Cationic Bis(phosphine) Cobalt(I) Arene Complexes as Precatalysts for the Asymmetric Synthesis of Sitagliptin
Cationic Bis(phosphine) Cobalt(I) Arene Complexes as Precatalysts for the Asymmetric Synthesis of Sitagliptin
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DOI：
10.1021/acscatal.2c01059
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发表时间：
2022-04
期刊：
影响因子：
12.9
通讯作者：
C. Macneil;Hongyu Zhong;Tyler P. Pabst;M. Shevlin;P. Chirik
中科院分区：
文献类型：
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作者：
C. Macneil;Hongyu Zhong;Tyler P. Pabst;M. Shevlin;P. Chirik
研究了钴催化脱氢西他列汀的不对称氢化反应，并将其应用于西他列汀（捷诺维）的合成。催化剂发现的努力加快了阳离子双（膦）钴η6-芳烃配合物的合成的一般方法的应用。在芳烃存在下，双膦钴（II）二烷基配合物的单电子氧化得到了相应的实验室稳定的钴预催化剂[（P-P）Co（η6-C6 H6）][BAr 4F].不对称氢化使用0.5 mol %的最佳催化剂[（R，R）-（iPrDuPhos）Co（η6-C6 H6）][BAr 4F]在THF溶液中，并且以>99%的产率和97%ee.Co催化剂与一系列溶剂相容，并且在固态下在空气中静置2周后保持优异的活性和选择性。氘标记研究支持烯胺-亚胺互变异构化过程，导致金属化亚胺的还原。值得注意的是，现有技术的中性双（膦）钴预催化剂是无效的，强调了一类阳离子钴预催化剂的实用性。
The cobalt-catalyzed asymmetric hydrogenation of dehydro-sitagliptin was studied and applied to the synthesis of sitagliptin (Januvia). Catalyst discovery efforts were accelerated by the application of a general method for the synthesis of cationic bis(phosphine) cobalt η6-arene complexes. One-electron oxidation of bis(phosphine) cobalt(II) dialkyl complexes in the presence of arenes furnished the corresponding, bench-stable cobalt precatalysts, [(P–P)Co(η6-C6H6)][BAr4F]. Asymmetric hydrogenation utilized 0.5 mol % of the optimal catalyst, [(R,R)-(iPrDuPhos)Co(η6-C6H6)][BAr4F], in THF solution and produced sitagliptin in >99% yield with 97%ee. Cobalt catalysts were compatible with a range of solvents and maintained excellent activity and selectivity after standing in air in the solid state for 2 weeks. Deuterium labeling studies support an enamine–imine tautomerization process resulting in the reduction of the metalated imine. Notably, state-of-the-art neutral bis(phosphine) cobalt precatalysts were ineffective, emphasizing the utility of a class of cationic cobalt precatalysts.