Difluoroalkylation of tertiary amides and lactams by an iridium-catalyzed reductive reformatsky reaction
An iridium-catalyzed, reductive alkylation of abundant tertiary lactams and amides using 1-2 mol % of Vaska's complex (IrCl(CO)(PPh<sub>3</sub>)<sub>2</sub>), tetramethyldisiloxane (TMDS), and difluoro-Reformatsky reagents (BrZnCF<s...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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ACS Publications
2022
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| _version_ | 1797109017464537088 |
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| author | Biallas, P Yamazaki, K Dixon, DJ |
| author_facet | Biallas, P Yamazaki, K Dixon, DJ |
| author_sort | Biallas, P |
| collection | OXFORD |
| description | An iridium-catalyzed, reductive alkylation of abundant tertiary lactams and amides using 1-2 mol % of Vaska's complex (IrCl(CO)(PPh<sub>3</sub>)<sub>2</sub>), tetramethyldisiloxane (TMDS), and difluoro-Reformatsky reagents (BrZnCF<sub>2</sub>R) for the general synthesis of medicinally relevant α-difluoroalkylated tertiary amines is described. A broad scope (46 examples), including <i>N</i>-aryl- and <i>N</i>-heteroaryl-substituted lactams, demonstrated an excellent functional group tolerance. Furthermore, late-stage drug functionalizations, a gram-scale synthesis, and common downstream transformations proved the potential synthetic relevance of this new methodology. |
| first_indexed | 2024-03-07T07:34:38Z |
| format | Journal article |
| id | oxford-uuid:3cf59b8e-1eb2-4c12-9ff5-9e52b5896e44 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:34:38Z |
| publishDate | 2022 |
| publisher | ACS Publications |
| record_format | dspace |
| spelling | oxford-uuid:3cf59b8e-1eb2-4c12-9ff5-9e52b5896e442023-03-08T08:57:39ZDifluoroalkylation of tertiary amides and lactams by an iridium-catalyzed reductive reformatsky reactionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3cf59b8e-1eb2-4c12-9ff5-9e52b5896e44EnglishSymplectic ElementsACS Publications2022Biallas, PYamazaki, KDixon, DJAn iridium-catalyzed, reductive alkylation of abundant tertiary lactams and amides using 1-2 mol % of Vaska's complex (IrCl(CO)(PPh<sub>3</sub>)<sub>2</sub>), tetramethyldisiloxane (TMDS), and difluoro-Reformatsky reagents (BrZnCF<sub>2</sub>R) for the general synthesis of medicinally relevant α-difluoroalkylated tertiary amines is described. A broad scope (46 examples), including <i>N</i>-aryl- and <i>N</i>-heteroaryl-substituted lactams, demonstrated an excellent functional group tolerance. Furthermore, late-stage drug functionalizations, a gram-scale synthesis, and common downstream transformations proved the potential synthetic relevance of this new methodology. |
| spellingShingle | Biallas, P Yamazaki, K Dixon, DJ Difluoroalkylation of tertiary amides and lactams by an iridium-catalyzed reductive reformatsky reaction |
| title | Difluoroalkylation of tertiary amides and lactams by an iridium-catalyzed reductive reformatsky reaction |
| title_full | Difluoroalkylation of tertiary amides and lactams by an iridium-catalyzed reductive reformatsky reaction |
| title_fullStr | Difluoroalkylation of tertiary amides and lactams by an iridium-catalyzed reductive reformatsky reaction |
| title_full_unstemmed | Difluoroalkylation of tertiary amides and lactams by an iridium-catalyzed reductive reformatsky reaction |
| title_short | Difluoroalkylation of tertiary amides and lactams by an iridium-catalyzed reductive reformatsky reaction |
| title_sort | difluoroalkylation of tertiary amides and lactams by an iridium catalyzed reductive reformatsky reaction |
| work_keys_str_mv | AT biallasp difluoroalkylationoftertiaryamidesandlactamsbyaniridiumcatalyzedreductivereformatskyreaction AT yamazakik difluoroalkylationoftertiaryamidesandlactamsbyaniridiumcatalyzedreductivereformatskyreaction AT dixondj difluoroalkylationoftertiaryamidesandlactamsbyaniridiumcatalyzedreductivereformatskyreaction |