Selective Reduction of Secondary Amides to Imines Catalysed by Schwartz's Reagent**

Abstract

The partial reduction of amides is a challenging transformation that must overcome the intrinsic stability of the amide bond and exhibit high chemoselective control to avoid overreduction to amine products. To address this challenge, we describe a zirconium‐catalysed synthesis of imines by the reductive deoxygenation of secondary amides. This reaction exploits the excellent chemoselectivity of Schwartz's reagent (Cp2Zr(H)Cl) and utilises (EtO)3SiH as a mild stoichiometric reductant to enable catalyst turnover. The reaction generally proceeds with high yields (19 examples, 51 to 95 % yield) and tolerates a variety of functional groups (alkene, ester, nitro, etc.). Stoichiometric mechanistic investigations suggest the regeneration of the active [Zr]−H catalyst is achieved through the metathesis of Si−H and Zr−OR σ‐bonds.

Zirconium-Catalysed Hydrosilylation of Esters and Depolymerisation of Polyester Plastic Waste

“…Polymethylhydrosiloxane (PMHDS), Et3SiH and Ph3SiH only gave trace yields of 3a, whereas (EtO)3SiH gave >95% yield after 5 h. This highlights the importance of having at least two alkoxy substituents on the hydrosilane, as noted previously for the reduction of secondary amides. 17 A solvent screen showed a rate increase in C6D6, with >95% yield of 3a already after 1 h (Table 1, Entry 8). Similar reactivity to that in THF-d8 was observed in CD2Cl2 and also in anisole (Table 1, Entries 9 and 10), which is regarded as a non-toxic and biodegradable solvent according to the CHEM21 guide.…”

Zirconium-catalysed hydrosilylation of esters and depolymerisation of polyester plastic waste

“…By overcoming the inherent low reactivity of these polymer materials due to their lack of solubility, inhomogeneity and relatively low purity, we provide an example of chemical upcycling by transforming waste materials into value-added monomer products. [18][19][20] Based on the work of Bayeh-Romero et al and our previous work on the reduction of secondary amides, 16,17 initial conditions were applied to the reduction of ethyl 4-methylbenzoate 2a, using 10 mol% of Cp 2 Zr(H)Cl (1) with 2.1 equiv. of DMMS in THF-d 8 at 80 °C (Table 1, entry 1).…”

“…16 The two alkoxyzirconocene complexes 3 Zr and 4 Zr perform a σbond metathesis with the hydrosilane to form the desired silyl ethers 3 Si and 4 Si , respectively, with concomitant regeneration of the catalyst 1. 16,17 Using the optimised conditions defined above for ethyl 4-methylbenzoate 2a (Table 1, entries 2 and 8), the generality of this system was explored through a substrate scope (Scheme 4). The benzoate esters 2a and 2b and methyl phenylacetate 2c were cleanly reduced to the corresponding alcohols.…”

“…Recently, we proved that Cp 2 Zr(H)Cl ( 1 ) could also catalyse the partial reduction of secondary amides to imines. 17 This reaction proceeded with high chemoselectivity, avoiding over reduction to amine products. The reactivity was enabled by the exquisite inherent selectivity of the catalyst and the use of hydrosilanes as mild reductants.…”

“…Polymethylhydrosiloxane (PMHS), Et 3 SiH and Ph 3 SiH only gave trace yields of 3a , whereas (EtO) 3 SiH gave >95% yield after 5 h. This highlights the importance of having a more Lewis acidic silicon centre on the hydrosilane, as noted previously for the reduction of secondary amides. 17 A solvent screen showed a rate increase in C 6 D 6 , with >95% yield of 3a already after 1 h (Table 1, entry 8). Similar reactivity to that in THF- d 8 was observed in CD 2 Cl 2 and in anisole (Table 1, entries 2, 9 and 10), which is regarded as a non-toxic and biodegradable solvent according to the CHEM21 guide.…”