Pyridylic anions are soft nucleophiles in the palladium-catalyzed C(sp3)-H allylation of 4-alkylpyridines

被引:15
作者
Wasfy, Nour [1 ]
Rasheed, Faizan [1 ]
Robidas, Raphael [2 ]
Hunter, Isabelle [1 ]
Shi, Jiaqi [1 ]
Doan, Brian [1 ]
Legault, Claude Y. [2 ]
Fishlock, Dan [3 ]
Orellana, Arturo [1 ]
机构
[1] York Univ, Dept Chem, 4700 Keele St, N York, ON M3J 1P3, Canada
[2] Univ Sherbrooke, Dept Chem, Ctr Green Chem & Catalysis, 2500 Blvd Univ, Sherbrooke, PQ J1K 2R1, Canada
[3] F Hoffmann La Roche Ltd, Proc Chem & Catalysis, Synthet Mol Tech Dev, CH-4070 Basel, Switzerland
基金
加拿大自然科学与工程研究理事会;
关键词
C-H BONDS; CROSS-COUPLING REACTIONS; GRIGNARD-REAGENTS; ENANTIOSELECTIVE FUNCTIONALIZATION; ALKYLIDENE DIHYDROPYRIDINES; REGIOSELECTIVE ADDITION; ARYL HALIDES; ALPHA; PYRIDINES; AZAARENES;
D O I
10.1039/d0sc03304a
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
We report a mild palladium-catalyzed method for the selective allylation of 4-alkylpyridines in which highly basic pyridylic anions behave as soft nucleophiles. This method exploits alkylidene dihydropyridines, which are semi-stable intermediates readily formed using a 'soft-enolization' approach, in a new mechanistic manifold for decarboxylative allylation. Notably, the catalytic generation of pyridylic anions results in a substantially broader functional group tolerance compared to other pyridine allylation methods. Experimental and theoretical mechanistic studies strongly suggest that pyridylic anions are indeed the active nucleophiles in these reactions, and that they participate in an outer-sphere reductive elimination step. This finding establishes a new pK(a) boundary of 35 for soft nucleophiles in transition metal-catalyzed allylations.
引用
收藏
页码:1503 / 1512
页数:10
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