New Regio- and Stereoselective Cascades via Unstabilized Azomethine Ylide Cycloadditions for the Synthesis of Highly Substituted Tropane and Indolizidine Frameworks.
New Regio- and Stereoselective Cascades via Unstabilized Azomethine Ylide Cycloadditions for the Synthesis of Highly Substituted Tropane and Indolizidine Frameworks.
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DOI：
10.1021/jacs.6b08355
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发表时间：
2016-09-28
影响因子：
15
通讯作者：
Ellman JA
中科院分区：
文献类型：
--
作者：
Chen S;Bacauanu V;Knecht T;Mercado BQ;Bergman RG;Ellman JA
以三甲基硅取代的1，2-二氢吡啶为原料，通过质子化或烷基化反应，再经脱硅反应，生成不稳定的甲亚胺叶立德，再经[3 + 2]环加成反应，以高的区域和立体选择性合成了多取代的托品烷和中氮茚。从在6-位带有环三甲基甲硅烷基取代基的1，2-二氢吡啶开始，分子间烷基化/脱甲硅烷基化提供了内环不稳定的叶立德，其成功地与一系列对称和不对称的炔和烯烃亲偶极试剂进行环加成，以良好的产率和高的区域和立体选择性提供包含季碳的密集取代的托品烷。此外，分子内烷基化/脱甲硅烷基化/环加成序列提供了方便和快速的进入桥连三环托烷骨架，允许在单一实验操作和温和条件下设置五个连续的碳立体中心。以氮原子上带有三甲基硅基甲基的1，2-二氢吡啶为原料，质子化后脱硅生成环外不稳定叶立德，再与不对称炔进行环加成反应，得到具有良好区域和立体选择性的中氮茚。N-三甲基甲硅烷基甲基1，2-二氢吡啶也可以烷基化，随后脱甲硅烷基化，得到内环不稳定的叶立德，该叶立德与羰基化合物进行分子间环加成，以良好的总产率得到双环恶唑烷产物。此外，与N-三甲基甲硅烷基甲基1，2-二氢吡啶的分子内烷基化/脱甲硅烷基化/环加成序列提供了三环吲嗪，其包含季碳和多达五个立体中心，具有良好的区域和非对映选择性。
Multisubstituted tropanes and indolizidines have been prepared with high regio- and stereoselectivity by the [3 + 2] cycloaddition of unstabilized azomethine ylides generated from readily prepared trimethylsilyl substituted 1,2-dihydropyridines via protonation or alkylation followed by desilylation. Starting from 1,2-dihydropyridines bearing a ring trimethylsilyl substituent at the 6-position, an intermolecular alkylation/desilylation provides endocyclic unstabilized ylides that successfully undergo cycloaddition with a range of symmetrical and unsymmetrical alkyne and alkene dipolarophiles to afford densely substituted tropanes incorporating quaternary carbons in good yields and with high regio- and stereoselectivity. Additionally, an intramolecular alkylation/desilylation/cycloaddition sequence provides convenient and rapid entry to bridged tricyclic tropane skeletons, allowing for five contiguous carbon stereocenters to be set in a single experimental operation and under mild conditions. Starting from 1,2-dihydropyridines with trimethylsilylmethyl groups on nitrogen, protonation followed by desilylation generates exocyclic unstabilized ylides that undergo cycloaddition with unsymmetrical alkynes to give indolizidines with good regio- and stereoselectivity. N-Trimethylsilylmethyl 1,2-dihydropyridines can also be alkylated and subsequently desilylated to give endocyclic unstabilized ylides that undergo intermolecular cycloadditions with carbonyl compounds to give bicyclic oxazolidine products in good overall yields. Moreover, an intramolecular alkylation/desilylation/cycloaddition sequence with the N-trimethylsilylmethyl 1,2-dihydropyridines affords tricyclic indolizidines that incorporate quaternary carbons and up to five stereocenters with good to excellent regio- and diastereoselectivity.
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影响因子：
16.6
作者：
Duttwyler, Simon;Chen, Shuming;Lu, Colin;Mercado, Brandon Q.;Bergman, Robert G.;Ellman, Jonathan A.
通讯作者：
Ellman, Jonathan A.
影响因子：
15
作者：
Ischay, Michael A.;Takase, Michael K.;Bergman, Robert G.;Ellman, Jonathan A.
通讯作者：
Ellman, Jonathan A.
通过脱甲硅烷基化产生的不稳定偶氮甲碱叶立德合成金盏茶碱 A 型瑞香生物碱的氮杂三环 ACD 环系统
影响因子：
1.8
作者：
Ma, Ding;Cheng, Hang;Xu, Liang
通讯作者：
Xu, Liang
影响因子：
2
作者：
Davoren, Jennifer E.;Gray, David L.;Xu, Wenjian
通讯作者：
Xu, Wenjian
DOI：
10.1039/b204464a
发表时间：
2002-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1
影响因子：
--
作者：
Novikov, MS;Voznyi, IV;Kostikov, RR
通讯作者：
Kostikov, RR