Synthesis of (+/-)- and (-)-vibralactone and vibralactone C

Mander reductive alkylation of methyl 2-methoxybenzoate with prenyl bromide and hydrolysis of the enol ether afforded methyl 6-oxo-1-prenyl-2-cyclohexenecarboxylate. This was converted in five steps (reduction of the ketone, saponification, iodolactonization, ozonolysis, and intramolecular aldol reaction) to a spiro lactone cyclopentenal. An efficient first synthesis of (+/-)-vibralactone was completed by retro-iodolactonization with activated Zn, formation of the beta-lactone (vibralactone C), and reduction of the aldehyde. Except for the novel use of an iodolactone to protect both the prenyl double bond and carboxylic acid, no protecting groups were used. A similar sequence starting with asymmetric reductive alkylation of the (2S)-2-methoxymethoxymethylpyrrolidine amide of 2-methoxybenzoic acid with prenyl bromide afforded (-)-vibralactone confirming the absolute stereochemical assignment that was based on computational methods.     

Synthesis of racemic nitramine, isonitramine and sibirine

Condensation of enol ether 6 with methyl vinyl ketone led easily to ketoaldehyde 7 whose cyclisation afforded the azaspiranic enone 8, a key intermediate for the synthesis of the title alkaloids.     

Ringerweiterung bei der Reaktion eines 1,3-Cyclohexandions mit Diphenylcyclopropenon

Ring Expansion during the Reaction of a 1,3-Cyclohexanedione with Diphenylcyclopropenone The reaction of 5,5-dimethyl-1,3-cyclohexanedione ( 1 ) in form of its Na-salt with diphenylcyclopropenone ( 2 ) in DMF yielded the bicyclic triketone 3 (58 %), the structure of which was deduced as an enolizeable bicyclo[5.2.0]nonane-β-diketone from spectral data and from the following reactions: hydrolysis or methanolysis of 3 cleaved the β-dicarbonyl moiety, thereby opening the 4-membered ring to yield the keto acid 9 or its methyl ester 10 . Methylation of 3 afforded the two enol ethers 4 and 5 . The ether 5 readily underwent a thermal electrocyclic ring opening to the monocyclic enol ether 8 , whereas the ether 4 was thermally stable. The same electrocylic ring opening (in boiling benzene) converted 3 (probably via 3b ) to the monocyclic triketone 7 , which was also the hydrolysis product of the ring-opened enol ether 8 . By heating 3 in DMF/H₂O, a partial (56 %) conversion to the lactone 6 took place. The tricyclic intermediate 11 was found useful to rationalize the ring expansion during the formation of 3 from 1 and 2 as well as the corresponding ring contraction during the conversion of 3 into 6 .     

Pd(0)-catalyzed conjugate addition of benzylzinc chlorides to alpha,beta-enones in an atmosphere of carbon monoxide: preparation of 1,4-diketones

Pd(0)-catalyzed conjugate addition of benzylzinc chloride to methyl vinyl ketone in the presence of chlorotrimethylsilane and lithium chloride in an atmosphere of carbon monoxide at room temperature afforded 1-phenyl-2,5-hexanedione monosilyl enol ether. In this catalytic carbonylation, four components are connected in one reaction. Successive acidic workup generated a variety of 1,4-diketones from substituted benzylzinc chlorides or related compounds and alpha,beta-enones. Some products were converted to cyclopentenones or five-membered heterocyclic compounds containing an N, O, or S atom.     

Acetyltrimethylsilane, trifluoromethyltrimethylsilane, and prenyl esters: a three-component system for the synthesis of gem-difluoroanalogues of monoterpenes

The preparation of 3,3-difluoro-6-methylhept-5-en-2-one 1, a key intermediate for the synthesis of 4,4-difluoroterpenes, and applications in linalool and geraniol series are described. The process involves 1,1-difluoro-2-trimethylsilyoxypropene, an enol silyl ether prepared from acetyltrimethylsilane and trifluoromethyltrimethylsilane, and its reaction in situ with prenyl benzoate, under catalysis by trimethylsilyl trifluoromethanesulfonate. Optimized conditions leading to either the desired enol silyl ether or the unprecedented methyl(trifluoromethyl)trimethylsilyl carbinol 4 have been achieved. The prenylation of the enol silyl ether gives a 9/1 mixture of regioisomers, in favor of the expected ketone 1. Treatment of 1 with vinylmagnesium bromide leads to (+/-)-4,4-difluorolinalool 7. Reaction with the lithium enolate of ethyl diethylphosphonoacetate, and then LAH reduction, converts 1 to 4,4-difluorogeraniol 11, with complete stereoselectivity.     

Combined XPS and DFT investigation of the adsorption modes of methyl enol ether functionalized cyclooctyne on Si(001)

The reaction of methyl enol ether functionalized cyclooctyne on the silicon (001) surface was investigated by means of X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT). Three different groups of final states were identified; all of them bind on Si(001) via the strained triple bond of cyclooctyne but they differ in the configuration of the methyl enol ether group. The majority of molecules adsorbs without additional reaction of the enol ether group; the relative contribution of this configuration to the total coverage depends on substrate temperature and coverage. Further configurations include enol ether groups which reacted on the silicon surface either via ether cleavage or enol ether groups which transformed on the surface into a carbonyl group.     

Reactions of 1,2-Dimethyl-5-nitroimidazole,novel methods of conversion of the 2-Methyl group to a nitrile

1, 2-Dimethyl-5-nitroimidazole( 1 )and N,N-dimethylformamide dicyclohexylacetal gave the 2-(β-dimethylaminovinyl) analog 2 and with iodine and pyridine gave the 2-(1-pyridinium)methyl compound 3 . Benzoyl chloride-triethylamine and 1 led to benzoylation of the 2-methyl group to give ketone 9 as the enol benzoate. Nitrous acid or nitrosylsulfuric acid with 9 or its enol ester afforded the oximinoketone 10 which was cleaved with thionyl chloride to give 2-cyano-1-methyl-5-nitroimidazole ( 11 ) in high overall yield. 1-Ethyl-2-methylbenzimidazole ( 22 ) was converted to 2-cyano-1-ethylbenzimidazole ( 25 ) similarly. Reaction of 1 with ethyl oxalyl chloride and triethylamine afforded ethyl 1-methyl-5-nitro-2-imidazolepyruvate ( 19 ) as the enol oxalate. Nitrous acid and 19 gave the oximino pyruvate 20 which effervesced on mild heating to give 2-cyano-1-methyl-5-nitroimidazole ( 11 ). The preparation of 1-methyl-5-nitro-2-imidazoleacetonitrile ( 39 ) is reported.     

Chiral base-catalyzed aldol reaction of trimethoxysilyl enol ethers: effect of water as an additive on stereoselectivities

An aldol reaction of trimethoxysilyl enol ether catalyzed by lithium binaphtholate is described. The aldol reaction of trimethoxysilyl enol ether derived from cyclohexanone under anhydrous conditions predominantly afforded the anti-aldol adduct with moderate enantioselectivity, whereas the reaction under aqueous conditions predominantly resulted in the syn-adduct and the enantioselectivity of the syn-adduct was considerably improved. The best enantioselectivity was obtained in the reaction of trimethoxysilyl enol ether derived from 1-indanone with cyclohexanecarboxaldehyde (97% ee (syn)). This is the first example of an aldol reaction of trimethoxysilyl enol ether catalyzed by a chiral base.     

Synthesis of 2-arylacrylic esters from aryl methyl ketones via Wittig reaction/singlet oxygen ene reaction

An efficient synthetic method has been developed for the synthesis of 2-arylacrylic esters from the corresponding aryl methyl ketones via Wittig reaction and singlet oxygen ene reaction. Wittig reaction to aryl methyl ketones with (methoxymethyl)triphenylphosphonium chloride in basic condition afforded the methyl enol ethers, and then 2-arylacrylic esters were obtained by singlet oxygen ene reaction, followed by tosylation and elimination in one-pot to the methyl enol ethers in good yields.     

Formation and reactivity of silacyclopropenes derived from siloxyalkynes: stereoselective formation of 1,2,4-triols

Silver phosphate-catalyzed silylene transfer to siloxyalkynes provided silacyclopropenes possessing a silyl enol ether functional group. Copper-catalyzed insertions of carbonyl compounds afforded the corresponding oxasilacyclopentenes. The embedded silyl enol ether functionality was treated with various aldehydes and a catalytic amount of Sc(OTf)3 to provide dioxasilacycloheptanones, which resulted from an aldol addition/rearrangement. Stereoselective reduction or allylation of the cyclic ketone, followed by n-Bu4NF deprotection, provided high yields of 1,2,4-triols possessing four contiguous stereocenters.     

New approaches toward the synthesis of (D-homo) steroid skeletons using Mukaiyama reactions

New, short, and flexible procedures have been developed for syntheses of steroid and D-homo steroid skeletons. A Mukaiyama reaction between the silyl enol ether of 6-methoxytetralone and 2-methyl-2-cyclopentenone or carvone, with transfer of the silyl group to the receiving enone, gave a second silyl enol ether. Addition of a carbocation, generated under Lewis acid conditions from 3-methoxy-2-butenol, 3-ethoxy-3-phenyl-2-propenol or 3-methoxy-2-propenol to this second silyl enol ether gave adducts, which could not be cyclized by aldol condensation to (D-homo) steroid skeletons. The Mukaiyama-Michael reaction of the silyl enol ether of 6-methoxy tetralone with 2-methyl-2-cylopentenone gave a second silyl enol ether, which reacted in high yield with a carbocation generated from 3-hydroxy-3-(4-methoxyphenyl)propene. Ozonolysis of the double bond in this adduct gave a tricarbonyl compound (Zieglers triketone), which has been used before in the synthesis of 9,11-dehydroestrone methyl ether. A second synthesis of C17 substituted CD-trans coupled (D-homo) steroid skeletons has been developed via addition of a carbocation, generated with ZnBr₂ from a Torgov reagent, to a silyl enol ether containing ring D precursor. The obtained seco steroids have been cyclized under formation of the 8-14 bond by treatment with acid. The double bonds in one of the cyclized products have been reduced to a C17-substituted all trans steroid skeleton.     

Functionalization of the Methyl Ketone Fragment in 1-[(1S,3R)-2,2-Dimethyl-3-(2-methoxymethyloxyethyl)cyclopropyl]-2-propanone

Deprotonation of 1-[(1S,3R)-2,2-dimethyl-3-(2-methoxymethyloxyethyl)cyclopropyl]-2-propanone with lithium diisopropylamide in THF at -78°C and subsequent treatment of the resulting enolate with Me₃SiCl yielded mainly the corresponding terminal silyl enol ether. The condensation of intermediate enolate with benzaldehyde regioselectively afforded a mixture of the corresponding aldol and its dehydration product. The reactions of the title ketone with NBS, as well as of the silyl enol ethers derived therefrom with I₂, led to formation of mixtures of products via opening of the cyclopropane ring.     

Novel Synthesis of 1,2,3,4-Tetrahydropyrazino[1,2-a]indoles

Condensation of 2-(3-methyl-1H-indol-1-yl)ethylamine (7) with benzotriazole and formaldehyde gave 2-(1H-1,2,3-benzotriazol-1-ylmethyl)-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole (8) in 96% yield. Nucleophilic substitutions of the benzotriazolyl group in 8 with NaBH(4), NaCN, triethyl phosphite, allylsilanes, silyl enol ether and Grignard reagents afforded novel 10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indoles 9a-i in 78-95% yields.     

Quenching of metal‐catalyzed living radical polymerization with silyl enol ethers

Various silyl enol ethers were employed as quenchers for the living radical polymerization of methyl methacrylate with the R Cl/RuCl₂(PPh₃)₃/Al(Oi–Pr)₃ initiating system. The most effective quencher was a silyl enol ether with an electron‐donating phenyl group conjugated with its double bond [CH₂C(OSiMe₃)(4‐MeOPh) ( 2a )] that afforded a halogen‐free polymer with a ketone terminal at a high end functionality [F̄_n ∼ 1]. Such silyl compounds reacted with the growing radical generated from the dormant chloride terminal and the ruthenium complex to give the ketone terminal via the release of the silyl group along with the chlorine that originated from the dormant terminal. In contrast, less conjugated silyl enol ethers such as CH₂C(OSiMe₃)Me were less effective in quenching the polymerization. The reactivity of the silyl compounds to the poly(methyl methacrylate) radical can be explained by the reactivity of their double bonds, namely, the monomer reactivity ratios of their model vinyl monomers without the silyloxyl groups. The lifetime of the living polymer terminal was also estimated by the quenching reaction mediated with 2a . © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4735–4748, 2000     

Formal synthesis of berkelic acid: a lesson in α-alkylation chemistry

The full details of our enantioselective formal synthesis of the biologically active natural product berkelic acid are described. The insertion of the C-18 methyl group proved challenging, with three different approaches investigated to install the correct stereochemistry. Our initial Horner-Wadsworth-Emmons/oxa-Michael approach to the berkelic acid core proved unsuccessful upon translation to the natural product itself. However, addition of a silyl enol ether to an oxonium ion, followed by a one-pot debenzylation/spiroketalisation/thermodynamic equilibration procedure, afforded the tetracyclic structure of the berkelic acid core as a single diastereoisomer.     

Highly enantioselective michael addition of silyl nitronates to alpha,beta-unsaturated aldehydes catalyzed by designer chiral ammonium bifluorides: efficient access to optically active gamma-nitro aldehydes and their enol silyl ethers

Highly enantioselective Michael addition of silyl nitronates to alpha,beta-unsaturated aldehydes has been accomplished by the utilization of designer N-spiro C2-symmetric chiral quaternary ammonium bifluoride 1 as an efficient catalyst, providing direct access to both optically active gamma-nitro aldehydes, a very useful precursor to various complex organic molecules including aminocarbonyls, and their enol silyl ethers, a Mukaiyama donor of potential synthetic utility for further selective transformations. For instance, the reaction of trimethylsilyl nitronate 2 (R1 = Me) with trans-cinnamaldehyde (R2 = Ph, R3 = H) in toluene in the presence of (R,R)-1 (2 mol %) proceeded smoothly at -78 degrees C to give the desired enol silyl ether 3 (R1 = Me, R2 = Ph, R3 = H) in 90% isolated yield (anti/syn = 83:17) with 97% ee (anti isomer), and simple treatment of 3 thus obtained with 1 N HCl in THF at 0 degrees C afforded the corresponding gamma-nitro aldehyde 4 quantitatively without loss of diastereo- and enantioselectivity.     

具有共轭体系的酮类烯醇硅醚与全氟碘代烷的反应

应用连二亚硫酸钠的引发，通过全氟碘代烷与醛类，酮类烯醇硅醚的反应，合成α－全氟烷基羰基类化合物的方法。利用该方法，还可以用“一锅法”合成含氟β－二酮类化合物。本文报道了在类似的反应条件下，与苯环或双键共轭的烯醇硅醚和全氟碘代反应的结果。     

从4-戊烯醛经增碳反应合成5-己烯酸甲酯类化合物(英文)

通过4,8,12-三甲基-4,8,12-三烯醛(1)类四戊烯醛衍生物的增一碳反应合成了5,9,13-三甲基-5,9,13-十四三烯醛甲酯(3)及5-己烯酸甲酯衍生物(7～9)。用甲氧基甲基三苯基膦处理4-戊烯醛类化合物生成烯基醚,PCC氧化所生成的烯醚则得到标题化合物,5-己烯酸甲酯类化合物。     

Domino Mukaiyama-Michael reactions in the synthesis of polycyclic systems

Good results were obtained in the Mukaiyama-Michael reaction of the silyl enol ether of cyclohexanone with 2-methyl-2-cyclopentenone and carvone, with transfer of the silyl group to the receiving enone and with TrSbCl₆ as catalyst. A second Mukaiyama-Michael reaction of this new silyl enol ether with methyl vinyl ketone and cyclization of the resulting adduct leads to tricyclic compounds in one-pot domino sequences. The scope and limitations of this domino reaction have been investigated.     

Synthesis of cyclobutanones and four-membered enol ethers by using a rearrangement reaction of enol triflates

A new synthetic method of cyclobutanone derivatives and four-membered enol ethers via an intramolecular cyclization of a ketone enolate was developed. The cyclization precursors, enol triflates having a silyloxy group at the β′-position, were synthesized from the corresponding β-hydroxy ketones, which were prepared via an aldol reaction of a cycloalkanone and an aldehyde. Under the influence of TBAF, the enol triflates afforded a cyclobutanone or a four-membered enol ether through rearrangement of the trifluoromethanesulfonyl group followed by an intramolecular C- or O-alkylation reaction.