2003 Fiscal Year Final Research Report Summary
Novel Domino Cross-aldol/Tishchenko Reaction Promoted by NaH
| Project/Area Number |
13450373
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Okayama University |
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Principal Investigator |
SAITO Seiki Okayama University, Department of Bioscience and Biotechnology, Professor, 工学部, 教授 (60033239)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Teruhiko Okayama University, School of Education, Associate Professor, 工学部(平成13年)・ 岡山大学・教育学部(平成14年以降), 助手, 助教授 (10263617)
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| Project Period (FY) |
2001 – 2003
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| Keywords | cross aldol-Tishchenko reaction / three-contiguous stereocenters / sodium hydride base / ammonium hydroxide base / acetylide addition / cyclohexene-1,3-diones / propargyl-allyl hybrid cation |
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| Research Abstract |
We have found that when an aldehyde (2 eq) was added to a mixture of a ketone and NaH (1.1 eq) in THF at 0℃, domino aldol-Tishchenko reaction took place to afford a 1,3-diol with C(2)-substituent as a single diastereoisomer. It should be noted that no evolution of hydrogen gas was observed when the mixture of the ketone and NaH in THF was stirred at that temperature, and the dropwise addition of the aldehyde triggered the evolution of hydrogen gas which interestingly synchronized to the addition of aldehyde. The aldol-Tishchenko product was proven to have unexceptionally anti-aldol and anti-Tishchenko stereochemical outcome. Furthermore, when the aldehyde (2 eq) was replaced with two different aldehydes A (1 eq) and B (1 eq), Sterically less demanding or, if demanding nature of A and B was similar, more reactive one was incorporated into the aldol process, remaining aldehyde being used as a hydride donor in the Tishchenko process. Also chlorotrimethylsilane didn't affect the reaction b
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y any means. All these findings might indicate that the four component involving the ketone, two of aldehydes, and NaH assemble together through weak interaction among them by keeping delicate balance of the assembly : no distinct enolate intermediate could not intervened.
Being strongly inspired by such chemistry, we paid attention to other traditional bases such as potassium tert-butoxide and found hidden aspects of thermodynamically-controlled enolate generated from simple ketone which plays an important role in domino Michael-Claisen reaction leading to cyclohexane-1,3-dione. We have also found that alkynes can lead to the corresponding acetylide anions on treatment with ammonium hydroxide base in DMSO. This chemistry gave strong incentive to be concerned with alkynes as two directional chain extension tool, and developed several synthetic organic reactions using propargyl-allyl hybrid cation which can be prepared from 1-allylpropargyl ssitrimethylsilyl ether by the action of Lewis acid. Less
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