Enantiospecific access to 10-N-substituted camphors

A general and straightforward enantiospecific access to synthetically valuable 10-N-substituted camphors (amines and secondary amides) has been developed. The synthetic method uses camphor as the starting enantiopure material and takes place in five individual steps with a high overall yield. The process involves a stereocontrolled double-Wagner-Meerwein-rearrangement strategy to generate key-intermediate 10-(triflyloxy)camphor, a peculiar and highly-reactive primary triflate, which is able to alkylate soft N-nucleophiles, such as amines and nitriles, easily and without producing Grob-like fragmentation of the β-(triflyloxy)ketone-based norbornane system.     

C10-substituted camphors and fenchones by electrophilic treatment of 2-methylenenorbornan-1-ols: enantiospecificity,scope, and limitations

Valuable chiral sources of C(10)-substituted camphors and C(10)-substituted fenchones can be straightforwardly obtained by treatment of an appropriate, easily obtainable, camphor- or fenchone-derived 2-methylenenorbornan-1-ol with an electrophilic reagent. The process takes place via a tandem regioselective carbon-carbon double-bond addition/stereocontrolled Wagner-Meerwein rearrangement. A complete study of the enantiospecificity, scope, and limitations of this process, as well as about the role played by the hydroxyl group attached at the C(1) bridgehead position of the starting 2-methylenenorbornan-1-ols, has been realized. The feasibility of the described methodology has been exemplified by the highly efficient enantiospecific preparation of several interesting C(10)-halogen-, C(10)-O-, C(10)-S-, C(10)-Se-, or C(10)-C-substituted camphors and fenchones.     

Exploring the solid-phase synthesis of 3,4-disubstituted beta-lactams: scope and limitations

This work describes a comprehensive study on the solid-phase synthesis of 3,4-disubstituted beta-lactams. In situ generated ketenes react with immobilized aldimines under mild conditions to generate libraries of beta-lactams in good to very good overall isolated yields. Different commercially available solid supports were studied, with the cost-effective Wang resin proving to be the most effective. The utility of the protocol was also demonstrated by the highly efficient asymmetric versions when homochiral ketenes or homochiral aldimines were used. A practical technique for the preparation of manual solid-phase parallel libraries of biologically interesting beta-lactam compounds, using Mukaiyama's salt as dehydrating agent, is also presented. Reactions were easily monitored by FT-IR and gel-phase 13C NMR using conventional equipment.     

2-(10-Diazo-10H-anthracen-9-ylidene)-malonodinitrile: A convenient precursor of 9,10-disubstituted anthracenes

Summary The acid promoted decomposition of 2-(10-diazo-10H-anthracen-9-ylidene)-malonodinitrile in the presence of water, methanol, ethanol, acetic and propionic acid, ethyl thioglycolate,p-thiocresole, and acetyl acetone yielding 9,10-disubstituted 9,10-dihydroanthracenes was investigated. Treatment of the reaction products with tri-ethyl amine followed by hydrochloric acid caused their tautomerization to the corresponding 9,10-disubstituted anthracenes. A mechanism for this reaction is proposed. The first example of an intermolecular C-C-bond formation during the protic acid promoted decomposition of a diazo compound in the presence of CH-acids was found. An improved procedure for the preparation of the starting diazo compound, which may serve as a convenient precursor of 9,10-disubstituted anthracenes, is described.Cordially dedicated to Prof. Dr.K. Winsauer on the occasion of his 70^th birthday     

Thermochemical properties from ab initio calculations: π- and σ-Free radicals of importance in soot formation: •C3H3 (propargyl), •C4H3, •C13H9 (phenalenyl), •C6H5 (phenyl), •C10H7 (naphthyl), •C14H9 (anthryl), •C14H9 (phenanthryl), •C16H9 (pyrenyl), •C12H7 (acenaphthyl), and •C12H9 (biphenylyl)

The calculated difference in the standard heat of formation Δ Δ_fH°(298.15) of n- and i-C₄H₃^• free radicals is 37.9 kJ mol⁻¹ for G3MP2B3 and 45.0 kJ mol⁻¹ for CCSD(T)-CBS (W1U) calculations, which seems to preclude the direct even-carbon radical pathway to benzene and higher PAH (polycyclic aromatic hydrocarbon) formation including soot in a hydrocarbon flame. For the phenyl-type σ-radicals listed in the title, absolute values of Δ_fH°(298.15) have been calculated using G3MP2B3-computed values of bond dissociation energies D°(298.15) and combined with experimental values of Δ_fH° (298.15) for the parent hydrocarbon because of a slight systematic overprediction of the thermodynamic stability of large PAHs by the applied computational G3MP2B3 method. Standard enthalpies of formation Δ_fH°(298.15) as well as absolute entropies S° and heat capacities C°_p are given for a series of π- and σ-free radicals important to combustion as a function of temperature. A spread of roughly 40 kJ mol⁻¹ in the average C H bond strength of PAH leading to σ-radicals has been calculated, the lowest leading to 4-phenanthryl (463.6 kJ mol⁻¹), the highest leading to 2-biphenylyl radical (502.5 kJ mol⁻¹). © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 395–415, 2008     

Amine-directed hydroboration: scope and limitations

Iodine activation induces intramolecular hydroboration of homoallylic and bis-homoallylic amine boranes with good to excellent control of regiochemistry compared to control experiments using excess THF*BH 3. Deuterium labeling and other evidence confirm that the iodine-induced hydroboration reaction of homoallylic amine boranes occurs via an intramolecular mechanism equivalent to the classical 4-center process and without competing retro-hydroboration. Longer carbon chain tethers result in lower regioselectivity, whereas the shorter tether in allylic amines results in a switch to dominant intermolecular hydroboration. Regioselectivity in THF*BH 3 control experiments is higher for the allylic amine boranes compared to the iodine activation experiments, whereas the reverse is true for homoallylic amine borane activation.     

Stereoselective epoxidation of 5(10),9(11)-estradienes

3,3-(2,2-Dimethyltrimethylene-1,3-dioxy)-5(10),9(11)-estradien- 17-one is converted to its 5α,10α-epoxide by iron phthalocyanine/iodosylbenzene in a highly stereoselective manner.     

A new access to 3,5-disubstituted piperazinones via Pd(0)-catalyzed amination

An original synthetic route toward 3,5-disubstituted piperazinones has been developed. The method relies upon a 6-exo intramolecular process between a sulfonylated nitrogen atom of amino acid derivation and an η³-allyl-palladium moiety. This cyclization process generates the two possible (cis and trans) diastereoisomers whose ratio depends on the amino acid employed. The bulkier the amino acid residue, the higher the observed cis:trans ratio. Convincing evidence for reversible intramolecular addition of the nitrogen nucleophile to the η³-allyl-palladium complex is put forward.     

The solid-phase Nicholas reaction: scope and limitations

Two libraries of alpha-substituted alkynes has been prepared on solid phase using a sequential Sonogashira/Nicholas reaction approach. The scope of nucleophiles in the Nicholas reaction on solid phase has been investigated, including carbon, oxygen, nitrogen, sulfur, fluoride, and hydride nucleophiles. The conditions for the reaction sequence have been optimized in terms of Lewis acid, catalyst for the Sonogashira step, temperature, reaction time, and decomplexation method, enabling the five-step sequence to be performed in 1 day.     

[(NHC)AuCl]-catalyzed Meyer-Schuster rearrangement: scope and limitations

An efficient catalytic system allowing for the synthesis of a variety of α,β-unsaturated ketones has been developed. [(NHC)AuCl] (NHCN-heterocyclic carbene) in the presence of a silver(I) salt was found to catalyze the Meyer-Schuster rearrangement, leading to α,β-unsaturated ketones from easily accessible propargylic alcohols in high yields. Catalysis was performed in a 2:1 mixture of methanol and water at 60 °C and afforded good yields even for tertiary alcohols and sterically demanding substrates. Thorough evaluation of the present catalytic system uncovered that it was unsuitable for terminal alkynes and primary alcohols. In these cases low yields of the target molecules were obtained due to the formation of unexpected by-products.     

Microwave-promoted insertion of Group 10 metals into free base porphyrins and chlorins: scope and limitations

The scope and limitations of microwave heating as a tool for insertion of Group 10 metals into meso-tetraphenyl-porphyrin, -porpholactone, and -2,3-dihydroxychlorin derivatives are discussed. In some cases it is possible to reduce reaction times dramatically while obtaining good yields of the metallated products while in others new issues arise relating to the metal salt used as well as acceleration not only of the metallation reaction but also of byproduct formation.     

Gold(I)-catalyzed intermolecular hydroarylation of allenes with nucleophilic arenes: scope and limitations

The addition of nucleophilic methoxyarenes to allenes proceeds at room temperature in dichloromethane with a catalytic amount of phosphite-gold(I) precatalyst and silver additive. The addition is regioselective for the allene terminus, and generates E-allylation products without the need for prefunctionalization of the synthons as organometallics or allyl bromides. Coordinating heteroaromatics and sterically hindered allenes do not participate in the reaction.     

Skin-photosensitizing properties of Zn(II)-2(3), 9(10), 16(17), 23(24)-tetrakis-(4-oxy-N-methylpiperidinyl) phthalocyanine topically administered to mice

A Zn-phthalocyanine derivative bearing four 4-oxy-N-methyl-piperidinyl peripheral substituents has been formulated in an azone-containing gel for topical administration and its potential as a photodynamic therapy agent has been investigated. The phthalocyanine displays an intense absorbance in the 680 nm range and shows a high photosensitizing activity toward a model biological substrate (N-acetyl-L-tryptophanamide). Upon administration of 20 microg cm(-2) onto the dorsal skin of Balb/c mice, maximal phthalocyanine concentrations (ca. 64.2 ng mg(-1) of skin) are reached at 1 h after the deposition. The photosensitizer appears to be localized in the epidermal layers, since (a) no detectable amounts of phthalocyanine are recovered from the mouse blood and liver; and (b) upon photoactivation with a diode laser at 675 nm, only the epidermis is heavily damaged, as shown by histological and ultrastructural analysis. The photodamage is largely of inflammatory nature and an essentially complete healing of the damaged skin is observed at 72 h after the end of the phototreatment. The minimal phototoxic dose for 20 microg cm(-2) photosensitizer and 675 nm irradiation is found to be (150 mW cm(-2)-120 J cm(-2)) or (180 mW cm(-2)-100 J cm(-2)).