A stereoselective approach to the synthesis of pseudodistomin D

A stereoselective total synthesis of the core unit of pseudodistomin D, starting from l-serine, is described. The key step is a stereoselective intramolecular Michael reaction in which the piperidine ring is formed with the obtention of 1.     

Rh(I)/DpenPhos catalyzed asymmetric hydrogenation of enol esters and potassium (E)-3-cyano-5-methylhex-3-enoate

Rh(I) complexes of a class of modular chiral monodentate phosphoramidites were highly efficient for the asymmetric hydrogenation of enol esters bearing α-aryl or α-alkyl groups, to afford the corresponding hydrogenation products in high enantioselectivities (87–95% ee) and reactivities (turnover number up to 10,000). These ligands were also shown to be effective in Rh(I)-catalyzed asymmetric hydrogenation of the potassium salt of (E)-3-cyano-5-methylhex-3-enoate, to give the corresponding product (a precursor to CI-1008) with up to 95% ee and complete conversion of substrate.     

A general method for the asymmetric synthesis of both enantiomers of 1-substituted 1,2,3,4-tetrahydro-β-carbolines employing pyroglutamic acid derivatives as chiral auxiliaries

9-(S)-Pyroglutaminyl-β-carbolines were allowed to react with a nucleophile (allyltributyltin or a silyl enol ether) in the presence of 2,2,2-trichloroethyl chloroformate to give 1,2-addition products in good yields and high diastereoselectivity. The chiral auxiliary at N-9 was readily removed by a mild hydrolysis. The same chiral source afforded both enantiomers by simply altering a protecting group of the amide nitrogen. That is, (S)-pyroglutaminyl groups which had an N-alkyl group afforded the (S) isomer, whereas the ones having an N-acyl group produced the (R) isomer of the addition products.     

Palladium‐Catalyzed Hydrolytic Cleavage of Aromatic C−O Bonds

Metallic palladium surfaces are highly selective in promoting the reductive hydrolysis of aromatic ethers in aqueous phase at relatively mild temperatures and pressures of H₂. At quantitative conversions, the selectivity to hydrolysis products of PhOR ethers was observed to range from 50 % (R=Ph) to greater than 90 % (R=n ‐C₄H₉, cyclohexyl, and PhCH₂CH₂). By analysis of the evolution of products with and without incorporation of H₂¹⁸O, the pathway was concluded to be initiated by palladium metal catalyzed partial hydrogenation of the phenyl group to an enol ether. Water then rapidly adds to the enol ether to form a hemiacetal, which then undergoes elimination to cyclohexanone and phenol/alkanol products. A remarkable feature of the reaction is that the stronger Ph−O bond is cleaved rather than the weaker aliphatic O−R bond.     

Deoxy-nitrosugars. 9th communication. Chain elongation of 1-C -nitroglycosyl halides by substitution with some weakly basic carbanions

The 1-C-nitroglycosyl chloride reacted with the anions form 2-nitropropane, nitromethane, and diethyl malonate, to give the chain-extended products 2 (81%), 5 (72%), and 6 (83%), respectively. Treatment of the 1-C -nitroglycosyl bromide 7 by the lithium salt obtained form 8 gave the dodecodiulose derivative 9 (76%). Th β-D-configuration of 2 and 9 was inferred form their NMR and CD spectra. Treatment of 2 and 9 with sodium sulfide gave the enol ethers 3 (96%) and 10 (92%), respectively. The (Z)-configuration of 10 was deduced form the configuration of its hydrogenation product 11 .     

Asymmetric synthesis of 2,4,5-trisubstituted piperidines from sulfinimine-derived delta-amino beta-ketoesters. Formal synthesis of pseudodistomin B triacetate

[reaction: see text] N-Sulfinyl delta-amino beta-ketoester enaminones, a new sulfinimine-derived chiral building block, undergoes, on hydrolysis in one pot, an intramolecular Michael addition followed by a retro-Michael-type elimination to give enantiopure 2,4,5-trisubstituted piperidines, a structural motif found in numerous biologically active alkaloids. This new chiral building block is readily prepared by treating N-sulfinyl delta-amino beta-ketoesters with dimethylformamide dimethyl acetal. This new protocol was illustrated with a concise formal asymmetric synthesis of marine alkaloid pseudodistomin B triacetate.     

Acrolein hydrogenation on Pt(211) and Au(211) surfaces: a density functional theory study

Partial hydrogenation of acrolein, the simplest α,β-unsaturated aldehyde, is not only a model system to understand the selectivity in heterogeneous catalysis, but also technologically an important reaction. In this work, the reaction on Pt(211) and Au(211) surfaces is thoroughly investigated using density functional theory calculations. The formation routes of three partial hydrogenation products, namely propenol, propanal and enol, on both metals are studied. It is found that the pathway to produce enol is kinetically favoured on Pt while on Au the route of forming propenol is preferred. Our calculations also show that the propanal formation follows an indirect pathway on Pt(211). An energy decomposition method to analyze the barrier is utilized to understand the selectivities at Pt(211) and Au(211), which reveals that the interaction energies between the reactants involved in the transition states play a key role in determining the selectivity difference.     

The photo-Nazarov cyclisation of 1-cyclohexenyl-phenyl-methanone revisited: II: Reaction between primary and secondary key intermediates

Trans-1-cyclohexenyl-phenyl-methanone (2) and enol 4, both key intermediates in the title reaction, react with each other in a Michael-type addition to form predominantly enol 10. This enol, kinetically stable but too reactive to be isolated, reveals its presence in the irradiated solutions by formation of the isomeric ketone 11 on acid catalysis, and by formation of the oxidation product 9 on exposure to atmospheric oxygen. In the absence of acid, formation of 10 competes significantly with the title reaction of cis-1-cyclohexenyl-phenyl-methanone (1). In a secondary photoreaction of 10, 1,6-hydrogen abstraction by the excited carbonyl group and cyclisation afford 13 and 14. Enols 4, 10, and 13, in striking contrast to enol ethers and to thermodynamically stable enols, are unstable towards atmospheric oxygen. Thus, 4 autoxidises to form five compounds (Ox-1 through Ox-5), 10 to form 9, and 13 to form 15.     

Diastereoselective synthesis of substituted tetrahydroquinoline-4-carboxylic esters by a tandem reduction-reductive amination reaction

A diastereoselective synthesis of 1-methyl-2-alkyl- and 2-alkyl-1,2,3,4-tetrahydroquinoline-4-carboxylic esters has been developed from methyl (2-nitrophenyl)acetate (1). The method involves alkylation of 1 with an allylic halide, ozonolysis of the double bond, and catalytic hydrogenation. The final hydrogenation initiates a tandem sequence involving (1) reduction of the aromatic nitro group, (2) condensation of the aniline or hydroxylamine(8) nitrogen with the side chain carbonyl, (3) reduction of the resulting nitrogen intermediate, and (4) reductive amination of the tetrahydroquinoline with formaldehyde produced in the ozonolysis to give a methyl (+/-)-1-methyl-2-alkyl-1,2,3,4-tetrahydroquinoline-4-carboxylate. Removal of the formaldehyde prior to hydrogenation gives the simple (+/-)-2-alkyl derivatives. The products are isolated in high yield as single diastereomers having the C-2 alkyl group cis to the C-4 carboxylic ester. The reaction has been extended to the synthesis of tricyclic structures with similar high diastereoselection.     

Heterocyclic analogs of prostaglandins: III. Synthesis of 10-oxa-13-aza, 11-oxa-13-aza, and 9-oxa-7-aza prostanoids from 3-acyl-and 3-(3-arylprop-2-enoyl)furan-2,4-diones

A number of new 10-oxa-13-aza, 11-oxa-13-aza, and 9-oxa-7-aza prostanoids belonging to the B series were synthesized on the basis of 3-acyl-and 3-(3-arylprop-2-enoyl)furan-2,4(3H,5H)-diones. The scheme of synthesis includes selective hydrogenation of the exocyclic carbonyl group and reduction of the conjugated double bond in the acyl fragment of 3-acyl-and 3-(3-arylprop-2-enoyl)furan-2,4(3H,5H)-diones to obtain 3-alkyl-and 3-(3-arylpropyl)furan-2,4(3H,5H)-diones, transformation of the latter into the corresponding regioisomeric enol ethers via regioselective O-alkylation, and treatment of the enol ethers with primary aliphatic amines.     

Synthesis and tautomerism of ethyl 2-(2-benzothiazolyl)-2-(6-purinyl)acetate and related compounds

Reaction of 6-chloro-9H-(2-tetrahydropyranyl)purine ( 2d ) with the sodium salt of ethyl benzothiazole-2-ace-tate ( 1 ) in dimethylformamide effects condensation of the two compounds (with loss of sodium chloride) to give the corresponding ethyl diarylacetate 4 (35%), present largely as an enol chelate tautomer. Isolated as a by-product is 6-(2-aminophenyl-1-thio)-9H-(2-tetrahydropyranyl)-purine (4%), formed via opening of the thiazole ring. Removal of the tetrahydropyranyl protective group from 4 occurs by treatment with p-toluenesulfonic acid in aqueous ethanol to produce ethyl benzothiazole-2-(6-purinyl)acetate (80%), existent largely as two enol chelate isomers. Spectral data for the various products are presented. An attempt to use 6-chloro-9-acetyl-9H-purine in place of 2d in the first reaction gives acetylation of 1 instead of condensation.     

Synthesis and antihelminthic action of 1,3-cyclohexanedione derivatives containing branched aliphatic chains

Summary 1,3-Cyclohexanedione was alkylated with branched allyl bromides. The resulting 2-alkyl derivatives and their enol acetates possess antihelminthic activity. The enol acetate of 2-(3,7,11-trimethyl-2-dodecenyl)-1,3-cyclohexanedione was found to be the most active.     

Asymmetric hydrogenation of di and trisubstituted enol phosphinates with N,P-ligated iridium complexes

The iridium-catalyzed asymmetric hydrogenation of various di- and trisubstituted enol phosphinates has been studied. Excellent enantioselectivities (up to >99% ee) and full conversion were observed for a range of substrates with both aromatic and aliphatic side chains. Enol phosphinates are structural analogues of enol acetates, and the hydrogenated alkyl phosphinate products can easily be transformed into the corresponding alcohols with conservation of stereochemistry. We have also hydrogenated, in excellent ee, several purely alkyl-substituted enol phosphinates, producing chiral alcohols that are difficult to obtain highly enantioselectively from ketone hydrogenations.     

New hydrofluoropolyethers: I. Synthesis and reaction pathway evaluation

A novel family of hydrofluoropolyethers (HFPEs) was obtained with 60-80% selectivity by hydrogenation of perfluoropolyether acyl chlorides with Pt/CaF₂. These compounds are characterized by a macromeric fluorinated body end-capped, on one or both sides, by a (1,1-difluoro)ethoxy group. A reaction pathway for the reduction was proposed consistently with the observed yields and side products. The hemiacetal originated by reaction of the aldehyde (first product of reduction) with the corresponding alcohol was postulated to be the key precursor leading to the HFPE. The metal appears to play a fundamental role promoting the hydrogenolysis of this unexpected intermediate. Exhaustive reduction of the alcohol, generally recognized as the path affording hydrocarbons in the hydrogenation of acyl chlorides, was excluded by products analysis and by specific experiments.     

FLP‐Catalyzed Transfer Hydrogenation of Silyl Enol Ethers

Herein we report the first catalytic transfer hydrogenation of silyl enol ethers. This metal free approach employs tris(pentafluorophenyl)borane and 2,2,6,6‐tetramethylpiperidine (TMP) as a commercially available FLP catalyst system and naturally occurring γ‐terpinene as a dihydrogen surrogate. A variety of silyl enol ethers undergo efficient hydrogenation, with the reduced products isolated in excellent yields (29 examples, 82 % average yield).     

New synthetic route to access (±) salinosporamide A via an oxazolone-mediated ene-type reaction

We report herein a racemic key intermediate in the synthesis of salinosporamide A via a tert-alkyl amino hydroxy carboxylic ester produced in an ene-type reaction of an oxazolone with an enol ether.     

Chemistry of 1,3-cyclohexanedione

Summary 1,3-Cyclohexanedione was alkylated with branched allyl bromides. The resulting 2-alkyl derivatives (IV), (V), and (VI), and also their enol acetates (VII), (VIII), and (IX), have an antihelminthic action. The highest antihelminthic activity is shown by the enol acetate (IX).     

Transformation of 5-hydroxymethylene-5H-6,7-dihydrodibenzo[a,c]cyclohepten-6-one over Ru-containing BEA zeolites

Ru–BEA catalysts with 1.0–2.5 wt.% Ru were prepared by ion exchange. The acidic properties of these catalysts were investigated using deuterated acetonitrile, pyridine, and 2,6-di-tert-butyl-pyridine. The deposited Ru was studied by CO-FTIR spectroscopy. The materials were tested as catalysts in the hydrogenation of a conjugated cyclic keto–enol, namely, 5-hydroxymethylene-5H-6,7-dihydrodibenzo[a,c]cyclohepten-6-one. Beside hydrogenation, hydrogenolysis products were identified by GC–MS and ¹H NMR techniques. Relations were sought between the selectivity and some physicochemical properties of the catalyst.     

Palladium‐Catalyzed Reductive Insertion of Alcohols into Aryl Ether Bonds

Palladium on carbon catalyzes C?O bond cleavage of aryl ethers (diphenyl ether and cyclohexyl phenyl ether) by alcohols (R?OH) in H₂. The aromatic C?O bond is cleaved by reductive solvolysis, which is initiated by Pd‐catalyzed partial hydrogenation of one phenyl ring to form an enol ether. The enol ether reacts rapidly with alcohols to form a ketal, which generates 1‐cyclohexenyl?O?R by eliminating phenol or an alkanol. Subsequent hydrogenation leads to cyclohexyl?O?R.     

Synthese d'une Serie de 2-(F-alkyl) Thioenol Ethers

2-(F-alkyl) enol ethers react easily with thiols. With one equivalent of the thiol, the corresponding 2-(F-alkyl) thioenol ethers were formed via an addition-elimination mechanism. With two equivalents of thiol or with one equivalent of 1,2-ethanedithiol, 2-(F-alkyl) thioacetals or 2-(F-alkyl) dithiolanes were obtained in good yields.