Cycloadditions concerted process

Figure 10 12 shows the interaction between the HOMO of one ethylene molecule and the LUMO of another In particular notice that two of the carbons that are to become ct bonded to each other m the product experience an antibondmg interaction during the cycloaddition process This raises the activation energy for cycloaddition and leads the reaction to be classified as a symmetry forbidden reaction Reaction were it to occur would take place slowly and by a mechanism m which the two new ct bonds are formed m separate steps rather than by way of a concerted process involving a sm gle transition state... 

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 ... 

Classify the following reactions as electrocyclizations, sigmatropic rearrangements, cycloadditions, etc., and give the correct symbolism for the electrons involved in each concerted process. Some of the reactions proceed by two sequential processes. 

The mechanism of the cycloaddition of sulfenes to enamines does not involve a concerted process in many if not all cases, but rather a two-step process in which a zwitterion is the initially formed intermediate (158,159). 

Concerted (Section 30.1) A reaction that Lakes place in a single step without intermediates. For example, the Diels-Alder cycloaddition reaction is a concerted process. 

Two issues are of essential for predicting the structure of 1,3-DCA products (1) What is the regiochemistry and (2) What is the stereochemistry Many specific examples demonstrate that 1,3-dipolar cycloaddition is a stereospecific syn addition with respect to the dipolarophile, as expected for a concerted process. 

Photocycloaddition of Alkenes and Dienes. Photochemical cycloadditions provide a method that is often complementary to thermal cycloadditions with regard to the types of compounds that can be prepared. The theoretical basis for this complementary relationship between thermal and photochemical modes of reaction lies in orbital symmetry relationships, as discussed in Chapter 10 of Part A. The reaction types permitted by photochemical excitation that are particularly useful for synthesis are [2 + 2] additions between two carbon-carbon double bonds and [2+2] additions of alkenes and carbonyl groups to form oxetanes. Photochemical cycloadditions are often not concerted processes because in many cases the reactive excited state is a triplet. The initial adduct is a triplet 1,4-diradical that must undergo spin inversion before product formation is complete. Stereospecificity is lost if the intermediate 1,4-diradical undergoes bond rotation faster than ring closure. 

In cycloadditions two components are commonly involved, and the feasibility of a concerted process will be determined by whether overlap can take place between the HOMO of one component and the LUMO of the other. Thus for a diene plus a monoene,... 

Many such reactions may indeed be carried out preparatively under photochemical conditions, though, for reasons that cannot be gone into here (the detailed mechanism of photochemical changes), they are often not concerted but proceed via biradical intermediates. One photochemical (2n + 2n) cycloaddition that does, however, proceed via a concerted process is the example we have already referred to ... 

There is mechanistic evidence to show that this formal (3 + 3) cycloaddition starts with attack of betaine-C at CI<2 of the three-ring (429) and leads to 2-pyrone formation either by a concerted process (429 — 428) or stepwise via cyclobutenone and 0-acyl vinylketene intermediates (430/431) depending on the leaving group ... 

Nowadays, it is commonly accepted that [3+ 2]-cycloaddition is a concerted process, and that the C,C double bond serves as the main type of dipolarophiles (Scheme 3.126). 

Dipolar species have been observed in the cycloaddition of polar intermediates. Thus cyclobutanes can be formed by non concerted processes involving zwitter ionic intermediates. The combination of an electron rich alkene (enamimes, enol ethers) and an alkene having electron withdrawing groups (nitro a cyano substituted alkenes) first gives a zwitter ion which can rotate about the newly formed bond before cyclization and gives both a cis and a trans adduct. 

Other examples are given in Table 12.3. The cycloaddition reactions take place even at 0 °C. A regioisomeric mixture was obtained from 1,1-dimethylallene [50]. As for the mechanism of the allene-ketene [2 + 2]-cycloaddition, it is not clear whether the reaction proceeds via a concerted process (ketene antrafacial) or a two-step process. 

The Diels-Alder reaction, inverse electronic demand Diels-Alder reaction, as well as the hetero-Diels-Alder reaction, belong to the category of [4+2]-cycloaddition reactions, which are concerted processes. The arrow pushing here is merely illustrative. 

As suggested in previous similar investigations, as intermediate have been proposed the non-stable, high-energy species 164, formed in low concentration in a reversible cycloaddition-elimination process of 161 with nitriles. This process either occurs in a concerted manner (pathway A) or involves a four-step sequence with the intermediacy of a bipolar species (pathway B). It has been argued that the reaction does not proceed through a thiatetra-azapentalene intermediate, but instead involves a transition state that resembles structure 164. 

A third mechanistically distinct [3 -1- 2] cycloaddition between vinyl ethers and vinyl-carbenoids was discovered and reported in 2001 [26]. This reaction is remarkable because when Rh2(S-DOSP)4 is used as the catalyst, the cis-cyclopentenes 142 are formed in up to 99% enantiomeric excess. The reaction occurs between vinylcarbenoids unsubstituted or alkyl-substituted at the vinyl terminus and vinyl ethers substituted with an aryl or vinyl group. Some illustrative examples are shown in Tab. 14.12. The reaction is considered to be a concerted process, which would be consistent with the highly stereoselective nature of the reaction [26]. Contrary to the [3-1-2] cycloaddition derived by means of vinylogous carbenoid reactivity, this latest [3 -1- 2] cycloaddition is not influenced by solvent effects. Due to steric demands on the carbenoid, the [3-1-2] cycloaddi-tion only occurs with cis-vinyl ethers. 

The reason for this difference is that if 16 were to undergo a concerted elimination, it would have to follow the forbidden (high-energy) [2ns + 2ns] pathway. For 17, the elimination can take place by the allowed [2ns + 4rcv] pathway. Thus, these reactions are the reverse of, respectively, the [2 + 2] and [4 + 2] cycloadditions, and only the latter is an allowed concerted process. The temperature at which 16 decomposes is fairly typical for strained azo compounds, and the decomposition presumably proceeds by a noncon-certed diradical mechanism. Because a C—N bond must be broken without concomitant compensation by carbon-carbon bond formation, the activation energy is much higher than for a concerted process. 

While arylnitrile oxides dimerize in protic solvents and in pure pyridine (cf. 4.04.8.1.3.), they form bis(adducts) (191) and (192) via zwitterions (189) with pyridine in apolar solvents (Scheme 83) <89JHC757,90Gi>. Significantly, the cycloaddition of the nitrile oxide to pyridine to give (190) is not a concerted process. Heterocycles (191) undergo base catalyzed ring cleavage (Scheme 84). 

In 2003, Gimeno, Bassetti and coworkers reported an unusual diastereoselective [2 + 2] cycloaddition of two C=C bonds under mild thermal conditions (Scheme 4.18) [128]. Heating the vinylidene complexes Rul leads to the bicyclic alkylidene complexes Ru2. In 2004, Sordo and coworkers investigated the mechanism of this [2 + 2] cycloaddition theoretically [25]. With model complexes in which the indenyl ligand was modeled with a Cp ligand, two different pathways (paths a and b) were studied, shown in Scheme 4.19. Path a considers a concerted process. In the stepwise pathway (path b), the vinylidene-to-alkyne tautomerization of R1 followed by... 

Singlet oxygen reacts through the [4- -2]-cycloaddition mode with the sterically hindered and non-planar 1,3-diene system in l,l -dimenthene (493) to afford the cis-endoperoxide 494, albeit in moderate yield (Scheme 135) ". Cycloaddition of O2 to more planar bis(dialine) (495) proceeds smoothly leading predominantly to the trans-endoperoxide trans-496 (70%), while cis-496, which would be expected to derive from a concerted process, constitutes the minor (15%) product (Scheme 136) . 

One of the most widely applied cycloaddition techniques for the preparation of thietanes is the reaction of sulfenes with enamines. The stereochemistry of these reactions has been extensively investigated by Truce and Rach. Whether the mechanism is a two-step or a concerted process, both in accordance with the stereoselective formation of the cis form in Scheme 1, is still unresolved. The special orientation of the 1,4-dipolar intermediate 64, in which the charged phenyl and dimethylamino moieties are in proximity, enforces the cis geometry of the resulting thietane dioxide. In the concerted mode of reaction, formation of the orthogonal oriented unsaturated system, 65 should also yield the cis cycloadduct. 

Several computational studies have addressed whether the dipolar cycloaddition of nitronates is a concerted or stepwise process (93,100). Natural population analysis reveals that their is very little zwitterionic character in the transition state. The formation of the C C bond marginally precedes the C—O bond on the basis of calculated bond lengths and orders in the transition structure. These calculations also show that the reaction is a concerted process that is shghtly asynchronous. In addition, the cycloaddition likely proceeds through an early transition state and is overall an exothermic process. 

Intramolecular ionic Diels-Alder reactions were carried out in highly polar media to afford carbocyclic ring systems. The strategy, which obviates the need for high temperatures and pressures, features in situ generation of heteroatom-stabUized allyl cations that undergo subsequent (4 + 2) cycloaddition at ambient temperature. Typically, reactions were complete within 1 hour after addition of substrate. Some cycloadducts were the result of a concerted process, whereas others were formed via a stepwise reaction mechanism (Grieco, 1996). 

Unlike thermal [2 + 2] cycloadditions which normally do not proceed readily unless certain structural features are present (see Section 1.3.1.1.), metal-catalyzed [2 + 2] cycloadditions should be allowed according to orbital symmetry conservation rules. There is now evidence that most metal-catalyzed [2 + 2] cycloadditions proceed stepwise via metallacycloalkanes as intermediates and both their formation and transformation are believed to occur by concerted processes. In many instances such reactions occur with high regioselectivity. Another mode for [2 + 2] cyclodimerization and cycloadditions involves radical cation intermediates (hole-catalyzed) obtained from oxidation of alkcnes by strong electron acceptors such as triarylammini-um radical cation salts.1 These reactions are similar to photochemical electron transfer (PET) initiated [2 + 2] cyclodimerization and cycloadditions in which an electron acceptor is used in the irradiation process.2 Because of the reversibility of these processes there is very little stereoselectivity observed in the cyclobutanes formed. 

The observation of optical activity in the cycloaddition of TBCK with optically active cy-clonona-1,2-diene was taken as evidence for a concerted process.12 Subsequent studies on TBCK addition to optically active 1,3-dimethylallene and the observation of partially racemic mixtures of products13 indicated that these cycloadditions involve zwitterionic intermediates. Racemization is not necessarily the consequence of intermediate formation. 

The introduction of carbenes and carbenoids into synthetic organic chemistry revolutionized the synthesis of cyclopropane derivatives21. In particular, cyclopropanation of methylenecycloalkanes became a very useful method for the preparation of SPC. Moreover, since cycloaddition of carbenes to olefins involves a very fast concerted process (i.e. it eliminates any intermediates during the formation of the three-membered ring)21, the method is equally efficient for the preparation of both unstrained and highly strained compounds. 

---