TADA reaction

29 December 2008 - reaction types

What: The TADA reaction or transannular Diels-Alder reaction.
Not to be confused with : the TA-DA reaction used to accompany or draw attention to a dramatic entrance or announcement'
Why: Big advantage: quick access to complex hydrocarbon skeletons for example steroids and other complex biomolecules. Big disadvantages: the macrocycles are floppy so you tend to end up with closely similar isomers. Use substituents at proper places to force favorable conformation. Macrocycles themselves present a challenge. A cis, trans, cis triene is required for DA lineup.

How: The first to try this reaction progressing from rearrangement reactions of cyclic dienes, was Dauben in 1981 (DOI). The C11 triene first rearranges in a sigmatropic 1,5-H shift which is then followed by the DA reaction forming trans-tricyclo(5.4.0.0)undec-2-ene.

Deslongchamps in 1987 extended the scope as a synthetic strategy by first examining a cis, trans,trans triene which forms a mixture of three isomers (DOI) before settling on a related trans, cis, cis one ( DOI).

Takahashi et al. in 1988 were the first to apply the methodology in steroid synthesis(DOI):

Most recently the reaction was used in total synthesis (Hayashi et al. 2008 DOI):