非表示:
キーワード:
HIGHLY STEREOSELECTIVE-SYNTHESIS; DYNAMIC KINETIC RESOLUTION; TANDEM
REACTION SEQUENCES; REDUCTIVE AMINATION; ENANTIOSELECTIVE HYDROGENATION;
SYNTHETIC APPLICATIONS; HYDROAMINOMETHYLATION; HYDROFORMYLATION; METAL;
ACIDChemistry; asymmetric synthesis; hydroformylation; hydroaminomethylation; cascade
reaction; hydrazide;
要旨:
The catalytic asymmetric hydroformylation of styrenes was combined with condensation of the resulting aldehydes with acetohydrazide as nucleophile leading to gamma-chiral N'-substituted acetohydrazones. This cascade reaction is called hydrohydrazonemethylation (HHM) in analogy to similar hydroformylation/condensation sequences. The catalyst was formed in situ from the commercially available chiral phosphine-ligand (R,R)-PhBPE and [Rh(acac)(CO)(2)] and used at a loading of 0.2 mol%. The stable condensation products are not prone to tautomerization providing versatile chiral intermediates. Their one-pot reduction with DMAB/TsOH resulted in the corresponding gamma-chiral N'substituted acetohydrazides (14 examples) with yields ranging from 73% to 91% and enantioselectivities from 77% to 97% ee. Deprotection of the acetohydrazides led to the corresponding beta-chiral hydrazines. Reduction and hydrogenolysis of the hydrazones over Raney-Ni yielded the corresponding beta-chiral primary amines with 95% ee. Diastereoselective functionalization of the C=N bond of the hydrazones is a further synthetic option, as demonstrated by allylation with (allyl)SiCl3.
