Cycloaddition reactions defined

The highly strained and reactive 2iT-azirines have been extensively studied for various synthetic purposes, such as ring expansion reactions, cycloaddition reactions, preparation of functionalized amines and substituted aziridines. The older literature on azirines in synthesis has extensively been reviewed [69]. Concerning azirines with defined chirality only scarce information is available. Practically all reactions of azirines take place at the activated imine bond. Reduction with sodium borohydride leads to cz5-substituted aziridines as is shown in Scheme 48 [26,28]. 

Concerted cycloaddition reactions provide the most powerful way to stereospecific creations of new chiral centers in organic molecules. In a manner similar to the Diels-Alder reaction, a pair of diastereoisomers, the endo and exo isomers, can be formed (Eq. 8.45). The endo selectivity in the Diels-Alder arises from secondary 7I-orbital interactions, but this interaction is small in 1,3-dipolar cycloaddition. If alkenes, or 1,3-dipoles, contain a chiral center(s), the approach toward one of the faces of the alkene or the 1,3-dipole can be discriminated. Such selectivity is defined as diastereomeric excess (de). 

Abstract 1,3-Dipolar cycloaddition reactions (DCR) are atom-economic processes that permit the construction of heterocycles. Their enantioselective versions allow for the creation of up to four adjacent chiral centers in a concerted fashion. In particular, well-defined half-sandwich iridium (111) catalysts have been applied to the DCR between enals or methacrylonitrile with nitrones. Excellent yield and stereoselectivities have been achieved. Support for mechanistic proposals stems from the isolation and characterization of the tme catalysts. 

The first synthesis of 1,3-dioxolium-4-olates (here defined as oxamiinchnones) was reported in 1980 by Berk et al. (64) but it was work of Hamaguchi and Nagai (65,66) that demonstrated the accessibility and utility of these new mesoionic heterocycles in cycloaddition reactions. Thus, reaction of diazoacetic benzoic anhydrides 108 with a 7t-allyl palladium complex affords oxamiinchnones 109. 

Because of their relatively high reactivity, the foregoing structures often appear as transient intermediates in a series of reactions rather than as end products. Several of the documented reactions of these intermediates include rearomatization (e.g., reduction to catechol and hydroquinone derivatives), further oxidation to mono- and dicarboxylic acids (see below), benzylic acid rearrangements (Corbett 1966, Corbett and Fooks 1967), cycloaddition reactions (Teuber et al. 1966), and various condensation reactions (Erdtman and Granath 1954). The last-named processes, which are accelerated in acidic and basic media, often give rise to structurally complex and poorly defined materials. 

The fact that the rate of some Diels-Alder [4 + 2] cycloaddition reactions is affected, albeit only slightly, by the solvent was used by Berson et al. [52] in establishing an empirical polarity parameter called Q. These authors found that, in the Diels-Alder addition of cyclopentadiene to methyl acrylate, the ratio of the endo product to the exo product depends on the reaction solvent. The endo addition is favoured with increasing solvent polarity cf. Eq. (5-43) in Section 5.3.3. Later on, Pritzkow et al. [53] found that not only the endojexo product ratio but also the absolute rate of the Diels-Alder addition of cyclopentadiene to acrylic acid derivatives increases slightly with increasing solvent polarity. The reasons for this behaviour have already been discussed in Section 5.3.3. Since reaction (5-43) is kinetically controlled, the product ratio [endo]l[exo] equals the ratio of the specific rate constants, and Berson et al. [52] define... 

Cycloaddition reactions can also be pseudopericyclic. Bimey examined a number of these and a few examples involving the reactions of formylketene (91) are covered here. Formylketene reacts with alcohols to produce p-ketoesters from the enols 92. Bimey examined the model reaction of formylketene with water (Reaction 4.6). The reactants first come together to form a hydrogen-bonded complex (93) before passing though the transition state 94 to give the enol product 95. The activation barrier, defined as the energy for the reaction 93 94, is 6.4 kcal... 

Cycloaddition reactions are transformations involving the fusion of open-chain substrates to cyclic products. Woodward and Hoffmann have divided all concerted cycloaddition reactions into allowed and forbidden categories defined by a complete set of selection rules (5). We address ourselves here to the catalytic operations required of a transition metal to switch the forbidden transformations to allowed. Our attention, therefore, will be directed exclusively to the forbidden reactions. Forbidden-to-allowed catalysis will be discussed as it applies to the simplest, and perhaps most important cycloaddition, the concerted, suprafacial, 1,2-addition of two olefins. 

The inside alkoxy effect is useful for predicting the stereoselectivity of nitrile oxide cycloaddition reactions with chiral lylic ethers. The hypothesis states that allylic ethers adopt the inside position and alkyl substituents prefer the sterically less-crowded anti conformation in transition states for these electrophilic cycloadditions . The terms inside and outside are defined in (17) for a hypothetical nitrile oxide cycloaddition transition state. Both ab initio (Gaussian 80 with 3-2IG basis set) and molecular mechanics calculations agree, each predicting the lowest-energy transition state to be the one described, i.e. (18 H outside) just above it lies one where the alkyl group is anti, OR outside and H inside (19 ). As illustrated, the former leads to a product wherein OR and the nitrile oxide oxygen are anti, the latter to one with them syn (Scheme 19). 

Palladium-catalysed processes typically utilise only 1-5 mol% of the catalyst and proceed through small concentrations of transient palladium species there is a sequence of steps, each with an organopalladium intermediate, and it is important to become familiar with these basic organopalladium processes in order to rationalise the overall conversion. Concerted, rather than ionic, mechanisms are the rule, so it is misleading to compare them too closely with apparently similar classical organic mechanisms, however curly arrows can be used as a memory aid (in the same way as one may use them for cycloaddition reactions), and this is the way in which palladium-catalysed reactions are explained in the following discussion. (For convenience, an organometallic component can be referred to as the nucleophilic partner and the halide as the electrophilic partner, but this should not necessarily be taken to imply reactivity as defined in classical chemistry. Also, references to the halide should be understood to include all related substrates, such as triflates.)... 

Recently, the group of Sharpless [144,145] popularized the 1,3-dipolar cycloaddition of azides and terminal alkynes, catalyzed by copper(I) in organic synthesis. This process was proven to be very practical, because it can be performed in several solvents (polar, nonpolar, protic, etc.) and in the presence of different functions. These cycloadditions were classified as click reactions, defined by Sharpless. 

---