Radical Domino Strategies

Ph3SnH (t.3 equiv.) AIBN(30mol%) Et3N (20 equiv.) PhH, reflux 

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Radical domino strategies have been scarcely described in the construction of polycyclic cyclopropanic structures. Indeed, radicals formed by 3-exo-trig cyclization are being rapidly reopened, and this property is notably used in radical clocks experiments. In order to suppress this unwanted event, Malacria and Fensterbank have devised a (dichloromethyl)dimethylsilyl ether able to play both roles of the initiation and termination sites of the radical process [108]. By designing an appropriate acyclic structure 98, the expected cyclopropanic compounds 99 have been obtained in good yields and diastereoselectivities after addition of MeLi to the silyloxycyclopentene intermediate (Scheme 5.35). 

Scheme 535 Polycyclization using a radical domino strategy.

Scheme 3.50. Domino radical cydization strategies from linear acylic precursors (the formed bonds are highlighted in bold).

The most recent highlight in enantioselective radical domino processes can be attributed again to the MacMillan group, in their development of an efficient polyene domino cyclization via the organo-SOMO catalysis strategy [85] (Scheme 5.57). 

Instead of simply using two radical reactions in a domino process, the combination of three and more radical C-C- or C-N-bond forming radical transformations is also possible. This makes this methodology one of the most powerful procedures in the synthesis of complex molecules starting from simple substrates [77]. During the years, several strategies have been developed, and these are depicted in Scheme 3.50. The strategies can be classified as three types ... 

The use of catalytic enantioselective domino transformations initiated by the addition of nucleophiles to a,p-unsaturated compounds, generating a new stereocenter that determines the stereochemistry of the following step, has been widely used for the synthesis of a variety of biologically active compounds. According to the mechanism involved in the first addition step, this strategy involves most of the time an ionic process, but in some specific cases radical-initiated sequences are also efficient. 

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