酰胺的可控还原策略
前期工作：
在汉斯酯（HEH，Hantzsch ester hydride，CAS：1149-23-1）和Tf2O的温和条件下可实现叔酰胺的还原。
仲酰胺的可控还原：
在前期工作的基础上，进一步对酰胺还原进行研究。通过对反应条件和后处理方式的调控，可以分别实现酰胺向亚胺，醛和胺的转化。
还原剂筛选
让酰胺还原停留在亚胺的关键在于选择比HEH亲核性更弱的氢源。根据文献报道，选择三乙基硅烷进行研究。
结果表明，Et3SiH作为氢源可以高选择性实现酰胺向亚胺的转化。而Et3SiH和HEH联用，则可以实现仲酰胺还原成胺。
通过进一步优化，以2-氟吡啶作为弱亲核性碱中和反应中生成的酸。
底物拓展：还原成亚胺和醛
该方法有着良好的底物兼容性和反应选择性。在还原酰胺的同时，底物中的氰基，硝基，叠氮，酯基，醛，都不受影响。
而且，当底物中同时存在叔酰胺和仲酰胺时，可以选择性还原仲酰胺（1h）。
下表中的收率，一列是亚胺，另一列是醛。二者的反应条件一致，只是后处理不同。在碱性条件下淬灭反应得到亚胺。而在柠檬酸条件下淬灭反应，则得到醛。
对炔烃，烯烃，不饱和酯以及不饱和酰胺都兼容。既适用于芳基酰胺又适用于脂肪族酰胺。
底物拓展：还原成胺
串联使用Et3SiH/HEH进行反应，则可以得到胺。同样对多种官能团兼容。而且后处理都是采用酸碱萃取进行简单分离，简化提纯步骤。
实验操作（还原成醛）
Procedure D: To a flame-dried 50-mL round-bottom flask equipped with a septum was added the amide (2.0 mmol, 1.0 equiv). The amide was diluted with 8 mL of anhydrous dichloromethane ([0.25M]) and 2-fluoropyridine (213.5 mg, 190 μL, 2.2mmol, 1.1 equiv) was added to the solution. The solution was then cooled to –78 °C using an acetone/dry ice cooling bath and stirred for 5 min. Trifluoromethanesulfonic(triflic) anhydride (Tf2O) (592.0 mg, 353 μL, 2.1 mmol, 1.05 equiv) was added dropwise via a syringe at –78 °C and the reaction was stirred for 10 min. The solution was heated at 0 °C using a water/ice bath and the reaction was stirred for 10 min. Triethylsilane (Et3SiH) (255.8 mg, 352 μL, 2.2 mmol, 1.1 equiv) was added dropwise at 0 °C and the reaction was stirred for 10 min. The solution was heated to room temperature and stirred for 5 h.
Then, the septum was removed and 8 mL of anaqueous solution of citric acid [0.08M] and 8 mL of THF were added to the flask. Areflux condenser was installed on the flask and the reaction was then heated to 45 °C and stirred for 2 h. The biphasic mixture was transferred to a separation funnel andthe layers were separated. The aqueous layer was extracted with dichloromethane(2x) and the organic layers were combined. The organic layer was dried over anhydrous sodium sulphate (Na2SO4 ), filtered over a sintered funnel and evaporated to dryness.
Note: Some synthesized aldehydes were found usually unstable when stored at room temperature on the bench over 1 or 2 days and showed decomposition by 1HNMR if no special storage precautions were taken. They should be kept under argon in the freezer (–20 °C) or use directly in a further reaction.
Summary
以Et3SiH/Tf2O体系作为还原剂，可以实现仲酰胺（注意，该方法仅对仲酰胺有效）分别向亚胺，醛和胺的转化。试剂廉价易得，反应兼容性强，选择性高。为酰胺的选择性还原提供一种非常具有参考意义的方法。
JACS, 2010, 12817。注：文中图片可能源于参考文献，若有侵权，请联系删除。
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