Cyclization, radicals Diels-Alder

Scheme 3.83. First domino radical cyclization/intramolecular Diels-Alder reaction process.

The ion-radical Diels-Alder reactions represent a new development (see, e.g., reviews by Hintz et al. 1996, Berger and Tanko 1997). These reactions initiated with ion-radicals proceed faster by several orders of rate magnitude than the corresponding conventional reactions. This section presents the most important cyclizations developed through cation- and anion-radical schemes and the scheme that includes both cation- and anion-radicals. 

Synthesis of carbocyclic systems intramolecular free-radical cyclization, the Diels-Alder reaction, and ring-closing metathesis... 

The fact that no cyclohexene was detected in the present experiments suggests that the rate of cyclization through Diels-Alder reaction between formed butadiene and olefins is smaller than the rate of cyclization caused by the reaction of ally radical with olefins at these temperatures. 

Sequential radical cyclizations are also featured in an efficient and clever synthesis of the cedrane framework 83 (see Scheme 15).30 Compound 81, the product of a regioselective Diels-Alder reaction between isoprene (79) and nitroethylene (80), participates in a nitroaldol reaction (Henry reaction) with 5-methyl-4-hexenal in the presence of a basic resin to give 82. Because the nitro group in... 

Ethyl l-cyano-2-methylcyclohexanecarboxylate has been prepared by catalytically hydrogenating the Diels-Alder adduct from butadiene and ethyl 2-cyano-2-butenoate3 and by the procedure described in this preparation.4 8 This procedure illustrates a general method for the preparation of alicyclic compounds by the cyclization of <5-ethylenic carbon radicals l.6 Whereas the primary 5-hexen-l-yl radical 1... 

The chemistry and utility of zinc-based Lewis acids are similar to those of their magnesium analogs. Their mild Lewis acidity promotes several synthetic reactions, such as Diels-Alder reactions, hetero Diels-Alder reactions,229 radical-mediated reactions,230 ene-type cyclization, and Simmons-Smith reactions. 

Diels-Alder catalysis.1 This radical cation can increase the endo-selectivity of Diels-Alder reactions when the dienophile is a styrene or electron-rich alkene. This endo-selectivity obtains even in intramolecular Diels-Alder reactions. Thus the triene 2, a mixture of (Z)- and (E)-isomers, cyclizes in the presence of 1 to 0° to the hydroindanes 3 and 4 in the ratio 97 3. Similar cyclization of (E)-2 results in 3 and 4 in the ratio 98 2 therefore, the catalyst can effect isomerization of (Z)-2 to (E)-2. Even higher stereoselectivity is observed when the styrene group of 2 is replaced by a vinyl sulfide group (SC6H5 in place of QHtOCT ). 

This section is devoted to cyclizations and cycloadditions of ion-radicals. It is common knowledge that cyclization is an intramolecular reaction in which one new bond is generated. Cycloaddition consists of the generation of two new bonds and can proceed either intra- or intermolecularly. For instance, the transformation of 1,5-hexadiene cation-radical into 1,4-cyclohexadienyl cation-radical (Guo et al. 1988) is a cyclization reaction, whereas Diels-Alder reaction is a cycloaddition reaction. In line with the consideration within this book, ring closure reactions are divided according to their cation- or anion-radical mechanisms. 

J. C. Lopez, A. M. Gomez, and B. Fraser-Reid, Silicon-tethered radical cyclization and intramolecular Diels-Alder strategies are combined to provide a ready route to highly functionalized decalins, J. Chem. Soc. Chem. Comtmm. p. 762 (1993). 

The photo Diels-Alder reaction of a-acetylnaphthalene 82 with the chiral oc-enaminonitril 83 yielded the cycloadduct 84 with excellent diastereoselec-tivity (Sch. 16) [57]. The intermediary formed biradical Y is particular stable due to delocalization of the radical on the aromatic moiety and to a captodative effect on the enamine part. The chiral induction occurred in two steps [58]. In the first step, a stereogenic center is created in the a-position of the acyl group. In the second step of the diastereoselection, one of the two diasteromeric intermediates undergoes preferentially cyclization to yield the final product 84, while the other one is more readily decomposed to form the starting material. For a more detailed discussion of the mechanism see Ref. [59]. 

The most likely multistep mechanism of this type is shown in the lower part of Figure 12.17. It is a two-step mechanism where the diastereomeric diradicals F and G are the two intermediates that allow for rotation about the configuration-determining C—C bond. Each of the two radical centers is part of a well-stabilized allyl radical (cf. Section 1.2.1). It is unknown whether the formation of biradical F is subject to simple diastereoselectivity in comparison to G (for the occurrence of simple diastereoselec-tivity in one-step Diels-Alder reactions, see Section 12.3.4). Biradicals F and G cyclize without diastereocontrol to deliver the [4+2]-cycloadducts biradical F forms a mixture of1 2trans,cis-[D]2-C and 1,2trans, trans [D]2-C, since a rotation about the C2—C3 bond is possible but not necessary. For the same reason, biradical G forms a mixture of 1 2cis,cis- I) 2-C and 1,2cis,trans [D]2-C. 

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