Other Cydoaddition Reactions

Cheletropic and other cydoaddition reactions conserve orbital symmetry and can occur both intramolecularly as well as tmermolecularly. Both versions are peri-cyclic reactions. The imermolecular set is discussed here (since reactions in that set may be viewed as addition reactions between two molecules). The m/ramolecular reactions, which can be considered rearrangements, will be treated in that section of this chapter. 

Cycloadditions give rise to four-membered rings. Thermal concerted [2+2] cycloadditions have to be antarafacial on one component and the geometrical and orbital constraints thus imposed ensure that this process is encountered only in special circumstances. Most thermal [2+2] cycloadditions of alkenes take place by a stepwise pathway involving diradical or zwitterionic intermediates [la]. Considerably fewer studies have been performed regarding the application of microwave irradiation in [2+2] cydoadditions than for other kinds of cydoaddition (vide supra). Such reactions have been commonly used to obtain /1-lactam derivatives by cycloaddition of ketenes with imines [18-20,117,118],... 

The nudeophile is activated by the formation of a titanium(IV)-imido complex 19. The next step is a [2 + 2] cydoaddition with one of the jt-bonds of the allene, depending on the regioselectivity leading to either 20 or 22. Compound 20 then delivers 21 by twofold stepwise proto-demetallation and the latter enamine tau-tomerizes to the imine 24 (Scheme 15.3). Compound 22, on the other hand, should provide allylamines 23, but as we shall see, there are no examples of that mode of reaction known so far. 

Dailey and coworkers [6] extended the studies of Prinzbach using 4-1 as substrate. These authors found that, by employing dicyanoacetylene 4-15 in the reaction with 4-1 the domino adduct 4-16 but not 4-17, as expected, is the main product (Scheme 4.4). In the formation of 4-16 one of the two 1,3-butadiene moieties in 4-1 has reacted with the dienophile 4-14 from the inside, followed by a second [4+2] cydoaddi-tion of the formed dicyanoethene moiety. 4-17 is observed as a side product here, in the first step, the dienophile reacts from the outside, while in the second step the other formed dienophile moiety undergoes a cydoaddition with the second 1,3-bu-tadiene moiety. This mode of action is actually favored in the reaction of all other dienophiles employed, due to their larger size when compared to 4-15. 

Takasu, Ihara and coworkers described an efficient synthesis of ( )-paesslerin A (4-73) using a combination of a [4+2] and a [2+2] cydoaddition (Scheme 4.16) [25], Reaction of 4-71 and propargylic add methyl ester in the presence of the Lewis acid EtAlClj led to 4-72 in 92 % yield, which was converted in six steps into the desired natural product 4-73 by transformation of one of the ester moieties into a methyl group, hydrogenation of one double bond, removal of the other ester moiety, and exchange of the TIPS group for an acetate. 

Initially applied to thermal cydoaddition of fumarates of chiral alcohols with anthracene [118] (Figure I.34.a), cooperativity was extended to other reactions of symmetrical diesters. While reactions of mixed diesters bearing a single chiral alcohol residue are poorly stereoselective, those of symmetrical diesters can be quite useful. Indeed, the formation of cyclopropane diesters 43 from succinic add diesters and BrCB Cl is poorly diastereoselective when using a mixed methyl and menthyl ester. But it becomes highly diastereoselective when performed with symmetrical dimenthyl esters (Figure I.34.b). 

Dipoles are the three-atom components of [3+2]-cydoadditions. These are 4n electrons species, so [3+2]-cycloadditions are thermally allowed according to the rules of orbital symmetry [624g], The interactions between the frontier orbitals of the two partners are of prime importance, and concerted reactions take place in a supra-suprafacial fashion. When the 1,3-dipoles are not symmetrical, their reactions with unsymmetrical dipolarophiles may give regioisomers. Lack of regioselectivity limits some types of cycloadditions. Chirality can be introduced other on the dipole or on the dipolarophile. 

Among other carboxylic acid derivatives, the a,p-unsaturated lactams 1.92 proposed by Meyers and cowotkers [327] give useful results. No catalysis is needed in cydoadditions with silyloxydienes reactions with 2,3-dimethylbutadiene (R = R I Me) (F %... 

Waldmann and coworkers [263, 264, 1605] used imines of a-aminoesters. These imines can be generated in situ from CH2O and an aminoester hydrochloride in water. Some selective cydoadditions have been observed between cyclic denes, aminoester 1.59 (R = tert-Bu, R = Me) and CH2O (Figure 9.42). However, the removal of the auxiliary could not be carried out due to a competitive retro Diels-Alder reaction. The use of other aminoesters or other dienes give less satisfactory results [264]. 

Cydoadditions, the subject of the last chapter, are just one of the three main classes of peri-cyclic rearrangement. In this chapter, we consider the other two classes—sigmatropic rearrangements and electrocyclic reactions. We will analyse them in a way that is similar to our dealings with cydoadditions. 

Tlie intramolecular nature of this cydoaddition helps lo make it a good reaction, an argument in favour of disconnections like (6a) and 6b). On the other hand, disconnections like 5> (3) + (4) allow us to find simple starting materials more quickly and these two contrary considerations require a balanced judgement. 

Two recent examples of Diels-Alder cydoadditions performed by microwave dielectric heating are described in Scheme 11.3. In both reactions diene and dien-ophile were employed neat, i.e. without the addition of solvent. The reaction described by Trost and Crawley between compounds 7 and 8 (irradiation for 20 min at 165 °C or for 60 min at 150 °C) produced the cycloadduct 9 in nearly quantitative yield [42]. In the process reported by de la Hoz et al., open-vessel irradiation of 3-(2-arylethenyl)chromones 10 with maleimides 11 at 160-200 °C for 30 min furnished tetracyclic adducts of type 12 with minor amounts of other diastereoisomers [43]. 

Dirhodium compounds have proved to be highly efficient and effective catalysts for diverse reactions, which has led to their reputation as being important players in synthetic organic chemistry. A wide range of synthetically useful transformations, such as cyclopropanation, cyclopropenation, insertion into C-H and heteroatom-H bonds, cydoadditions, ylide formation and rearrangement, and other processes are mediated by the catalytic formation of dirhodium(II) carbenes via diazocarbonyl compounds [77],... 

Baylis-Flillman acetates 87 and 89 were involved in the nucleophilic substitution with sodium azide followed by the copper(I) catalyzed 1,3-dipolar cydoaddition of the generated azide to terminal alk5mes (Scheme 51) [80]. The geometry of the products was found to depend on the type of substituents at the Baylis-Hillman acetates. In case of methoxycarbonyl substituent, E-isomers 88 were isolated, while cyano-substituted substrates 89 afforded Z-isomers 90. The reaction of aliphatic alkynes with long chain gave lower yields (e.g., 88, R=hexyl, 58% R=octyl, 42%). It should also be noted that with respect to other solvents, PEG 400 allowed performing the reaction in the absence of... 

The synthetic potential of RRM can be amphfied with the introduction of a third olefin, permitting the access to much more complex structures in one single transformation, by a further intermolecular CM or a second RCM. As discussed above, two mechanistic pathways can be envisaged. The metathesis cascade may involve an initial formation of a ruthenium-alkyhdene complex at the terminal olefin, or alternatively, the sequence may begin with [2+2]-cydoaddition of the ruthenium carbene onto endocychc double bond, followed by ROM-RCM or CM. Neither of these possibihties can be ruled out, and the occurrence of one or the other may be influenced according to ring strain, steric and electronic properties of the corresponding olefins, and also the reaction conditions employed (Scheme 11.22). 

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