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

基于钛级联的串联环化-光学活性多环化合物的短步合成研究进展

• 批准号: 11650886
• 负责人: URABE Hirokazu
• 金额: $ 1.98万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11650886/
• 关键词: asymmetric reaction; bicyclic ketone; conjugated diene; cyclopentadienol; Diels-Alder reaction; tandem cyclization; titanacycle; titanium reagent; アセチレン; チタナシクロペンタジエン; ラクタム; ラクトン; チタナシクロペンテン

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.

根据最初提出的项目顺序，总结了以下结果。用（η^2-丙烯）Ti (O-i-Pr)_2(1)反应得到旋光性8-苯薄荷醇衍生的3-烷基-2-烯烃-7-乙烯酸酯，得到相应的钛环戊烯。这些钛环用等摩尔量的质子淬灭，使第二环闭合，得到具有角烷基的光学活性双环[3.3.0]oct- 10 -3- 1，其ee值高达93%。接着研究了另一个串联环合反应。因此，由内炔、3-丁炔基酯和1生成的钛环戊二烯，或者由3,8 -或3,9 -烷炔基酯和1生成的钛环戊二烯，在分子内连续将两个碳-钛键加成到酯羰基上，得到单环或双环环戊二烯醇，收率很高。从5,10 -生物二酸酯开始，串联反应一步得到三环环戊二醇。将这种转化扩展到不对称版本，以及使用钛环戊二烯构建多环产品的其他尝试，到目前为止都没有取得成功。然而，在我们的研究过程中，我们发现，1介导的与酯或酰胺基团相连的各种二烯的分子内环化很好地进行了外环、外环二烯连接到内酯或内酰胺链上。所得到的外环、外环二烯与乙炔酮、酯或马来酰亚胺发生Diels-Alder反应，生成具有高区域选择性和/或不对称诱导的（光学活性）双环化合物。由此，建立了利用钛环形成和Diels-Alder反应组成的串联反应制备多环化合物的简便方法。

项目成果

Hirokazu Urabe: "Asymmetric Synthesis of Bicyclic Ketones Having an Angular Substituent via Ti(II) Alkoxide-Mediated Tandem Cyclization of Tri-substituted Olefinic Substrates"Org.Lett.. 2,3. 381-383 (2000)

Hirokazu Urabe：“通过三取代烯烃底物的 Ti(II) 醇盐介导的串联环化来不对称合成具有角取代基的双环酮”Org.Lett.. 2,3。

H.Urabe: "Asymmetric Synthesis of Bicyclic Ketones Having an Angular Substituent via Ti (II) Alkoxide-Mediated Tandem Cyclization of Tri-substituted Olefinic Substrates"Org.Lett.. 2・3. 381-383 (2000)

H.Urabe：“通过Ti(II)醇盐介导的三取代烯烃底物的串联环化来不对称合成具有角取代基的双环酮”Org.Lett.. 2・3 (2000)。

占部弘和: "有機合成における華やかな金属試薬・チタン"ファルマシア. 36・7. 612-613 (2000)

Hirokazu Urabe：“钛，有机合成中的华丽金属试剂” Pharmacia 36・7（2000）。

F.Sato, H.Urabe, and S.Okamoto: "Synthesis of Organotitanium Complexes from Alkenes and Alkynes, and Their Synthetic Application"Chem.Rev.. 100(8). 2835-2886 (2000)

F.Sato、H.Urabe 和 S.Okamoto：“从烯烃和炔烃合成有机钛配合物及其合成应用”Chem.Rev.. 100(8)。

H.Urabe: "A Facile Preparation of exo-Cyclic Conjugated Dienes Fused to Lactams or Lactones via Intramolecular Coupling of Acetylenes and Their Behavior in Diels-Alder Reactions"Org.Lett.. 2・22. 3481-3484 (2000)

H.Urabe：“通过乙炔分子内偶联与内酰胺或内酯稠合的外环共轭二烯及其在 Diels-Alder 反应中的行为的简便制备”Org.Lett. 2・22 (2000)。