Intramolecular -Cycloadditions

In addition to the [4+2] cycloaddition, intramolecular [2+2] photocycloaddition was also successfully used as a main procedure in the synthesis of (i)-ginkgolide B <00JA8453>. The studies on the model reactions and molecular mechanics calculation show that the stereochemistry of the substituents at C6 and C8 should influence severely the reaction diastereoselectivity. When syn-diastereomer 41 is subjected to irradiation the reaction gives a single diastereomer 42 in a quantitative yield since two substituents at C6 and C8 would be in pseudo-equatorial orientation in the chair-like transition state. 

Intramolecular Cycloaddition Intramolecular nitrile oxide cycloaddition (INOC) is widely used in the synthesis of various compounds, particularly, natural products. This field is reviewed in detail in Chapter 6 of the mono-graph/Reference 5 and also in Reference 400 limited to nitrile oxides generated from nitroalkenes. Some features of INOC are illustrated in this subsection by new data and those omitted in Reference 5. 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cycloaddition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-catalyzed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41-43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cycloadditions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

In addition to these intramolecular [2+2+2] cycloadditions, intramolecular [4+2] cycloaddition of yne-enones 29 leading to fused pyrans 30 has been achieved by means of the ruthenium catalysis with a cationic complex, CpRu(MeCN)3PF6 (Eq. 15) [24], Such hetero Diels-Alder cycloaddition was considered to proceed via an oxaruthenacycle 31. 

Heathcock used as concerted cycloaddition intramolecular photochemical (2 + 2) addition to create the quaternary center in his projected synthesis. A cationic rearrangement Wagner-Meerwein rearrangement) was intended as further key step but failed (162). 

Weinreb and Sisko have reported the first examples of Diels-Alder reactions of Af-tosyl imines derived from enolizable aldehydes [12]. The imines were generated in situ from the aldehyde, N-sulfinyl-p-toluenesulfonamide and boron trifluoride etherate. Two examples of these cycloadditions are shown in Egs. (50) and (51). It was also possible to effect the cycloaddition intramolecularly [Eq. 

Intramolecular Cycloadditions. - Intramolecular (2 + 2)-photocycloaddi-tion has been reported within diene 1,1-dicarbonitriles. Both direct and sensitized irradiation is effective. Unlike the singlet process, where an exciplex is involved, the sensitized process proceeds via 1,4-biradicals. The singlet and triplet reactivity has been investigated for a series of 1-alkene-1,1-dicarbonitriles with additional unsaturation at the 5, 6 or 7 positions. The cyclophane moiety shown in the derivative (23) has been suggested as a useful reaction control system. The irradiation of this cinnamate derivative affords the (3-truxinic acid derivative (24), which can be uncoupled from the paracyclophane. ... 

Scheme 11.23 Intermolecular [2+2+2] cycloaddition/intramolecular Diels-Alder (IMDA) cascade [38].

Kobayashi, M., Suda, T., Noguchi, K., Tanaka, K. (2011). Enantioselective construction of bridged multicyclic skeletons intermolecular [2+2+2] cycloaddition/intramolecular Diels-Alder reaction cascade. Angewandte Chemie, International Edition, 50,1664-1667. 

Address stereochemistry and regiochemistry issues by making the cycloaddition intramolecular... 

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