Crossed -cycloaddition

A phase-selective photochemical reaction of 2-pyridones is observed. Irradiation of 225 in benzene gives mainly rearrangement products 226, whereas, in the solid state, [4+4] photocycloaddition to the photodimer 227 occurred in quantitative yield (Scheme 39) <20040L683>. The stereochemistry of the photodimer was exclusively the trans- /+configuration, as shown. This is presumably due to Jt-rt-stacking and dipole-dipole interactions between the pyridones. Intermolecular photocycloaddition of 2-pyridone mixtures can be selective and lead to useful quantities of [4+4] cycloaddition cross-products <1999JOC950>. 

Keywords Cyclization Dipole cycloaddition Cross-coupling Axially biaryls Radical-mediated coupling Planar chirality... 

Scheme 13.3 Cycloaddition cross-linking of cinnamate groups...

Besides cycloadditions, cross-coupling reactions were applied to the site-specific modification of DNA. In addition to Sonogashira couplings, we developed a selective variant of the Suzuki-Miyaura coupling reaction that allows the one-step postsynthetic modification of commercially available iodo-modified DNA with a variety of boronic acids to form functional DNA derivatives (in this case, photoswitchable derivatives) [16a]. This methodology shortened the synthetic pathway to such modified DNA by 10 synthetic steps. Recent work identified Stille-Migita coupling as a much milder and potentially very useful reaction (Krause and Jaschke, to be published). 

The polymeric hydroperoxides formed in this sequence apparently undergo decomposition leading to chain scission since it has been found that there is a preliminary decline in molecular weight when poly(vinyl chloride) is heated in air. This decline in molecular weight is followed by an increase, presumably through the Diels-Alder cycloaddition cross-linking described above. 

The importance of both electronic and steric effects is clear in cycloadditions as in cross-oxidations. One example is a heterocycHc modification leading to the thermodynamically less stable natural form of juglone derivatives such as ventiloquinones JT [124917-64-2] (84) and I [124917-65-3] (85) (83). The yields are 97% (84) from 6-chloro-2,3-dimethoxy-l,4-ben2oquinone [30839-34-0] and 100% (85) upon hydrolysis. 

Clearly, in the case of (66) two amide tautomers (72) and (73) are possible, but if both hydroxyl protons tautomerize to the nitrogen atoms one amide bond then becomes formally cross-conjugated and its normal resonance stabilization is not developed (c/. 74). Indeed, part of the driving force for the reactions may come from this feature, since once the cycloaddition (of 72 or 73) has occurred the double bond shift results in an intermediate imidic acid which should rapidly tautomerize. In addition, literature precedent suggests that betaines such as (74) may also be present and clearly this opens avenues for alternative mechanistic pathways. 

Reactions of azines and imines (including criss-cross cycloaddition) 76S349... 

Burger s criss-cross cycloaddition reaction of hexafluoracetone-azine (76S349) is also a synthetic method of the [CNN + CC] class. In turn, the azomethines thus produced, (625) and (626) (79LA133), can react with alkenes and alkynes to yield azapentalene derivatives (627) and (628), or isomerize to A -pyrazolines (629) which subsequently lose HCF3 to afford pyrazoles (630 Scheme 56) (82MI40401). 

The first example of a cycloaddition reaction of a multiple bond to a diene was reported in 1917 Surprisingly, it was found that benzal azine adds to 2 equivalents of several unsaturated systems, when offered in excess, to yield bicyclie compounds. This reaction was named criss-cross" cycloaddition [190], Exploitation of the preparative potential of criss-cross cycloaddition began only in the early 1970s, when hexafluoroacetone azine became available on a larger scale [191,192] The study of this reaction proved to be an impetus tor the development of azine chemistry [183, 193]... 

Because the criss-cross cycloaddition reaction is a sequence of two [3+2] cycloaddition steps, the reaction with a,co-diolefins offers a new entry into macro-molecular chemistry New types of polymers with interesting structures and prop erties can be synthesized [213, 214, 215] (equation 48)... 

Dienamine 56a has been reported to undergo a 1,4 cycloaddition with acrylonitrile to form bicycloaminonitrile 57 in a 74% yield (61). A recent report has indicated that both possible 1,4-cycloaddition adducts are obtained from the reaction of acrylonitrile with a 1 1 equilibrium mixture of the linear- and cross-conjugated isomers of dienamine 56b (61a). 

A two-step sequence of nitrile oxide-olehn cycloaddition and reduction of the resulting A -isoxazolines offers a unique and attractive alternative to the classical aldol reaction and its many variants (2J). The procedure bypasses traditional problems, including enolate equilibrium and cross condensation (20). 

Enyne metathesis starting either from acetylenic boronates and homoallylic alcohols [104a,c] or from propargyl alcohols and allylboronates [104b] has recently been described. The resulting boronated dienes can be converted to allenes or cycloaddition products. The cross metathesis of vinylcyclopropyl-boronates directed toward the total synthesis of natural products has very recently been investigated by Pietruszka et al. [104d]. 

It has been shown that cross-coupling reactions constitute a very mild method to introduce different alkyl and aryl groups to the most active C-3 position of the pyrazinone ring [26]. The broadly functionahzed 2-azadiene system of the title compounds was studied in cycloaddition reactions with various electron-reach and electron-poor dienophiles to provide highly substituted heterocycles [24]. 

Uemura M (2004) (Arene)Cr(Co)3 Complexes Cyclization,Cycloaddition and Cross Coupling Reactions. 7 129-156 Ujaque G, see Drudis-Sole G (2005) 12 79-107... 

Keywords Allylic substitution Catalysis Cross-coupling Cycloaddition Cycloisomerisation DNIC Ferrate Hydrogenase Iron... 

Another recent development in the field of palladium-catalyzed reactions with alkynes is a novel multicomponent approach devised by the Lee group. Starting from a-bromovinyl arenes and propargyl bromides, the assembly ofeight-membered car-bocycles can be realized via a cross-coupling/[4+4] cycloaddition reaction. The authors also presented the combination of a cross-coupling and homo [4+2], hetero [4+2], hetero [4+4] or [4+4+1] annulation leading to various cyclic products [147]. 

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