyl or ethyl β-keto esters with primary, secondary, or tertiary alcohols in the presence of a catalytic amount of hexamethylenetetramine results in good to high yields of the corresponding esters. Georg Thieme Verlag Stuttgart.

Bromodimethylsulfonium bromide has been found to be an effective and regioselective reagent for α-monobromination of β-keto esters and 1,3-diketones. A wide variety of β-keto esters and 1,3-diketones undergo chemoselective α-monobromination with excellent yields at 0-5 °C or room temperature. The notable advantages of this protocol are no need of chromatographic separation, use of less hazardous reagent than molecular bromine, and no added base, Lewis acid, or other catalyst.

(Chemical Equation Presented) Chiral multifunctionalized pyrrolines have been synthesized by a ruthenium porphyrin catalyzed three-component coupling reaction. In a one-pot reaction, ruthenium porphyrins catalyzed in situ generation of chiral azomethine ylides from chiral diazo esters and imines. Asymmetric 1,3-dipolar cycloaddition reactions of the chiral azomethine ylides with dipolarophiles afforded the corresponding pyrrolines in good yields and high diastereoselectivity (up to 92% de).

NaIO4, KIO4 and anhydrous CaCl2 catalyzed selective transesterification of β-keto esters is described. Neutral reaction conditions and inexpensive catalysts are important features of this method.

A facile transesterification of β-ketoesters using catalytic iodine is described.

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A process for the transesterification of keto esters and alcohols in approximately stoichiometric amounts using a solid acid catalyst. Solid acid catalysts may be sulfated zirconia, sulfated tin oxide, sulfated titania, sulfated iron oxide, heteropoly acids, acidic clays, acidic zeolites, or any other solid acids with high acidity or super acidity, with or without dopants. One equivalent or more of keto ester, one equivalent or more of alcohol, the solid acid catalyst, and an appropriate solvent are mixed and heated to 70 to 120° C. at atmospheric or reduced pressure to furnish the keto transester in high yields.

The transesterification of ketoesters using zinc and iodine is described. The reaction has been done on a variety of alcohols and phenols. Alcohols furnish transesterified products whereas phenols gave 4-methylcoumarins. The method is highly promising compared with existing methods.

Facile and selective transesterification of β-keto esters using N-bromosuccinimide (NBS) as an efficient and neutral catalyst is described.

Microwave technique has been utilised in the preparation of β-keto esters. Two different procedures are described: transesterification of β- keto esters and ring opening of 2,2,6-trimethyl-1,3-dioxin-4-one.

A spiro sesquiterpene alcohol, (-)-gleenol (1) was synthesized from (-)-1-menthol in 16 steps, using the C-H insertion reaction of the alkylidenecarbene as the key step. The absolute configuration of (-)-1 was determined to be IS, 6R, 7S. 10R.

Non-naturally occuring dynemicin analogs are provided, which are useful as DNA cleaving agents, cytotoxic agents, and/or anti-tumor compounds. Methods of making dynemicin analogs are also provided.

Substituted α-silylacetic esters have been prepared in good yields and with reasonable diastereoselectivities by three different routes. The first two involved alkylation of the parent α-silylacetic ester enolates, with the chiral auxiliaries being present either on silicon or on the ester function. The third route involving asymmetric insertion of metal-carbenoids into the Si-H band was found to afford better diastereoselectivities, using pantolactane as chiral auxiliary.

An enantioselective synthetic route to (+)-dynemicin A (1) is described that involves as the key and final step the Diels-Alder cycloaddition of the quinone imine 6 with the isobenzofuran 107 followed by an oxidative workup to provide (+)-1 in 40% yield. The synthetic route begins with the condensation of (-)-menthyl acetoacetate and trans-ethyl crotonate to form the crystalline cyclohexanedione 14, which is then transformed to the enantiomerically pure quinone imine 6 in 23 steps with an average yield of 85% and an overall yield of 2-3%. Key features of this sequence include the coupling of the enol triflate 11 and the arylboronic acid 10 (90%), the thermal deprotection/internal amidation of the coupling product 18 (84%), the use of 2-chloropyridine as an economical alternative to 2,6-di-tert-butylpyridine to promote the reaction of the quinolone 9 and triflic anhydride (85%), the highly stereoselective addition of the (Z)-enediyne 31 to the quinoline 61 (89%), intramolecular acetylide addition within the acetylenic ketone 66 (94%), and oxidation of the phenol 76 with iodosobenzene to afford the quinone imine precursor 77 in 89% yield. Both the quinone imine and isobenzofuran components of the final coupling reaction can be varied, thus providing an ideal route for the preparation of a wide variety of dynemicin analogs.

Chiral non-raemic α,α'-dioxothiones 2a-g and 17 are obtained from chiral β-ketoesters using the phthalimidesulfenyl chloride 1 as key reagent. The ability of these thiones to discriminate between the enantiotopic faces of several dienophiles has been evaluated. The best diastereoisomeric excesses (67-80%) were obtained when the a-acyl thiones were involved as electron-poor dienes in inverse electron demand Diels-Alder reactions with electron-rich styrenes as dienophiles. The possibility to obtain thiones bearing two chiral groups as well as the reactions where the a-acyl thiones 2 participate as dienophiles are also shown.

The stereochemical outcome of the 1,3-dipolar cycloaddition of nitrilimines to γ-oxygenated α,β-unsaturated enones and esters was investigated. By means of X-ray and NMR analysis the main diastereomers were assigned as the syn-derivatives. Novel enantiomerically pure nitrilimines were included in the investigations but did not influence the stereochemical course of the cycloaddition significantly.

α-silyl-α-substituted acetic esters have been prepared in good yields and reasonable diastereoselectivities using an asymmetric metal carbene insertion into the Si-H bond. Optically active 1,2-diols were then prepared after reduction of the ester and conv

The development of new methods for the asymmetric synthesis of highly functionalized 2-amino-4-aryl-4H-pyrans is described.Two alternative synthetic routes: the 1,4-conjugate addition of chiral β-ketoesters 3 or the N-acetoacetyl sultam 11 to arylidenemal

Carboxylate and carboxamide ligands on dirhodium(II) catalysts can provide enormous regiocontrol in carbon-hydrogen insertion reactions of diazoacetate esters. Whereas 2,3,4-trimethyl-3-pentyl diazoacetoacetate (1) forms γ-lactone products from insertion into primary and tertiary C-H bonds in a statistical distribution (61:39) with dirhodium(II) tetrakis(perfluorobutyrate), only tertiary C-H insertion is observed with dirhodium(II) tetraacetamide. Similar results are obtained with 2-methyl-2-octyl diazoacetoacetate (3), where competition for insertion exists between secondary and primary C-H bonds and electronic factors govern regioselection. However, with 2-methyl-3-isopropyl-3-heptyl diazoacetoacetate (2) and 2-methyl-l-phenyl-2-propyl diazoacetoacetate (4), product distributions from C-H insertion are invariant with the dirhodium(II) ligands; insertion into a secondary C-H bond is favored over tertiary C-H insertion with 2 (95:5), and insertion into a primary C-H bond is preferred to benzylic secondary C-H insertion with 4 (70:30). In such cases, which are amenable to analyses by MM2 calculations, regioselectivity is determined by conformational preferences for which C-H insertion selectivity can be as random as that found with 2 and 4. When only one C-H bond site is available for insertion to form a five-membered ring product, only one γ-lactone is observed from reactions catalyzed by dirhodium(II) tetraacetate, and that product is not necessarily the one predicted by presumed electronic preferences.

Rhodium(II) acetate and rhodium(II) acetamide catalyzed decomposition of diazo esters forms γ-lactones in high yield and with exceptionally high regio- and diastereoselectivity.

Onium salt and acid catalyzed addition of diketene to (-)-menthone gives improved yields of 2 and 3.Excess of diketene leads to diastereomeric mixtures of compounds 4 and 6 from menthone and menthol, respectively. - Key words: 1,3-Dioxin-4-ones from Ketones

Cyclization of 3, prepared from 1-menthol, led to a 1:1 mixture of 4 and 5.These diastereomeric ketones, readily separated by chromatography, are versatile intermediates for the preparation of alkylated cyclohexanones.The absolute configuration of 5 was assigned by conversion to the known hydroxy ketal 9.This approach works equally well for the cyclopentane series.Thus, alkylated cyclohexanones and cyclopentanones of known absolute configuration will for the first time be routinely available.

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