2000 Fiscal Year Final Research Report Summary
Tandem cyclization based on titanium cascade-Development of short-step synthesis of optically active polycyclic compounds
| Project/Area Number |
11650886
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Synthetic chemistry
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
URABE Hirokazu Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology, Associate Profess, 大学院・生命理工学研究科, 助教授 (10176745)
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| Project Period (FY) |
1999 – 2000
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| Keywords | asymmetric reaction / bicyclic ketone / conjugated diene / cyclopentadienol / Diels-Alder reaction / tandem cyclization / titanacycle / titanium reagent |
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| Research Abstract |
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.
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