Michael Initiated Ring Closure Research Articles

Synthesis of Enantiopure 1,4‐Dioxanes, Morpholines, and Piperazines from the Reaction of Chiral 1,2‐Diols, Amino Alcohols, and Diamines with Vinyl Selenones

The reactions of readily available vinyl selenones with enantiopure 1,2-diols, N-protected-1,2-aminoalcohols, and diamines gave substituted enantiopure 1,4-dioxanes, morpholines, and piperazines, respectively, in good to excellent yields. The same procedure was extended to the synthesis of thiomorpholine, benzodiazepine, and benzoxazepine. The reactions proceeded in one pot, in the presence of base, through a simple and novel application of the Michael-initiated, ring-closure (MIRC) reactions. The formed heterocycles constitute a framework that is observed in a large number of pharmaceutical compounds.

ChemInform Abstract: Convenient Synthesis of Dimethyl-1-aryl-4-hydroxy-N-methylcarbazole-2, 3-dicarboxylates via Michael Initiated Ring Closure Methodology.

ChemInform 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.

Probing the Reactivity of Dimethylsulfoxonium Methylide with Conjugated and Nonconjugated Carbonyl Compounds: An Undergraduate Experiment Combining Synthesis, Spectral Analysis, and Mechanistic Discovery

We introduce students to dimethylsulfoxonium methylide (DMSY) epoxidation of aryl and nonconjugated aliphatic aldehydes and ketones without revealing that DMSY cyclopropanates enones by Michael-initiated ring closure (MIRC). Each student performs the reaction of DMSY with one of nine carbonyl compounds, including four enones, and then analyzes the 13C NMR and IR spectra of their reaction product in comparison with spectra of their carbonyl substrate. The spectra of products from aryl and nonconjugated aldehydes and ketones show the expected absence of a carbonyl peak and the addition of two upfield 13C peaks (indicating carbonyl epoxidation), whereas spectra of products from enones unexpectedly (to the student) display a carbonyl peak, no alkene 13C peaks, and three (instead of two) additional upfield 13C peaks. Identification of the latter products as cyclopropyl ketones leads to a discussion of conjugate addition and MIRC, and it stresses the avoidance of making false assumptions regarding the outcome of chemical reactions.

Nucleophilic heterocyclic carbene as a novel catalyst for cyclopropanation of cyano acrylates

Nucleophilic heterocyclic carbenes (NHCs) have been used for the first time as catalysts in the cyclopropanation of ethyl cyanocinnamates with phenacyl bromide by Michael-initiated ring-closure (MIRC).

An Unexpected Highly Stereoselective Bisaziridination of (E,E)-1,4-Dialkyl-2,3-dinitrobutadienes Followed by a Nitro Group Driven Ring Enlargement

(+/-)-2,2'-Dinitro-2,2'-biaziridines were obtained by a direct aza-MIRC (Michael initiated ring closure) reaction on (E,E)-1,4-dialkyl-2,3-dinitro-l,3-butadienes under very mild conditions. The reactions occur with high stereoselectivity as shown by the enantioselective HPLC analyses performed on the crude mixtures. Ring enlargement to 3,3'-bi(1,2,4-oxadiazole) derivatives was easily obtained by a simple treatment with sodium iodide in DMSO, with an unforeseen regioselective aziridine C-C cleavage.

One-pot synthesis of chiral multifunctionalized aziridines

A direct synthetic procedure to obtain chiral aziridines is reported, involving a diastereoselective aza-MIRC (Michael Initiated Ring Closure) reaction. Multifunctionalized aziridines are obtained in high overall yields (82–92%) and with a diastereomeric ratio up to 99:1. Further synthetic elaboration can lead to the formation of interesting biochemical molecules, such as amino glycosides. The diastereomeric induction seems to be strongly controlled both by the choice of chiral moiety and by the electron withdrawing groups (EWG) present on the starting alkenes.

ChemInform Abstract: Diastereoselective Michael Initiated Ring Closure on Vinyl Sulfone‐Modified Carbohydrates: A Stereospecific and General Route to α‐Substituted Cyclopropanes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.

Diastereoselective Michael Initiated Ring Closure on Vinyl Sulfone-Modified Carbohydrates: A Stereospecific and General Route to α-Substituted Cyclopropanes

Suitably designed vinyl sulfone-modified furanosides act as substrates for Michael initiated ring closure reactions yielding cyclopropanated carbohydrates. The strategy is general in nature and gives access to cyclopropanes with predefined chiralities on three consecutive carbons with varying substitutions at the alpha-position.

Construction of stereodefined 1,1,2,2-tetrasubstituted cyclopropanes by acid catalyzed reaction of aryldiazoacetates and α-substituted acroleins

Michael-initiated ring closure of aryldiazoacetates and alpha-substituted acroleins under acid catalysis offers a unique opportunity for the stereoselective formation of various tetrasubstituted cyclopropanes.

Facile Synthesis of β‐Azidocyclopropanecarboxylates by MIRC Reaction.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Aziridines versus Vinyl Carbamates from the Direct Amination of Electron‐Withdrawing Group‐Substituted Trifluoromethyl Enoates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Graphical Abstracts

Synth. Commun. 2005, 35, 1427 Facile Synthesis of β‐Azidocyclopropanecarboxylates by MIRC Reaction Jiangtao Su, Guofu Qiu, Shucai Liang, and Xianming Hu College of Pharmacy, Wuhan University, Wuhan, China Two β‐azidocyclopropanecarboxylates are readily synthesized in the lab from β‐bromoalkyliden malonates via a Michael‐initiated ring closure (MIRC) reaction in moderate yields, which are regarded as precursors of β‐aminocyclopropanecarboxylic acids. They are important building blocks in the organic synthesis.

Facile Synthesis of β‐Azidocyclopropanecarboxylates by MIRC Reaction

Two β‐azidocyclopropanecarboxylates are readily synthesized from β‐bromoalkyliden malonates via a Michael–initiated ring closure (MIRC) reaction in moderate yields, which are regarded as precursors of β‐aminocyclopropanecarboxylic acids.

Aziridines versus Vinyl Carbamates from the Direct Amination of Electron-Withdrawing Group-Substituted Trifluoromethyl Enoates

Aza-MIRC (Michael-initiated ring closure) and C-H insertion products were obtained in the reactions of trifluoromethylated olefins with different nosyloxycarbamates by changing base and solvent. Aza-Michael addition products were not isolated. The presence and the position of the trifluoromethyl group allow control of the outcome of the reactions.

Simple Large-Scale Preparationof 1,2,3-Tris-Acceptor Substituted Cyclopropanes

Triethyl (1α,2α,3β)cyclopropane-1,2,3-tricarboxylate (3aa), as well as diethyl (4ab) and dimethyl (1α,2β,3α)-1-acetylcyclopropane-2,3-dicarboxylate (4bb) have been prepared on a scale of up to 60 g by Michael initiated ring-closure (MIRC) cyclopropanation of dialkyl fumarates 1a,b with ethyl chloroacetate (2a) and chloroacetone (2b) in 62%, 51% and 56% yield, respectively. For the success of the new procedure it is essential to slowly add (within 5-7 h) the mixture of compounds 1 and 2 to a vigorously stirred suspension of K2CO3 in DMF in the presence of benzyltriethylammonium chloride.

MIRC reactions using sulfoxides and synthesis of dictyopterene A

Michael initiated ring closure reactions, using alkyl imidazolyl sulfoxides as nucleophiles, provided a 2-substituted cyclopropanecarboxylate 2 and cyclohexanecarboxylate 5, with high yields and excellent diastereoselectivity. Thermal elimination of the imidazolylsulfinyl group gave an alkene 3. This method was used to carry out a short synthesis of dictyopterene A. A 2- hexenylcyclopropanecarboxylate 13 was prepared using a MIRC reaction of hexyl 1-methyl-2- imidazolyl sulfoxide with 4-bromocrotonate, followed by pyrolytic elimination of the imidazolylsulfinyl group. Straightforward conversion of the ester group into a vinyl group furnished dictyopterene A.

Intermolecular [3+2] MIRC reactions with alkynoates. Asymmetric Michael addition leading to a nonracemic cyclopentene-annulated α,β-butenolide

A novel Michael-initiated ring closure reaction involving allylic chlorosulfone ( 2) and γ-alkoxy-α,β-ynoates to afford 4-methylenecyclopentenecarboxylates is reported, while with γ-alkylynoates no reaction occurred. With chiral phenyl ynoates 4, the reaction proceeds by 1,3-asymmetric induction and leads further to a nonracemic annulated α,β-butenolide ( 7).

Stereoselective and enantioselective synthesis of five-membered rings via conjugate additions of allylsulfone carbanions

Abstract This lecture describes some of our studies of lithio derivatives of allyl sulfone carbanions which add α-regioselectively as well as anti diastereoselectively to Michael acceptor olefins. This can be ascribed to chelation in the Michael addition step. When the reaction leads to subsequent ring closure by using a bromoallyl sulfone, the latter acts as a methylenemethane synthon in a (3+2) Michael-initiated ring closure, affording highly functionalized cyclopentane derivatives. Such additions proceed with high stereoselectivity and with asymmetric induction leading to nonracemic substituted cyclopentanones. Additions of allyl sulfone carbanions also proceed stereoselectively to C=N systems containing a chiral auxiliary on N. These can be used in the synthesis of optically active five- and six-membered ring N-heterocycles. Furthermore, chiral groups on the allyl sulfone moiety can induce significant remote asymmetric induction, made possible by the presence of an aromatic π-system which promotes intramolecular chelation to the Li cation.

Synthesis of pinnaic acid; Asymmetric construction of spirocyclic core

An asymmetric synthesis of the spirocyclic core of pinnaic acid, a cPLA 2 inhibitor, is described. A key transformation in the sequence involves an asymmetric Michael-initiated ring closure.

ChemInform Abstract: Stereochemistry. Part 88. Asymmetric Synthesis of Substituted Cyclopentanes via Michael Initiated Ring Closure Reactions.

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.