Intramolecular Nitrile Oxide Cycloaddition Research Articles

Development of the First Spiro Bis(isoxazoline) Ligands (SPRIXs) and Their Applications to Catalytic Enantioselective Reactions

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Development of the First Spiro Bis (isoxazoline) Ligands (SPRIXs) and Their Applications to Catalytic Enantioselective Reactions

The first chiral isoxazoline ligands bearing spiro skeleton are developed. The spiro bis (isoxazoline) ligands (SPRIXs) are readily synthesized from diethyl malonate via double intramolecular nitrile oxide cycloaddition as a key step. The complex of (M, S, S) -R-SPRIX and Pd (OCOCF3)2 promoted the catalytic asymmetric Wacker-type cyclization of alkenyl alcohols to give optically active cyclic ethers for the first time. Furthermore, starting from dialkenyl alcohol, the enantioselective tandem cyclization via oxy-palladation was achieved with up to 95% ee. Asymmetric ligands other than SPRIXs promote neither the Wacker-type reaction nor the tandem reaction.

Asymmetric epoxidation catalyzed by d-glucose-derived uloses

Three ulose catalysts ( 1– 3 ) were prepared from d-glucose via an intramolecular nitrile oxide cycloaddition (INOC) as the key step. The enantioselectivity of ulose 2 and 3 in asymmetric epoxidation was poor (up to 26% ee). Ulose 1 afforded good chemical yields (up to 83% yield) and the enantiomeric excess is up to 71% for the formation of (−)- trans-stilbene oxide.

Role of conformational effects on the regioselectivity of macrocyclic INOC reactions: two new asymmetric total syntheses of (+)-brefeldin A.

We have gained some insight into the role of conformational effects on the regioselectivity of the macrocyclic intramolecular nitrile oxide cycloaddition observed in our (+)-brefeldin A synthesis. During the course of this regiochemical study, we have developed two novel stereoselective and regioselective schemes for total synthesis of (+)-brefeldin A (i.e. intramolecular nitrile oxide cycloaddition-isomerization and intermolecular nitrile oxide cycloaddition-ring closing metathesis strategies).

ChemInform Abstract: Synthesis of Chiral 10, 11 and 12‐Membered Nitrogen and Oxygen Heterocycles by Intramolecular Nitrile Oxide Cycloaddition of Tethered N‐ and O‐Allyl Carbohydrate Derivatives.

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Synthesis of Chiral 10, 11 and 12-Membered Nitrogen and Oxygen Heterocycles by Intramolecular Nitrile Oxide Cycloaddition of Tethered N- and O-Allyl Carbohydrate Derivatives

Chiral 10 to 12-membered nitrogen and oxygen heterocycles fused to isoxazoline rings have been prepared in a highly regioselective and stereoselective manner by intramolecular nitrile oxide cycloaddition of tethered N- and O-allyl carbohydrate derivatives. The use of a –Y–Ar-CH 2 tether containing a 1,2-disubstituted aromatic ring between the heteroatom attached to the nitrile oxide-bearing carbohydrate scaffold, and the allyl group, facilitates the formation of the medium-sized rings. The cycloaddition afforded bridged isoxazolines in the cases of O-tethered allyl carbohydrate derivatives, whereas a fused isoxazoline resulted when a N(Ts)-tethered allyl derivative was used.

Sequential 1,3-dipolar cycloadditions in the synthesis of bis-isoxazolo substituted piperidinones

A strategy for the efficient synthesis of novel bis-isoxazolo substituted piperidinones has been developed. The protocol consists of the Michael addition of an unsaturated alkoxide to beta-nitrostyrene followed by an intramolecular nitrile oxide cycloaddition (INOC) or an intramolecular silyl nitronate olefin cycloaddition (ISOC) to give III. Grignard addition to this isoxazoline intermediate followed by DCC coupling of the resulting isoxazolidine with nitroacetic acid gave II, and a second intramolecular cycloaddition via 1,3-dipoles result in the formation of the targeted novel tetracycles (I). A solid-supported scavenger was employed to increase the efficiency and yield of the Michael addition step.

Studies Directed Toward the Synthesis of Taxanes: Evaluation of the B-Ring Formation By an Intramolecular Nitrile Oxide Cycloaddition

Several models for the formation of the 8-membered B-ring of taxanes by an intramolecular nitrile oxide [3+2] cycloaddition were prepared from the monoacetal of 2,2-dimethylcyclohexane-1,3-dione (5). The nitrile oxides were then generated under high-dilution conditions. In most cases only oligomers were obtained. The isoxazoline 19, containing a 9-membered ring, was formed from the nitrile oxide 17, and a bis(isoxazoline) 21was isolated from the reaction of the nitro compound 16c.

Design and Synthesis of the First Spiro Bis(isoxazoline) Derivatives as Asymmetric Ligands

A chiral bis(isoxazoline) ligand (SPRIX) containing a rigid spiro skeleton was designed and synthesized via a double intramolecular nitrile oxide cycloaddition. The optically pure SPRIX greatly accelerated the Cu(acac)2-catalyzed asymmetric reaction of diisopropylzinc with cyclohexenone to give the Michael adduct with 49% ee. This is the first example of the use of an isoxazoline ligand for a transition metal-catalyzed reaction. The X-ray crystallographic analysis of the hexacoordinated copper complex of SPRIX confirmed the ligand character.

Synthesis of Enantiopure Pyranoisoxazole and Oxepanoisoxazole Derivatives from O-Alkynyl Carbohydrate Ethers by the Application of Intramolecular Nitrile Oxide Cycloaddition

Synthesis of Enantiopure Pyranoisoxazole and Oxepanoisoxazole Derivatives from O-Alkynyl Carbohydrate Ethers by the Application of Intramolecular Nitrile Oxide Cycloaddition

A catalytic asymmetric synthesis of a versatile intermediate for phorbol derivatives

A catalytic asymmetric cyclopropanation of enol silyl ether 9 gave the lactone 3 in up to 78% ee. The lactone 3 was then transformed into 2, potentially a very versatile intermediate for phorbol analogs, using an intramolecular nitrile oxide cycloaddition as a key step.

Fused pyrazolo heterocycles: intramolecular [3+2]-nitrile oxide cycloadditions applied to syntheses of pyrazolo [3,4-g] [2,1] dihydrobenzoisoxazol (in) es

A general method is described to prepare pyrazolo [3,4-g] - [2,1] dihydrobenzoisoxazol (in) es utilizing intramolecular nitrile oxide cycloaddition (INOC) as the key step.

Synthesis of chiral pyranocyclohexane, oxepanocyclohexane, and furylpyran and -oxepane systems by the application of intramolecular nitrone and nitrile oxide cycloaddition of carbohydrate derivatives

Chiral nonracemic pyranocyclohexanes 7 and 8 and oxepanocyclohexane 11 and 12 were obtained from a single 1,2-isopropylidene-3- O-cyclohexenyl carbohydrate aldehyde 4 via intramolecular nitrile oxide cycloaddition, and were converted to 2-(2′-tetrahydrofuryl)pyran 28, which incorporates the lasalocid skeleton, and the related oxepane derivative 32 respectively, through modification of the furanoside ring by applying 2- O-allyl carbohydrate nitrone cycloaddition.

Synthesis of 6,6-Disubstituted Tetrahydrothiopheno [3,4-c] Isoxazolines from β-Nitroenones

β-Nitrosulfides 2, formed by Michael addition of prop-2-en-1-thiol to β-nitroenones 1 in the presence of a catalytic amount of triethylamine, undergo either Intramolecular Nitrile Oxide Cycloadditions (INOC) or Intramolecular Silylnitronate Cycloadditions (ISOC) to functionalized 6,6-disubstituted tetrahydrothiopheno [3,4-c] isoxazolines 3 and 4. The stereoselectivity, poor by the INOC reactions starting from acyclic β-nitroenones, is markedly increased with the ISOC procedure.

Construction of A and C Ring Intermediates for Taxol by Using (3+2)-Cycloaddition of Nitrile Oxide

Syntheses of the A-ring and the chiral C-ring model of taxol by using the intramolecular nitrile oxide cycloaddition and its diastereoselectivity based on MM2 transition state model are described. © 1997 Elsevier Science Ltd.

A Highly Stereoselective One-Pot Tandem Consecutive 1,4-Addition-Intramolecular 1,3-Dipolar Cycloaddition Strategy for the Construction of Functionalized Five- and Six-Membered Carbocycles(,)(1).

Nitronates 3, possessing a suitably located olefinic moiety and arising from conjugate addition of Grignard reagent 2 to nitro olefins 1, are trapped as silyl nitronates 8 which undergo a facile intramolecular 1,3-dipolar cycloaddition. The resulting N-(silyloxy)isoxazolidines 9 are readily transformed into isoxazolines 6 and 7 upon treatment with acid, thus completing the entire sequence in one pot. While cycloaddition to the five-membered carbocycles, in general, proceeds smoothly at rt in a stereospecific manner, that to the six-membered ring is sluggish and less selective. The advantages of this strategy over the intramolecular nitrile oxide cycloaddition, namely greater stereoselectivity and adaptability to one-pot conditions, have been demonstrated. Extensive NMR investigations unravelled the stereochemistry unambiguously and underscored the inadequacy of coupling constants alone in determining the stereochemistry in cyclopentane systems. The explanation advanced to account for the selectivities, in terms of subtle differences among the putative transition state geometries, is in qualitative agreement with widely accepted assumptions pertaining to 1,3-dipolar cycloadditions.

Intramolecular nitrile oxide cycloaddition (INOC) of substituted amido-oximes

Functionalized enantiomerically pure 3,4-dehydropyrrolidin-2-one and 1,2-dehydropyrrolizidin-3-one systems have been achieved by intramolecular nitrile oxide cycloaddition, starting from enamido-oximes, and by subsequent reduction of the obtained cycloadducts.

Synthetic studies on zoapatanol: Construction of oxepanes via an intramolecular 1,3-dipolar cycloaddition strategy

Abstract The nitrones derived from β-allyloxyaldehydes with a β-quaternary centre cyclized to give six- instead of seven-membered O -heterocycles exclusively whereas a nitrile oxide derived from a γ-allyloxyaldehyde with a γ-quaternary center cyclized to yield an oxepane ring as the sole product. Using the latter intramolecular nitrile oxide cycloaddition as the key step, optically active oxepane 5 , which is a suitable intermediate for a synthesis of zoapatanol 1 , has been constructed from d -glucose.

An intramolecular 1,3-dipolar cycloaddition approach to a pyrimidoazepinone derivative. A potentially useful intermediate towards the synthesis of pyrimidoazepine based folic acid derivatives

An intramolecular nitrile oxide cycloaddition route to the isoxazolinopyrimidoazepine derivative 21 is described. This was transformed to the pyrimidoazepinone derivative 22, a potentially useful intermediate for the synthesis of pyrimidoazepine based folic acid derivatives. [Display omitted]

An enantiospecific entry to fluoro substituted aminocyclopentanols through intramolecular nitrile oxide, nitrone, and oxime cycloaddition reactions

Starting from (2 R,3 S)-2-benzyloxy-3-fluoro-5-hexenale 2 and its (2 R,3 R) epimer, cyclopentanoisoxazolidines 4 and 7 are obtained with complete diastereoselectivity through nitrone and oxime intiainolecular cycloaddition reactions. In contrast, cyclopentanoisoxazolines 6 are formed with only medium stereoselectivily through intramolecular nitrile oxide cycloaddition reactions. Further elaboration of these bicyclic compounds affords fluoro substituted aminocyclopetanols 8 and 10 in enantiomerically and diastereoisomerically pure form.