Intramolecular Nitrile Oxide Cycloaddition Research Articles

Toward the Briarane Core via 1,3-Dipolar Cycloaddition.

The complete C20 framework of brianthein W was established, featuring hydroboration/allylation, to provide the C1-C2 quaternary/tertiary stereoarray with excellent stereocontrol. Intramolecular nitrile oxide cycloaddition (INOC) was adopted as the key transformation to establish the trans-fused 6/10-bicyclic ring system. Evolution of the second INOC event revealed the intricacies governing regioselectivity, which ultimately led to construction of the highly strained 10-membered carbocycle.

Synthesis of a Novel Tetracyclic Isoxazole by Intramolecular Nitrile Oxide Cycloaddition

Intramolecular cycloadditions have the great advantage of forming two rings simultaneously. We report the use of intramolecular [3 + 2] cycloaddition of the nitrile oxide derived from an N-propargylbenzimidazole oxime in the synthesis of a hitherto unreported tetracyclic isoxazole-containing ring system bearing “6-5-5-5”-membered ring fusions. The initial condensation was achieved through reaction of o-phenylenediamine with ethyl diethoxyacetate, followed by alkylation with propargyl bromide, deprotection of the acetal to the aldehyde, formation of an aldoxime, and intramolecular nitrile oxide cycloaddition (INOC). Characterization of the aldoxime and tetracyclic isoxazole is included herein.

PIDA Mediated Synthesis of Benzopyranoisoxazoles via an Intramolecular Nitrile Oxide Cycloaddition (INOC): Application to the Synthesis 4H‐chromeno[4,3‐c]isoxazol‐4‐ones.

AbstractPresented herein is an approach for the synthesis of highly substituted tricyclic benzopyranoisoxazoles from the corresponding aldoximes via an intramolecular nitrile oxide cycloaddition (INOC) reaction using a hypervalent iodine reagent (Diacetoxyiodo)benzene (PIDA/DIB/(PhI(OAc)2) as the single inexpensive oxidizing agent. The key step involved in this reaction is a sequential intramolecular C−C and C−O bond formation. A variety of benzopyranoisoxazoles were constructed in moderate to high yields. In addition, some of the benzopyranoisoxazoles were converted to 4H‐chromeno[4,3‐c]isoxazol‐4‐ones via allylic oxidation using CrO3 as an oxidant.

Convenient Synthesis of Pyrazolo[4',3':5,6]pyrano[4,3-c][1,2]oxazoles via Intramolecular Nitrile Oxide Cycloaddition.

A simple and efficient synthetic route to the novel 3a,4-dihydro-3H,7H- and 4H,7H-pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazole ring systems from 3-(prop-2-en-1-yloxy)- or 3-(prop-2-yn-1-yloxy)-1H-pyrazole-4-carbaldehyde oximes has been developed by employing the intramolecular nitrile oxide cycloaddition (INOC) reaction as the key step. The configuration of intermediate aldoximes was unambiguously determined using NOESY experimental data and comparison of the magnitudes of 1JCH coupling constants of the iminyl moiety, which were greater by approximately 13 Hz for the predominant syn isomer. The structures of the obtained heterocyclic products were confirmed by detailed 1H, 13C and 15N NMR spectroscopic experiments and HRMS measurements.

Microwave induced synthesis of new class of pyrano isoxazoline and isoxazole annulated chromones - an intramolecular nitrile oxide cycloaddition with tethered olefins and alkynes

Microwave induced synthesis of new class of pyrano isoxazoline and isoxazole annulated chromones - an intramolecular nitrile oxide cycloaddition with tethered olefins and alkynes

Iminosugar C-Nitromethyl Glycoside: Stereoselective Synthesis of Isoxazoline and Isoxazole-Fused Bicyclic Iminosugars.

A simple and efficient method for the stereoselective synthesis of isoxazoline/isoxazole-fused iminosugar derivatives has been developed using intramolecular nitrile oxide cycloaddition (INOC) as a key step. Iminosugar C-nitromethyl glycosides, derived from simple carbohydrates, served as excellent nitrile oxide precursors in 1,3-dipolar cycloaddition reactions. N-Alkenyl iminosugar C-nitromethyl glycosides afforded novel isoxazoline-fused indolizidine-, pyrrolizidine-, and quinolizidine-based iminosugars in excellent yields with a high degree of stereoselectivity, whereas N-alkynyl iminosugar C-nitromethyl glycosides furnished the corresponding isoxazole containing tricyclic iminosugars in very good yields.

A new scalable synthesis of entecavir

A new synthesis of entecavir from d-glucose in an average total yield of 3.5% was achieved via an intramolecular nitrile oxide cycloaddition (INOC) reaction and a Peterson olefination as key-steps. The present process was designed for industrial application, using widely available raw materials, simple and cheap reagents and avoiding low reaction temperatures, which are very common in the synthetic approaches towards similarly complex structures.

Total Synthesis of (+)-Pochonin D and (+)-Monocillin II via Chemo- and Regioselective Intramolecular Nitrile Oxide Cycloaddition.

Asymmetric total syntheses of (+)-pochonin D (1) and (+)-monocillin II (2), Hsp90 inhibitors with potent anticancer activity, have been accomplished where the macrolactone 3 was constructed through a chemo- and regioselective intramolecular nitrile oxide cycloaddition of diene 4.

Synthesis of pyrano isoxazoline/isoxazole annulated coumarins via intramolecular nitrile oxide cycloaddition and their cytotoxicity

An efficient and straight forward procedure for the syntheses of isoxazoline/isoxazole fused coumarin analogues 7a–7g and 8a–8g from the corresponding 7-O-allyloxy coumarin oximes 5a–5g and 7-O-propargyloxy coumarin oximes 6a–6g is presented. High yields and simple experimental procedures are important features of this methodology. This method is useful for the construction of many biologically active fused heterocycles. The structures of synthesized compounds are established on the basis of IR, NMR, and MS data. The products were tested for in vitro cytotoxic activity against three human cancer cell lines. All tested compounds demonstrated high cytotoxic activity.

Synthesis of macrocyclic conjugated ψ-disacharides via nitrile oxide cycloaddition: Alkenyl chain length controlled unprecedented formation of di-oxa heterocycles from monosaccharides

Various symmetrical and unsymmetrical isoxazoline embodied chiral macroheterocycles were synthesized from carbohydrate derived oximes. Our result shows that the mode of cycloaddition is dependent on the length and tether present in alkenyl chain of sugar moiety. Thus in some cases inter- and intramolecular cycloaddition of nitrile oxide were observed with high selectivity. The cycloadducts contains two sugar units linked via macrocycles thus they are considered as pseudo-disacharides. The stereochemistry of the newly formed chiral centers was established by 2D-NMR techniques and X-ray crystallographic studies.

Two new entries to the ABF tricyclic ring system of 7,17-seco-type C19-diterpenoid alkaloids via free radical cyclization and [3+2] cycloaddition of nitrile oxide

Two new approaches for the construction the ABF ring systems of 7,17-seco-type C19-diterpenoid alkaloids have been successfully developed by using free radical cyclization and intramolecular nitrile oxide cycloaddition, respectively, as the key steps. Both methods would probably provide alternative strategies for the elaboration of AEF-rings in the total synthesis of 7,17-seco-type C19-diterpenoid alkaloids based on our previously prepared BCD ring systems.

Remote Stereoinductive Intramolecular Nitrile Oxide Cycloaddition: Asymmetric Total Synthesis and Structure Revision of (-)-11β-Hydroxycurvularin.

The first total synthesis and structure revision of (-)-11β-hydroxycurvularin (1b), a macrolide possessing a β-hydroxyketone moiety, were accomplished. The β-hydroxyketone moiety in this natural product was introduced by cleavage of the N-O bond in an isoxazoline ring that was formed diastereoselectively in a 1,5-remote stereocontrolled fashion by employing intramolecular nitrile oxide cycloaddition.

Synthesis of Bicyclic Isoxazoles and Isoxazolines via Intramolecular Nitrile Oxide Cycloaddition.

An efficient and straight forward procedure for the syntheses of bicyclic isoxazole/isoxazoline derivatives from the corresponding dimethyl-2-(2-nitro-1-aryl/alkyl)-2-(prop-2-yn-1yl)malonates or dimethyl 2-allyl-2-(2-nitro-1-aryl/alkyl ethyl)malonate is described. High yields and simple operations are important features of this methodology.

ChemInform Abstract: Stereoselective Synthesis of the CDE Ring System of Antitumor Saponin Scillascilloside E‐1.

AbstractThe tricyclic ring portion (I) of the eucosterol oligoglycoside scillascilloside E‐1 is synthesized via an Ireland—Claisen rearrangement and an intramolecular nitrile oxide cycloaddition.

Stereoselective Synthesis of the CDE Ring System of Antitumor Saponin Scillascilloside E-1

A stereoselective synthesis of the CDE ring portion of the antitumor saponin scillascilloside E-1 has been achieved, utilizing an Ireland-Claisen rearrangement to construct the contiguous tetrasubstituted stereocenters at C13 and C17 simultaneously and intramolecular nitrile oxide cycloaddition to form the five-membered ring as key steps.

ChemInform Abstract: An Expedient Approach to the Total Synthesis of (+)‐5‐epi‐Eudesm‐4(15)‐ene‐1β,6β‐diol.

AbstractThe title compound (V) is synthesized via an Ireland—Claisen rearrangement of glycolate ester (I) and an intramolecular nitrile oxide cycloaddition [→ (IV)] as key steps.

Synthesis of furan derivatives of cyclic β-amino acid cispentacin via intramolecular nitrile oxide cycloaddition

Two furan derivatives of cispentacin have been synthesized starting from a d-mannitol derived conjugated nitroolefin through intramolecular nitrile oxide cycloaddition (INOC) as a key step.

Synthesis of Entecavir (BMS-200475)

A synthesis of Entecavir (BMS-200475) was achieved starting from 1,3-propanediol in 15 steps and 23.4% overall yield. A unique feature of the synthetic route is that the five-membered carbocyclic core is installed by an intramolecular nitrile oxide cycloaddition (INOC) reaction and the guanine moiety is introduced by a Mitsunobu reaction. The route is characteristic of low cost, high yield and easy operation.

Recent Advances in Intramolecular Nitrile Oxide Cycloadditions in the Synthesis of 2-Isoxazolines

Recent Advances in Intramolecular Nitrile Oxide Cycloadditions in the Synthesis of 2-Isoxazolines

Synthesis of new 2-substituted 3-amino-4-hydroxymethylthiophenes through intramolecular nitrile oxide cycloaddition processes and N,O-bond cleavage

A synthesis of new 2-substituted 3-amino-4-hydroxymethylthiophenes 7 is reported as a useful alternative to the long known oximation of oxothiophenes 8, followed by treatment with gaseous hydrochloric acid in a polar solvent. The synthesis consists of an INOC process of unsaturated sulfide nitrile oxides, obtained from the condensation of corresponding nitroalkenes and allylmercaptan and then dehydration, which leads to tetrahydrothieno(3,4-c)isoxazoline 4. N,O- Bond cleavage of 4 upon hydride reduction affords to thiophenes 7 of biological interest.