Oxidopyrylium Ylides Research Articles

Enantioselective [5+2] Cycloaddition of Oxidopyrylium Ylides and Enals

Enantioselective [5+2] Cycloaddition of Oxidopyrylium Ylides and Enals

ChemInform Abstract: Dearomative Indole [5 + 2] Cycloaddition Reactions: Stereoselective Synthesis of Highly Functionalized Cyclohepta[b]indoles.

The first dearomative indole [5+2] cycloaddition reaction with an oxidopyrylium ylide resulted in efficient and diastereoselective construction of some highly functionalized and synthetically challenging oxacyclohepta[b]indoles. The protocol proceeds under very mild reaction conditions, thus enabling high functional-group tolerance and unique endo selectivity.

Catalytic enantioselective [5+2] cycloaddition between oxidopyrylium ylides and enals under dienamine activation.

Benzopyrylium ylides generated in situ from 1-acetoxyisochroman-4-ones reacted with α,β-unsaturated aldehydes in the presence of a bifunctional secondary-amine/squaramide catalyst to furnish [5+2] cycloaddition products in good yield with high diastereo- and enantioselectivity. The reaction proceeds by dienamine activation and involves β,γ-functionalization of the enal. The dienamine intermediates showed exclusive β,γ-reactivity and provided direct access to compounds with the 8-oxabicyclo[3.2.1]octane framework. The ability of the bifunctional secondary-amine/squaramide catalyst to engage in hydrogen-bonding interactions with the ylide made it particularly effective in terms of both the yield and the stereoselectivity of the transformation.

Catalytic Enantioselective [5+2] Cycloaddition between Oxidopyrylium Ylides and Enals under Dienamine Activation

AbstractBenzopyrylium ylides generated in situ from 1‐acetoxyisochroman‐4‐ones reacted with α,β‐unsaturated aldehydes in the presence of a bifunctional secondary‐amine/squaramide catalyst to furnish [5+2] cycloaddition products in good yield with high diastereo‐ and enantioselectivity. The reaction proceeds by dienamine activation and involves β,γ‐functionalization of the enal. The dienamine intermediates showed exclusive β,γ‐reactivity and provided direct access to compounds with the 8‐oxabicyclo[3.2.1]octane framework. The ability of the bifunctional secondary‐amine/squaramide catalyst to engage in hydrogen‐bonding interactions with the ylide made it particularly effective in terms of both the yield and the stereoselectivity of the transformation.

Dearomative indole [5+2] cycloaddition reactions: stereoselective synthesis of highly functionalized cyclohepta[b]indoles.

The first dearomative indole [5+2] cycloaddition reaction with an oxidopyrylium ylide resulted in efficient and diastereoselective construction of some highly functionalized and synthetically challenging oxacyclohepta[b]indoles. The protocol proceeds under very mild reaction conditions, thus enabling high functional-group tolerance and unique endo selectivity.

Dearomative Indole [5+2] Cycloaddition Reactions: Stereoselective Synthesis of Highly Functionalized Cyclohepta[b]indoles

AbstractThe first dearomative indole [5+2] cycloaddition reaction with an oxidopyrylium ylide resulted in efficient and diastereoselective construction of some highly functionalized and synthetically challenging oxacyclohepta[b]indoles. The protocol proceeds under very mild reaction conditions, thus enabling high functional‐group tolerance and unique endo selectivity.

Silicon-Tethered Intramolecular [5+2] Oxidopyrylium-Based Cycloaddition and Reductive Cleavage of Ether Bridge: Synthetic Studies Toward Arteminolides

Arteminolides A-D (1-4), natural triterpene lactones, were isolated from the leaves of Artemisia sylvatica Maxim and have been reported to be strong inhibitiors of farnesyltrnasferase (FTase) targeting members of the Ras superfamily of small GTP-binding proteins critical to cell cycle progression. Thus, arteminolides have displayed the tumor cell growth inhibition in a dose-dependent manner. In addition, arteminolide A (1) exhibited selective inhibition of recombinant rat FTase with no significant inhibition of rat squalene synthase or geranylgeranyltransferase (GGTase), and arteminolide C (3) blocked in vivo growth of human colon and lung tumor xenograft without the loss of body weight in nude mice. As well as the biological profile their structural complexity with the rigid ring skeleton could facilitate the study on the structure-activity relationships (SARs) with three dimensional information, which can direct new FTase inhibitor with high therapeutic value. Despite their favorable biological profile and intriguing structural complexity the success in the synthesis of arteminolides has not been reported since their first isolation in 1998. Due to identification of dehydromatricarin A (5) and arglabin diene (6), the biogenic synthesis of arteminolides are believed to be accomplished via Diels-Alder reaction between the two precursors (Scheme 1). Since the most logical precursors for the total synthesis of these natural products are the two biogenic precursors, we envisioned a common intermediate 9 which could offer the two precursors, 5 and 6, via Pauson-Khand reactions of 7 and 8, respectively. The intermediate 9 contains the silicon which could serve as surrogates for both hydroxyl group and hydrogen corresponding to C8-OH of 5 and C8'-H of 6, respectively, and was expected to be obtained through intramolecular [5+2] dipolar cycloaddition reaction of oxidopyrylium ylide. The silyl group would be stable under various reaction conditions and readily converted to the hydroxyl with the retention of the configuration. We previously found that base-mediated cleavage of the ether bridge in 7' (R = H, R' = PMB) afforded 11 in low yield (32%). In addition, attempts to oxidize alcohol 11 into ketone 12 under various reaction conditions for introduction of the exo methylene and methyl group at C10 and C10', respectively, resulted in ketone 12 with unacceptable low yields and, unexpectedly, TPAP oxidation produced a 1:1 mixture of ketone 12 and initial ether bridged 7'. These unfavorable results directed our efforts to prepare intermediate 13 possessing iodomethyl group which could allow to cleave the ether bridge using reductive deiodination, resulting in exo methylene (Scheme 2). The synthesis of 13 commenced with aldehyde 15 which was prepared by selective mono-silylation of 1,3-propanediol, followed by Swern oxidation. Coupling of 15 with lithiated furan 16 produced furanyl alcohol 17 in 60% yield, which was then converted to vinylsilyl ether 18 having necess-

Synthesis of (-)-Silvestrol

Silvestrol, isolated from the Aglaia foveolata, possesses cytotoxic activity comparable to paclitaxel. The first enantioselective synthesis of silvestrol is reported here; it involved an enantioselective [3+2] photocycloaddition of an oxidopyrylium ylide derived from excited-state intramolecular proton transfer of 3-hydroxyflavone C using a chiral Brønsted acid D.

The role of the transfer group in the intramolecular [5+2] cycloadditions of substituted β-hydroxy-γ-pyrones: a DFT analysis

The intramolecular [5+2] cycloaddition reactions of a series of 3-OR (R=SiMe3, H, CHO, Me) substituted β-hydroxy-γ-pyrones bearing tethered alkenes were studied using DFT methods at the B3LYP/6–31G* level. The role of the transfer R group was analyzed considering two alternative channels: (i) in channel a the process is initialized by the transfer of the R group with formation of an oxidopyrylium ylide intermediate, which is followed of an intramolecular [5+2] cycloaddition; (ii) in channel b, the process is initialized by the intramolecular [5+2] cycloaddition on the γ-pyrone followed by the transfer of the R group. Copyright © 2005 John Wiley & Sons, Ltd.

A theoretical rationalization of the asymmetric induction in sulfinyl-directed [5C + 2C] intramolecular cycloadditions.

A computational DFT examination (B3LYP/6-31G and B3LYP/6-311+G//B3LYP/6-31G) of the thermal [5C + 2C] cycloaddditions of 6-acetoxy-3-pyranones and 3-silyloxy-4-pyrones with tethered alkenyl sulfoxides confirms that the high level of diastereofacial selectivity obtained is ultimately due to the preference of the alkenesulfinyl group to adopt a well-defined conformation in the transition state of the reaction. This conformation, which is different from that found in the ground state, is most probably dictated by dipolar interaction effects between the sulfoxide and the oxidopyrylium ylide intermediate.

ChemInform Abstract: Toward an Understanding of the Mechanisms of the Intramolecular [5 + 2] Cycloaddition Reaction of γ-Pyrones Bearing Tethered Alkenes. A Theoretical Study.

The molecular mechanism for the intramolecular [5 + 2] cycloaddition reaction of β-silyloxy-γ-pyrones bearing tethered alkenes has been characterized using ab initio methods. A comparative study for this sort of cycloaddition carried out at different computational levels points out that the B3LYP/6-31G* calculations give similar barriers to those obtained with the MP3/6-31G* level. Analysis of the energetic results shows that the reaction takes place along a stepwise process: first, the migration of the neighboring silyl group to the carbonyl group of the γ-pyrone takes place to give a weak oxidopyrylium ylide intermediate, which by a subsequent concerted intramolecular [5 + 2] cycloaddition affords the final cycloadduct. The cycloaddition process is very stereoselective due to the constraints imposed by the tether. The [5 + 2] cycloaddition reaction has a large barrier, and the presence of the silyloxy group and the intramolecular character of the process are necessary to ensure the thermodynamic and ki...

Toward an understanding of the mechanisms of the intramolecular

The molecular mechanism for the intramolecular [5 + 2] cycloaddition reaction of beta-silyloxy-gamma-pyrones bearing tethered alkenes has been characterized using ab initio methods. A comparative study for this sort of cycloaddition carried out at different computational levels points out that the B3LYP/6-31G calculations give similar barriers to those obtained with the MP3/6-31G level. Analysis of the energetic results shows that the reaction takes place along a stepwise process: first, the migration of the neighboring silyl group to the carbonyl group of the gamma-pyrone takes place to give a weak oxidopyrylium ylide intermediate, which by a subsequent concerted intramolecular [5 + 2] cycloaddition affords the final cycloadduct. The cycloaddition process is very stereoselective due to the constraints imposed by the tether. The [5 + 2] cycloaddition reaction has a large barrier, and the presence of the silyloxy group and the intramolecular character of the process are necessary to ensure the thermodynamic and kinetic feasibility of these cycloadditions.

ChemInform Abstract: INTRAMOLECULAR CYCLOADDITIONS WITH OXIDOPYRYLIUM YLIDES

Chemischer InformationsdienstVolume 14, Issue 6 Preparative Organic Chemistry ChemInform Abstract: INTRAMOLECULAR CYCLOADDITIONS WITH OXIDOPYRYLIUM YLIDES P. G. SAMMES, P. G. SAMMESSearch for more papers by this authorL. J. STREET, L. J. STREETSearch for more papers by this author P. G. SAMMES, P. G. SAMMESSearch for more papers by this authorL. J. STREET, L. J. STREETSearch for more papers by this author First published: February 8, 1983 https://doi.org/10.1002/chin.198306097Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume14, Issue6February 8, 1983 RelatedInformation