Cycloadditions mechanistic possibilities

Other mechanistic possibilities also exist for the [5-1-2] cycloaddition reaction and cannot be mled out at this point In addition to the stepwise pathways depicted in Scheme 13.8, it is also possible that coordination of the 27r-component to 42 could lead directly to 48 through simultaneous insertion and cleavage. Variations on these events, such as direct insertion into the cyclopropane to form a metaUacyclobutane, are also possible. 

Larsen has recently described an interesting synthetic use for the cycloadducts of thiooxomalonate (Scheme 21). Bunte salt (176) can be converted in situ to thiooxomalonate (177) which undergoes regioselective [4 + 2] cycloaddition with 1,3-dienes at 25-70 C to afford adducts. Thus with 1,3-di-methylbutadiene a 1 12 mixture of (178) and (179) are formed in excellent yield. It was found that treatment of major isomer (179) with base, followed by methyl iodide, yielded a 16 1 mixture of epimeiic thiomethylcyclopentenes (180) and (181). Some mechanistic possibilities for formation of these products have been offered. ... 

However, there are still a number of problems that will have to be solved Synthetic equivalents will have to be found for those cosubstrates that do not undergo this cycloaddition. The possibilities of inversion the polarity (e.g. by the introduction of a nitro-group at the unsaturated cosubstrate) remain to be examined as does the extension of these cycloaddition reactions to an intramolecular version leading to cyclopentane annulation. Although the regioselectivity may be manipulated by changing the catalyst (e.g. Pd(0) versus Ni(0)), there is still room for improvement and a deeper understanding of the mechanistic details of these reactions is needed. But the activity and the interest in this field assure that most of these problems will be solved in the near future. 

Several mechanistic possibilities were proposed to account for the formation of furan products in the Rh(II)-catalyzed [3 + 2] cycloaddition reaction between... 

The enormous synthetic potential of the Diels-Alder reaction for the construction of a wide array of substituted cyclohexenes is mirrored in the versatility of the hetero-Diels-Alder reaction for the formation of 6-membered heterocycles. The mechanistic possibilities of the hetero-Diels-Alder reaction span the range from concerted to stepwise ionic processes, which is likely a function of the particular catalysts and reaction conditions employed. Although the hetero-Diels-Alder cycloaddition reaction was historically slower than its all-carbon counterpart in gaining widespread recognition, its utilization has been the subject of intense investigations in more recent years [13, 36, 37]. 

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. 

The different possibilities for the creation of the pyrazole ring according to the bonds formed are shown in Scheme 46. It should be noted that this customary classification lacks mechanistic significance actually, only two procedures have mechanistic implications the formation of one bond, and the simultaneous formation of two bonds in cycloaddition reactions (disregarding the problem of the synchronous vs. non-synchronous mechanism). 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

In order to gain more insight into this proposed mechanism, Montgomery and co-workers tried to isolate the intermediate metallacycle. This effort has also led to the development of a new [2 + 2 + 2]-reaction.226 It has been found that the presence of bipyridine (bpy) or tetramethylethylenediamine (TMEDA) makes the isolation of the desired metallacycles possible, and these metallacycles are characterized by X-ray analysis (Scheme 56).227 Besides important mechanistic implications for enyne isomerizations or intramolecular [4 + 2]-cycloadditions,228 the TMEDA-stabilized seven-membered nickel enolates 224 have been further trapped in aldol reactions, opening an access to complex polycyclic compounds and notably triquinanes. Thus, up to three rings can be generated in the intramolecular version of the reaction, for example, spirocycle 223 was obtained in 49% yield as a single diastereomer from dialdehyde 222 (Scheme 56).229... 

The first metal-catalyzed [4 +2]-reaction of tethered dienes with 7r-systems was reported by Wender and Jenkins using alkynes initially as the two-carbon component.21 This study was based on the earlier observation by Wender and Ihle that in the [4 + 4]-cycloaddition of bis-dienes a competing side-reaction is the [4 + 2]-cycloaddition of the diene with a mono-ene portion of a second diene. The extension of this reaction to the synthesis of seven-membered rings by trapping the metallacycloheptadiene with CO, a formal [4 + 2 + l]-cycloaddition, has been shown in preliminary studies to be feasible. For example, tethered diene-yne 160 can be converted to cycloheptadienone 163 in an Rh(l)-catalyzed [4 + 2 + l]-reaction with CO, albeit the [4 + 2]- and [2 + 2 + l]-reaction products dominate (Equation (29)). The mechanistic scheme (Scheme 44) illustrates the possible metallacyclic intermediates leading to the observed products and provided the conceptual basis for the realization of three novel reaction types ([4 + 2], [2 + 2 + 1], and [4 + 2 + 1 ]).1... 

In 1981 we published the first paper [22] on the synthesis of s-triazolo[4,3-a]pyridinium salts, 4, by the anodic oxidation of hydrazones 3 in the presence of pyridine (Scheme 5). In our working mechanistic scheme we proposed nitrilimine as the possible intermediate and pointed out that this reaction opens the door to a wide range of heterocyclic systems via anodic oxidation of aldehyde hydrazones through 1,3-dipolar cycloaddition reactions of the nitrilimine involved. 

Ishihara has reported an unusual enantioselective [2h-2] cycloaddition of unactivated alkenes with a-acyloxyacroleins catalysed by triamine 150 [203]. Although the precise mechanistic details of this transformation are unclear at present, a possible... 

Due to space limitations, it is not possible to provide a comprehensive coverage of all 1,3-dipolar cycloaddition chemistry carried out using diazo compounds over the past two decades. Rather, attention will be given to the most significant developments, including the synthesis of novel heterocyclic systems, the preparation of well-established heterocycles (such as pyrazoles and pyrazolines) with novel functionalities, as well as stereoselective cycloadditions. A discussion of the theoretical, mechanistic, and kinetic aspects of these 1,3-dipolar cycloaddition reactions will be kept to a minimum, but references to important work in these areas will be given at appropriate places. Authoritative reviews dealing with the... 

In an another mechanistic study, Foote and co-workers reported a possible charge-transfer mechanism for the photochemical [2+2] cycloadditions of electron-rich ynamines [56-58]. Further studies on the regio- and stereoselectivity upon addition of less electron-rich substrates such as alkyl-substituted 1,3-bu-tadienes [59], acyclic enones [60], and aryl alkenes [61] to C60 were performed in more recent years. 

Diels-Alder reactions of heterodienophiles have been known for decades, but only recently has this methodology become widely accepted by the synthetic community. There is enormous diversity in the structural types of compounds which can act as heterodienophiles, and a wide array of heterocyclic adducts can be prepared via these [4 + 2] cycloadditions. It seems clear that hetero Diels-Alder reactions span a range of mechanism from concerted to stepwise ionic processes. In many instances, mechanistic information is totally lacking. The discussion below therefore classifies heterodienophiles by structural rather than mechanistic class. Only the major types of synthetically useful heterodienophiles have been included. Moreover, the significant regio- and stereo-chemical features of the reactions have been exemplified as much as possible using recently reported cases. Other more comprehensive and more specialized reviews should be consulted for older material and more obscure hetero Diels-Alder cycloadditions. 

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