Other thermal cycloadditions

Our rationale focuses on the Diels-Alder reaction, but it can also be applied to other thermal cycloadditions. The acceptor is modeled as a low-energy vacant orbital A whose energy reflects the nature of the substituent. Hiickel values for common acceptors are C=N (A = a — 0.781/ ), C=0 (A = a - 0.618/1) and NOz (A is almost non-bonding). As 7t CN lies between n cc and Tf, the cyanobutadiene LUMO (a — 0.325/ ) is Fg lowered in energy by interaction with A. On the other hand, the acrylonitrile LUMO (a - 0.460/ ) is A lowered in energy by interaction with 7r cc, which explains why it lies relatively close to the cyanobutadiene LUMO (scheme a below). For more powerful attractors such as C=0 or NOz, A lies at the same... 

To understand why these reactions work, we need to consider a new and potentially fruitful way for two alkenes to approach each other. Thermal cycloadditions between two alkenes do not work because the HOMO/LUMO combination is antibonding at one end. 

Summary the three major approaches to the synthesis Other thermal cycloadditions 894... 

A variety of other highly-strained electron-rich donors also form colored complexes (similar to homobenzvalene) with various electron acceptors, which readily undergo thermal cycloadditions (with concomitant bleaching of the color).209 For example, Tsuji et al.210 reported that dispiro[2.2.2.2]deca-4,9-diene (DDD), with an unusually low ionization potential of 7.5 eV,211 readily forms a colored charge-transfer complex with tetracyanoquinodimethane (TCNQ). The [DDD, TCNQ] charge-transfer complex undergoes a thermal cycloaddition to [3,3]paracyclophane in excellent yield, i.e.,... 

Our initial studies focused on the transition metal-catalyzed [4+4] cycloaddition reactions of bis-dienes. These reactions are thermally forbidden, but occur photochemically in some specific, constrained systems. While the transition metal-catalyzed intermole-cular [4+4] cycloaddition of simple dienes is industrially important [7], this process generally does not work well with more complex substituted dienes and had not been explored intramolecularly. In the first studies on the intramolecular metal-catalyzed [4+4] cycloaddition, the reaction was found to proceed with high regio-, stereo-, and facial selectivity. The synthesis of (+)-asteriscanoHde (12) (Scheme 13.4a) [8] is illustrative of the utihty and step economy of this reaction. Recognition of the broader utiHty of adding dienes across rc-systems (not just across other dienes) led to further studies on the use of transition metal catalysts to facilitate otherwise difficult Diels-Alder reactions [9]. For example, the attempted thermal cycloaddition of diene-yne 15 leads only... 

The thermal cycloaddition of 3-acyl-2(3/7)-oxazolones 157 to dialkyl azodicar-boxylates 228 proceeds smoothly under mild conditions (at 80 °C) to give the regiocontrolled cycloadducts 229 exclusively, although two other possible addition modes exist neither diazetidines 230 (1,2-addition) nor isoxazolidines 231 (1,3-addition) are detected. In the case of chiral N-substituents diastereoselectivities of up to 72% de have been obtained. Treatment of the chiral cycloadducts 229 with acidic methanol gives tra i-5-hydrazino-4-methoxy-2-oxazolidmone derivatives 232 that are precursors for a variety of optically active a-amino acids 233 and 2-oxazolidinone auxiliaries 234 (Fig. 5.56 Table 5.10, Fig. 5.57)7 ... 

Other selenocarbonyl cycloaddition products react similarly. Thermal cleavage of the dimeric 163 leads to unstable a,/3-unsaturated selones which can be trapped by a diene affording the selenin 164 (Equation 67) <1994CL2283>. 

Other thermal 1,3-dipolar cycloadditions are the reactions between nitrile sulfides and electron-deficient aldehydes and ketones forming 1,3,4-oxathiazolines (98 Scheme 19) between aryl thioketones and thiofluorenone 5-tosylimide to yield the 1,3,4-dithiazolidines (204) and between thioketene S-oxides and imines, yielding in one case the 1,2,4-oxathiazolidine (136). 

Few examples of [4 + 2] cycloadditicMis of aromatic aldehydes with simple alkyl-, halo- and alkoxy-substituted 1,3-dienes exist. Ansell and Charalambides found that benzaldehydes substituted with electron-withdrawing groups such as nitro and cyano undergo thermal cycloaddition.Other benzaldehydes were found to cycloadd only in the presence of p-toluenesulfonic acid. 

The stereochemistry at the remaining centre comes from the way in which the two molecules approach each other. The two components are orthogonal and the dotted lines in the middle diagram below show how the new bonds are formed. The carbonyl group of the ketene will prefer to e in the middle of the ring and the side chain on the ketene will bend down away from the top ring. These [2 + 2] thermal cycloadditions normally give the all-ds product. 

Cycloaddition of TCNE to homobenzvalene yields various tetracyanocycloadducts. The photochemical process yields products that differ from the ones obtained by thermal cycloaddition ". Other polycyclic unsaturated hydrocarbons were also reacted to tetracyano cycloadducts. Hence the dihydrobullvalene 393 yielded 394. Pyrolysis of 394 gave 393 rather than elimination products" ". ... 

In the previous, and almost in every calculation on Diels-Alder reactions, it has been assumed that diene and dienophile lie on top of each other in parallel (or roughly parallel) planes. Under this condition, the endo approach is theoretically better than the exo approach only because of secondary interactions. However, it has been shown that, for cyclopentadiene dimerisation, if the two molecules are allowed to approach in a non-parallel way, the endo preference can be mainly attributed to a more favourable primary interaction, due to an approach at an angle of ca. 60°, which could be allowed only to the c/ido-oriented dienophile because of steric reasons . The pmo method has also been applied to a simplified treatment of some competing 1,4 and 1.2 thermal cycloadditions involving diradical intermediates . 

Thermal cycloadditions of chiral vinylsulfoxides B with cyclopentadiene, 1,3-cyclohexadiene and 1,3-butadiene have been examined in toluene at high temperature leading to the adducts in moderate selectivities. The electron-deficient sulfur residue activates the alkene unit and serves as a temporary substituent that can be easily removed by reduction or transformed into a variety of other functionalities. An increase in reactivity and excellent selectivities are observed in the presence of additional electron-withdrawing substituents at the alkene unit as shown for the examples and in the table below. At 20°C in dichloromethane the cycloadditions of C with cyclopentadiene proceed smoodily and highly stereoselective. In reactions of menthyl-3-(3-trifluoromethyl-2-pyridylsulfinyl)acrylate A with dienes, e.g. 2-methoxyfliran or cyclopentadiene, high diastereoselectivities (>98 2) were obtained, too. 

Cycloadditions represent an important class of photochemical reactions. We discussed thermal cycloadditions extensively in Chapter 15, with the prototype being the [4+2] cycloaddition of the Diels-Alder reaction. Orbital symmetry reasoning would lead us to expect that photochemical cycloadditions should be typified by a [2+2] reaction. Indeed, formal [2+2] photocycloadditions are common. However, most photochemical cycloadditions involve triplet states and biradical intermediates. Concerted photochemical cycloadditions are rare. As such, orbital symmetry arguments are not directly relevant, and instead we must focus on potential biradical intermediates and possible funnels and other surface crossing points. Some photochemical cycloadditions do proceed via singlet states, and usually these involve the formation of exciplexes. 

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