Enantioselective Assembly of Fully Substituted α‐Amino Allenoates Through a Mannich Addition and Stepwise [3,3]‐σ Rearrangement Sequence
Abstract Chiral fully‐substituted allenes are synthetically significant and pivotal building blocks that can engage in diverse transformations toward a variety of bioactive molecules. The enantioselective assembly of these skeletons using readily available reactants offers significant advantages but...
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| Format: | Article |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409334 |
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| author | Haoxuan Yuan Yi Zhou Xiongda Xie Ming Bao Kewei Chen Kemiao Hong Zhixiang Yu Xinfang Xu |
| author_facet | Haoxuan Yuan Yi Zhou Xiongda Xie Ming Bao Kewei Chen Kemiao Hong Zhixiang Yu Xinfang Xu |
| author_sort | Haoxuan Yuan |
| collection | DOAJ |
| description | Abstract Chiral fully‐substituted allenes are synthetically significant and pivotal building blocks that can engage in diverse transformations toward a variety of bioactive molecules. The enantioselective assembly of these skeletons using readily available reactants offers significant advantages but remains challenging. Herein, an asymmetric formal Michael‐type addition of alkynyl imines with the key alkylgold intermediates derived in situ from N‐propargylamides is accomplished under gold‐complex and chiral quinine‐derived squaramide (QN‐SQA) synergetic catalysis. Control experiments and the density functional theory (DFT) calculations indicated that this cascade reaction involves a Mannich‐type addition and stepwise [3,3]‐σ rearrangement sequence, leading to the fully substituted α‐amino allenoates, which are elusive and take multi‐step to prepare with other methods, in high yields and excellent enantioselectivity. |
| format | Article |
| id | doaj-art-550ba6e02f9f40e4833a3fb07aab25b9 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-550ba6e02f9f40e4833a3fb07aab25b92025-01-13T15:29:43ZengWileyAdvanced Science2198-38442025-01-01122n/an/a10.1002/advs.202409334Enantioselective Assembly of Fully Substituted α‐Amino Allenoates Through a Mannich Addition and Stepwise [3,3]‐σ Rearrangement SequenceHaoxuan Yuan0Yi Zhou1Xiongda Xie2Ming Bao3Kewei Chen4Kemiao Hong5Zhixiang Yu6Xinfang Xu7School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 ChinaBeijing National Laboratory for Molecular Sciences (BNLMS) Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education College of Chemistry Peking University Beijing 100871 ChinaSchool of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 ChinaSchool of Chemistry and Chemical Engineering Zhejiang Sci‐Tech University Hangzhou 310018 ChinaSchool of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 ChinaSchool of Chemistry and Chemical Engineering Zhejiang Sci‐Tech University Hangzhou 310018 ChinaBeijing National Laboratory for Molecular Sciences (BNLMS) Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education College of Chemistry Peking University Beijing 100871 ChinaSchool of Chemistry and Chemical Engineering Zhejiang Sci‐Tech University Hangzhou 310018 ChinaAbstract Chiral fully‐substituted allenes are synthetically significant and pivotal building blocks that can engage in diverse transformations toward a variety of bioactive molecules. The enantioselective assembly of these skeletons using readily available reactants offers significant advantages but remains challenging. Herein, an asymmetric formal Michael‐type addition of alkynyl imines with the key alkylgold intermediates derived in situ from N‐propargylamides is accomplished under gold‐complex and chiral quinine‐derived squaramide (QN‐SQA) synergetic catalysis. Control experiments and the density functional theory (DFT) calculations indicated that this cascade reaction involves a Mannich‐type addition and stepwise [3,3]‐σ rearrangement sequence, leading to the fully substituted α‐amino allenoates, which are elusive and take multi‐step to prepare with other methods, in high yields and excellent enantioselectivity.https://doi.org/10.1002/advs.202409334alkyne functionalizationasymmetric catalysiscooperative catalysisgold catalysisα‐amino allenoate |
| spellingShingle | Haoxuan Yuan Yi Zhou Xiongda Xie Ming Bao Kewei Chen Kemiao Hong Zhixiang Yu Xinfang Xu Enantioselective Assembly of Fully Substituted α‐Amino Allenoates Through a Mannich Addition and Stepwise [3,3]‐σ Rearrangement Sequence Advanced Science alkyne functionalization asymmetric catalysis cooperative catalysis gold catalysis α‐amino allenoate |
| title | Enantioselective Assembly of Fully Substituted α‐Amino Allenoates Through a Mannich Addition and Stepwise [3,3]‐σ Rearrangement Sequence |
| title_full | Enantioselective Assembly of Fully Substituted α‐Amino Allenoates Through a Mannich Addition and Stepwise [3,3]‐σ Rearrangement Sequence |
| title_fullStr | Enantioselective Assembly of Fully Substituted α‐Amino Allenoates Through a Mannich Addition and Stepwise [3,3]‐σ Rearrangement Sequence |
| title_full_unstemmed | Enantioselective Assembly of Fully Substituted α‐Amino Allenoates Through a Mannich Addition and Stepwise [3,3]‐σ Rearrangement Sequence |
| title_short | Enantioselective Assembly of Fully Substituted α‐Amino Allenoates Through a Mannich Addition and Stepwise [3,3]‐σ Rearrangement Sequence |
| title_sort | enantioselective assembly of fully substituted α amino allenoates through a mannich addition and stepwise 3 3 σ rearrangement sequence |
| topic | alkyne functionalization asymmetric catalysis cooperative catalysis gold catalysis α‐amino allenoate |
| url | https://doi.org/10.1002/advs.202409334 |
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