Carbon oxides 5+1 cycloaddition reactions

Dienes may react with nucleophiles to give allyl complexes or they may react with electrophiles to afford dienyl compounds [equations (8.24) and (8.25)]. Some diene reactions were already discussed in Chapter 7. The nucleophiles which may attack the terminal carbon atom to give allyl compounds are H , Cl, RCO , RO , OAc, etc. In complexes, the diene molecules often undergo oxidative cycloaddition reaction, and allyl compounds are subsequently formed [equation (7.40), Table 1.4]. 

The [3S+1C] cycloaddition reaction with Fischer carbene complexes is a very unusual reaction pathway. In fact, only one example has been reported. This process involves the insertion of alkyl-derived chromium carbene complexes into the carbon-carbon a-bond of diphenylcyclopropenone to generate cyclobutenone derivatives [41] (Scheme 13). The mechanism of this transformation involves a CO dissociation followed by oxidative addition into the cyclopropenone carbon-carbon a-bond, affording a metalacyclopentenone derivative which undergoes reductive elimination to produce the final cyclobutenone derivatives. 

Olefination Reactions Involving Phosphonium Ylides. The synthetic potential of phosphonium ylides was developed initially by G. Wittig and his associates at the University of Heidelberg. The reaction of a phosphonium ylide with an aldehyde or ketone introduces a carbon-carbon double bond in place of the carbonyl bond. The mechanism originally proposed involves an addition of the nucleophilic ylide carbon to the carbonyl group to form a dipolar intermediate (a betaine), followed by elimination of a phosphine oxide. The elimination is presumed to occur after formation of a four-membered oxaphosphetane intermediate. An alternative mechanism proposes direct formation of the oxaphosphetane by a cycloaddition reaction.236 There have been several computational studies that find the oxaphosphetane structure to be an intermediate.237 Oxaphosphetane intermediates have been observed by NMR studies at low temperature.238 Betaine intermediates have been observed only under special conditions that retard the cyclization and elimination steps.239... 

Hassner and coworkers have developed a one-pot tandem consecutive 1,4-addition intramolecular cycloaddition strategy for the construction of five- and six-membered heterocycles and carbocycles. Because nitroalkenes are good Michael acceptors for carbon, sulfur, oxygen, and nitrogen nucleophiles (see Section 4.1 on the Michael reaction), subsequent intramolecular silyl nitronate cycloaddition (ISOC) or intramolecular nitrile oxide cycloaddition (INOC) provides one-pot synthesis of fused isoxazolines (Scheme 8.26). The ISOC route is generally better than INOC route regarding stereoselectivity and generality. 

Organometals and metal hydrides as electron donors in addition reactions 245 Oxidative cleavage of carbon-carbon and carbon-hydrogen bonds 253 Electron-transfer activation in cycloaddition reactions 264 Osmylation of arene donors 270... 

The carbon-nitrogen triple bond of aryl thiocyanates acts as a dipolarophile in 1,3-dipolar cycloadditions. Reactions with nitrile oxides yield 5-arylthio-1,2,4-oxadiazoles 227 (X = O Y = S). Aryl selenocyanates behave similarly forming 5-arylseleno-l,2,4-oxadiazoles 227 (X = 0 Y = Se). Reactions of 5-aryl-... 

A strategy based on the diastereoselective dipolar cycloaddition reaction of nitrile oxides and allylic alcoholates, has been applied to the synthesis of bis-(isoxazolines) that are precursors to polyketide fragments. These intermediates can be elaborated into protected polyols, for example, 439, by sequential chemos-elective reductive opening of each isoxazoline or, alternatively, by simultaneously, providing access to all stereoisomers of this carbon skeleton (479). 

Enyne metathesis is unique and interesting in synthetic organic chemistry. Since it is difficult to control intermolecular enyne metathesis, this reaction is used as intramolecular enyne metathesis. There are two types of enyne metathesis one is caused by [2+2] cycloaddition of a multiple bond and transition metal carbene complex, and the other is an oxidative cyclization reaction caused by low-valent transition metals. In these cases, the alkyli-dene part migrates from alkene to alkyne carbon. Thus, this reaction is called an alkylidene migration reaction or a skeletal reorganization reaction. Many cyclized products having a diene moiety were obtained using intramolecular enyne metathesis. Very recently, intermolecular enyne metathesis has been developed between alkyne and ethylene as novel diene synthesis. 

Another route involves a palladium-copper-catalyzed tandem carbon-carbon formation/cycloaddition sequence (Equation 12) <2005TL8531>. Notably, cycloadditions of azide to the internal alkynes failed under click chemistry reaction conditions <2003DDT1128>. Cyclization under oxidative conditions has been reported from dithioacetal 163 (Equation 13) <1996TL3925>. The formation of 164 as a single diastereoisomer has been explained by stereoelectronic effects. 

Accordingly, many reactions can be performed on the sidewalls of the CNTs, such as halogenation, hydrogenation, radical, electrophilic and nucleophilic additions, and so on [25, 37, 39, 42-44]. Exhaustively explored examples are the nitrene cycloaddition, the 1,3-dipolar cycloaddition reaction (with azomethinylides), radical additions using diazonium salts or radical addition of aromatic/phenyl primary amines. The aryl diazonium reduction can be performed by electrochemical means by forming a phenyl radical (by the extrusion of N2) that couples to a double bond [44]. Similarly, electrochemical oxidation of aromatic or aliphatic primary amines yields an amine radical that can be added to the double bond on the carbon surface. The direct covalent attachment of functional moieties to the sidewalls strongly enhances the solubility of the nanotubes in solvents and can also be tailored for different... 

A very remote secondary H/D isotope effect has been measured for the 2 + 2-cycloaddition of TCNE to 2,7-dimethylocta-2,fran -4,6-triene. The reaction of nitric oxide with iV-benzylidene-4-methoxyaniline to produce 4-methoxybenzenediazonium nitrate and benzaldehyde is thought to proceed via a 2 + 2-cycloaddition between nitric oxide and the imine double bond. A novel mechanism for the stepwise dimerization of the parent silaethylene to 1,3-disilacyclobutane involves a low-barrier [1,2]-sigmatropic shift. Density functional, correlated ab initio calculations, and frontier MO analysis support a concerted 2 + 2-pathway for the addition of SO3 to alkenes. " The enone cycloaddition reactions of dienones and quinones have been reviewed. The 2 + 2-photocycloadditions of homochiral 2(5H)-furanones to vinylene carbonate are highly diastereoisomeric. ... 

Nitrile oxides are widely used as dipoles in cycloaddition reactions for the synthesis of various heterocyclic rings. In order to promote reactions between nitrile oxides and less reactive carbon nucleophiles, Auricchio and coworkers studied the reactivity of nitrile oxides towards Lewis acids. They observed that, in the presence of gaseous BF3, nitrile oxides gave complexes in which the electrophilicity of the carbon atom was so enhanced that it could react with aromatic systems, stereoselectively yielding aryl oximes 65 and 66 (Scheme 35). ... 

The synthesis of various heterocyclic systems via 1,3-dipolar cycloaddition reactions of 1,3-oxazolium-5-oxides (32) with different dipolarophiles was reported. The cycloaddition reactions of mesoionic 5H,7H-thiazolo[3,4-c]oxazolium-l-oxides (32), which were prepared from in situ N-acyl-(/J)-thiazolidine-4-carboxyIic acids and N,N -dicyclohexylcarbodiimide, with imines, such as N-(phenylmethylene)aniline and N-(phenylmethylene)benzenesulfonamide, gave 7-thia-2,5-diazaspiro[3,4]octan-l-one derivatives (33) and lH,3H-imidazo[ 1,5-cJthiazole derivative (35). The nature of substituents on imines and on mesoionic compounds influenced the reaction. A spirocyclic p-lactam (33) may be derived from a two-step addition reaction. Alternatively, an imidazothiazole (35) may be obtained from a typical 1,3-dipolar cycloaddition via a tricyclic adduct (34) which loses carbon dioxide and benzenesulfinic acid. [95T9385]... 

In general, on chemical modification carbon nanotubes exhibit much less toxicity or nontoxicity to living cell lines that have been investigated so far.117,118 For instance, Dumortier et al. conducted an in vitro cell uptake study of the functionalized SWNTs with B and T lymphocytes and macrophages.117 Two types of functionalized SWNTs were used, one prepared via 1,3-dipolar cycloaddition reaction and the other obtained through oxidation/amidation treatment. Both types of the functionalized nanotubes were rapidly taken up by lymphocytes and macrophages without affecting the overall... 

Arylcyclopropanes and their heterocyclic analogues are liable to electron transfer induced fragmentation of a carbon-carbon bond that in some cases leads to synthetically useful products. Thus, 1,2-diarylcyclopropanes [240-243] as well as 2,3-diaryloxirans [244-246] and -aziridines (in the last case, also 2-monophenyl derivatives) [247,248] are cleaved upon photoinduced electron transfer sensitization. The final result, after back electron transfer, is trans-cis isomerization of the ring. In the presence of a suitable trap, however, a cycloaddition reaction takes place, involving either the radical cation or the ylide. Thus, dioxoles, ozonides or azodioxoles, respectively, are formed in the presence of oxygen and oxazolidines have been obtained from cyclopropanes in the presence of nitrogen oxide (Sch. 23). 

Among the carbonylative cycloaddition reactions, the Pauson-Khand (P-K) reaction, in which an alkyne, an alkene, and carbon monoxide are condensed in a formal [2+2+1] cycloaddition to form cyclopentenones, has attracted considerable attention [3]. Significant progress in this reaction has been made in this decade. In the past, a stoichiometric amount of Co2(CO)8 was used as the source of CO. Various additive promoters, such as amines, amine N-oxides, phosphanes, ethers, and sulfides, have been developed thus far for a stoichiometric P-K reaction to proceed under milder reaction conditions. Other transition-metal carbonyl complexes, such as Fe(CO)4(acetone), W(CO)5(tetrahydrofuran), W(CO)5F, Cp2Mo2(CO)4, where Cp is cyclopentadienyl, and Mo(CO)6, are also used as the source of CO in place of Co2(CO)8. There has been significant interest in developing catalytic variants of the P-K reaction. Rautenstrauch et al. [4] reported the first catalytic P-K reaction in which alkenes are limited to reactive alkenes, such as ethylene and norbornene. Since 1994 when Jeong et al. [5] reported the first catalytic intramolecular P-K reaction, most attention has been focused on the modification of the cobalt catalytic system [3]. Recently, other transition-metal complexes, such as Ti [6], Rh [7], and Ir complexes [8], have been found to be active for intramolecular P-K reactions. 

The use of nitro aromatics as dipolarophiles in cycloaddition reactions has shown great utility in heterocyclic synthesis. The reaction of 3-substituted-4-nitroisoxazoles (299) with trisubstituted oxazolium 5-oxides (300) affords an intermediate adduct (301) which eliminates carbon dioxide and nitrous acid to afford 3,4,6-trisubstituted pyrrolo[3,4-r/]isoxazoles (302) (Scheme 56) <93G633>. 

Oxazole N-oxides having a 4-methyl substituent are attacked by acetic anhydride to yield 4-acetoxyoxazoles (equation 21). The combined action of benzoyl chloride and potassium cyanide leads to compounds of the Reissert type, e.g. (177). The reaction of 4-methyloxazole Yoxides with phenyl isocyanate gives 5-hydroxy-4-methylene-l-phenyl-4,5-dihy-droimidazoles by cycloaddition, extrusion of carbon dioxide and recyclization (Scheme 12) with 4-phenyloxazole JV-oxides the reaction takes a different course, yielding imi-dazooxazolidinones (Scheme 13). 

One approach is to use the native oxygen groups as a reagent and site of attachment. Usually, only one kind of group can be used for the reaction. As a result, only part of the surface is available for reaction, even when oxidized blacks are used. Another approach is to use the most abimdant part of the surface, carbon, for the reaction. Several methods of this type have been explored including those based on diazonium chemistry, azo chemistry, peroxide chemistry, sulfonation, cycloaddition chemistry and other methods. ... 

I became involved in carbodiimide chemistry in my research work on isocyanates at the former Donald S. Gilmore Research Laboratories of the Upjohn Company in North Haven, CT. Carbodiimides are readily synthesized from isocyanates using a phospholene oxide catalyst. This reaction can be conducted without a solvent, and the byproduct is carbon dioxide. We used this reaction in the manufacture of a liquid version of MDI (4,4 -diisocyanatodiphenylmethane), which today is sold in huge quantities worldwide. By reacting MDI with dicarboxylic acids in a vented extruder we manufactured a family of thermoplastic polyamide elastomers, which are sold today by the Dow Chemical Company. Also, N-sulfonylcarbodiimides were synthesized for the first time in our laboratories. They are the precursors of the antidiabetic sulfonamides, such as Upjohn s Tolbutamide (Orinase). Because of the close relationship of isocyanates with carbodiimides we studied many linear and cyclic carbodiimide reactions, especially their cycloaddition reactions. 

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