Simmons-Smith Research Articles

Synthesis of cyclopropylsilanols by the Simmons-Smith reaction of alkenylsilanols and lithium alkenylsilanolates

Alkenylsilanols and the corresponding lithium silanolates prepared in situ by the reaction of cyclic siloxanes with alkenyllithiums are transformed to the corresponding cyclopropylsilanols under the Simmons-Smith reaction conditions. The obtained cyclopropylsilanols are further converted into the corresponding cyclopropanols by the Tamao oxidation.

N,N,N′,N′-Tetraalkyl-2,2′-dihydroxy-1,1′-binaphthyl-3,3′-dicarboxamides: Novel Chiral Auxiliaries for Asymmetric Simmons–Smith Cyclopropanation of Allylic Alcohols and for Asymmetric Diethylzinc Addition to Aldehydes

Abstract The newly introduced title compounds were found to be efficient chiral auxiliaries for the asymmetric Simmons–Smith cyclopropanation of allylic alcohols and for asymmetric addition of diethylzinc to aldehydes. For example, Simmons-Smith cyclopropanation of cinnamyl alcohol in the presence of N,N,N′,N′-tetraethyl-2,2′-dihydroxy-1,1′-binaphthyl-3,3′-dicarboxamide (1b) proceeded with high enantioselectivity of 94% ee and addition of diethylzinc to benzaldehyde in the presence of N,N,N′,N′-tetraisopropyl-2,2′-dihydroxy-1,1′-binaphthyl-3,3′-dicarboxamide (1e) proceeded with enantioselectivity of 99% ee. Although the reaction mechanism of these reactions is still nuclear, a monomeric seven-membered 2,2′-dihydroxy-1,1′ -binaphthyl-3,3′-dicarboxamide (1)–Zn complex is considered to be an active species which catalyzes the above reactions, on the basis of NMR experiments.

Assembly of the antifungal agent FR-900848 and the CETP inhibitor U-106305: studies on remarkable multicyclopropane natural products

The full structural elucidation of FR-900848, an antifungal pentacyclopropane nucleoside natural product from Streptoverticillum fervens, is reported. A series of model compounds are prepared using multiple asymmetric Simmons–Smith cyclopropanation reactions. Comparisons of spectroscopic data of synthetic 1,2-dicyclopropylethene, quatercyclopropane-2,2′′′-dimethanol and 2-methylcyclo-propanecarbaldehyde derivatives of defined absolute stereochemistry with FR-900848 and its degradation products are used to unequivocally establish the absolute stereochemistry of the natural product. A C 2 -symmetric quatercyclopropane-2,2′′′-dimethanol is converted by a sequence of desymmetrisation, selective monocyclopropanation of a 5-(quatercyclopropyl)penta-2,4-dien-1-ol derivative, deoxygenation and Horner–Emmons homologation into the fatty acid side chain ofFR-900848. Coupling of this carboxylic acid with 5′-amino-5′-deoxy-5,6-dihydrouridine gives synthetic FR-900848. The unusual helical structure of FR-900848 is discussed and compared with U-106305, a cholesteryl ester transfer protein inhibitor from the fermentation broth of Streptomyces sp. UC 11136. The full structure and stereochemistry of U-106305 is established by total synthesis using a bidirectional strategy closely following the route to FR-900848.

カルベノイド反応の新展開：新たな不斉合成反応の開発に向けて

Carbenoid, a complex of metal and carbene, undergoes various reactions such as C-H insertion, cyclopropanation, and ylid formation reactions with a range of substrates. Stereo- and chemoselectivity of these reactions is well known to depend upon the nature of the central metal ion and its bystander ligand. Thus, we synthesized new type of optically active metal complexes : bipyridine-copper (I) complex, (salen) cobalt (III) complex, and zinc-1, 1' -bi-2, 2' -naphthol-3, 3' -dicarboxamide complex and used them as catalysts for carbenoid-mediated asymmetric reactions. With these chiral metal complexes, we could achieve i) the first highly enantiospecific ring expansion reaction of oxetane to tetrahydrofurans, ii) highly enantio- and trans-selective cyclopropanation, iii) highly enantioselective Simmons-Smith reaction, and iv) highly stereoselective catalytic [2, 3] Wittig rearrangement. This study greatly expanded the scope of asymmetric carbenoid reactions.

Asymmetric synthesis of bicyclopropane derivatives

Both syn-and anti-bicyclopropane derivatives have been prepared with good relative and absolute stereocontrol using reagent controlled asymmetric cyclopropanation reactions. Double Simmons-Smith cyclopropanation of 2,4-dien-1-ols stereoselectively gave the corresponding anti-bicyclopropane derivatives.

Efficient asymmetric synthesis of cis-2-methylcyclopropanecarboxylic acid

Abstract We have developed a versatile method for the synthesis of enantiomerically pure cis -2-methylcyclopropanecarboxylic acid (−)- 2 , a component of curacin A, and its enantiomer, (+)- 2 . Double-asymmetric Simmons-Smith cyclopropanation of the dienes 5 and 9 derived from diethyl L -tartrate proceeded with excellent diastereofacial selectivity (>99% de) to give the dicyclopropanes 6 and 10 , which were converted to both enantiomers of 2 .

Asymmetric total synthesis of curacin A

Curacin A ( 1), a novel antimitotic agent, was synthesized in a highly stereo-controlled manner. The key steps were (1) an asymmetric allylation using a chiral allyltitanium reagent and a double-asymmetric Simmons-Smith cyclopropanation to introduce three chiral centers, (2) Wittig and Wittig-Horner reactions to construct the C(3–4) and C(7–10) alkenes, and (3) a direct conversion of the thiazolidine to the thiazoline.

Site and Stereoselectivity of the Cyclopropanation of Unsymmetrically Substituted 1,3-Dienes by the Simmonssmith Reaction.+

Abstract In the Simmons-Smith reaction, 1,3-dienes are preferentially cyclopropanated at the more electron-rich double bond to afford the trans-vinylcyclopropane; an allylic hydroxyl group increases the reactivity and directs the cyclopropanation to the adjacent double bond. +Part of the results was presented at the XVIth International Conference on Organometallic Chemistry, Brighton, July 1994, abstract P228.

Density functional study on the mechanism of the Simmons–Smith reaction

Quantum chemical calculations based on density functional theory (DFT) including relativistic effects either through relativistic core potentials or an explicit, quasi-relativistic approach were used to study the mechanism of the Simmons–Smith cyclopropanation reaction. Under the assumption that the reactive organo-zinc–iodine species is monomeric, and neglecting solvent effects, a concerted one-step mechanistic scenario, postulated to be the most likely mechanism in the literature previously, has indeed been identified as the energetically most favourable pathway for the parent reaction of ethene with ICH2Znl to give cyclopropane and ZnI2. The attack of the cyclopropanating agent is electrophilic in character. Depending on the computational model applied, activation energies with respect to the educts are between 48 and 61 kJ mol–1, while the overall reaction is predicted to be exothermic by 140–158 kJ mol–1.

New vistas in organoelement chemistry

Abstract

Asymmetric Simmons-Smith Cyclopropanation of E-Allylic Alcohols Using 1,1′-Bi-2-naphthol-3,3′-dicarboxamide as a Chiral Auxiliary

Abstract N,N,N′,N′-Tetraethyl-1,1′-bi-2-naphthol-3,3′-dicarboxamide (1b) was found to be an effective chiral auxiliary for asymmetric Simmons-Smith cyclopropanation and high enantioselectivity greater than 85% ee was achieved in the reaction of E-allylic alcohols.

A catalytic enantioselective reaction using a C 2-symmetric disulfonamide as a chiral ligand: Simmons-Smith cyclopropanation of allylic alcohols by the Et 2Zn-CH 2I 2-disulfonamide system

A catalytic and enantioselective Simmons-Smith Cyclopropanation of an allylic alcohol was developed by the reaction of an allylic alcohol with Et 2Zn and CH 2I 2 in the presence of a catalytic amount of chiral disulfonamide 4.

Synthesis of 1,2-cyclopropanated sugars from glycals

Syntheses of both forms of cyclopropanated sugars from glycals by (i) Simmons–Smith reaction and (ii) dichiorocarbene addition followed by dehalogenation are described.

Studies towards the synthesis of FR-900848: stereoselective preparation of anti-bicyclopropane derivatives

Double Simmons–Smith cyclopropanation of 2,4-dien-1-ols stereoselectively gives the corresponding anti-bicyclopropane derivatives.

A Dramatic Effect of a Catalytic Amount of Lead on the Simmons-Smith Reaction and Formation of Alkylzinc Compounds from Iodoalkanes. Reactivity of Zinc Metal: Activation and Deactivation

A trace amount of lead found in zinc derivedfrom the pyrometallurgy smelting method decreases the reactivity of zinc toward diiodomethane and iodoalkanes substantially, and this negative effect can be suppressed by the addition of a catalytic amount of Me 3 SiCl

Design of Amphoteric Bifunctional Ligands: Application to the Enantioselective Simmons-Smith Cyclopropanation of Allylic Alcohols

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign of Amphoteric Bifunctional Ligands: Application to the Enantioselective Simmons-Smith Cyclopropanation of Allylic AlcoholsAndre B. Charette and Helene JuteauCite this: J. Am. Chem. Soc. 1994, 116, 6, 2651–2652Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://doi.org/10.1021/ja00085a068RIGHTS & PERMISSIONSArticle Views3069Altmetric-Citations171LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (829 KB) Get e-AlertsSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts

Synthesis of 20-hydroxy-17,21 -cyclopregnane derivatives: potential C-20 oxo steroid oxidoreductase inhibitors

20α- and 20β-Hydroxy-17α,21α-cyclopregnane derivatives, potential mechanism-based-inhibitors of 20α- and 20β-steroid oxidoreductases, have been synthesized by conversion of the steroid 17β-aldehyde into the 20-tert-butyldimethylsilyl enol ether followed by addition of methylene prepared from the Simmons–Smith reagent. Enzyme inhibition studies show that neither 20α- nor 20β-hydroxy-17α,21 α-cyclopregn-4-en-3-one were inhibitors of the respective enzymes from Streptomyces hydrogenans.

Approaches to the assembly of the antifungal agent FR-900848: studies on double asymmetric cyclopropanation and an X-ray crystallographic study of (1R,2R)-1,2-bis-[(1S,2S)-2-methylcyclopropyl]-1,2-ethanediyl 3,5-dinitrobenzoate

Double asymmetric Simmons–Smith cyclopropanation and Whitham elimination were used to prepare (E)-1,2-bis-[(1S,2S)-2-methylcyclopropyl]ethane, the dicyclopropylethene unit of FR-900848.

Enantioselective Cyclopropanation of Allylic Alcohols Catalyzed by a Chiral Disulfonamide-Aluminum Complex

Abstract A chiral disulfonamide-alkylaluminum complex prepared from (1R,2R)-N,N′-bis(benzenesulfonyl)-1,2-cyclohexanediamine and trialkylaluminum or i-Bu2AlH has been found to catalyze a Simmons-Smith cyclopropanation of allylic alcohols with Et2Zn and CH2I2 to afford the corresponding cyclopropanes in excellent yields with high enantiomeric excesses.

Synthesis of optically active cis- and trans-1,2-disubstituted cyclopropane derivatives by the Simmons-Smith reaction of allyl alcohol derivatives derived from (R)-2,3-O-isopropylideneglyceraldehyde

The Simmons-Smith reactions of Z- and E-allyl alcohol derivatives 6 derived from (R)-2,3-O-isopropylideneglyceraldehyde (6) were used for the synthesis of optically active cis- and trans-1,2-disubstituted cyclopropane derivatives. Reaction of 6 with diethyl zinc and diiodomethane gave cyclopropane derivatives 7 in 84% to quantitative yields with 35 to ≃100% des. Identical facial selectivities toward the double bonds, 1re-2si for Z-6 and 1re-2re for E-6, were observed in the cyclopropanations. The diastereoselectivity was dependent on the protecting group on the terminal allylic oxygen (R of 6, TBDPS>MOM>Bn) and on the stereochemistry of the double bond (Z >E). For TBDPS ethers Z-and E-6c, cis- and trans-7c were obtained as single distereomers, respectively. It was clearly demonstrated that the stereoselectivity of the cyclopropantion is controlled by the directing effect of the allylic oxygen (O-1) of the dioxolane ring, which coordinates to the reagent. The terminal allylic oxygen (O-2) lowered the diastereoselectivity. This reaction was applied to the synthesis of optically active cyclopropane analogs of γ-aminobutyric acid (GABA) 18,22, and ent-22