Acid-induced transannular reactions

In 10(4)c and 10(5)c the alkane tether of the rings is elongated as compared to 10(3)c. This leads to a nonparallel orientation of the 1,3-butadiyne units with distances between the terminal sp centers of 310 pm and about 400 to 430 pm [33], 

These studies show that if the two 1,3-butadiyne units are in close proximity on one side, only three of the four alkyne units are involved in the transannular ring closure. 

3-butadiyne units are forced close together due to the methyl groups so that valence isomerization occurs during the reaction. 

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Bicyclic 3a//-cyclopentene[8 annulcnc-l,4-(5//,9a//)-dioncs undergo three types of acid-induced transannular reactions (1) Michael addition (5-exo-trig or 6-exo-trig) leading to the tetracyclic diones, (2) 3 + 2-cycloaddition followed by a novel sequential skeletal rearrangement to 2-naphthalenone derivatives, (3) ipso-Friedel-Crafts alkylation accompanied by the rearomatization and the loss of water (Scheme 25). The factors that control the reaction mode of these transannular cyclizations are discussed... 

Further transannular cyclization studies start from (E)- or(Z)-5-cyclodecenone while radical-induced reactions form hydroazulene skeletons predominantly, the acid-catalyzed reactions generate hydronaphthalene systems. Only 1,6-cyclization products are observed, the L -config-urated cyclodecenone leads to the tram, while the Z-configurated material yields the cis ring... 

Transannular cyclization can be induced by acid-mediated activation of a,/J-unsaturated carbonyl groups. Treatment of an a./J-unsaturated ketone with formic acid/boron trifluoridc-di-ethyl ether complex produces the tricycle 1423. Ketone 14 is a precursor in the pentalene 8 synthesis (Prins reaction analog). Transannular Prins cyclizations are described in Section 1.5.5.2.2.2.26-27. 

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. 

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