Methyl Diazoacetate Research Articles

The Enantioselectivity and the Stereochemical Course of Copper-Catalyzed Intramolecular CH Insertions of Phenyliodonium Ylides

The Cu-catalyzed intramolecular CH insertion of phenyliodonium ylide 1b was investigated at 0° in the presence of several chiral ligands. Enantioselectivities varied in the range 38–72%, and were higher than those resulting from reaction of the diazo compound 1c at 65°. The intramolecular insertion of the enantiomerically pure methyl diazoacetate (R)-20 and of the corresponding phenyliodonium ylide (R)-21 proceeded to (R)-23 with retention of configuration with [Cu(hfa)2] (hfa=hexafluoroacetylacetone=1,1,1,5,5,5-hexafluoropentane-2,4-dione) and [Rh2(OAc)4]. These results are consistent with a carbenoid mechanism for the Cu-catalyzed insertion with phenyliodonium ylides. However, the insertion of the perfluorosulfonated phenyliodonium ylide (R)-29 afforded with [Cu(hfa)2] as well as with [Rh2(OAc)4] the cyclopentanone derivative 30 as a cis/trans mixture with only 56–67% enantiomeric excess.

ChemInform Abstract: Rh2(OAc)4‐Catalyzed Reaction of 1,3‐Dioxanes with Methyl Diazoacetate.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Reactions of Aliphatic Diazo Compounds: V. Reaction of Methyl Diazoacetate with Imides of Itaconic Acid

Methyl diazoacetate regioselectively adds to N-substituted imides of itaconic acid to afford 2-pyrazolines, methyl 7-aryl-6,8-dioxo-1,2,7-triazaspiro[4.4]non-2-ene-3-carboxylates that in reaction with halogens (Cl2, Br2) yield methyl 5-aryl-1-halo-4,6-dioxo-5-azaspiro[2.4]heptane-1-carboxylates as a mixture of syn- and anti-isomers.

Interaction of Unsymmetrical 1,3-Dioxolanes with Methyl Diazoacetate

Interaction of Unsymmetrical 1,3-Dioxolanes with Methyl Diazoacetate

ChemInform Abstract: Reaction of 2‐Phenyl‐1,3‐oxathiolane with Methyl Diazoacetate.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Catalytic and Photochemical Cyclopropanation of Alkenes with Methyl Diazo(trialkylsilyl)acetates: Steric Effects and Thermodynamic Stabilities of Cyclopropanes

Diazo esters 1 (N2C(SiR3)COOMe; R = Me (1a), Et (1b), i-Pr (1c)) have been decomposed in styrene, 1-hexene, and cyclohexene under Cu, Rh, or Ru catalysis as well as by photochemical means with the objective to evaluate the effectiveness and diastereoselectivity of the respective cyclopropanation reaction. With styrene and 1-hexene as substrates, the ability of the catalysts followed the order CuOTf > [Ru2(CO)4(μ-OAc)2]n ≈ Rh2(OAc)4, but even CuOTf (copper(I) triflate) did not promote cyclopropanation of 1-hexene with the bulky 1c. Cyclopropanation of cyclohexene with 1a,b succeeded only with the ruthenium catalyst. In all cases, the diastereoisomer having the silyl group anti to the vicinal methyl or phenyl substituent(s) was formed preferentially. In contrast, in the photochemical reactions of 1a,c with styrene and of 1a with 1-hexene the diastereoisomer having the silyl group syn to the vicinal substituent(s) was formed preferentially. The fluoride-induced desilylation of cyclopropanes 2a,c,e was accompanied by a loss of stereochemical integrity. The X-ray crystal structure analysis of the cyclopropane (E)-2f has been determined. The relative thermodynamic stabilities of various 2-R-1-X-cyclopropanecarboxylates (R = Me, Ph; X = Me, t-Bu, SiH3, SiMe3, Si(i-Pr)3) have been calculated by density functional theory methods. These calculations show that for X = SiMe3 and R = Ph the syn−anti energy difference is ca. 0, while for R = Me the anti isomer is more stable.

Theoretical (DFT) insights into the mechanism of copper-catalyzed cyclopropanation reactions. Implications for enantioselective catalysis.

The mechanism of the copper(I)-catalyzed cyclopropanation reaction has been extensively investigated for a medium-size reaction model by means of B3LYP/6-31G(d) calculations. The starting ethylene complex of the N,N'-dimethylmalonaldiimine--copper (I) catalyst undergoes a ligand exchange with methyl diazoacetate to yield a reaction intermediate, which subsequently undergoes nitrogen extrusion to generate a copper--carbene complex. The cyclopropanation step takes place through a direct carbene insertion of the metal--carbene species to yield a catalyst--product complex, which can finally regenerate the starting complex. The stereochemical predictions of a more realistic model (by considering a chiral bis(oxazoline)--copper (I) catalyst) have been rationalized in terms of steric repulsions, showing good agreement with experimental data.

ChemInform Abstract: Photoreaction of Methyl (p‐Nitrophenyl)diazoacetate in the Presence of an Electron‐Donating Amine: Evidence for Intermediacy of the Carbene Radical Anion.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Reactions of diazoalkanes with unsaturated compounds. 14. Reactions of diazomethane, diazocyclopropane, and methyl diazoacetate with 1,1,2,2-tetrafluoro-3-vinylcyclobutane and 2,3,3-trifluoro-1-vinylcyclobutene to form [3+2]and [1+2] cycloadducts

The reactions of diazomethane and diazocyclopropane generated in situ with 1,1,2,2-tetrafluoro-3-vinylcyclobutane (1) and 2,3,3-trifluoro-1-vinylcyclobutene (2) proceeded at the double bond of the substituent as the 1,3-dipolar cycloaddition to form the corresponding 1-pyrazolines. Under the conditions of thermolysis (340—400 °C), the resulting cyclobutylpyrazolines 4 and 5 selectively lost the dinitrogen molecule to generate 3-cyclopropyl-1,1,2,2-tetrafluorocyclobutane (6) or 1,1,2,2-tetrafluoro-3-spiropentylcyclobutane (7), respectively, in high yields. In the presence of Pd(acac)2, the reactions of these fluorine-containing unsaturated compounds and 2-chloro-1,1,2-trifluoro-3-vinylcyclobutane (3) with diazomethane gave rise directly to cyclopropane derivatives 6, 11, and 12, respectively. The reactions of compounds 1 and 2 with methyl diazoacetate in the presence of Rh2(OAc)4 proceeded analogously to yield cis- and trans-disubstituted cyclopropanes.

Rh2(OAc)4-catalyzed reaction of 1,3-dioxanes with methyl diazoacetate

The reactions of methyl diazoacetate with 1,3-dioxanes in the presence of Rh2(OAc)4 afford 1,4-dioxepanes in up to 46% yields. The insertion of methoxycarbonylcarbene into the C—O bond occurs only in the case of 2-phenyl-1,3-dioxanes.

Reactions of methoxycarbonylcarbene with 3-ethyl-2-phenyl- and 2,3-diphenyloxazolidines

The reactions of methoxycarbonylcarbene, which was generated by catalytic thermal decomposition of methyl diazoacetate, with 3-ethyl-2-phenyl- or 2,3-diphenyloxazolidines resulted in the insertion of the former predominantly at the C—N bond of the oxazolidine ring to produce substituted esters of morpholine-3-carboxylic acid.

Photoreaction of Methyl (p-Nitrophenyl)diazoacetate in the Presence of an Electron-Donating Amine: Evidence for Intermediacy of the Carbene Radical Anion

Abstract The product distribution in the photolysis of methyl (p-nitrophenyl)diazoacetate in MeCN–MeOH (9:1) was dramatically changed by the addition of an electron-donating amine, where the formation of the products derived from the carbene was quenched completely. On the basis of the direct observation of transient species and the dependence of the products on amine concentration, the reaction scheme involving a single electron transfer to afford the carbene radical anion is proposed.

Pd-Catalyzed Reactions of Donor−Acceptor-Substituted Cyclopropanes and Their Ring-Opened Derivatives: Attempted Heck Cyclization and Novel One-Pot Enolate Arylations

Donor−acceptor substituted cyclopropane derivatives 4a−g were synthesized in good yields from ketones, via the corresponding silyl enol ethers 2a−g, by cyclopropanation with methyl diazoacetate followed by alkylation using o-iodobenzyl iodide. The γ-oxo esters 5a−g were prepared in high yield, employing NEt3 · 3 HF. A novel Pd-catalyzed one-pot transformation of 4a−f into 1,2-disubstituted indanes 6a−f was accomplished using either CsF (Method A or B) or Bu4NF (Method C) as the fluoride source to achieve the in situ ring-opening of 4a−f. The two reagents CsF and Bu4NF function in a complementary manner. For example, CsF works better with enones 4b and 4c, while Bu4NF functions well with aryl/alkyl ketones 4d−f. Pd-catalyzed Heck cyclization of vinyl ketone 5a furnished mainly the 7-exo-trig cyclization product 7 but isopropenyl ketone 5b gave a moderate yield of indane derivative 6b, arising from enolate arylation. When the carbonyl group in 5b was protected, a novel tricyclic compound 13 was obtained in low yield.

Pd-Catalyzed Reactions of Donor−Acceptor-Substituted Cyclopropanes and Their Ring-Opened Derivatives: Attempted Heck Cyclization and Novel One-Pot Enolate Arylations

Donor−acceptor substituted cyclopropane derivatives 4a−g were synthesized in good yields from ketones, via the corresponding silyl enol ethers 2a−g, by cyclopropanation with methyl diazoacetate followed by alkylation using o-iodobenzyl iodide. The γ-oxo esters 5a−g were prepared in high yield, employing NEt3 · 3 HF. A novel Pd-catalyzed one-pot transformation of 4a−f into 1,2-disubstituted indanes 6a−f was accomplished using either CsF (Method A or B) or Bu4NF (Method C) as the fluoride source to achieve the in situ ring-opening of 4a−f. The two reagents CsF and Bu4NF function in a complementary manner. For example, CsF works better with enones 4b and 4c, while Bu4NF functions well with aryl/alkyl ketones 4d−f. Pd-catalyzed Heck cyclization of vinyl ketone 5a furnished mainly the 7-exo-trig cyclization product 7 but isopropenyl ketone 5b gave a moderate yield of indane derivative 6b, arising from enolate arylation. When the carbonyl group in 5b was protected, a novel tricyclic compound 13 was obtained in low yield.

ChemInform Abstract: Diethyl Acetylaminoallylmalonate in Reaction with Methyl Diazoacetate.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Unusual formation of 7-vinylcycloheptatriene derivatives in the catalytic cyclopropanation of cyclooctatetraene with diazocarbonyl compounds in the presence of rhodium catalysts

The reaction of cyclooctatetraene with methyl diazoacetate or diazoacetone in the presence of rhodium binuclear complexes gives, besides 9-substituted bicyclo[6.1.0]nona-2,4,6-trienes (mixture ofanti- andsyn-isomers, total yields 60–75%), isomeric β-(cyclohepta-2,4,6-trien-1-yl)acrylates or 4-(cyclohepta-2,4,6-trien-1-yl)but-3-en-2-one in 20–34% yields. In the case of methyl diazoacetate, a mixture ofE- andZ-isomers in a ratio of −3.5∶1 was obtained, while diazoacetone gave onlyE-isomer.

A fluorous phase approach to rhodium-catalyzed carbenoid reactions with diazoacetates

The cyclopropanation of alkenes with methyl diazoacetate in dichloromethane was catalyzed by rhodium(II) carboxylates containing a perfluoralkyl chain (Rh 2L 4, L = OOCC 7F 15 and OOCC 6H 4-4-C 6F 13). The catalysts could be extracted into perfluoro(methylcyclohexane) and were reused several times without significant loss of activity. The same catalysts were used to achieve carbene transfer to toluene in the solvent system toluene-perfluoro(methylcyclohexane) at 60 °C.

Reaction of methyl diazoacetate with aldehydes, amines, thiols, alcohols and acids over transition metal-exchanged clays

Metal-exchanged clays (M = Rh and Cu) catalyze effectively the reaction of methyl diazoacetate with various aldehydes, affording the corresponding β-keto esters in high yields. They have also been effective in the decomposition of methyl diazoacetate to form metallocarbenes which, in turn, successfully insert into X–H (X = N, O, S, CO2) bonds of a variety of amines, aldehydes, thiols and acids, thereby producing the corresponding esters.

Cis-Disubstituted Cyclopropanesvia Asymmetric Catalytic Cyclopropenation: Synthesis of Cyclopropyl-dehydroamino Acids and of Dictyopterene C′

The cyclopropenation of diethoxypropyne (1) with methyl diazoacetate in the presence of [Rh₂{(2S)‐mepy}₄] (mepy=methyl 5‐oxopyrrolidine‐2‐carboxylate) proceeds with >95% ee. The resulting cyclopropenecarboxylate 2 underwent stereoselective hydrogenation to the cis‐cyclopropane 3. Hydrolysis of the acetal function of 3 liberated the formyl cyclopropenecarboxylate 4, which was transformed by Wittig reaction with the phosphonate 5 to afford dehydroamino acid 6 as a mixture of (Z)‐ and (E)‐isomers in various proportions. The (Z)‐isomer 6a was hydrolyzed, and the structure and the absolute configuration of the (Z)‐dicarboxylic acid 7a were established by X‐ray crystallography. The cis‐divinylcyclopropane 11 (ee>95%), in turn, was synthesized from 4 via Wittig reaction to afford 8, which was transformed to the aldehyde 10 and subjected to a second Wittig reaction. Thermolysis of 11 afforded (+)‐dictyopterene C′ (12) in quantitative yield.

Screening of Various Catalysts for the Asymmetric Cyclopropanation of Structurally Typical Silyl Enol Ethers—Scope and Limitations of Evans's Bisoxazoline Copper Catalyst

AbstractThe scope and limitations of asymmetric syntheses of 2‐siloxycyclopropanecarboxylates 3 were examined by combination of structurally typical silyl enol ethers and methyl diazoacetate with various chiral catalysts. It was found that the Schiff base complex 5ṁCu(OAc)2 and the bisoxazoline complex 6ṁCuOTf gave the highest stereoselectivities (e.g., 72% ee for cis‐3d with 5ṁCu(OAc)2 as catalyst or 76% and 73% ee for cis‐ and trans‐3a, respectively, with 6‐CuOTf as catalyst). High enantioselectivities or diastereoselectivities were obtained. Other catalysts based on copper, rhodium or ruthenium complexes afforded significantly lower values. In further investigations, Evans's bisoxazoline complex 6‐CuOTf proved to be limited to 1,1‐disubstituted silyl enol ethers (e.g. 1a and 1e) for high enantiomeric excesses (up to > 95%, poor diastereoselectivities) and to 1,2‐substituted enol ethers (e.g. 1e) for high diastereoselectivities (cis:trans < 3:97, eetrans = 49%).