Diastereoselective nitrile oxide cycloadditions to chiral allyl ethers derived from 1,1-dithio-3-buten-2-ols

Highly diastereoselective cycloaddition of nitrile oxides to the title compounds gives masked polyfunctional products amenable to a variety of synthetic elaboration; an entry to enantiomerically pure derivatives is described.     

Intramolecular 1,3-dipolar cycloadditions of aliphatic nitrile oxides

Treatment of functionalized 1-chloro-oximes ( 3c and 4a,b ) with triethylamine originates nitrile oxides ( 1c and 2a,b ) which undergo an intramolecular cycloaddition providing fused-ring isoxazole derivatives ( 7c and 8a,b ). The latter reaction was not observed for one substrate ( 2c ).     

Diastereoselective and intramolecular cycloadditions of asymmetric p-nitroso phosphine oxides

Benzyl phenyl P-nitroso phosphine oxide (5) reacts as an N-O heterodienophile with 1,3-cyclopentadiene to give the diastereomeric cycloadducts 6a,b in a ratio of 1.5:1 (6a:6b). The same reaction in the presence of tin tetrachloride produces 6a,b in a ratio of 2.9:1 (6a:6b). Cycloaddition of the structurally modified P-nitroso phosphine oxide (18) with 1,3-cyclopentadiene forms the diastereomeric cycloadducts 16a,b in a ratio of 3.1:1 (16a:16b). These results suggest the reactions of these P-nitroso phosphine oxides and 1,3-cyclopentadiene occur through a transition state where the heterodienophile adopts an s-cis conformation and approaches the diene in an exo fashion syn to the phenyl group. This model resembles those proposed for the cycloadditions of the structurally similar asymmetric vinyl phosphine oxides. Reaction of 18 with 1,3-cyclopentadiene in the presence of a Lewis acid produces cycloadducts 16a,b in a ratio of 7:1 (16a:16b), which approaches synthetic utility. Similar experiments show that 1,3-cyclohexadiene likely reacts with P-nitroso phosphine oxides through a different transition state, limiting current predictions regarding the diastereoselectivity of these reactions. The intramolecular cycloaddition of an asymmetric P-nitroso phosphine oxide (19) for the first time produces a unique phosphorus-containing heterocyclic compound (20).     

Stereoconvergent and stepwise 1,3-dipolar cycloadditions of nitrile oxides and nitrile imines

The first example of stereoconvergent 1,3-dipolar cycloaddition of nitrile oxides and nitrile imines with E/Z isomeric mixture of electron-deficient olefins is reported, delivering isoxazolines and pyrazolines bearing two vicinal stereogenic tertiary and trifluoromethylated quaternary carbon centers with perfect regioand diastereoselectivities. The possibility of concerted cycloaddition/epimerization sequence under basic condition to form the thermodynamically stable diastereomers is excluded th...     

Activation of nitriles by hydrogen bonding in cycloadditions with nitrile oxides

The dipolarophilic activity of aromatic nitriles in cycloaddition with benzonitrile oxides is remarkably enhanced by ortho-acylamino substituents. The activation depends upon the solvent and can be ascribed to a hydrogen bond which assists cycloaddition.     

Intramolecular 1,3-dipolar cycloadditions of norbornadiene-tethered nitrile oxides.

Efficient routes to the synthesis of norbornadiene-tethered nitrile oxides have been developed, and their intramolecular 1,3-dipolar cycloadditions were studied. The cycloadditions occurred in good yields for a variety of substrates and were found to be highly regio- and stereoselective, giving single regio- and stereoisomers in most cases.     

Cycloaddition of nitrile oxides to substituted vinylphosphonates

Cycloaddition of nitrile oxides to substituted vinylphosphonates was performed. A series of 4,5‐dihydroisoxazoles containing phosphonyl group were synthesized under very mild condition in excellent regiospecificity. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:309–311, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10149     

Preparation of substituted allyl acetates and sulfones from Baylis-Hillman adducts in ionic liquid media

Reactions of potassium acetate and the sodium salt of p-toluenesulfinic acid with acetates of Baylis-Hillman adducts produce substituted allyl acetates and allyl sulfones respectively. Ionic liquids are utilized in place of conventional solvents.     

Amine-promoted cyclocondensation of highly substituted aromatic nitrile oxides with diketones

Base-promoted cyclocondensation of hindered nitrile oxides and cyclic diketones affords highly functionalized, sterically-encumbered isoxazole products in good yield. The mild reaction conditions (NEt₃, EtOH) are tolerant to a wide variety of functionality and permit the preparation of precursors to complex polycycles typically inaccessible via direct, intermolecular carboncarbon bond forming reactions. The ability to effect the cyclocondensation reaction with a catalytic amount of amine points to the intermediacy of an ammonium enolate as a key reactive species. A convenient, single step preparation of crystalline, stable nitrile oxides from the corresponding oximes enhances the advantages of this methodology for the preparation of functionalized polycycles.     

1,3-Dipolar cycloadditions of 2-thio-3-chloroacrylamides with nitrile oxides and nitrones

1,3-Dipolar cycloadditions of 2-thio-3-chloroacrylamides with nitrile oxides and nitrones is described. A series of novel isoxazolines are isolated from the nitrile oxide cycloadditions, whilst the isoxazolines generated from the nitrone cycloadditions undergo further ring opening to yield piperidines.     

Regioselectivity of cycloadditions of nitrile oxides and nitrones to 4-methylene-tetrahydrothiopyrane

Summary The cycloaddition of nitrile oxides and nitrones to 4-methylene-tetrahydrothiopyrane proceeds regioselectively under the formation of spiro-substituted isoxazole derivatives4 and9. Semiempirical calculations (AM1) were used to analyze the electronic structure of reactants, energies of products, and activation barriers leading to these products in order to rationalize this exclusive regioselectivity. It was shown that the main factor responsible for the high stereoselectivity of this reaction is not frontier orbital control, but mainly electrostatic and steric interactions. The spiro compounds4 were cleaved by hydrogenolysis to -amino-alcohols11, which were recyclized to spiro-oxazines12 and13.4 and9 as well as12 and13 are derivatives of novel heterocylic systems.

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Regioselektive Cycloadditionen von Nitriloxiden und Nitronen an 4-Methylen-tetrahydrothiopyran

Zusammenfassung Die Cycloaddition von Nitrilen und Nitriloxiden an 4-Methylen-tetrahydrothiopyran zeigt einen regioselektiven Verlauf unter Bildung der spiro-substituierten Isoxazolderivate4 und9. Die elektronischen Strukturen von Reaktanden, Energien von möglichen Reaktionsprodukten und die Aktivierungsbarrieren der durchgeführten Reaktionen wurden mittels semiempirischer Verfahren (AM1) untersucht, um die beobachteten eindeutigen Regioselektivitäten zu interpretieren. Es zeigte sich, daß dafür nicht ausschließlich Frontorbitalkontrolle, sondern vor allem elektrostatische und sterische Wechselwirkungen verantwortlich sind.Die Spiroverbindungen4 wurden in weiterer Folge durch Reduktion zu den entsprechenden -Aminoalkoholen11 gespalten, welche wiederum zu Spiro-oxazinen des Typs12 und13 recyclisiert wurden. Die Verbindungen4 und9 sind ebenso wie12 und13 Derivate von neuen heterocyclischen Grundsystemen.

     

Asymmetric 1,3-dipolar cycloadditions of chiral carboxyloyl nitrile oxides to cycloalkenes

Asymmetric 1,3-dipolar cycloadditions of chiral carboxyloyl nitrile oxides derived from (2R)-bornane-10,2-sultam, (1R)-8-phenylmenthol, N,N-dicyclohexyl-10-sulfamoyl-(2R)-isoborneol, and 7,7-dimethylnorbornane-(1S,2R)-oxazolidinone to four cycloalkenes, leading to the corresponding 2-isoxazolines in both moderate yields and diastereoselectivities, are presented. All cycloadducts were converted into the corresponding alcohols, which were used for the determination of enantiomeric purity via chiral gas chromatography. In the case of the six-membered ring cycloadduct, the absolute configuration was determined by X-ray analysis.     

1,3-Dipolar cycloadditions of prop-1-ene-1,3-sultone with nitrile oxides/nitrones

The scope and limitations of dipolar cycloaddition reactions between nitrile oxides/nitrones and prop-1-ene-1,3-sultone have been investigated. A remarkably high degree of regioselectivity and stereoselectivity was observed. The homochiral sultam 8e was synthesized in a four-step reaction sequence starting from the substituted isoxazoline 4e obtained from the cycloaddition. The absolute stereochemistry of this material was assigned by an X-ray crystallographic investigation of the intermediate 7e.     

Diastereoselective cobalt-mediated [2 + 2 + 2] cycloadditions of substituted linear enediynes phosphine oxides: scope and limitations

Variously substituted linear enediynes phosphines oxides possessing the double bond at either the terminal or internal position and with the phosphine oxide appended onto the alkyne or the alkene terminus have been prepared. Their cobalt(I)-mediated cyclizations produce the eta(4)-complexed tricyclic compounds in high yields. The endo/exo selectivity depends on both the position of the phosphine oxide on the enediyne and the position of the double bond in the tether. With chiral phosphine oxides, a certain degree of induction was observed, and depending on the substituents on the phosphorus atom, the diastereoselectivity can reach 74%. Up to now, it is the highest level reported for such a cyclization in which a stereogenic center is created. Regarding all of our results, two reaction pathways involving an initial coordination of the cobalt moiety on the chelating site of the substituent have been suggested to explain the observed selectivities.     

Highly regio- and stereoselective intramolecular 1,3-dipolar cycloadditions of norbornadiene-tethered nitrile oxides

[reaction: see text] Intramolecular cycloadditions with high regio- and stereocontrol are important methods for the efficient assembly of complex molecular structures. Efficient routes to the synthesis of norbornadiene-tethered nitrile oxides have been developed, and their intramolecular 1,3-dipolar cycloadditions were studied. The cycloadditions occurred in good yields for a variety of substrates and were found to be highly regio- and stereoselective.     

1,3-Dipolar cycloaddition reaction of a d-galactose derived nitrone with allyl alcohol: synthesis of polyhydroxylated perhydroazaazulene alkaloids

Diastereofacial intermolecular 1,3-dipolar cycloaddition of d-galactose derived nitrone with allyl alcohol followed by tosylation afforded, in a 1:1 ratio endo- and exo-isooxazolidines 4a and 4b with complete diastereoselectivity at the nitrone carbon. The N–O bond reductive cleavage and S_N2 displacement afforded the pyrrolidine ring with a galactose appendage that on acetonide cleavage and reductive amino-cyclization afforded pentahydroxylated perhydroazaazulenes 1a and 1b.     

Transition structures of diastereoselective 1,3-dipolar cycloadditions of nitrile oxides to chiral homoallylic alcohols

Transition structures of the 1,3-dipolar cycloaddition of substituted nitrile oxides with chiral homoallylic alcohols were explored with density functional theory (B3LYP/6-311+G(d,p)+CPCM(dichloromethane)//B3LYP/6-31+G(d)). The diastereoselectivity observed in these reactions was explained. The anti product is favored in both the thermal and magnesium-mediated reactions. Selectivity is predicted to increase in the presence of magnesium, in agreement with experimental results. The energetics of the magnesium-mediated reaction are similar to those previously found for allylic alcohols. [structure: see text].     

Synthesis of stable functionally substituted nitrile oxides of the aromatic series

Stable functionally substituted mononitrile oxides were obtained from the previously obtained sterically hindered aldehydes of the mesitylene series. The previously unknown bisnitrile oxide was also synthesized from triethyl-benzene; the compound is an effective crosslinking agent. The synthesis was carried out via the stage of oximation and oxidation of the oxime by sodium hypochlorite.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1201–1203, May, 1991.