Transannular cyclization natural product synthesis

A quite detailed review of transannular cyclizations was published201 wherein their important role in biomimetic syntheses of sesquiterpenes as well as explanation of the biogenetic formation of the polycyclic natural compounds from their monocyclic precursors is discussed. The great significance of these transformations for the synthesis of natural products is also emphasized in a series of reviews which describe the cyclizations to form terpene derivatives, e.g., of the germacrane and humulene systems202-206. 

Transannular cyclizations are an important class of radical reactions that are nowadays frequently used as a key step in the synthesis of polycyclic natural product... 

The intramolecular Diels-Alder cyclization of cyclohexadiene-l,2-dicarboxylic anhydride-derived diester-tethered triene (86) produces the cycloadducts in a ratio of 7 1 (Scheme 31). The intramolecular Diels-Alder reactions of amino acid-derived trienes (87) yield cycloaddition products (88) and (89) which are mainly cw-fused and derived from the exo-transition states (Scheme 32). A key reaction in the synthesis of the natural product momilactone A is the transannular Diels-Alder cyclization of the trans-trans-cis alkene (90) to the trans-syn-trans tricycle (91) (Scheme 33). The Diels-Alder cycloaddition of 1 l-oxapentacyclo[6,5,2,2 0 0 ]-heptadeca-4,14,16-triene-4,5-dicarboxylic anhydride (92) with cyclopentadiene proceeds with 5yn-facial selectivity to produce syn,endo and syn,exo cycloadducts (93) and (94)... 

The second one-pot cascade reaction was used to complete the synthesis of the natural product from acid 69. Reduction of the two azide groups of 69 produced the highly polar diamine 70, which was treated with EDC and HOBt to induce an intramolecular lactam cyclization and deliver the macro-palau amine 71. When the crude reaction mixture of 71 was heated in TEA, compound 72, proceeding through amidine tautomer 71, elicited the key transannular cyclization and delivered the palau amine in 17% overall yield from 69. The outcome stereochemistry was all in the control of the stereocenters within the substrate. 

TRANSANNULAR CYCLIZATION IN NATURAL PRODUCT TOTAL SYNTHESIS... 

The following examples of transannular cyclizations in the context of natural product total synthesis and related settings are grouped according to the reaction types except the last section where memory of chirality is discussed. Because of space limitations, the authors apologize for the omission of many excellent examples. 

Transannular Cyclization in Natural Product Total Synthesis... 

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