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In this account, we summarize our work on the synthesis of monofluoroalkenes starting from difluoropropenes. 1 Introduction 2 Metal-Catalyzed Transformations of 3,3-Difluoropropenes 2.1 Palladium Catalysis 2.2 Platinum Catalysis 3 Metal-Free Reactions 3.1 Organolithium Reagents 3.2 Lithium Amides 4 Conclusions

The synthesis of monofluoroalkenes using a Pt-catalyzed amination reaction of cyclic 3,3-difluoropropenes is reported. The use of secondary aliphatic amines and cyclic 3,3-difluoropropenes is necessary for the success of the reaction.

The direct formation of C—F bonds by photodecarboxylation of aryloxyacetic acid derivatives is developed.

Upon irradiation a number of N-mesyloxylactams such as (I), (IV), (VI), and (VIII) undergo efficient ring-contraction yielding pyrrolidine, piperidine, and azepane derivatives.

The solid-state structure of nefopam methiodide, a quaternary ammonium salt of nefopam hydrochloride (a non-narcotic analgesic drug), has been determined by single crystal X-ray diffraction analysis. Nefopam methiodide gives crystals belonging to the monoclinic P21/c space group and, at 298 K, a = 10.001(1), b = 9.928(1), c = 17.598(1) A, β = 94.41(1)°, V = 1742.2(2) A3, Z = 4, R(F) = 0.086, and Rw(F) = 0.108. Due to disorder, the boat (flattened chair) and twist-chair (flattened chair) conformations of the 2,5-benzoxazocine eight-membered ring were both observed in the crystal with 55:45 occupancy, respectively. Positional disorder was also observed for the iodide counterion, which showed occupancies of 81:9.5:9.5. Keywords: nefopam, analgesic, X-ray crystallography, conformation.

Alkylsilylketeneacetals have been prepared by a one-step copper-catalyzed 1,4-addition of Grignard reagents to acrylic, crotonic, methacrylic and 3,3-dimethylacrylic esters in the presence of ClSiMe3. Their Z/E ratio could be modified using CuI (in the presence of HMPA) or CuII salts (without HMPA).

The solid-state structure of (–)-α-lobeline hydrobromide has been determined by single crystal X-ray diffraction analysis. (–)-α-Lobeline hydrobromide gives crystals belonging to the orthorhombic P212121 space group, and at 298 K: a= 6.0100(3), b= 11.7177(4), c= 28.977(2)A, V= 2040.7(2), Z= 4, R(F)= 0.030, and Rw(F)= 0.022. The (2R,6S,CβS)-absolute configuration was determined from the effects of anomalous dispersion of the bromine atom. The N-methyl group exists in an axial configuration similar to that previously described for the hydrochloride salt. However, in the hydrobromide salt the β-hydroxyphenethyl residue exhibits a different conformation from that noted for the hydrochloride salt. 1H and 13C NMR spectroscopy for the hydrochloride salt dissolved in CD2Cl2 shows axial- and equatorial-N-methyl solution-state diastereoisomers in the ratio ca. 5 : 1, respectively. The major contributors to the time-averaged structures of the salt in D2O and the free base in CDCl3 also show axial N-methyl orientations. Conformational differences for the acetophenonyl and β-hydroxyphenethyl moieties were found in the two N-methyl epimers, as well as in the time-averaged salt (D2O) and free base (CDCl3) structures. The putative bioactive conformation of the nicotine agonist was found to have a different acetophenonyl arm conformation than that found in both crystals.

Upon irradiation 6- and 7-membered N-chlorolactams are found to undergo novel ring contraction yielding pyrrolidine or piperidine derivatives.

A model 15-membered trans-cis-cis macrocyclic triene, (trans-cis-cis)-tetramethyl (4E,11Z,13E)-5-formylcyclo-pentadeca-4, 11,13-triene-1,1,8,8-tetracarboxylate, C 24 -H 32 O 9 , was synthesized and led to the exclusive formation of a trans-syn-cis [6.6.7] tricyclic compound upon a transannular Diels-Alder reaction. The structure of the precursor and a p-bromobenzoyl analog of the product, (trans-syn-cis)-tetramethyl rac(1S,2S,7R,10R)-(8Z)-1-(4-bromobenzoyloxymethyl)tricyclo[8.5.0.0 2,7 ]pentadec-8-ene-5,5,13,13-tetracarboxylate ethanol solvate, 3C 31 H 37 BrO 10 .0.76C 2 H 6 O, were determined in order to establish their exact geometries and ring-junction stereochemistries.

A novel 14-membered macrocyclic ring with trans-trans-trans triene geometry, trimethyl (4E,10E,12E)-(1R*,14S*)-5-methyl-17-oxobicyclo[12.3.0]heptadeca-4,10,12-triene-1,8,8-tricarboxylate, C 24 H 32 O 7 , which usually undergoes a Diels-Alder cycloaddition upon formation, has been isolated. From four possible contractions, the transannular reaction produces three adducts from which trimethyl rac-(5β,9β,10α)-17-oxoandrost-6-ene-3,3,18-tricarboxylate, C 24 H 32 O 7 , was isolated and crystallized.

Reversible prototropic shifts from a stable 14-membered ring macrocycle (4Z, 10E, 12Z) - [1R * , 14S*]-1,8,8-tris-(methoxycarbonyl)-5-methyl-3,17-dioxobicydo[12.3.0]-heptadeca-4,10,12-triene, C 24 H 30 O 8 , occurred when the compound was heated to form rac-(5Z,11Z,13Z)-1,8,8-tris(methoxycarbonyl)-5-methyl-3,l7-dioxobicyclo-[12.3.0]heptadeca-5,11,13-triene, C 24 H 30 O 8 . The resulting compound crystallizes in a highly disordered fashion. After a transannular Diels-Alder reaction, the resulting adduct rac-3,3-bis(methoxycarbonyl)-18-oxo-5α,9β-androst-6-en-11,17-dione, C 24 H 30 O 8 , was then easily converted to a 5α-steroid core, rac-3,3-bis-(methoxycarbonyl)-18-oxο-5α-androst-6-en-11,17-dione, C 24 H 30 O 8 . The final adduct is an highly advanced intermediate for the total synthesis of naturally occurring aldosterone.

A chiral polynuclear Gd complex derived from Gd(OiPr)3 and FujiCAPO (2 or 3) catalytically generated Gd enolates through two distinct methods; transmetalation from enol silyl ethers and conjugate addition of cyanide to α,β-unsaturated N-acyl pyrroles. These chiral enolates can be enantioselectively protonated by a proton in an asymmetric environment in the polynuclear catalyst. Thus, catalytic enantioselective protonation of enol silyl ethers was promoted by the Gd catalyst (5−10 mol %) in the presence of a stoichiometric amount of 2,6-dimethylphenol. Kinetic studies and dependencies of the enantioselectivity on the silyl group structure and the proton source suggest that the reaction proceeds through a Gd enolate generated through transmetalation. Moreover, the same Gd complex (5−10 mol %) promoted conjugate addition of a cyanide−enantioselective protonation sequential reaction from α,β-unsaturated N-acyl pyrroles. Because Gd isocyanide was determined to be the active nucleophile in the conjugate additio...

An investigation is undertaken into the roles of pro-tecting groups and the solvent in the electrochemical-mediated -glycosylation of MANNO thioglycosides. Herein notable differences are observed between electrochemical and chemical glycosylation.

We report herein the first total synthesis of the alkaloid manzacidin D, in 11 steps and 16% overall yield from commercially available glycine tert-butyl ester hydrochloride. Our synthesis demonstrates for the first time in a total synthesis the utility of two different methodologies. A highly diastereoselective iodocyclization of an olefinic isothiourea is used to induce stereocontrol at the quaternary centre, and to form the heterocyclic core. Conversion of a thiourea to the requisite formamidine is achieved in good yield using our modified procedure.