Tandem cyclization based on titanium cascade-Development of short-step synthesis of optically active polycyclic compounds

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The following results are summarized according to the order of the initially proposed projects.3-Alkyl-2-alkene-7-ynoates derived from optically active 8-phenylmenthol were treated with (η^2-propene) Ti (O-i-Pr)_2 (1) to give the corresponding titanacyclopentenes. These titanacycles were quenched with an equimolar amount of proton to effect the second ring closure to give optically active bicyclo [3.3.0] oct-ten-3-ones having an angular alkyl group with high ee values of up to 93%.Another tandem cyclization was next examined. Thus, titanacyclopentadienes generated from internal alkyne, 3-butynyl ester, and 1 or, alternatively, from 3, 8- or 3, 9-alkadiynyl ester and 1 underwent the successive intramolecular addition of the two carbon-titanium bonds to the ester carbonyl group to give mono- or bicyclic cyclopentadienols in good yields. Starting from a 5, 10-alkadiynoate, this tandem reaction afforded a tricyclic cyclopentadienol in one step. The extension of this transformation to an asymmetric version and other attempts to use titanacyclopentadienes for the construction of multi-ring products so far did not meet with success.However, during the course of our study, we found that 1-mediated intramolecular cyclization of various diynes tethered with an ester or amide group nicely proceeded to give exo, exo-cyclic dienes attached to the lactone or lactam linkage. The resulting exo, exo-cyclic dienes are very reactive towards Diels-Alder reaction with acetylenic ketones, esters, or maleimides to give (optically active) bicyclic compounds with high regioselectivity and/or asymmetric induction. Thus, the convenient preparation of polycyclic compounds taking advantage of the tandem reaction consisting of the titanacycle formation and Diels-Alder reaction was established.