Description:
<jats:title>Abstract</jats:title><jats:p>The catalytic asymmetric hydroformylation of styrenes was combined with condensation of the resulting aldehydes with acetohydrazide as nucleophile leading to γ‐chiral N’‐substituted aceto‐hydrazones. This cascade reaction is called hydrohydrazonemethylation (HHM) in analogy to similar hydroformylation/condensation sequences. The catalyst was formed <jats:italic>in situ</jats:italic> from the commercially available chiral phosphine‐ligand (<jats:italic>R</jats:italic>,<jats:italic>R</jats:italic>)<jats:italic>‐</jats:italic>Ph‐BPE and [Rh(acac)(CO)<jats:sub>2</jats:sub>] 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 γ‐chiral N’‐substituted acetohydrazides (14 examples) with yields ranging from 73% to 91% and enantioselectivities from 77% to 97% <jats:italic>ee</jats:italic>. Deprotection of the acetohydrazides led to the corresponding β‐chiral hydrazines. Reduction and hydrogenolysis of the hydrazones over Raney‐Ni yielded the corresponding β‐chiral primary amines with 95% <jats:italic>ee</jats:italic>. Diastereoselective functionalization of the C=N bond of the hydrazones is a further synthetic option, as demonstrated by allylation with (allyl)SiCl<jats:sub>3</jats:sub>.</jats:p><jats:p><jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/adsc202200804-toc-0001-m.png"><jats:alt-text>magnified image</jats:alt-text></jats:graphic></jats:boxed-text>
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