Use of CaH2 as a reductive hydride source: reduction of ketones and imines with CaH2/ZnX2 in the presence of a Lewis acid

Main Group Multiple C–H/N–H Bond Activation of a Diamine and Isolation of A Molecular Dilithium Zincate Hydride: Experimental and DFT Evidence for Alkali Metal–Zinc Synergistic Effects

“…155−158 Highly soluble, stable, and well-defined zincate hydride species are thus highly desirable. Despite this, however, structurally characterized alkali metal zincate hydrides are extremely rare.…”

Carbonyl reduction with CaH2 and R3SiCl catalyzed by ZnCl2

“…4 Meanwhile, although there had been no report for the use of CaH 2 as a reductive hydride, except for reactions through synthesis of boron 5 and alminium 6 hydrides and reductions of sulfates to sulfides, 7 we have recently reported the first example of a direct use of CaH 2 for the reduction of carbonyl compounds, where a mixture of CaH 2 and ZnX 2 reduced ketones and imines in the presence of a catalytic amount of a Lewis acid such as Ti(O-i-Pr) 4 , B(O-i-Pr) 3 , Al(O-i-Pr) 3 and ZnF 2 . 8 Carbonyl reduction with these stable metal hydrides is promising as a practical process applicable to a large-scale synthesis. However, the reaction of aldehydes having α-hydrogen with the LiH-based reagent gave a complex mixture including aldol condensation products 2,9 and the CaH 2 -based reagent also resulted in formation of a complex mixture from aldehydes and no reaction with acyclic aliphatic ketones.…”

“…However, the reaction of aldehydes having α-hydrogen with the LiH-based reagent gave a complex mixture including aldol condensation products 2,9 and the CaH 2 -based reagent also resulted in formation of a complex mixture from aldehydes and no reaction with acyclic aliphatic ketones. 8 Herein we report development of a new CaH 2 -based reagent, cat. ZnX 2 /CaH 2 /R 3 SiCl, which effectively reduced (hydrosilylated) a variety of carbonyl compounds including aromatic, aliphatic ketones with a cyclic and acyclic form and aldehydes.…”

“…Possibility of the use of other metal salts instead of ZnX 2 was also examined. As revealed from the results of the reaction of acetophenone (1a) (entries [1][2][3][4][5][6][7][8], in the absence of metal salt the reaction did not take place at all (entry 1), whereas, in the presence of ZnX 2 the reaction proceeded to afford the Pergamon TETRAHEDRON LETTERS expected alcohol (entries 2-4). Though the reaction at room temperature sometimes faced the problem of reproducibility (entry 2), performing the reaction at 40 o C helped to overcome this matter (entries 3 and 4).…”

“…Thus, the present method overcame the aforementioned limitation of the reported LiH-and CaH 2 -based carbonyl reduction. 2,8 Since the reaction with cat. ZnX 2 /CaH 2 /Me 3 SiCl system provided a mixture of the reduced alcohol and its silyl ether after neutral aqueous work-up or on TLC analysis of the reaction mixture, the reaction might initially formed the corresponding Me 3 Si ethers but they often were unstable to isolate.…”